Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits.

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

Association of lifelong occupation and educational level with subclinical atherosclerosis in different European regions. Results from the IMPROVE study.

BACKGROUND AND AIMS: We aimed to examine the association between socioeconomic status (SES) and subclinical atherosclerosis, as assessed by carotid intima-media-thickness (C-IMT) and to investigate whether the effect of social inequality on C-IMT is mediated by cardiovascular (CV) risk factors and whether it is dissimilar in men and women, and in different European countries. METHODS: We assessed the association of lifelong occupation and educational level with C-IMT in the IMPROVE study cohort including 3703 subjects (median age 64.4 years; 48% men) from Southern (Italy), Western (France and the Netherlands) and Northern Europe (Finland and Sweden). Three summary measures of C-IMT (IMTmean, IMTmax, IMTmean-max), obtained from four segments of both carotids, were considered. RESULTS: After adjusting for conventional CV risk factors, current employment status and diet, C-IMT was higher in manual workers than in white collars (+7.7%, +5.3%, +4.6% for IMTmax, IMTmean-max and IMTmean, respectively; all p<.0001). Similar results were obtained by stratification for educational level. The effect of occupation on C-IMT was comparable in men and women and in different age groups, and was only partially mediated by differences in CV risk factors. Of note, the association of C-IMT with occupation was significant in Western and Northern Europe but not in Italy, with a significant statistical interaction (p = .0005). CONCLUSIONS: Low SES was associated with subclinical atherosclerosis in subjects with at least three CV risk factors. Such association was stronger in Northern and Western Europe than in Italy. This difference was not completely explained by inequalities in CV risk factors and behavioural variables.

Carotid plaque-thickness and common carotid IMT show additive value in cardiovascular risk prediction and reclassification.

BACKGROUND AND AIMS: Carotid plaque size and the mean common carotid intima-media thickness measured in plaque-free areas (PF CC-IMTmean) have been identified as predictors of vascular events (VEs), but their complementarity in risk prediction and stratification is still unresolved. The aim of this study was to evaluate the independence of carotid plaque thickness and PF CC-IMTmean in cardiovascular risk prediction and risk stratification. METHODS: The IMPROVE-study is a European cohort (n = 3703), where the thickness of the largest plaque detected in the whole carotid tree was indexed as cIMTmax. PF CC-IMTmean was also assessed. Hazard Ratios (HR) comparing the top quartiles of cIMTmax and PF CC-IMTmeanversus their respective 1-3 quartiles were calculated using Cox regression. RESULTS: After a 36.2-month follow-up, there were 215 VEs (125 coronary, 73 cerebral and 17 peripheral). Both cIMTmax and PF CC-IMTmean were mutually independent predictors of combined-VEs, after adjustment for center, age, sex, risk factors and pharmacological treatment [HR (95% CI) = 1.98 (1.47, 2.67) and 1.68 (1.23, 2.29), respectively]. Both variables were independent predictors of cerebrovascular events (ischemic stroke, transient ischemic attack), while only cIMTmax was an independent predictor of coronary events (myocardial infarction, sudden cardiac death, angina pectoris, angioplasty, coronary bypass grafting). In reclassification analyses, PF CC-IMTmean significantly adds to a model including both Framingham Risk Factors and cIMTmax (Integrated Discrimination Improvement; IDI = 0.009; p = 0.0001) and vice-versa (IDI = 0.02; p < 0.0001). CONCLUSIONS: cIMTmax and PF CC-IMTmean are independent predictors of VEs, and as such, they should be used as additive rather than alternative variables in models for cardiovascular risk prediction and reclassification.

The impact of time cost of physical exercise on health outcomes by older adults: the DR's EXTRA Study.

