Usefulness of C-Reactive Protein Plasma Levels to Predict Exercise Intolerance in Patients With Chronic Systolic Heart Failure

Abstract

Patients with heart failure (HF) have evidence of chronic systemic inflammation. Whether inflammation contributes to the exercise intolerance in patients with HF is, however, not well established. We hypothesized that the levels of C-reactive protein (CRP), an established inflammatory biomarker, predict impaired cardiopulmonary exercise performance, in patients with chronic systolic HF. We measured CRP using high-sensitivity particle-enhanced immunonephelometry in 16 patients with ischemic heart disease (previous myocardial infarction) and chronic systolic HF, defined as a left ventricular ejection fraction ≤ 50% and New York Heart Association class II-III symptoms. All subjects with CRP >2 mg/L, reflecting systemic inflammation, underwent cardiopulmonary exercise testing using a symptom-limited ramp protocol. CRP levels predicted shorter exercise times (R = -0.65, p = 0.006), lower oxygen consumption (VO2) at the anaerobic threshold (R = -0.66, p = 0.005), and lower peak VO2 (R = -0.70, p = 0.002), reflecting worse cardiovascular performance. CRP levels also significantly correlated with an elevated ventilation/carbon dioxide production slope (R = +0.64, p = 0.008), a reduced oxygen uptake efficiency slope (R = -0.55, p = 0.026), and reduced end-tidal CO2 level at rest and with exercise (R = -0.759, p = 0.001 and R = -0.739, p = 0.001, respectively), reflecting impaired gas exchange. In conclusion, the intensity of systemic inflammation, measured as CRP plasma levels, is associated with cardiopulmonary exercise performance, in patients with ischemic heart disease and chronic systolic HF. These data provide the rationale for targeted anti-inflammatory treatments in HF.