In this study, we established that apart from older age and known concomitant comorbidities such as atrial fibrillation, diabetes mellitus, CKD stages 1–3 and dilated cardiomyopathy, altered levels of hs-CRP, visfatin and irisin (which belong to the adipokines/myokines) were predictors for cumulative clinical endpoint for 3 years in patients with HFpEF and low levels of NT-proBNP. This evidence concerns the gene FNDC5 and diabetes mellitus.