201. 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.
- Author
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Olson KA, Beatty AL, Heidecker B, Regan MC, Brody EN, Foreman T, Kato S, Mehler RE, Singer BS, Hveem K, Dalen H, Sterling DG, Lawn RM, Schiller NB, Williams SA, Whooley MA, and Ganz P
- Subjects
- Age Factors, Aged, Coronary Disease blood, Coronary Disease mortality, Female, Heart Failure blood, Heart Failure mortality, Humans, Hypertrophy, Left Ventricular blood, Male, Myocardial Ischemia blood, Prognosis, Prospective Studies, Risk Factors, Stroke blood, Stroke mortality, Bone Morphogenetic Proteins metabolism, Growth Differentiation Factor 9 metabolism, Growth Differentiation Factors metabolism, Hypertrophy, Left Ventricular mortality, Myocardial Ischemia mortality
- Abstract
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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)
- Published
- 2015
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