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1.  Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events 
PLoS ONE  2015;10(7):e0132321.
Background
Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.
Methods
We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity.
Results
Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites.
Conclusion
The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.
doi:10.1371/journal.pone.0132321
PMCID: PMC4489855  PMID: 26134404
2.  The Role of Alcohol Consumption in Regulating Circulating Levels of Adiponectin: A Prospective Cohort Study 
Context:
The role of alcohol intake in influencing longitudinal trajectories of adiponectin is unclear.
Objective:
The objective of the study was to examine the association between alcohol intake and changes in the circulating levels of adiponectin over repeat measures.
Design, Setting, and Participants:
A prospective cohort study of 2855 men and women (74% men with a mean age of 50 y at baseline) drawn from the Whitehall II study. Data from study phases 3 (1991–1993), 5 (1997–1999), and 7 (2002–2004) were used.
Main Outcome Measure:
Adiponectin serum concentrations (nanograms per milliliter) were measured, and alcohol intake was defined in terms of number of UK units (1 U = 8 g ethanol) consumed in the previous 7 days on three occasions. Cross-sectional associations between alcohol and adiponectin levels were calculated using linear regression. A bivariate dual-change score model was used to estimate the effect of alcohol intake on upcoming change in adiponectin. Models were adjusted for age, sex, ethnicity, and smoking status.
Results:
Alcohol consumption was cross-sectionally associated with (log transformed) adiponectin levels (β ranging from .001 to .004, depending on phase and level of adjustment) but was not associated with changes in adiponectin levels over time [γ = −0.002 (SE 0.002), P = 0.246].
Conclusion:
Alcohol intake is not associated with changes in circulating adiponectin levels in this cohort. This finding provides evidence that adiponectin levels are unlikely to mediate the relationship between moderate alcohol consumption and reduced risk of type 2 diabetes. It is important to consider dynamic longitudinal relationships rather than cross-sectional associations.
doi:10.1210/jc.2015-1845
PMCID: PMC4490299  PMID: 26000546
3.  Reasons Why People Change Their Alcohol Consumption in Later Life: Findings from the Whitehall II Cohort Study 
PLoS ONE  2015;10(3):e0119421.
Purpose
Harmful alcohol consumption among the ageing population is an important public health issue. Very few studies ask drinkers why they change their consumption in later life. The aim of this paper was to determine whether a group of people aged over 60 years increased or decreased their alcohol consumption over the past decade and to determine the reasons for their change. We also examined whether the responses varied by age, sex and socio-economic position (SEP).
Subjects and Methods
Data were taken from 6,011 participants (4,310 men, 1,701 women, age range 61 to 85 years) who completed questionnaires at phase 11 (2012-2013) of the Whitehall II Cohort Study.
Results
Over half the study members reported a change in alcohol consumption over the past decade (40% decreased, 11% increased). The most common reasons given for decreases were as a health precaution and fewer social occasions. Common reasons for increases were more social occasions and fewer responsibilities. The lowest SEP group was less likely to increase consumption compared to high SEP (RR 0.57, 95% CI 0.40 to 0.81). Women were more likely to increase consumption in response to stress/depression than men (RR1.53, 95% CI 1.04 to 2.25). Compared to high SEP, the lowest SEP group was less likely to reduce as a health precaution (RR 0.61, 95% CI 0.38 to 0.76).
Conclusions
Alcohol consumption in late life is not fixed. Reasons for change vary by age, sex and SEP. Such information could be used to tailor intervention strategies to reduce harmful consumption.
doi:10.1371/journal.pone.0119421
PMCID: PMC4355077  PMID: 25756213
4.  Life course trajectories of alcohol consumption in the United Kingdom using longitudinal data from nine cohort studies 
BMC Medicine  2015;13:47.
Background
Alcohol consumption patterns change across life and this is not fully captured in cross-sectional series data. Analysis of longitudinal data, with repeat alcohol measures, is necessary to reveal changes within the same individuals as they age. Such data are scarce and few studies are able to capture multiple decades of the life course. Therefore, we examined alcohol consumption trajectories, reporting both average weekly volume and frequency, using data from cohorts with repeated measures that cover different and overlapping periods of life.
Methods
Data were from nine UK-based prospective cohorts with at least three repeated alcohol consumption measures on individuals (combined sample size of 59,397 with 174,666 alcohol observations), with data spanning from adolescence to very old age (90 years plus). Information on volume and frequency of drinking were harmonised across the cohorts. Predicted volume of alcohol by age was estimated using random effect multilevel models fitted to each cohort. Quadratic and cubic polynomial terms were used to describe non-linear age trajectories. Changes in drinking frequency by age were calculated from observed data within each cohort and then smoothed using locally weighted scatterplot smoothing. Models were fitted for men and women separately.
