A Systematic Review of Key Issues in Public

Health

Stefania BocciaPaolo VillariWalter Ricciardi

Editors

A Systematic Review of Key

Issues in Public Health

13

Editors
Stefania Boccia
Universit Cattolica del Sacro Cuore
Institute of Hygiene Faculty of Medicine
Rome
Italy

Walter Ricciardi
Institute of Hygiene, Faculty of Medicine
Universit Cattolica del Sacro Cuore
Rome
Italy

Paolo Villari
Public Health and Infectious Diseases
Sapienza University of Rome
Rome
Italy

ISBN 978-3-319-13619-6ISBN 978-3-319-13620-2 (eBook)

DOI 10.1007/978-3-319-13620-2
Library of Congress Control Number: 2015933293
Springer Cham Heidelberg New York Dordrecht London
Springer International Publishing Switzerland 2015
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Preface

Anyone watching the television news or reading a newspaper today, in 2014, could
be forgiven for lapsing into despair. Europe has yet to emerge from the longest
economic recession in over 500 years and its leading political institutions show no
sign of even understanding its main cause, their collective failure to tackle the reckless, and in some cases criminal behaviour of the corporate financial institutions. In
several parts of the globe, such as Central Africa and the Middle East, conflicts are
wreaking carnage among innocent bystanders on a massive scale, often involving
unspeakable atrocities, in some cases by states using sophisticated modern weapons
to attack densely populated areas. Countries that once aspired to lofty principles of
democracy and freedom have been exposed as being engaged in kidnapping (now
sanitised by the term rendition) and torture. In many places, including parts of
Western Europe, anyone who is in any way different, by virtue of their skin colour
or the outward signs of their religious belief, risks persecution or worse, with explicitly racist parties achieving significant electoral success for the first time since
the 1930s. Politicians, who now including a vanishingly small number of individuals with any scientific training, let alone understanding, are incapable of responding
to the profound damage we are doing to our environments, remaining in denial and
the evidence of harm accumulates. Media commentators offer not hope for a better
future but gloom and doom, representing older people who would once have been
valued for their accumulated wisdom as a burden that can no longer be afforded.
Yet, as has so often been the case in the past, times of crisis bring out the best
in some people, who have the vision to see into the future, to make the connections, and to propose workable solutions. The challenges listed above have two
main things in common. They all have profound implications for population health
and they are all what are termed wicked problems, characterised by incomplete
information and complex interdependencies and thus resistant to easy solutions.
They require joined up thinking on a large-scale, drawing on a broad range of disciplinary perspectives, from epidemiology and statistics to sociology and political
science. As the editors of this excellent volume note, the skills required are those of
a participant in the decathlon. The decathlete may not have the speed off the blocks
of Usain Bolt or the endurance of Mo Farah, but they instead have the combination
v

vi

Preface

of talents in a broad range of areas that are required to find possible solutions to
these wicked problems.
This book is in many ways a manual for the public health decathlete, although
the editors have gone much further by including 15, not 10, items. These items cover many of the contemporary challenges confronting population health. Seven chapters review the changing burden of disease and injury, providing many examples of
the tremendous successes of the public health community. The most celebrated have
been those in the struggle against communicable disease, with the authors noting
achievements in transforming acquired immune deficiency syndrome (AIDS) into
a condition that those infected die with rather than from. However, there are others, less well-recognised, such as the 50% decline in mortality from cardiovascular
disease in North Western Europe in the past four decades. Yet, as the authors of all
of these chapters note, progress is not inevitable. Communicable diseases that once
seemed to be coming under control are reappearing, such as tuberculosis, but now
in a much more alarming drug-resistant form. Indeed, antimicrobial resistance is
now recognised as a global threat, potentially posing an existential threat to humanity, just like climate change. Failure by governments to act against the vectors of
non-communicable disease, and especially the major corporations that profit from
sales of unhealthy products, for example by placing considerations of health above
those of trade liberalisation, has permitted the spread of obesogenic and alcogenic
environments, with profound consequences for our future health.
Other chapters in this volume explore topics that, while not exactly new, have
achieved much greater importance in recent decades. These include the topic on urban health. Even though it has long been known that those who moved to the cities
that emerged during the industrial revolution became less healthy than those who
stayed in the countryside, the growth of megacities has created health challenges
on an entirely different scale. They also include public mental health, long put in a
distant second place by public health professionals, echoing the way in which those
with mental illness were themselves confined in faraway places, behind high walls
where they could be kept out of sight. 150 years on, Gregor Mendel would be astonished at the progress that has been made since his experiments with cross pollination of peas. Genomics brings many opportunities for our understanding of the aetiology of disease and, by enabling improved therapeutic targeting, potentially some
advances in treatment. Yet, by creating yet another way to separate groups within
the population, it also poses threats to collective actions based on solidarity. It is an
issue that is poorly understood by many commentators, as is ageing, also addressed
in this volume. The fact that populations are ageing should surely be celebrated as
a success, yet too often it is seen as a threat. As the authors note, the challenge is to
achieve active ageing, adding life to years and not simply years to life.
As the authors of these individual chapters show, the challenge of understanding
and responding to these issues must be based on concerted interdisciplinary activities, drawing together those with a range of skills and expertise. However, the whole
is greater than the sum of the individual parts, so two concluding chapters look at
the ways of bringing these issues together, highlighting the need to embed health in
all policies (including those where it is too often absent, such as fiscal, defence, and

Preface

vii

criminal justice policies) and to undertake assessments of the health impacts of all
policies. Reflecting on the situation today, had someone assessed, and taken seriously, the health impact of the austerity policies still being pursued in many countries, many of those who found life no longer worth living might still be alive today.
The need for active, engaged, informed, and highly skilled public health professionals is greater now than ever, if we are to raise awareness of the health consequences of the many challenges we now face and are to offer workable solutions.
This excellent book, written by some of Europes leading experts on public health,
will help to achieve this goal.
Professor of European Public Health
London School of Hygiene and Tropical Medicine

Martin McKee

Contents

1Introduction and Global Burden of Disease 1

Andrea Silenzi, Maria Rosaria Gualano and Walter Ricciardi
2Health Trends of Communicable Diseases 5
Alessio Santoro, Benedetto Simone and Aura Timen
3Global Burden and Health Trends
of Non-Communicable Diseases 19
Silvio Capizzi, Chiara de Waure and Stefania Boccia
4Cardiovascular Disease (CVD) 33
Elvira DAndrea, Iveta Nagyova and Paolo Villari
5Epidemiology of Cancer and Principles of Prevention 65
Stefania Boccia, Carlo La Vecchia and Paolo Boffetta
6Obesity and Diabetes 89
Anna Maria Ferriero and Maria Lucia Specchia
7Respiratory Diseases and Health Disorders Related to
Indoor and Outdoor Air Pollution 109
Francesco Di Nardo and Patrizia Laurenti
8Public Health Gerontology and Active Aging 129
Andrea Poscia, Francesco Landi and Agnese Collamati
9Some Ethical Reflections in Public Health 153
Maria Luisa Di Pietro
10Injury Prevention and Safety Promotion 169
Johan Lund, Paolo Di Giannantonio and Alice Mannocci
ix

Contents

11Migrant and Ethnic Minority Health 189

M.L. Essink-Bot, C.O Agyemang, K Stronks and A Krasnik
12Public Mental Health 205
Chiara Cadeddu, Carolina Ianuale and Jutta Lindert
13Urban Public Health 223
Umberto Moscato and Andrea Poscia
14Genomics and Public Health 249
Stefania Boccia and Ron Zimmern
15Health Impact Assessment: HIA 263
Roberto Falvo, Marcia Regina Cubas and Gabriel Gulis
16Health in All Policies 277
Agnese Lazzari, Chiara de Waure and Natasha Azzopardi-Muscat
Index 287

Contributors

C.O Agyemang Department of Public Health, Academic Medical Center

University of Amsterdam, Amsterdam, The Netherlands
Natasha Azzopardi Muscat Department of Health Services Management,
Faculty of Health Sciences, University of Malta, Msida, Malta
Benedetto SimoneInstitute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, L. go F. Vito 1, Rome, Italy
Paolo Boffetta Mount Sinai School of Medicine Tisch Cancer Institute, New
York, NY, USA
Chiara Cadeddu Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
Silvio Capizzi Institute of Public Health, Section of Hygiene, Universit Cattolica
del Sacro Cuore, L. go F. Vito 1, Rome, Italy
Agnese Collamati Institute of Gerontology, Universit Cattolica del Sacro Cuore,
[Link] F. Vito 1, Rome, Italy
Elvira DAndrea Department of Public Health and Infectious Diseases, Sapienza
University of Rome, ple Aldo Moro 5, Rome, Italy
Chiara de Waure Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
Paolo Di Giannantonio Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
Francesco Di Nardo Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
M.L. Essink-Bot Department of Public Health, Academic Medical Center
University of Amsterdam, Amsterdam, The Netherlands
Roberto Falvo Section of Hygiene, Institute of Public Health, Universit
Cattolica del Sacro Cuore, Rome, Italy
xi

xii

Contributors

Anna Maria Ferriero Section of Hygiene, Institute of Public Health, Universit

Cattolica del Sacro Cuore, Rome, Italy
Gualano Department of Public Health Sciences, University of Turin, Turin, Italy
Gabriel Gulis Unit for Health Promotion Research, University of Southern
Denmark, Esbjerg, Denmark
Carolina Ianuale Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
A Krasnik Faculty of Health Sciences Department of Public Health CSS,
Danish Research Centre for Migration Ethnicity and Health (MESU) University of
Copenhagen, Copenhagen, Denmark
Carlo La Vecchia Department of Clinical Sciences and Community Health,
Universit degli Studi di Milano, Milan, Italy
Francesco Landi Institute of Gerontology, Catholic University of Sacred Heart,
Rome, Italy
Patrizia Laurenti Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
Agnese Lazzari Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
Jutta Lindert Protestant University of Ludwigsburg, Ludwigsburg, Germany
University of Leipzig, Leipzig, Germany
Harvard School of Public Health, Boston, USA
Maria Luisa Di Pietro Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
Johan Lund Institute of Health and Society, Section for Social Medicine,
University of Oslo, Oslo, Norway
Alice Mannocci Department of Public Health and Infectious Diseases, Sapienza
University of Rome, Rome, Italy
Umberto Moscato Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, [Link] F. Vito 1, Rome, Italy
Iveta Nagyova Department of Public Health, PJ Safarik University, Kosice, Tr
SNP 1, Slovakia
Andrea Poscia Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
Marcia Regina Cubas Ps-Graduao em Tecnologia em Sade, Pontifcia
Universidade Catlica do Paran, Curitiba, PR, Brazil

Contributors

xiii

Walter Ricciardi Institute of Public Health, Section of Hygiene, Universit

Cattolica del Sacro Cuore, Rome, Italy
Alessio Santoro Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
Andrea Silenzi Institute of Public Health, Section of Hygiene, Universit
Cattolica del Sacro Cuore, Rome, Italy
Maria Lucia Specchia Section of Hygiene, Institute of Public Health, Universit
Cattolica del Sacro Cuore, Rome, Italy
K Stronks Department of Public Health, Academic Medical CenterUniversity
of Amsterdam, Amsterdam, The Netherlands
Aura Timen Centre for Infectious Disease Control, National Institute of Public
Health and the Environment, Bilthoven, The Netherlands
Paolo Villari Department of Public Health and Infectious Diseases, Sapienza
University of Rome, ple Aldo Moro 5, Rome, Italy
Ron Zimmern PHG Foundation, Cambridge, UK

Chapter 1

Introduction and Global Burden of Disease

Andrea Silenzi, Maria Rosaria Gualano and Walter Ricciardi

In 1920, when two young undergraduates of Yale University visited Charles-Edward Amory Winslow in his laboratory and asked him whether to take up a career
in public health, he answered: it is essential that worker in this domain of applied
science should see clearly the goal toward which he is aiming, however far ahead of
the immediate possibilities of the moment it may appear to be.
This advice, after about a 100 years, is valid now more than ever. Every worker
involved in the protean field of public health has to face multifactorial problems
that, actually, represent extremely interesting challenges and incentives to practice
the science and art of preventing disease, prolonging life and promoting health
through the organized efforts of society [1].
If we want to compare the public health professional with an athlete and his
sport, certainly the discipline that is more likely to be used as a paradigm would be
the decathlon. In fact, if the decathlon is a combined event in athletics consisting
of ten track and field events, public health incorporates a real interdisciplinary approach based on epidemiology, biostatistics and health planning [2]. Environmental health, community health, behavioural health, health economics, public policy,
insurance medicine and occupational medicine are other important and apparently
different subfields, linked by the mainstream of prevention.

[Link]() [Link]
Institute of Public Health, Section of Hygiene, Universit Cattolica del Sacro Cuore,
[Link] F. Vito 1, 00168 Rome, Italy
e-mail: [Link]@[Link]
[Link]
Department of Public Health Sciences University of Turin [Link] Polonia 94,
10126 Turin, Italy
e-mail: [Link]@[Link]
[Link]
e-mail: wricciardi@[Link]
Springer International Publishing Switzerland 2015
S. Boccia et al. (eds.), A Systematic Review of Key Issues in Public Health,
DOI 10.1007/978-3-319-13620-2_1

A. Silenzi et al.

It is intuitive and also supported by evidences that tackling causes of diseases

can prevent much premature death and suffering.
In fact, the removal of upstream causes is often more cost-effective than the removal of proximal medical causes since upstream causes bring about a plethora of
downstream sufferings: this is one of the goals of public health.
Similarly, another goal of this discipline is to take care of health and wellbeing
of people, both in the individual dimension and in the community. This means,
primarily, promoting a longer life with a better quality of living, free from disease
and disability.
Several key principles are inherent in the public health approach: the importance of analysing the problem (any disease but also a new policy, a new model of
health care delivery, etc.) with an epidemiologic method, proposing a solution and,
finally, assessing the impact of interventions; the need for flexibility and urgency
in response to ongoing monitoring and operational research; the need to intervene
against health inequalities, no matter how difficult it is to access occurrences of the
problem or how minor the perceived problem is in a particular community [3].
Indubitably, the epidemiological transition that signed the last century, witnessed
by a sudden and stark increase in population growth rates (brought about by medical
innovation in disease or sickness therapy and treatment), accounts for the replacement of infectious diseases by non-communicable diseases over time. This was due
to better treatments and new technologies used in medical practice and widespread
sanitation, but even more to a growing public health approach all over the world. In
fact, during the twentieth century, heart diseases, cancer and other chronic conditions assumed more dominant roles and new concerns also came to medical attention (e.g. the terrifying consequences of thermonuclear war, the effects of environmental pollution and climate change) [4]. At the moment, optimism about prospects
for the health of future generations persists but remains tempered by the concern
about the pathologies of civilization. An obesity epidemic, feared at the beginning
of the 1900s, has become a reality and the management of an increasing community
of elderly people represents the most challenging duty to face nowadays. Our previously steady increase in life expectancy has stalled, as reported in different national
statistical and epidemiological reports, and may even be reversed [5].
Currently, the protean dynamism of the burden of disease poses challenges: how
do we define disease meaningfully, and how do we measure our burden of disease
and set health policy priorities? Although repeated assessment of burden of disease
would allow comparisons between populations and over time, since mortality and
morbidity are multifactorial, any changes in terms of incidence and prevalence are
difficult to attribute to actions taken by the health sector in terms of planning and
management.
A given health system might achieve the best possible population health, given
its budget, but burden of disease could increase because of changes in other causes
of disease (e.g. changing food supply or climatic conditions). Similarly, a system
might provide substandard care while burden of disease falls. Even in high-income
countries, the correlation between quality of care and mortality is low [6].

1 Introduction and Global Burden of Disease

Public health shapes the context within people and communities can be safe
and healthy and, by its very nature, it requires support by citizens, its beneficiaries
[7]. For this reason, some authors suggest that the best way to improve population
health is to think less about the organization and more about the solutions and highvalue interventions, starting from the citizens perspectives [8].
We need to know that, due to budget limits, a decision to invest in a particular set
of interventions means that we are implicitly deciding not to invest in others. And
even if an effective intervention is delivered at high quality without waste, it may
still represent low value if greater value could be achieved by using that resources
to treat another group of patient [9].
Often there is only a tenuous link between research questions and the decision on
problems faced by policymakers aiming to maximise health, and only by prioritising high-value interventions, we will make the most of available resources.
The mission of public health is to maximise population health, changing culture,
orienting and influencing decision-making, taking into account and promoting equity and social values.
The important issues are those we can do something about, those for which we
have effective interventions because the world changes when the boldest thinking
is directed at the toughest problems.
Public health is innovation and
[] it simply requires thinking in new ways about the barriers that prevent progress
[because] innovation is not a single solution. It is a process. It is a frame of mind, a way of
constantly looking at problems from new angles so that you can see more and more powerful solutions, try them out, and keep improving on them. [10]

The topics addressed with this book are relevant more than ever at this time, because the financial crisis across Western countries has increased the awareness of
maximizing health benefits with the lowest possible expenditure.
In this book, a comprehensive review of different key issues in public health
will illustrate some of the challenges they pose worldwide and a systematic report
of the best practice example in terms of cost-effectiveness of certain health policy
intervention might help policymakers to engage more meaningful and successful
decisions.

References
1. Winslow CEA (1920) The untilled fields of public health. Science 51(1306):2333
2. Decathlon Wikipedia. Available at [Link] Accessed 28
March 2014
3. Guest C, Ricciardi W, Kawachi I, Lang I (2013) Oxford handbook of public health practice, 3rd
edn. Oxford University Press, Oxford
4. Jones DS, Podolsky SH, Greene JA (2012) The burden of disease and the changing task of
medicine. N Engl J Med 366:23332338
5. The National Observatory on Health Status in the Italian Regions (2012). Osservasalute Report. Prex, Milan, Italy

A. Silenzi et al.

6. Roberts I, Jackson R (2013) Beyond disease burden: towards solution-oriented population

health. Lancet 381(9884):22192221
7. Institute of Medicine (1988) The future of public health. National Academies Press, Washington, DC
8. Gray JAM (2007) How to get better value healthcare. Offox, Oxford
9. Gray JAM (2013) The shift to personalised and population medicine. Lancet 382(9888):200
201
10. Gates M (2013) Reinvent a better world: a series. Impatient Optimists Blog by Bill and
Melinda Gates Fundation. Avaible at [Link] Accessed 28 March 2014

Chapter 2

Health Trends of Communicable Diseases

Alessio Santoro, Benedetto Simone and Aura Timen

Introduction
Although the burden of communicable diseases has been steadily decreasing in
past decades in industrialised countries, it is still considerable worldwide. Lower
respiratory infections, diarrhoeal disease and HIV/acquired immunodeficiency syndrome (AIDS) are still among the top major killers in 2011 (Fig.2.1, the ten leading
causes of death in the world in 2011 according to the World Health Organization),
and communicable diseases in general are responsible for considerable morbidity
in all parts of the world [1].
There is, however, a marked difference in terms of burden of disease, morbidity
and mortality between industrialized low-income countries.
In industrialized countries, chronic diseases such as cardiovascular diseases,
cancer and diabetes have the highest burden. In low-income countries, infectious
diseases still represent the biggest issue. Lower respiratory infections, HIV/AIDS,

[Link]() [Link]
Institute of Public Health, Section of Hygiene, Universit Cattolica del Sacro Cuore,
[Link] F. Vito 1, 00168 Rome, Italy
e-mail: [Link]@[Link]
[Link]
e-mail: [Link]@[Link]
[Link]
Centre for Infectious Disease Control, National Institute of Public Health and the Environment,
P.O. box 1, 3720 BA Bilthoven, The Netherlands
e-mail: [Link]@[Link]
Springer International Publishing Switzerland 2015
S. Boccia et al. (eds.), A Systematic Review of Key Issues in Public Health,
DOI 10.1007/978-3-319-13620-2_2

A. Santoro et al.
/

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KW



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Fig. 2.1 The ten leading causes of death in the world in 2011 according to the World Health Organization [1]. COPD chronic obstructive pulmonary disease

diarrhoeal diseases, malaria and tuberculosis (TB) collectively account for around
one third of all deaths.
Despite these differences, there is a wide range of emerging and re-emerging
infectious diseases with varying potentials for spread in the world. Multidrug-resistant (MDR) TB and vancomycin-resistant Staphylococcus aureus are examples of
emerging infections that do not immediately involve large numbers of persons but
that will ultimately have a serious impact on public health throughout the world [1].
This chapter considers a selected number of infectious diseases, or of groups of
diseases, which, for their burden, are of particular importance in low-income or in
industrialized countries.

