The objective of this study was to investigate associations between leisure-time physical activity, low high-density lipoprotein cholesterol (HDL-C) and mortality. Self-reported leisure-time physical activity, HDL-C concentration, and mortality were assessed in 37,059 adults in Health Survey for England and Scottish Health Survey. Meeting physical activity guidelines was defined as ≥150 min wk−1 of moderate-intensity activity, ≥75 min wk−1 of vigorous-intensity activity, or equivalent combinations. Low HDL-C was defined as <1.03 mmol L−1. Cox proportional hazard models were adjusted for age, sex, smoking, total cholesterol, systolic blood pressure, body mass index, longstanding illness, and socioeconomic status. There were 2250 deaths during 326,016 person-years of follow-up. Compared with those who met physical activity guidelines and whose HDL-C was normal (reference group), all-cause mortality risk was not elevated in those who met physical activity guidelines and whose HDL-C concentration was low (hazard ratio: 1.07; 95% confidence interval: 0.75, 1.53). Compared with the reference group, all-cause mortality risk was elevated in those who did not meet physical activity guidelines and whose HDL-C was normal (1.37; 1.16, 1.61), and in those who did not meet physical activity guidelines and whose HDL-C was low (1.65; 1.37, 1.98). Cardiovascular disease mortality hazard ratios were similar, although confidence intervals were wider. There was no statistically significant evidence of biological interaction between physical inactivity and low HDL-C. This novel study supports the notion that leisure-time physical activity be recommended in those with low HDL-C concentration who may be resistant to the HDL-raising effect of exercise training.
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