Results
We found that, for men, mean consumption rose sharply during adolescence, peaked at around 25 years at 20 units per week, and then declined and plateaued during mid-life, before declining from around 60 years. A similar trajectory was seen for women, but with lower overall consumption (peak of around 7 to 8 units per week). Frequent drinking (daily or most days of the week) became more common during mid to older age, most notably among men, reaching above 50% of men.
Conclusions
This is the first attempt to synthesise longitudinal data on alcohol consumption from several overlapping cohorts to represent the entire life course and illustrates the importance of recognising that this behaviour is dynamic. The aetiological findings from epidemiological studies using just one exposure measure of alcohol, as is typically done, should be treated with caution. Having a better understanding of how drinking changes with age may help design intervention strategies.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-015-0273-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s12916-015-0273-z
PMCID: PMC4351673  PMID: 25858476
Alcohol; Life course; Longitudinal
5.  The relationship between labour market categories and alcohol use trajectories in midlife 
Background and aims
Studies on the role of labour market position and change in alcohol use during midlife are scarce and their results are inconclusive mainly due to their failure to define comprehensive and distinct labour market groups and the short periods of time studied. In this study we used different activity categories for men and women to examine alcohol use trajectories in midlife covering a period of 17 years.
Methods
Using data from four sweeps of the National Child Development Study covering ages 33–50 (N=9960), we used multilevel growth models to study the association between labour market categories and longitudinal changes in weekly units of alcohol consumed.
Results
In the reference group of full-time employed men alcohol trajectory decreased over the follow-up period (β=−0.14; 95% CI −0.18 to −0.11) while in the reference group of employed women it increased (β=0.06; 95% CI 0.04 to 0.08). Men and women who were ‘mainly sick’ had significantly steeper declines in their alcohol consumption trajectory. Women who became employed after being homemakers had the steepest increase in alcohol use (β=0.05; 95% CI 0.01 to 0.09).
Conclusions
Being employed is a strong determinant of alcohol use for men and women in midlife, making the workplace a good target for health promotion programmes and policies aimed at reducing alcohol use. Caution is needed when interpreting the health effects of alcohol consumption as low alcohol users may have previously been heavy drinkers.
doi:10.1136/jech-2014-204164
PMCID: PMC4215347  PMID: 25073593
ALCOHOL; EMPLOYMENT; Life course epidemiology; LONGITUDINAL STUDIES
6.  Increased risk of coronary heart disease among individuals reporting adverse impact of stress on their health: the Whitehall II prospective cohort study 
European Heart Journal  2013;34(34):2697-2705.
Aim
Response to stress can vary greatly between individuals. However, it remains unknown whether perceived impact of stress on health is associated with adverse health outcomes. We examined whether individuals who report that stress adversely affects their health are at increased risk of coronary heart disease (CHD) compared with those who report that stress has no adverse health impact.
Methods and results
Analyses are based on 7268 men and women (mean age: 49.5 years, interquartile range: 11 years) from the British Whitehall II cohort study. Over 18 years of follow-up, there were 352 coronary deaths or first non-fatal myocardial infarction (MI) events. After adjustment for sociodemographic characteristics, participants who reported at baseline that stress has affected their health ‘a lot or extremely’ had a 2.12 times higher (95% CI 1.52–2.98) risk of coronary death or incident non-fatal MI when compared with those who reported no effect of stress on their health. This association was attenuated but remained statistically significant after adjustment for biological, behavioural, and other psychological risk factors including perceived stress levels, and measures of social support; fully adjusted hazard ratio: 1.49 (95% CI 1.01–2.22).
Conclusions
In this prospective cohort study, the perception that stress affects health, different from perceived stress levels, was associated with an increased risk of coronary heart disease. Randomized controlled trials are needed to determine whether disease risk can be reduced by increasing clinical attention to those who complain that stress greatly affects their health.
doi:10.1093/eurheartj/eht216
PMCID: PMC3766148  PMID: 23804585
Epidemiology; Stress; Coronary heart disease; Prospective studies
7.  Drinking Pattern, Abstention and Problem Drinking as Risk Factors for Depressive Symptoms: Evidence from Three Urban Eastern European Populations 
PLoS ONE  2014;9(8):e104384.
Purpose
To examine whether the frequency and amount of alcohol consumed in binge drinking sessions, total annual volume of alcohol consumed, problem drinking and abstaining from alcohol are associated with depressive symptoms in Eastern Europe.