When the motivation for exercise is high and people are retired, the cost of time used for physical exercise may be lower and individuals may exercise more compared to individuals with a low motivational level and in working life. The aim was to study the effect of time cost of physical exercise on the amount of physical exercise and on health-related quality of life. We used 2-year data (n = 1,292) from a 4-year randomised controlled trial in a population-based sample of Eastern Finnish men and women, 57-78 years of age at baseline, in 2005-2006. In the statistical analysis, physical exercise and health outcomes were assumed to be endogenous variables explained with a set of exogenous variables. The statistical modelling was done by panel data instrumental variable regressions. Health-related quality of life was evaluated by the RAND 36-item survey and motives for exercise with a questionnaire. Joy as the motivation for physical exercise and retirement increased the amount of physical exercise per week (p < 0.001). A higher amount of exercise was associated with physical (p < 0.001) and mental (p < 0.001) components of quality of life. Moreover, a higher amount of physical exercise decreased the metabolic risk factor score (p < 0.001). The motivation and extra time, i.e. retirement, have a significant impact on the time spent on physical exercise (p < 0.001). Our data agree with the theory that high motivation and retirement lower the time cost of physical exercise. The results emphasise that motivation and the labour market position are important in determining the cost of physical exercise.

Age, marital status and changes in dietary habits in later life: a 21-year follow-up among Finnish women.

OBJECTIVE: To examine 21-year longitudinal changes in dietary habits and their associations with age and marital status among women aged 50-60 years at baseline. DESIGN: Prospective, longitudinal study of a cohort in the FINMONICA population-based risk factor survey with clinical assessments in 1982, 1992 and 2003. Dietary habits were assessed via self-reported consumption of foods typically contributing to SFA, cholesterol and sugar intakes in the Finnish diet. A dietary risk score based upon five items was used. SETTING: Kuopio region, Finland. SUBJECTS: Complete data from all three assessments for 103 women of the original cohort of 299 were included for two age groups: 50-54 and 55-60 years at baseline. RESULTS: Dietary habits improved between 1982 and 1992 and showed continued but less pronounced improvement between 1992 and 2003: within the younger age group, 78 % of the women reduced the number of dietary risk points from the 1982 to 2003 scores, whereas 3 % increased them and 19 % reported no change. In the older age group these percentages were 61 %, 23 % and 16 %, respectively. Women who remained married showed a steadier decline in dietary risk points than single women or women who were widows at the beginning of the follow-up. CONCLUSIONS: Older women make positive changes to their dietary habits but the consistency of these changes may be affected by the ageing process, marital status and changes in the latter.

Sedentary lifestyle and emergence of hopelessness in middle-aged men.

BACKGROUND: A sedentary lifestyle and psychosocial factors such as hopelessness and depression increase cardiovascular risk. Cross-sectional evidence suggests positive effects of physical exercise on psychological well being, but the time order of the relationship between physical activity and hopelessness has not been addressed. DESIGN: Population-based prospective cohort study with 630 middle-aged men participating in the 4-year follow-up and 509 men in the 11-year follow-up. METHODS: We investigated the association of leisure-time physical activity (LTPA) with the development of hopelessness during the follow-up. LTPA and hopelessness were quantified with questionnaires. RESULTS: In cross-sectional analyses, LTPA was inversely associated with hopelessness, independently of depression. Among men who did not have feelings of hopelessness at baseline, those who reported engaging in at least 2.5 h/week of moderate-to-vigorous physical activity had a lower risk (odds ratio 0.65, 95% confidence interval: 0.39-1.09, P for the trend=0.047) to feel hopeless than sedentary men 4 years later after adjustment for age, smoking, alcohol consumption, cardiovascular disease and socioeconomic status. Furthermore, this relationship was not explained by body mass index or maximal oxygen uptake. Adjustment for depressive symptoms slightly weakened the association (odds ratio 0.66, 95% confidence interval: 0.39-1.11, P for the trend=0.060). After 11 years, men who reported being physically active at baseline were still less likely to feel hopeless, after adjusting for age. However, after further adjustment for other confounding factors the association was no longer significant. CONCLUSION: Moderate-to-vigorous physical activity seems to prevent development of hopelessness in middle-aged men. This protective effect may diminish over time.