Plasma Total‐Tau is Related to Risk of Heart Failure in the Community

Abstract

AbstractBackgroundTau is mainly expressed in the neurons of the central nervous system, with elevated cerebrospinal fluid and plasma levels noted when pathologic extracellular aggregation of tau occurs in the setting of neurodegeneration. Plasma tau and phosphorylated tau species are currently being studied as biomarkers for diagnosis, prognosis, or to measure susceptibility risk for conditions such as Alzheimer’s disease. However, the potential for circulating tau protein or other toxic entities upstream or along the tau pathway to cause cardiac dysfunction via protein misfolding or abnormal aggregation has only received limited study.MethodsWe evaluated the association of plasma total‐tau and risk of congestive heart failure in a community‐based sample from the prospective Framingham Heart Study. Adult participants free from clinical heart failure at time of blood sample (Exam 8, 2005‐2008) were included. Participants with renal failure or on dialysis were excluded. Plasma total‐tau was measured using the Simoa platform. Total‐tau plasma values were natural log‐transformed to approximate a normal distribution. Using Cox regression models, total‐tau was related to incident congestive heart failure (up to 2019), adjusting for age and sex (Model 1) and additionally adjusting for cardiovascular risk factors: systolic blood pressure, prevalent diabetes, antihypertensive medication use, smoking status, total cholesterol‐to‐high density lipoprotein ratio, and prevalent atrial fibrillation (Model 2).ResultsWe studied 2792 participants (mean age 67±9 years, 55% women) over a mean follow‐up period of 10.7±3.2 years (Table 1). There were 215 incident cases of heart failure. Each standard deviation unit increase in the log of plasma total‐tau was associated with a 42% increased risk of incident heart failure (95% confidence interval:1.26‐1.61; p<0.0001) in Model 2 (Table 2). Among individuals with plasma total‐tau values in the top quintile compared to the bottom four quintiles, risk for incident heart failure was increased by 69% (1.26‐2.28; p = 0.0005).ConclusionElevated levels of plasma total‐tau at baseline in this community‐based sample were associated with incidence of congestive heart failure. Circulating tau protein, or possibly byproducts of related neurodegenerative pathways, may represent a shared substrate of protein misfolding, in the brain and the heart, resulting in Alzheimer’s disease and heart failure.