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Olle Melander

Principal investigator

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A genetic risk score for CAD, psychological stress, and their interaction as predictors of CAD, fatal MI, non-fatal MI and cardiovascular death

Author

  • Thomas Svensson
  • Mariusz Kitlinski
  • Gunnar Engström
  • Olle Melander

Summary, in English

Background Psychological stress is an independent risk factor for cardiovascular disease (CVD), but the mechanism by which stress is associated with CVD is not entirely understood. Although genetic factors are implied in both stress responsivity and cardiovascular reactivity, no studies to date have investigated their interactions with stress for cardiovascular end points. The objective was to elucidate the association and interactions between a genetic risk score (GRS), individual genetic variants and stress for three cardiovascular end points: Coronary artery disease (CAD), fatal myocardial infarction (MI), non-fatal MI, and cardiovascular death. Methods and findings 18,559 participants from the Malmö Diet Cancer Study, a population-based prospective study, were included in the analyses. Cox proportional hazards regression models were used and adjusted for a large number of known predictors of cardiovascular end points. Mean follow-up time in years was 14.6 (CAD; n = 1938), 14.8 (fatal MI; n = 436), 14.8 (nonfatal MI; n = 1108), and 15.1 (cardiovascular death; n = 1071) respectively. GRS was significantly associated with increased risks of CAD (top quartile hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.51±1.96), fatal MI (top quartile HR, 1.62; 95%CI, 1.23-2.15), nonfatal MI (top quartile HR, 1.55; 95%CI, 1.31±1.84), and cardiovascular death (top quartile HR, 1.29; 95%CI, 1.08-1.53). Stress was not independently associated with any end point and did not interact with GRS. Four individual genetic variants interacted unfavorably with stress for end points with mortality outcomes. Conclusion A GRS composed of 50 SNPs and predictive of CAD was found for the first time to also strongly predict fatal MI, non-fatal MI and cardiovascular death. A stress-sensitive component of the GRS was isolated on the basis of individual genetic variants that interacted unfavorably with stress.

Department/s

  • Cardiovascular Research - Hypertension
  • Cardiovascular Research - Epidemiology
  • Department of Clinical Sciences, Malmö
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2017-04-20

Language

English

Publication/Series

PLoS ONE

Volume

12

Issue

4

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Project

  • Psychological stress and sleep duration as determinants of health

Research group

  • Cardiovascular Research - Hypertension
  • Cardiovascular Research - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1932-6203