Hypertension is associated with better brain health outcomes in older-age asymptomatic carotid disease populations - A Multi-Cohort Study

Background: Blood pressure (BP) management is highly relevant for cardiovascular and brain health outcomes. Although clinical guidelines are trending towards increasingly strict BP control, some discordant results evaluating dementia-related outcomes indicate that more research is needed. Asymptomatic extracranial carotid atherosclerotic disease (aECAD), a hallmark cerebrovascular disease affecting > 10% of those over the age of 60, may represent a key subpopulation unaccounted for in previous studies. Methods: Using our Carotids and Minds prospective study and TriNetX, a US nationwide medical record database, we evaluated the association of hypertension status with dementia-related outcomes in adults ≥ 50 years of age with and without aECAD. We investigated secondary effects of age, systolic BP (SBP) ranges, hypertension medications, cardiovascular outcomes, and treatment of aECAD with carotid endarterectomy (CEA). Results After controlling for relevant confounders, hypertension was significantly associated with higher cognitive scores (β = 0.47, p< .01), lower pTau217 (β= -0.52, p<.01) and lower AD (HR = 0.56 [0.52–0.61]), non-AD dementia (HR = 0.66 [0.63–0.68]), and MCI risk (HR = 0.69 [0.64–0.74]) in patients with aECAD. Effect sizes were moderate to large and congruous across both cohorts, with strongest risk reduction in aECAD patients 81 + years of age. CEA mitigated these protective associations, and significantly higher risk of ADRD was seen in hypertensives without aECAD. Still more, a SBP range of 140–159 mmHg optimized protective effects with no significant increase in major cardiovascular events and death. Conclusion In summary, hypertension is associated with lower risk of dementia-related outcomes in aECAD patients. This promotes the need for future clinical trials focusing on individualized BP goals and addressing cerebrovascular disease. More broadly, these data further highlight cerebrovascular disease as relevant in brain health and aging.