METHODS: In a sample of 9448 participants followed for a mean of 15.3 years (186,158.5 person-years) from the Monitoring of Trends and Determinants in Cardiovascular Disease Augsburg/Cooperative Health Research in the Region of Augsburg population-based cohort conducted in Germany, we investigated the association of social connectivity, measured by the Social Network Index, and body mass index (BMI) with the risk of clinically validated T2D incidence using stratified Cox proportional hazards regression models adjusted for sociodemographic, life-style, cardiometabolic, and psychosocial risk factors.
RESULTS: During a mean follow-up of 14.1 years (186,158.5 person-years), 975 (10.3%) participants developed T2D. Participants with low social connectivity developed T2D at a higher rate than socially connected participants (10.0 versus 8.0 cases/10,000 person-years); however, BMI played a significant role in the association of social connectivity with T2D ( p < .001). In comparison to their socially connected counterparts, low social connectivity was associated with a higher rate of T2D incidence in normal-weight (6.0 versus 2.0 cases/10,000 person-years), but not overweight (13.0 versus 13.0 cases/10,000 person-years) or obese participants (32.0 versus 30.0 cases/10,000 person-years). Correspondingly, Cox regression analysis showed that 5-unit increments in BMI increased the risk of T2D in socially connected participants (hazard ratio = 3.03, 95% confidence interval = 2.48-3.79, p < .001) at a substantially higher rate than in low socially connected participants (hazard ratio = 1.77, 95% confidence interval = 1.45-2.16, p < .001).
CONCLUSION: The detrimental link between low social connectivity and increased risk of T2D is substantially stronger in participants with a lower BMI.
METHODS AND RESULTS: In a sample of 11 146 adults (51.5% men and 48.5% women) with a mean age of 47.1 years (SD ± 12.3) from a German population-based cohort, we analyzed risk factors and CVD mortality risk associated with an alerting reaction. An alerting reaction was prevalent in 10.2% of the population and associated with sociodemographic, lifestyle, and somatic CVD risk factors. Within a mean follow-up period of 22.7 years (SD ± 7.05 years; max: 32 years; 253 201 person years), 1420 (12.7%) CVD mortality cases were observed. The CVD mortality rate associated with an alerting reaction was significantly higher than in normotension (64 vs. 32 cases/10 000 person-years), but lower than hypertension (118 cases/10 000 person-years). Correspondingly, the alerting reaction was associated with a 23% higher hazard ratio of CVD mortality than normal blood pressure [hazard ratio 1.23 (95% confidence interval 1.02-1.49), P = 0.04]. However, adjustment for antihypertensive medication use attenuated this association [1.19 (0.99-1.44), P = 0.06].
CONCLUSION: The results may warrant monitoring of an alerting reaction as a preventive measure of CVD mortality in untreated individuals with elevated first BP readings, as well as optimized treatment in treated individuals.
DESIGN: Individual participant meta-analysis using data from 25 cohorts participating in the CHANCES consortium. Data were harmonised, analysed separately employing Cox proportional hazard regression models, and combined by meta-analysis.
RESULTS: Overall, 503,905 participants aged 60 and older were included in this study, of whom 37,952 died from cardiovascular disease. Random effects meta-analysis of the association of smoking status with cardiovascular mortality yielded a summary hazard ratio of 2.07 (95% CI 1.82 to 2.36) for current smokers and 1.37 (1.25 to 1.49) for former smokers compared with never smokers. Corresponding summary estimates for risk advancement periods were 5.50 years (4.25 to 6.75) for current smokers and 2.16 years (1.38 to 2.39) for former smokers. The excess risk in smokers increased with cigarette consumption in a dose-response manner, and decreased continuously with time since smoking cessation in former smokers. Relative risk estimates for acute coronary events and for stroke events were somewhat lower than for cardiovascular mortality, but patterns were similar.
CONCLUSIONS: Our study corroborates and expands evidence from previous studies in showing that smoking is a strong independent risk factor of cardiovascular events and mortality even at older age, advancing cardiovascular mortality by more than five years, and demonstrating that smoking cessation in these age groups is still beneficial in reducing the excess risk.
METHODS: Relative mortality and mortality rate advancement periods (RAPs) were estimated by Cox proportional hazards models for the population-based prospective cohort studies from Europe and the U.S. (CHANCES [Consortium on Health and Ageing: Network of Cohorts in Europe and the U.S.]), and subsequently pooled by individual participant meta-analysis. Statistical analyses were performed from June 2013 to March 2014.
RESULTS: A total of 489,056 participants aged ≥60 years at baseline from 22 population-based cohort studies were included. Overall, 99,298 deaths were recorded. Current smokers had 2-fold and former smokers had 1.3-fold increased mortality compared with never smokers. These increases in mortality translated to RAPs of 6.4 (95% CI=4.8, 7.9) and 2.4 (95% CI=1.5, 3.4) years, respectively. A clear positive dose-response relationship was observed between number of currently smoked cigarettes and mortality. For former smokers, excess mortality and RAPs decreased with time since cessation, with RAPs of 3.9 (95% CI=3.0, 4.7), 2.7 (95% CI=1.8, 3.6), and 0.7 (95% CI=0.2, 1.1) for those who had quit <10, 10 to 19, and ≥20 years ago, respectively.
CONCLUSIONS: Smoking remains as a strong risk factor for premature mortality in older individuals and cessation remains beneficial even at advanced ages. Efforts to support smoking abstinence at all ages should be a public health priority.
METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls.
RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2.
CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.
METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P