Iribarren Carlos, Lu Meng, Gulati Martha, Wong Nathan D, Elosua Roberto, Rana Jamal S
Kaiser Permanente Northern California Division of Research, Oakland, CA, USA.
Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Int J Cardiol Cardiovasc Risk Prev. 2024 Nov 6;23:200350. doi: 10.1016/j.ijcrp.2024.200350. eCollection 2024 Dec.
The objective of this study was to examine the interplay of polygenic risk and individual lifestyle factors (and a composite score of lifestyle) as antecedents of CHD in a large multiethnic cohort.
We used Genetic Epidemiology Resource in Adult Health and Aging (GERA) cohort participants free of CHD at baseline (n = 60,568; 67 % female; 18 % non-European). The individual and joint associations of smoking, Mediterranean diet pattern, level of physical activity and polygenic risk with incident CHD were assessed using Cox regression adjusting for genetic ancestry and non-mediating risk factors. Hazard ratios (HRs) and number needed to treat (NNT) were estimated according to these lifestyle factors and polygenic risk categories. Strengths included large sample size, long-follow-up, ethnic diversity, a clinically-validated polygenic risk score (PRS), and rich phenotype information.
After 14 years of follow-up, there were 3159 incident CHD events. We observed no statistically significant interactions between individual lifestyle factors and polygenic risk (all p > 0.23). For individuals with a high genetic risk, moving from the worse lifestyle combination (no favorable lifestyle factors) to the best lifestyle combination (all three) is associated with 52 % lower rate of CHD. The NNT was highest in the low polygenic risk group (34), lowest in the high polygenic risk group [19] and in-between (Jin et al., 2011) [24] in the intermediate polygenic risk group.
Lifestyle and polygenic risk together influence the risk of incident CHD. Our results support consideration of polygenic risk in lifestyle interventions because those with high polygenic risk are likely to derive the most benefit.
本研究的目的是在一个大型多民族队列中，探讨多基因风险与个体生活方式因素（以及生活方式综合评分）作为冠心病（CHD）发病前因之间的相互作用。
我们使用了成人健康与衰老遗传流行病学资源（GERA）队列中的参与者，这些参与者在基线时无冠心病（n = 60568；67%为女性；18%为非欧洲人）。使用Cox回归评估吸烟、地中海饮食模式、身体活动水平和多基因风险与新发冠心病之间的个体及联合关联，并对遗传血统和非中介风险因素进行校正。根据这些生活方式因素和多基因风险类别估计风险比（HRs）和需治疗人数（NNT）。优势包括样本量大、随访时间长、种族多样性、经过临床验证的多基因风险评分（PRS）以及丰富的表型信息。
经过14年的随访，有3159例新发冠心病事件。我们未观察到个体生活方式因素与多基因风险之间存在统计学显著的相互作用（所有p>0.23）。对于遗传风险高的个体，从最差的生活方式组合（无有利生活方式因素）转变为最佳生活方式组合（所有三个因素均具备），冠心病发病率降低52%。需治疗人数在低多基因风险组中最高（34），在高多基因风险组中最低（19），在中等多基因风险组中介于两者之间（Jin等人，2011年）[24]。
生活方式和多基因风险共同影响新发冠心病的风险。我们的结果支持在生活方式干预中考虑多基因风险，因为多基因风险高的个体可能获益最大。
