Ahmadi Matthew N, Mundell Hamish D, Sutherland Greg T, Hamer Mark, Sillanpää Elina, Blodgett Joanna M, Cruz Borja Del Pozo, Stamatakis Emmanuel
Mackenzie Wearables Research Hub, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
J Sport Health Sci. 2025 May 10;14:101055. doi: 10.1016/j.jshs.2025.101055.
It is unclear whether physical activity can benefit participants with high genetic predisposition to cardiovascular disease. We examined the joint associations of intensity-specific physical activity and genetic predisposition (based on polygenetic risk score) with incident coronary heart disease (CHD), stroke, and atrial fibrillation (AF).
This prospective cohort study included 303,950 adults (age = 56.4 ± 8.0 years, mean ± SD; 52.5% females) from the UK Biobank with physical activity and disease-related genotypes. Moderate-to-vigorous physical activity (MVPA) and intensity-specific activity was classified according to volume (e.g., MVPA was classified as none, low, medium, and high). Genetic predisposition for CHD, stroke, and AF were classified as low (Quintile 1), intermediate (Quintiles 2-4), and high (Quintile 5).
During 11.6 ± 2.1 years of follow-up: 19,865 CHD, 7907 stroke, and 16,688 AF events occurred. Compared to the no MVPA and high genetic risk group, we observed lower CHD risk for increasing levels of MVPA over and above genetic risk groupings. These associations were primarily driven by vigorous-intensity activity. For example, in the high genetic risk group, those with low vigorous-intensity activity levels (compared to none) had a hazard ratio (HR) of 0.78 (95% confidence interval (95%CI): 0.72-0.86) compared to an HR of 0.92 (95%CI: 0.86-0.99) for low moderate-intensity activity levels. For stroke incidence, we observed a protective association for MVPA across genetic risk groups that was mostly driven by moderate-intensity activity volume. Among the high genetic risk group, low moderate-intensity had an HR of 0.77 (95%CI: 0.66-0.90), whereas low vigorous-intensity had no association (HR = 0.95, 95%CI: 0.82-1.09). We did not observe a consistent joint association of MVPA and AF genetic predisposition.
We observed lower CHD and stroke risk for low to high MVPA among participants with high genetic predisposition. The associations of moderate- and vigorous-intensity activity volume differed considerably across cardiovascular disease sub-types. Overall, our findings suggest vigorous-intensity activity may mitigate genetic predisposition for CHD while moderate intensity activity may be associated with similar effects for stroke. Joint associations were less consistent across AF genetic predisposition groups. Our results inform precision medicine approaches and future lifestyle modification interventions by quantifying the potential benefits of physical activity among at-risk individuals.
尚不清楚身体活动是否能使心血管疾病遗传易感性高的参与者受益。我们研究了特定强度身体活动与遗传易感性（基于多基因风险评分）与冠心病（CHD）、中风和心房颤动（AF）发病的联合关联。
这项前瞻性队列研究纳入了英国生物银行的303950名成年人（年龄=56.4±8.0岁，均值±标准差；52.5%为女性），他们有身体活动和疾病相关基因型。中度至剧烈身体活动（MVPA）和特定强度活动根据量进行分类（例如，MVPA分为无、低、中、高）。冠心病、中风和房颤的遗传易感性分为低（五分位数1）、中（五分位数2 - 4）和高（五分位数5）。
在11.6±2.1年的随访期间：发生了19865例冠心病、7907例中风和16688例房颤事件。与无MVPA且遗传风险高的组相比，我们观察到在遗传风险分组之上，随着MVPA水平增加，冠心病风险降低。这些关联主要由剧烈强度活动驱动。例如，在高遗传风险组中，低剧烈强度活动水平（与无相比）的风险比（HR）为0.78（95%置信区间（95%CI）：0.72 - 0.86），而低中度强度活动水平的HR为0.92（95%CI：0.86 - 0.99）。对于中风发病率，我们观察到在各遗传风险组中MVPA都有保护关联，这主要由中度强度活动量驱动。在高遗传风险组中，低中度强度的HR为0.77（95%CI：0.66 - 0.90），而低剧烈强度无关联（HR = 0.95，95%CI：0.82 - 1.09）。我们未观察到MVPA与房颤遗传易感性有一致的联合关联。
我们观察到在遗传易感性高的参与者中，低至高水平的MVPA可降低冠心病和中风风险。中度和剧烈强度活动量的关联在心血管疾病亚型中差异很大。总体而言，我们的研究结果表明剧烈强度活动可能减轻冠心病的遗传易感性，而中度强度活动可能对中风有类似作用。在房颤遗传易感性组中联合关联不太一致。我们的结果通过量化高危个体身体活动的潜在益处，为精准医学方法和未来生活方式改变干预提供了信息。
