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Genetic risk, adherence to a healthy lifestyle, and coronary disease

Khera, Amit V.; Emdin, Connor A.; Drake, Isabel LU ; Natarajan, Pradeep; Bick, Alexander G.; Cook, Nancy R.; Chasman, Daniel I.; Baber, Usman; Mehran, Roxana and Rader, Daniel J., et al. (2016) In New England Journal of Medicine 375(24). p.2349-2358
Abstract

BACKGROUND Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown. METHODS Using a polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts - 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women's Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) - And in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system... (More)

BACKGROUND Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown. METHODS Using a polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts - 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women's Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) - And in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet. RESULTS The relative risk of incident coronary events was 91% higher among participants at high genetic risk (top quintile of polygenic scores) than among those at low genetic risk (bottom quintile of polygenic scores) (hazard ratio, 1.91; 95% confidence interval [CI], 1.75 to 2.09). A favorable lifestyle (defined as at least three of the four healthy lifestyle factors) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle (defined as no or only one healthy lifestyle factor), regardless of the genetic risk category. Among participants at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk of coronary events than an unfavorable lifestyle (hazard ratio, 0.54; 95% CI, 0.47 to 0.63). This finding corresponded to a reduction in the standardized 10-year incidence of coronary events from 10.7% for an unfavorable lifestyle to 5.1% for a favorable lifestyle in ARIC, from 4.6% to 2.0% in WGHS, and from 8.2% to 5.3% in MDCS. In the BioImage Study, a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category. CONCLUSIONS Across four studies involving 55,685 participants, genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. Among participants at high genetic risk, a favorable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease than was an unfavorable lifestyle.

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New England Journal of Medicine
volume
375
issue
24
pages
10 pages
publisher
Massachusetts Medical Society
external identifiers
  • scopus:85005980701
  • wos:000390036500006
ISSN
0028-4793
DOI
10.1056/NEJMoa1605086
language
English
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yes
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325b6596-f603-40ba-919a-c4567101a4b4
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2016-12-28 14:12:58
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2017-11-19 04:36:14
@article{325b6596-f603-40ba-919a-c4567101a4b4,
  abstract     = {<p>BACKGROUND Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown. METHODS Using a polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts - 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women's Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) - And in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet. RESULTS The relative risk of incident coronary events was 91% higher among participants at high genetic risk (top quintile of polygenic scores) than among those at low genetic risk (bottom quintile of polygenic scores) (hazard ratio, 1.91; 95% confidence interval [CI], 1.75 to 2.09). A favorable lifestyle (defined as at least three of the four healthy lifestyle factors) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle (defined as no or only one healthy lifestyle factor), regardless of the genetic risk category. Among participants at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk of coronary events than an unfavorable lifestyle (hazard ratio, 0.54; 95% CI, 0.47 to 0.63). This finding corresponded to a reduction in the standardized 10-year incidence of coronary events from 10.7% for an unfavorable lifestyle to 5.1% for a favorable lifestyle in ARIC, from 4.6% to 2.0% in WGHS, and from 8.2% to 5.3% in MDCS. In the BioImage Study, a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category. CONCLUSIONS Across four studies involving 55,685 participants, genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. Among participants at high genetic risk, a favorable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease than was an unfavorable lifestyle.</p>},
  author       = {Khera, Amit V. and Emdin, Connor A. and Drake, Isabel and Natarajan, Pradeep and Bick, Alexander G. and Cook, Nancy R. and Chasman, Daniel I. and Baber, Usman and Mehran, Roxana and Rader, Daniel J. and Fuster, Valentin and Boerwinkle, Eric and Melander, Olle and Orho-Melander, Marju and Ridker, Paul M. and Kathiresan, Sekar},
  issn         = {0028-4793},
  language     = {eng},
  month        = {12},
  number       = {24},
  pages        = {2349--2358},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Genetic risk, adherence to a healthy lifestyle, and coronary disease},
  url          = {http://dx.doi.org/10.1056/NEJMoa1605086},
  volume       = {375},
  year         = {2016},
}