Subjects and Methods
Cross-sectional data from a total of 24,381 participants from general population samples of the Czech Republic (N = 7,601), Russia (N = 6,908) and Poland (N = 9,872) aged 45–69 years in 2002–2005. Depressive symptoms were defined as ≥16 points on the Centre for Epidemiological Studies – Depression (CES-D) scale. Several alcohol related measures were derived using responses from the graduated frequency questionnaire. Binge drinking was defined at several sex-specific thresholds (ranging from 60+ to 140+ g of ethanol) and two frequencies (at least monthly or weekly). Total annual alcohol intake in grams was also extracted. Problem drinking was defined as ≥2 positive answers on the CAGE questionnaire.
Results
Problem drinking was consistently associated with approximately a 2-fold increase in odds of depressive symptoms across all countries and in both sexes. Abstaining from alcohol was typically associated with increased odds of depressive symptoms. Analyses separating lifelong abstainers and former drinkers in the Russian cohort revealed that this increased odds was driven by former drinkers. Amongst men, heavy frequent binge drinking was associated with increased odds of depressive symptoms in the Czech Republic and Poland. In women, heavy infrequent binge drinking was associated with increased odds of depressive symptoms in Russia and Poland. Only in Polish men was higher annual volume of alcohol intake associated with increased odds of depressive symptoms.
Conclusion
Abstaining from alcohol and problem drinking were associated with increased odds of depressive symptoms in these Eastern European populations. Annual volume of alcohol intake as well as frequency and amount of alcohol consumed in a binge drinking session were less consistently associated with depressive symptoms.
doi:10.1371/journal.pone.0104384
PMCID: PMC4131916  PMID: 25118714
8.  An exploration of the dynamic longitudinal relationship between mental health and alcohol consumption: a prospective cohort study 
BMC Medicine  2014;12:91.
Background
Despite intense investigation, the temporal sequence between alcohol consumption and mental health remains unclear. This study explored the relationship between alcohol consumption and mental health over multiple occasions, and compared a series of competing theoretical models to determine which best reflected the association between the two.
Methods
Data from phases 5 (1997 to 1999), 7 (2002 to 2004), and 9 (2007 to 2009) of the Whitehall II prospective cohort study were used, providing approximately 10 years of follow-up for 6,330 participants (73% men; mean ± SD age 55.8 ± 6.0 years). Mental health was assessed using the Short Form (SF)-36 mental health component score. Alcohol consumption was defined as the number of UK units of alcohol drunk per week. Four dynamic latent change score models were compared: 1) a baseline model in which alcohol consumption and mental health trajectories did not influence each other, 2) and model in which alcohol consumption influenced changes in mental health but mental health exerted no effect on changes in drinking and 3) vice versa, and (4) a reciprocal model in which both variables influenced changes in each other.
Results
The third model, in which mental health influenced changes in alcohol consumption but not vice versa, was the best fit. In this model, the effect of previous mental health on upcoming change in alcohol consumption was negative (γ = -0.31, 95% CI -0.52 to -0.10), meaning that those with better mental health tended to make greater reductions (or shallower increases) in their drinking between occasions.
Conclusions
Mental health appears to be the leading indicator of change in the dynamic longitudinal relationship between mental health and weekly alcohol consumption in this sample of middle-aged adults. In addition to fuelling increases in alcohol consumption among low-level consumers, poor mental health may also be a maintaining factor for heavy alcohol consumption. Future work should seek to examine whether there are critical levels of alcohol intake at which different dynamic relationships begin to emerge between alcohol-related measures and mental health.
doi:10.1186/1741-7015-12-91
PMCID: PMC4053287  PMID: 24889765
Alcohol; Mental health; Longitudinal; Reciprocal; Self-medication; Temporality
9.  Alcohol consumption and cognitive decline in early old age 
Neurology  2014;82(4):332-339.
Objective:
To examine the association between alcohol consumption in midlife and subsequent cognitive decline.
Methods:
Data are from 5,054 men and 2,099 women from the Whitehall II cohort study with a mean age of 56 years (range 44–69 years) at first cognitive assessment. Alcohol consumption was assessed 3 times in the 10 years preceding the first cognitive assessment (1997–1999). Cognitive tests were repeated in 2002–2004 and 2007–2009. The cognitive test battery included 4 tests assessing memory and executive function; a global cognitive score summarized performances across these tests. Linear mixed models were used to assess the association between alcohol consumption and cognitive decline, expressed as z scores (mean = 0, SD = 1).
