International journal of epidemiology, Jan 14, 2015
This study investigated associations between work-family life courses and biomarkers of inflammat... more This study investigated associations between work-family life courses and biomarkers of inflammation and stress in mid-life among British men and women. Gender differences in these associations were also explored. A novel statistical method-multi-channel sequence analysis-defined work-family life courses between the ages of 16 and 42 years, combining annual information on work, partnership and parenthood. Associations between work-family life courses and inflammation [C-reactive protein (CRP), fibrinogen and von Willebrand factor] and cortisol at age 44/45 years were tested using multivariate linear regression using multiply-imputed data on almost 6500 participants from the National Child Development Study 1958 British birth cohort. Compared with those who combined strong ties to paid work with later transitions to stable family lives ('Work, later family' group), 'Teen parents' had higher CRP [40.6% higher, 95% confidence interval (CI): 5.6, 87.0] and fibrinogen (7....
Evidence suggests that short and long sleep are associated with a higher risk of type 2 diabetes.... more Evidence suggests that short and long sleep are associated with a higher risk of type 2 diabetes. Using successive data waves spanning >20 years, we examined whether a change in sleep duration is associated with incident diabetes. Sleep duration was reported at the beginning and end of four 5-year cycles: 1985-1988 to 1991-1994 (n = 5,613), 1991-1994 to 1997-1999 (n = 4,193), 1997-1999 to 2002-2004 (n = 3,840), and 2002-2004 to 2007-2009 (n = 4,195). At each cycle, change in sleep duration was calculated for participants without diabetes. Incident diabetes at the end of the subsequent 5-year period was defined using 1) fasting glucose, 2) 75-g oral glucose tolerance test, and 3) glycated hemoglobin, in conjunction with diabetes medication and self-reported doctor diagnosis. Compared with the reference group of persistent 7-h sleepers, an increase of ≥2 h sleep per night was associated with a higher risk of incident diabetes (odds ratio 1.65 [95% CI 1.15, 2.37]) in analyses adjust...
We examined the effect of salivary cortisol on cognitive performance and decline in 3229 adults (... more We examined the effect of salivary cortisol on cognitive performance and decline in 3229 adults (79% men), mean age 61 years. Six saliva samples over the day along with a cognition test battery were administered twice in 5 years. In fully-adjusted cross-sectional analyses from 2002 to 2004, higher waking cortisol was associated with higher reasoning score (β = 0.08, 95% confidence interval: 0.01, 0.15) but this finding was not replicated using data from 2007 to 2009. Over the mean 5 years follow-up there was decline in all cognitive tests but this decline did not vary as a function of cortisol levels; the exception was among APOE e4 carriers where a flatter diurnal slope and higher bedtime cortisol were associated with faster decline in verbal fluency. Changes in cortisol measures between 2002/2004 and 2007/2009 or chronically elevated levels were not associated with cognitive performance in 2007/2009. These results, based on a large sample of community-dwelling adults suggest that ...
Background—The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, a... more Background—The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. Methods and Results—This was a double-blind case-control study of
Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pre... more Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blo...
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a herit... more The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein i...
The association between fatigue and reduced activity in the hypothalamo-pituitary-adrenal (HPA) a... more The association between fatigue and reduced activity in the hypothalamo-pituitary-adrenal (HPA) axis has been described. However the temporal association between fatigue and HPA activity is under debate. We examine whether alterations in cortisol secretion play a role in the development of fatigue or whether changes occur later as a consequence of fatigue in a longitudinal cohort study of 4299 community dwelling adults (mean age 61). Cortisol secretion was measured from saliva samples collected waking, waking + 0.5, 2.5, 8, 12 h and bedtime at phase 7 (2003-2004) of the Whitehall II study. Fatigue was measured at phase 6 (2001), phase 7 and phase 8 (2006) of the Whitehall II study. Three elements of secretion were examined: waking cortisol, the cortisol awakening response and diurnal slope in cortisol secretion. Fatigue was determined using the vitality sub-scale of the Short Form-36. A wide variety of co-variates were measured. We find that fatigue measured at phase 6 was not associated with cortisol secretion at phase 7. At phase 7, low waking cortisol levels and a flat slope in diurnal cortisol secretion were associated with fatigue independently of co-variates. In participants low or free of fatigue at phase 7 low waking cortisol and flatter slope in cortisol secretion were associated with new-onset fatigue at phase 8 (for example, odds ratio for lowest vs. highest tertile of waking cortisol 1.50; 95% confidence intervals, 1.08, 2.09 after adjusting for all co-variates). In conclusion, we find that low waking salivary cortisol and a flat slope in cortisol secretion is associated with fatigue. Cortisol is also associated with future onset of fatigue suggesting that changes in cortisol secretion are etiologic or occur early in the genesis of fatigue.
