HFpEF and Atrial Fibrillation: The Enigmatic Interplay of Dysmetabolism, Biomarkers, and Vascular Endothelial Dysfunction

Abstract

Background. Heart failure with preserved ejection fraction (HFpEF) has a complex pathophysiology that encompasses systemic proinflammatory state and dysregulated levels of cardiometabolic and oxidative stress biomarkers. The prevalence of both HFpEF and atrial fibrillation (AF) is continuously rising, especially in the elderly. The aim of our study was to explore if there were any differences in biomarker levels and vascular function in the elderly patients with HFpEF with and without AF and to assess interconnections between clinically relevant biomarkers and cardiac and vascular function. Methods. This was a cross-sectional study of patients ≥ 65 years with HFpEF who were divided into 2 groups based on the presence or absence of AF. We have sonographically assessed echocardiographic parameters of left ventricular systolic and diastolic function and the peripheral vascular function parameters, namely, pulse wave velocity (PWV) and flow-mediated dilation (FMD). NT-proBNP, irisin, leptin, adiponectin, insulin-like growth factor 1 (IGF-1), and malondialdehyde (MDA) blood levels were determined. Results. Fifty-two patients (mean age 80 ± 7 years, 67% females) were included. Patients with HFpEF and AF had significantly lower levels of irisin (median 4.75 vs. 13.5 ng/mL, p = 0.007 ), leptin (median 9.5 vs. 15.0 ng/L, p = 0.023 ), and MDA (median 293 vs. 450 ng/mL, p = 0.017 ) and significantly higher values of NT-proBNP (median 2365 vs. 529 ng/L, p < 0.001 ) but not vascular function parameters, as compared to HFpEF patients without AF. MDA was significantly correlated with diastolic function ( r = 0.395 , p = 0.007 ) and FMD ( r = 0.394 , p = 0.011 ), while adiponectin was inversely associated with FMD ( r = − 0.325 , p = 0.038 ) and left ventricular ejection fraction ( r = − 0.319 , p = 0.029 ). Conclusions. Our results have demonstrated that patients with HFpEF and AF have significantly lower leptin, irisin, and MDA levels compared to patients with HFpEF but without AF. These results offer new insights into the complexity of vascular function and cardiometabolic and oxidative stress biomarkers in the context of HFpEF, AF, and aging.

New Insights into Endothelial Dysfunction in Cardiometabolic Diseases: Potential Mechanisms and Clinical Implications

“…Thus, in HFpEF, endothelial dysfunction has emerged as a hallmark of dysmetabolic vascular impairment and contributes to detrimental effects on cardiac metabolism and diastolic dysfunction [ 52 ]. In such a context, adiponectin levels in patients with HFpEF are inversely related to flow-mediated dilation, which is a marker of endothelial dysfunction [ 53 ]. Furthermore, irisin (a thermogenic hormone that leads to causes energy expenditure by increasing brown adipose tissue) is increased in response to volume and pressure overload, and it has been shown to alleviate cardiac inflammation, oxidative stress, lipotoxicity, apoptosis, myocardial inflammation, and hypertrophic remodeling of the heart [ 53 ].…”

Biomarkers of Atrial Fibrillation Recurrence in Patients with Paroxysmal or Persistent Atrial Fibrillation Following External Direct Current Electrical Cardioversion

“…On the contrary, acute HF, acute coronary syndrome, and acute myocardial infarction were associated with an increase in irisin levels, which is considered an adaptive factor that reduces endothelial damage by inhibiting inflammatory reactions and suppressing oxidative stress [185][186][187]. A low irisin level was described as an independent predictor of clinical outcomes in HF patients [188,189]. Although patients with HFpEF and AF had significantly lower irisin levels than those without AF [190], the role of irisin in predicting AF-related events, including relapse after electric cardioversion, has not yet been investigated.…”

Heart failure with preserved left ventricular ejection fraction in non-obstructive coronary artery disease: clinical utility of heart rate variability

“…В последнее десятилетие получено множество данных, указывающих на большое разнообразие этиологических факторов и описывающих особенности их влияния на патогенез синдрома сердечной недостаточности с сохраненной фракцией выброса (СНсФВ). У одного и того же пациента часто сосуществуют несколько механизмов, инициирующих симптоматическую хроническую сердечную недостаточность (ХСН), но степень активации каждого из них у пациентов с СНсФВ может сильно различаться [1,2].…”