Results:
In men, there were no differences in cognitive decline among alcohol abstainers, quitters, and light or moderate alcohol drinkers (<20 g/d). However, alcohol consumption ≥36 g/d was associated with faster decline in all cognitive domains compared with consumption between 0.1 and 19.9 g/d: mean difference (95% confidence interval) in 10-year decline in the global cognitive score = −0.10 (−0.16, −0.04), executive function = −0.06 (−0.12, 0.00), and memory = −0.16 (−0.26, −0.05). In women, compared with those drinking 0.1 to 9.9 g/d of alcohol, 10-year abstainers showed faster decline in the global cognitive score (−0.21 [−0.37, −0.04]) and executive function (−0.17 [−0.32, −0.01]).
Conclusions:
Excessive alcohol consumption in men (≥36 g/d) was associated with faster cognitive decline compared with light to moderate alcohol consumption.
doi:10.1212/WNL.0000000000000063
PMCID: PMC3929201  PMID: 24431298
10.  Sitting Behavior and Obesity 
Background
Prospective studies report associations between indicators of time spent sitting and obesity risk. Most studies use a single indicator of sedentary behavior and are unable to clearly identify whether sedentary behavior is a cause or a consequence of obesity.
Purpose
To investigate cross-sectional and prospective associations between multiple sitting time indicators and obesity and examine the possibility of reverse causality.
Methods
Using data from the Whitehall II cohort, multiple logistic models were fitted to examine associations between prevalent obesity (BMI ≥30) at Phase 5 (1997–1999), and incident obesity between Phases 5 and 7 (2003–2004) across four levels of five sitting exposures (work sitting, TV viewing, non-TV leisure-time sitting, leisure-time sitting, and total sitting). Using obesity data from three prior phases (1985–1988, 1991–1993; and recalled weight at age 25 years), linear regression models were fitted to examine the association between prior obesity and sitting time at Phase 5. Analyses were conducted in 2012.
Results
None of the sitting exposures were associated with obesity either cross-sectionally or prospectively. Obesity at one previous measurement phase was associated with a 2.43-hour/week (95% CI=0.07, 4.78) increase in TV viewing; obesity at three previous phases was associated with a 7.42-hour/week (95% CI=2.7, 12.46) increase in TV-viewing hours/week at Phase 5.
Conclusions
Sitting time was not associated with obesity cross-sectionally or prospectively. Prior obesity was prospectively associated with time spent watching TV per week but not other types of sitting.
doi:10.1016/j.amepre.2012.10.009
PMCID: PMC3550520  PMID: 23332328
11.  Combined Effects of Depressive Symptoms and Resting Heart Rate on Mortality: The Whitehall II Prospective Cohort Study 
The Journal of clinical psychiatry  2010;72(9):1199-1206.
Objective
To examine the combined effects of depressive symptoms and resting heart rate (RHR) on mortality.
Methods
Data come from 5936 participants, aged 61 ± 6 years, from the Whitehall II study. Depressive symptoms were assessed in 2002–2004 using the center-for-epidemiologic-studies-depression-scale (score ≥ 16). RHR was measured at the same study phase via electrocardiogram. Participants were assigned to 1 of 6 risk-factor-groups based on depression status (yes/no) and RHR categories (<60, 60 – 80, >80 bpm). Mean follow-up for mortality was 5.6 years.
Results
In mutually adjusted Cox regression models, depression (hazard ratio = 1.93 p<0.001) and RHR>80 bpm (hazard ratio = 1.67, p<0.001) were independent predictors of mortality. After adjustment for potential confounding and mediating variables, participants with both depression and high RHR had a 3.0-fold higher (p<0.001) risk of death compared to depression-free participants with RHR ranging from 60 to 80 bpm. This risk is particularly marked in participants with prevalent CHD.
Conclusions
This study provides evidence that the coexistence of depressive symptoms and elevated RHR is associated with substantially increased risk of death compared to those without these two factors. This finding raises the possibility that treatments that improve both depression and RHR might improve survival.
doi:10.4088/JCP.09m05901blu
PMCID: PMC3226937  PMID: 21208592
depression; resting heart rate and mortality
12.  Combined effects of depressive symptoms and resting heart rate on mortality: the Whitehall II prospective cohort study 
The Journal of Clinical Psychiatry  2010;72(9):1199-1206.
Objective
To examine the combined effects of depressive symptoms and resting heart rate (RHR) on mortality.
Methods
Data come from 5936 participants, aged 61 ±6 years, from the Whitehall II study. Depressive symptoms were assessed in 2002–2004 using the center-for-epidemiologic-studies-depression-scale (score ≥16). RHR was measured at the same study phase via electrocardiogram. Participants were assigned to 1 of 6 risk-factor-groups based on depression status (yes/no) and RHR categories (<60, 60–80, >80 bpm). Mean follow-up for mortality was 5.6 years.
