Lipoprotein(a), remnant cholesterol, and high-sensitivity C-reactive protein as complementary biomarkers for myocardial infarction risk assessment

BACKGROUND: The predictive value of lipoprotein(a) (Lp[a]), high-sensitivity C-reactive protein (hsCRP), and remnant cholesterol (RC) beyond low-density lipoprotein cholesterol (LDL-C) varies across cardiovascular disease (CVD) outcomes. This analysis evaluates the extent to which concentrations of these non-LDL-C biomarkers improve MI-specific risk prediction in a primary prevention population. METHODS: We analyzed 306,183 UK Biobank participants free of cardiovascular disease at baseline with available Lp(a), RC, and hsCRP measurements. RC was calculated as total cholesterol minus LDL-C minus high-density lipoprotein cholesterol (HDL-C). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression across biomarker quintiles and cumulative biomarker burden. The primary endpoint was the first MI event. RESULTS: Over 15 years of follow-up, 10,824 MI events occurred. In fully adjusted models comparing quintile 5 with quintile 1, HRs (95% CI) were 1.09 (1.08-1.11) for Lp(a), 1.14 (1.13-1.16) for RC, and 1.08 (1.06-1.10) for hsCRP. Per-SD increases were associated with higher MI risk for RC 1.22 (1.20-1.25), Lp(a) 1.16 (1.13-1.18), and hsCRP 1.13 (1.10-1.15). The risk of MI increased stepwise with cumulative biomarker burden; compared with individuals with no biomarker in the top quintile, HRs (95% CI) were 1.45 (1.39-1.51), 2.14 (2.02-2.26), and 2.83 (2.48-3.24) for those with one, two, or all three elevated biomarkers, respectively. CONCLUSIONS: Lp(a), RC, and hsCRP each provide independent and complementary information for MI risk. Their combined elevation identifies individuals at higher MI risk, suggesting selective testing of all three biomarkers in primary prevention.