Background-A lack of longitudinal studies has made it difficult to establish the direction of ass... more Background-A lack of longitudinal studies has made it difficult to establish the direction of associations between circulating concentrations of low-grade chronic inflammatory markers, such as C-reactive protein and interleukin-6, and cognitive symptoms of depression. The present study sought to assess whether C-reactive protein and interleukin-6 predict cognitive symptoms of depression or whether these symptoms predict inflammatory markers.
Background: Low muscle mass and function have been associated with poorer indicators of physical ... more Background: Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.
Minireview: Mechanisms by Which the Metabolic Syndrome and Diabetes Impair Memory
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2000
Type 2 diabetes is associated with an increased risk of cognitive dysfunction. These effects seem... more Type 2 diabetes is associated with an increased risk of cognitive dysfunction. These effects seem particularly true for memory functions. This article examines how diabetes and the biological changes that occur with diabetes such as hyperglycemia, changes in insulin concentration, hypertension, and changes in lipid levels might lead to these alterations in cognitive functioning, with an emphasis on the mechanisms leading to changes in memory.
Objective: To examine change in health functioning as women progress through the menopausal trans... more Objective: To examine change in health functioning as women progress through the menopausal transition. Study Design and Setting: Prospective study of 2,489 women followed through four phases of the Whitehall II study. Health functioning was assessed with the eight subscales of the SF-36.
only adult height was related to region of birth, after adjustment for region of examination (P ¼... more only adult height was related to region of birth, after adjustment for region of examination (P ¼ 0.002) Conclusions Although individual disease risk is predicted by early life factors, early exposures do not explain regional variations in cardiovascular and respiratory risk factors among middle-aged adults in Britain. Geographical inequalities in cardiorespiratory health are more strongly related to factors associated with region of examination that influence obesity, BP and ventilatory function.
Sleep deprivation (Յ5 hour per night) was associated with a higher risk of hypertension in middle... more Sleep deprivation (Յ5 hour per night) was associated with a higher risk of hypertension in middle-aged American adults but not among older individuals. However, the outcome was based on self-reported diagnosis of incident hypertension, and no gender-specific analyses were included. We examined cross-sectional and prospective associations of sleep duration with prevalent and incident hypertension in a cohort of 10 308 British civil servants aged 35 to 55 years at baseline (phase 1: 1985-1988). Data were gathered from phase 5 (1997-1999) and phase 7 (2003-2004). Sleep duration and other covariates were assessed at phase 5. At both examinations, hypertension was defined as blood pressure Ն140/90 mm Hg or regular use of antihypertensive medications. In cross-sectional analyses at phase 5 (nϭ5766), short duration of sleep (Յ5 hour per night) was associated with higher risk of hypertension compared with the group sleeping 7 hours, among women (odds ratio: 2.01; 95% CI: 1.13 to 3.58), independent of confounders, with an inverse linear trend across decreasing hours of sleep (Pϭ0.003). No association was detected in men. In prospective analyses (mean follow-up: 5 years), the cumulative incidence of hypertension was 20.0% (nϭ740) among 3691 normotensive individuals at phase 5. In women, short duration of sleep was associated with a higher risk of hypertension in a reduced model (age and employment) (6 hours per night: odds ratio: 1.56 [95% CI: 1.07 to 2.27]; Յ5 hour per night: odds ratio: 1.94 [95% CI: 1.08 to 3.50] versus 7 hours). The associations were attenuated after accounting for cardiovascular risk factors and psychiatric comorbidities (odds ratio: 1.42 [95% CI: 0.94 to 2.16]; odds ratio: 1.31 [95% CI: 0.65 to 2.63], respectively). Sleep deprivation may produce detrimental cardiovascular effects among women. (Hypertension. 2007;50:693-700.) by guest on January 25, 2016 http://hyper.ahajournals.org/ Downloaded from by guest on January 25, 2016 http://hyper.ahajournals.org/ Downloaded from by guest on January 25, 2016 http://hyper.ahajournals.org/ Downloaded from (Hypertension. 2007;50:e170.)
