Remnant cholesterol, low-density lipoprotein cholesterol and atherosclerotic cardiovascular disease in metabolic dysfunction-associated steatotic liver disease: a cohort study.

BACKGROUND: Recent studies highlighted the independent role of remnant cholesterol (RC) on the risk of atherosclerotic cardiovascular disease (ASCVD). We explored interrelationships among low-density lipoprotein cholesterol (LDL-C), RC, and ASCVD in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: Analyzing 25,418 MASLD and 57,501 non-MASLD ASCVD- free Chinese adults from the Kailuan Study (2006-2011), we used Fine-Gray models to evaluate LDL-C and RC associations with ASCVD across varying cut-offs, incorporating China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) 10-year risk. RESULTS: The MASLD group had comparable LDL-C but elevated RC levels compared to the non-MASLD. In MASLD individuals, associations of LDL-C (J-shaped) and RC (linear) with ASCVD were observed, contrasting with the monotonically increasing relationships in non-MASLD individuals. Even with guideline-recommended LDL-C levels, the MASLD group with elevated RC alone showed a higher ASCVD risk. Among individuals with low ASCVD risk evaluated by the China-PAR model, MASLD patients with LDL-C < 1.8 mmol/L and RC < 0.6 mmol/L had comparable ASCVD risk to the non-MASLD group with LDL-C < 3.4 mmol/L and RC < 0.6 mmol/L (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 0.55-2.47). For those with moderate to high predicted ASCVD risk, the MASLD with the same lipid levels (LDL-C < 1.8 mmol/L and RC < 0.6 mmol/L) had a similar risk of ASCVD to that of the non-MASLD with LDL-C < 2.6 mmol/L and RC < 0.6 mmol/L (HR: 1.15; 95% CI: 0.71-1.86). CONCLUSIONS: The findings indicate that MASLD alters the relationship between lipids and ASCVD, underscoring the necessity for integrated and stricter management of both LDL-C and RC to mitigate risk in this population.