Papers by Roberto Ferrari
Nature reviews. Cardiology, 2016
Elevated heart rate is known to induce myocardial ischaemia in patients with coronary artery dise... more Elevated heart rate is known to induce myocardial ischaemia in patients with coronary artery disease (CAD), and heart rate reduction is a recognized strategy to prevent ischaemic episodes. In addition, clinical evidence shows that slowing the heart rate reduces the symptoms of angina by improving microcirculation and coronary flow. Elevated heart rate is an established risk factor for cardiovascular events in patients with CAD and in those with chronic heart failure (HF). Accordingly, reducing heart rate improves prognosis in patients with HF, as demonstrated in SHIFT. By contrast, data from SIGNIFY indicate that heart rate is not a modifiable risk factor in patients with CAD who do not also have HF. Heart rate is also an important determinant of cardiac arrhythmias; low heart rate can be associated with atrial fibrillation, and high heart rate after exercise can be associated with sudden cardiac death. In this Review, we critically assess these clinical findings, and propose hypoth...
Zoological Science, Dec 15, 1998
The present paper presents an application of the Triple Mark Recapture technique on two Italian p... more The present paper presents an application of the Triple Mark Recapture technique on two Italian populations of the subterranean termite (Reticulitermes lucifugus). Two large infested areas in the historical center of the town Bagnacavallo (Ravenna) were chosen. Two dye markers were utilized, Nile Blue A or Neutral Red respectively for the two sites. The first population was estimated at 1,085,000 ± 92,000 insects, foraging on a surface of 1500 m 2 ; the second, smaller, population has been estimated to be 640,000 ± 33,000 insects, foraging on an area of 675 m 2 . Maximum linear distance observed in both sites was 45-50 m. Population dynamics look different in the two sites: in the first site the spread distribution with a few insects at each feeding point probably indicates an old, well established, population which grows slowly in all directions during the hot season. In the second site the expansion was much more rapid and it is possible to hypothesise that the termite colony settled in this area more recently and that it is a relatively young, growing colony. The gathered data appear of great utility in extending the knowledge about biology, ecology and behaviour of the Italian subterranean termite.
Giornale italiano di cardiologia (2006), Jun 1, 2016
Atherosclerotic cardiovascular disease still represents the leading cause of death in western cou... more Atherosclerotic cardiovascular disease still represents the leading cause of death in western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proven effective in improving clinical outcomes. This document is focused on the clinical management of hypercholesterolemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors have considered with particular attention the role of hypercholesterolemia in the genesis of atherosclerotic cardiovascular disease. Besides, the implications of high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analyzed, while all available therapeutic options for blood cholesterol reduction and cardiovascula...
Journal of Entomological and Acarological Research, Aug 20, 2011
We relate and discuss the application of a monitoring-baiting program with the IGR hexaflumuron t... more We relate and discuss the application of a monitoring-baiting program with the IGR hexaflumuron to termite control in Bagnacavallo (Ravenna, Northern Italy), where a massive Reticulitermes urbis infestation existed in the old town. Termite control was carried out in different zones over a period of 15 years, starting from the centre of the infested area and extending towards the peripheral areas. The treatment succeeded in eliminating termites from Bagnacavallo old town, using a total of 63 g of hexaflumuron.
European journal of heart failure, Jan 16, 2015
Many uncertainties surround the syndrome of heart failure with preserved ejection fraction (HFpEF... more Many uncertainties surround the syndrome of heart failure with preserved ejection fraction (HFpEF), which was the topic reviewed in an Expert Meeting at the University of Ferrara. This concluded that the absence of clear diagnostic clinical criteria was the major barrier to progress. There was general agreement that symptoms or signs of heart failure, normal LVEF despite an elevated plasma concentration of natriuretic peptides, and signs of abnormal LV relaxation, LV filling, LV hypertrophy, or left atrial enlargement, or diastolic dysfunction supported the diagnosis. However, HFpEF, like all heart failure syndromes, is heterogeneous in aetiology and pathophysiology, rather than being a single disease. HFpEF may account for about half of all patients with heart failure. The classical risk factors for developing HFpEF include age and co-morbidities, notably hypertension, atrial fibrillation, and the metabolic syndrome. When complicated by increasing congestion requiring hospital admi...
