Epidemiologic Patterns and Disparities in Cardiovascular Deaths Associated With Respiratory Failure Across Two Decades in the U.S

Background Cardiovascular disease (CVD) remains the leading cause of death worldwide, with its burden in the U.S. continuing to rise despite substantial advances in prevention and care. Respiratory failure (RF) is a frequent terminal event in advanced CVD, yet national patterns and demographic disparities in CVD-related deaths involving RF remain poorly characterized. This study aimed to quantify temporal trends and regional variations in CVD mortality with RF as a contributing cause from 1999 to 2020. Methods We obtained U.S. death certificate data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database (1999–2020). Deaths were identified using ICD-10 codes I00–I99 for CVD as the underlying cause and J96.0–J96.1, J96.9 for RF as a contributing cause. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 population using the 2000 U.S. standard population. Joinpoint regression analysis was applied to estimate annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs) across sex, ethnicity, census regions, urbanization, and state categories. Results From 1999 to 2020, the national AAMR for CVD-related deaths with RF increased markedly. In males, AAMR rose from 22.9 (95% CI, 22.5–23.3) to 32.9 (95% CI, 32.6–33.3) with an AAPC of 1.71% (95% CI, 1.37–2.05); in females, from 17.3 (95% CI, 17.1–17.6) to 24.5 (95% CI, 24.2–24.7) with an AAPC of 1.56% (95% CI, 0.83–2.29). Non-Hispanic Black adults consistently exhibited the highest mortality, whereas nonmetropolitan areas showed a steeper rise (AAPC, 2.67%; 95% CI, 2.27–3.08) than metropolitan regions (AAPC, 1.50%; 95% CI, 0.88–2.11). All four census regions demonstrated upward trends, with the Midwest showing the greatest increase (AAPC, 2.40%; 95% CI, 1.92–2.89). State-level analysis revealed pronounced geographic heterogeneity, with Idaho showing the largest rise in AAMR (AAPC, 7.44%; 95% CI, 2.17–12.98). Multiple joinpoints indicated distinct inflection periods, particularly after 2010, corresponding to accelerated increases across several subgroups. Conclusion Between 1999 and 2020, CVD-related mortality with RF as a contributing cause increased substantially across the U.S., with notable disparities by sex, ethnicity, geography, and urbanization. These findings underscore the growing intersection between cardiovascular and respiratory diseases and highlight the need for integrated prevention and management strategies targeting high-risk populations and regions.