Longitudinal high-sensitivity C-reactive protein assessment predicts cardiovascular risk in apparently healthy individuals

Background High-sensitivity C-reactive protein (hsCRP) is the guideline-recommended biomarker for assessment of residual inflammatory risk in atherosclerotic cardiovascular disease (ASCVD). Clinical adoption remains limited, especially in individuals without established ASCVD. This study used longitudinal measurements to evaluate the intra-individual stability and prognostic value of hsCRP, clarifying its clinical utility and refining interpretation of inflammatory risk in preventive strategies. Methods Levels of hsCRP at two time points (T0 and T1) were available in 15,967 UK Biobank participants without known history of ASCVD. Median time between repeated measurements was 4.4 years. Levels of hsCRP were categorized at 2 mg/L and <1, 1–3 and >3 mg/L according to guideline recommendations. The primary endpoints were all-cause and cardiovascular death. Results Median levels of hsCRP were similar at T0 (1.16 [0.59–2.37] mg/L) and T1 (1.21 [0.61–2.42] mg/L). 884 deaths occurred during a follow-up of 15.3 years. At both time points, hsCRP levels above 2 mg/L and the categories of <1, 1–3, and >3 mg/L were associated with higher all-cause death (log-rank p<0.001). Similar results were observed for cardiovascular death (log-rank p<0.001). Higher hsCRP levels were associated with an increased risk of death at both time points (T0: Hazard ratio (HR): 1.42; 95% confidence interval (CI): 1.30, 1.54; p<0.001; T1: HR: 1.58; 95% CI: 1.45, 1.72; p<0.001). Dichotomizing hsCRP at ≥2 mg/L yielded comparable associations (T0: HR: 1.46; 95% CI: 1.33, 1.60; p<0.001; T1: HR: 1.63; 95% CI: 1.49, 1.78; p<0.001). All results remained significant after adjustment for age, sex, body mass index, type 2 diabetes mellitus, smoking, systolic blood pressure, low-density lipoprotein cholesterol and estimated glomerular filtration rate. Conclusion This large-scale cohort study affirmed hsCRP as a strong and independent predictor of mortality in individuals without ASCVD. Its predictive value remained stable across two time points. These findings demonstrate the temporal stability and prognostic robustness of hsCRP and support its clinical use as a reliable marker of inflammatory risk in primary prevention.