Increased Remnant Cholesterol Explains Part of Residual Risk of All-Cause Mortality in 5414 Patients with Ischemic Heart Disease

Abstract

Background: Increased concentrations of remnant cholesterol are causally associated with increased risk of ischemic heart disease. We tested the hypothesis that increased remnant cholesterol is a risk factor for all-cause mortality in patients with ischemic heart disease.

Methods: We included 5414 Danish patients diagnosed with ischemic heart disease. Patients on statins were not excluded. Calculated remnant cholesterol was nonfasting total cholesterol minus LDL and HDL cholesterol. During 35836 person-years of follow-up, 1319 patients died.

Results: We examined both calculated and directly measured remnant cholesterol; importantly, however, measured remnant cholesterol made up only 9% of calculated remnant cholesterol at nonfasting triglyceride concentrations <1 mmol/L (89 mg/dL) and only 43% at triglycerides >5 mmol/L (443 mg/dL). Multivariable-adjusted hazard ratios for all-cause mortality compared with patients with calculated remnant cholesterol concentrations in the 0 to 60th percentiles were 1.2 (95% CI, 1.1-1.4) for patients in the 61st to 80th percentiles, 1.3 (1.1-1.5) for the 81st to 90th percentiles, 1.5 (1.1-1.8) for the 91st to 95th percentiles, and 1.6 (1.2-2.0) for patients in the 96th to 100th percentiles (trend, P < 0.001). Corresponding values for measured remnant cholesterol were 1.0 (0.8-1.1), 1.2 (1.0-1.4), 1.1 (0.9-1.5), and 1.3 (1.1-1.7) (trend, P = 0.006), and for measured LDL cholesterol 1.0 (0.9-1.1), 1.0 (0.8-1.2), 1.0 (0.8-1.3), and 1.1 (0.8-1.4) (trend, P = 0.88). Cumulative survival was reduced in patients with calculated remnant cholesterol ≥1 mmol/L (39 mg/dL) vs <1 mmol/L [log-rank, P = 9 × 10(-6); hazard ratio 1.3 (1.2-1.5)], but not in patients with measured LDL cholesterol ≥3 mmol/L (116 mg/dL) vs <3 mmol/L [P = 0.76; hazard ratio 1.0 (0.9-1.1)].

Conclusions: Increased concentrations of both calculated and measured remnant cholesterol were associated with increased all-cause mortality in patients with ischemic heart disease, which was not the case for increased concentrations of measured LDL cholesterol. This suggests that increased concentrations of remnant cholesterol explain part of the residual risk of all-cause mortality in patients with ischemic heart disease.