Low-density lipoprotein cholesterol, C-reactive protein, and lipoprotein(a) universal one-time screening in primary prevention: the EPIC-Norfolk study

Jordan M Kraaijenhof; Nick S Nurmohamed; Ask T Nordestgaard; Laurens F Reeskamp; Erik S G Stroes; G Kees Hovingh; S Matthijs Boekholdt; Paul M Ridker

doi:10.1093/eurheartj/ehaf209

Low-density lipoprotein cholesterol, C-reactive protein, and lipoprotein(a) universal one-time screening in primary prevention: the EPIC-Norfolk study

Eur Heart J. 2025 Apr 1:ehaf209. doi: 10.1093/eurheartj/ehaf209. Online ahead of print.

Authors

Jordan M Kraaijenhof¹, Nick S Nurmohamed^{1

2}, Ask T Nordestgaard³, Laurens F Reeskamp¹, Erik S G Stroes¹, G Kees Hovingh¹, S Matthijs Boekholdt², Paul M Ridker⁴

Affiliations

¹ Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
² Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
³ Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.
⁴ Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, 900 Commonwealth Ave, Boston, MA 02215, USA.

PMID: 40167249
DOI: 10.1093/eurheartj/ehaf209

Abstract

Background and aims: Recent data from a large American cohort of women strongly support universal one-time screening for LDL cholesterol, high-sensitivity C-reactive protein (hsCRP), and lipoprotein(a) [Lp(a)] in primary prevention. This study addresses the validity and generalizability of this novel primary prevention strategy in a large prospective European cohort of initially healthy men and women.

Methods: Plasma levels of LDL cholesterol, hsCRP, and Lp(a) were measured at study entry in 17 087 participants from the EPIC-Norfolk study who were subsequently followed over a period of 20 years for major adverse cardiovascular events (MACEs). Competing risk- and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MACE across quintiles of each biomarker and sought evidence of independent as well as additive effects over time were calculated.

Results: During the 20-year follow-up, a total of 3249 MACEs occurred. Increasing quintiles of baseline LDL cholesterol, hsCRP, and Lp(a) all predicted 20-year risks; the multivariable-adjusted HRs in a comparison of the top to bottom quintile were 1.78 (95% CI: 1.57-2.00) for LDL cholesterol, 1.55 (95% CI: 1.37-1.74) for hsCRP, and 1.19 (95% CI: 1.07-1.33) for Lp(a). Compared with individuals with no biomarker elevations, the multivariable-adjusted HRs for incident MACE were 1.33, 1.68, and 2.41 for those with one, two, or three biomarkers in the top quintile, respectively (all P < .001). Each biomarker demonstrated independent contributions to overall risk and findings were consistent in analyses stratified by sex.

Conclusions: A single combined measure of LDL cholesterol, hsCRP, and Lp(a) among initially healthy European men and women was predictive of incident MACE during a 20-year period. These data replicate findings from a recent American cohort and strongly support universal screening for all three biomarkers in primary prevention.

Keywords: Atherosclerotic cardiovascular disease; High-sensitivity C-reactive protein; LDL cholesterol; Lipoprotein(a); Primary prevention.