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

Richard Kazibwe1, Christopher L Schaich2, Jeff A Kingsley3

  • 1Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America.

Progress in Cardiovascular Diseases
|May 2, 2026
PubMed

Insights

Lipoprotein(a) (Lp[a]), remnant cholesterol (RC), and high-sensitivity C-reactive protein (hsCRP) improve myocardial infarction (MI) risk prediction. Elevated levels of these biomarkers, especially when combined, identify individuals at significantly higher MI risk in primary prevention.

Area of Science:

  • Cardiovascular Disease Research
  • Biomarker Discovery and Validation
  • Preventive Cardiology

Background:

  • Traditional lipid markers like LDL-C have limitations in predicting cardiovascular disease (CVD) events.
  • Emerging biomarkers including lipoprotein(a) (Lp[a]), remnant cholesterol (RC), and high-sensitivity C-reactive protein (hsCRP) show potential beyond LDL-C.
  • The incremental predictive value of these non-LDL-C biomarkers for specific CVD outcomes, particularly myocardial infarction (MI), requires further elucidation in primary prevention.

Purpose of the Study:

  • To assess the extent to which Lp[a], RC, and hsCRP concentrations enhance MI-specific risk prediction.
  • To evaluate these biomarkers in a large, primary prevention population using UK Biobank data.
  • To determine if these non-LDL-C markers provide independent and complementary information for MI risk stratification.

Main Methods:

  • Analysis of 306,183 UK Biobank participants without prevalent CVD at baseline.
  • Measurements of Lp[a], hsCRP, and calculation of RC (Total Cholesterol - LDL-C - HDL-C).
  • Cox regression models were used to estimate hazard ratios (HRs) for incident MI across biomarker quintiles and cumulative burden, adjusting for confounders.

Main Results:

  • Over 15 years, 10,824 MI events were recorded.
  • Elevated Lp[a], RC, and hsCRP were independently associated with increased MI risk (HRs ranging from 1.08 to 1.14 comparing Q5 vs Q1).
  • Cumulative burden of these three biomarkers significantly amplified MI risk; individuals with all three in the top quintile had an HR of 2.83 (95% CI: 2.48-3.24) compared to those with none.

Conclusions:

  • Lp[a], RC, and hsCRP provide independent and complementary predictive information for MI risk.
  • The combined elevation of these biomarkers identifies a significantly higher-risk group in primary prevention.
  • Selective testing of Lp[a], RC, and hsCRP is suggested for enhanced MI risk assessment in primary prevention strategies.
Abstract

Keywords:
CVDInflammationLipoprotein(a)Myocardial infarctionRemnant cholesterolUK BiobankhsCRP

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