Cardiac Biomarkers, Subclinical Brain Vascular Changes, and Cognitive Decline: Post Hoc Analysis of the SPRINT Trial

Abstract Background The association between subclinical cardiovascular disease (CVD) and cognitive decline in hypertensive adults and the underlying brain pathologies remain unclear. It is also undetermined whether intensifying blood pressure (BP) treatment slows down cognitive decline associated with subclinical CVD. Methods We conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial. Subclinical CVD at baseline was identified by elevated levels of high-sensitivity cardiac troponin T (hs-cTnT≥14 ng/L) and N-terminal pro-B-type natriuretic peptide (NT-proBNP≥125 pg/mL). Global cognitive function and domain-specific measures (memory, processing speed, language, and executive function) were assessed at baseline and follow-up (years 2, 4, and 6) in 2733 participants. White matter lesions, cerebral blood flow, and brain tissue volume were assessed by MRI at baseline and years 4 in a subset of 639 participants. Results Both elevated hs-cTnT and NT-proBNP levels at baseline were associated with accelerated cognitive decline across all domains after adjusting for potential confounding factors. The group with elevated levels of both cardiac biomarkers showed the fastest decline, with a larger annual decline rate of 0.033 (95% CI: 0.024-0.041) in the z-score of global cognitive function compared to the group with normal levels. Elevated levels of both biomarkers were also associated with a faster progression in white matter lesions, but not with changes in total brain tissue volume or cerebral blood flow. Intensive BP treatment did not attenuate these associations compared to standard treatment. Conclusions Subclinical CVD may contribute to faster white matter lesion progression and accelerated cognitive decline in patients with hypertension, regardless of intensive BP treatment.