High circulating adropin levels predict long-term blood pressure variability in old adults: evidence from the Multidomain Alzheimer Prevention Trial

Abstract

Hypertension and elevated visit-to-visit variability in blood pressure (BP) increase the lifetime risk of cardiovascular, kidney, and neuro-degenerative diseases. Adropin, a hepatokine with autocrine/paracrine actions, contributes to cardiometabolic cross talk and mediates cellular stress responses across metabolic and cardiovascular tissues. Human cross-sectional and exercise studies suggest links between adropin, endothelial function, and vascular elasticity. Whether circulating adropin levels reflect risk of poor BP control remains unclear. We examined relationships between plasma adropin concentrations, BP, and visit-to-visit BP variability in older, com-munity-dwelling participants from the Multidomain Alzheimer Prevention Trial (MAPT: n = 443; means ± SD age, 75.9 ± 4.5 yr; 60% female). BP and heart rate while in the supine position were assessed every 6 mo for 5 yr (8.1 ± 1.3 measurements/participant).Multivariate regression modeling revealed a positive association between adropin and variation independent of the mean (VIM) in sys-tolic BP (R = 0.329, F7,429 = 7.454, P < 0.001). Predictors included adropin (b = 0.165, P < 0.001), age (b = 0.146, P < 0.005), sex (male = 1, female = 0; b = —0.130, P = 0.005), and antihypertensive medication use (yes = 1, no = 0; b = 0.188, P < 0.001). Stratification by medication use suggested that the association between adropin and systolic BP VIM is confined to participants on antihypertensive therapy (R = 0.347, F6,188 = 4.302, P < 0.001; adropin, b = 0.233, P = 0.001). However, analysis by grouping participants in tertiles ranked by adropin or systolic BP VIM suggests that, although the relationship is notably weaker, it is not absent for participants not on antihypertensive medications. In conclusion, elevated plasma adropin concentrations associate with systolic BP variability in older adults with hypertension. These findings identify adropin as a potential biomarker of poor BP control. NEW & NOTEWORTHY This study identifies circulating levels of the hepatokine adropin as a novel biomarker of blood pressure (BP) variability in older adults. Using longitudinal data from the Multidomain Alzheimer Prevention Trial, we show that higher adropin levels predict greater systolic BP variability, particularly in participants receiving antihypertensive therapy. These findings link a hepatokine with cardiovascular risk and suggest that adropin measurement may improve stratification of individuals at risk for poor BP control and treatment resistance.