Nutr Metab Cardiovasc Dis. 2026 Apr 25:104773. doi: 10.1016/j.numecd.2026.104773. Online ahead of print.
ABSTRACT
BACKGROUND AND AIM: Remnant cholesterol (RC), lipoprotein(a) [Lp(a)], and inflammation are considered key residual cardiovascular risk (RCVR) factors. This study aimed to prospectively evaluate the independent and combined associations of RC, Lp(a), and C-reactive protein (CRP) with myocardial infarction (MI) risk in a general population with baseline low-density lipoprotein cholesterol (LDL-C) <2.6 mmol/L.
METHODS AND RESULTS: Baseline RC, Lp(a), and CRP levels were categorized as high or low according to reference thresholds derived from a restricted cubic spline model. Participants were further classified by the number of elevated RCVR factors (0-3). Independent and combined associations of these biomarkers with MI risk were assessed, and their predictive performance was compared. Over a median follow-up of 13.6 years, 1,665 MI events were documented. Multivariate-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were 1.042 (0.924-1.175) for elevated RC, 1.255 (1.137-1.385) for high Lp(a), and 1.246 (1.123-1.384) for high CRP. Compared with participants with no elevated RCVR factors, adjusted HRs (95% CIs) for those with 1, 2, and 3 elevated factors were 1.413 (1.147-1.740), 1.566 (1.271-1.931), and 1.870 (1.493-2.343), respectively. The combined model including all three biomarkers demonstrated superior predictive performance compared with individual markers (DeLong test p < 0.01).
CONCLUSIONS: Elevated Lp(a) and CRP were independently associated with increased MI risk, whereas RC was not. A combined assessment of RCVR factors provided greater predictive value than any single biomarker.
PMID:42115079 | DOI:10.1016/j.numecd.2026.104773