Abstract Body: Background: Ischemic stroke (IS) and hypertension are closely linked cardiovascular conditions, with hypertension being the most significant modifiable risk factor for the development of IS. While stroke-related mortality has been widely studied, the burden of IS mortality with comorbid hypertension remains insufficiently characterized.

Hypothesis: We hypothesized that mortality from IS with comorbid hypertension has increased over the past two decades and varies significantly by sex, race, and geographic region.

Methods: We analyzed national mortality data from the CDC WONDER database for individuals aged >35 years from 2000 to 2020. IS was defined as the underlying cause of death (ICD-10: I63, I69.3) with hypertensive disease (I10–I15) listed as a contributing cause. Age-adjusted mortality rates (AAMRs) per 1,000,000 were calculated. Joinpoint regression was used to evaluate temporal trends and annual percent change (APC).

Results: A total of 61,595 deaths were attributed to IS with comorbid hypertension. AAMRs declined from 20.8 (95% CI, 20.1–21.6) in 2000 to 10.7 (95% CI, 10.2–11.1) in 2012 (APC = –6.9%; p<0.001), followed by a marked increase to 30.3 (95% CI, 29.6–31.1) in 2020 (APC = 16.5%; p<0.001). Cumulatively, females had slightly higher AAMRs than males (16.7 [95% CI, 16.6–16.9] vs. 16.5 [95% CI, 16.3–16.7]). Racial disparities were substantial: African Americans had the highest AAMR (25.7 [95% CI, 25.1–26.3]), followed by White (16.0 [95% CI, 15.9–16.1]), Asian (15.6 [95% CI, 14.9–16.2]), and American Indian (13.4 [95% CI, 11.8–15.0]) populations. AAMRs were highest in micropolitan rural areas (19.1 [95% CI, 18.6–19.5]) and lowest in large fringe metropolitan regions (14.0 [95% CI, 13.7–14.3]). Regionally, the West had the highest AAMR (19.5 [95% CI, 19.2–19.9]), followed by the South (18.7 [95% CI, 18.5–18.9]), the Midwest (16.1 [95% CI, 15.9–16.4]), and the Northeast (12.0 [95% CI, 11.7–12.2]).

Conclusions: While IS mortality with comorbid hypertension declined from 2000 to 2012, the sharp increase observed in subsequent years represents a concerning shift in national trends. This burden disproportionately affects African Americans, rural residents, and those living in the Western and Southern United States. These findings underscore the need for targeted public health and clinical strategies focused on hypertension control, early stroke prevention, and the reduction of disparities across vulnerable, marginalized populations.