Interaction of accelerometer-measured physical activity and genetic risk on cardiovascular diseases: a prospective...

Area of Science:

• Cardiovascular Epidemiology
• Genetics and Public Health
• Physical Activity Research

Background:

• Cardiovascular diseases (CVDs) remain a leading cause of mortality worldwide.
• Genetic predisposition, assessed by polygenic risk scores (PRS), influences individual CVD risk.
• The interplay between lifestyle factors like physical activity and genetic risk is crucial for CVD prevention.

Purpose of the Study:

• To investigate the combined effects of physical activity and polygenic risk score (PRS) on the risk of atrial fibrillation, coronary heart disease (CHD), hypertension, and ischaemic stroke.
• To determine if physical activity mitigates CVD risk across different levels of genetic predisposition.

Main Methods:

• Utilized data from 91,629 UK Biobank participants with accelerometer-measured physical activity.
• Quantified total physical activity (TPA), moderate-to-vigorous (MVPA), and light-intensity physical activity (LPA).
• Employed Cox proportional hazard models to assess associations and interactions between physical activity, PRS, and CVD outcomes.

Main Results:

• All measured physical activity levels (TPA, MVPA, LPA) were associated with reduced risk for the four CVD outcomes, largely independent of genetic risk.
• Specific interactions were observed, such as a U-shaped association between LPA and atrial fibrillation in low-PRS individuals and attenuated TPA-hypertension risk with increasing genetic risk.
• The attributable risk of inactivity was higher in high-PRS individuals, with greater risk reductions for CHD observed in high-PRS individuals who increased MVPA.

Conclusions:

• Increased physical activity, encompassing light-intensity activity, is linked to a lower risk of major cardiovascular diseases.
• The magnitude of cardiovascular health benefits derived from physical activity can be modulated by an individual's underlying genetic risk profile.