Results
In mutually adjusted Cox regression models, depression (hazard ratio = 1.93 p<0.001) and RHR>80 bpm (hazard ratio = 1.67, p<0.001) were independent predictors of mortality. After adjustment for potential confounding and mediating variables, participants with both depression and high RHR had a 3.0-fold higher (p<0.001) risk of death compared to depression-free participants with RHR ranging from 60 to 80 bpm. This risk is particularly marked in participants with prevalent CHD.
Conclusions
This study provides evidence that the coexistence of depressive symptoms and elevated RHR is associated with substantially increased risk of death compared to those without these two factors. This finding raises the possibility that treatments that improve both depression and RHR might improve survival.
doi:10.4088/JCP.09m05901blu
PMCID: PMC3226937  PMID: 21208592
depression; resting heart rate and mortality
13.  Do We Need Age-Specific Alcohol Consumption Guidelines? 
doi:10.1093/alcalc/ags023
PMCID: PMC3331620  PMID: 22398024
14.  Rising adiposity curbing decline in the incidence of myocardial infarction: 20-year follow-up of British men and women in the Whitehall II cohort 
European heart journal  2011;33(4):478-485.
Aims
To estimate the contribution of risk factor trends to 20-year declines in myocardial infarction (MI) incidence in British men and women.
Methods and results
From 1985 to 2004, 6379 men and 3074 women in the Whitehall II cohort were followed for incident MI and risk factor trends. Over 20 years, the age–sex-adjusted hazard of MI fell by 74% (95% confidence interval 48–87%), corresponding to an average annual decline of 6.5% (3.2–9.7%). Thirty-four per cent (20–76%) of the decline in MI hazard could be statistically explained by declining non-HDL cholesterol levels, followed by increased HDL cholesterol (17%, 10–32%), reduced systolic blood pressure (13%, 7–24%), and reduced cigarette smoking prevalence (6%, 2–14%). Increased fruit and vegetable consumption made a non-significant contribution of 7% (−1–20%). In combination, these five risk factors explained 56% (34–112%). Rising body mass index (BMI) was counterproductive, reducing the scale of the decline by 11% (5–23%) in isolation. The MI decline and the impact of the risk factors appeared similar for men and women.
Conclusion
In men and women, over half of the decline in MI risk could be accounted for by favourable risk factor time trends. The adverse role of BMI emphasizes the importance of addressing the rising population BMI.
doi:10.1093/eurheartj/ehr142
PMCID: PMC3272419  PMID: 21653562
Myocardial infarction; Incidence; Time Trends; Population; Prevention; Risk factors
15.  Limitations to functioning and independent living after the onset of coronary heart disease: what is the role of lifestyle factors and obesity? 
Background: People with coronary disease have a higher risk of functional limitations than their same-age counterparts without disease. This study examined prospectively the extent to which functioning and independent living among individuals with coronary disease in early old age are associated with lifestyle factors before and after disease onset. Methods: Participants were 986 British civil servants (657 men and 329 women aged 35–55 years), who were free of coronary disease at study entry in 1985–88 but developed disease during 21 years follow-up (the Whitehall II study). Lifestyle factors (obesity, smoking, alcohol, diet and physical activity) were measured at baseline and follow-up in 2007–09. Post-disease limitations to functioning were measured in 2006–09 at mean age is 68 years using activities of daily living scales. Results: Low physical activity and being overweight [body mass index (BMI) ≥25] before and after disease onset were associated with having one or more limitations in activities of daily living among coronary patients [age-, sex- and socio-economic position adjusted odds ratios for pre-disease inactivity and obesity 1.53 [95% confidence interval (95% CI) 0.99–2.35] and 2.53 (95% CI 1.53–4.18), respectively]. A decrease in physical activity [odds ratio (OR): 2.42, 95% CI 1.59–3.68] and an increase of >5 U in BMI (OR: 2.05, 95% CI 1.34–3.13) were also related to limitations in activities of daily living after disease onset. These relationships were not accounted for by measured co-morbidities. No robust associations were observed for smoking, alcohol use and diet. Conclusion: Physical activity and weight control across the adult life course are associated with fewer limitations to functioning and independent living after the onset of coronary disease.
doi:10.1093/eurpub/ckr150
PMCID: PMC3505445  PMID: 22037803
16.  Rising adiposity curbing decline in the incidence of myocardial infarction: 20-year follow-up of British men and women in the Whitehall II cohort 
European Heart Journal  2011;33(4):478-485.
