Does Physical Activity Modify The Association Between High-density Lipoprotein Cholesterol And All-cause Mortality?

Introduction: There is well-known inverse dose-response relationship between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease and all-cause mortality. However, only recently is the entire spectrum of HDL-C being examined with mortality. A similar dose-response relationship with mortality exists with physical activity (PA). Engaging in regular PA has consistently been shown to lower both CVD and all-cause mortality by 20-30%. This study examined the association between HDL-C and mortality by PA categories created around the current federal PA guidelines for United States Adults. Hypothesis: Level of PA participation will modify mortality risk across a spectrum of HDL-C levels. Methods: The study sample (n=8,535) included participants (age 20-79 years) from the 1999-2006 National Health and Nutrition Examination Survey. PA was classified into three distinct categories: Those meeting neither of the PA guidelines (category 1), those meeting only the aerobic PA guideline (category 2), and those meeting both the aerobic PA and muscular strengthening activity guidelines (category 3). HDL-C was categorized into eight groups (≤30, 31-40, 41-50, 51-60 [referent group], 61-70, 70-80, and >80 mg/dL). All-cause mortality served as the dependent variable in this study. Cox proportional hazard models were used for all analyses. Results: Among those in PA category 1, a statistically significant increase in all-cause mortality risk was found for those with an HDL-C of 71-80 (HR 1.94, 95% CI 1.14-3.32) and >80 mg/dL (HR 2.18, 95% CI 1.25-3.79). In those with an HDL-C <30 mg/dL, a borderline significant increase in all-cause mortality risk was found (HR 1.67, 95% CI 0.96-2.89, p=0.06) Among those in PA categories 2 and 3, no significant increases in all-cause mortality risk were found. Conclusions: Results suggest that meeting at least the aerobic PA guideline mitigates the increased risk for all-cause mortality in those with very high HDL-C and potentially very low HDL-C. Future studies are warranted to investigate the effects of PA on mortality across measures of HDL-C.