Abstract Body (Do not enter title and authors here): Background:
Stroke is the fifth leading cause of mortality in the United States (US), with diverse etiologies. Evidence suggests that cancer is a significant predisposing factor, with studies demonstrating an elevated risk of stroke in cancer patients. However, mortality trends due to concomitant stroke and cancer remain underexplored. Therefore, our study aims to investigate mortality trends attributable to stroke and cancer in the US across demographics and regions.

Methods:
The CDC WONDER multiple cause of death database was used to extract death certificate data for adults aged ≥ 25 years. Age-adjusted mortality rates (AAMR) per 100,000 persons were calculated, and annual trends were determined by calculating annual percent change (APC) and the average APC (AAPC) in AAMR using Joinpoint regression analysis.

Results:
From 1999 to 2023, a total of 538,858 stroke and cancer-related deaths were recorded in the US. The AAMR decreased from 1999 to 2009 (APC: -3.76, 95% CI: -4.90 to -3.06) and then till 2014 (APC: -2.36, 95% CI: -3.98 to -0.97), followed by a stable trend till 2018 (APC: 0.85, 95% CI: -1.36 to 2.21). Subsequently, the AAMR surged between 2018 and 2021 (APC: 7.86, 6.29 to 9.10) and then a stable disease period was observed till 2023 (APC:0.72, 95% CI: -1.20 to 2.60). Males had higher AAMRs than females. Non-Hispanic (NH) Black or African Americans displayed the highest AAMR, followed by NH White, other NH populations, and Hispanic or Latino group. Midwest region reported the highest AAMR while Northeast reported the lowest. Rural areas exhibited a higher AAMR (11.09, 95% CI: 11.01 to 11.16) than urban areas (AAMR: 9.2, 95% CI: 9.17 to 9.23). When stratified by cancer types, gastrointestinal and lung cancer experienced the highest AAMRs. Upon stratification by stroke subtype, intracerebral hemorrhage had the highest AAMRs during early years of study period; however, ischemic stroke-related AAMR showed the highest increase between 2017 and 2023 (APC: 11.89, 95% CI: 8.14 to 13.82).

Conclusions:
While the overall stroke and cancer-related mortality is decreasing, ischemic stroke-related cancer deaths are on the rise. Highest mortality rates were found in men, NH Black or African Americans, residents of the Midwest region, and rural areas. Our findings underscore the critical need for early cardiovascular care for cancer patients. Furthermore, efforts are needed to improve equitable access to healthcare for socioeconomically disadvantaged populations.