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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

Svensson, Thomas LU ; Kitlinski, Mariusz LU ; Engström, Gunnar LU and Melander, Olle LU (2017) In PLoS ONE 12(4).
Abstract

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... (More)

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.

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author
organization
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published
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in
PLoS ONE
volume
12
issue
4
publisher
Public Library of Science
external identifiers
  • scopus:85017677989
  • wos:000399875900089
ISSN
1932-6203
DOI
10.1371/journal.pone.0176029
language
English
LU publication?
yes
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f65327d2-237f-40c6-955d-3b202ae9286a
date added to LUP
2017-05-11 07:02:10
date last changed
2017-09-18 11:35:37
@article{f65327d2-237f-40c6-955d-3b202ae9286a,
  abstract     = {<p>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.</p>},
  articleno    = {e0176029},
  author       = {Svensson, Thomas and Kitlinski, Mariusz and Engström, Gunnar and Melander, Olle},
  issn         = {1932-6203},
  language     = {eng},
  month        = {04},
  number       = {4},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {A genetic risk score for CAD, psychological stress, and their interaction as predictors of CAD, fatal MI, non-fatal MI and cardiovascular death},
  url          = {http://dx.doi.org/10.1371/journal.pone.0176029},
  volume       = {12},
  year         = {2017},
}