Methods and Results-10,308 London-based male and female civil servants aged 35-55 at phase 1 (198... more Methods and Results-10,308 London-based male and female civil servants aged 35-55 at phase 1 (1985)(1986)(1987)(1988) of the Whitehall II study. Exposures included work stress (assessed at phases 1 and 2). Outcomes included behavioural risk factors (phase 3), the metabolic syndrome (phase 3), heart rate variability, morning rise in cortisol (phase 7) and incident CHD (phases 2 to 7) based on CHD death, non-fatal myocardial infarction or definite angina. Chronic work stress was associated with CHD and this association was stronger among participants aged under 50 (RR 1.68, 95% CI 1.17-2.42). There were similar associations between work stress and low physical activity, poor diet, the metabolic syndrome, its components, and lower heart rate variability. Cross-sectionally, work stress was associated with a higher morning rise in cortisol. Around 32% of the effect of work stress on CHD was attributable to its effect on health behaviours and the metabolic syndrome.
professor of genetic epidemiology, 2,3 Jackie A Cooper, biostatistician, 1 Michael G Marmot, MRC ... more professor of genetic epidemiology, 2,3 Jackie A Cooper, biostatistician, 1 Michael G Marmot, MRC professor of epidemiology and public health, 2 Eric J Brunner, reader in epidemiology and public health, 2 Meena Kumari, senior research fellow in population health, 2 Mika Kivimäki, professor of social epidemiology, 2 Steve E Humphries, BHF professor of cardiovascular genetics 1 ABSTRACT Objectives To assess the performance of a panel of common single nucleotide polymorphisms (genotypes) associated with type 2 diabetes in distinguishing incident cases of future type 2 diabetes (discrimination), and to examine the effect of adding genetic information to previously validated non-genetic (phenotype based) models developed to estimate the absolute risk of type 2 diabetes. Design Workplace based prospective cohort study with three 5 yearly medical screenings. Participants 5535 initially healthy people (mean age 49 years; 33% women), of whom 302 developed new onset type 2 diabetes over 10 years. Outcome measures Non-genetic variables included in two established risk models-the Cambridge type 2 diabetes risk score (age, sex, drug treatment, family history of type 2 diabetes, body mass index, smoking status) and the Framingham offspring study type 2 diabetes risk score (age, sex, parental history of type 2 diabetes, body mass index, high density lipoprotein cholesterol, triglycerides, fasting glucose)-and 20 single nucleotide polymorphisms associated with susceptibility to type 2 diabetes. Cases of incident type 2 diabetes were defined on the basis of a standard oral glucose tolerance test, self report of a doctor's diagnosis, or the use of anti-diabetic drugs.
There is mounting evidence that inflammation plays a role in the development of coronary heart di... more There is mounting evidence that inflammation plays a role in the development of coronary heart disease (CHD). Observations have been made linking the presence of infections in the vessel wall with atherosclerosis, and epidemiological data also implicate infection in remote sites in the aetiology of CHD. In this article we propose a key role for the proinflammatory cytokine interleukin-6 (IL-6) in several mechanisms that contribute to the development of CHD. IL-6 is a powerful inducer of the hepatic acute phase response. Elevated concentrations of acute phase reactants, such as C-reactive protein (CRP), are found in patients with acute coronary syndromes, and predict future risk in apparently healthy subjects. The acute phase reaction is associated with elevated levels of fibrinogen, a strong risk factor for CHD, with autocrine and paracrine activation of monocytes by IL-6 in the vessel wall contributing to the deposition of fibrinogen. The acute phase response is associated with increased blood viscosity, platelet number and activity. Furthermore, raised serum amyloid A lowers HDL-cholesterol levels. IL-6 decreases lipoprotein lipase (LPL) activity and monomeric LPL levels in plasma, which increases macrophage uptake of lipids. In fatty streaks and in the atheromatous 'cap' and 'shoulder' regions, macrophage foam cells and smooth muscle cells (SMC) express IL-6, suggesting a role for this cytokine along with interleukin-1 (IL-1) and tumour necrosis factor-a (TNF-a), in the progression of atherosclerosis. Both these cytokines induce the release of IL-6 from several cell types, including SMC. During vascular injury SMC are exposed to platelets or their products, and cytokine production by SMC further contributes to vascular damage. Furthermore, circulating IL-6 stimulates the hypothalamic-pituitary-adrenal (HPA) axis, activation of which is associated with central obesity, hypertension and insulin resistance. Thus we propose a role for IL-6 in the pathogenesis of CHD through a combination of autocrine, paracrine and endocrine mechanisms. This hypothesis lends itself to testing using interventions to influence IL-6 secretion and actions.
