Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts.

AIMS: Growth differentiation factor 11 and/or its homologue growth differentiation factor 8 (GDF11/8) reverses age-related cardiac hypertrophy and vascular ageing in mice. We investigated whether GDF11/8 associates with cardiovascular outcomes, left ventricular hypertrophy (LVH), or age in humans. METHODS AND RESULTS: We measured plasma GDF11/8 levels in 928 participants with stable ischaemic heart disease in the Heart and Soul study. We adjudicated heart failure hospitalization, stroke, myocardial infarction, death, and their composite endpoint. Left ventricular hypertrophy was evaluated by echocardiography. We used multivariable Cox proportional hazards models to compare rates of cardiovascular events and death across GDF11/8 quartiles and logistic regression models to evaluate the association between GDF11/8 and LVH. Four hundred and fifty participants (48.5%) experienced a cardiovascular event or death during 8.9 years of follow-up. The adjusted risk of the composite endpoint was lower in the highest compared with the lowest GDF11/8 quartile [hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.33-0.60; P < 0.001]. We replicated this relationship of GDF11/8 to adverse events in 971 participants in the HUNT3 cohort (adjusted HR, 0.34; 95% CI, 0.23-0.51; P < 0.001). Left ventricular hypertrophy was present in 368 participants (39.7%) at baseline. Participants in the highest quartile of GDF11/8 were less likely to have LVH than those in the lowest quartile (adjusted OR, 0.55; 95% CI, 0.35-0.86; P = 0.009). GDF11/8 levels were lower in older individuals (P < 0.001). CONCLUSION: In patients with stable ischaemic heart disease, higher GDF11/8 levels are associated with lower risk of cardiovascular events and death. Our findings suggest that GDF11/8 has similar cardioprotective properties in humans to those demonstrated in mice.

Effect of physical activity level on biomarkers of inflammation and insulin resistance over 5 years in outpatients with coronary heart disease (from the Heart and Soul Study).

Higher levels of physical activity are associated with lower rates of coronary heart disease (CHD). Previous studies have suggested that this is due partly to lower levels of inflammation and insulin resistance. The aim of this study was to determine whether physical activity level was associated with inflammation or insulin resistance during a 5-year period in outpatients with known CHD. A total of 656 participants from the Heart and Soul Study, a prospective cohort study of outpatients with documented CHD, were evaluated. Self-reported physical activity frequency was assessed at baseline and after 5 years of follow-up. Participants were classified as low versus high activity at each visit, yielding 4 physical activity groups: stable low activity, decreasing activity (high at baseline to low at year 5), increasing activity (low at baseline to high at year 5), and stable high activity. Year 5 markers of inflammation (C-reactive protein [CRP], interleukin-6, and fibrinogen) and insulin resistance (insulin, glucose, and glycated hemoglobin) were compared across the 4 activity groups. After 5 years of follow-up, higher activity was associated with lower mean levels of all biomarkers. In the fully adjusted regression models, CRP, interleukin-6, and glucose remained independently associated with physical activity frequency (log CRP, p for trend across activity groups = 0.03; log interleukin-6, p for trend = 0.01; log glucose, p for trend = 0.003). Subjects with stable high activity typically had the lowest levels of biomarkers. In conclusion, in this novel population of outpatients with known CHD followed for 5 years, higher physical activity frequency was independently associated with lower levels of CRP, interleukin-6, and glucose.

Association of alcohol use biomarkers and cognitive performance in veterans with problematic alcohol use and posttraumatic stress disorder: data from the mind your heart study.

The authors conducted a study of alcohol use biomarkers and cognitive performance among 85 veterans with problematic alcohol use and posttraumatic stress disorder (PTSD). All analyses were adjusted for demographics, depression, anxiety, and PTSD symptoms. Elevated levels of aspartate aminotransferase were associated with worse performance on the Trail Making Test Part A and Hopkins Verbal Learning Test. Two other biomarkers were not associated with any neurocognitive measures. Indirect alcohol use biomarkers (e.g., aspartate aminotransferase) may have a specific role in identifying veterans with problematic alcohol use and PTSD who show a change in psychomotor speed and immediate verbal memory performance.

Hostility, health behaviors, and risk of recurrent events in patients with stable coronary heart disease: findings from the Heart and Soul Study.

BACKGROUND: Hostility is a significant predictor of mortality and cardiovascular events in patients with coronary heart disease (CHD), but the mechanisms that explain this association are not well understood. The purpose of this study was to evaluate potential mechanisms of association between hostility and adverse cardiovascular outcomes. METHODS AND RESULTS: We prospectively examined the association between self-reported hostility and secondary events (myocardial infarction, heart failure, stroke, transient ischemic attack, and death) in 1022 outpatients with stable CHD from the Heart and Soul Study. Baseline hostility was assessed using the 8-item Cynical Distrust scale. Cox proportional hazard models were used to determine the extent to which candidate biological and behavioral mediators changed the strength of association between hostility and secondary events. During an average follow-up time of 7.4 ± 2.7 years, the age-adjusted annual rate of secondary events was 9.5% among subjects in the highest quartile of hostility and 5.7% among subjects in the lowest quartile (age-adjusted hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.30 to 2.17; P < 0.0001). After adjustment for cardiovascular risk factors, participants with hostility scores in the highest quartile had a 58% greater risk of secondary events than those in the lowest quartile (HR: 1.58, 95% CI: 1.19 to 2.09; P = 0.001). This association was mildly attenuated after adjustment for C-reactive protein (HR: 1.41, 95% CI, 1.06 to 1.87; P = 0.02) and no longer significant after further adjustment for smoking and physical inactivity (HR: 1.25, 95% CI: 0.94 to 1.67; P = 0.13). CONCLUSIONS: Hostility was a significant predictor of secondary events in this sample of outpatients with baseline stable CHD. Much of this association was moderated by poor health behaviors, specifically physical inactivity and smoking.