There is some evidence to suggest that obesity is a risk factor for the development of depression, although this is not a universal finding. This discordance might be ascribed to the existence of a ‘healthy obese phenotype’– that is, obesity in the absence of the associated burden of cardio-metabolic risk factors. We examined whether the association of obesity with depressive symptoms is dependent on the individual’s metabolic health. Participants were 3851 men and women (aged 63.0 ± 8.9 yrs, 45.1% men) from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Obesity was defined as body mass index ≥ 30 kg/m2. Based on blood pressure, HDL-cholesterol, triglycerides, glycated haemoglobin, and C-reactive protein, participants were classified as ‘metabolically healthy’ (0 or 1 metabolic abnormality) or ‘unhealthy’ (≥ 2 metabolic abnormalities). Depressive symptoms were assessed at baseline and at 2 years follow up using the 8-item Centre of Epidemiological Studies Depression (CES-D) scale. Obesity prevalence was 27.5%, but 34.3% of this group was categorized as metabolically healthy at baseline. Relative to non-obese healthy participants, after adjustment for baseline CES-D score and other covariates, the metabolically unhealthy obese participants had elevated risk of depressive symptoms at follow-up (odds ratio [OR] = 1.50, 95% CI, 1.05–2.15), although the metabolically healthy obese did not (OR = 1.38, 95% CI, 0.88–2.17). The association between obesity and risk of depressive symptoms appears to be partly dependent on metabolic health, although further work is required to confirm these findings.

OBJECTIVE

C-reactive protein (CRP) is associated with the risk of cardiovascular disease (CVD); whether the effects are modified by diabetes status still is unclear. This study investigated these issues and assessed the added value of CRP to predictions.

RESEARCH DESIGN AND METHODS

Participants were drawn from representative samples of adults living in England and Scotland. Cox proportional hazards regression models were used to relate baseline plasma CRP with all-cause and CVD mortality during follow-up in men and women with and without diabetes. The added value of CRP to the predictions was assessed through c-statistic comparison and relative integrated discrimination improvement.

RESULTS

A total of 25,979 participants (4.9% with diabetes) were followed for a median of 93 months, during which period there were 2,767 deaths (957 from CVD). CRP (per SD loge) was associated with a 53% (95% CI 43–64) and 43% (38–49) higher risk of cardiovascular and all-cause mortality, respectively. These associations were log linear and did not differ according to diabetes status (both P ≥ 0.08 for interaction), sex, and other risk factors. Adding CRP to conventional risk factors improved predictions overall and separately by diabetes status but not for CVD mortality, although such improvements only were marginal based on several discrimination statistics.

CONCLUSIONS

The association between CRP and CVD was similar across diabetes status, and the effects are broadly similar across levels of other conventional risk factors.

Background

There are few longitudinal data on physical activity patterns from mid-life into older age. The authors examined associations of self-reported physical activity, adiposity and socio-demographic factors in mid-life with objectively assessed measures of activity in older age.

Methods

Participants were 394 healthy men and women drawn from the Whitehall II population-based cohort study. At the baseline assessment in 1997 (mean age 54 years), physical activity was assessed through self-report and quantified as metabolic equivalent of task hours/week. At the follow-up in 2010 (mean age 66 years), physical activity was objectively measured using accelerometers worn during waking hours for seven consecutive days (average daily wear time 891±68 min/day).

Results

Self-reported physical activity at baseline was associated with objectively assessed activity at follow-up in various activity categories, including light-, moderate- and vigorous-intensity activity (all ps<0.04). Participants in the highest compared with lowest quartile of self-reported activity level at baseline recorded on average 64.1 (95% CI 26.2 to 102.1) counts per minute more accelerometer-assessed activity at follow-up and 9.0 (2.0–16.0) min/day more moderate-to-vigorous daily activity, after adjusting for baseline covariates. Lower education, obesity and self-perceived health status were also related to physical activity at follow-up. Only age and education were associated with objectively measured sedentary time at follow-up.

