High-Sensitive Troponin T, Natriuretic Peptide, and Cognitive Change

• Type of Material: Article
• Authors: Yashashwi Pokharel, University of Missouri Kansas City; Farah Mouhanna, George Washington University; Andrea L. C. Schneider, Johns Hopkins University; Andreea M. Rawlings, Johns Hopkins University; David S. Knopman, Mayo Clinic; Vijay Nambi, Baylor College of Medicine; Salim S. Virani, Baylor College of Medicine; Ron C. Hoogeveen, Baylor College of Medicine; Alvaro Alonso, Emory University; Gerardo Heiss, University of North Carolina; Josef Coresh, Johns Hopkins University; Thomas Mosley, University of Mississippi; Rebecca Gottesman, Johns Hopkins University; Elizabeth Selvin, Johns Hopkins University; Christie Ballantyne, Baylor College of Medicine; Melinda C. Power, George Washington University
• Language: English
• Date: 2019-07-30
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 The American Geriatrics Society
• Final Published Version (URL): http://dx.doi.org/10.1111/jgs.16092
• Title of Journal or Parent Work: JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
• Volume: 67
• Issue: 11
• Start Page: 2353
• End Page: 2361
• Grant/Funding Information: This work was supported in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I and HHSN268201700005I). Neurocognitive data are collected by the support of the National Heart, Lung, and Blood Institute U01 HL096812, HL096814, HL096899, HL096902, and HL096917, with previous brain magnetic resonance imaging examinations funded by R01‐HL70825. This research was also supported by National Institutes of Health/ National Heart, Lung, and Blood Institute grant R01 HL134320 to Drs. Ballantyne and Selvin.; Dr. Pokharel was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number T32HL110837 and the American Heart Association SWA Summer 2014 Postdoctoral Fellowship Award (15POST23080014).; Dr. Power was supported by the National Institute of Aging R03AG055485 during the period of this work.; Dr. Schneider was supported by the NIH/NINDS through an administrative supplement to award R25NS065729.; Dr. Selvin was supported by NIH/NIDDK grants K24DK106414 and R01DK089174.
• Keywords: BIOMARKERS; N-terminal pro-B-type natriuretic peptide; Gerontology; MIDLIFE; dementia; ATHEROSCLEROSIS RISK; high-sensitivity troponin; cognitive change; HEART-FAILURE; NT-PROBNP; Science & Technology; ALZHEIMERS-DISEASE; INCIDENT DEMENTIA; HYPERTENSION; CARDIOVASCULAR EVENTS; ASSOCIATION; Geriatrics & Gerontology; Life Sciences & Biomedicine
• Research Categories: Gerontology

Abstract

OBJECTIVES: Cardiac troponin T, measured using a high-sensitive assay (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased stroke risk and perhaps with cognitive decline. However, few well-designed prospective studies with extended follow-up have been conducted. We aimed to estimate the association of hs-cTnT and NT-proBNP with 15-year cognitive change in the Atherosclerosis Risk in Communities (ARIC) study. DESIGN: Prospective cohort study. SETTING: Four US communities. PARTICIPANTS: A total of 9114 and 9108 participants from the Atherosclerosis Risk in Communities study for analyses of hs-cTnT and NT-proBNP, respectively. MEASUREMENTS: We examined association of hs-cTnT and NT-proBNP with 15-year change (1996-1998 to 2011-2013) in three cognitive tests of executive function (Digit Symbol Substitution Test), verbal learning memory (Delayed Word Recall Test), and semantic fluency (Word Fluency Test), and an overall score combining the three tests using multivariable linear mixed effect models. We conducted several sensitivity analyses including multiple imputations to address bias due to missing data and attrition, and we compared associations within groups combining hs-cTnT and NT-proBNP into a three-level categorical variable. RESULTS: At baseline (1996-1998), mean age was 63.4 (standard deviation [SD] = 5.7) years; 56.4% were women, and 17.5% were black. The hs-cTnT at baseline was not associated with cognitive change in any measure. Some evidence indicated accelerated decline in verbal learning and memory when comparing those in the highest with the lowest NT-proBNP quintiles; however, this association was not replicated when considering clinically relevant cutoffs or deciles of exposure in survivors. Sensitivity analyses were consistent with our primary analyses. There was little evidence to support effect modification by any considered factors. People with highest levels of both biomarkers had excessive decline in global z scores vs people with lowest levels (−.34; 95% confidence interval = −.63 to −.04). CONCLUSION: Markers of myocardial injury and stretch were not associated with cognitive decline following 15 years among survivors, but when combined together they were suggestive in post hoc analysis. Whether this represents targets of intervention should be examined in the future.