ArticleFrontiers in medicine2026
Trends, disparities, and forecasts of peripheral artery disease- and sepsis-associated mortality in the United States, 1999-2023.
Article in Frontiers in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Peripheral artery disease (PAD) and sepsis may co-occur as a high-risk mortality phenotype, yet U.S. surveillance has largely assessed them separately. We examined long-term trends, disparities, geographic heterogeneity, and near-term forecasts for mortality with concurrent documentation of PAD and sepsis in the United States. Methods: We conducted a retrospective, population-based mortality study using CDC WONDER Multiple Cause-of-Death data (1999-2023) among adults aged ≥45 years. PAD-sepsis-associated deaths were defined by co-listing of PAD (ICD-10 I70.2, I73.9) and sepsis (A40.0-A40.3, A40.8-A40.9, A41.0-A41.5, A41.8-A41.9) anywhere on the death certificate. We estimated annual age-adjusted mortality rates (AAMRs) per 100,000, assessed trends with joinpoint regression, and evaluated disparities by sex, age, race/ethnicity, Census region, and rural-large metropolitan status (rate ratio [RR], rate difference [RD]). Forecasts for 2024-2033 used ARIMA, ARIMAX with a prespecified COVID-19 pulse (2020-2021), and a 2010-2023 joinpoint-aware ARIMA approach. Results: From 1999-2023, 101,369 deaths met criteria; the period-average AAMR was 3.28 (95% CI, 3.26-3.30). AAMR declined from 4.46 (1999) to 3.06 (2023), with a nadir in 2019 (2.91), a transient increase in 2020-2021 (3.15-3.22), and attenuation in 2022-2023. Mortality was higher in males than females (period-average AAMR 3.96 vs. 2.76). Rates increased with age; crude mortality declined in adults aged ≥85 years (34.59 in 1999 to 16.90 in 2023; AAPC -3.20%/year) but increased in ages 45-54 (0.35 to 0.44; AAPC +0.91%/year). Rural-large metropolitan disparities emerged after 2010 (2010-2019 mean RR 1.21) and peaked in 2018 (RR 1.37). NH Black individuals had the highest burden (period-average AAMR 6.48 vs. 3.02 in NH White) but declined from 11.16 (1999) to 5.74 (2023; AAPC -2.84%/year). Forecasts for 2024-2033 suggested no rapid escalation (ARIMA: 3.05 to 2.95; ARIMAX: 3.06 to 3.09; 2010-2023 joinpoint-aware approach: 3.12 to 3.23). Conclusions: PAD-sepsis-associated mortality declined overall with a transient increase during 2020-2021, while inequities persisted, including sustained rural excess after 2010 and an unfavorable trajectory in adults aged 45-54 years. Projections through 2033 indicated relative stability, supporting continued surveillance and integrated prevention and care strategies.
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