Abstract Body: Purpose: While hypercholesterolemia is a well-established risk factor for cardiovascular mortality in diabetes,
national trends in diabetes-related mortality specifically within this comorbid population are poorly defined. This
study aimed to quantify trends in diabetes-related mortality among U.S.adults with hypercholesterolemia over two
decades.

Methods:
We performed a retrospective longitudinal analysis using mortality data from the CDC WONDER database. Death certificates for adults aged ≥25 years from 1999–2020 were included if they listed hypercholesterolemia as a contributing factor and diabetes mellitus as the underlying cause of death. Age-adjusted mortality rates (AAMR per 100,000)were calculated. Trends were analyzed using joinpoint regression to compute
the annual percent change(APC) and average annual percent change (AAPC),identifying significant temporal shifts.

Results:
From 1999 to 2020, there were an estimated 450,000 deaths meeting the criteria. The overall AAMR exhibited a biphasic trend, rising significantly by an APC of 2.1%(95% CI: 1.7, 2.5) to a peak in 2006, followed by sustained decline with an APC of -1.8%(95% CI: -2.0, -1.6) through 2020. The overall AAPC for 1999-2020 was -0.9% (95% CI:-1.1, -0.7). Significant demographic disparities were observed; for instance, the rate of decline was slowest among Non-Hispanic Black individuals(AAPC: -0.4%) and residents of the Midwest census region(AAPC: -
0.6%).

Conclusion:
Despite an overall decline since 1999, the reversal from an increasing mortality trend after 2006 and the persistent demographic inequities underscore an unfinished public health agenda. Targeted interventions to improve the integrated management of diabetes and hypercholesterolemia are crucial, especially in populations experiencing a slower decline in mortality.