Aims
To estimate the contribution of risk factor trends to 20-year declines in myocardial infarction (MI) incidence in British men and women.
Methods and results
From 1985 to 2004, 6379 men and 3074 women in the Whitehall II cohort were followed for incident MI and risk factor trends. Over 20 years, the age–sex-adjusted hazard of MI fell by 74% (95% confidence interval 48–87%), corresponding to an average annual decline of 6.5% (3.2–9.7%). Thirty-four per cent (20–76%) of the decline in MI hazard could be statistically explained by declining non-HDL cholesterol levels, followed by increased HDL cholesterol (17%, 10–32%), reduced systolic blood pressure (13%, 7–24%), and reduced cigarette smoking prevalence (6%, 2–14%). Increased fruit and vegetable consumption made a non-significant contribution of 7% (−1–20%). In combination, these five risk factors explained 56% (34–112%). Rising body mass index (BMI) was counterproductive, reducing the scale of the decline by 11% (5–23%) in isolation. The MI decline and the impact of the risk factors appeared similar for men and women.
Conclusion
In men and women, over half of the decline in MI risk could be accounted for by favourable risk factor time trends. The adverse role of BMI emphasizes the importance of addressing the rising population BMI.
doi:10.1093/eurheartj/ehr142
PMCID: PMC3272419  PMID: 21653562
Myocardial infarction; Incidence; Time Trends; Population; Prevention; Risk factors
17.  How does variability in alcohol consumption over time affect the relationship with mortality and coronary heart disease? 
Addiction (Abingdon, England)  2010;105(4):639-645.
Objective
To examine the relationship between alcohol consumption and risk of mortality and incident coronary heart disease (CHD) taking account of variation in intake during follow up
Method
Prospective cohort study of 5,411 male civil servants aged 35-55 years at entry to the Whitehall II study in 1985-88. Alcohol consumption was reported five times over a 15 year period. Mortality, fatal CHD, clinically verified incident non-fatal myocardial infarction and definite angina were ascertained during follow-up.
Results
We found evidence that drinkers who vary their intake during follow-up, regardless of average level, have increased risk of total mortality (hazard ratio of high versus low variability 1.52: 95% CI 1.07 to 2.17), but not of incident CHD. Using average consumption level, as opposed to just a baseline measure, gave slightly higher risk estimates for CHD compared to moderate drinkers, at the extremes of the drinking range.
Conclusions
Multiple repeated measures are required to explore the effects of variation in exposure over time. Caution is needed when interpreting risks of exposures measured only once at baseline, without consideration of changes over time.
doi:10.1111/j.1360-0443.2009.02832.x
PMCID: PMC2862167  PMID: 20148795
18.  Socioeconomic status moderates the association between carotid intima-media thickness and cognition in midlife: evidence from the Whitehall II study 
Atherosclerosis  2007;197(2):541-548.
Background
Common carotid artery intima media thickness (IMT) is a measure of generalized atherosclerosis and has been shown to be associated with cognitive function. We examine two questions: does socioeconomic status (SES) moderate this association and is IMT more strongly associated with specific aspects of cognitive function?
Methods
Data are drawn from the Phase 7 (2003–2004) of the Whitehall II study (N=3896). In cross-sectional analyses the association between IMT and six measures of cognition (short term verbal memory, inductive reasoning, vocabulary, semantic and phonemic fluency and a measure of global cognitive status) was examined in analyses adjusted for previous history of coronary heart disease, health behaviours and other vascular risk measures such as blood pressure, cholesterol and body mass index.
Results
The overall association between IMT and the 6 measures of cognition was restricted to the low SES group (p=0.02). Within this group, IMT was significantly associated with inductive reasoning (p=0.001), vocabulary (p=0.002), phonemic (p=0.006) and semantic fluency (p=0.02). The covariates examined explained about a quarter of the association between IMT and cognition in the low SES group. The associations with the measure of inductive reasoning (p=0.02), vocabulary (p=0.02) and phonemic fluency (p=0.04) remained after adjustment for all covariates.
Conclusions
SES is an important modifier of the association between IMT and cognition, an inverse association between the two was observed only in the low SES group. It is possible that high cognitive reserve among the high SES individuals prevents the functional manifestations of atherosclerosis. Verbal memory was not one of the cognitive domains associated with IMT.
doi:10.1016/j.atherosclerosis.2007.08.010
PMCID: PMC2759091  PMID: 17854813
cerebrovascular diseases; cognitive aging; carotid intima-media thickness
19.  History of coronary heart disease and cognitive performance in midlife: the Whitehall II study 
Aims
Some studies show coronary heart disease (CHD) to be a risk factor for cognitive function while others report no association between the two. We examine the effect of CHD history and duration on cognition in a middle-aged population.
