Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, FINLAND.
Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, FINLAND.
Med Sci Sports Exerc. 2024 Oct 1;56(10):1954-1963. doi: 10.1249/MSS.0000000000003482. Epub 2024 May 15.
We investigated whether longitudinally assessed physical activity (PA) and adherence specifically to World Health Organization PA guidelines mitigate or moderate mortality risk regardless of genetic liability to cardiovascular disease (CVD). We also estimated the causality of the PA-mortality association.
The study used the older Finnish Twin Cohort with 4897 participants aged 33 to 60 yr (54.3% women). Genetic liability to coronary heart disease and systolic and diastolic blood pressure was estimated with polygenic risk scores (PRS) derived from the Pan-UK Biobank ( N ≈ 400,000; >1,000,000 genetic variants). Leisure-time PA was assessed with validated and structured questionnaires three times during 1975 to 1990. The main effects of adherence to PA guidelines and the PRS × PA interactions were evaluated with Cox proportional hazards models against all-cause and CVD mortality. A cotwin control design with 180 monozygotic twin pairs discordant for meeting the guidelines was used for causal inference.
During the 17.4-yr (mean) follow-up (85,136 person-years), 1195 participants died, with 389 CVD deaths. PRS (per 1 SD increase) were associated with a 17% to 24% higher CVD mortality risk but not with all-cause mortality except for the PRS for diastolic blood pressure. Adherence to PA guidelines did not show significant independent main effects or interactions with all-cause or CVD mortality. Twins whose activity levels adhered to PA guidelines over a 15-yr period did not have statistically significantly reduced mortality risk compared with their less active identical twin sibling. The findings were similar among high, intermediate, and low genetic risk levels for CVD.
The genetically informed Finnish Twin Cohort data could not confirm that adherence to PA guidelines either mitigates or moderates genetic CVD risk or causally reduces mortality risk.
我们研究了无论心血管疾病（CVD）的遗传易感性如何，纵向评估身体活动（PA）和对世界卫生组织 PA 指南的依从性是否可以减轻或缓和死亡率风险。我们还估计了 PA 与死亡率之间的因果关系。
该研究使用了年龄在 33 至 60 岁的较年长的芬兰双胞胎队列，共有 4897 名参与者（女性占 54.3%）。通过来自泛英国生物银行（约 40 万人；超过 100 万个遗传变异）的多基因风险评分（PRS）来估计冠心病和收缩压及舒张压的遗传易感性。在 1975 年至 1990 年期间，使用经过验证和结构化的问卷三次评估休闲时间 PA。使用 Cox 比例风险模型评估依从 PA 指南的主要效果和 PRS×PA 相互作用与全因和 CVD 死亡率的关系。使用 180 对不符合指南的同卵双胞胎的双胞胎对照设计进行因果推断。
在 17.4 年（平均）的随访期间（85136 人年），有 1195 名参与者死亡，其中 389 名死于 CVD。PRS（每增加 1 个标准差）与 CVD 死亡率风险增加 17%至 24%相关，但与全因死亡率无关，只有舒张压的 PRS 除外。PA 指南的依从性与全因或 CVD 死亡率没有显著的独立主效应或相互作用。在 15 年期间，活动水平符合 PA 指南的双胞胎与不太活跃的同卵双胞胎相比，其死亡率风险并没有统计学上显著降低。在 CVD 的高、中、低遗传风险水平中，研究结果均相似。
芬兰双胞胎队列的遗传信息数据不能证实，遵守 PA 指南可以减轻或缓和遗传 CVD 风险，或者可以因果降低死亡率风险。
