Cardiovascular–kidney–metabolic syndrome stage modifies the efficacy of intensive blood pressure control on cognitive outcomes: A post hoc analysis of SPRINT MIND

INTRODUCTION: Whether cardiovascular-kidney-metabolic (CKM) syndrome stage modifies cognitive benefits of intensive blood pressure (BP) control remains unclear. METHODS: This post hoc analysis of ‌Systolic Blood Pressure Intervention Trial - Memory and Cognition in Decreased Hypertension (SPRINT MIND) classified participants into non-advanced CKM (Stage 2, n = 5,632) and advanced CKM (Stages 3-4, n = 2,931). The primary outcome was probable dementia; secondary outcomes included mild cognitive impairment (MCI) and probable dementia or MCI composite. Treatment effects were evaluated using Cox models and generalized linear models. RESULTS: In non-advanced CKM, intensive BP control reduced risks of probable dementia (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.46-0.85) and composite outcome (HR 0.74, 95% CI 0.62-0.89). No benefit was observed in advanced CKM (probable dementia: HR 1.15; composite: HR 0.97). Significant interactions between treatment and CKM stage were observed for probable dementia (p = 0.009). CONCLUSION: Among patients with hypertension and non-advanced CKM syndrome, intensive BP control was associated with lower risk of probable dementia, whereas no such benefit was observed in advanced CKM (see Graphical Abstract).