Tuberculosis
Mycobacterium tuberculosis is an aerogenic transmitted agent which represents the
most frequent cause of TB. Mycobacterium tuberculosis can stay latent for years;
symptoms, which can be both pulmonary and extra-pulmonary, occur when, under
favourable conditions, the agent multiplies. Correct treatment of active cases is crucial to prevent the occurrence of MDR TB and extensively drug-resistant (XDR) TB.
The Bacille CalmetteGurin (BCG) vaccine is a live, weakened vaccine; hence,
every sort of immunosuppression, as well as pregnancy, represents absolute contraindications. BCG vaccine protects against severe forms of TB, particularly nonpulmonary localizations. WHO recommends BCG vaccination in all newborns in
high-incidence TB countries. In Europe, vaccination is recommended in all people
with an increased risk of contracting TB: among them, children with parents coming
from high-incidence countries and who travel regularly to their home countries [2].

2 Health Trends of Communicable Diseases

Table 2.1 Economic impact
of tuberculosis (TB) in
European countries according to the European Centre
for Disease Prevention and
Control [5]

In the old EU-15 countries

(+Cyprus, Malta and Slovenia), the costs per case were:

In the remaining new EU

countries, the costs per
case were:

10,282 for drug-susceptible

TB

3,427 for drug-susceptible TB

57,213 for multidrug-resistant (MDR) TB

24,166 for M/XDR-TB

170,744 for extensively

drug-resistant (XDR) TB

Twenty-two high-burden countries account for over 80% of the worlds TB cases; in those countries, both incidence and mortality for TB are downscaling. These
findings are consistent with the global data which reveal that incidence and mortality are falling down in all WHO Regions. However, within the global scenario,
huge variations can be underlined: the Millennium Development Goals (MDGs) of
halving the 1990 levels by 2015 are not on track to be achieved in the African and
European Regions [2].
Although enormous progress has been done, despite regional variations, the
global burden of TB is still relevant; data referring to 2011 revealed 8.7 million new
cases of TB (13% coinfected with HIV) and 1.4 million people deaths due to such
disease. TB prevalence is higher in Asia and Africa. In Asia, India and China together account for almost 40% of the worldwide TB cases while the African Region
registered the 24% of all the global cases, and the highest rates of cases and deaths
per capita [2]. In the WHO European Region, the estimated TB prevalence is more
than 500,000 cases; most recent data reported 44,000 victims, the vast majority in
Eastern Europe and Central Asia [3, 4].
Unfortunately, steps further in responding to M/XDR-TB are still slow. India,
China, the Russian Federation and South Africa have almost 60% of the worldwide
cases of M/XDR-TB. However, with over half of the worlds countries with the
highest percentage of M/XDR-TB cases, the WHO European Region is a gravity
centre for such disease, particularly Eastern European and Central Asian countries
[3, 4].
In 2004, WHO recommended the implementation of collaborative TB/HIV activities on a global scale; progress on this issue has proceeded. Around 80% of TB
cases among people living with HIV were located in Africa. In 2011, in the WHO
European Region, 6% of TB patients were coinfected with HIV [2].
With regard to TB costs, most recent data, referring to 2011, strengthened the
awareness of the gigantic economic impact of TB in the WHO European Region.
Table2.1 reports the economic impact of TB [5].
Other relevant data reported that:
The 70,340 susceptible TB cases, the 1.488 MDR-TB and the 136 XDR-TB
cases notified in 2011 cost 536.890.315 in 2012.
The 103,104 disability adjusted life years (DALYs) caused by these cases, when
stated in monetary terms, amounted to [Link] in 2012.

A. Santoro et al.

In 2006, the Global Plan to Stop TB 20062015 reiterated WHO pledges in halting,
and beginning to reverse, the TB epidemic by 2015 and in halving TB prevalence
and death rates by 2015 compared with 1990 levels. The directly observed treatment, short course (DOTS) strategy of the global plan points out main issues to be
strengthened. They are:
Political commitment (through long-term strategic plans) and financing (through
national governments)
Case detection through quality-assured bacteriology (by using sputum smear microscopy and then culture/drug susceptibility testing)
Standardized treatment, with supervision and patient support (through the most
effective, standardized, short-course regimens to facilitate adherence)
Effective drug supply and management system (through a reliable system of
procurement and distribution of all essential anti-TB drugs to all health facilities)
Monitoring/evaluation of system, and measure of the impact [6]
In Cambodia, the adherence to the Stop TB Plan resulted in a downscale of the TB
prevalence in 2011 by 45% compared to 2002 through the decentralization of TB
control services from provincial/district hospitals to health centres [7].
At the European level, Switzerland implemented a strategic plan to fight against
TB; it represents a benchmark with regard to the strict collaboration between a
national government and WHO EURO. This nationwide plan aims at specifically
focusing the fight against TB towards the reduction of inequalities, the access to
screening and diagnosis, the strengthening of the treatment according to DOTS
guidance, the improvement of the epidemiologic surveillance network, the upgrade
of communication/information campaigns and the setting of new international collaborations [8].
With regard to MDR/XDR TB, in the high-prevalence Eastern European and
Central Asian countries, stakeholders and decision-makers are recommended to address targeted evidence-based interventions policies. Main efforts have to be focused on:
Identifying and addressing risk factors contributing to the spread of drug-resistant TB
Strengthening the health system response in providing accessible, affordable and
acceptable services
Working in regional, national and international partnerships on TB prevention,
control and care
Monitoring the trends of M/XDR-TB and measuring the impact of interventions
[9, 10]

HIV/AIDS
The pathogenetic mechanism of the HIV consists in attacking the immune system.
The long incubation period ends with a lifelong severe disease culminating in AIDS.
AIDS is defined by the presence of one or more opportunistic illnesses. Sexual

2 Health Trends of Communicable Diseases

contacts with an infected person and sharing needles/syringes with someone who
is infected represent the most common modalities of transmission. Less commonly,
HIV can be contracted through transfusions of infected blood. Finally, newborns of
HIV-infected women may become infected before or during birth, or through breast
feeding. Since the mid-1990s, the quality of life of HIV patients has been deeply
scaled up through effective combination therapies. These drugs delayed the onset of
AIDS and the related death; however, the occurrence of side effects raises concerns
[11].
In 2011, the global prevalence of HIV accounted for 34 million people; 69%
of them lived in Sub-Saharan Africa. Around five million people are living with
HIV in South, South-East and East Asia combined. Other high-prevalence regions
include the Caribbean, Eastern Europe and Central Asia [11].
Worldwide, HIV incidence is in downturn. In 2011, 2.5 million people acquired
HIV infection; this number was 20% lower than in 2001. Sharpest declines in the
incidence have been recorded in the Caribbean (42%) and Sub-Saharan Africa
(25%). However, variation among regions gives rise to concerns; since 2001, a
35% increase of HIV incidence has been reported in the Middle East and North
Africa. The number of newly infected people in Eastern Europe and Central Asia
has been scaling up since 2001, as well [11].
As for HIV mortality rates, the number of people dying from AIDS-related
causes has been reducing since the mid-2000s, because of the improved antiretroviral therapy [12, 13]. In 2011, the Joint United Nations Programme on HIV and
AIDS (UNAIDS) estimated that 1.7 million people died from AIDS-related causes
worldwide, thus recording a 24% decline compared with 2005 statistics. However,
huge variations between regions have been reported, as well. Although Sub-Saharan Africa still accounts for 70% of all AIDS-related deaths, a 32% downturn was
underlined in this region, in 2011. Consistent findings have been reported in the
Caribbean, (reduction achieved was 48%), in Oceania (41%) and in Latin America
(10%). According to data referring to incidence rates, increased AIDS-related mortality has been highlighted in Eastern Europe/Central Asia (21%) and in the Middle
East/North Africa (17%) [11].
The steady scaling up of HIV incidence in the WHO European Region raises
many concerns and underpinned further investigations to point out high-risk groups.
The highest number of HIV cases in Europe was reported among men who have sex
with men (MSM, 38%), individuals infected by heterosexual contact (24%) and
injecting drug use (4%). Noteworthy, transmission patterns are widely different
across Europe: MSM route of transmission accounted for a disproportionate amount
cases in the UK and in the Netherlands, heterosexual contacts in Western/Central
Europe and injection drug users in Eastern Europe [14, 15].
Although evidence of cost-effective interventions is not clear and straightforward neither for Western countries nor for developing ones, some analysis outlined
interesting results. In developing countries, mass media campaigns and interventions for sex workers, preventative measures to interrupt mother-to-child transmission, voluntary counselling and school-based education have been shown to be costeffective [16].

10

A. Santoro et al.

In Europe, interesting findings have been reported with regard to structural interventions (as mass media campaigns and large-scale condom distributions), and
individually focused interventions to change risk behaviour, respectively in lowand high-prevalence populations [17]. However, with regard to behavioural interventions in high-prevalence settings, a UK study pointed out the effectiveness of
group- and community-level interventions but unclear findings were recorded in
terms of individual-level interventions [18].
Globally, others evaluations reported the cost-effectiveness of:
Community empowerment approach to HIV prevention and treatment across sex
workers, with projected impact beyond the sex worker community
Needle/syringe programmes among drug users groups
Behavioural interventions for MSM to reduce the rate of unprotected anal intercourse (27% downturn vs. no HIV-preventive interventions) [19, 20, 21].
In Europe, most successful HIV control programmes emerge from the awareness
that HIV transmission is higher among injecting drug users; in turn, people who
inject drugs are at greater risk of contracting TB. Hence, in order to foster people
to seek and maintain treatment, the city of Porto has brought services for opioid
substitution therapy (OST), HIV and TB together, focusing services on peoples
needs instead than on diseases. The WHO assessment of the Portos model showed
that integrating services for HIV, TB and drug-dependence treatments improve the
accessibility and quality of care for people who inject drugs [22].
Crucial tools to drive decisions of stakeholders and policymakers should rely on
scientific evidence and on the burden of disease. As for the latter, statistics show
that in Europe high-risk groups are MSM (36 and 22% in Western and Central
Europe, respectively), injecting drug users (33% in Eastern Europe) and male and
transgender sex workers [19, 23]. Policymakers and HIV programme implementers should target their policies to high-prevalence groups, in order to streamline
efforts. According to most recent evidence-based recommendations, stakeholders
and policymakers should take into account that most successful HIV campaigns
should be addressed to social change as decriminalization of sex workers, de-stigmatisation of sex between men and of drug use. In this framework, policies should
be focused on HIV testing and distribution of condoms (at individual level), and on
policy efforts to decriminalize MSM behaviour and anti-homophobia programmes
(at community level) [23].

Other Sexually Transmitted Infections

Sexually transmitted infections (STIs) are a heterogeneous group of infections
which recognize a common transmission pathway. They include:
Chlamydia, caused by the Chlamydia trachomatis bacteria
Gonorrhoea, caused by Neisseria gonorrhoeae bacteria

2 Health Trends of Communicable Diseases

11

Syphilis caused by Treponema pallidum bacteria (syphilis may also be transmitted from mother to child, thus resulting in congenital syphilis)
Blood-borne viruses which could be sexually transmitted, as well (HIV, hepatitis
B and hepatitis C viruses are the most common ones) [24]
STIs are contracted through vaginal, oral and anal sexual intercourse.
STIs raise public health concerns because of the profound consequences of these
infections on sexual and reproductive health. During pregnancy, syphilis leads to
foetal/neonatal deaths, prematurity, low birth weight or congenital disease. As for
gonorrhoea and chlamydia, they represent an important cause of infertility. Noteworthy, contracting an STI increases the chances of acquiring HIV infection by
threefold or more.
In recent years, HIV addressed all the public health efforts and the strong association between STIs and HIV acquisition has been underestimated [24].
Worldwide, an estimated 499million new cases of curable STIs (as gonorrhoea,
chlamydia and syphilis) occurred in 2008; these findings suggested no improvement compared to the 448million cases occurring in 2005. However, wide variations in the incidence of STIs are reported among different regions; the burden of
STIs mainly occurs in low-income countries [24].
In the European Union (EU), chlamydia is the most frequently reported STI;
more than 340,000 new cases have been reported in 2010. However, the true incidence of chlamydia is likely to be higher than the officially reported one; underreporting and asymptomatic disease are common when referring to chlamydia
infection. On the other hand, the scaling up of the reported cases of chlamydia infection (incidence rates have more than doubled over the past 10 years) represents a
straightforward attempt of Member States to tackle the problem of STIs by improving the diagnosis of the infection. In Europe, three quarters of all new cases of chlamydia were contracted by young people (particularly women). Furthermore, almost
95% of cases are reported from six Western/Northern Europe countries reflecting
the considerable variation in screening, diagnostic and surveillance programmes
across EU countries [15].
With regard to gonorrhoea, more than 25% of cases are reported among MSM.
Furthermore, almost 40% of the overall incidence occurs in people below 25 years
of age. Main public health concerns on gonorrhoea arose after 2009; indeed, the
European Gonococcal Antimicrobial Surveillance Programme (EuroGASP) reported decreased susceptibility to cefixime. As ceftriaxone, cefixime represents
the recommended therapy for gonorrhoea across Europe; decreased susceptibility
to this orally administered antibiotic may have major health and economic implications in the case of parenterally administered ceftriaxone becomes the only viable
option [25].
As for syphilis, in 2010 the overall incidence rate was around 4.4 per 100,000
people within the EU. Around 83% of all cases were reported among people older
than 25 years of age. The highest incidence occurred in MSM. However, the 2010
incidence of 4.4 represents a huge achievement compared to the 8.4 per 100,000
people, recorded in 2000 [15].

12
Table 2.2 Implementation
steps for control of chlamydia
infections according to the
European Centre for Disease
Prevention and Control [27]

A. Santoro et al.
Level A

Primary prevention: health promotion,

sex education, school programmes and
condom distribution

Level B

Case management: Level A+chlamydia

diagnostic and clinical services, and
patient/partner management services, supported by clear evidence-based guidance

Level C

Opportunistic testing: Level B+testing

with the aim of case finding of asymptomatic cases

Level D

Screening programme: Level C+as it is

difficult to identify asymptomatic cases, a
more systematic screening programme

Level C/D

The evidence for the impact of Level C/D

programmes is limited; therefore, whether
implemented, they need to be evaluated to
guide future policies

HIV discussion has been developed separately, in a dedicated section.

As for the cost-effectiveness of STIs interventions, further investigation is required. However, evidence-based cost-saving interventions include: widespread
condom provision, school education programmes, safe sex training for high-risk
groups, wide choice of contraceptive services and high-quality rapid access to STI
services [26].
According to the crucial burden of chlamydia infection in Europe, we decided to
focus our further discussion around this disease. The economic impact of chlamydia
infection has been deeply investigated; in the UK, the cost of chlamydia complications has been estimated to a minimum of 110million, annually [26]. Each year,
in the USA, direct costs of chlamydia and its complications range between 1 and
3billion.
To tackle the burden of chlamydia in Europe, in 2009, the European Centre for
Disease Control in Stockholm (ECDC) released a guidance to develop an effective
chlamydia national control programme which, as a prerequisite, requires the involvement of national authorities, key stakeholders and policymakers. Implementations steps are reported in Table2.2 [27].
In 2008, the ECDC evaluated in depth the availability of national chlamydia
control programmes across EU Member States. Results of the assessment showed
a wide variability among countries; main findings are reported in Table2.3 [28].

