Prognostic impact of high-sensitivity C-reactive protein trajectories and sustained residual inflammation for prediction of cardiovascular outcomes
F Kahles, M Reugels, K M Schneider, F A Wenzl, H Shimokawa, G Liuzzo, L Togkozoglu, F Crea, T F Luescher, P Libby, P M Ridker, N Marx, C V Schneider, A Sharma, B KurtAbstract
Background
Traditional risk factors for atherosclerotic cardiovascular disease (ASCVD) fail to fully reflect the residual risk, driven by chronic low-grade inflammation, observed in many. Generally, high-sensitivity C-reactive protein (hsCRP) concentrations remain stable, but some individuals may experience increases. More information on whether longitudinal inflammatory burden, quantified by changes in serial hsCRP levels, provides prognostic information may improve our understanding of how persistent inflammation drives residual risk.
Methods
In this population-based cohort study, sequential hsCRP measurements were available in 15,967 UK Biobank participants without known history of ASCVD. The hsCRP cutoff value of 2 mg/L defined individuals with low-grade inflammation. The primary outcomes were all-cause and cardiovascular death.
Results
Median time between baseline (T0) and follow-up (T1) hsCRP measurement was 4.4 years. During a median follow-up of 15.3 years, 884 participants died. Compared with participants with consistently low inflammation, individuals with persistently elevated hsCRP had the highest risk of death (Hazard ratio (HR): 2.19; 95% confidence interval (CI):1.87, 2.56; p<0.001), followed by those with newly increased hsCRP (HR: 1.65; 95% CI: 1.35, 2.01; p<0.001), while participants whose hsCRP decreased (HR: 1.41; 95% CI: 1.13, 1.75; p<0.001) and those with consistently low hsCRP showed the lowest risk. Similar results were observed for cardiovascular death. These results were largely independent of age, sex, body mass index, type 2 diabetes mellitus, smoking, systolic blood pressure, low-density lipoprotein cholesterol and estimated glomerular filtration rate.
Conclusion
In this longitudinal assessment of hsCRP, sustained or newly developed low-grade inflammation independently identified individuals at higher risk of death. These findings emphasize the prognostic importance of cumulative persistent inflammation as a marker of residual cardiovascular risk and highlight the potential clinical value of serial hsCRP measurements to improve long-term risk stratification and preventive strategies.Graphical abstract