Elevated remnant cholesterol explains a substantial part of excess cardiovascular risk in the metabolic syndrome

Background Individuals with the metabolic syndrome have elevated remnant cholesterol and increased cardiovascular risk.1, 2 Purpose We tested the hypothesis that elevated remnant cholesterol explains part of the excess risk of myocardial infarction and atherosclerotic cardiovascular disease(ASCVD) in the metabolic syndrome. Methods We included 117,108 and 420,777 individuals from the 2003-2015 Copenhagen General Population Study and the 2006-2010 UK Biobank, of which 35,050 and 143,909 had the metabolic syndrome. All individuals were followed in national health registers until December 2021, during which time 3,187 and 9,166 developed myocardial infarctions and 14,263 and 39,860 ASCVD in the two studies, respectively. Results In both studies, individuals with versus without the metabolic syndrome had higher remnant cholesterol. In individuals with the metabolic syndrome in the Copenhagen General Population Study, a 1 mmol/L (39 mg/dL) higher remnant cholesterol conferred a hazard ratio for myocardial infarction of 1.39 (95% CI: 1.15-1.69) and 1.21 (1.07-1.36) in those with and without lipid-lowering therapy. Corresponding values in the UK Biobank were 1.34 (1.12-1.61) and 1.24 (1.10-1.40), respectively. In the two cohorts, elevated remnant cholesterol explained 16-48% and 12-24% of the excess risk of myocardial infarction from the metabolic syndrome in those with and without lipid-lowering therapy. The corresponding results for ASCVD were similar, but with lower hazard ratios and a smaller fraction of the excess risk explained. Results were similar in women and men. Conclusions In individuals with the metabolic syndrome, elevated remnant cholesterol explains a substantial part of the excess risk of myocardial infarction and ASCVD.