A cross-sectional analysis of liver disease-hypertension comorbid mortality trends in the United States, 1999-2023.

Background: The co-listing of liver disease and hypertension (HTN) codes on U.S. death certificates is a documentation pattern that may reflect changing clinical recognition, certification practices, or underlying disease burden; however, these explanations cannot be distinguished from death certificate data alone. Understanding co-listing patterns may help identify populations warranting further clinical and epidemiological investigation. This study analyzed 25 years of U.S. mortality data to characterize temporal, demographic, and geographic patterns in deaths due to both conditions. Methods: We conducted a population-based cross-sectional analysis of CDC WONDER multiple cause-of-death data (1999-2023) for adults aged ≥25 years. Deaths listing both liver disease (ICD-10: K70-K76) and HTN (I10-I15) were identified. Age-adjusted mortality rates (AAMRs) per 100 000 people were standardized to the 2000 U.S. population. Temporal trends were assessed using Joinpoint regression with annual percent changes (APCs). Analyses were stratified by sex, race/ethnicity, region, urbanization, and place of death. Sensitivity analyses using four alternative certificate definitions, including underlying-cause-only and co-listed definitions, were conducted to assess robustness to cause-of-death coding choices. Results: Between 1999 and 2023, 208 666 deaths listed both conditions, increasing from 2307 to 18 769 annually. The national AAMR increased from 1.30 to 6.75 per 100 000 (average APC: +6.71%, 95% CI: 5.64-7.80). Joinpoint regression identified four phases: rapid early growth (1999-2001, APC +19.50%), steady increase (2001-2018, APC +4.27%), substantial increase (2018-2021, APC +17.64%), and stabilization (2021-2023, APC +0.28%). Males showed higher rates than females (9.02 vs 4.71 per 100 000 in 2023). Non-Hispanic American Indian/Alaska Native populations showed the highest rates (12.74 per 100 000), followed by Hispanic (8.15), non-Hispanic White (6.95), and non-Hispanic Black (6.84) populations. Geographic variation ranged from 2.87 (Connecticut) to 21.54 (Oklahoma) per 100 000. Sensitivity analyses confirmed that increasing trends were robust to the choice of cause definition, although the post-2021 trajectory was definition-sensitive. Conclusion: The number of deaths listed with both liver disease and hypertension codes increased substantially over 25 years, with notable acceleration during 2018-2021 that coincided temporally with the COVID-19 pandemic; however, causal attribution cannot be made from death certificate data. Because the findings reflect death certificate documentation rather than validated clinical comorbidity, they should be interpreted as surveillance indicators identifying demographic and geographic patterns that warrant further investigation through clinical registries and prospective study designs.