Cerebral Small Vessel Disease Mediates the Effect of Arterial Stiffness on Cognitive Decline in Patients With Heart Failure With Preserved Ejection Fraction

Objective: Epidemiological data indicate a high prevalence of cognitive dysfunction and dementia risk in patients with heart failure with preserved ejection fraction (HFpEF). However, underlying mechanisms are yet not fully understood. Common risk factors for HFpEF and cognitive decline are hypertension and arterial stiffness, which are characterized by structural and functional vascular changes causing microvascular dysfunction and end organ damages. We hypothesize that the effect of arterial stiffness on cognition in patients with HFpEF is mediated by microvascular brain disease (cerebral small vessel disease, CSVD). Design and method: In this prospective cohort study we included 14 HFpEF patients (age: 66.6 ± 10.0 years) and 11 cognitively normal, healthy controls (age: 69.4 ± 9.4), who underwent comprehensive cardiovascular assessment. Arterial stiffness was assessed with pulse wave velocity measurements. The CERAD-plus neuropsychological test battery was used to estimate cognitive decline. CSVD severity (summary SVD score) was quantified in accordance with the STandards for ReportIng Vascular changes on nEuroimaging criteria (STRIVE) using 3-Tesla brain magnetic resonance imaging. Results: Results: Patients with HFpEF showed increased arterial stiffness [F(1,20) = 7.33, p = .014], impaired cognition [F(1,20) = 33.34, p <.001), and higher CSVD burden [F(1,23) = 32.39, p <.001] in comparison to healthy, age-matched controls, whereas arterial stiffness correlated with cognitive dysfunction (r = -.44, p = .046) and summary SVD scores (r = .71, p = .0002). Moreover, summary SVD scores fully mediated the relationship of arterial stiffness and cognition (Figure 1). Conclusions: We showed that CSVD mediates the effect of arterial stiffness on cognition in patients with HFpEF. Our study demonstrated the fundamental role of cardiovascular factors in the development of cognitive decline, and the urgent need for interdisciplinary heart-brain research investigating the interrelationship of heart and brain diseases. Figure 1: Mediation Analysis. CSVD burden (summary SVD scores) fully mediated the relation between arterial stiffness (pulse wave velocity) and cognitive decline (assessed with CERAD-plus). Age was included as covariate into the model. Significant paths are marked with ∗∗/∗∗∗ for p < .01/.001.