Methods
Data come from the Whitehall II study of 10308 participants (33% women), aged 35–55 years at baseline (phase 1; 1985–1988). CHD events were assessed up to Phase 7 (2002–2004) when 5837 participants (28.4% women) undertook 6 cognitive tests: reasoning, vocabulary, phonemic and semantic fluency, memory and the Mini-Mental-State-Examination (MMSE); standardized to T-scores (mean=50, standard deviation=10). Analysis of covariance was used first to model the association between CHD history and cognition and then to examine the effect of time since first CHD event (in the last 5 years, 5–10 years ago, over 10 years ago).
Results
Among men, in analyses adjusted for age, education, marital status and medication for cardiovascular disease, CHD history was associated with lower T-scores on reasoning (−1.16; 95% Confidence Interval (CI)= −2.07, −0.25), vocabulary (−2.11; 95% CI=−3.01, −1.21), and the MMSE (−1.45; 95% CI=−2.42, −0.49). In women, these effects were also evident for phonemic and semantic fluency. Among men, the trend within CHD cases suggested progressively lower scores on reasoning, vocabulary and semantic fluency among those with longer duration of CHD.
Conclusion
Our findings go some way towards suggesting an association between CHD history and cognitive performance in middle-aged adults.
doi:10.1093/eurheartj/ehn298
PMCID: PMC2740873  PMID: 18648106
20.  History of coronary heart disease and cognitive performance in midlife: the Whitehall II study 
European Heart Journal  2008;29(17):2100-2107.
Aims
Some studies show coronary heart disease (CHD) to be a risk factor for cognitive function while others report no association between the two. We examined the effect of CHD history and duration on cognition in a middle-aged population.
Methods and results
Data come from the Whitehall II study of 10 308 participants (33% women), aged 35–55 years at baseline (Phase 1; 1985–88). CHD events were assessed up to Phase 7 (2002–04) when 5837 participants (28.4% women) undertook six cognitive tests: reasoning, vocabulary, phonemic and semantic fluency, memory and the mini-mental-state-examination (MMSE); standardized to T-scores (mean = 50, standard deviation = 10). Analysis of covariance was used first to model the association between CHD history and cognition and then to examine the effect of time since first CHD event (in the last 5 years, 5–10 years ago, >10 years ago). Among men, in analyses adjusted for age, education, marital status and medication for cardiovascular disease, CHD history was associated with lower T-scores on reasoning [−1.16; 95% confidence interval (CI) = −2.07, −0.25], vocabulary (−2.11; 95% CI = −3.01, −1.21), and the MMSE (−1.45; 95% CI = −2.42, −0.49). In women, these effects were also evident for phonemic and semantic fluency. Among men, the trend within CHD cases suggested progressively lower scores on reasoning, vocabulary and semantic fluency among those with longer duration of CHD.
Conclusion
Our findings go some way towards suggesting an association between CHD history and cognitive performance in middle-aged adults.
doi:10.1093/eurheartj/ehn298
PMCID: PMC2740873  PMID: 18648106
Coronary heart disease; Epidemiology; Cognitive function
21.  Successful aging: the contribution of early-life and midlife risk factors 
Objectives
To test whether early life factors (education, height, father’s social position) and midlife social, behavioral and psychosocial factors were associated with entering older age without disease and good functioning.
Design
A longitudinal, British civil service-based cohort study. Participants were followed for 17 years to assess successful aging. This was defined as being free of major disease and in the top tertile of physical and cognitive functioning measured in 2002–4.
Setting
Twenty London-based Civil Service departments
Participants
Four thousand, one hundred and forty men and 1823 women, free of major disease at baseline in 1985–8 (mean age 44, range 35–55 years)
Measurements
Behavioral, biological and psychosocial risk factors, physical and cognitive functioning and disease outcomes
Results
548 (12.8%) men and 246 (14.6%) women were successfully aging at follow up. This was strongly predicted by midlife socioeconomic position (age adjusted odds ratio for men highest vs. lowest 7.06, 95% CI 3.4, 14.6). Height, education (men), not smoking, diet, exercise, moderate alcohol (women) and work support (men) were related to a favorable older life after adjustment for age and socioeconomic position.
