NEWS & PERPECTIVE
hsCRP emerges as a key predictor of cardiovascular risk beyond LDL-C
Cardiovascular disease (CVD) risk assessment has traditionally focused on lipid parameters, particularly low-density lipoprotein-cholesterol (LDL-C).1,2 However, a substantial proportion of cardiovascular events continue to occur in individuals on lipid-lowering therapies, highlighting the need for improved risk stratification.1,2 Emerging evidence suggests that chronic, low-grade inflammation plays a central role in atherosclerosis and its complications, with high-sensitivity C-reactive protein (hsCRP) increasingly recognized as a robust biomarker of vascular inflammation.3 The 2025 American College of Cardiology (ACC) scientific statement indicates that hsCRP may provide prognostic information comparable to, or even exceeding, that of cholesterol, even among apparently healthy individuals, underscoring its potential to enhance cardiovascular risk prediction.3
hsCRP is an acute-phase reactant produced by the liver in response to inflammatory cytokines, particularly interleukin-6, reflecting underlying vascular inflammatory activity.3 Clinical evidence supports its role in driving cardiovascular events independently of traditional risk factors, yet its integration into routine clinical testing remains inconsistent due to limited evidence.3 The 2025 ACC scientific statement was therefore developed to consolidate current data and clarify the role of hsCRP in cardiovascular risk assessment, and provides guidance on hsCRP use across primary and secondary prevention.3 This comprehensive statement was developed by an expert ACC writing committee through review of seminal publications, with clinical recommendations formulated with sufficient rigorous evidence and consensus achieved among the committee.3
In clinical practice, silent vascular inflammation can be assessed through hsCRP measurement, which has been shown to be a strong and independent predictor of cardiovascular events, with predictive value comparable to blood pressure and LDL-C.3 hsCRP may also be used as a risk predictor in chronic heart failure.3 hsCRP levels of <1mg/L, 1-3mg/L and >3mg/L correspond to low, average, and high cardiovascular risk, respectively.3 In stable outpatients, hsCRP demonstrates long-term stability and variability similar to traditional risk markers, and a single measurement can effectively stratify long-term risk, often outperforming LDL-C or lipoprotein(a) in predicting future cardiovascular events.3 Accordingly, the ACC recommends universal hsCRP screening in clinically stable patients alongside lipid parameters to enhance cardiovascular risk evaluation.3
In primary prevention settings, elevated hsCRP identifies individuals at increased risk of future cardiovascular events, with each 1-standard deviation increase associated with a 37% higher risk of coronary heart disease and 55% higher risk of cardiovascular death.3 The magnitude of risk associated with hsCRP was comparable to that of systolic blood pressure and exceeded that of conventional lipid parameters.3 Furthermore, hsCRP retains predictive value even among individuals without standard modifiable risk factors, reinforcing its role in identifying otherwise unrecognized high-risk populations.3 A single hsCRP measurement >3mg/L can therefore be used as a biomarker in routine practice to identify individuals at increased inflammatory risk, and may prompt early lifestyle interventions and, if hsCRP remains elevated, initiation or intensification of statin therapy even when LDL-C is not markedly elevated.3
Patients with hsCRP >2mg/L remain at increased risk for recurrent cardiovascular events and death despite well-controlled LDL-C.3 Real-world data indicate that up to 60% of patients with established atherosclerotic disease have persistently elevated hsCRP despite contemporary care.3 Among individuals with known cardiovascular disease, irrespective of statin treatment, hsCRP is at least as powerful a predictor of recurrent vascular events as LDL-C, and an even stronger predictor of recurrent myocardial infarction, stroke, and cardiovascular death.3 These findings highlight the clinical importance of residual inflammatory risk and support hsCRP measurement in guiding risk reduction strategies.3 Hence, the ACC statement recommends broad hsCRP screening in secondary prevention populations, with persistently elevated levels ≥2mg/L prompting consideration of intensifying statin therapy in patients already receiving statin therapy, regardless of LDL-C.
In conclusion, the ACC statement highlights inflammation, measured by hsCRP, as a critical driver of cardiovascular risk in both primary and secondary prevention.3 Targeting residual inflammatory risk reduces events independent of LDL-C.3 Broad hsCRP screening alongside LDL-C and implementation of anti-inflammatory strategies, including lifestyle interventions, can improve outcomes.3 Raising physician awareness and integrating inflammatory biomarkers with traditional risk factors represents a paradigm shift toward earlier identification and more precise cardiovascular risk management.3
