Sex differences in the association of late-life blood pressure decline with postmortem brain vessel pathology

Although hypertension is the leading modifiable risk factor for cerebrovascular disease, less is known about the relation of late-life change in blood pressure (BP) and cerebrovascular pathology beyond brain infarcts. Our previous work found sex-specific associations between declining systolic BP (SBP) and cognitive decline in late-life, suggesting that cerebrovascular pathology may be an upstream contributor to these sex differences. However, postmortem studies have not examined whether BP change differentially relates to vascular brain pathology in men and women, despite well-established sex differences in BP trajectories and cerebrovascular pathology. We examined associations between change in late-life BP and postmortem cerebrovascular (arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy) pathology from 2033 community-dwelling older adults (mean baseline age = 79.7 [SD = 7.1] years; 69% women) from four longitudinal cohort studies with brain autopsy (mean age-at-death = 89.8 [6.6] years). Person-specific late-life BP slopes estimated from annual clinical evaluations over an average of 9.1 [5.7] years were entered in ordinal regressions adjusted for age-at-death, sex, antihypertensive medication use, and BP slope × sex, age-at-death × sex, and BP slope × age-at-death interactions. Faster SBP decline was associated with greater severity of arteriolosclerosis (OR = 1.24, 95%CI 1.08–1.42) and atherosclerosis (OR = 1.41, 95%CI 1.22–1.63). A sex × SBP slope interaction ( p = 0.01) revealed a stronger association of SBP decline with arteriolosclerosis severity in women than men. This longitudinal, clinical-pathologic study of older decedents showed sex differences in the association of declining SBP in late-life with severity of arteriolosclerosis, extending prior associations with cognitive decline to cerebrovascular pathology, and suggests potential for longitudinal BP monitoring for precision medicine approaches in cerebrovascular disease risk stratification.