Routine measurement of hsCRP in primary prevention
December 2025
In individuals without atherosclerotic cardiovascular disease (ASCVD), a single measurement of high-sensitivity C-reactive protein (hsCRP) added prognostic value beyond traditional cardiovascular risk factors. These findings make the case for routine measurement of hsCRP to improve ASCVD prevention.
Kurt B, Reugels M, Schneider KM, et al. C-reactive protein and cardiovascular risk in the general population. Eur Heart J 2025; doi.org/10.1093/eurheartj/ehaf937 ,
STUDY SUMMARY
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Objective |
To investigate the utility of hsCRP as a routine clinical predictor of cardiovascular risk in individuals without ASCVD.
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Study design |
Population-based cohort study using data from individuals without ASCVD from the UK Biobank.
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Study population |
448,653 UK Biobank subjects (median age 57 years, 55.4% female) without known ASCVD and with hsCRP data. Median hsCRP levels were 1.32 [interquartile range 0.65, 2.74] mg/L.
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Main study variables
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The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (major adverse cardiovascular events, MACE). Additional endpoints included cardiovascular death and all-cause death.
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Methods |
Kaplan-Meier survival analyses were used to evaluate time-to-event data for MACE, cardiovascular death and all-cause death. Hazard ratios and 95% confidence intervals (CI) for hsCRP in relation to the primary endpoints were calculated using both univariable and multivariable Cox proportional hazards models. Analyses were performed with hsCRP as a continuous variable (interquartile hazard ratio) and comparing median levels of hsCRP categories (<1 mg/L, 1–3 mg/L, >3 mg/L; ≥2 mg/L, <2 mg/L). Multivariable-adjusted analyses were performed in a two-step approach with a model including established cardiovascular risk factors (Model 1), as well as a fully-adjusted model including additional potential confounders of hsCRP levels (Model 2). |
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Results |
Over a median follow-up of 13.7 years, MACE occurred in 23,624 subjects, cardiovascular death in 6,176 subjects, and all-cause death in 35,983 subjects. There was a stepwise increase in the incidence of MACE incidence, with increasing hsCRP levels, with the highest event rates observed in individuals with hsCRP levels >3 mg/L (p < 0.001). Additionally, subjects with hsCRP levels ≥2 mg/L had higher event rates than those with hsCRP <2 mg/L (p< 0.001). Similar results were observed for cardiovascular death and all-cause death. In adjusted models, subjects with hsCRP levels >3 mg/L had a 34% higher risk of MACE, a 61% higher risk of cardiovascular death and 54% increased risk of all-cause death compared with those with hsCRP <1 mg/L. Furthermore, compared with subjects with hsCRP levels <2 mg/L, those with higher hsCRP levels had 22% higher risk of MACE, 37% higher risk of cardiovascular death and 34% higher risk of all-cause death (Table 1). As a predictive prognostic marker, hsCRP ranked above conventional risk factors including low-density lipoprotein cholesterol (LDL-C). Table 1. Relative risk estimates for the association of hsCRP with cardiovascular outcomes
Finally, the addition of hsCRP improved the predictive performance of SCORE2 for 10-year risk of MACE and enhanced cardiovascular risk prediction in subjects without ASCVD.
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Author conclusions |
Data from this study confirm hsCRP as a clinically relevant predictor of cardiovascular events in individuals without known ASCVD and support its assessment in primary prevention. |
Comment
Despite therapeutic advances, cardiovascular disease remains the leading cause of disease burden and death worldwide (1), highlighting the need for more effective risk assessment and preventive strategies. Moreover, several traditional factors which are integral to ASCVD prevention, such as elevated cholesterol, fail to account for the substantial residual risk observed in many individuals.
Inflammation drives the process of atherosclerosis and contributes to the associated complications (2-4), with hsCRP established as a biomarker for low-grade systemic inflammation. Although there is clear evidence that inclusion of hsCRP can improve cardiovascular risk prediction, translation of this information to guidelines and risk assessment scores has been variable (5-9).
The results of the current study make a clear case for universal hsCRP measurement. A single elevated hsCRP determination (>3 mg/L) predicted higher risk of MACE, cardiovascular death and all-cause death, and provided incremental value in SCORE2 risk assessment, ranking above risk associated with elevated LDL-C. Measurement of hsCRP also has practical advantages, as testing is readily available, inexpensive, and, as shown in the current study, measurements are durable over time These findings align with a recent statement from the American College of Cardiology (10), which recommended a single measurement of elevated hsCRP to identify increased inflammatory risk in primary prevention settings, which could be managed by early initiation of lifestyle interventions, or if persistent, initiation or intensification of statin therapy. Finally, measurement of hsCRP has value in tailoring anti-inflammatory treatment to those patients with residual inflammatory risk, clearly relevant in the context of ongoing trials assessing interleukin-6 inhibition among individuals with elevated hsCRP.
It is increasingly evident that residual risk is multifaceted. Beyond the well-founded emphasis on lipid-related residual risk, attention should also encompass the relevance of residual inflammatory risk. The current study provides the foundation for a shift in clinical practice, emphasizing inflammation as a critical and actionable risk factor alongside lipids.
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Key words: high-sensitivity C-reactive protein; cardiovascular risk prediction; primary prevention; residual inflammatory risk