International journal of epidemiology, Jan 14, 2015
This study investigated associations between work-family life courses and biomarkers of inflammat... more This study investigated associations between work-family life courses and biomarkers of inflammation and stress in mid-life among British men and women. Gender differences in these associations were also explored. A novel statistical method-multi-channel sequence analysis-defined work-family life courses between the ages of 16 and 42 years, combining annual information on work, partnership and parenthood. Associations between work-family life courses and inflammation [C-reactive protein (CRP), fibrinogen and von Willebrand factor] and cortisol at age 44/45 years were tested using multivariate linear regression using multiply-imputed data on almost 6500 participants from the National Child Development Study 1958 British birth cohort. Compared with those who combined strong ties to paid work with later transitions to stable family lives ('Work, later family' group), 'Teen parents' had higher CRP [40.6% higher, 95% confidence interval (CI): 5.6, 87.0] and fibrinogen (7....
Evidence suggests that short and long sleep are associated with a higher risk of type 2 diabetes.... more Evidence suggests that short and long sleep are associated with a higher risk of type 2 diabetes. Using successive data waves spanning >20 years, we examined whether a change in sleep duration is associated with incident diabetes. Sleep duration was reported at the beginning and end of four 5-year cycles: 1985-1988 to 1991-1994 (n = 5,613), 1991-1994 to 1997-1999 (n = 4,193), 1997-1999 to 2002-2004 (n = 3,840), and 2002-2004 to 2007-2009 (n = 4,195). At each cycle, change in sleep duration was calculated for participants without diabetes. Incident diabetes at the end of the subsequent 5-year period was defined using 1) fasting glucose, 2) 75-g oral glucose tolerance test, and 3) glycated hemoglobin, in conjunction with diabetes medication and self-reported doctor diagnosis. Compared with the reference group of persistent 7-h sleepers, an increase of ≥2 h sleep per night was associated with a higher risk of incident diabetes (odds ratio 1.65 [95% CI 1.15, 2.37]) in analyses adjust...
We examined the effect of salivary cortisol on cognitive performance and decline in 3229 adults (... more We examined the effect of salivary cortisol on cognitive performance and decline in 3229 adults (79% men), mean age 61 years. Six saliva samples over the day along with a cognition test battery were administered twice in 5 years. In fully-adjusted cross-sectional analyses from 2002 to 2004, higher waking cortisol was associated with higher reasoning score (β = 0.08, 95% confidence interval: 0.01, 0.15) but this finding was not replicated using data from 2007 to 2009. Over the mean 5 years follow-up there was decline in all cognitive tests but this decline did not vary as a function of cortisol levels; the exception was among APOE e4 carriers where a flatter diurnal slope and higher bedtime cortisol were associated with faster decline in verbal fluency. Changes in cortisol measures between 2002/2004 and 2007/2009 or chronically elevated levels were not associated with cognitive performance in 2007/2009. These results, based on a large sample of community-dwelling adults suggest that ...
Background—The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, a... more Background—The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. Methods and Results—This was a double-blind case-control study of
Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pre... more Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blo...
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a herit... more The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein i...
The association between fatigue and reduced activity in the hypothalamo-pituitary-adrenal (HPA) a... more The association between fatigue and reduced activity in the hypothalamo-pituitary-adrenal (HPA) axis has been described. However the temporal association between fatigue and HPA activity is under debate. We examine whether alterations in cortisol secretion play a role in the development of fatigue or whether changes occur later as a consequence of fatigue in a longitudinal cohort study of 4299 community dwelling adults (mean age 61). Cortisol secretion was measured from saliva samples collected waking, waking + 0.5, 2.5, 8, 12 h and bedtime at phase 7 (2003-2004) of the Whitehall II study. Fatigue was measured at phase 6 (2001), phase 7 and phase 8 (2006) of the Whitehall II study. Three elements of secretion were examined: waking cortisol, the cortisol awakening response and diurnal slope in cortisol secretion. Fatigue was determined using the vitality sub-scale of the Short Form-36. A wide variety of co-variates were measured. We find that fatigue measured at phase 6 was not associated with cortisol secretion at phase 7. At phase 7, low waking cortisol levels and a flat slope in diurnal cortisol secretion were associated with fatigue independently of co-variates. In participants low or free of fatigue at phase 7 low waking cortisol and flatter slope in cortisol secretion were associated with new-onset fatigue at phase 8 (for example, odds ratio for lowest vs. highest tertile of waking cortisol 1.50; 95% confidence intervals, 1.08, 2.09 after adjusting for all co-variates). In conclusion, we find that low waking salivary cortisol and a flat slope in cortisol secretion is associated with fatigue. Cortisol is also associated with future onset of fatigue suggesting that changes in cortisol secretion are etiologic or occur early in the genesis of fatigue.