International Journal of Cardiology, 2015
Cardiovascular disease, especially ischemic heart disease, is a major comorbidity in chronic obst... more Cardiovascular disease, especially ischemic heart disease, is a major comorbidity in chronic obstructive pulmonary disease (COPD) patients. Several studies suggested that after acute exacerbation of COPD (AECOPD), there is a significant increase of mortality (cardiac and all-cause) and of myocardial infarction. Whether cardiac troponin (Tn) elevation during AECOPD could be considered a prognostic marker of all-cause mortality is still debated. To assess the prognostic role of cardiac Tn elevation during AECOPD, we performed a systematic review and meta-analysis. We included studies with patients admitted to the hospital for AECOPD, with at least one Tn assessment and reporting the relationship (after multivariable analysis) between Tn elevation and all-cause mortality. Secondarily, studies were stratified according to: i) type of troponin (Tn I or Tn T), and ii) follow-up length (≤6months vs. >6months). Ten studies were included in the systematic review and 8 in the meta-analysis. Cardiac Tn elevation ranges from 18% to 73%. We found that cardiac Tn elevation was significantly related to an increased risk for all-cause mortality (OR 1.69; 95% CI 1.25-2.29; I(2) 40%). This finding was independent to the follow-up length of studies (≤6months: OR 3.22; 95% CI 1.31-7.91; >6months: OR 1.38; 95% CI 1.02-1.86). Finally, Tn T seems to be more helpful in predicting all-cause mortality as compared to Tn I (OR 1.54; 95% CI 1.2-1.96 vs. OR 3.39, 95% CI 0.86-13.36, respectively). In patients admitted to the hospital for AECOPD, cardiac Tn elevation emerged as an independent predictor of increased risk of all-cause mortality.
The American Journal of Medicine, 2015
Background: Elevated resting heart rate is associated with increased cardiovascular risk, particu... more Background: Elevated resting heart rate is associated with increased cardiovascular risk, particularly in patients with left ventricular systolic dysfunction. Heart rate is not routinely monitored in these patients. We hypothesized that routine monitoring of heart rate would increase its prognostic value in patients with left ventricular systolic dysfunction. We analyzed the relationship between heart rate measurements and a range of adverse cardiovascular outcomes, including hospitalization for worsening heart failure, in the pooled placebo-treated patients from BEAUTIFUL and SHIFT, using standard and time-varying covariate Cox proportional hazards models. Adjusting for other prognostic factors, models were fitted for baseline heart rate alone or for time-updated heart rate (latest heart rate) alone or corrected for baseline heart rate or for immediate previous time-updated heart rate. Results: Baseline heart rate was strongly associated with all outcomes apart from hospitalization for myocardial infarction. Time-updated heart rate increased the strengths of associations for all outcomes. Adjustment for baseline heart rate or immediate previous time-updated heart rate modestly reduced the prognostic importance of timeupdated heart rate. For hospitalization for worsening heart failure, each 5 beats per minute increase in baseline heart rate and time-updated heart rate was associated with a 15% (95% CI 12%-18%) and 22% (19%-40%) increase in risk, respectively. Even after correction, the prognostic value of time-updated heart rate remained greater. In patients with LVSD, time-updated heart rate is more strongly related with adverse cardiovascular outcomes than baseline heart rate. Heart rate should be measured to assess cardiovascular risk at all assessments of patients with left ventricular systolic dysfunction.
PLOS ONE, 2015
Few data are available regarding the use of antithrombotic strategies in coronary artery disease ... more Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF…
Archivos de Cardiología de México, 2015
To evaluate the use of β-blockers and to monitor heart rate in Mexican patients with coronary art... more To evaluate the use of β-blockers and to monitor heart rate in Mexican patients with coronary artery disease. CLARIFY is an outpatients registry with stable CAD. A total of 33,283 patients from 45 countries were enrolled between November 2009 and July 2010 from which 1342 were Mexican patients. The mean HR pulse was 70bpm (beats per minute). Patients in Mexico were compared with the remaining global CLARIFY population. Patients in Mexico had a higher incidence of acute myocardial infarction and percutaneous coronary intervention, and lower incidence of revascularization surgery compared with the remaining CLARIFY population. More often, Mexican patients presented with diabetes, but less often hypertension and stroke. These patients were split into three mutually exclusive groups of HR ≤60 (N=263), HR 61-69 (N=356) and HR ≥70 (N=722). Patients with elevated HR had a higher incidence of diabetes and higher diastolic blood pressure on average than those with controlled HR. Regarding the use of β-blockers, they were used in 63.3% of patients, 2.7% showed intolerance or contraindication to treatment to monitor heart rate, and ivabradine was used in 2.3%. Out of approximately 849 patients receiving treatment of β-blockers, 52.1% had ≥70bpm HR. In a large proportion of Mexican patients with stable coronary disease the HR remain elevated, >70bpm, even with the use of β-blockers; this requires further attention.
