Remnant cholesterol: an independent determinant of coronary artery disease and future cardiovascular events beyond traditional risk factors
F Sousa, M Mendonca, G Abreu, M Ferreira, F Escorcio Silva, S Freitas, E Henriques, M Rodrigues, S Borges, I Ornelas, A Drumond, A C Sousa, R Palma dos ReisAbstract
Introduction
Remnant cholesterol (RC) is a proven independent and causal risk factor for coronary artery disease (CAD), beyond LDL-C, HDL-C, triglycerides, diabetes, and other traditional risk factors. It reflects the cholesterol content of triglyceride-rich lipoproteins and is strongly associated with subclinical inflammation and endothelial dysfunction.
Objective
Determine whether remnant cholesterol is independently associated with CAD in a coronary population.
Methods
A case-control study performed between 2000 and 2023 included 1,722 successive coronary patients (mean age 53.3±7.9 years, 78.8% male) and 1,435 controls (mean age 52.7±7.8 years, 76.2% male). RC was calculated by the formula: total cholesterol - (LDL-C + HDL-C) (mmol/L) and categorised as below or above the median. Multivariate logistic regression was performed to assess the association between RC and CAD, adjusting for age, sex, smoking, physical inactivity, type 2 diabetes, hypertension, body mass index, alcohol consumption, and chronic kidney disease. Patients were prospectively followed for an extended period (median 7.6±6.7 years), and an adjusted Cox regression analysis was applied to identify independent predictors of cardiovascular (CV) events.
Results
The median RC value was 26.4 (19.0-39.0), and this value was used in the statistical analyses. Multivariate logistic regression showed that RC remained independently associated with CAD (OR=1.004; CI95%-1.001-1.008; p=0.023), together with smoking, type 2 diabetes, physical inactivity and chronic kidney disease (all p<0.0001). During the follow-up, 715 CV events were recorded. Cox regression showed that RC is independently associated with CV events (HR=1.004; 95% CI 1.001-1.007; p=0.005), together with age (p=0.045); sedentary lifestyle (p<0.0001) and diabetes (p=0.047).
Conclusion
Elevated RC was associated with CAD and long-term CV events, independently of major traditional risk factors. These findings underscore the potential value of targeted RC reduction, which may refine lipid risk profiles and reduce the burden of coronary disease.Remanant cholesterol