Conclusion

Physical activity behaviour in middle age was associated with objectively measured physical activity in later life after 13 years of follow-up, suggesting that the habits in adulthood are partly tracked into older age.

Background

Shorter telomere length and poor sleep are more prevalent at older ages, but their relationship is uncertain. This study explored associations between sleep duration and telomere length in a sample of healthy middle and early old age people.

Methods

Participants were 434 men and women aged 63.3 years on average drawn from the Whitehall II cohort study. Sleep duration was measured by self-report.

Results

There was a linear association between sleep duration and leukocyte telomere length in men but not in women (P = 0.035). Men reporting shorter sleep duration had shorter telomeres, independently of age, body mass index, smoking, educational attainment, current employment, cynical hostility scores and depressive symptoms. Telomeres were on average 6% shorter in men sleeping 5 hours or fewer compared with those sleeping more than 7 hours per night.

Conclusion

This study adds to the growing literature relating sleep duration with biomarkers of aging, and suggests that shortening of telomeres might reflect mechanisms through which short sleep contributes to pathological conditions in older men.

Summary

Background

Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies.

Methods

We used individual records from 13 European cohort studies (1985–2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death.

Findings

30 214 (15%) of 197 473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10–1·37). This effect estimate was higher in published (1·43, 1·15–1·77) than unpublished (1·16, 1·02–1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15–1·48) and 5 years (1·30, 1·13–1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%.

Interpretation

Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking.

Funding

Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.

Predictive power, for total and vascular mortality, of selected indices measured at baseline in the British National Diet and Nutrition Survey (community-living subset) of People Aged 65 Years and Over was tested. Mortality status and its primary and underlying causes were recorded for 1100 (mean age 76·7 (SD 7·5) years, 50·2 % females) respondents from the baseline survey in 1994–5 until September 2008. Follow-up data analyses focussed especially on known predictors of vascular disease risk, together with intakes and status indices of selected nutrients known to affect, or to be affected by, these predictors. Total mortality was significantly predicted by hazard ratios of baseline plasma concentrations (per SD) of total homocysteine (tHcy) (95 % CI) 1·19 (1·11, 1·27), pyridoxal phosphate 0·90 (0·81, 1·00), pyridoxic acid 1·10 (1·03, 1·19), α1-antichymotrypsin 1·21 (1·13, 1·29), fibrinogen 1·14 (1·05, 1·23), creatinine 1·20 (1·10, 1·31) and glycosylated Hb 1·23 (1·14, 1·32), and by dietary intakes of energy 0·87 (0·80, 0·96) and protein 0·86 (0·77, 0·97). Prediction patterns and significance were similar for primary-cause vascular mortality. The traditional risk predictors plasma total and HDL cholesterol were not significant mortality predictors in this age group, nor were the known tHcy-regulating nutrients, folate and vitamin B12 (intakes and status indices). Model adjustment for known risk predictors resulted in the loss of significance for some of the afore-mentioned indices; however, tHcy 1·34 (1·04, 1·73) remained a significant predictor for vascular mortality. Thus, total and primary vascular mortality is predicted by energy and protein intakes, and by biochemical indices including tHcy, independent of serum folate or vitamin B12.

Background:

Little is known about psychological risk factors in cerebrovascular disease. We examined the association between psychological distress and risk of death due to cerebrovascular disease.

Methods:

We obtained data from 68 652 adult participants of the Health Survey for England (mean age 54.9 [standard deviation 13.9] yr, 45.0% male sex) with no known history of cardiovascular diseases at baseline. We used the 12-item General Health Questionnaire (GHQ-12) to assess the presence of psychological distress. We followed participants for eight years for cause-specific death using linkage to national registers.

