Association of remnant cholesterol with unhealthy lifestyle and risk of coronary heart disease: a population-based cohort study

Background: Unhealthy lifestyle is a major risk factor for coronary heart disease, which may be explained by elevated remnant cholesterol. However, this question remains incompletely clarified. In this study, we aimed to investigate whether elevated remnant cholesterol explains part of the excess risk of myocardial infarction and coronary heart disease in individuals with unhealthy lifestyle. Methods: We included 104,867 individuals (58,286 women and 46,581 men) from the Copenhagen General Population Study free from coronary heart disease at examination. During a median follow-up of 9.2 years, 2484 developed myocardial infarction and 3570 developed coronary heart disease. To understand explained risk from elevated remnant cholesterol due to unhealthy lifestyle on risk of myocardial infarction and coronary heart disease, we used mediation analyses. Findings: Current smoking, low physical activity, and low adherence to dietary guidelines were all associated with higher levels of remnant cholesterol. For current smoking, remnant cholesterol explained 15% (95% confidence interval: 9.7%–20%) of the excess risk of myocardial infarction and 16% (11%–21%) of the excess risk of coronary heart disease. Corresponding values for low physical activity were 20% (13%–27%) and 21% (15%–28%), and for low adherence to dietary guidelines 12% (6.6%–18%) and 14% (8.0%–19%), respectively. Results were similar in women and men separately and in analyses where each lifestyle factor were additionally adjusted for the other three lifestyle factors. Interpretation: Elevated remnant cholesterol explained part of excess myocardial infarction and coronary heart disease in individuals with an unhealthy lifestyle. Clinically, these novel findings underline the importance of both elevated remnant cholesterol and promotion of healthy lifestyle in primary prevention of myocardial infarction and coronary heart disease. Funding:Independent Research Fund Denmark;Johan Boserup and Lise Boserups Grant;Medical Research Council.