High-sensitivity C-reactive protein (hsCRP), a marker of inflammation, has a debated role in primary cardiovascular (CV) prevention. A large, population-based study using UK Biobank data has provided further insight into its utility as a clinical biomarker for identifying individuals at residual risk who do not have known atherosclerotic cardiovascular disease (ASCVD).¹

Methodology

This population-based cohort study analysed data from 448,653 UK Biobank participants aged 40 years or older without a known history of ASCVD. Researchers measured hsCRP at baseline and assessed its association with CV outcomes using Cox proportional hazards models. The primary endpoints were a composite of major adverse cardiovascular events (MACE), defined as CV death, non-fatal myocardial infarction, or non-fatal stroke, as well as CV death and all-cause death individually. The median follow-up period was 13.7 years for MACE.¹

Results

The study found that hsCRP levels were a significant predictor of adverse outcomes. After adjustment for multiple covariates, individuals with hsCRP levels >3 mg/L had a 34% higher risk of MACE (adjusted HR 1.34; 95% CI: 1.29–1.39), a 61% higher risk of CV death (adjusted HR 1.61; 95% CI: 1.50–1.72), and a 54% higher risk of all-cause death (adjusted HR 1.54; 95% CI: 1.50–1.58) compared to those with levels <1 mg/L.

Similarly, participants with hsCRP levels ≥2 mg/L showed a 22% increased risk of MACE (adjusted HR 1.22; 95% CI: 1.19–1.24) and a 37% increased risk of CV death (adjusted HR 1.37; 95% CI: 1.31–1.44) versus those with levels <2 mg/L. The predictive value of hsCRP was consistent across various clinical subgroups, including those without standard modifiable risk factors (SMuRF-less). Furthermore, integrating hsCRP into the Systematic COronary Risk Evaluation 2 (SCORE2) model improved its predictive performance, yielding a total net reclassification improvement of 14.1% for MACE.² A repeat measurement in a subset of participants after a median of 4.4 years also demonstrated the long-term stability of hsCRP levels.¹

In Practice

These findings suggest that hsCRP is a relevant and independent predictor of CV events and mortality in a primary prevention setting. The authors concluded, "These data confirm hsCRP as a clinically relevant predictor of CV events in individuals without known ASCVD and support its assessment in primary prevention."¹ The biomarker's ability to enhance established risk scores like SCORE2, even in individuals considered low-risk, highlights its potential to refine risk stratification.

Next Steps

Given the link between inflammation and ASCVD, the study authors suggest that future research should explore whether hsCRP measurement can help identify patients who would benefit most from targeted anti-inflammatory therapies, potentially guiding more personalised prevention strategies.

This study was funded by the Clinician Scientist Programme of the Faculty of Medicine RWTH Aachen University, the German Research Foundation (DFG), the National Heart, Lung, and Blood Institute, and the European Foundation for the Study of Diabetes (EFSD)/Novo Nordisk Foundation, among others.

References

1. Kurt B, Reugels M, Schneider KM, et al. C-reactive protein and cardiovascular risk in the general population. _Eur Heart J_ 2026;47(15):1799–1810. https://doi.org/10.1093/eurheartj/ehaf937

2. Hageman S, Pennells L, Ojeda F, et al. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. _Eur Heart J_ 2021;42(25):2439–2454. https://doi.org/10.1093/eurheartj/ehab309

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