Carotid Arterial Stiffness and Its Relationship to Exercise Intolerance in Older Patients With Heart Failure and Preserved Ejection Fraction

Abstract

Heart failure with a preserved ejection fraction (HFpEF) is the dominant form of heart failure in the older population. The primary chronic symptom in HFpEF is severe exercise intolerance, however, its pathophysiology and therapy are not well understood. We tested the hypothesis that older patients with HFpEF have increased arterial stiffness beyond that which occurs with normal aging and that this contributes to their severe exercise intolerance. Sixty-nine patients ≥ 60 years with HFpEF and 62 healthy volunteers (24 young healthy subjects ≤ 30 years (YHC) and 38 older healthy subjects ≥ 60 years old (OHC) were examined. Carotid arterial stiffness was assessed using high-resolution ultrasound and peak exercise oxygen consumption (VO2) was measured using expired gas analysis. Peak VO2 was severely reduced in the HFpEF patients compared to OHC (14.1±2.9 vs. 19.7±3.7 ml/kg/min; p<0.001) and in both was reduced compared to YHC subjects, (32.0±7.2 ml/kg/min; both p<0.001). In HFpEF compared to OHC, carotid arterial distensibility was reduced (0.97±0.45 vs. 1.33±0.55 × 10−3 mmHg−1, p=0.008) and Young’s elastic modulus (YEM) was increased (1320±884 vs. 925±530 kPa, p<0.02). Carotid arterial distensibility was directly (0.28; p=0.02) and YEM was inversely (−0.32; p=0.01) related with peak VO2. Carotid arterial distensibility is decreased in HFpEF beyond the changes due to normal aging and is related to peak VO2. This supports the hypothesis that increased arterial stiffness contributes to exercise intolerance in HFpEF and is a potential therapeutic target.

Opposite Predictive Value of Pulse Pressure and Aortic Pulse Wave Velocity on Heart Failure With Reduced Left Ventricular Ejection Fraction

“…In line with this, several groups have reported that patients with HF and preserved LVEF have increased central aortic stiffness relative to age-matched healthy and hypertensive subjects without HF. 29,30 Only 1 study in HF and LVEF <45% revealed that PWV predicts adverse clinical outcomes. 31 Such alterations suggest that abnormal ventricular-vascular coupling may contribute to the pathophysiology of HF with preserved ejection fraction and even may become especially important in the setting of severe decompensated HF, in which significant correlations between PWV and LVEF have not been observed.…”

Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction

“…The major effect of age on the vasculature is systolic hypertension with widening of the pulse pressure that results from age‐related increase in arterial stiffness and early wave reflections 43, 44. Arterial stiffening and early wave reflections are steady vascular features in HFpEF 45, 46, 47, 48, 49, 50, 51, 52. In the proximal arterial tree, vascular smooth cell loss of elastin increases systolic arterial pressure by lessening the “windkessel” effect 44, 45, 53.…”

Activation of DNA demethylases attenuates aging‐associated arterial stiffening and hypertension

“…Coincidently, the prevalence of arterial stiffness and hypertension also increases with age (Sun, 2015). Arterial stiffening is an independent predictor of cardiovascular outcomes, such as hypertension, myocardial infarction, cognitive decline in aging, stroke, and kidney diseases (Hashimoto & Ito, 2011, 2013; Karras et al., 2012; Kitzman et al., 2013; Sun, 2015). However, the relationship of DNA methylation and aging‐related arterial stiffening is unclear.…”