Last updated:
Author(s):
Berkan Kurt, Martin Reugels, Kai M Schneider, Jens Spiesshoefer, Andrea Milzi, Alexander Gombert, Christopher B Fordyce, Florian A Wenzl, Neha J Pagidipati, Viviane Rocha, Marat Fudim, Abhinav Sharma, Michael Lehrke, Hiroaki Shimokawa, Giovanna Liuzzo, Lale Tokgozoglu, Filippo Crea, Thomas F Lüscher, Peter Libby, Paul M Ridker, Nikolaus Marx, Carolin V Schneider, Florian Kahles
Publish date:
11 December 2025
Journal:
European Heart Journal
PubMed ID:
41378999

Abstract

BACKGROUND AND AIMS: High-sensitivity C-reactive protein (hsCRP) is a marker of inflammation and predicts cardiovascular (CV) risk in individuals without known atherosclerotic CV disease (ASCVD). More information about its clinical relevance will help evaluate the general utility of hsCRP as a routine clinical biomarker to identify patients at residual risk.

METHODS: In this population-based study, hsCRP was measured in 448 653 UK Biobank participants without known ASCVD. The association of hsCRP with major adverse cardiovascular events (MACE), CV death and all-cause death was assessed using Cox proportional hazards models.

RESULTS: The cohort had a median age of 57 years, 55.4% were female, and median hsCRP levels were 1.32 mg/L. A repeat hsCRP measurement in 15 967 participants after 4.4 years showed long-term stability. In covariate-adjusted models individuals with hsCRP levels >3 mg/L had a 34% higher risk of MACE, a 61% and 54% increased risk of CV death and all-cause death compared to those with hsCRP <1 mg/L. Subjects with hsCRP levels ≥2 mg/L vs <2 mg/L had a 22% increased risk of MACE, and a 37% and 34% higher risk of CV death and all-cause death. The association of hsCRP with all endpoints was consistent across subgroups. Predictive performance of hsCRP ranked above conventional risk factors. Integration of hsCRP improved SCORE2 and provided a total net reclassification improvement of 14.1% for prediction of MACE.

CONCLUSIONS: These data confirm hsCRP as a clinically relevant predictor of CV events in individuals without known ASCVD and support its assessment in primary prevention.

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Uniklinik RWTH Aachen, Germany

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