2 Health Trends of Communicable Diseases

13

Table 2.3 Availability of national chlamydia control programmes across EU Member States.
(Source: Review of chlamydia control activities in EU countries. ECDC Technical Report, 2008)
Opportunistic
testing
Case finding+either
guidelines stating
that at least one
specified group
of asymptomatic
people is offered
chlamydia tests or
guidelines include a
list of asymptomatic
people to whom
chlamydia testing
should be offered

Organized
screening
Opportunistic
testing+organised chlamydia
screening
available to a
substantial part
of the population
within the public
health system

Denmark

The Netherlands

Estonia

The UK

No organized
activities
No guidelines
for effective
diagnosis and
management of
diagnosed chlamydia cases

Case
management
Guidelines covering minimum
of diagnostic
tests and
antibiotic treatment, for at
least one group
of health care
professionals

Case finding
Case management+either
guidelines
covering partner notification
or guidelines
including offer
of chlamydia
testing for
sexual contacts
of people with
chlamydia

Bulgaria

Austria

Belgium

Finland

Czech Republic France

Greece

Germany

Hungary

Latvia

Ireland

Italy

Sweden

Luxembourg

Lithuania

Malta

Portugal

Romania

Slovenia

Spain

At the EU level, the reduction of countries reporting no organised activity should be set as the
minimal target [27, 29]

Influenza
Seasonal influenza viruses are classified into three groups according to the specific variety of the haemagglutinin (or H protein) and the neuraminidase (or N
protein). Specific combinations of these two proteins label A, B and C seasonal
influenza viruses; furthermore, type A influenza viruses are further divided into
subtypes [30].
In temperate climates, seasonal influenza tends to spread in winter months, following a person-to-person transmission pattern. The continuous evolution of seasonal influenza viruses explains why people can contract the disease multiple times,
throughout life [30].
The currently circulating seasonal influenza A virus subtypes are the influenza
A(H1N1) and A(H3N2). Influenza A(H1N1) virus is the same virus that caused
pandemic influenza in 2009, which is currently circulating seasonally. In addition,
there are two type B viruses that are circulating as seasonal influenza viruses, as

14

A. Santoro et al.

well. A and B influenza viruses are included in the seasonal influenza vaccine,
which represents the most effective way to prevent the disease and its potential
severe outcomes. Influenza C virus is excluded from the vaccine, according to the
lower burden of disease [30].
A pandemic influenza occurs when an influenza virus, which was not previously
circulating among humans and to which most people do not have immunity, emerges and transmits among humans; whether this happens, these viruses may result in
large influenza outbreaks outside seasonal patterns. Pandemic influenza outbreaks
can occur when humans are infected with influenza viruses that are routinely circulating in animals, such as avian influenza virus and swine influenza virus. Indeed,
animal viruses neither easily transmit to humans nor, if it happens, transmit among
them. Occasionally, some animal viruses infect humans but human infections of
zoonotic influenza do not spread far among humans. If such a virus acquires the
capacity to spread easily among people, either through adaptation or through acquisition of certain genes from human viruses, a pandemic could start. Currently, there
are no pandemic viruses circulating in the world [30].
The burden of seasonal influenza varies, globally, in different regions. The 2012
2013 influenza season was characterized by crucial differences, reported below:
Influenza A(H3N2) was the most common virus in North America and in temperate Asia
A(H1N1)pdm09 (pandemic 2009) affected Europe, North Africa and the Middle
East
Influenza type B was reported in North America and Europe, by the end of the
season [31]
With regard to costs of influenza, results of a 2007 study, referring to 2003 data,
highlighted the huge economic brunt of the burden of influenza in the USA, accounting for US$87.1billion across all age groups [32].
As reported above, vaccination is the most effective modality to prevent the occurrence of influenza and of its potential severe outcomes. Two types of influenza
vaccines are available: trivalent inactivated influenza vaccine (TIV) and live attenuated influenza vaccine (LAIV). Both TIV and LAIV contain three strains of
influenza viruses and are administered annually.
The selection of strains to be included in the vaccine is taken according to the
information gathered from the Global Influenza Surveillance Network (GISN), a
partnership which encompasses 5 WHO Collaborating Centres, 136 National Influenza Centres in 106 countries and several laboratories. Apart from the crucial role
of obtaining reliable virus information to update influenza vaccines, other GISN
functions are to:
Monitor the burden of human influenza
Detect and obtain isolates of pandemic potential viruses [33]
The influenza vaccine is made up of strains of influenza A(H3N2) viruses, A(H1N1)
and B. Each year, one or more virus strains might be changed according to results
provided by GISN in order to reflect the most recent circulating influenza A(H3N2),

2 Health Trends of Communicable Diseases

15

A(H1N1) and B viruses. In the large majority of countries, TIV remains the cornerstone of influenza vaccination [33].
Although influenza vaccination rates are scaling up globally, particularly in Central/Eastern Europe and in Latin America, no country has fully implemented WHO
vaccine recommendations, so far. Consistent findings also encompass industrialized countries where significant proportions of the groups at risk of complications
from influenza are not vaccinated. In high-risk groups, influenza is a serious public
health problem, potentially leading to severe illness and death. For these reasons,
WHO specifically recommends vaccination to the following categories:
Pregnant women (even to extend protection to infants under 6 months who are
not eligible for immunization)
Children 659 months of age (particularly in children 623 months)
Elderly individuals who are above a nationally defined age limit (often >65
years)
Persons>6 months with specific chronic diseases (pulmonary, cardiovascular,
metabolic, renal dysfunction, immunosuppression as AIDS and transplant recipients)
Health care workers (even to protect vulnerable patients) [34]
Hence, policymakers and stakeholders should address their efforts towards the implementation and the strengthening of influenza vaccination programmes, taking
into account the potential health impacts of influenza in high-risk groups as well as
its huge economic brunt.

Malaria
Malaria is caused by the parasite Plasmodium, which is borne by mosquitoes of the
species Anopheles. In the human body, the parasites multiply in the liver, and then
infect red blood cells [35].
Symptoms of malaria include fever, headache and vomiting, and usually appear
between 10 and 15 days after contact with the mosquito. If not treated, malaria is
potentially lethal as it can disrupt the blood supply to vital organs. In many parts of
the world, the parasites have developed resistance to a number of malaria medicines
[36].
It is estimated that in 2010 alone, malaria caused 216million clinical episodes
and 655,000 deaths. An estimated 91% of deaths in 2010 were in the African Region, followed by 6% in the South-East Asian Region and 3% in the Eastern Mediterranean Region (3%). About 86% of deaths globally were in children. A total
of 3.3billion people (half the worlds population) live in areas at risk of malaria
transmission in 106 countries and territories [35, 36].
Malaria imposes substantial costs to both individuals and governments. Direct
costs for malaria have been estimated to be at least US$12billion per year worldwide [35, 36].

16

A. Santoro et al.

Key interventions to control malaria include: prompt and effective treatment

with artemisinin-based combination therapies, use of insecticidal nets by people at
risk, and indoor residual spraying with insecticide to control the vector mosquitoes.
Success in malaria control, however, requires strong, sustained political and budgetary commitment at national and international levels.
Zambia and Ethiopia, which achieved substantial progress in malaria control, are
examples of strong political support behind malaria control programmes. The Zambian government has supported the establishment and implementation of a 6-year
strategy and has taken the lead on coordinating all partners. The Ethiopian government has established joint steering committees at the national and regional levels to
strengthen accountability by removing taxes and tariffs on malaria preventive tools
and by promoting demand through communication efforts [36].

Diarrhoeal Diseases
Diarrhoea is defined as the passage of three or more loose or liquid stools per day
(or more frequent passage than is normal for the individual). It is generally the
symptom of an infection in the intestinal tract, which can be caused by several of
bacterial, viral and parasitic organisms. Infection is spread through contaminated
food or drinking water, or from person to person as a result of poor hygiene [37].
Globally, most cases in children are caused by rotavirus. In adults, norovirus and
Campylobacter are the most common. Less common causes include other bacteria
(or their toxins) and parasites. Transmission can occur due to consumption of improperly prepared foods or contaminated water or via close contact with individuals
who are infectious [38].
Diarrhoeal diseases amount to an estimated 4.1% of the total disability-adjusted
life years (DALY) global burden of disease, and are responsible for 1.8 million
deaths every year. An estimated 88% of that burden is attributable to unsafe supply
of water, sanitation and hygiene [39]. Children in the developing world are the most
affected by diarrhoeal disease: It is estimated that diarrhoeal diseases account for
one in nine child deaths worldwide, making diarrhoea the second leading cause of
death among children under the age of 5 after pneumonia [40].
Two recent advances in managing diarrhoeal disease(1) oral rehydration salts
(ORS) containing lower concentrations of glucose and salt, and zinc supplementation as part of the treatment; and (2) rotavirus vaccinecan drastically reduce the
number of child deaths. These new methods, used in addition to prevention and
treatment with appropriate fluids, breastfeeding, continued feeding and selective
use of antibiotics, have been shown to reduce the duration and severity of diarrhoeal
episodes and lower their incidence [41].
Diarrhoea prevention focused on safe water and improved hygiene and sanitation,
however, remains the most successful and cost-effective intervention in diarrhoeal
diseases control: every US$1 invested yields an average return of US$25.50 [42].

2 Health Trends of Communicable Diseases

17

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Jan 2015

Chapter 3

Global Burden and Health Trends

of Non-Communicable Diseases
Silvio Capizzi, Chiara de Waure and Stefania Boccia

The non-communicable disease (NCD) epidemic, which is expected to increase in

the future, has a serious negative impact on development in human, social and economic realms. NCDs reduce productivity and contribute to poverty. NCDs already
pose a substantial economic burden: The macroeconomic simulations suggest a cumulative output loss of US$47 trillion over the next two decades. Cardiovascular
disease is the dominant contributor to the global economic burden of NCDs.
The majority of NCDs can be prevented through population-wide and individual
interventions that reduce major risk factors. Best practices related to reducing risks
and preventing diseases exist in many countries with different income levels. Interventions that combine a range of evidence-based approaches show better results.

Definition of NCDs
NCDs are defined as diseases of long duration and, generally, slow progression, and
they are the major cause of adult mortality and morbidity worldwide [1]. Four main
diseases are generally considered to be dominant in NCDs mortality and morbidity: cardiovascular diseases, diabetes, cancer and chronic respiratory diseases (see
Table3.1) [2].

[Link]() [Link] Waure [Link]

Institute of Public Health, Section of Hygiene, Universit Cattolica del Sacro Cuore,
L. go F. Vito 1, 00168 Rome, Italy
e-mail: silviocapizzi@[Link]
[Link] Waure
e-mail: [Link]@[Link]
[Link]
e-mail: sboccia@[Link]
Springer International Publishing Switzerland 2015
S. Boccia et al. (eds.), A Systematic Review of Key Issues in Public Health,
DOI 10.1007/978-3-319-13620-2_3

19

20

S. Capizzi et al.

Table3.1 A snapshot of the four major NCDs [2]

Cardiovascular disease
(CVD)

A group of diseases involving the heart, blood vessels or the sequelae of poor
blood supply due to a diseased vascular supply. Over 82% of CVD mortality
burden is caused by ischaemic or coronary heart disease (IHD), stroke (both
haemorrhagic and ischaemic), hypertensive heart disease or congestive heart
failure (CHF). Over the past decade, CVD has become the single largest cause
of death worldwide, representing nearly 30% of all deaths and about 50% of
NCDs deaths. In 2008, CVD caused an estimated 17 million deaths and led
to 151 million disability adjusted life years (DALYs) (representing 10% of
all DALYs in that year). Behavioural risk factors such as physical inactivity,
tobacco use and unhealthy diet explain nearly 80% of the CVD burden

Cancer

A rapid growth and division of abnormal cells in a part of the body. These
cells outlive normal cells and have the ability to metastasize, or invade parts
of the body and spread to other organs. There are more than 100 types of
cancers, and different risk factors contribute to the development of cancers in
different sites. Cancer is the second largest cause of death worldwide, representing about 13% of all deaths (7.6 million). Recent literature estimated the
number of new cancer cases in 2009 alone at 12.9 million, and this number is
projected to rise to nearly 17 million by 2020

Diabetes

A metabolic disorder in which the body is unable to appropriately regulate the

level of sugar, specifically glucose, in the blood, either by poor sensitivity to
the protein insulin or due to an inadequate production of insulin by the pancreas. Type 2 diabetes accounts for 9095% of all cases. Diabetes itself is not
a high-mortality condition (1.3 million deaths globally), but it is a major risk
factor for other causes of death and has a high attributable disability. Diabetes
is also a major risk factor for CVD, kidney disease and blindness

Chronic
respiratory
diseases

Chronic diseases of the airways and other structures of the lung. Some of the
most common are asthma, chronic obstructive pulmonary disease (COPD),
respiratory allergies, occupational lung diseases and pulmonary hypertension, which together account for 7% of all deaths worldwide (4.2 million).
COPD refers to a group of progressive lung diseases that make it difficult
to breatheincluding chronic bronchitis and emphysema (assessed by
pulmonary function and x-ray evidence). Affecting more than 210 million
people worldwide, COPD accounts for 38% of total deaths in high-income
countries and 49% of total deaths in low- and middle-income countries

Global Burden and Health Trends: Mortality

and Morbidity
NCDs are the leading global cause of death worldwide, being responsible for more
deaths than all other causes combined. In fact, more than 60% of all deaths worldwide currently stem from NCDs [3].
In 2008, the leading causes of all NCD deaths (36million) were:

CVD (17 million, or 48% of NCD deaths);

Cancer (7.6 million, or 21% of NCD deaths);
Respiratory diseases (4.2 million, or 12% of NCD deaths)
Diabetes (1.3 million, 4% of NCD deaths) [4].

3 Global Burden and Health Trends of Non-Communicable Diseases

21

Fig. 3.1 Total deaths by broad cause group, by WHO Region, World Bank income group and sex
(2008). (Reproduced from WHO 2011) [4]

Population growth and improved longevity are leading to an increased number

and proportion of elderly. Because of populations ageing, annual NCD deaths are
projected to rise to 52 million in 2030. Contrary to popular opinion, nearly 80%
of NCD deaths occur in low- and middle-income countries [4], up sharply from
just under 40% in 1990 [5]. NCDs are the most frequent causes of death in most
countries in the Americas, Eastern Mediterranean, Europe, South-East Asia and the
Western Pacific. In the African Region, there are still more deaths from infectious
diseases than NCDs (Fig.3.1) [4]. Even there, however, NCDs are rising rapidly
and are projected to exceed communicable, maternal, perinatal and nutritional diseases as the most common causes of death by 2030 [6].
Low- and lower-middle-income countries have the highest proportion of deaths
from NCDs under 60 years. Premature deaths under 60 years for high-income countries were 13 and 25% for upper-middle-income countries. In lower-middle-income
countries, the proportion of premature NCD deaths under 60 years rose to 28%,
more than double the proportion in high-income countries. In low-income countries, the proportion of premature NCD deaths under 60 years is 41%, three times
the proportion in high-income countries [7].
With respect to trends, from 1990 to 2010, an important decrease in agestandardized death rates has been observed for major vascular diseases, especially heart disease and strokes, as well as chronic respiratory disease and cancer
(respectively, 21.2, 41.9 and 13.8%). Notwithstanding, an increase in absolute
number of deaths from CVD and cancer has been shown. Similarly, the number

22

S. Capizzi et al.

Fig. 3.2 Shifts in leading causes of DALYs from 1990 to 2010. (Reproduced from Institute for
Health Metrics and Evaluation 2011)[9]

of deaths due to diabetes has increased as well as age-standardized mortality rates

[8]. Generally speaking, death rates from NCDs decreased from 645.9 to 520.4 per
100,000 over 19902010 [9].
In addition to information about NCD-related deaths, morbidity data are important for the management of health care systems and for planning and evaluation of
health service delivery.
However, reliable data on NCD morbidity are unavailable in many countries. It
is anyway well known that ageing, increase in NCDs, shifts toward disabling causes
and away from fatal causes and changes in risk factors have led to a shift in the
leading causes of DALYs worldwide [9] (Fig.3.2).
Overall, NCDs account for more than 50% of DALYs in most counties. This percentage rises to over 80% in Australia, Japan and the richest countries of Western
Europe and North America worldwide [9].

3 Global Burden and Health Trends of Non-Communicable Diseases

23

Fig. 3.3 Estimated annual number of new cases and deaths for the ten most common cancers, by
World Bank income groups and sex, 2008. (Reproduced from WHO 2011) [4]

The most comprehensive and available morbidity data relate to cancer and
diabetes.
Cancer is predicted to be an increasingly important cause of morbidity in the
next few decades in all regions of the world. The estimated incidence of 12.7million new cancer cases in 2008 [10] will rise to 21.4 million by 2030, with nearly
two thirds of all cancer occurring in low- and middle-income countries. This estimated percentage increase in cancer incidence by 2030 (compared with 2008) will
be greater in low- (82%) and lower-middle-income countries (70%) compared with
the upper-middle- (58%) and high-income countries (40%). Without any changes
in underlying risk factors and on the base of anticipated demographic changes only,
between 10 and 11 million cancers will be diagnosed annually in 2030 in low- and
lower-middle-income countries [11].
Within upper-middle-income and high-income countries, prostate and breast
cancers are the most common in males and females, respectively, with lung and
colorectal cancers representing the next most common types in both sexes. Within
low-income countries, lung and breast cancers remain among the most common
but cancers with an infection-related aetiologycervix, stomach and liver are also
frequent. Within the lower-middle-income countries, the three most common types
of cancer are lung, stomach and liver cancers in males, and breast, cervix and lung
cancer in females (Fig.3.3) [4].

24

S. Capizzi et al.

The global prevalence of diabetes was estimated to be 10% in adults aged 25+
years. The prevalence of diabetes was highest in the Eastern Mediterranean Region
and Americas (11% for both sexes) and lowest in the WHO European and Western
Pacific Regions (9% for both sexes).
Moreover, the estimated prevalence of diabetes was relatively consistent
across countries with low-income ones showing the lowest prevalence (8% for
both sexes), and the upper-middle-income countries showing the highest (10%
for both sexes) [4]. People with diabetes have a twofold increase in the risk of
stroke [12]. Diabetes is the leading cause of renal failure in many populations in
both developed and developing countries [4]. Lower-limb amputations are at least
10 times more common in people with diabetes than in nondiabetic individuals in
developed countries, and more than half of all nontraumatic lower limb amputations are due to diabetes [13].
Furthermore, diabetes is one of the leading causes of visual impairment and
blindness in developed countries [14]. People with diabetes require at least two
to three times health care resources compared to people who are not affected [15].

Risk Factors
With respect to etiopathogenesis, NCDs are due to a complex of interacting factors
and recognize several risk factors.

Behavioural Risk Factors

A large percentage of NCDs are preventable through the reduction of five main
behavioural risk factors:
1. Tobacco: Almost six million people die from tobacco each year, from both direct
use and second-hand smoke [16]. By 2020, this number will increase to 7.5 million, accounting for 10% of all deaths [17]. Smoking is estimated to cause about
71% of lung cancer, 42% of chronic respiratory disease and nearly 10% of CVD
[18]. Smoking prevalence is generally higher in upper-middle-income countries
than lower-middle-income ones [4].
2. Physical inactivity: Approximately 3.2 million people die each year due to
physical inactivity [19]. People who are insufficiently physically active have a
2030% increased risk of all-cause mortality. Regular physical activity reduces
the risk of CVD, including high blood pressure, diabetes, breast and colon cancer
and depression [20]. Insufficient physical activity is higher in high-income countries, but very high levels are now also seen in some middle-income countries
especially in women [4].
3. Alcohol: Approximately 2.3 million die each year from the harmful use of alcohol. More than half of these deaths occur from NCDs including cancers, CVD

3 Global Burden and Health Trends of Non-Communicable Diseases

25

and liver cirrhosis [21]. Adult per capita consumption is higher in high-income
countries [4].
4. Unhealthy diet: approximately 16.0 million (1%) DALYs (a measure of the
potential life lost due to premature mortality and of years of productive life
lost due to disability) and 1.7 million (2.8%) of deaths worldwide are attributable to low fruit and vegetable consumption. Adequate consumption of fruit
and vegetables reduces the risk for CVD, stomach cancer and colorectal cancer [22]. Most populations consume much higher levels of salt than recommended by WHO for disease prevention; high salt consumption is an important
determinant of high blood pressure and cardiovascular risk [23, 24]. High consumption of saturated fats and trans-fatty acids is linked to heart disease [25].
Unhealthy diet is rising quickly in lower-resource settings. Available data suggest that fat intake has been rising rapidly in lower-middle-income countries
since the 1980s [4].
5. Infections associated to cancer: At least two million cancer cases per year (18%
of the global cancer burden) are attributable to chronic infections by human papillomavirus, hepatitis B virus, hepatitis C virus and Helicobacter pylori. These
infections are largely preventable or treatable [4].

Metabolic Risk Factors

1. Raised blood pressure: it is a major risk factor for CVD and it is estimated to
cause 7.5 million deaths, about 12.8% of all [22]. The prevalence of raised blood
pressure is similar across all income groups, though it is generally lowest in
high-income populations [4].
2. Overweight and obesity: At least 2.8 million people die each year as a result
of being overweight or obese. Raised body mass index (BMI) increases risks
of heart disease, strokes, diabetes and certain cancers. Once considered a highincome country problem, overweight and obesity are now on the rise in low- and
middle-income countries too, particularly in urban settings. In 2011, more than
40 million children under the age of 5 were overweight (more than 30 million are
living in developing countries and 10 million in developed countries) [26].
3. Raised cholesterol: Raised cholesterol increases the risks of heart disease and
stroke and causes 2.6 million deaths annually. Raised cholesterol is highest in
high-income countries [4].

