Systemic endothelial dysfunction and incident heart failure in a population-based cohort

Background Premature vascular ageing and endothelial dysfunction (ED) have been consistently observed in patients with prevalent heart failure (HF) of various etiologies, and are considered to contribute to HF pathophysiology. However, data on the prognostic value of ED in predicting the future HF onset are limited and largely derived from selected clinical cohorts. Purpose This study investigated the association of noninvasively assessed ED with the subsequent development of symptomatic HF in a population-based cohort. Methods We used longitudinal data from the Study of Health in Pomerania (SHIP) with the baseline assessment of the participants in the SHIP-START-2 cohort (n=2,332). After exclusion of individuals without a follow-up assessment in SHIP-START-3, with prevalent HF and with missing covariables, a total of 1098 participants were included in the final analysis (mean age 56 ±13 years, 51% female). ED was quantified using the brachial artery flow-mediated vasodilation test (baFMD). Incident cases of symptomatic HF at SHIP-START-3 were identified based on NT-pro-BNP values, clinical assessment data, transthoracic echocardiography, and cardiopulmonary exercise testing. Associations between baFMD at SHIP-START-2 and HF incidence at SHIP-START-3 were evaluated using a multivariable logistic regression model adjusted for traditional cardiovascular risk factors and baseline brachial artery diameter. Results Over a median follow-up period of 4.9 (4.1–5.5) years, 118 participants from the SHIP-START-2 cohort developed HF, having significantly lower baseline baFMD values than those who remained HF-free (n=980) at SHIP-START-3 (4.79 ± 4.06% vs. 5.71 ± 3.81%, p = 0.01, respectively). In adjusted analyses, higher baFMD values were independently associated with a reduced risk of incident HF. Specifically, each 1 mm increase in absolute baFMD diameter corresponded to 85% lower odds of developing HF (adjusted OR 0.14; 95% CI 0.03–0.76; p = 0.02, Figure 1). Interestingly enough, we found no significant association between baFMD values and prevalent HF in the SHIP-START-2 cohort (Figure 2). Conclusions In this population-based cohort, a systemic ED at baseline was independently associated with an increased risk of developing symptomatic HF over five years of follow-up, but not with the clinically manifesting prevalent HF in a cross-sectional analysis. These findings support the hypothesis that overt HF is preceded by early vascular ageing, which may contribute to its pathogenesis through maladaptive ventricular–vascular coupling and impaired myocardial perfusion. In contrast, in established HF, the role of ED may be overshadowed by advanced cardiac structural and neurohormonal alterations, disease heterogeneity, and pharmacological treatment effects.Figure 1Figure 2