Results:

There were 2367 deaths due to cardiovascular disease during follow-up. Relative to participants with no symptoms of psychological distress (GHQ-12 score 0) at baseline, people with psychological distress (GHQ-12 score ≥ 4, 14.7% of participants) had an increased risk of death from cerebrovascular disease (adjusted hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.32–2.08) and ischemic heart disease (adjusted HR 1.59, 95% CI 1.34–1.88). There was also evidence of a dose–response effect with increasing GHQ-12 score (p for trend < 0.001 in all analyses). Associations were only marginally attenuated after we adjusted for possible confounders, including socioeconomic status, smoking and use of antihypertensive medications.

Interpretation:

Psychological distress was associated with increased risk of death due to cerebrovascular disease in a large population-representative cohort. These data suggest that the cardiovascular effects of psychological distress are not limited to coronary artery disease.

Background

Both anaemia and cardiovascular disease (CVD) are common in people with diabetes. While individually both characteristics are known to raise mortality risk, their combined influence has yet to be quantified. In this pooling project, we examined the combined impact of baseline haemoglobin levels and existing CVD on all-cause and CVD mortality in people with diabetes. We draw comparison of these effects with those apparent in diabetes-free individuals.

Methods/Principal Findings

A combined analyses of 7 UK population-based cohorts resulted in 26,480 study members. There were 946 participants with physician-diagnosed diabetes, 2227 with anaemia [haemoglobin<13 g/dl (men) or <12 (women)], 2592 with existing CVD (stroke, ischaemic heart disease), and 21,396 with none of the conditions. Across diabetes and anaemia subgroups, and using diabetes-free, non-anaemic participants as the referent group, the adjusted hazard ratios (HR) were 1.46 (95% CI: 1.30–1.63) for anaemia, 1.67 (1.45–1.92) for diabetes, and 2.10 (1.55–2.85) for diabetes and anaemia combined. Across combined diabetes, anaemia and CVD subgroups, and compared with non-anaemic, diabetes-free and CVD-free participants, HR (95% CI) for all-cause mortality were 1.49 (1.32–1.69) anaemia, 1.60 (1.46–1.76) for existing CVD, and 1.66 (1.39–1.97) for diabetes alone. Equivalents were 2.13 (1.48–3.07) for anaemia and diabetes, 2.68 (2.14–3.36) for diabetes and existing CVD, and 3.25 (1.88–5.62) for the three combined. Patterns were similar for CVD mortality.

Conclusions/Significance

Individually, anaemia and CVD confer similar mortality risks in people with diabetes, and are excessively fatal in combination. Screening for anaemia would identify vulnerable diabetic patients whose outcomes can potentially be improved.

Objective To quantify the link between lower, subclinically symptomatic, levels of psychological distress and cause-specific mortality in a large scale, population based study.

Design Individual participant meta-analysis of 10 large prospective cohort studies from the Health Survey for England. Baseline psychological distress measured by the 12 item General Health Questionnaire score, and mortality from death certification.

Participants 68 222 people from general population samples of adults aged 35 years and over, free of cardiovascular disease and cancer, and living in private households in England at study baseline.

Main outcome measures Death from all causes (n=8365), cardiovascular disease including cerebrovascular disease (n=3382), all cancers (n=2552), and deaths from external causes (n=386). Mean follow-up was 8.2 years (standard deviation 3.5).

Results We found a dose-response association between psychological distress across the full range of severity and an increased risk of mortality (age and sex adjusted hazard ratio for General Health Questionnaire scores of 1-3 v score 0: 1.20, 95% confidence interval 1.13 to 1.27; scores 4-6: 1.43, 1.31 to 1.56; and scores 7-12: 1.94, 1.66 to 2.26; P<0.001 for trend). This association remained after adjustment for somatic comorbidity plus behavioural and socioeconomic factors. A similar association was found for cardiovascular disease deaths and deaths from external causes. Cancer death was only associated with psychological distress at higher levels.

