Low-density lipoprotein cholesterol, C-reactive protein, and lipoprotein(a) universal one-time screening in primary prevention: the EPIC-Norfolk study.
Summary
In 17,087 initially healthy adults followed for 20 years, baseline LDL-C, hsCRP, and Lp(a) independently predicted MACE, with top vs bottom quintile HRs of 1.78, 1.55, and 1.19. Having one, two, or three elevated markers conferred progressively higher risk (HR 1.33, 1.68, 2.41), supporting universal one-time screening.
Key Findings
- Top vs bottom quintile HRs for 20-year MACE: LDL-C 1.78, hsCRP 1.55, Lp(a) 1.19 (all adjusted).
- Risk increased additively with the number of elevated biomarkers: HR 1.33 (one), 1.68 (two), 2.41 (three).
- Each biomarker contributed independently to risk across sexes.
Clinical Implications
Universal one-time measurement of LDL-C, hsCRP, and Lp(a) in primary prevention can identify higher-risk individuals and guide earlier lipid-lowering, anti-inflammatory strategies, and Lp(a)-targeted evaluation.
Why It Matters
This provides long-term, population-level evidence that a combined, one-time measure of LDL-C, hsCRP, and Lp(a) robustly stratifies primary prevention risk, replicating prior US findings and informing screening policy.
Limitations
- Observational design limits causal inference; residual confounding possible.
- Single baseline measurement; biomarker changes over time not captured.
Future Directions
Evaluate implementation strategies for universal screening, cost-effectiveness across health systems, and integration with polygenic risk and imaging to refine prevention.
Study Information
- Study Type
- Cohort
- Research Domain
- Prevention
- Evidence Level
- II - Large prospective cohort study with long-term follow-up and multivariable analyses.
- Study Design
- OTHER