Longitudinal High-Sensitivity C-Reactive Protein and Longer-Term Cardiovascular Outcomes in Optimally-Treated
Iryna Dykun1, Donald Clark2, Julie Carlo3
1Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio; Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Essen, Germany.
Insights
Serial high-sensitivity C-reactive protein (hsCRP) monitoring in optimally treated patients with cardiovascular disease can predict major cardiovascular events (MACEs). Longitudinal hsCRP levels, even below 2 mg/L, independently associate with increased MACE risk.
Area of Science:
- Cardiology
- Biomarkers
- Preventive Medicine
Background:
- Major cardiovascular events (MACEs) remain a concern in optimally treated atherosclerotic cardiovascular disease (ASCVD) patients.
- The prognostic value of serial high-sensitivity C-reactive protein (hsCRP) in this population is underexplored.
Purpose of the Study:
- To investigate the association between longitudinal hsCRP levels and 30-month MACE rates in patients with high-risk vascular disease receiving optimal treatment.
- To determine if serial hsCRP measurements improve cardiovascular risk prediction beyond baseline levels.
Main Methods:
- Post hoc analysis of the ACCELERATE trial data from 8,563 optimally treated patients with available baseline and follow-up hsCRP levels.
- Multivariable Cox proportional hazard models were used to assess the association between longitudinal hsCRP and 30-month MACE.
- hsCRP levels were measured at baseline and at multiple follow-up time points.
Main Results:
- Patients experiencing MACE had higher baseline hsCRP levels and an upward hsCRP trajectory during follow-up compared to those without MACE.
- Higher longitudinal hsCRP levels were independently associated with increased MACE risk (HR per SD 1.19; 95% CI 1.10-1.29; P < 0.001).
- Models incorporating longitudinal hsCRP demonstrated improved MACE prediction compared to baseline hsCRP alone.
Conclusions:
- Longitudinal hsCRP monitoring is independently associated with long-term MACE in patients receiving optimal medical therapy.
- Serial hsCRP measurements offer a novel approach to identifying residual cardiovascular risk, even when levels remain below 2 mg/L.
- These findings highlight the importance of tracking hsCRP trends for comprehensive cardiovascular risk assessment.
Abstract:
The relation between serial high-sensitivity C-reactive protein (hsCRP) and long-term major cardiovascular events (MACEs; cardiovascular death, myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) has not been explored in optimally-treated patients with atherosclerotic cardiovascular disease. We tested the hypothesis that longitudinal follow-up hsCRP (repeated measures over time) would associate with 30-month MACE rates. We performed a post hoc analysis of ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibitor with Evacetrapib in Patients with High-Risk for Vascular Outcomes), involving optimally-treated patients with high-risk vascular disease, with available baseline and at least 1 follow-up hsCRP level. Using multivariable Cox proportional hazard models, we determined the association of longitudinal follow-up hsCRP with MACE at 30 months among 8,563 patients (aged 64.6 ± 9 years, 22% women). Patients with incident MACE (n = 961) had higher baseline hsCRP levels (1.77 vs 1.46 mg/L, p <0.0001 for patients with and without MACE, respectively) and showed an upward trajectory during follow-up, whereas median hsCRP levels remained <2 mg/L at all time points (1.83 vs 1.53 mg/L, 1.91 vs 1.53 mg/L, 1.76 vs 1.37 mg/L, at 3, 12, and 24 months, respectively). In a multivariable analysis, higher longitudinal hsCRP levels were independently associated with MACE (hazard ratio [95% confidence interval] per SD 1.19 [1.10 to 1.29], p <0.001), the majority of its individual components and all-cause death. Multivariable models containing longitudinal hsCRP provided improved predictive ability of MACE over baseline hsCRP. In the setting of established medical therapies, longitudinal follow-up hsCRP was independently associated with long-term MACE. In conclusion, these findings suggest that longitudinal hsCRP represents a novel approach of residual cardiovascular risk even when on-treatment hsCRP levels remain <2 mg/L.
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