Even mild elevations of C-reactive protein levels predict long-term prognosis in heart failure with mildly reduced ejection fraction

OBJECTIVE: C-reactive protein (CRP) levels reflect systemic inflammation which may mediate adverse outcomes in heart failure (HF). The present study sought to investigate the prognostic impact of baseline CRP levels in patients hospitalized with HF with mildly reduced ejection fraction (HFmrEF). BACKGROUND: While inflammation is recognized as a key pathophysiological component of HF, data on the prognostic relevance of CRP in HFmrEF patients remain limited. METHODS: Consecutive patients hospitalized with HFmrEF were retrospectively included at a single centrer. The primary analysis included unselected all-comer patients, while a secondary analysis excluded patients with conditions associated with increased CRP levels. CRP was analyzed in predefined categories (i.e., <5 mg/L, 5-<10 mg/L, 10-<50 mg/L, ≥50 mg/L) and as a continuous variable (log-transformed). The prognostic impact of CRP levels was investigated with regard to the primary endpoint all-cause mortality at 30 months;, key secondary endpoint was HF-related rehospitalization. RESULTS: A total of 1,978 HFmrEF patients were hospitalized with a median CRP level of 13.3 mg/L (interquartile range 3.5-43.7 mg/L). Compared with CRP <5 mg/L, CRP levels of 5-<10 mg/L (HR 1.720; 95% CI 1.250-2.366; p = 0.001), 10-<50 mg/L (HR 1.813; 95% CI 1.400 2.348; p = 0.001), and ≥50 mg/L (HR 2.275; 95% CI 1.731-2.991; p = 0.001) were independently associated with increased all-cause mortality after multivariable adjustment. This association was consistent when CRP was analyzed as a continuous variable ((ln)CRP: HR 1.250; 95% CI 1.167-1.339; p = 0.001), as well after excluding patients with conditions associated with elevated CRP levels. By contrast, CRP was not independently associated with the risk of HF-related rehospitalization. CONCLUSION: In patients hospitalized with HFmrEF, elevated CRP levels, even mild CRP elevations, were independently associated with an increased risk of long-term all-cause mortality. These findings support the prognostic relevance of even low-grade systemic inflammation in HFmrEF.