Elevated remnant cholesterol, plasma triglycerides, and cardiovascular and non-cardiovascular mortality

Cholesterol carried in triglyceride-rich lipoproteins, also called remnant cholesterol, is being increasingly acknowledged as an important causal risk factor for atherosclerosis. Elevated remnant cholesterol, marked by elevated plasma triglycerides, is associated causally with an increased risk of atherosclerotic cardiovascular disease. The association with cause-specific mortality is, however, unclear. The aim of this study was to test the hypothesis that elevated remnant cholesterol and plasma triglycerides are associated with increased mortality from cardiovascular disease, cancer, and other causes.

Using a contemporary population-based cohort, 87 192 individuals from the Copenhagen General Population Study aged 20-69 years at baseline in 2003-2015 were included. During up to 13 years of follow-up, 687 individuals died from cardiovascular disease, 1594 from cancer, and 856 from other causes, according to the National Danish Causes of Death Registry. In individuals with remnant cholesterol ≥1.0 mmol/L (≥39 mg/dL; 22% of the population) compared with those with levels <0.5 mmol/L (<19 mg/dL), multivariable-adjusted mortality hazard ratios were 2.2 (95% confidence interval 1.3-3.5) for cardiovascular disease, 1.0 (0.7-1.3) for cancer, and 2.1 (1.4-3.3) for other causes. Exploratory analysis of the cause of death subcategories showed corresponding hazard ratios of 4.4 (1.6-11) for ischemic heart disease, 8.4 (2.0-34) for infectious diseases, and 9.1 (1.9-43) for endocrinological diseases. Results for plasma triglycerides >2 vs. <1 mmol/L (>177 vs. <89 mg/dL) were similar.

Remnant cholesterol of ≥1 mmol/L (39 mg/dL), present in 22% of the population, and plasma triglycerides of ≥2 mmol/L (177 mg/dL), present in 28% of the population, were associated with two-fold mortality from cardiovascular and other causes, but not from cancer. This novel finding should be confirmed in other cohorts.