Conclusions Psychological distress is associated with increased risk of mortality from several major causes in a dose-response pattern. Risk of mortality was raised even at lower levels of distress.

The predictive power, for total, vascular, cancer and respiratory mortality, of selected redox-modulatory (vitamin and mineral nutrient) indices measured at baseline, was studied in the British National Diet and Nutrition Survey (community-living subset) of people aged 65 years and over. Mortality status and its primary and underlying causes were recorded for 1054 (mean age 76·6 (SD 7·4) years and 49·0 % female) participants, from the baseline survey in 1994–5 until September 2008. During this interval, 74 % of the male and 62 % of the female participants died. Total mortality was significantly predicted by baseline plasma concentrations (per SD) of vitamin C (hazard ratio (HR) 0·81; 95 % CI 0·74, 0·88), α-carotene (HR 0·90; 95 % CI 0·81, 0·99), Se (HR 0·76; 95 % CI 0·69, 0·84), Zn (HR 0·79; 95 % CI 0·72, 0·87), Cu (HR 1·27; 95 % CI 1·14, 1·42) and Fe (HR 0·81; 95 % CI 0·74, 0·89). Total mortality was also significantly predicted by baseline dietary intakes (per SD) of food energy (HR 0·86; 95 % CI 0·79, 0·94), vitamin C (HR 0·88; 95 % CI 0·80, 0·94), carotenoids (HR 0·89; 95 % CI 0·83, 0·96), Zn (HR 0·89; 95 % CI 0·82, 0·96) and Cu (HR 0·91; 95 % CI 0·84, 1·00). Prediction patterns and significance for primary vascular, cancer and respiratory mortality differed in certain respects, but not fundamentally. Model adjustment for known disease or mortality risk predictors resulted in loss of significance for some of the indices; however, plasma Se and Zn, and food energy remained significant predictors. We conclude that total and primary vascular, cancer and respiratory mortality in older British people of both sexes is predicted by several biochemical indices of redox-modulatory nutrients, some of which may reflect the respondents’ acute-phase status at baseline, whereas others may reflect the healthiness of their lifestyle.

Objectives

To examine the association between objectively measured second–hand-smoke (SHS) exposure and incident CVD death, and assess the extent to which this association can be explained through novel circulating markers of inflammation and haemostasis.

Background

Existing evidence suggests there is an association between SHS and cardiovascular disease (CVD) risk, although the mechanisms remain poorly understood.

Methods

In a prospective study of 13,443 participants living in England and Scotland [aged 53.5, (SD 12.6 yrs), 52.3% women] we measured salivary cotinine (an objective marker of SHS exposure) and novel CVD biomarkers (C-reactive protein, fibrinogen) at baseline.

Results

20.8% of the sample had high SHS exposure based on elevated levels of salivary cotinine (0.71 – 14.99 ng/mL). During a mean follow-up of 8 years, there were 1221 all-cause deaths and 364 CVD deaths. High SHS was associated with all-cause (age adjusted HR= 1.25, 95% CI, 1.02 – 1.53) and CVD death (age adjusted HR= 1.21, 95% CI, 0.85 – 1.73). High SHS was also associated with elevated CRP, which explained 48% of the association between SHS and CVD death. The excess risk of CVD associated with active smoking was exaggerated in relation to self report (age adjusted HR= 3.27, 95% CI, 2.48 – 4.31) compared with objective assessment (age adjusted HR= 2.44, 95% CI, 1.75 – 3.40).

Conclusion

Among a large representative sample of British adults we observed elevated levels of low grade inflammation in otherwise healthy participants exposed to high SHS, and this partly explained their elevated risk of CVD death.

