Plasma amyloid-beta in relation to cardiac function and risk of heart failure in the general population

Abstract

Abstract Background Amyloid-β is a major hallmark of Alzheimer's disease, and its pathology has been hypothesized as a multiple organ syndrome that may also affect cardiac function. There are limited data on association of plasma amyloid-β with cardiac dysfunction and risk of HF in the general population. Objective To determine the association of plasma amyloid-β40 (Aβ40) and amyloid-β42 (Aβ42) with echocardiographic measurements of cardiac dysfunction, and with incident heart failure (HF) in the general population. Methods We included 4156 participants of the population-based cohort (mean age 71.4 years, 57.1% women), who had plasma amyloid-β measured between 2002 and 2005, and were free of dementia and HF at baseline. Multivariable linear regression models were used to explore the associations of plasma Aβ40 and Aβ42 with echocardiographic measures. Participants were followed for the occurrence of HF until December 2016. Cause-specific hazard models were used to assess the association of plasma amyloid-β with incident HF and competing risk event. Models were adjusted for cardiovascular risk factors. Results Higher plasma Aβ40 concentrations were associated with lower left ventricular ejection fraction (β, −0.39; 95% CI, −0.68 to −0.10) and larger left ventricular mass (β, 0.70; 95% CI, 0.06 to 1.34). Aβ42 was not significantly associated with echocardiographic measures cross-sectionally. During follow-up (median 10.2 years), 472 incident HF cases were identified. Higher plasma Aβ40 was associated with an increased risk of incident HF (HR, 1.32; 95% CI, 1.15 to 1.51), more profound in men than in women (P value for interaction: 0.022). One SD increase in Aβ40 was associated with a 31% increase in the hazard of HF in men (HR, 1.32; 95% CI, 1.14 to 1.54) but the association was not significant in women (HR, 1.06; 95% CI, 0.93 to 1.20). Higher plasma Aβ42 concentrations were associated with increased risk of HF (HR, 1.12; 95% CI, 1.02 to 1.24), while further adjustment for concomitant Aβ40 attenuated this association (HR, 1.03; 95% CI, 0.92 to 1.16). Conclusion Higher levels of plasma Aβ40 were independently associated with worse cardiac function and higher risk of new-onset HF in the general population, in particular among men. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Netherlands Organization for Health Research and Development (ZonMw); the Dutch Heart Foundation;This study is further funded by the European Union's Horizon 2020 research and innovation programme as part of the Common mechanisms and pathways in Stroke and Alzheimer's disease (CoSTREAM) project.