C-reactive protein at hospitalization and risk of new-onset heart failure in patients with acute myocardial infarction

Background C-reactive protein (CRP), a circulating biomarker of inflammation, is associated with myocardial infarct size in animal models. We have previously shown that CRP at hospitalization is a predictor of both short- and long-term death in patients with acute myocardial infarction (MI). However, whether CRP is associated with new-onset heart failure (HF) in such individuals is unknown. Purpose To assess the association between CRP and risk of incident HF in persons with acute MI, without a prior history of HF. Methods We used the Danish nationwide registries to identify patients with a first MI diagnosis (International Classification of Diseases, Tenth Revision diagnostic code: I21) from 2012 through 2020. Those who underwent CRP and high-sensitivity troponin measurements within 24 hours of this index hospitalization were included, while subjects with acute infection were excluded. For this analysis, individuals with a history of heart failure were also excluded. Patients were stratified into quartiles (Q1-Q4) based on their first CRP measurement. Absolute and relative risks for hospitalization or outpatient contact for heart failure at days 0-30 and 31-365 were calculated through multivariable Cox regression with average treatment effect modeling. Models were standardized for demographic and clinical features, including prior cardiovascular or inflammatory disease, hemoglobin concentration, and high-sensitivity troponin concentration. Results A total of 31,528 individuals were included of whom 2,813 were excluded due to a history of heart failure. Thus, this analysis was based on the remaining 28,715 persons. Median age was 68.1 (interquartile range: 57.6 to 77.2) years, and 33.6% were women. Median CRP in the entire cohort was 4.9 (interquartile range: 2.8 to 13) mg/l, and quartile intervals were: Q1: <2.9 mg/l, Q2: 2.9 to <4 mg/l, Q3: 4 to <14 mg/l, and Q4: ≥14 mg/l. CRP was significantly and nonlinearly associated with the primary outcome (p<0.001). At 0-30 days, 2,317 patients had been diagnosed with heart failure, and another 1,595 had developed heart failure between days 31-365. The standardized absolute risk of heart failure at both 0-30 and 31-365 days was lowest among patients in Q1 (0-30 days: 5.6%; 31-365 days: 4.2%) and highest among patients in Q4 (0-30 days: 12.9%; 31-365 days: 10.4%). The standardized relative risks of heart failure as compared with Q1 were: Q2: 1.08 (95% CI 0.93 to 1.23), Q3: 1.55 (1.37 to 1.74), and Q4: 2.30 (2.03 to 2.57) at 30 days, and Q2: 1.13 (0.95 to 1.31), Q3: 1.40 (1.19 to 1.60), and Q4: 2.46 (2.11 to 2.81) at 365 days. Conclusion In patients with acute MI who did not have a history of HF, we found a graded, positive association between CRP concentration and the risk of new-onset heart failure, independently of high-sensitivity troponin concentration. This finding highlights inflammation as a potential target for both risk stratification and secondary prevention of HF after MI.