Social Determinants
There is strong evidence of association between social determinants (especially
education level, household income and access to health care) and NCDs. In fact,
vulnerable and socially disadvantaged people get sicker and die sooner than people

26

S. Capizzi et al.

belonging to a higher social position, especially because they are at greater risk of
being exposed to harmful products, such as tobacco or unhealthy food, and have
limited access to health services.
Moreover, since in poorer countries most health care costs must be paid by patients out of pocket, NCDs creates significant strain on household budgets, particularly for lower-income families. In low-resource settings, health care costs for
CVD, cancers, diabetes or chronic lung diseases can quickly drain household resources, driving families into poverty. Each year, an estimated 100 million people
are pushed into poverty because they have to pay directly for health services [27].

Economic Burden
NCDs have been established as a clear threat not only to human health but also to
the economic growth. Claiming more than 60% of all deaths, these diseases are
currently the worlds main killers. Eighty percent of these deaths now occur in lowand middle-income countries. Half of those who die of NCDs are in the prime of
their productive years, and thus, disability and lives lost are also endangering the
market [2].
Globally, NCDs have reduced the quality and quantity of the labour force and
human capital [28]. In the USA, men with chronic disease worked 6.1% fewer
hours and women worked 3.9% fewer hours [29]. A healthy lifestyle in the US
working-age population reduced health care costs by 49% in adults aged 40 or
older. Instead, obesity increased individual annual health care costs by 36%, smoking by 21% and heavy drinking by 10% [28].
Over the next 20 years, NCDs will cost more than US$47 trillion, representing
75% of global gross domestic product in 2010, and pushing millions of people
below the poverty line [2].
In particular, the global cost of CVD is estimated in 2010 at US$863 billion (an
average per capita of US$125), and it is estimated to rise to US$1044 billion in
2030a 22% increase. Overall, the cost for CVD could be as high as US$20 trillion over the 20-year period (an average per capita of nearly US$3000). Currently,
about US$474 billion (55%) is due to direct health care costs and the remaining
45% to productivity loss from disability or premature death, or time loss from work
because of illness or the need to seek care.
Diabetes costs the global economy nearly US$500 billion in 2010, and that figure is projected to rise to at least US$745 billion in 2030, with developing countries
increasingly taking on a much greater share of the outlays.
The 13.3 million new cases of cancer in 2010 were estimated to cost US$290
billion. Medical costs accounted for the greatest share at US$154 billion (53% of
the total), while non-medical costs and income losses accounted for US$67 billion
and US$69 billion, respectively. The total costs were expected to rise to US$458
billion in the year 2030.

3 Global Burden and Health Trends of Non-Communicable Diseases

27

The global cost of illness for COPD will rise from US$2.1 trillion in 2010 to
US$4.8 trillion in 2030. Approximately half of all global costs for COPD will arise
in developing countries [2].
By contrast, mounting evidence highlights how millions of deaths can be
averted and economic losses reduced by preventive initiatives: population-based
measures for reducing tobacco and harmful alcohol use, as well as unhealthy diet
and physical inactivity, are estimated to cost US$2 billion per year for all lowand middle-income countries, which in fact translates to less than US$0.40 per
person [2].

Reducing Risks and Preventing Disease: PopulationWide and Individual Interventions Effectiveness and
Cost-Effectiveness
Interventions to prevent NCDs on a population-wide basis are not only feasible but
also cost-effective [30]. Moreover, low-cost solutions can work anywhere to reduce
the major risk factors for NCDs.
While many interventions may be cost-effective, some are considered best
buysactions that should be undertaken immediately to produce accelerated results in terms of lives saved, diseases prevented and heavy costs avoided [4].
Best buys include:

Protecting people from tobacco smoke and banning smoking in public places;
Warning about the dangers of tobacco use
Enforcing bans on tobacco advertising, promotion and sponsorship
Raising taxes on tobacco
Restricting access to retailed alcohol
Enforcing bans on alcohol advertising
Raising taxes on alcohol
Reduce salt intake and salt content of food
Replacing transfat in food with polyunsaturated fat
Promoting public awareness about diet and physical activity

In addition to best buys, there are many other cost-effective and low-cost population-wide interventions that can reduce risk factors for NCDs [4]. These include:
Nicotine dependence treatment
Promoting adequate breastfeeding and complementary feeding
Enforcing drink-driving laws
Restrictions on marketing of foods and beverages high in salt, fats and sugar,
especially to children
Food taxes and subsidies to promote healthy diets

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S. Capizzi et al.

Also, there is strong evidence for the following interventions:

Healthy nutrition environments in schools

Nutrition information and counselling in health care
National physical activity guidelines
School-based physical activity programmes for children
Workplace programmes for physical activity and healthy diets
Community programmes for physical activity and healthy diets
Designing workplace and environmental spaces in order to promote physical
activity

There are also population-wide interventions that focus on cancer prevention. Vaccination against hepatitis B, a major cause of liver cancer, is a best buy. Vaccination against human papillomavirus (HPV), the main cause of cervical cancer, is
also recommended. Protection against environmental or occupational risk factors
for cancer, such as aflatoxin, asbestos and contaminants in drinking water, can be
included in effective prevention strategies. Screening for breast and cervical cancer
can be effective in reducing the cancer burden [4].
Population-wide interventions for NCDs prevention and control can be complemented by efforts to reduce the burden of NCDs on individuals and families. In fact,
like population-wide interventions, there are also best buys in individual health care
interventions:
Counselling and multidrug therapy, including glycaemic control for diabetes
for people 30 years old with a 10-year risk of fatal or nonfatal cardiovascular
events 30%
Aspirin therapy for acute myocardial infarction
Screening for cervical cancer, once, at age 40, followed by removal of any discovered cancerous lesion
Early case finding for breast cancer through biennial mammographic screening
(5070 years) and treatment of all stages
Early detection of colorectal and oral cancer
Treatment of persistent asthma with inhaled corticosteroids and beta-2 agonists
Financing and strengthening health systems to deliver cost-effective individual
interventions through a primary health care approach is a pragmatic first step to
achieve the long-term vision of universal care coverage [4].

Identification of the Best Practice

Best practices related to reducing risks and preventing diseases exist in many countries with different income levels.
For example, declines in tobacco use prevalence are apparent in high-income
countries that conduct regular population-based surveys of tobacco use (e.g.
Australia, Canada, Finland, the Netherlands and the UK) [4].

3 Global Burden and Health Trends of Non-Communicable Diseases

29

Moreover, there are some low- and middle-income countries that have also a
documented decline:
Turkey recently became one of the 17 smoke-free countries in the world. It increased tobacco taxes by 77%, which led to a 62% price increase on cigarettes.
Turkey also adopted and implemented comprehensive tobacco control measures,
including pictorial health warnings on tobacco packaging, a comprehensive ban
on tobacco advertising, promotion and sponsorship in all media, as well as a
comprehensive smoke-free law for all public and work places.
Egypt increased taxes by 87% for cigarettes and 100% for loose tobacco. This
will lead to an estimated increase of 44% in average retail prices and a 21%
reduction in cigarette consumption.
Ukraine elevated taxes by 127% on filtered cigarettes, leading to a 73% increase
in retail prices between February 2009 and May 2010 [4, 31, 32].
As regards the promotion of healthy diets, the UK salt reduction programme has involved working with industry to reduce levels of salt in food, raise consumer awareness and improve food labelling. The average intake was 9.5g/day in 20002001,
considerably above the recommended national level of no more than 6g/day for
adults. Voluntary salt reduction targets were set, and industry made public commitments to reduce the amount of salt in food products.
Public awareness campaigns about health issues, recommended salt intakes and
consumer advice took place between 2004 and 2010. Levels of salt in foods have
been reduced in some products by up to 55%, with significant reductions in those
food categories contributing most salt to the diet. Consumer awareness of the 6-g/
day maximum recommended intake increased tenfold, and the number of people
who say they make a special effort to reduce their intake doubled. By 2008, average
intake declined from 9.0 to 8.6g/day, which is estimated to prevent more than 6,000
premature deaths and save 1.5 billion every year, dramatically more than the cost
of running the salt reduction programme [23, 33].
Another successful community-based programmethe North Karelia Project
was launched in 1972 in Finland. It addressed diet and smoking through a model
which relied on media, health services and community activities in partnership with
various organizations and environmental and policy actions [34]. Before the launch
of the project, almost all people used butter on their bread and in cooking; afterwards, less than 5% used butter and 60% used mainly vegetable oil in cooking.
As far as smoking is concerned, prevalence of smokers in men declined from more
than 50% in the early 1970s to around 20% in 2006. Furthermore, the overall average level of blood cholesterol dropped by over 20%. This ended up in an 85-%
reduction of mortality from 19691971 to 2006 with a gain of 7 and 6 years in life
expectancy for men and women, respectively [35].
Several countries have explored fiscal measures such as increased taxation on
foods that should be consumed in lower quantities and decreased taxation, price
subsidies or production incentives for foods that are encouraged. A longitudinal
study of food prices and consumption in China found that increases in the prices
of unhealthy foods were associated with decreased consumption of those foods

30

S. Capizzi et al.

[36]. In the USA, programmes to reduce the price of healthy foods led to a 78%
increase in their consumption [37]. Modelling studies suggest that a combination
of tax reduction on healthy foods and tax increases on unhealthy foods may result
in a stimulation of the consumption of healthy food, particularly in lower-income
populations [38].

Key Elements for Decision Makers

NCDs are the biggest global killers today. More than 60% of all deaths are
caused by NCDs.
Nearly 80% of these deaths occur in low- and middle-income countries, where
the highest proportion of deaths under the age of 60 from NCDs occur.
The prevalence of NCDs, and the resulting number of related deaths, is expected
to increase substantially in the future, particularly in low- and middle-income
countries.
The NCD epidemic has a serious negative impact on development in human, social and economic realms. NCDs reduce productivity and contribute to poverty.
NCDs already pose a substantial economic burden: The macroeconomic simulations suggest a cumulative output loss of US$ 47 trillion over the next two
decades.
Cardiovascular disease is the dominant contributor to the global economic burden of NCDs.
The majority of NCDs can be averted through population-wide and individual
interventions that reduce major risk factors. Interventions that combine a range
of evidence-based approaches show better results.

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13. Icks A etal (2009) Incidence of lower-limb amputations in the diabetic compared to the nondiabetic population. Findings from nationwide insurance data, Germany, 2005-2007. Exp
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18. Line H etal (2007) Tobacco smoke, indoor air pollution and tuberculosis: a systematic review
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[Link]. Accessed 04 April 2014

Chapter 4

Cardiovascular Disease (CVD)

Elvira DAndrea, Iveta Nagyova and Paolo Villari

Introduction
Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The majority of deaths from CVD (almost 80%) are due to coronary heart disease (CHD; e.g., heart attack) and cerebrovascular disease (e.g., stroke) [1]. These
two types of CVD share a common underlying pathological process of the blood
vessels known as atherosclerosis. There is strong scientific evidence that behavioral
(e.g., tobacco use; physical inactivity; harmful use of alcohol; unhealthy dietrich
in salt, fat, and calories) and metabolic (e.g., hypertension, diabetes, dyslipidemia,
overweight and obesity) risk factors play a key role in the etiology of atherosclerosis [2].
CVD is often thought to be a problem of industrialized and wealthy (high-income) nations, but it also has an important impact on developing (low- and middleincome) countries, where they account for over two thirds of deaths. In fact, over
the past two decades, deaths from CVD have been declining in high-income countries, while they have increased in low- and middle-income countries [1, 2].
When a countrys economy and health system develops, it undergoes a phenomenon called epidemiological transition, referring to the changes in the predominant
types of disease and mortality burdening a population. Typically, there is a shift
from infectious to chronic diseases [3]. This transition is caused by improvements

[Link]() [Link]
Department of Public Health and Infectious Diseases, Sapienza University of Rome, ple Aldo
Moro 5, 00185 Rome, Italy
e-mail: [Link]@[Link]
[Link]
e-mail: [Link]@[Link]
[Link]
Department of Public Health, PJ Safarik University, Tr SNP 1, 04011 Kosice, Slovakia
e-mail: [Link]@[Link]
Springer International Publishing Switzerland 2015
S. Boccia et al. (eds.), A Systematic Review of Key Issues in Public Health,
DOI 10.1007/978-3-319-13620-2_4

33

34

E. DAndrea et al.

in health care, leading to a decrease in infant mortality rate; by ageing of the population, with a corresponding increase in rates of chronic diseases that affect older
people; and by public health interventions such as vaccinations and the provision
of clean water and sanitation, which reduce the incidence of infectious diseases.
As life expectancy increases, populations face new risks such as smoking and
alcohol abuse, physical inactivity, overweight and obesity, etc. The impact of these
risks varies at different levels of socioeconomic development, and the major causes
of death and disability shift to the chronic and noncommunicable diseases (NCDs).
Increasing exposure to these behavioral risks is not inevitable, and scientific
evidence suggests that two thirds of premature deaths due to chronic diseases, including CVD, can be prevented by primary prevention, and another one third by
improving health systems to respond more effectively and equitably to health care
needs [3]. Therefore, the implementation of preventive interventions through population-wide measures and individual health care interventions can reduce and potentially eliminate the health and socioeconomic burden caused by these diseases and
their risk factors. These interventions, which are evidence based and cost-effective,
are known as best buys, and they provide workable solutions and represent the
best economic investment both in high-income and in low- and middle-income nations [4, 5]. Cost-effective prevention strategies and interventions are needed if the
growing burden of CVD is to be arrested; this is one of the major health challenges
to be overcome in the near future in both developed and developing countries.
This chapter describes the current burden, CVD trends over time, and strategies for prevention of CVD globally, with a particular focus on Europe. It lays out
the major risk factors associated with CHD and stroke throughout the course of
life. It aims to review and discuss the scientific evidence on the effectiveness and
cost-effectiveness of primary and secondary prevention policies. Finally, a reasoned
analysis has been performed to identify best practices for CVD prevention strategies and to provide guidance on what drivers play a key role in the decision-making
process required to actually implement and improve these prevention strategies.
To provide an overview of the current literature, we conducted a systematic
search of current epidemiological (descriptive and analytic), public health (primary and secondary prevention strategies), and health economic literature on CVD,
as well as documentation on regulatory and policy issues. For the descriptive and
analytical epidemiology of CVD and for primary and secondary prevention strategies, institutional websites of authoritative scientific societies, international organizations, and referenced universities were surveyed and the relevant reports,
textbooks, and position papers on the topic were collected. For the effectiveness
and cost-effectiveness of primary and secondary prevention policies, a search was
performed on several electronic databases (Cochrane Database, PubMedMedline,
NHS Economic Evaluation Database, and SCOPUS), using keywords related to
CVD and cost-effectiveness of the primary and secondary CVD policies to retrieve
reviews and systematic reviews. In addition, key references from relevant articles
were selected.

4 Cardiovascular Disease (CVD)

35

Cardiovascular Disease: Definitions and Classifications

CVD encompasses a group of medical conditions caused by disorders of the heart
and blood vessels. There are different types of CVD that can be classified into two
groups based on whether or not the disease results from atherosclerosis. The first
group, which involves atherosclerosis, comprises CHD, i.e., disease of the blood
vessels supplying the heart muscle (e.g., heart attack); cerebrovascular disease, i.e.,
disease of the blood vessels supplying the brain (e.g., stroke); diseases of the aorta
and arteries, including hypertension; and peripheral vascular disease (PVD), i.e.,
disease of the blood vessels supplying the arms and legs. The second group includes congenital heart disease, i.e., malformations of heart structure existing at
birth; rheumatic heart disease, i.e., damage to the heart muscle and heart valves
from rheumatic fever caused by streptococcal bacteria; deep vein thrombosis and
pulmonary embolism, i.e., blood clots that occur in the leg veins and can dislodge
and move to the heart and lungs; and cardiomyopathies and arrhythmias [4, 6].
Among all types of CVD, heart attack and stroke are responsible for almost 80%
of deaths [1, 4]. These disorders are usually acute events and are mainly caused by a
blockage that prevents blood from flowing to the heart or brain. The most common
reason for such a blockage is a buildup of fatty deposits on the inner walls of the
blood vessels that supply the heart or the brain; this process is known as atherosclerosis [4].
Atherosclerosis is a multifactorial, multistep pathological process that involves
chronic inflammation in medium- and large-sized blood vessels. When blood vessel
endothelium is exposed to raised levels of low-density lipoprotein (LDL) cholesterol and other substances, it becomes permeable to cells of the immune system, such
as monocytes and lymphocytes. The migration of these cells into the deep layers of
the endothelium causes the breakdown of various substances and the attraction of
LDL cholesterol particles to the site. These LDL particles are engulfed by monocytes, which then differentiate into macrophages (foam cells). From deeper layers
of the vessel lining (the media), smooth muscle cells migrate to the site and combine
with collagen fibers to form a fibrous cap. At the same time, the macrophages die,
so that a necrotic core develops under the fibrous cap. These lesions, known as atheromatous plaques, enlarge as cells and lipids accumulate in them, and they begin
to protrude into the vessel lumen. Later, the fibrous cap thins and a fissure on the
endothelial surface of the plaque occurs. With the rupture of the plaque, lipid fragments and cellular debris are released into the vessel lumen. These particles are exposed to thrombogenic agents on the endothelial surface, resulting in the formation
of a thrombus, or blood clot. If the thrombus is large enough to block circulation
of coronary or cerebral blood vessels, this results in a heart attack or stroke [4, 6].
Atherosclerosis with thrombus formation has been recognized as a major cause of
cardiovascular death. It begins early in childhood and progresses in adult life when
it can potentially manifest as CHD, stroke, and/or PVD [4, 6].
CHD, also called coronary artery disease or ischemic heart disease, is responsible for over 40% of the global burden due to CVD [1]. Disease develops when

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an atherosclerotic plaque builds up in the arteries that supply the heart, i.e., the
coronary arteries. Through these arteries, the heart muscle (myocardium) acquires
the oxygen and other nutrients it needs to continue pumping blood. When the blood
flow to the heart is decreased, different symptoms start to appear. These usually
occur during exercise or activity because the heart muscles increased demand for
nutrients and oxygen is not being met by the blocked coronary blood vessel. The
most common symptom is chest pain (angina pectoris) due to ischemia. Other common symptoms are shortness of breath on exertion, jaw pain, back pain, or arm pain
(especially on the left side, either during exertion or at rest), palpitations, dizziness,
light-headedness or fainting, weakness on exertion or at rest, and irregular heartbeat. The most devastating sign of CHD is abrupt, unexpected cardiac arrest, while
the opposite extreme is represented by the condition known as silent ischemia, in
which no symptoms occur, even though an electrocardiogram (ECG, or heart tracing) and/or other tests show evidence of ischemia [4, 6].
Stroke is responsible for over 30% of the global burden due to CVD; it is caused
by the interruption of the blood supply to the brain because a blood vessel bursts
(hemorrhagic stroke) or is blocked by a clot (ischemic stroke) [1]. In the first case,
the cause is usually a rupture of a blood vessel as a result of an aneurysm or damage due to uncontrolled high blood pressure or atherosclerosis. In the second case,
thrombus formation in an atherosclerotic cerebral blood vessel or traveling blood
clots trapped in a cerebral blood vessel can block the blood flow to an area of the
brain. These events cut off the supply of oxygen and nutrients, causing damage to
the brain tissue. The symptoms depend on what part of the brain and how much
of the brain tissue is affected. The most common are weakness in the arm or leg
(or both) on the same side of the body, ranging from total paralysis to a very mild
weakness; complete numbness or a pins-and-needles feeling that may be present on
one side of the body or part of one side of the body; weakness in the muscles of the
face, potentially associated with speech difficulties; coordination problems, leading
to difficulty in walking or picking up objects; dizziness; vision problems; sudden
severe headache; and loss of consciousness [4, 6].

