Double burden: Bleeding disorders and their impact on cardiovascular mortality across demographics and geography in the United States, 1999–2020

Abstract

Abstract Background: Bleeding disorders, though classically linked to hemorrhagic complications, also influence cardiovascular disease (CVD) outcomes due to altered hemostatic balance, treatment effects, and comorbid risk factors. Despite this interplay, population-level trends for CVD mortality with bleeding disorders as underlying or multiple causes of death remain underexplored. Methods: This study utilized mortality data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple Cause of Death database for the years 1999 through 2020. Death records in which a bleeding disorder (ICD-10 codes D65–D69) was listed as a multiple cause of death (MCD) in combination with cardiovascular disease (ICD-10 codes I00–I99) were included. Data were extracted as annual death counts and corresponding population denominators, stratified by census region, state, 2013 NCHS urban–rural classification, sex, race, Hispanic origin, and ten-year age groups. Result: From 1999 to 2020, cardiovascular-related mortality involving bleeding disorders in the United States increased at an overall annual percent change (APC) of +0.78%. When examined by census region, the sharpest rise occurred in the West (+3.03% per year), followed by the South (+1.45%) and Midwest (+0.81%), while the Northeast demonstrated a slight decline (–0.11%). At the state level, Minnesota (+5.43%), Washington (+6.22%), and Arizona (+6.10%) recorded the highest APCs, suggesting a steep rise in deaths involving bleeding disorders and cardiovascular conditions. In contrast, states like Vermont (–3.75%), Michigan (–1.62%), and Alabama (–1.23%) showed a marked reduction over the same period. Notably, several states such as Wyoming and Alaska lacked sufficient data for trend calculation. Urbanization-wise, the steepest increases occurred in Small Metro areas (+2.15%) and Medium Metro areas (+2.04%), while Large Central Metros showed the slowest increase (+0.70%). These trends suggest a growing burden outside major urban hubs. Sex-specific trends revealed a sharper rise among males (+1.95%) compared to females (+0.76%). Racial analysis showed the highest APC among American Indian or Alaska Native populations (+3.93%), followed closely by Asian or Pacific Islanders (+3.61%), White (+1.29%), and Black or African American (+1.14%). Hispanic-origin analysis showed an even more pronounced rise: Hispanic or Latino populations had an APC of +4.47%, compared to +1.14% in non-Hispanic individuals. Data listed as Not Stated had an extremely high APC of +8.45%, likely due to misclassification or reporting inconsistencies. When stratified by age, the highest APC was seen in the 25–34 years group (+3.58%), followed by 55–64 years (+3.20%) and 35–44 years (+2.30%). While individuals aged 75–84 years showed a modest decline (–0.35%). Conclusion: Cardiovascular mortality with bleeding disorders as contributing or underlying causes has risen modestly over the past two decades, with disproportionate increases in the West, among Hispanic and American Indian or Alaska Native populations, and in younger adults. The widening geographic and demographic gradients underscore the persistence of structural and access-related inequities in care. Targeted strategies that integrate specialized hematology expertise into cardiovascular prevention and management, with a focus on high-risk populations and underserved regions, are essential to reverse these trends.