Abstract Background Remnant cholesterol (Remnant-C) has emerged as a significant contributor to atherosclerosis. Nevertheless, the distinct contribution of Remnant-C to the residual risk of coronary heart disease (CHD) beyond other lipids, and among subgroups is not clarified. Objective This study aims to evaluate the association between Remnant-C and the incidence of CHD. Methods This prospective cohort study included 4,800 individuals aged ≥40 years without a prior history of CHD with a mean age of 54 years old and 54% women participants from the Tehran Lipid and Glucose Study, followed annually until March 2020. Remnant-C was calculated by subtracting HDL-C and LDL-C levels from total cholesterol. CHD was defined as cases of definite or probable myocardial infarction diagnosed by ECG and biomarkers, unstable angina, angiographically-proven CHD, and CHD death. Cox models, adjusted for sex, age, eGFR, BMI, LDL-C, HDL-C, diabetes mellitus, hypertension, family history of CVD, marital status, education level, physical activity, smoking status, and use of lipid-lowering medications were employed to estimate associations. Participants were stratified into four categories of: 1) Low Remnant-C/LDL-C (Remnant-C ≤ 39 mg/dL, LDL-C ≤ 130 mg/dL, reference group); 2) High Remnant-C/Low LDL-C (Remnant-C 39 mg/dL, LDL-C ≤ 130 mg/dL); 3) Low Remnant-C/High LDL-C (Remnant-C ≤ 39 mg/dL, LDL-C 130 mg/dL); 4) High Remnant-C/LDL-C (Remnant-C 39 mg/dL, LDL-C 130 mg/dL). Moreover, subgroup analyses were performed based on age (65 vs. ≥65 years old), sex, smoking status, HDL-C, BMI, baseline CKD, diabetes mellitus, hypertension, metabolic syndrome. Results Over a median follow-up of 18.5 years, 1017 CHD events occured. A continuous (per-unit) increase in Remnant-C was significantly associated with a heightened CHD risk (HR:1.06, 95% CI: 1.01-1.13). Individuals in the highest quartile of Remnant-C (37mg/dL) exhibited a significantly elevated risk of CHD (1.30, 1.05-1.62) compared to those in the lowest quartile (23 mg/dL). When stratified by Remnant-C and LDL-C levels, all groups exhibited significantly increased risks relative to the reference group, with HRs of 1.45 (1.09-1.94) for high Remnant-C/low LDL-C, 1.43 (1.21-1.68) for low Remnant-C/high LDL-C, and 1.88 (1.56-2.26) for high Remnant-C/LDL-C. Among subgroups, elevated remnant-C in men, younger participants, individuals with hypertension, current smokers, those without diabetes, and those without CKD were associated with a higher risk compared to their counterparts. Conclusion Elevated Remnant-C levels were found to be independently and significantly associated with an increased risk of CHD, beyond the effects of LDL-C and HDL-C. Notably, the co-occurrence of high Remnant-C and high LDL-C demonstrated the strongest association with CHD risk, suggesting that these lipid parameters contribute to coronary risk through separate as well as complementary pathways.Remnant-C & LDL-C groups and CHD risk
Abdi et al. (Sat,) studied this question.