Current Burden of Cardiovascular Disease

The evaluation and analysis of CVD burden and trends worldwide cannot be tackled without addressing the most important key drivers of rapid transition in global
health [7]. The first pattern responsible for the growth in CVD burden is the demographic increase in both size and average age of the population. Clearly, an ageing
population must contribute to the increment in these diseases, given that the first
CVD event occurs at an average age of greater than 50 years. The second pattern of
transition is the change in causes of death. From 1990 to 2010, the combined mortality and disability rates of all communicable, maternal, neonatal, and nutritional
diseases decreased, due principally to better maternal education, prenatal care, and
early-childhood interventions; improvements in preventive and medical care, where
the use of new technologies has had a significant impact; improvements in socio-

4 Cardiovascular Disease (CVD)

37

economic status (SES); and increasing health expenditure, including greater provision for public health and medical care. At the same time, the burden of NCDs
increased significantly, with only modest decreases in rates of NCDs and risk factor
exposure in developed countries, and increasing rates of NCDs in the developing
countries. The third element is the change in causes of disability, shifting from premature death to years lived with disability in the context of a significant increase in
NCDs [2, 7].

Prevalence and Incidence

Information on the magnitude of CVD in high-income countries is available from
three large longitudinal studies that collect multidisciplinary data from a representative sample of European and American individuals aged 50 and older [8, 9, 10].
Thus, according to the Health Retirement Survey (HRS) in the USA, almost one in
three adults have one or more types of CVD [11, 12]. By contrast, the data of Survey
of Health, Ageing and Retirement in Europe (SHARE), obtained from 11 European
countries, and English Longitudinal Study of Aging (ELSA) show that disease rates
(specifically heart disease, diabetes, and stroke) across these populations are lower
(almost one in five) [11, 13, 14].
Among adults with one or more forms of CVD, the most prevalent conditions
are, in decreasing order, hypertension, CHD, stroke, heart failure, and congenital
heart defects. Although advancing age is the most powerful risk factor for CVD, in
high-income countries, particularly in the USA and Europe, many adults with wellestablished CVD are younger than 65. Of particular concern are men and women
aged 5564: In this age-specific group, 52% of men and 56.5% of women live with
one or more forms of CVD [9, 11].
Children and young adults also represent an important age group. Although the
overall incidence is low, sudden cardiac death, due to congenital heart defects, accounts for one in five unexpected sudden deaths among children aged 113 and for
one in three among those aged 1421 [11]. Both congenital heart disease and acquired heart disease affect children and are particularly burdensome for children in
low- and middle-income countries. Many of these children die prematurely because
of late diagnosis and/or lack of access to appropriate treatment. Those who survive
may face a lifetime of disability caused by a disease that is not well managed. In
low- and middle-income countries, the problem of nutritional insufficiencies among
infants and children, combined with greater access to nutrition-poor food, has been
found to increase the risk of CVD later in life [1, 15].

Mortality
In 2008, the World Health Organization (WHO) reported that, with the exception
of the African Region, NCDs mortality had surpassed the sum of the death rates of
all communicable, maternal, neonatal, and nutritional diseases. In Europe, deaths of

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men from NCDs are 13 times higher than those of all other causes combined, while
in the Western Pacific Region, they are estimated to be eight times higher [2, 4].
CVD causes 30% of all deaths worldwide and almost half of deaths due to
NCDs. The global distribution of age-adjusted CVD mortality is uneven and more
than 80% of these deaths occurred in low- and middle-income countries [1, 4]. The
lowest mortality rates are now recorded in high-income countries and in parts of
Latin America, whereas the highest rates are in Eastern Europe and in a number of
low- and middle-income countries. Overall, age-adjusted CVD death rates are higher in most low- and middle-income countries than in developed countries [1, 4, 16].
CHD and stroke together are the first and third leading causes of death in developed
and developing countries, respectively. In fact, excluding deaths from cancer, these
two conditions were responsible for more deaths in 2008 than all remaining causes
among the ten leading causes of death combined (including chronic diseases of the
lungs, accidents, diabetes, influenza, and pneumonia) [1, 4, 16].
In Europe, CVD causes over four million deaths per year (52% of deaths in
women and 42% of deaths in men), and they are the main cause of death in women
in all European countries. Over a third of deaths are caused by CHD (1.8 million
deaths each year) and just over a quarter are from stroke (almost 1.1 million deaths
each year). Death rates from CHD and stroke are generally higher in Central and
Eastern Europe than in Northern, Southern and Western Europe. CVD mortality is
now falling in most European countries, including Central and Eastern European
countries, which saw large increases until the beginning of the twenty-first century
[16, 17].

Disability
In 1990, the major fraction of morbidity worldwide was due to communicable, maternal, neonatal, and nutritional disorders (47%), while 43% of disability adjusted
life years (DALYs) lost were attributable to NCDs. Within two decades, these estimates had undergone a drastic change, shifting to 35% and 54%, respectively [18].
The global burden of disease is continuing to shift away from communicable to
NCDs, as well as from premature death to years lived with disability. The increased
disability rates due to CVD represent a significant loss of healthy life and an increasing cost for health care systems [7].
According to the Global Burden of Disease Study 2010 estimates, CVD is responsible for 18% of DALYs in high-income countries and 10% of DALYs in
low- and middle-income countries [1, 19]. In 2010, CHD and stroke were the first
and third cause, respectively, of disability worldwide, while in 1990, they were not
among the first three major causes of morbidity. Compared to 1990, in 2010, the
burden of CVD, in terms of DALYs, increased by 29%, while the burden of stroke
increased by 19% [7, 18].

4 Cardiovascular Disease (CVD)

39

Disease Trends
The annual number of CVD deaths has increased from 14.4 million in 1990 to 18.5
million in 2010, of which 7.6 million are attributed to CHD and 5.7 million to stroke
[19]. According to the WHO, this estimate will rise to 25 million in 2030, accounting for 30% of all deaths worldwide. Over the next few decades, it is expected that
NCDs will account for more than three quarters of deaths worldwide. CVD alone
will be responsible for more deaths in low-income countries than infectious diseases (including HIV/AIDS, tuberculosis, and malaria), maternal and perinatal conditions, and nutritional disorders combined [16]. CVD will continue to be the largest
single contributor to global mortality, dominating mortality trends in the future [4].
The US national academies (National Academy of Sciences, National Academy
of Engineering, Institute of Medicine, and National Research Council) observed
three different CHD mortality trends across a range of nations. The first is a riseand-fall pattern, where mortality rates increase, peak, and then fall significantly.
The second is a rising pattern, where rates are steadily increasing, indicating an ongoing epidemic. The third pattern is flat, i.e., CHD mortality rates are relatively low
and stable. The rise-and-fall pattern is most notable in high-income countries (e.g.,
European countries, USA, and Australia), because in these countries, CHD mortality rates peaked in the 1960s or early 1970s and have since fallen precipitously, by
an average of about 50%. The rising pattern is notable in low- and middle-income
countries, where mortality rates are increasing, sometimes to an alarming level. By
contrast, CHD mortality rates in other countries (e.g., Japan and several European
Mediterranean countries) are relatively low, following the flat pattern [16].

Economic Burden of CVD

The economic cost of CVD to families and society is high and escalating, caused
not only by health care costs but also by production losses due to the death and
illness of people of working age, as well as the financial impact on friends and relatives who act as informal carers of those with the disease [17, 20].
Estimates of the direct health care and nonhealth care costs attributable to CVD
in many countries, especially in low- and middle-income countries, are unclear and
fragmentary. In high-income countries (e.g., USA and Europe), CVD is the most
costly disease both in terms of economic costs and human costs. Over half (54%) of
the total cost is due to direct health care costs, while one fourth (24%) is attributable
to productivity losses and 22% to the informal care of people with CVD. Overall,
CVD is estimated to cost the EU economy, in terms of health care, almost 196 billion per year, i.e., 9% of the total health care expenditure across the EU and a cost
per capita of 212 per annum. CHD is estimated to cost the EU economy 60 billion
per year, while stroke costs over 38 billion per year, i.e., around one third and one

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fifth of the overall health care cost of CVD, respectively. Costs of inpatient hospital
care for people who have CVD accounted for about 49% of health care costs, and
drugs for their treatment about 29%. The health care costs for people with CVD
varies widely across the EU, e.g., by tenfold in 2009, from 37 in Romania to 374
in Germany [17].

Major Risk Factors

In the past two decades, the contribution of different risk factors to the global disease burden has changed substantially, with a shift from risks for communicable
towards those for NCDs. Factors associated with an increased risk of CVD are
generally classified into two categories, i.e., either modifiable or nonmodifiable
risk factors. Those of the first group can be controlled, treated, or modified through
health interventions, while those of the second group relate to individual characteristics that cannot be changed [4, 21].
The Global Burden of Disease Study 2010, through an assessment of the leading
risk factors across 187 countries, identified the risk factors that account for the leading cause of DALYs worldwide (Table4.1). All modifiable risk factors associated
with the development of CVD rank among the top 15 risk factors overall. The two
leading risk factors for global disease burden are high blood pressure and tobacco
smoking, including secondhand exposure to smoke. Other modifiable risk factors
for CVD included alcohol abuse, high body mass index (BMI), high fasting plasma
glucose level, high total cholesterol level, dietary risk factors (diets low in fruit and
vegetables, and diets high in sodium), and physical inactivity [7, 18, 19].

Short History of CVD Risk Factors

The term risk factor appeared for the first time in a paper published in Annals of
Internal Medicine and written by William B. Kannel, first director of the Framingham Heart Study [22]. The Framingham Heart Study, founded in 1948 under the
direction of the National Heart Institute of Boston, analyzing the epidemiology of
CVD in Framingham, a small town outside of Boston, has become the worldwide
standard for cardiovascular epidemiology. At the beginning of the study, not much
was known about the causes of CHD and stroke, at a time when the increasing death
rates for CVD were becoming alarming. Therefore, the initial objective of the study
was to identify the common environmental factors or personal characteristics that
contribute to the development of CVD events by following a large multigenerational asymptomatic group over a long period of time [23]. This pioneering work,
followed by the Seven Countries Study in the 1960s [24] and many others studies since then, including the WHO-MONICA Project [25] and the INTERHEART
study [26], have resulted in the identification of the major factors and determinants

4 Cardiovascular Disease (CVD)

41

Table 4.1 Global DALYs attributable to the 25 leading risk factors in 1990 and 2010 (in bold the
CVD risk factors). Results from Global Burden of Disease Study 2010 (GBD 2010) [7]
Risk factor

2010

1990

Rank

DALYs (95% UI) in Rank DALYs (95% UI) in

thousands
thousands

High blood pressure

173,556
(155,939189,025)

137,017
(124,360149,366)

Tobacco smoking (including exposure to secondhand

smoke)

156,838
(136,543173,057)

151,766
(136,367169,522)

Household air pollution

from solid fuels

108,084
(84,891132,983)

170,693
(139,087199,504)

Diet low in fruit

104,095
(81,833124,169)

80,453 (63,29895,763)

Alcohol use

97,237
(87,087107,658)

73,715 (66,09082,089)

High body mass index

93,609
(77,107110,600)

10

51,565 (40,78662,557)

High fasting plasma glucose level or diabetes

89,012
(77,743101,390)

56,358 (48,72065,030)

Childhood underweight

77,316
(64,49791,943)

197,741
(169,224238,276)

Exposure to ambient particulate matter pollution

76,163
(68,08685,171)

81,699 (71,01292,859)

Physical inactivity or low

level of activity

10

69,318
(58,64680,182)

Diet high in sodium

11

61,231
(40,12480,342)

12

46,183 (30,36360,604)

Diet low in nuts and seeds

12

51,289
(33,48265,959)

13

40,525 (26,30851,741)

Iron deficiency

13

48,225
(33,76967,592)

11

51,841 (37,47771,202)

Suboptimal breast-feeding

14

47,537
(29,86867,518)

110,261
(69,615153,539)

High total cholesterol level

15

40,900
(31,66250,484)

14

39,526 (32,70447,202)

Diet low in whole grains

16

40,762
(32,11248,486)

18

29,404 (23,09735,134)

Diet low in vegetables

17

38,559
(26,00651,658)

16

31,558 (21,34941,921)

Diet low in seafood n-3

fatty acids

18

28,199
(20,62435,974)

20

21,740 (15,86927,537)

Drug use

19

23,810
(18,78029,246)

25

15,171 (11,71419,369)

Occupational risk factors

for injuries

20

23,444
(17,73630,904)

21

21,265 (16,64426,702)

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Table 4.1 (continued)

Risk factor

2010

1990

Rank

DALYs (95% UI) in Rank DALYs (95% UI) in

thousands
thousands

21

21,750
(14,49230,533)

23

17,841 (11,84624,945)

Diet high in processed meat 22

20,939
(698233,468)

24

17,359 (513727,949)

Intimate partner violence

23

16,794
(11,37323,087)

Diet low in fiber

24

16,452
(740125,783)

26

13,347 (597020,751)

Lead exposure

25

13,936
(11,75016,327)

31

5,365 (45346279)

Occupation-related low
back pain

DALYs disability-adjusted life years, UI uncertainty interval

correlated with CVD. The notion of CVD risk factor is today an integral part of the
modern medical vocabulary and has led to the development of effective treatments
in clinical practice and preventive strategies in public health.

Modifiable Risk Factors

High Blood Pressure
In 2008, the worldwide prevalence of high blood pressure, in adults over 25 years,
was around 40% and higher in the African Region (46% for both sexes combined)
[2, 4]. According to the Global Burden of Disease Study 2010, raised blood pressure is the first ranking risk factor contributing to the global burden of disease
and the number of people with elevated blood pressure (systolic blood pressure
140mmHg or diastolic blood pressure 90mmHg) has increased from 600 million in 1980 to a billion in 2010 [7]. In 2010, high blood pressure was estimate to
cause almost 9.4 million (95% uncertainty interval (UI), 8.6 million to 10.1 million)
of global deaths and 7% of the total DALYs (Table4.1) [7, 19].
The relationship between hypertension and CVD, especially CVD due to atherosclerosis, has been widely demonstrated and blood pressure levels are positively
and continuously correlated with the risk of stroke and CHD. In some age groups,
the CVD risk doubles for each increment of 20/10mmHg of blood pressure, starting
from 115/75mmHg [2, 4]. In addition to CHD and stroke, complications of raised
blood pressure include heart failure, PVD, renal impairment, retinal hemorrhage,
and visual impairment [2, 4].
The major underlying risks for hypertension are sodium in the diet, body weight,
and limited access to treatment. Therefore, nonpharmacological (sodium reduction, increase of fruit and vegetable intake, weight control) and pharmacological

4 Cardiovascular Disease (CVD)

43

strategies can improve health outcomes of people with high blood pressure. Treating systolic blood pressure and diastolic blood pressure until they are less than
140/90mmHg is associated with a reduction in complications, including CVD [2,
4, 19].
Tobacco Smoking
Worldwide, almost six million deaths each year are attributable to smoking, both
from direct tobacco use and secondhand smoke [27]. By 2030, this number will increase to eight million [27]. Smoking is estimated to cause nearly 10% of CVD and
other important disorders such as lung cancer (71%) and chronic respiratory disease (42%) [27]. According to the Global Burden of Disease Study 2010, smoking,
including secondhand smoke, is the second leading risk factor contributing to the
burden of disease worldwide (6.3 million deaths and 6.3% of DALYs; Table4.1)
[7]. Smoking prevalence is higher in high- and middle-income countries, but, within
countries, there is an inverse relationship between income levels and prevalence of
tobacco use [4].
The impact of smoking on increasing CVD incidence has been widely demonstrated and the estimated risk increases with the number of cigarettes smoked per
day. The risk of a cardiovascular event in heavy smokers (greater than 40 cigarettes
per day) is twice that of light smokers (fewer than 10 cigarettes per day) [28].
Smoking cessation has been shown to have a significant impact on the reduction
of CHD mortality. Further, it leads to significantly lower rates of recurrent CVD
events in people who have had a heart attack and reduces the risk of sudden cardiac
death among people with well-established CHD. Although the specific time line of
risk reduction depends on the number of years of smoking and the quantity of tobacco consumed daily, it is considered possible that, over time, the CVD risk among
former smokers can drop to levels similar to that of the general population [29].
Unhealthy Diet
A healthy diet has a good balance of macronutrients (fats, proteins, and carbohydrates) to support energy needs without excessive weight gain from overconsumption, micronutrients to meet the needs for human nutrition without inducing toxicity, and an adequate amount of water. The leading problems of an unhealthy diet are
an insufficient intake of fruit, vegetables, fish, legumes, whole grains, and nuts; an
excessive intake of salt and total fats (exceeding 30% of the total energy per day);
and the consumption of saturated fat and trans-fatty acids. Low-income and socioeconomic levels are significant determinants of an unhealthy diet [4].
It has been widely demonstrated that a healthy diet is important for reducing
many chronic health risks, such as obesity, high blood cholesterol, high blood pressure, and diabetes, which are closely related to excessive consumption of fatty, sugary, and salty foods [4].

