Irisin Predicts Poor Clinical Outcomes in Patients with Heart Failure with Preserved Ejection Fraction and Low Levels...

Despite existing evidence of the high predictive value of natriuretic peptides (NPs) in patients with heart failure (HF), patients treated with guideline-directed therapy who have low or near-normal NP levels are unlikely to be correctly stratified for risk of clinical outcomes. The aim of this study is to detect plausible predictors for poor one-year clinical outcomes in patients with HFpEF and low NT-proBNP treated with in accordance with conventional guidelines.

A total of 337 patients with HF with preserved ejection fraction (HFpEF) who had low levels of N-terminal natriuretic pro-peptide (NT-proBNP) at discharge due to optimal guideline-based therapy were enrolled in the study. The course of the observation was 3 years. Echocardiography and the assessment of conventional hematological and biochemical parameters, including NT-proBNP, tumor necrosis factor-alpha, high-sensitivity C-reactive protein (hs-CRP), adropin, irisin, visfatin, and fetuin-A, were performed at baseline and at the end of the study.

Three-year cumulative clinical endpoints (cardiovascular death, myocardial infarction or unstable angina or acute coronary syndrome, worsening HF, sudden cardiac death, or cardiac-related surgery or all-cause death) were detected in 104 patients, whereas 233 did not meet the endpoint. After adjusting for an age ≥ 64 years and a presence of atrial fibrillation, diabetes mellitus, chronic kidney disease (CKD) stages 1-3 and dilated cardiomyopathy, the multivariable Cox regression analysis showed that an irisin level of ≤7.2 ng/mL was an independent predictor of cumulative clinical endpoint. Moreover, patients with levels of irisin > 7.2 ng/mL had a better Kaplan-Meier survival rate than those with a lower serum irisin level (≤7.2 ng/mL).

Multivariable analysis showed that an age ≥ 64 years; the presence of atrial fibrillation, diabetes mellitus, CKD stages 1-3 and dilated cardiomyopathy; an LAVI ≥ 39 mL/m²; and serum levels of hs-CRP ≥ 6.10 mg/L, irisin ≤ 7.2 ng/mL, and visfatin ≤ 1.1 ng/mL were predictors of poor clinical outcomes in HFpEF with low levels of NT-proBNP. A serum level of irisin ≤ 7.2 ng/mL could emerge as valuable biomarker for predicting long-term prognosis among HFpEF patients with low or near-normal levels of NT-proBNP.