eLife, Jan 7, 2015
Methylation of cytosines (5(me)C) is a widespread heritable DNA modification. During mammalian de... more Methylation of cytosines (5(me)C) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves of de novo DNA methylation. In vivo mechanisms of DNA methylation establishment are largely uncharacterized. Here we use Saccharomyces cerevisiae as a system lacking DNA methylation to define the chromatin features influencing the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4 methylation are mutually exclusive and that DNMT3B is co-localized with H3K36 methylated regions. In support of this observation, DNA methylation analysis in yeast strains without Set1 and Set2 show an increase of relative 5(me)C levels at the TSS and a decrease in the gene-body, respectively. We extend our observation to the murine male germline, where H3K4me3 is strongly anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These results show the importance of H3K36 methylation for gene-body DNA methyl...
Pharmacological research : the official journal of the Italian Pharmacological Society, Jan 3, 2015
Verbascoside, a phenolic compound, showed several favorable biological activities, including an a... more Verbascoside, a phenolic compound, showed several favorable biological activities, including an antiplatelet activity. No in vivo studies tested its efficacy and safety in subjects with cardiovascular (CV) factors. The aim of this randomized, single-center, double-blind, phase II study was to assess the efficacy and tolerability of verbascoside intake for the modulation of platelet aggregation (PA) values in subjects with cardiovascular (CV) risk factors. One-hundred subjects with at least one CV risk factor (age >65 years, diabetes mellitus, hypertension, current cigarettes use, hyperlidemia, waist circumference >102cm in male or >88cm in female) were enrolled and randomly assigned to receive placebo or verbascoside 50mg or verbascoside 100mg. PA was measured at baseline and after 2 weeks of study drug assumption, with light transmittance aggregometry (arachidonic acid, AA, 1μM and adenosine diphosphate, ADP, 5μM). Two weeks of treatment with placebo or verbascoside 50mg d...
Archives of cardiovascular diseases
Improvements in the treatment of coronary artery disease mean that an increasing number of patien... more Improvements in the treatment of coronary artery disease mean that an increasing number of patients survive acute cardiovascular events and live as outpatients with or without anginal symptoms. To determine the characteristics and management of contemporary outpatients with stable coronary artery disease in Western Europe, and to compare France with the other Western European countries. CLARIFY (prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is an international, prospective, observational, longitudinal study. Between November 2009 and July 2010, 32,954 adult outpatients with stable coronary artery disease (defined as a history of documented myocardial infarction [of >3 months], prior coronary revascularization, chest pain with myocardial ischaemia, or coronary stenosis of>50% proven by angiography) were enrolled in 45 countries. The demographics and management of CLARIFY patients enrolled in France were compared with those enro...
International journal of cardiology, 2014
To use CLARIFY, a prospective registry of patients with stable CAD (45 countries), to explore hea... more To use CLARIFY, a prospective registry of patients with stable CAD (45 countries), to explore heart rate (HR) control and beta-blocker use. We analyzed the CLARIFY population according to beta-blocker use via descriptive statistics with Pearson's χ(2) test for comparisons, as well as a multivariable stepwise model. Data on beta-blocker use was available for 32,914 patients, in whom HR was 68 ± 11 bpm; patients with angina, previous myocardial infarction, and heart failure had HRs of 69 ± 12, 68 ± 11, and 70 ± 12 bpm, respectively. 75% of these patients were receiving beta-blockers. Bisoprolol (34%), metoprolol tartrate (16%) or succinate (13%), atenolol (15%), and carvedilol (12%) were mostly used; mean dosages were 49%, 76%, 35%, 53%, and 45% of maximum doses, respectively. Patients aged <65 years were more likely to receive beta-blockers than patients ≥ 75 years (P<0.0001). Gender had no effect. Subjects with HR ≤ 60 bpm were more likely to be on beta-blockers than patie...