There is conflicting evidence regarding the association of hypertension with psychological distress, such as anxiety and depressive symptoms. The association may be due to a direct effect of the raised blood pressure; side effects of treatment; or the consequences of labelling. In a representative study of 33,105 adults (aged 51.7 ±12.1 yrs, 45.8% men) we measured levels of psychological distress using the 12-item General Health Questionnaire and collected blood pressure, data on history of hypertension diagnosis, and medication usage. Awareness of hypertension was confirmed through a physician’s diagnosis or the use of anti-hypertensive medication and unaware hypertension was defined by elevated clinic blood pressure (systolic/diastolic ≥140/90 mm Hg) without prior treatment or diagnosis. In comparison with normotensive participants, an elevated risk of distress (General Health Questionnaire score ≥4) was observed in aware hypertensive participants (multivariable adjusted odds ratio [OR]=1.57, 95% CI, 1.41 – 1.74), although not in unaware hypertensives (OR = 0.91, 95% CI, 0.78 – 1.07). Anti-hypertensive medication and co-morbidity was also associated with psychological distress although this did not explain the greater risk of distress in aware hypertensives. We observed a weak curvilinear association between systolic blood pressure and distress which suggested that distressed participants were more likely to have low or highly elevated blood pressure. These findings suggest that labelling individuals as hypertensive, rather than elevated blood pressure per se, may partially explain the greater levels of distress in patients treated for hypertension.

Background

Tooth loss is associated with increased cardiovascular disease (CVD) mortality risk. This association may however be due to residual confounding. We aimed to assess whether tooth loss is associated with specific CVD mortality endpoints in a national population sample adjusting for potential confounders.

Methods and Results

We used a prospective cohort design and data from the Scottish Health Survey. We combined data from surveys in 1995, 1998, 2003 and linked this to mortality records. Dental status was classified through self-reports as natural teeth only, natural teeth and dentures, and no natural teeth (edentate). Cox proportional hazards models were used to estimate risk of CVD mortality by dental status adjusting for potential confounders. The sample consisted of 12871 participants. They were followed for 8.0 (SD: 3.3) years. During 103173 person-years, there were 1480 cases of all-cause mortality, 498 of CVD, and 515 of cancer. After adjusting for demographic, socio-economic, behavioural and health status, edentate subjects had significantly higher risk of all-cause (HR, 1.30; 95% CI, 1.12,1.50) and CVD mortality (HR, 1.49; 95% CI, 1.16,1.92) compared to subjects with natural teeth only. Dental status was not significantly associated with cancer mortality in fully adjusted analysis. Further analysis for CVD mortality showed that in the fully adjusted model, edentate subjects had 2.97 (95% CI, 1.46, 6.05) times higher risk for stroke-related mortality.

Conclusions

In a national population sample of Scottish adults, being edentate was an independent predictor of total CVD mortality, although this was mainly driven by fatal stroke events.

The Mendelian randomization approach exploits genetic variants to improve causal inference when using observational data. The authors examined the relation between long-term obesity and common mental disorders (CMD) by utilizing the known relation between fat mass and obesity-associated (FTO) genotype and body mass index (BMI; weight (kg)/height (m)2). Data collection in 2,981 men and 1,164 women (mean age at baseline = 44 years) from the Whitehall II Study (London, United Kingdom) included 4 repeated examinations of BMI and CMD over a 19-year follow-up period (1985–2004), plus an assessment of FTO polymorphism rs1421085. In men, there was an association of FTO genotype with all measures of adiposity (mean BMI, number of times obese, and, in nonobese persons, number of times overweight). FTO was also associated with CMD in men. This was independent of adiposity, thus potentially violating the exclusion restriction assumption. According to both conventional and FTO-instrumented regression analysis, measurement of obesity was associated with an increased occurrence of CMD. In the FTO-instrumented analysis only, higher BMI and overweight were also associated with CMD. In women, there was no link between FTO and adiposity. Mendelian randomization analyses supported the status of long-term obesity as a risk factor for CMD in men—a finding that should be interpreted cautiously because the function of the FTO gene is unknown.

