Background Microvascular inflammation may contribute to the pathogenesis of both heart failure with preserved ejection fraction (HFpEF) and pulmonary hypertension (PH). We investigated whether the inflammation biomarker C-reactive protein (CRP) was associated with clinical characteristics, disease severity or PH in HFpEF. Methods Patients in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart failure (RELAX) trial had baseline high-sensitivity CRP levels measured (n = 214). Clinical characteristics, exercise performance, echocardiographic variables and biomarkers of neurohumoral activation, fibrosis and myocardial necrosis were assessed. Patients with normal (<= 3mg/L) versus high (> 3mg/L) CRP levels were compared. Results The median CRP level was 3.69mg/L. CRP was elevated in 57% of patients. High CRP levels were associated with younger age, higher body mass index (BMI), chronic obstructive pulmonary disease (COPD), lower peak oxygen consumption and higher endothelin-1 and aldosterone levels. CRP increased progressively with the number of comorbidities (0.7mg/L per increment in comorbidity number, P = 0.02). Adjusting for age, BMI and statin use, high CRP levels were additionally associated with atrial fibrillation, right ventricular dysfunction, and higher N-terminal pro-B-type natriuretic peptide levels (P< 0.05 for all). CRP was not associated with PH or left ventricular function. CRP did not identify responders to sildenafil (P-value for interaction 0.13). Conclusions In HFpEF, high CRP is associated with greater comorbidity burden and some markers of disease severity but CRP was normal in 40% of patients. These findings support the presence of comorbidity-driven systemic inflammation in HFpEF but also the need to study other biomarkers which may better reflect the presence of systemic inflammation.
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