Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease.
Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease.
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DOI：
10.1056/nejmoa1605086
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发表时间：
2016-12-15
期刊：
影响因子：
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通讯作者：
Kathiresan S
中科院分区：
文献类型：
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作者：
Khera AV;Emdin CA;Drake I;Natarajan P;Bick AG;Cook NR;Chasman DI;Baber U;Mehran R;Rader DJ;Fuster V;Boerwinkle E;Melander O;Orho-Melander M;Ridker PM;Kathiresan S
遗传和生活方式因素都对冠状动脉疾病的个人风险有影响。增加的遗传风险在多大程度上可以被健康的生活方式所抵消尚不清楚。使用DNA序列多态性的多基因评分，我们量化了三个前瞻性队列中冠状动脉疾病的遗传风险——7814名社区动脉粥样硬化风险研究（ARIC）参与者，21222名女性基因组健康研究（WGHS）参与者，22389名Malmö饮食和癌症研究（MDCS）参与者，以及4260名可获得基因型和共变量数据的横断面生物图像研究参与者。我们还通过一个由四个因素组成的评分系统来确定参与者是否坚持健康的生活方式：目前不吸烟、不肥胖、有规律的体育活动和健康的饮食。高遗传风险（多基因评分的前五分之一）的参与者发生冠状动脉事件的相对风险比低遗传风险（多基因评分的后五分之一）的参与者高91%（风险比，1.91；95%可信区间[CI]， 1.75至2.09）。无论遗传风险类别如何，良好的生活方式（定义为四种健康生活方式因素中的至少三种）与不良的生活方式（定义为没有或只有一种健康生活方式因素）相比，冠状动脉事件的风险显著降低。在高遗传风险的参与者中，良好的生活方式与不良生活方式相比，冠状动脉事件的相对风险降低46%（风险比，0.54;95% CI, 0.47 - 0.63）。这一发现对应于标准化10年冠状动脉事件发生率从不良生活方式组的10.7%降低到良好生活方式组的5.1%，WGHS组从4.6%降低到2.0%，MDCS组从8.2%降低到5.3%。在BioImage研究中，在每个遗传风险类别中，良好的生活方式与显著减少冠状动脉钙化相关。在涉及55,685名参与者的四项研究中，遗传和生活方式因素与冠状动脉疾病的易感性独立相关。在高遗传风险的参与者中，良好的生活方式与不良生活方式相比，冠状动脉疾病的相对风险降低了近50%。（由美国国立卫生研究院和其他机构资助。）
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. 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. 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. 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. (Funded by the National Institutes of Health and others.)