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According to the Global Burden of Disease Study 2010, a diet low in fruit is the
fourth leading cause of DALYs worldwide, causing 4.9 million deaths and 4.2%
of global DALYs (Table 4.1) [7]. Adequate consumption of fruit and vegetables
reduces the risk not only of CVD but also of stomach and colorectal cancer.
Most populations consume much higher levels of salt than recommended by
the WHO (5g/day) and high salt consumption is an important determinant of high
blood pressure and cardiovascular risk. A diet with high sodium intake is the 11th
ranking risk factor contributing to the global burden disease worldwide and it is
responsible for four million of deaths and 2.5% of global DALYs (Table4.1) [7,
19]. It is estimated that even a modest reduction in salt intake, from levels of 9 to
12g/day to the recommended level of 5g/day, may significantly lower blood pressure [30].
High consumption of saturated fats and trans-fatty acids is strongly linked with
CHD. The elimination of trans-fatty acids and the replacement of saturated fats with
polyunsaturated vegetable oils have a positive impact on CVD risk. Available data
suggest that fat intake has been rising rapidly in lower- and middle-income countries since the 1980s [4].
Other dietary risk factors, which have strong impact on the global burden of
disease and are correlated with CVD events, are diets low in nuts and seeds (2.5
million of deaths in 2010, 2.1% of DALYs), low in whole grains (1.7 million of
deaths, 1.6% of DALYs), and low in seafood omega-3 fatty acids (0.6 million of
deaths, 0.5% of DALYs; Table4.1) [7, 19].
Alcohol Use
Alcohol use is one of the most important avoidable risk factors, ranking fifth in the
Global Burden of Disease Study 2010, which accounted for 4.9 million deaths and
5.5% of global DALYs (Table4.1) [7]. While the adult per capita consumption is
higher in high-income countries, alcohol use is also significant in some middle-income countries, and as a result is the leading risk factor in Eastern Europe, Andean
Latin America, and southern sub-Saharan Africa [19]. Alcohol abuse is responsible
for 3.8% of all deaths (half of which are due to CVD, cancer, and liver cirrhosis)
and 4.5% of the global burden of disease [27].
The relationship between alcohol consumption and the development of CVD
is complex. Excessive and hazardous alcohol intake is associated with increased
risk of hypertension, stroke, CHD, and other forms of CVD. However, several epidemiological studies suggest a cardioprotective association for low or moderate
average alcohol consumption, and the correlation may follow a U or J curve,
with the lowest rates of CVD associated with light and moderate intakes of alcohol
[31]. However, a cardioprotective relationship between alcohol use and CHD and
stroke cannot be assumed for all drinkers, even at low levels of intake [31]. Moreover, alcohol may also contribute to overweight and obesity, since it is a significant
source of daily calories in many countries. Finally, it is important to emphasize the
association of alcohol misuse with many other diseases (neuropsychiatric disorders,

4 Cardiovascular Disease (CVD)

45

cirrhosis, and cancer), which outweighs the potential and small cardioprotective
effects [32].
Overweight and Obesity
Obesity is a CVD risk factor closely linked to diet and physical activity and it results
when there is an imbalance between energy intake in the diet and energy expenditure. To achieve optimal health, the median BMI for adult populations should be in
the range of 2123kg/m2, while the goal for individuals should be to maintain a
BMI in the range 18.524.9kg/m2 [4].
The incidence of high BMI has increased globally and at present 3.4 million
people die prematurely each year as a result [19]. High BMI is responsible for 3.8%
DALYs worldwide, resulting as the sixth leading risk of global DALYs in 2010
[7, 19] (Table4.1). It is the major risk factor in Australia, Asia, and southern Latin
America, and it also ranks highly in other high-income regions, and in North Africa,
the Middle East, and Oceania [7]. The prevalence of overweight is highest in upperto-middle-income countries, but very high levels are also reported in some lowerto-middle-income countries. In the WHO European Region, the Eastern Mediterranean Region, and the Region of the Americas, over 50% of women are overweight. The highest prevalence of overweight among infants and young children
is in upper-to-middle-income populations, while the fastest rise in overweight is in
the lower-to-middle-income group [19]. Globally, in 2008, 9.8% of men and 13.8%
of women were obese compared to 4.8% of men and 7.9% of women in 1980 [27].
Obesity is strongly related to some of the major cardiovascular risk factors such
as raised blood pressure, glucose intolerance, type 2 diabetes, and dyslipidemia [4].
Risks of heart disease, stroke, and diabetes increase steadily with increasing BMI
[4].
Diabetes
Diabetes is defined as a group of metabolic diseases in which an individual have a
fasting plasma glucose value of 7.0mmol/l (126mg/dl) or higher. Impaired glucose
tolerance and fasting glycemia are categories of risk for the future development of
diabetes [2]. In 2010, diabetes was responsible for 3.4 million deaths globally and
3.6% of DALYs [7, 19] (Table4.1). The prevalence is lower in low- and middleincome countries (8%) compared to developed countries (10%) [27].
There is a clear relationship between diabetes and CVD. Several studies showed
a two- to threefold increased incidence of CVD in patients with diabetes compared
to people without diabetes [33]. Furthermore, people with diabetes also have a
poorer prognosis after cardiovascular events compared to people without diabetes [33]. In fact, CVD is by far the most frequent cause of death in both men and
women with diabetes, accounting for about 60% of all mortality [27]. Other severe

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complications resulting from lack of early detection and care of diabetes are renal
failure, blindness, foot ulcers, and amputation.
It has been widely demonstrated that the risk of diabetes is increased with some
conditions or types of behavior, such as obesity and overweight, which are the primary risk factors for type 2 diabetes, fat distribution, and physical inactivity [6].
Primary care with measurement of blood glucose levels and cardiovascular risk
assessment, as well as the provision of essential medicines, including insulin, can
significantly improve the health outcomes of people with diabetes [4].
Physical Inactivity
A low level of physical activity is defined as less than five episodes of 30min of
moderate activity per week, or less than three times of 20min of vigorous activity
per week [4]. In 2010, 3.2 million deaths and 2.8% of global DALYs were due to insufficient physical activity (Table4.1) [7, 19]. The prevalence of insufficient physical activity is higher in high-income countries (41% of men and 48% of women)
compared to low-income countries (18% of men and 21% of women) as a likely
consequence of the automation of work and overuse of vehicles [19]. Similarly to
tobacco use and unhealthy diet, there is a relationship, in high-income countries,
between physical inactivity and low-income level and SES [19].
According to the Global Burden of Disease Study 2010, physical inactivity or
low physical activity is the tenth leading risk factor worldwide contributing to the
global burden of disease (Table4.1) [7]. In fact, physical activity plays a key role
in regulating energy balance and weight control, and people who are insufficiently
physically active have a 2030% increased risk of all-cause mortality [7]. Regular
physical activity also reduces the risk of CVD through better control of high blood
pressure and diabetes. This protective action is due to an improvement in endothelial function and, consequently, an enhancement in vasodilatation and vasomotor
functions in the blood vessels. In addition, physical activity contributes positively
to weight loss, glycemic control, lipid profile, and insulin sensitivity [4].
Dyslipidemia
The main functions of cholesterol are to assist in building and maintaining membranes in the body and to ensure membrane flexibility over a wide temperature
range. Within membranes, cholesterol is needed for nerve and cell signaling and
conduction. Moreover, cholesterol is stored in the adrenal glands, ovaries, and the
testes and is converted to steroid hormones. It is also required for the manufacture
of fat-soluble vitamins and bile acids. The lipid profile of body fat is composed of
LDL cholesterol, which is also known as the bad cholesterol, high-density lipoprotein (HDL), known as the good cholesterol, and triglycerides [6, 34].
LDL levels are closely correlated with CVD. Raised cholesterol is considered the
15th leading risk factor for the global burden of disease and it is estimated to cause
two million deaths and 1.6% of total DALYs annually [7] (Table4.1). The preva-

4 Cardiovascular Disease (CVD)

47

lence of raised total cholesterol varies according to the income level of the country.
In low-income countries, around 25% of adults have raised total cholesterol, while
in high-income countries, over 50% of adults have raised total cholesterol [4, 34].
Overall, one third of CHD disease is attributable to high cholesterol levels, and
lowering blood cholesterol reduces the risk of heart disease [27].
Social Determinants
Social determinants of health represent the social conditions in which individuals
live and work. They are shaped by the distribution of power, income, and access to
resources, as much on a global and national level as on a local level. SES has been
widely acknowledged as the most powerful social determinant of health [35].
While the relationship between CVD and the traditional risk factors described
above has been widely studied, fewer studies have analyzed social determinants
such as the level of education, working conditions, housing, or social relationships.
Social determinants influence indirectly global health, as well as the cardiovascular
health state, by impacting behavioral and metabolic cardiovascular risk factors, psychosocial status, and living conditions, and it is difficult to examine these underlying triggers [35].
Social determinants have been shown to be related to CVD in various ways.
Work-related stress and depression have been linked to the development of cardiovascular risk factors, such as hypertension and atherosclerosis [35]. Negative social
interactions were found to be related to higher blood pressure levels [35]. The poor
have limited opportunities for healthy choices and have a high prevalence of smoking [2, 35]. Finally, also the access to health care may explain the link between SES
and CHD [35].
Social determinants influence both the incidence and management of traditional
risk factors and the management of CVD events [2, 35]. Thus, ignoring patients
social status, when scoring total cardiovascular risk using traditional models, may
lead to the underestimation of the true cardiovascular risk for patients of low SES
[35].

Nonmodifiable Risk Factors

Age
Age is a powerful cardiovascular risk factor, and the rapidly growing burden of
CVD in low- and middle-income countries is accelerated by population ageing.
The first CVD event occurs in the vast majority of people after the age of 55 years
in males and 65 years in females [27]. As a person gets older, the heart undergoes
subtle physiological changes, even in the absence of disease. The heart muscle of
the aged heart may relax less completely between beats and, as a result, the pumping chambers become stiffer and may work less efficiently [6].

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Gender
Males are at greater risk of CHD than females (premenopausal woman). After the
menopause, the risk in women is similar to that in men [36]. Risk of stroke, however, is similar for men and women throughout life [36].
Family History
Family history is an independent predictor of CVD [37]. A positive family history
for CVD captures the underlying complexities of genegene and geneenvironment interactions by identifying families with combinations of risk factors, both
measured and unmeasured, which lead to disease expression. Family history is a
useful tool for identifying the relatively small subset of families in the population
at highest risk of CVD who may benefit most from targeted screening and intensive
interventions [37].

Reducing the Burden of Cardiovascular Disease:

Strategies for Prevention
Prevention of CVD requires a stratified approach involving population-wide, highrisk, and secondary prevention strategies. These three strategies are not mutually
exclusive, and indeed must be integrated for maximum CVD prevention [38].
The concepts of population-wide (or community-based) and high-risk prevention strategies were introduced into the public health arena by Geoffrey Rose in
1981 [39]. According to several reports published by the WHO on primary prevention of CVD, it is fundamental that the high-risk approach is complemented by a
population-based strategy [40]. Without population-wide prevention efforts, CVD
will continue to occur in people with low and moderate levels of risk, who represent
the majority in any population. A community-based prevention strategy may also
induce lifestyle changes in the high-risk population. The passage between primary
and secondary prevention is correlated with the development of an established CVD
and with a gradual increase in an individuals global risk. For this subgroup population, intensive behavioral interventions and drug treatments are recommended, and
health care actions may switch from mainly nondrug interventions to drug interventions [38, 40].
Success in the prevention of CVD events is maximized when all three prevention strategies are applied simultaneously. The choice of the interventions to be
implemented should depend on the proven effectiveness and cost-effectiveness of
particular interventions and on the resources available.

4 Cardiovascular Disease (CVD)

49

Population-Wide Prevention Strategy

A community-based prevention strategy attempts to shift the distribution of exposure to risk factors in a population through lifestyle and environmental changes that
affect the whole population, without requiring interventions at the individual level.
The central concept behind this strategy is the recognition that exposure to risk factors reflects the functioning of society as a whole. A population-based prevention
strategy is essential for the reduction of both the incidence and burden of CVD
when there is a clear relationship between risk and exposure and the risk is widely
distributed across the whole target population. This type of prevention strategy is
mostly achieved by establishing health policies and community interventions. Rose
in 1981 considered this approach more capable of preventing burden of disease than
targeting the high-risk population because a large number of people exposed to a
low risk is likely to produce more cases than a small number of people exposed to
a high risk [39]. At present, it seems clear that, without a well-resourced national
community strategy plan and without monitoring the major determinants, CVD will
remain a leading cause of premature death and disability [18].
The European Society of Cardiology, the American Heart Association, and the
WHO have identified several goals to be achieved through the implementation of
national and international policies and community interventions: avoidance of tobacco, adequate physical activity, healthy food choices, avoidance of overweight,
regulation of blood pressure (below 140/90mmHg), and reduction of total cholesterol (below 200mg/dl) [4]. Many of the interventions adopted in a population-wide
prevention strategy are relatively inexpensive and easy to implement. They have a
relevant public health impact and are highly cost-effective and, therefore, they are
considered to be best buys for investors [5]. Examples of these types of actions
are tobacco control measures (raising taxes on tobacco, protecting people from tobacco smoke, warning messages on cigarettes packs, enforcing bans on tobacco
advertising, etc.), control measures against the harmful use of alcohol (raising taxes
on alcohol, restricting access to alcohol demand, enforcing bans on alcohol advertising, etc.), and measures that promote a healthy diet and physical activity (reducing salt intake in foods, replacing trans-fat with polyunsaturated fat, promotion of
physical activity, etc.). In addition to health policy interventions such as taxes, subsidies and regulation of price, availability, and marketing, the WHO identified also
the main elements of the urban environment for preventing chronic diseases, such
as providing bicycles and cycleways as well as parks and green spaces to increase
physical activity [41] The main limitation of the population strategy is the small
benefit perceived at individual level, but if healthy behaviors become social norms,
it is easier for individuals not to initiate, or to change, risky behaviors [38].

High-Risk Primary Prevention Strategy

A high-risk primary prevention strategy is a clinically oriented approach that focuses efforts at an individual level, dealing with healthy population subgroups with

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high absolute risk of future CVD. The aim is to reduce the total cardiovascular risk
of healthy individuals belonging to the upper part of the risk distribution, and it
represents the natural approach for medical practitioners who are concerned with
the occurrence of CVD in individuals [39, 42].
The probability that an individual could develop CVD in a given period of time
(absolute risk) depends more on the combination of multiple cardiovascular risk
factors than on the presence of any single risk factor, because the cumulative effect
of causal factors is additive or synergistic. It is reasonable to expect that a primary
prevention strategy based on estimating the total cardiovascular absolute risk would
be more effective and cost-effective than a clinical approach based on identifying
and correcting single risk factors [42].
Electronic and paper-based tools, tailored to each specific population (American, European, Australian, African, etc.), are available to calculate the individual
risk of CVD in people who do not have established CHD, stroke, or other atherosclerotic disease. These risk charts, and the relative guidelines for intervention, are
based on risk equations derived from large prospective cohort studies (Framingham, PROCAMMunster, Seven Countries Study, SCORE, CUORE Project, etc.)
and include the following variables: age, sex, blood pressure, cigarette smoking,
total cholesterol and HDL cholesterol, and diabetes. To estimate the absolute risk,
expressed as a percentage, it is necessary, as a first step, to select the appropriate
chart depending on the gender (male/female tables) and on the presence or absence
of diabetes. Then, after indicating an individuals smoking habits, systolic blood
pressure (mmHg), and total blood cholesterol level (mmol/l), an output is obtained
showing level of risk. When adjusted for the different thresholds used in each country, the risk is graded as low, moderate, or severe [4, 42].
The main strengths of this strategy are that it provides high-risk individuals with a
strong motivation to change their behavior and it allows health professionals to promote change on an individual basis through direct communication. Moreover, the selectivity of the interventions may increase the likelihood that resources are used costeffectively. By contrast, this strategys main weaknesses are that (a) it underestimates
the fact that a large number of people exposed to a small risk may generate more cases
of CVD than a small number of individuals exposed to a large risk; (b) it results in
a higher propensity for pharmacological intervention; (c) individual-level strategies
tend to be either palliative or temporary, and are not focused on influencing behavior.

Secondary Prevention Strategy

A secondary prevention strategy focuses on the rapid initiation of treatments to
stop the progression of disease in individuals with well-established CVD. Since
the cardiovascular risk is a continuum, the transition between primary (first step)
and secondary (second step) prevention represents the passage from interventions
on high-risk groups (with asymptomatic evidence of CVD) to those on highest-risk
groups (with symptomatic CVD). Secondary prevention involves identifying, treating, and rehabilitating these patients to reduce their risk of recurrence, to decrease

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their need for interventional procedures, to improve their quality of life, and to
extend their overall survival [38, 39].
Programs for secondary prevention have proven to be effective in improving
recovery and functional status, and in reducing readmissions to hospital. Several
studies have demonstrated the effectiveness of secondary prevention strategies in
the control of CVD, such as the WHO-MONICA study that from the early 1980s
monitored trends in CHD over 10 years, across 38 populations, and in 21 countries.
Data from this study indicate that secondary prevention interventions and changes
in coronary care are strongly linked with declining CVD end points [25].

Making Choices to Reduce the Burden

of Cardiovascular Disease
This section provides an overview of reviews and systematic reviews on the effectiveness and cost-effectiveness of CVD-preventive interventions. Clinical guidelines and reports of authoritative institutions were also reviewed to detect the best
buy interventions and to provide examples of best practices. The section follows
the conceptual framework set out earlier, following the three levels of prevention,
components of a comprehensive approach that systematically integrates policy, and
action (identifying population-level health promotion and disease prevention program, targeting groups and individuals at high risk, maximizing population coverage with effective treatment and care).
Box 1. Characteristics of included studies
The initial search yielded 635 results from all databases investigated
(Cochrane Database, PubMedMedline, NHS Economic Evaluation Database, SCOPUS), of which 62 were retrieved as full text after review of title
and abstract. Fifty-three studies were included and analyzed (Fig.4.1).
Publication date of the retrieved reviews range from 1998 to 2013, with
the majority (29/53) published within the past 5 years. The large majority
of the reviews (43/53) reported both effectiveness and cost-effectiveness
information.
Twenty-two reviews were focused on community-based interventions.
Seventeen evaluated only community-based interventions, while five reviews
also evaluated interventions at the individual level. Different CVD risk factors were evaluated: unhealthy diet [4352], physical inactivity [44, 45, 49,
50, 5255], smoking [20, 45, 50, 56, 57], obesity, especially in childhood [49,
5862], and alcohol [63]. In general, reviews on population-based prevention
reported evidence on cost-effectiveness for the interventions considered in
the setting/s of interest.

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E. DAndrea et al.
Cochrane Database
(182)

Pubmed-MEDLINE
(302)

NHS Economic Evaluation

Database (151)

SCOPUS
(109)

635 articles retrieved

231 duplicates removed

404 articles screened

347 articles removed

after title and abstract
review

62 full-text articles
assessed for eligibility

9 full-text articles
excluded:
- no reviews or
systematic reviews (4)
- no data on
effectiveness/costeffectiveness of
preventive
interventions (5)

53 articles included
in the overview

Fig. 4.1 Study selection process for the identification of reviews and systematic reviews on effectiveness and cost-effectiveness of CVD-preventive interventions

Twenty-nine reviews on primary prevention were identified. Eighteen considered only primary prevention, while another five and six also evaluated
community-based interventions and secondary prevention, respectively. Different types of interventions were evaluated, specific to different risk factors:
high blood pressure [6474], dyslipidemia [6469, 71, 7375], smoking [20,
45, 50, 57, 68, 69, 7678], physical inactivity [45, 50, 54, 77, 79], diabetes
[57, 70, 8083], unhealthy diet [45, 50, 77], obesity [45, 84, 85], and alcohol
[77]. Three reviews, using the absolute risk-based approach, evaluated the
effectiveness or cost-effectiveness of providing preventive lifestyle interventions and/or medication on the basis of absolute risk determined from risk
charts [8587]. Many of the primary prevention interventions examined in
the reviews have been reported to be effective or cost-effective in the setting/s
analyzed.
Thirteen papers evaluated pharmacological interventions within a secondary prevention strategy, and six of these also in a primary prevention context.
In the vast majority of cases, preventive therapy was against high blood pressure [64, 71, 73, 8894], high blood cholesterol [45, 64, 71, 73, 88, 94], and
diabetes [80, 82]. Drugs to lower high blood pressure were found to be in the
very cost-effective or cost-effective range in all studies.