Background-A lack of longitudinal studies has made it difficult to establish the direction of ass... more Background-A lack of longitudinal studies has made it difficult to establish the direction of associations between circulating concentrations of low-grade chronic inflammatory markers, such as C-reactive protein and interleukin-6, and cognitive symptoms of depression. The present study sought to assess whether C-reactive protein and interleukin-6 predict cognitive symptoms of depression or whether these symptoms predict inflammatory markers.
Background: Low muscle mass and function have been associated with poorer indicators of physical ... more Background: Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.
Minireview: Mechanisms by Which the Metabolic Syndrome and Diabetes Impair Memory
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2000
Type 2 diabetes is associated with an increased risk of cognitive dysfunction. These effects seem... more Type 2 diabetes is associated with an increased risk of cognitive dysfunction. These effects seem particularly true for memory functions. This article examines how diabetes and the biological changes that occur with diabetes such as hyperglycemia, changes in insulin concentration, hypertension, and changes in lipid levels might lead to these alterations in cognitive functioning, with an emphasis on the mechanisms leading to changes in memory.
Objective: To examine change in health functioning as women progress through the menopausal trans... more Objective: To examine change in health functioning as women progress through the menopausal transition. Study Design and Setting: Prospective study of 2,489 women followed through four phases of the Whitehall II study. Health functioning was assessed with the eight subscales of the SF-36.
only adult height was related to region of birth, after adjustment for region of examination (P ¼... more only adult height was related to region of birth, after adjustment for region of examination (P ¼ 0.002) Conclusions Although individual disease risk is predicted by early life factors, early exposures do not explain regional variations in cardiovascular and respiratory risk factors among middle-aged adults in Britain. Geographical inequalities in cardiorespiratory health are more strongly related to factors associated with region of examination that influence obesity, BP and ventilatory function.
Sleep deprivation (Յ5 hour per night) was associated with a higher risk of hypertension in middle... more Sleep deprivation (Յ5 hour per night) was associated with a higher risk of hypertension in middle-aged American adults but not among older individuals. However, the outcome was based on self-reported diagnosis of incident hypertension, and no gender-specific analyses were included. We examined cross-sectional and prospective associations of sleep duration with prevalent and incident hypertension in a cohort of 10 308 British civil servants aged 35 to 55 years at baseline (phase 1: 1985-1988). Data were gathered from phase 5 (1997-1999) and phase 7 (2003-2004). Sleep duration and other covariates were assessed at phase 5. At both examinations, hypertension was defined as blood pressure Ն140/90 mm Hg or regular use of antihypertensive medications. In cross-sectional analyses at phase 5 (nϭ5766), short duration of sleep (Յ5 hour per night) was associated with higher risk of hypertension compared with the group sleeping 7 hours, among women (odds ratio: 2.01; 95% CI: 1.13 to 3.58), independent of confounders, with an inverse linear trend across decreasing hours of sleep (Pϭ0.003). No association was detected in men. In prospective analyses (mean follow-up: 5 years), the cumulative incidence of hypertension was 20.0% (nϭ740) among 3691 normotensive individuals at phase 5. In women, short duration of sleep was associated with a higher risk of hypertension in a reduced model (age and employment) (6 hours per night: odds ratio: 1.56 [95% CI: 1.07 to 2.27]; Յ5 hour per night: odds ratio: 1.94 [95% CI: 1.08 to 3.50] versus 7 hours). The associations were attenuated after accounting for cardiovascular risk factors and psychiatric comorbidities (odds ratio: 1.42 [95% CI: 0.94 to 2.16]; odds ratio: 1.31 [95% CI: 0.65 to 2.63], respectively). Sleep deprivation may produce detrimental cardiovascular effects among women. (Hypertension. 2007;50:693-700.) by guest on January 25, 2016 http://hyper.ahajournals.org/ Downloaded from by guest on January 25, 2016 http://hyper.ahajournals.org/ Downloaded from by guest on January 25, 2016 http://hyper.ahajournals.org/ Downloaded from (Hypertension. 2007;50:e170.)
