High sensitivity C-Reactive Protein in Chronic Heart Failure: Patient Characteristics, Phenotypes and Mode of Death

Aims: Plasma concentrations of high sensitivity C-reactive protein (hsCRP) are often raised in chronic heart failure (CHF) and might indicate inflammatory processes that could be a therapeutic target. We aimed to study the associations between hsCRP, mode and cause of death in patients with CHF. Methods and Results: We enrolled 4,423 patients referred to a heart failure clinic serving a local population. CHF was defined as relevant symptoms or signs with either a reduced left ventricular ejection fraction (LVEF) <40% or raised plasma concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP >125 pg/ml). The median (IQR) plasma hsCRP for patients diagnosed with CHF (n = 3,756) was 3.9 (1.6-8.5) mg/L and 2.7 (1.3-5.1) mg/L for those who were not (n=667; p<0.001). Patients with hsCRP >10 mg/L (N=809; 22%) were older and more congested than those with hsCRP <2 mg/L (N=1,117, 30%). During a median follow up of 53 (IQR: 28-93) months, 1,784 (48%) patients with CHF died. Higher plasma hsCRP was associated with greater mortality, independent of age, symptom severity, creatinine and NT-proBNP. Comparing a hsCRP >10mg/L to <2mg/L, the hazard ratio for all-cause mortality was 2.49 (95% confidence interval: 2.19-2.84); P<0.001), for cardiovascular (CV) mortality was 2.26 (1.91-2.68; p<0.001) and for non-CV mortality was 2.96 (2.40-3.65; p<0.001). Conclusions: In patients with CHF, a raised plasma hsCRP is associated with more congestion and a worse prognosis. The proportion of deaths that are non-CV also increases with higher hsCRP.