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53

Effectiveness and Cost-Effectiveness

of Population-Wide Interventions
Reducing the rate of tobacco use worldwide is one of the most important health
care goals for the prevention of chronic diseases, including CVD. Tobacco control
and prevention policies described in the literature as population-wide prevention
strategies have proved very cost-effective. Although the estimates in the literature
are subject to local variations and each country is guided by local policies, increasing taxes on cigarettes and tobacco has been found to be the most cost-effective
antismoking intervention [20, 45, 50, 56, 57]. Furthermore, interventions based
on tobacco taxation have a proportionally greater effect on smokers of lower SES
and younger smokers, who might otherwise be difficult to influence. Several studies suggest that the application of a 10% rise in price could lead to as much as a
2.510% decline in smoking [20, 45, 50, 56]. Other public health actions reported
as cost-saving are the creation of completely smoke-free environments in indoor
workplaces, public places, and transportation; warning the population of the dangers
of tobacco through educational campaigns; and the banning tobacco advertising,
promotion, and sponsorship [20, 45, 50, 56, 57]. All preventive actions evaluated in
the reviews retrieved are included in the important treaty WHO Framework Convention for Tobacco Control, embraced by 173 countries and covering almost 90%
of the worlds population. This treaty identifies several actions and policies that
each country must implement, including increased taxation, legislated restrictions
on smoking in public places, comprehensive bans on advertising of tobacco products, information dissemination through health warning labels, counter advertising,
various consumer information packages, the creation of national tobacco control
program, and the protection of public health policies from commercial and other
interests of the tobacco industries [95]. According to WHO data, the total expenditure for implementation of tobacco control policies would range from US$0.10 to
US$0.23/person/year in low- and middle-income countries, and from US$0.11 to
US$0.72/person/year in upper-middle-income countries [4, 96]. An important fraction of this expenditure is attributed to educational media campaigns, while other
measures come at a lower cost (e.g., increasing taxes, completely smoke-free indoor
environments, health warnings, banning tobacco advertising).
Preventive interventions aimed at the avoidance of an unhealthy diet, at controlling overweight and obesity, and at the promotion of physical activity could achieve
a downward shift in the distribution of blood pressure, cholesterol level, and diabetes risk across a population, thus potentially reducing morbidity, mortality, and
the lifetime risk of developing CVD. Nutrition policies evaluated by the literature
are mainly focused on programs aiming to reduce salt, saturated fats and trans-fatty
acids, and free sugars in the diet [4352]. The current literature on reducing salt intake suggests that all correlated interventions are very cost-effective [43, 4548, 51,
52]. The most valued intervention reported, especially in studies from high-income
countries, is the lowering of salt levels in processed food and condiments by manufacturers. Other studies have estimated the cost-effectiveness of a sustained mass

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media campaign aimed at encouraging dietary change within households and communities [47, 52]. These interventions appear to be the best choices for encouraging
people to use less salt in rural areas in low- and middle-income countries, where
most of the sodium intake comes from salt added during cooking or from sauces
and additives. The evidence on the cost-effectiveness of reducing the marketing
of foods with high levels of saturated fats, trans-fatty acids, or sugar-free is less
convincing, but these interventions are also likely to be very cost-effective [48, 49,
59]. The maximum benefit of interventions for the implementation of a healthy diet
would be achieved by targeting early stages of life (childhood and adolescence) [49,
5861]. Relevant programs include the use of economic regulation (e.g., taxes or
subsidies) to reduce the marketing to children and adolescents of foods and nonalcoholic beverages with high levels of salt, fats, and sugar. Nationwide and international food markets that comply with healthy dietary guidelines based on compelling evidence are potentially the basis for large health gains, and cost-effectiveness
studies tend to support their adoption [4, 5861]. Physical activity could play a
substantial role in reducing overweight and obesity [44, 45, 49, 50, 5355]. Intersectoral and multidisciplinary action is required to improve physical activity levels.
Appropriate actions include the combination of social support in a variety of setting
(e.g., school-based programs, activities at worksites, community walking events),
transport policies (e.g., creating walking and cycling trains, providing easy access
to weight and aerobic fitness places, facilities and equipment in community centers), primary care support (e.g., counseling and seminars provided by physicians),
and community-wide campaigns (e.g., increasing public awareness through mass
media and social networks). All these physical activity programs appear to be very
cost-effective compared to other well-accepted preventive strategies. The WHO,
according to the existing evidence [5355], reported that creating an enabling environment, providing appropriate information, and ensuring the wide accessibility
of venues for physical activity are critical actions that influence behavior changes,
regardless of the setting [4].
Another category of effective and cost-effective population-based measures is
the reduction of alcohol-related harms. There is substantial evidence in the literature
of systematic reviews and meta-analyses informing alcohol policies, not only for
the prevention of CVD but also to control other chronic diseases such as cancer,
liver cirrhosis, and injuries [32]. Particular alcohol-related policies include restrictions on the availability of alcoholic beverages (e.g., state monopolies and licensing
systems, restrictions in off-premise retail sale, age requirements for purchase and
consumption of alcoholic beverages), drink driving legislation, price and taxation of
alcoholic beverages, advertising and sponsorship (e.g., restrictions on sponsorship,
enforcement of advertising), and alcohol-free environments [63]. All these population-based interventions represent a cost-effective use of resources and compare
favorably with treatment strategies for disease and injury. An unclear result was
obtained for school-based education interventions, because this approach seems unable to reduce alcohol consumption [63].

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Effectiveness and Cost-Effectiveness of Individual High-Risk

Primary Prevention Interventions
Primary prevention is characterized by measures that decrease the likelihood of a
first occurrence of CVD through health promotion, screening for risk factors, and
risk factor modification with an individual approach. The most cost-effective route
of action is often attained by choosing interventions targeted at the risk profile of a
specific population group. Therefore, knowledge of the risk profile is essential for
a targeted delivery of intensive lifestyle interventions and appropriate drug therapy.
Specific risk prediction charts, providing approximate estimates of CVD risk in
people without established CVD, are available. The use of these tools to identify
subjects at higher cardiovascular risk, to motivate them to introduce behavioral
changes, and, where appropriate, to prescribe antihypertensive therapy, lipid-lowering drugs, and aspirin, is an effective and, depending on the setting, cost-effective
measure [8587].
Primary prevention interventions include both lifestyles changes and pharmacological treatments. The evidence suggests that counseling by physicians to reduce
intake of total fat, saturated fat intake, and daily salt, and to increase fruit and vegetable intake, is very cost-effective, leading to dietary changes, improved weight
control, and increased physical activity [6469]. The threshold for the introduction
of drugs in preventive programs is not defined, but, generally, when people belong
to the high-risk profile subgroup, the use of drugs may be cost-effective [7173].
Reduction of serum cholesterol levels of high-risk subjects has been shown to lower
the risk of adverse cardiovascular events [74, 75]. Statins and dietary modifications
are effective tools in lowering levels of serum LDL cholesterol, although different
settings and comparators were considered in literature. The role of statins as a costeffective means of preventing CVD depends on the risk profile and the drug price is
the main determinant of cost-effectiveness within a given risk group. As more statin
drugs become generic, patients at low risk for coronary disease may be treated costeffectively [69]. However, there is no universal consensus on the use of statins for
primary prevention of CHD for persons at high risk but with no symptoms [74, 75].
A medical solution aimed at reducing the CVD risk by attacking several biological processes simultaneously, and that could be viewed potentially as the therapy
of the future, is the polypill, containing a fixed dose of aspirin, a statin to lower
cholesterol, and one or two blood pressure-lowering drugs [97]. Our systematic
review did not include the studies on the polypill use, because this kind of treatment
has not been marked anywhere in the world to date, and the full benefits of such pill
remain unclear. However, it is important to mention this kind of multidrug strategy
for the extensive discussion about its use in the primary prevention and the future
next marketing in USA [98, 99]. Polypill has been proposed as a public health intervention for use by all adults more than 55 years of age regardless of risk factor
levels. Multiple different polypill formulations have been developed over the past 5
years, with randomized controlled trials of their benefit currently underway [100].
Preliminary results reported the efficacy of this pill in high-risk populations and the

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enormous potential for developing countries, where principal barriers are both the
cost and complexity of multiple drug use [101].
Drug therapy was also found to be cost-effective for moderate and high-risk
profile subgroups with persistent raised blood pressure (130/80mmHg) that are
unable to lower blood pressure through lifestyle changes. Drugs evaluated for firstline therapy and primary prevention are thiazide-like diuretics, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers. The beta-blockers
are considered more suitable for secondary prevention [86, 8890].
According to the available scientific evidence, smoking cessation with health
care professional counseling and nicotine replacement treatment is highly cost-effective in high-risk populations. Health care providers play a central role in creating
dedicated places for antismoking counseling and in educating physicians to discourage people, especially the young, from becoming smokers, to strongly encourage all
high-risk subgroups to stop smoking and to support those who decide to quit with
pharmaceutical and psychological interventions. Nicotine replacement therapy and/
or nortriptyline or amfebutamone (bupropion) should be offered to moderate and
high-risk subgroups who fail to quit with counseling [20, 45, 57, 76]. By contrast,
the mass media promotion of smoking cessation was found to be less cost-effective
than physician counseling and nicotine replacement treatment, especially in subjects with more than one risk factor [7678].
In conclusion, a wide range of evidence-based individual interventions have
been demonstrated to be effective, with a significant impact on the health outcomes
of people at high risk of CVD. Improved access to highly cost-effective interventions at the primary health care level will have the greatest potential in reversing the
progression of the disease, preventing complications and reducing hospitalizations,
health care costs, and out-of-pocket expenditures. However, individual interventions need to be targeted to subjects at high total cardiovascular risk based on the
presence of combinations of risk factors. If interventions are aimed at single risk
factor levels above traditional thresholds, such as hypertension and hypercholesterolemia, they become less cost-effective.

Effectiveness and Cost-Effectiveness of Secondary Prevention

Interventions for secondary prevention of CVD include both modification of risk
behaviors (smoking cessation, promotion of healthy diet, and physical activity) and
the use of medication. The vast majority of secondary prevention interventions deal
with several pharmacological treatments, including aspirin and other oral antiplatelet drugs (dipyridamole, clopidogrel), ACE inhibitors, lipid-lowering drugs, and
beta-blockers; these treatments reduce raised blood pressure and cholesterol levels
[64, 70, 73, 80, 82, 8894]. The target population is generally represented by individuals with well-established CVD or people with very high-risk profile but with
no established CVD, and different protocols of treatment are compared. However,
pharmacological interventions were always delivered in association with nonphar-

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57

macological interventions. In all reviews, this combination is considered a key contribution to the reduction of recurrences and cardiovascular mortality in people with
established CVD.
The benefits of aspirin for the secondary prevention of CVD are well established
among patients at high risk of cardiovascular events [88, 89]. Several recent studies
have documented the effectiveness of dipyridamole for the secondary prevention of
stroke, and clopidogrel for the treatment of symptomatic CVD [9193]. The costeffectiveness of these antiplatelet drugs is correlated with the price of the treatment
and can be optimized by individualizing the treatment decision on the basis of the
patient risk profile and the expected risk reduction [8894].
Strong evidence for the efficacy of these drugs has been obtained from studies
that were mostly carried out in affluent societies, while few studies were performed
in low- and middle-income countries. Therefore, many recommended medical interventions evaluated in developed countries may cause economic hardship when
applied in developing nations [71]. In low- and middle-income countries, there are
major gaps in the implementation of secondary prevention interventions for CVD,
which could be best delivered at the primary care level.

Best Buys for Prevention and Control of Cardiovascular Disease

The decision to allocate resources for implementing a particular health intervention
depends not only on the strength of the evidence (effectiveness of intervention) but
also on the cost of achieving the expected health gain. Cost-effectiveness analysis
is the primary tool for evaluating health interventions on the basis of the magnitude of their incremental net benefits in comparison with others, which allows the
economic attractiveness of one program over another to be determined [102]. If an
intervention is both more effective and less costly than the existing one, there are
compelling reasons to implement it. However, the majority of health interventions
do not meet these criteria, being either more effective but more costly, or less costly
but less effective, than the existing interventions. Therefore, in most cases, there
is no best or absolute level of cost-effectiveness, and this level varies mainly on
the basis of health care system expenditure and needs [102]. Furthermore, costeffectiveness information indicates solutions, but not their feasibility, affordability,
and acceptability.
The best buy is defined as a highly cost-effective intervention for which there
is compelling evidence that it is also feasible, low cost, and appropriate to implement within the constraints of a national health system [2, 5]. Policymakers can
consider best buys the best investment for governments and a core set of essential
health programs. Interventions that do not meet the above criteria, but which still
offer good value for money and other features that recommend their use, can be
defined as highly cost-effective programs although not as best buys, and they
can be considered part of an expanded set of measures to be made available if
resources allow it. The best buy is a very pragmatic concept, and evidence has

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demonstrated that, even in the poorest countries with absence of income growth,
deaths and illnesses can be reduced using existing knowledge and strategies [5].
The derived health improvements will help countries to achieve their development
goals: Low-income countries need not wait until they are wealthy before becoming
healthier [5].
This overview highlights the literature evidence in favor of the implementation
of best buys. The vast majority of best buys are community-based interventions
and the target is the whole population. Concerning tobacco control, four interventions, included in the WHO Framework Convention on Tobacco Control (increasing taxes, legislation for smoke-free indoor workplaces and public places, health
information and warnings about the effects of tobacco, and bans on advertising,
promotion, and sponsorship), constitute best buys [20, 41, 46, 52, 53]. The available evidence, based on the analysis of the implementation of all four programs in
23 low- and middle-income countries, quantifies five million deaths avoided at an
average cost of US$0.20/person/year [96]. Enhanced taxation of alcoholic beverages and bans on their marketing also show favorable cost-effectiveness and feasibility and are recommended as best buys [59]. Reducing salt intake through
mass media campaigns and regulation of processed food, and substitution of hydrogenated trans-fat with polyunsaturated fats in packaged food, are the best buys
for improving the diet [43, 4549, 51, 52, 5861]. In combination with these interventions, promoting physical activity through the media to combat obesity, high
blood pressure, dyslipidemia, and diabetes is reported to be both cost-effective and
feasible [5355]. Individual high-risk interventions that could be considered best
buys include providing aspirin to people with high-risk profile or who have already
suffered a heart attack; reducing the cardiovascular risk (controlling blood pressure,
blood cholesterol, and blood sugar; reducing tobacco use) in people, including those
with diabetes, who are at high risk of heart attacks and strokes; and controlling glucose levels in people with diabetes, preventing complications such as blindness and
kidney failure [4, 5]. These preventive actions can be combined with more targeted
approaches to improve health, depending on the resources available.
In conclusion, the association between behavioral risk factors and CVD has been
widely demonstrated in the past 50 years and a great amount of evidence on effectiveness and cost-effectiveness interventions for preventing CVD has been provided. As WHO advocates, we have now the required bases of science and technology
to effectively reduce the public health impact of CVD [2].
Lifestyle and behavioral interventions, mainly referred to a population-wide approach, appear generally to be very cost-effective, while pharmacological interventions have an impact of greater certainty and magnitude in both primary and
secondary prevention. The two strategies of interventions can thus be seen as complementary. They have to be implemented together, taking into account that the
nature of policy-making is increasingly interdependent and multidimensional. The
fact that health is affected by policies of other sectors has been recognized for a
long time, and the need to cooperate with sectors such as those of education, social
affairs, transport, environment, housing, agriculture, and nutrition is widely recognized [41].

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59

Box 2. Examples of best practices

In 1972, Finland had the worlds highest CVD mortality rate. Planners examined existing policies and major factors contributing to CVD and introduced
appropriate changes (low-fat dairy products, antismoking legislation, and
healthy school meals), providing one of the best-documented examples of
community intervention [103]. They used mass media, courses in schools and
worksites, and spokespersons from sports, education, and agriculture to educate residents. After 5 years, significant improvements were documented in
smoking, cholesterol, and blood pressure. In 1995, CHD mortality rates for
men aged 3564 years were reduced by 65%. The program was so successful
that it was expanded, including other lifestyle-related diseases. Twenty years
later, major reductions in CVD risk factor levels, morbidity, and premature
mortality were attributed to the project [103].
In 2003, Denmark introduced mandatory compositional restrictions on
trans-fatty acids in fats and oils to less than 2% of total fatty acids. A 2006
survey indicated that industrially produced trans-fatty acids in Denmark had
been virtually eliminated from the food supply and that both the population
average and the high-risk groups consume less than 1g of industrially produced trans-fatty acids per day [104].
In 2006, the Massachusetts health care system reformed the law on
tobacco cessation for the Massachusetts Medicaid population. For Medicaid
subscribers, two 90-day courses per year, medications like nicotine replacement therapy, and individual or group counseling sessions were available.
A total of 37% of all Medicaid smokers used the newly available benefit
between 2006 and 2008. After implementation, in just over 2 years, 26% of
Medicaid smokers quit smoking, and there was a decline in the use of other
costly health care services (38% decrease in hospitalizations for CHD, 17%
drop in emergency room and clinic visits for asthma, and a 17% drop in
claims for adverse maternal birth complications). Additional research showed
that comprehensive coverage led to reduced hospitalizations for CHD and
net savings of US$10.5 million or a US$3.07 return on investment for every
dollar spent [50].

Despite some preventive approaches are so cost-effective that country income

levels could not be perceived as major barriers to actual implementation, the costeffectiveness analyses of CVD-preventive interventions and strategies should be
performed taking into account the local contexts, such as the prevailing burden of
disease, the existing health interventions, and the financial capacity of the health
system. Since each community is unique, every country should develop its own
health policy to win the battle against CVD [2, 41].

60

E. DAndrea et al.

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[Link] Accessed 17 July 2013.

Chapter 5

Epidemiology of Cancer and Principles

of Prevention
Stefania Boccia, Carlo La Vecchia and Paolo Boffetta

Introduction
Neoplasms include several hundreds of diseases, which can be distinguished by
localization, morphology, clinical behaviour and response to therapy [1]. They are
classified according to the International Classification of DiseasesOncology [2]
into topographical categories (according to the organ where the neoplasm arises)
and morphological categories (according to the characteristics of the cells).
Benign neoplasms represent localized growths of tissue with predominantly
normal characteristics: In most cases, they cause relatively minor symptoms and
are amenable to surgical therapy. Benign tumours, however, can become clinically
important when they occur in organs in which compression is possible and surgery
cannot be easily performed (e.g. the brain), and when they produce hormones or
other substances with a systemic effect (e.g. epinephrine produced by benign pheochromocytoma) [2].
Malignant neoplasms are characterized by progressive growth of tissue with
structural and functional alterations with respect to the normal tissue. A peculiarity
of most malignant tumours is the ability to migrate and colonize other organs (metastatization) via blood and lymph vessel penetration [2].