Methods and Results-10,308 London-based male and female civil servants aged 35-55 at phase 1 (198... more Methods and Results-10,308 London-based male and female civil servants aged 35-55 at phase 1 (1985)(1986)(1987)(1988) of the Whitehall II study. Exposures included work stress (assessed at phases 1 and 2). Outcomes included behavioural risk factors (phase 3), the metabolic syndrome (phase 3), heart rate variability, morning rise in cortisol (phase 7) and incident CHD (phases 2 to 7) based on CHD death, non-fatal myocardial infarction or definite angina. Chronic work stress was associated with CHD and this association was stronger among participants aged under 50 (RR 1.68, 95% CI 1.17-2.42). There were similar associations between work stress and low physical activity, poor diet, the metabolic syndrome, its components, and lower heart rate variability. Cross-sectionally, work stress was associated with a higher morning rise in cortisol. Around 32% of the effect of work stress on CHD was attributable to its effect on health behaviours and the metabolic syndrome.
professor of genetic epidemiology, 2,3 Jackie A Cooper, biostatistician, 1 Michael G Marmot, MRC ... more professor of genetic epidemiology, 2,3 Jackie A Cooper, biostatistician, 1 Michael G Marmot, MRC professor of epidemiology and public health, 2 Eric J Brunner, reader in epidemiology and public health, 2 Meena Kumari, senior research fellow in population health, 2 Mika Kivimäki, professor of social epidemiology, 2 Steve E Humphries, BHF professor of cardiovascular genetics 1 ABSTRACT Objectives To assess the performance of a panel of common single nucleotide polymorphisms (genotypes) associated with type 2 diabetes in distinguishing incident cases of future type 2 diabetes (discrimination), and to examine the effect of adding genetic information to previously validated non-genetic (phenotype based) models developed to estimate the absolute risk of type 2 diabetes. Design Workplace based prospective cohort study with three 5 yearly medical screenings. Participants 5535 initially healthy people (mean age 49 years; 33% women), of whom 302 developed new onset type 2 diabetes over 10 years. Outcome measures Non-genetic variables included in two established risk models-the Cambridge type 2 diabetes risk score (age, sex, drug treatment, family history of type 2 diabetes, body mass index, smoking status) and the Framingham offspring study type 2 diabetes risk score (age, sex, parental history of type 2 diabetes, body mass index, high density lipoprotein cholesterol, triglycerides, fasting glucose)-and 20 single nucleotide polymorphisms associated with susceptibility to type 2 diabetes. Cases of incident type 2 diabetes were defined on the basis of a standard oral glucose tolerance test, self report of a doctor's diagnosis, or the use of anti-diabetic drugs.
There is mounting evidence that inflammation plays a role in the development of coronary heart di... more There is mounting evidence that inflammation plays a role in the development of coronary heart disease (CHD). Observations have been made linking the presence of infections in the vessel wall with atherosclerosis, and epidemiological data also implicate infection in remote sites in the aetiology of CHD. In this article we propose a key role for the proinflammatory cytokine interleukin-6 (IL-6) in several mechanisms that contribute to the development of CHD. IL-6 is a powerful inducer of the hepatic acute phase response. Elevated concentrations of acute phase reactants, such as C-reactive protein (CRP), are found in patients with acute coronary syndromes, and predict future risk in apparently healthy subjects. The acute phase reaction is associated with elevated levels of fibrinogen, a strong risk factor for CHD, with autocrine and paracrine activation of monocytes by IL-6 in the vessel wall contributing to the deposition of fibrinogen. The acute phase response is associated with increased blood viscosity, platelet number and activity. Furthermore, raised serum amyloid A lowers HDL-cholesterol levels. IL-6 decreases lipoprotein lipase (LPL) activity and monomeric LPL levels in plasma, which increases macrophage uptake of lipids. In fatty streaks and in the atheromatous 'cap' and 'shoulder' regions, macrophage foam cells and smooth muscle cells (SMC) express IL-6, suggesting a role for this cytokine along with interleukin-1 (IL-1) and tumour necrosis factor-a (TNF-a), in the progression of atherosclerosis. Both these cytokines induce the release of IL-6 from several cell types, including SMC. During vascular injury SMC are exposed to platelets or their products, and cytokine production by SMC further contributes to vascular damage. Furthermore, circulating IL-6 stimulates the hypothalamic-pituitary-adrenal (HPA) axis, activation of which is associated with central obesity, hypertension and insulin resistance. Thus we propose a role for IL-6 in the pathogenesis of CHD through a combination of autocrine, paracrine and endocrine mechanisms. This hypothesis lends itself to testing using interventions to influence IL-6 secretion and actions.
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