Background

Psychosocial stress is a risk factor for coronary heart disease (CHD). The mechanisms are incompletely understood, although dysfunction of the hypothalamic pituitary adrenal (HPA) axis might be involved. We examined the association between cortisol responses to laboratory-induced mental stress and the progression of coronary artery calcification (CAC).

Methods and Results

Participants were 466 healthy men and women (mean age = 62.7±5.6 yrs), without history or objective signs of CHD, drawn from the Whitehall II epidemiological cohort. At the baseline assessment salivary cortisol was measured in response to mental stressors, consisting of a 5-min Stroop task and a 5-min mirror tracing task. CAC was measured at baseline and at 3 years follow up using electron beam computed tomography. CAC progression was defined as an increase >10 Agatston units between baseline and follow up. 38.2% of the sample demonstrated CAC progression over the 3 years follow up. There was considerable variation in the cortisol stress response, with approximately 40% of the sample responding to the stress tasks with an increase in cortisol of at least 1 mmol/l. There was an association between cortisol stress reactivity (per SD) and CAC progression (odds ratio = 1.27, 95% CI, 1.02–1.60) after adjustments for age, sex, pre-stress cortisol, employment grade, smoking, resting systolic BP, fibrinogen, body mass index, and use of statins. There was no association between systolic blood pressure reactivity and CAC progression (odds ratio per SD increase = 1.03, 95% CI, 0.85–1.24). Other independent predictors of CAC progression included age, male sex, smoking, resting systolic blood pressure, and fibrinogen.

Conclusion

Results demonstrate an association between heightened cortisol reactivity to stress and CAC progression. These data support the notion that cortisol reactivity, an index of HPA function, is one of the possible mechanisms through which psychosocial stress may influence the risk of CHD.

Aims

The association between antidepressant use and risk of cardiovascular disease (CVD) remains controversial, particularly in initially healthy samples. Given that antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are now prescribed not only for depression, but also for a wide range of conditions, this issue has relevance to the general population. We assessed the association between antidepressant medication use and future risk of CVD in a representative sample of community-dwelling adults without known CVD.

Methods and results

A prospective cohort study of 14 784 adults (aged 52.4 ± 11.9 years, 43.9% males) without a known history of CVD was drawn from the Scottish Health Surveys. Of these study participants, 4.9% reported the use of antidepressant medication. Incident CVD events (comprising CVD death, non-fatal myocardial infarction, coronary surgical procedures, stroke, and heart failure) over 8-year follow-up were ascertained by a linkage to national registers; a total of 1434 events were recorded. The use of tricyclic antidepressants (TCAs) was associated with elevated risk of CVD [multivariate-adjusted hazard ratio (HR) = 1.35, 95% confidence interval (CI), 1.03–1.77] after accounting for a range of covariates. There was a non-significant association between TCA use and coronary heart disease events (969 events, multivariate-adjusted HR = 1.24, 95% CI, 0.87–1.75). The use of SSRIs was not associated with CVD. Neither class of drug was associated with all-cause mortality risk.

Conclusion

Although replication is required, the increased risk of CVD in men and women taking TCAs was not explained by existing mental illness, which suggests that this medication is associated with an excess disease burden.

The use of anti-depressant medication has been linked to cardiovascular disease (CVD). We examined the association between anti-depressant medication use and a marker of low grade systemic inflammation as a potential pathway linking anti-depressant use and CVD in two population based studies. Data were collected in a representative sample of 8,131 community dwelling adults (aged 47.4 ± 15.9 yrs, 46.7% male) from the Scottish Health Surveys (SHS). The use of anti-depressant medication was coded according to the British National Formulary and blood was drawn for the measurement of C-reactive protein (CRP). In a second study, we attempted to replicate our findings using longitudinal data from the Whitehall II study (n=4584, aged 55.5 ± 5.9 yrs, mean follow-up 5.5 years). Antidepressants were used in 5.6% of the SHS sample, with selective serotonin reuptake inhibitors (SSRIs) being the most common. There was a higher risk of elevated CRP (>3 mg/L) in users of tricyclic antidepressant (TCA) medication (multivariate adjusted odds ratio (OR) = 1.52, 95% CI, 1.07 – 2.15), but not in SSRI users (multivariate adjusted OR = 1.07, 95% CI, 0.81 – 1.42). A longitudinal association between any antidepressant use and subsequent CRP was confirmed in the Whitehall cohort. In summary, the use of anti-depressants was associated with elevated levels of systemic inflammation independently from the symptoms of mental illness and cardiovascular co-morbidity. This might be a potential mechanism through which antidepressant medication increases CVD risk. Further data are required to explore the effects of dosage and duration of antidepressant treatment.

