Yashashwi Pokharel1, Farah Mouhanna2,3, Andrea L C Schneider4, Andreea M Rawlings5, David S Knopman6, Vijay Nambi7,8,9, Salim S Virani7,8,9, Ron C Hoogeveen7, Alvaro Alonso10, Gerardo Heiss11, Josef Coresh5, Thomas Mosley12, Rebecca Gottesman4,5, Elizabeth Selvin5, Christie Ballantyne7,8, Melinda C Power2. 1. Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri. 2. Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, District of Columbia. 3. Department of Behavioral Sciences and Health Education, Rollins School of Public Health, Emory University, Atlanta, Georgia. 4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 5. Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland. 6. Department of Neurology, Mayo Clinic, Rochester, Minnesota. 7. Department of Medicine, Section of Cardiovascular Research, Baylor College of Medicine, Houston, Texas. 8. Center for Cardiovascular Disease Prevention, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas. 9. Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. 10. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia. 11. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina. 12. Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
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. J Am Geriatr Soc 67:2353-2361, 2019.
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. J Am Geriatr Soc 67:2353-2361, 2019.
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