Association Between High-Sensitivity C-Reactive Protein (hs-CRP) Levels and Cardiovascular Disease

Abstract

Aim – This review aims to systematically evaluate the prognostic and clinical utility of high-sensitivity C-reactive protein (hs-CRP) across the full spectrum of cardiovascular diseases, from coronary artery disease and heart failure to stroke, arrhythmias, valvular disease, cardiomyopathies, and infectious cardiac conditions. Background – Cardiovascular disease (CVD) remains the leading cause of global mortality, with chronic low-grade inflammation increasingly recognized as a central driver alongside traditional risk factors. hs-CRP, an acute-phase reactant synthesized under interleukin-6 stimulation, offers a widely available and reproducible window into systemic inflammatory burden. Its associations with atherosclerosis, endothelial dysfunction, myocardial fibrosis, and adverse vascular remodeling have generated substantial clinical interest across diverse cardiac conditions. Review Results – Elevated hs-CRP independently predicts major adverse cardiovascular events in coronary artery disease, acute myocardial infarction, and unstable angina, with prognostic gradients persisting after lipid adjustment. In ischemic stroke, admission hs-CRP forecasts recurrence and 3-month functional outcomes, whereas associations with hemorrhagic stroke are weak and non-causal. In heart failure, raised hs-CRP correlates with worse remodeling, higher hospitalization rates, and increased mortality across both HFrEF and HFpEF phenotypes. Co-elevation with hypertension confers synergistic cardiovascular mortality risk. In peripheral artery disease, the CRP-to-albumin ratio outperforms hs-CRP alone for predicting limb and cardiovascular outcomes. Modest but significant associations are observed in atrial fibrillation and TAVI candidates. In myocarditis and pericarditis, serial hs-CRP monitoring guides disease activity assessment and therapy duration. Mendelian randomization studies consistently position CRP as a downstream inflammatory marker rather than an independent causal agent. Conclusion – hs-CRP provides clinically meaningful prognostic information across virtually the entire cardiovascular disease spectrum. Its signal is strongest in ischemic and inflammatory disorders, moderate in heart failure and peripheral artery disease, and modest in hemorrhagic stroke and atrial fibrillation. It functions as an adjunctive prognostic biomarker reflecting downstream cytokine-driven pathology rather than a causal mediator. Clinical Significance – As a low-cost, broadly available biomarker, hs-CRP can meaningfully refine cardiovascular risk stratification when integrated into multimarker clinical frameworks. Serial monitoring adds prognostic value in myocarditis, pericarditis, and heart failure. Future research should prioritize validated condition-specific cut-points, multimarker panel strategies, and interventional trials targeting inflammatory signaling to determine whether reducing hs-CRP translates to improved patient outcomes.