Physical Activity, Blood Lipids, and Incident Cardiovascular Diseases: A Prospective Study Based on UK Biobank and China Kadoorie Biobank Participants

Background: Cardiovascular diseases (CVDs) are leading global causes of mortality and morbidity. Although physical activity (PA) and healthy blood lipid levels are both well-established independent protective factors, their joint associations and potential interactions on the risk of CVDs—including coronary heart disease (CHD), stroke, and a composite of them—remain inadequately studied. We aimed to investigate the joint association of PA and lipid profiles with the risk of CVDs in two large prospective cohorts. Methods: This prospective study leveraged data from two independent large cohorts: the UK Biobank (UKB, N = 230,972), to evaluate associations of PA and blood lipids with CVDs, and the China Kadoorie Biobank (CKB, N = 18,174), to examine associations with stroke. PA was assessed via questionnaire and categorized as inactive, active, or highly active. Blood lipids (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, total cholesterol, apolipoprotein A1, and apolipoprotein B) were classified as high risk, borderline, or ideal. Cox proportional hazards models were used to analyze independent and joint associations between PA and lipids and incident CVDs. Complementary analyses including device-measured PA and polygenic risk scores for lipids were performed. Results: In UKB, participants in the active and highly active groups had a significantly lower risk of incident CVD (active: hazard ratio [HR] 0.94; 95% confidence interval [CI], 0.90–0.98; highly active: HR 0.90; 95% CI, 0.88–0.93; P for trend < 0.001) and CHD events (active: HR 0.92; 95% CI, 0.88–0.96; highly active: HR 0.89; 95% CI, 0.86–0.92; P for trend < 0.001), but no significant association was observed for stroke ( P for trend = 0.244). In CKB, higher PA was significantly associated with lower stroke risk (active: HR 0.79; 95% CI, 0.69–0.91; highly active: HR 0.66; 95% CI, 0.60–0.74; P for trend < 0.001), consistent with the protective effects observed for favorable lipid profiles. No significant multiplicative interactions between PA and lipids were detected. However, joint analyses showed a graded reduction in risk and participants who were highly active or had ideal lipid levels had the lowest cardiovascular risk. Complementary analyses reinforced the results. Conclusion: Targeting both PA and lipid profiles is important for cardiovascular health, as these factors may exert complementary and partially independent effects on cardiovascular risk. Accordingly, improvements in either PA or lipid profiles may confer additional cardiovascular benefits, even among individuals with favorable levels of the other factor.