HFpEF and Atrial Fibrillation: The Enigmatic Interplay of Dysmetabolism, Biomarkers, and Vascular Endothelial Dysfunction
Jure Bosanac, Lara Straus, Marko Novaković, Daniel Košuta, Mojca Božič Mijovski, J Tasić, Borut Jug
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 <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mtext>patients</a:mtext> <a:mo>≥</a:mo> <a:mn>65</a:mn> </a:math> 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 <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mn>80</c:mn> <c:mo>±</c:mo> <c:mn>7</c:mn> </c:math> years, 67% females) were included. Patients with HFpEF and AF had significantly lower levels of irisin (median 4.75 vs. 13.5 ng/mL, <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>p</e:mi> <e:mo>=</e:mo> <e:mn>0.007</e:mn> </e:math> ), leptin (median 9.5 vs. 15.0 ng/L, <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>p</g:mi> <g:mo>=</g:mo> <g:mn>0.023</g:mn> </g:math> ), and MDA (median 293 vs. 450 ng/mL, <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>p</i:mi> <i:mo>=</i:mo> <i:mn>0.017</i:mn> </i:math> ) and significantly higher values of NT-proBNP (median 2365 vs. 529 ng/L, <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>p</k:mi> <k:mo><</k:mo> <k:mn>0.001</k:mn> </k:math> ) but not vascular function parameters, as compared to HFpEF patients without AF. MDA was significantly correlated with diastolic function ( <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mi>r</m:mi> <m:mo>=</m:mo> <m:mn>0.395</m:mn> </m:math> , <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" id="M8"> <o:mi>p</o:mi> <o:mo>=</o:mo> <o:mn>0.007</o:mn> </o:math> ) and FMD ( <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" id="M9"> <q:mi>r</q:mi> <q:mo>=</q:mo> <q:mn>0.394</q:mn> </q:math> , <s:math xmlns:s="http://www.w3.org/1998/Math/MathML" id="M10"> <s:mi>p</s:mi> <s:mo>=</s:mo> <s:mn>0.011</s:mn> </s:math> ), while adiponectin was inversely associated with FMD ( <u:math xmlns:u="http://www.w3.org/1998/Math/MathML" id="M11"> <u:mi>r</u:mi> <u:mo>=</u:mo> <u:mo>−</u:mo> <u:mn>0.325</u:mn> </u:math> , <w:math xmlns:w="http://www.w3.org/1998/Math/MathML" id="M12"> <w:mi>p</w:mi> <w:mo>=</w:mo> <w:mn>0.038</w:mn> </w:math> ) and left ventricular ejection fraction ( <y:math xmlns:y="http://www.w3.org/1998/Math/MathML" id="M13"> <y:mi>r</y:mi> <y:mo>=</y:mo> <y:mo>−</y:mo> <y:mn>0.319</y:mn> </y:math> , <ab:math xmlns:ab="http://www.w3.org/1998/Math/MathML" id="M14"> <ab:mi>p</ab:mi> <ab:mo>=</ab:mo> <ab:mn>0.029</ab:mn> </ab:math> ). 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.