[Link]()
Section of Hygiene, Institute of Public Health,
Universit Cattolica del Sacro Cuore, [Link] F. Vito 1, 00168 Rome, Italy
e-mail: sboccia@[Link]
[Link] Vecchia
Department of Clinical Sciences and Community Health,
Universit degli Studi di Milano, Via Augusto Vanzetti 5, 20122 Milan, Italy
e-mail: [Link]@[Link], lavecchia@[Link]
[Link]
Mount Sinai School of Medicine Tisch Cancer Institute,
1190 5th Avenue, 10029 New York, NY, USA
e-mail: [Link]@[Link]
Springer International Publishing Switzerland 2015
S. Boccia et al. (eds.), A Systematic Review of Key Issues in Public Health,
DOI 10.1007/978-3-319-13620-2_5

65

66

S. Boccia et al.

Knowledge about the causes and consequently the possible preventive strategies
for malignant neoplasms has greatly advanced during the past decades. This has
been largely based on the development of cancer epidemiology. Indeed, the identification of the determinants of cancer relies on two complementary approaches, the
epidemiological and the experimental, and the epidemiological one has produced
both general and specific evidence for the role of different types of agents in cancer
causation.
Genetic determinants of cancer have also been demonstrated. Several inherited
conditions carry a very high risk of one or several cancers. High-penetrance genes
are identified through family-based and other linkage studies. These conditions are
rare and explain only a small proportion of human cancers. Genetic factors are also
likely to play an important role in interacting with non-genetic factors to determine
individual susceptibility to cancer, although the observation of changes of incidence
in migrant groups after they have moved to a new living environment suggests a
major role of non-genetic factors.
In parallel to the identification of the causes of cancer, primary preventive strategies have been developed. Secondary preventive approaches have also been proposed and in some cases their effectiveness has been evaluated. A careful consideration of the achievements of cancer research, however, suggests that the advancements in knowledge about the causes of cancer have not been followed by an equally important reduction in the burden of cancer. Part of this paradox is explained by
the long latency occurring between exposure to carcinogens and development of
the clinical disease. Thus, changes in exposure to risk factors are not followed immediately by changes in disease occurrence. The main reason for the gap between
knowledge and public health action, however, rests with the cultural, societal and
economic aspects of exposure to most carcinogens.

Epidemiology
Global Burden of Disease
The number of new cases of cancer worldwide in 2008 has been estimated at about
12,700,000 [3]. Of these, 6,600,000 occurred in men and 6,000,000 in women.
About 5,600,000 cases occurred in high-resource countries (North America, Japan,
Europe including Russia, Australia and New Zealand) and 7,100,000 in low- and
middle-income countries. Among men, lung, stomach, colorectal, prostate and liver
cancers are the most common malignant neoplasms (Fig.5.1), while breast, colorectal, cervical, lung and stomach are the most common neoplasms among women
(Fig. 5.2). The number of deaths from cancer was estimated at about 7,600,000
in 2008 [3]. No global estimates of survival from cancer are available: Data from
selected cancer registries suggest wide disparities between high- and low-income

5 Epidemiology of Cancer and Principles of Prevention

67

>
W

^
>
K

E,
>
>
<
W
>

K

>

D

Fig. 5.1 Estimated number of new cancer cases (1000), 2008men [3]




>
^

K
>
d
>
E,
K
W

<

>

D

Fig. 5.2 Estimated number of new cancer cases (1000), 2008women [3]

68

S. Boccia et al.

^

>


K
 &
 &
K &

h^ ^Z

Fig. 5.3 Five-year relative survival from cancer in selected populations [46]

countries for neoplasms with effective but expensive treatment, such as leukaemia,
while the gap is narrow for neoplasms without an effective therapy, such as lung
cancer (Fig.5.3) [46]. The overall 5-year survival of cases diagnosed during 1995
1999 in 23 European countries was 49.6% [5]. A complementary approach in assessing the global burden of neoplasms is to estimate the loss in disability-adjusted
life-years (DALYs). This indicator weighs the years of life with disability and adds
them to the years lost because of premature death. An estimate for 2008 resulted
in about 169,000,000 DALYs lost worldwide because of malignant neoplasms. In
absolute terms, Asia and Europe contributed to 73% of DALYs lost because of
cancer, and China for 25%. Lung, liver, breast, stomach, colorectal, cervical and
oesophageal cancers and leukaemia had the highest proportion of DALYs, with a
combined contribution of 65% to the total cancer burden [7].

Risk Factors
Tobacco Smoking
Tobacco smoking is the main single cause of human cancer worldwide [8] and the
largest cause of death and disease. It is the key cause of lung cancer, and a major
cause of cancers of the oral cavity, pharynx, nasal cavity, larynx, oesophagus, stomach, pancreas, uterine cervix, kidney and bladder, as well as of myeloid leukaemia.
In high-income countries, tobacco smoking causes approximately 30% of all human cancers [9]. In many middle- and low-income countries, the burden of tobaccorelated cancer is still lower, given the relatively recent start of the epidemics of

5 Epidemiology of Cancer and Principles of Prevention

69

smoking, which will however result in a greater number of cancers in the future, in
the absence of adequate intervention to control tobacco.
A benefit of quitting tobacco smoking in adulthood has been shown for all major
cancers causally associated with the habit. Smokers who stop around age 50 avoid
over 50% of overall excess mortality from all causes [1012], from lung cancers
[13] as well as from other tobacco-related cancers [14], and those who stop around
age 40 or earlier avoid most of their tobacco-related cancer risk.
This emphasizes the need to devise anti-smoking strategies that address avoidance of the habit among the young, as well as reduction of smoking and quitting
among adults. In fact, the decline in tobacco consumption that has taken place
during the past half century among men in North America and several European
countries, and which has resulted in decreased incidence of and mortality from
lung cancer [1517], was caused primarily by quitting at middle age. The great
challenge for the control of tobacco-related cancers, however, lies today in middleand low-income countries, in particular in China and other Asian countries: The
largest increase in tobacco-related cancers has been forecasted in this region of the
world [18]. The control of tobacco-related cancers in the first half of this century is
essentially due to stopping in middle age, since diseases and deaths in adolescents
who stand now with occur in the second half of the century. Despite growing efforts from medical and public health institutions and the growing involvement of
non-governmental organizations, the fight against the spread of tobacco smoking
among women and in middle-low-income countries remains the biggest and most
difficult challenge of cancer prevention in the next decades. In 2008, the World
Health Organization (WHO) established the MPOWER policy package highlighting priority interventions towards tobacco control [19]. The evidence base for the
effect of the MPOWER recommendations is still limited, though the prevalence
of tobacco smoking has declined across the WHO regions. Modelling suggests,
however, that it will be difficult to achieve rates below 10% within a 20-year time
horizon [20].
Use of smokeless tobacco products has been associated with increased risk of
cancer of the head and neck and the pancreas [8], though the data remain open to
discussion [21]. Chewing of tobacco-containing products is particularly prevalent
in Southern Asia, where it represents a major cause of oral and pharyngeal cancer.

Dietary Factors
The role of dietary factors in causing human cancer remains largely obscure. For
no dietary factor other than alcohol and aflatoxin (a carcinogen produced by some
fungi in certain tropical areas), there is sufficient evidence of an increased or decreased risk of cancer. In particular, a role of intake of fat in determining breast
and colorectal cancer risk has not been confirmed by recent meta-analyses [22,
23]. A high intake of red and processed meat, instead, has been associated with an
increased risk of colorectal cancer in a meta-analysis of prospective studies [24],

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S. Boccia et al.

and a protective effect has been reported for fish intake [25], milk and total dairy
products [26] and magnesium intake [27].
Thus, the World Cancer Research Foundation 2007 [28] recommends the population average consumption of red meat to be no more than 300g (11oz) a week,
very little if any of which is processed.
Concerning vegetable intake, the World Cancer Research Foundation 2007 report [28] gave probable evidence of risk reduction with cancers of the mouth and
pharynx, larynx, oesophagus and stomach, and limited evidence for nasopharynx,
lung, colorectum, ovary and endometrium. With reference to fruit, it gave probable
evidence of risk reduction for mouth and pharynx, larynx, oesophagus, lung and
stomach, and limited for nasopharynx, pancreas, liver and colorectum.
A number of vitamins and other micronutrients or food components (including
carotenoids, lycopene and flavonoids) showed an inverse relation with cancer risk.
With reference to flavonoids, there are suggestions for a protective role of flavanones on upper aerodigestive tract, proanthocyanidins on gastric cancer, flavonols
and proanthocyanidins on colorectal, flavonols and flavones on breast and isoflavones on ovarian cancers [29].
There is evidence of lack of cancer-preventive activity for preformed vitamin A
[30] and for -carotene when used at high doses [31], and a lack of evidence of increased cancer risk associated with vitamin D status [32]. Systematic reviews have
concluded that nutritional factors may be responsible for about one fourth of human
cancers in high-income countries, although, because of the limitations of the current
understanding of the precise role of diet in human cancer, the proportion of cancers
known to be avoidable in practicable ways is much smaller [9]. The only justified
dietary recommendation for cancer prevention is to reduce the total caloric intake,
which would contribute to a decrease in overweight and obesity, an established risk
factor for human cancer.

Obesity and Physical Exercise

There is sufficient evidence for a cancer-preventive effect of avoidance of weight
gain, with reference to risk of cancers of the colon, gallbladder, postmenopausal
breast, endometrium, kidney and oesophagus (adenocarcinoma) [33]. The recommendation number one of the World Cancer Research Foundation 2007 report [28]
suggests to be as lean as possible within the normal range of body weight.
It is likely that obesity exerts a carcinogenic effect in conjunction with other
factors such as insulin resistance, low physical activity and menopausal status.
The magnitude of the excess risk is not very high (for most cancers, the relative
risk (RR) ranges between 1.5 and 2 for body weight higher than 35% above the
ideal weight). Estimates of the proportion of cancers attributable to overweight
and obesity in Europe range from 2% [9] to 5% [34]. However, this figure is
likely to be larger in North America, where the prevalence of overweight and
obesity is higher.

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Increasing physical activity should be a part of any comprehensive cancer prevention strategy. Increased workplace or recreational physical activity decreased
the risk of colon and breast cancers and that of endometrial and prostate cancers
[33]. The RR of colon and breast cancers for regular versus no activity is in the order of 1.52. Worldwide, physical inactivity (defined as do not engage in any brisk
walking for at least 30min every day) causes 10% (5.614.1) of breast cancer and
10% (5.713.8) of colon cancer cases [35].

Alcohol Drinking
Alcohol drinking increases the risk of cancers of the oral cavity, pharynx, larynx,
oesophagus and liver, colorectum and female breast [36]. For all cancer sites, risk
is a function of the amount of alcohol consumed. Alcohol drinking and tobacco
smoking show an interactive (i.e. multiplicative) effect on the risk of cancers of the
head and neck.
Heavy alcohol consumption (i.e. 4 drinks/day) is significantly associated with
an about fivefold increased risk of oral and pharyngeal cancer and oesophageal
squamous cell carcinoma (SqCC), 2.5-fold for laryngeal cancer, 50% for colorectal
and breast cancers and 30% for pancreatic cancer [37]. These estimates are based
on a large number of epidemiological studies, and are generally consistent across
strata of several covariates. The evidence suggests that at low doses of alcohol consumption (i.e. 1 drink/day) the risk is also increased by about 20% for oral and
pharyngeal cancer and 30% for oesophageal SqCC. While consumption of less than
three alcoholic drinks/week is not associated with an increased risk of breast cancer,
an intake of 36 drinks/week might already yield a (small) increase in risk. On the
other hand, intakes up to one drink/day are not associated with the risk of laryngeal,
colorectal and pancreatic cancer [38].
The positive association between alcohol consumption and the risk of head and
neck cancers is independent from tobacco exposure [37]. The global burden of cancer attributable to alcohol drinking has been estimated at 3.6 and 3.5% of cancer
deaths [39], although this figure is higher in high-income countries (e.g. the figure
of 6% has been proposed for UK [9] and 9% in Central and Eastern Europe).
These included over 5% of cancers and cancer deaths in men and about 1.5% of
cancers and cancer deaths in women. Restriction of alcohol drinking to the limits indicated by the European Code Against Cancer [40] (20g/day for men and 10g/day
for women) would avoid about 90% of alcohol-related cancers and cancer deaths in
men and over 50% of cancers in women, i.e. about 330/360,000 cancer cases and
about 200/220,000 cancer deaths. Avoidance or moderation of alcohol consumption
to 2 drinks/day in men and 1 drink/day in women is therefore a global public health
priority.

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Infectious Agents
There is growing evidence that chronic infection with some viruses, bacteria and
parasites represents a major risk factor for human cancer, in particular in low-income countries. A number of infectious agents have been evaluated within the International Agency for Research on Cancer (IARC) Monograph programme, and
the evidence of a causal association has been classified as sufficient for several of
them. A global burden of cancers attributable to infections in 2008 has been published in 2012 [41]. The population attributable fraction for infectious agents was
16.1% in 2008, meaning that around two million new cancer cases were attributable to infections. Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related
liver cancer, human papillomavirus (HPV)-related cervical cancer and Helicobacter
pylori-related stomach cancer overall are responsible for 95% of the total number
of infection-related cancers. The estimate of the attributable fraction is higher in
low- and middle-income countries than in high-income countries (22.9% of total
cancer vs. 7.4%).
Use of safe, effective (and ideally cheap) vaccines represents the best preventive strategy for cancers caused by viruses, and HBV and HPV infection can be
effectively prevented today. Chronic infection with H. pylori can be prevented by
eradication treatment and sanitation measures, and changes in dietary practices (e.g.
avoidance of raw fish) can prevent infection by carcinogenic parasites.

Occupation and Pollution

Approximately 40 occupational agents, groups of agents and mixtures have been
classified as carcinogenic by IARC. While some (e.g. bis-chloromethythes) represent today a historic curiosity, exposure is still present for carcinogens such as
asbestos, silica, arsenic and polycyclic aromatic hydrocarbons (PAHs). Estimates
of the global burden of cancer attributable to occupation in high-income countries
result in the order of 15% [9, 42]. In the past, almost 50% of these were due to asbestos alone, while in recent years the impact of asbestos on lung cancer (but not yet
mesothelioma in several populations) is levelling off [43]. However, these cancers
concentrate in some sectors of the population (mainly male blue-collar workers),
among whom they may represent a sizable proportion of total cancers. Furthermore, unlike lifestyle factors, exposure is involuntary. An appreciable reduction of
exposure to occupational and environmental carcinogens has taken place in highincome, but also in several middle-income, countries during recent decades. Still,
further efforts should be made to further control exposure, particularly in low- and
middle-income countries.
The available evidence suggests, in most populations, a small role of air, water
and soil pollutants. Global estimates are in the order of 1% or less of total cancers [9, 42]. This is in striking contrast with public perception, which often identifies pollution as a major cause of human cancer. However, in selected areas (e.g.

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residence near asbestos processing plants or in areas with drinking water contaminated by arsenic), environmental exposure to carcinogens may represent an important cancer hazard.

Reproductive Factors and Exogenous Hormones

There is a strong association between reproductive history and risk of cancer of the
breast, ovary and endometrium. However, the role played by specific hormones
and the mechanisms by which they act are still unclear. The reproductive factors
with the strongest effect on breast cancer risk are parity and age at first full-term
pregnancy. Nulliparity or low parity is also related to increased risk of endometrial
and ovarian cancer. In contrast, high parity is associated with an increased risk of
cervical cancer. Oestrogenic stimulation is probably a major cause of breast cancer,
as shown by the strong reduction in breast cancer risk among women enrolled in
randomized trials of tamoxifen and other antioestrogenic drugs. Exogenous oestrogens and progestins given in combination as hormone replacement therapy (HRT)
in menopause and in steroid contraceptives increase the risk of breast cancer [44].
The risk is present, but considerably smaller, for use of oestrogen-only HRT. In
contrast, unopposed oestrogens are strongly related to endometrial cancer. Oral contraceptives (OCs) exert a consistent and long-term protection against ovarian and
endometrial cancer, but current use of OCs is associated with an increased risk of
breast and cervical cancer [44]. Current OC use has also been associated with an
excess risk of benign liver cancer and a modest increase of liver cancer [45]. No
detailed estimates are available of the contribution of reproductive factors to the
global burden of cancer, and given the uncertainties in the definition of the relevant
circumstances of exposure, proposed figures for high-income countries range from
3% [46] to 15% [9].
An effect of sex hormones on testicular and prostate cancer is plausible, but the
epidemiological evidence is currently inadequate to draw any conclusion.

Perinatal and Growth Factors

Excess energy intake early in life is probably associated with an increased risk of
breast and colon cancer [47]. The role of attained height, growth factors and other
factors such as insulin resistance is unclear. In addition, high birth weight is possibly associated with an increased risk of breast, prostate cancer and head and neck
cancer. The implications of these findings for preventive strategies should be clarified by a more complete understanding of the underlying carcinogenic mechanisms.

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Ionizing and Nonionizing Radiation

Ionizing radiation causes several neoplasms, including in particular acute lymphocytic leukaemia, acute and chronic myeloid leukaemia and cancers of the breast,
lung, bone, brain and thyroid [48]. Theoretical considerations and extrapolations
from high doses lead to the conclusion that a threshold below which no excess
cancer risk is present is unlikely, although the quantification of the excess risk at
low doses, at which most people are commonly exposed, is difficult. For most individuals, the main exposure is natural radiation, including indoor radon, although
artificial sources (e.g. radiotherapy) might be important in particular cases. The
estimates of the contribution of ionizing radiation to human cancer in high-income
countries are in the order of 3% [46] to 5% [9].
Solar (ultraviolet, UV) radiation is carcinogenic to the skin. Over 90% of skin
neoplasms are attributable to sunlight; because of the low fatality of non-melanocytic skin cancer, solar radiation is responsible for about 1% of total cancer deaths
[9]. Avoidance of sun exposure, in particular during childhood, is an important
cancer-preventive behaviour. The evidence of a carcinogenic effect of other types
of nonionizing radiations, in particular electric and magnetic fields, is inconclusive
and likely negligible, if any [49].

Medical Procedures and Drugs

The drugs that may cause or prevent cancer fall into several groups. Many cancer
chemotherapy drugs are active on the DNA, which might also result in damage to
normal cells. The main neoplasm associated with chemotherapy treatment is leukaemia, although the risk of solid tumours might also be increased. A second group
of carcinogenic drugs includes immunosuppressive agents, notably used in transplanted patients. Non-Hodgkins lymphoma (NHL) is the main neoplasm caused by
these drugs. The effects of HRT and OCs are discussed above. Phenacetin-containing analgesics increase the risk of cancer of the renal pelvis.
No precise estimates are available for the global contribution of drug use to human cancer. It is unlikely, however, that they represent more than 1% in high-resource countries [9]. Furthermore, the benefits of therapies are usually much greater
than the potential cancer risk.
Use of ionizing radiation for diagnostic purposes is likely to carry a small risk
of cancer, which has been demonstrated only for childhood leukaemia following
intrauterine exposure. Radiotherapy increases the risk of cancer in the irradiated
organs. There is no evidence of an increased cancer risk following other medical
procedures, including surgical implants.
Chemoprevention can also be considered for primary and secondary prevention
of cancer, but data are negative or inconsistent for most micronutrients or other
substances considered.

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Data are however more promising for aspirin. In fact, aspirin has been associated
with a reduced risk of colorectal and possibly of a few other common cancers, but
quantification remains open to discussion [50]. A meta-analysis of observational
studies on aspirin and 12 cancer sites published up to September 2011 included
a total of 139 studies [51]. Regular aspirin is associated with a reduced risk of
colo