Revista española de cardiología (English ed.), 2014
Coronary artery disease is associated with high morbidity and mortality. The objective of the CLA... more Coronary artery disease is associated with high morbidity and mortality. The objective of the CLARIFY registry is to study the treatment of outpatients with coronary artery disease in the setting of daily clinical practice. The CLARIFY registry is a prospective registry conducted in 41 countries that included outpatients with stable coronary artery disease attending primary care or specialist units between October 2009 and June 2010. The present study describes the baseline characteristics of the Spanish cohort compared with the western European cohorts included in the registry. A total of 33,248 patients were included: 14,726 in western Europe and 2257 in Spain (selected by 192 cardiologists). The majority of the participants in Spain were men (81%) with a mean age of 65 years. There was a higher frequency of diabetes (34% vs 25%; P<.0001), coronary artery disease family history (19% vs 31%; P<.0001), myocardial infarction (64% vs 60%; P<.0001), and stroke (5% vs 3%; P=.00...
Italian heart journal : official journal of the Italian Federation of Cardiology, 2005
Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy, 2001
Acta vitaminologica et enzymologica, 1983
When cardiac muscle becomes hypoxic the cells become oedematous and the fine ultrastructure is al... more When cardiac muscle becomes hypoxic the cells become oedematous and the fine ultrastructure is altered. Developed tension declines and resting tension increases. The cellular stores of ATP and CP are depleted and the mitochondria exhibit an altered respiration, characterized by a reduced state III respiration and a lowered respiratory control index. Reoxygenation results in a further increase of the hypoxic damage. Using these changes in function as indices of the severity of the damage caused by hypoxia and reoxygenation, we have investigated whether the administration of alfa-tocopherol provides protection. Adult male New Zealand white rabbits were used. The hearts were isolated, Langendorff perfused and then made hypoxic. Alfa-tocopherol acetate was infused directly into the aorta inflow cannula, 20 minutes before the onset of hypoxia and was continued for the remainder of the perfusion. Hypoxia was established by substituting 95% N2 and 5% CO2 + CO2 in the gas mixture. The alfa-...
Global Cardiology Science and Practice, 2013
The renin-angiotensin-aldosterone system (RAAS) regulates the body&amp;amp;amp;amp;amp;amp;am... more The renin-angiotensin-aldosterone system (RAAS) regulates the body&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s hemodynamic equilibrium, circulating volume, and electrolyte balance, and is a key therapeutic target in hypertension, the world&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s leading cause of premature mortality. Hypertensive disorders are strongly linked with an overactive RAAS, and RAAS inhibitors, like angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), are routinely used to treat high blood pressure (BP). BP reduction is one of the main goals of current European hypertension guidelines. Oral ACE inhibitors, the oldest category of RAAS inhibitor, were commercially released over 30 years ago in the early 1980s, over a decade before the first ARBs became available. The introduction of ACE inhibitors heralded major changes in the way hypertension and cardiovascular disease were treated. Although the decision of the medical community to replace older ACE inhibitors with more modern ARBs in the 1990s was debatable, it did nevertheless allow scientists to learn more about the angiotensin receptors involved in RAAS stimulation. This and much else of value have been discovered since RAAS inhibitors first became available, but some surprising gaps in our knowledge exist. Until recently, the effect of RAAS inhibition on mortality in hypertension was unknown. This question was recently addressed by a meta-analysis of randomized controlled trials in populations who received contemporary antihypertensive medication. The results of this meta-analysis have helped elucidate the long-term consequences of treatment with RAAS inhibitors on mortality in hypertension. This article will consider the differences between RAAS inhibitors in terms of pharmacological and clinical effects and analyze the impact of the main types of RAAS inhibitor, ACE inhibitors and ARBs, on mortality reduction in hypertensive patients with reference to this latest meta-analysis.
Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy, 2002
Angiotensin-converting enzyme (ACE) activation and the de novo production of angiotensin II contr... more Angiotensin-converting enzyme (ACE) activation and the de novo production of angiotensin II contribute to cardiovascular disease through direct pathological tissue effects, including vascular remodeling and inflammation, as well as indirect action on nitric oxide bioavailability and its consequences. The endothelium plays a pivotal role in both vascular function and structure; thus, the predominant localization of ACE to the endothelium has implications for the pathobiology of vascular disease, such as coronary artery disease. Numerous experimental studies and clinical trials support the emerging realization that tissue ACE is a vital therapeutic target, and that its inhibition may restore endothelial function or prevent endothelial dysfunction. These effects exceed those attributable to blood pressure reduction alone; hence, ACE inhibitors may exert an important part of their effects through direct tissue action. Pharmacologic studies show that while ACE inhibitors may differ accor...
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Papers by Roberto Ferrari