High-Sensitivity Troponin T, NT-proBNP, and Cognitive Outcomes in SPRINT

Abstract

Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.

Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.

Results: Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; P_interaction=0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively.

Conclusions: In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar.

Keywords: biomarkers; cognition; dementia; hypertension; natriuretic peptides; troponin T.

Figure 1. Cumulative incidence of mild cognitive impairment or probable dementia stratified by combined cardiac biomarker categories in SPRINT.

Cumulative incidence of the composite outcome of MCI or PD in patients after intensive SBP control in the troponin and natriuretic peptide tertiles. (1) both hs-cTnT and NT-proBNP in the lower two sex-specific tertiles, (2) hs-cTnT or NT-proBNP in the highest sex-specific tertile, (3) both hs-cTnT and NT-proBNP in the highest sex-specific tertile. hs‐cTnT (high‐sensitivity cardiac troponin T); PD (probable dementia); MCI (mild cognitive impairment); NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide).

Figure 2.. Associations of combined cardiac biomarker categories with cognitive outcomes in SPRINT.

Hazard ratios represent subdistribution hazard ratio accounting for the competing risk of death, adjusted for treatment group, age, sex, race/ethnicity, smoking, alcohol use, education level, history of cardiovascular disease, body mass index, estimated glomerular filtration rate, log of urine albumin creatinine ratio, systolic and diastolic blood pressure, low density lipoprotein cholesterol, number of medications at baseline, number of antihypertensive medications at baseline, and baseline scores from the PHQ-9, VR-12 Mental Summary Score, MoCA, and Digit Symbol Coding test. Combined biomarker categories and abbreviations same as in Figure 1.