OBJECTIVE

To examine antidepressant medication use as a risk factor for type 2 diabetes and weight gain.

RESEARCH DESIGN AND METHODS

A series of nested studies within a prospective cohort of 151,347 working-aged men and women including 9,197 participants with continuing antidepressant medication, 224 with severe depression, and 851 with incident type 2 diabetes during a mean follow-up of 4.8 years, as indicated by national health and prescription registers (the Public Sector study, Finland 1995–2005).

RESULTS

In the first analysis, the case subjects were individuals with incident type 2 diabetes compared with matched diabetes-free control subjects. Antidepressant use of ≥200 defined daily doses was associated with a doubling of diabetes risk in both participants with no indication of severe depression (odds ratio 1.93 [95% CI 1.48–2.51]) and participants with severe depression (2.65 [1.31–5.39]). In further analyses, the exposed group was antidepressant users and the reference group was nonusers matched for depression-related characteristics. The 5-year absolute risk of diabetes was 1.1% for nonusers, 1.7% for individuals treated with 200–399 defined daily doses a year, and 2.3% for those with ≥400 defined daily doses (Ptrend < 0.0001). An average self-reported weight gain, based on repeated surveys, was 1.4 kg (2.5%) among nonusers and 2.5 kg (4.3%) among users of ≥200 defined daily doses (Ptrend < 0.0001). Separate analyses for tricyclic antidepressants and selective serotonin reuptake inhibitors replicated these findings.

CONCLUSIONS

In these data, continuing use of antidepressant medication was associated with an increased relative risk of type 2 diabetes, although the elevation in absolute risk was modest.

Background

Previous research suggests a link between antidepressant use and diabetes, but it is unclear whether the association is causal or attributable to detection/ascertainment bias. To examine this, we assessed the associations of antidepressant use with change in glucose levels and incidence of undiagnosed and diagnosed diabetes.

Methods

During an 18-year period, we monitored antidepressant use, glucose levels, and diabetes status in 5978 civil servants (70.9% male, age range 39–64 years) free of diabetes at baseline (the Whitehall II study). Use of medication and plasma glucose were assessed at four study screenings: 1991/1993, 1997/1999, 2003/2004, and 2008/2009. Incident diabetes cases were classified as either diagnosed (n = 294) if detected using self-report of physician diagnosis and/or the use of diabetes medication or undiagnosed (n = 346) if detected based on fasting and/or 2-hour postload glucose levels using an oral glucose tolerance test at the study screenings.

Results

Incidence of diagnosed diabetes was higher among antidepressant users than nonusers (odds ratio 3.10, 95% confidence interval: 1.66–5.78). However, antidepressant use was not associated with undiagnosed diabetes at any follow-up examination nor with higher fasting or 2-hour postload plasma glucose levels or increasing glucose levels over time. Odds ratio for undiagnosed diabetes for antidepressant users versus nonusers was .88 (95% confidence interval: .45–1.72, p = .70). The mean difference in glucose changes between participants reporting antidepressant use at three screenings compared with those not on antidepressant treatment was .0 mmol/L.

Conclusions

The link between antidepressant use and diabetes risk may not be causal in nature.

