Abstract 4144426: How does intensive blood pressure control reduce the risk of cardiovascular disease events? A biomarker-based mediation analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)

Introduction: Intensive blood pressure (BP) control is associated with a significant reduction in the risk of heart failure (HF) or all-cause death. However, the extent to which intensive BP control-associated HF risk reduction is mediated by changes in subclinical markers of cardiovascular (CV) disease (CVD) and stage B HF is not well-characterized. Methods: Participants of the Systolic Blood Pressure Intervention Trial (SPRINT) with hypertension and available data on subclinical CVD markers at baseline and follow-up (1- or 2-year visit) were included. The key subclinical markers of CVD analyzed included chronic myocardial injury (assessed by high-sensitivity cardiac troponin I [hs-cTnI]), neurohormonal stress (assessed by N-terminal pro-B-type natriuretic peptide [NT-proBNP]), left ventricular (LV) mass (assessed by electrocardiogram Cornell voltage [CV]), and arterial stiffness (assessed by estimated pulse wave velocity [ePWV]). A counterfactual framework was used to assess the effects of the exposure and mediator on key outcomes, including 1) HF / all-cause death; 2) atherosclerotic CVD (ASCVD), including nonfatal myocardial infarction, nonfatal stroke, or CV death. Results: The present study included 8,872 participants (35% women, 31% Black). Over the 3.3-year median follow-up, there were 333 (3.8%) HF / all-cause death events and 200 (2.3%) ASCVD events. Reductions in neurohormonal stress and LV mass mediated up to 15% of the reduction in risk of HF / all-cause death with intensive BP control ( Table ). In contrast, treatment-related changes in chronic myocardial injury and arterial stiffness did not mediate the benefits of intensive BP reduction on HF / all-cause death risk. Furthermore, changes in any subclinical CVD markers did not mediate the effect of intensive BP control on ASCVD risk ( Table ). Conclusions: In this post-hoc analysis of SPRINT, improvements in neurohormonal stress and LV mass, as identified by surrogate markers of hs-cTnI and CV, were important mediators of the beneficial effects of intensive BP control in reducing the risk of HF / all-cause death. Mediators of the effect of intensive vs. standard BP control for reducing HF / all-cause death differ from those for ASCVD.