Long-Term High-Sensitivity C-Reactive Protein Trajectories and Risk of Major Adverse Cardiovascular Events in Statin-Treated Patients: A Retrospective Cohort

Background: Highsensitivity Creactive protein (hsCRP) is a key inflammatory marker in atherosclerosis; however, the association between its long-term patterns and cardiovascular prognosis under statin therapy remains incompletely understood. This study characterized hs-CRP trajectories and their prognostic value for MACE in statin users, aiming to refine risk assessment and tailored therapy.

Methods: We conducted a retrospective cohort study at the Center for Coronary Artery Disease, Beijing Anzhen Hospital, Capital Medical University (Beijing, China), using data from patients who received statin therapy for at least 12 months between January 2023 and December 2024. Eligible participants had three or more hs-CRP measurements and were free from major adverse cardiovascular events (MACE) six months before enrollment. Latent class growth modeling was applied to categorize hs-CRP trajectories. The primary composite outcome included cardiovascular death, nonfatal MI, nonfatal stroke, or rehospitalization for unstable angina. Event-free survival was compared across trajectory groups using Kaplan-Meier curves with log-rank testing. Multivariable Cox proportional hazards regression evaluated the association between hs-CRP trajectories and MACE, with adjustments for age, sex, hypertension, diabetes, baseline lipids, and statin intensity.

Results: This study included 210 patients with a median follow-up of 11.9 months. Latent class growth modeling identified three distinct hs-CRP trajectories: persistently low (45.2%, <2 mg/L), moderately fluctuating (40.0%, 2–5 mg/L), and persistently high (14.8%, ≥5 mg/L). Over follow-up, 38 patients (18.1%) experienced a MACE. Kaplan-Meier analysis revealed significantly higher cumulative MACE incidence in persistently high compared to persistently low (38.7% vs. 5.3%, P<0.001), with moderately fluctuating also showing elevated risk (25.0% vs. 5.3%, P<0.001). Following multivariable adjustment, both persistently high (HR 4.21, P=0.015) and moderately fluctuating (HR 3.46, P=0.016) hs-CRP trajectories remained independent predictors of MACE in patients receiving statins.

Conclusions: Statin-treated patients with rising hs-CRP levels face elevated MACE risk. Longitudinal patterns show prognostic promise but need validation in future trials.