Disturbances in circadian rhythm might play a central role in the neurobiology of depression. We examined the association between depressive symptoms and 24-hour ambulatory BP in a sample of 405 (197 black and 208 Caucasian) urbanized African teachers aged 25 to 60 yrs (mean 44.6 ± 9.6 yrs). Depressive symptoms were assessed using the self-administered 9-item Patient Health Questionnaire (PHQ-9). After adjusting for age, sex, and ethnicity, participants with severe depressive symptoms (PHQ-9 ≥ 15) had higher odds of hypertension defined from ambulatory BP and/or use of antihypertensive medication (odds ratio = 2.19, 95% CI, 1.00–4.90) in comparison to participants with no symptoms. Compared to Caucasians with no depressive symptoms, those with severe symptoms had blunted nocturnal systolic BP drop of 4.7 mmHg (95% CI, −0.5 to 10.0, P = 0.07). In summary, depressive symptoms were associated with the circadian BP profile in black and Caucasian Africans.

Background

Long hours are associated with increased risk of coronary heart disease. Adding information on long hours to traditional risk factors could potentially help improve risk prediction.

Objective

To examine whether information on long working hours improves the ability of the Framingham risk model to predict coronary heart disease in a low-risk employed population.

Design

Prospective cohort study; baseline medical examination (1991-1993) and coronary heart disease follow-up to 2004.

Settings

Civil service departments in London (the Whitehall II study).

Participants

7095 adults (2109 women) aged 39 to 62, working full time, and free of coronary heart disease at baseline.

Measurements

Working hours and the Framingham risk score were measured at baseline. Coronary death and non-fatal myocardial infarction were ascertained from three sources: medical screenings every 5 years, hospital data and register linkage.

Results

192 persons had incident coronary heart disease during a median 12.3 year follow-up. After adjustment for the Framingham score, participants working ≥11 hours per day had a 1.67-fold (95% CI: 1.10-2.55) increased risk of coronary heart disease relative to those working 7-8 hours. The addition of working hours to the Framingham score led to a net reclassification improvement of 4.7% (p=0.034), resulting from a better identification of individuals who later developed coronary heart disease (sensitivity gain).

Limitations

The findings may not be generalizable to populations with a larger proportion of high-risk individuals. Furthermore, the predictive utility of working hours was not validated in an independent cohort.

Conclusion

Information on working hours may improve prediction of coronary heart disease risk based on the Framingham risk score in low-risk working populations.

Primary Funding Source

Medical Research Council, British Heart Foundation, BUPA Foundation, UK; National Heart, Lung and Blood Institute and National Institute on Aging, NIH, US.

In this study, the health-related selection hypothesis (that health predicts social mobility) and the social causation hypothesis (that socioeconomic status influences health) were tested in relation to cardiometabolic factors. The authors screened 8,312 United Kingdom men and women 3 times over 10 years between 1991 and 2004 for waist circumference, body mass index, systolic and diastolic blood pressure, fasting glucose, fasting insulin, serum lipids, C-reactive protein, and interleukin-6; identified participants with the metabolic syndrome; and measured childhood health retrospectively. Health-related selection was examined in 2 ways: 1) childhood health problems as predictors of adult occupational position and 2) adult cardiometabolic factors as predictors of subsequent promotion at work. Social causation was assessed using adult occupational position as a predictor of subsequent change in cardiometabolic factors. Hospitalization during childhood and lower birth weight were associated with lower occupational position (both P’s ≤ 0.002). Cardiometabolic factors in adulthood did not consistently predict promotion. In contrast, lower adult occupational position predicted adverse changes in several cardiometabolic factors (waist circumference, body mass index, fasting glucose, and fasting insulin) and an increased risk of new-onset metabolic syndrome (all P’s ≤ 0.008). These findings suggest that health-related selection operates at younger ages and that social causation contributes to socioeconomic differences in cardiometabolic health in midlife.