Conclusion
Interventions to promote adult healthy behavior may attenuate harmful effects of less modifiable risk factors and reduce social inequalities.
doi:10.1111/j.1532-5415.2008.01740.x
PMCID: PMC2696176  PMID: 18482302
Adult; Aging; psychology; Female; Health Behavior; Health Promotion; Health Status; Humans; Life Style; Logistic Models; London; epidemiology; Male; Middle Aged; Risk Factors; Social Support; Socioeconomic Factors; Aging, cohort studies, health behaviors; inequalities
22.  The Association between Heart Rate Variability and Cognitive Impairment in Middle-Aged Men and Women. The Whitehall II Cohort Study 
Neuroepidemiology  2008;31(2):115-121.
Background
To examine the relationship between reduced heart rate variability (HRV) and cognitive function in middle aged adults in the general population
Methods
HRV, in both time and frequency domains, and cognitive function were measured twice, at mean ages 55 and 61 years, in 5,375 male and female participants of the UK Whitehall II study. Logistic regression was used to model associations between HRV and cognition (short-term verbal memory, reasoning (AH4-I), vocabulary, phonemic and semantic fluency). Cross-sectional associations were assessed at both waves and longitudinal associations as change in cognition over the 5 year follow-up.
Results
No consistent associations were found in men or women, either in cross-section, prospective or the longitudinal analysis of decline in cognition.
Conclusion
Reduced cardiovascular autonomic function does not contribute to cognitive impairment in this middle-aged population. Further studies are needed to verify the potential role of HRV measures in predicting the degeneration of cognitive function at older ages.
doi:10.1159/000148257
PMCID: PMC2527026  PMID: 18667838
autonomic function; cognitive impairment; heart rate variability; cohort studies
23.  Does High C-reactive Protein Concentration Increase Atherosclerosis? The Whitehall II Study 
PLoS ONE  2008;3(8):e3013.
Background
C-reactive protein (CRP), a marker of systemic inflammation, is associated with risk of coronary events and sub-clinical measures of atherosclerosis. Evidence in support of this link being causal would include an association robust to adjustments for confounders (multivariable standard regression analysis) and the association of CRP gene polymorphisms with atherosclerosis (Mendelian randomization analysis).
Methodology/Principal Findings
We genotyped 3 tag single nucleotide polymorphisms (SNPs) [+1444T>C (rs1130864); +2303G>A (rs1205) and +4899T>G (rs 3093077)] in the CRP gene and assessed CRP and carotid intima-media thickness (CIMT), a structural marker of atherosclerosis, in 4941 men and women aged 50–74 (mean 61) years (the Whitehall II Study). The 4 major haplotypes from the SNPs were consistently associated with CRP level, but not with other risk factors that might confound the association between CRP and CIMT. CRP, assessed both at mean age 49 and at mean age 61, was associated both with CIMT in age and sex adjusted standard regression analyses and with potential confounding factors. However, the association of CRP with CIMT attenuated to the null with adjustment for confounding factors in both prospective and cross-sectional analyses. When examined using genetic variants as the instrument for serum CRP, there was no inferred association between CRP and CIMT.
Conclusions/Significance
Both multivariable standard regression analysis and Mendelian randomization analysis suggest that the association of CRP with carotid atheroma indexed by CIMT may not be causal.
doi:10.1371/journal.pone.0003013
PMCID: PMC2507732  PMID: 18714381
24.  The Association between Heart Rate Variability and Cognitive Impairment in Middle-Aged Men and Women 
Neuroepidemiology  2008;31(2):115-121.
Background
To examine the relationship between reduced heart rate variability (HRV) and cognitive function in middle-aged adults in the general population.
Methods
HRV, in both time and frequency domains, and cognitive functioning were measured twice in 5,375 male and female participants of the UK Whitehall II study (mean ages = 55 and 61 years, respectively). Logistic regression was used to model associations between HRV and cognition [short-term verbal memory, reasoning (Alice Heim 4-I), vocabulary, phonemic and semantic fluency]. Cross-sectional associations were assessed at both waves, and longitudinal associations were measured as changes in cognition over the 5-year follow-up.
Results
No consistent associations were found in men or women, either in the cross-sectional, prospective or the longitudinal analyses of declines in cognition.
Conclusion
Reduced cardiovascular autonomic function does not contribute to cognitive impairment in this middle-aged population. Further studies are needed to verify the potential role of HRV measures in predicting the degeneration of cognitive function at older ages.
doi:10.1159/000148257
PMCID: PMC2527026  PMID: 18667838
Autonomic function; Cognitive impairment; Heart rate variability; Cohort studies
25.  How much and how often should we drink? 
BMJ : British Medical Journal  2006;332(7552):1224-1225.
PMCID: PMC1471939  PMID: 16735306

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