National trends in cardiovascular deaths with concurrent accidental drug poisoning coding in the United States: a 22-year analysis of the CDC WONDER database (1999–2020)

While the overdose epidemic garners significant public health attention, cardiovascular deaths with concurrent accidental drug poisoning coding remain understudied in the United States.Traditional drug mortality surveillance primarily focuses on direct overdose fatalities, with limited integration of modern CDC-aligned multi-cause coding frameworks and atherosclerotic cardiovascular disease (ASCVD) cardiotoxicity mechanisms.We examined national trends in this phenomenon from 1999 to 2020. We analyzed CDC WONDER data, identifying deaths where cardiovascular disease (ICD-10: I00-I99) was the underlying cause and accidental drug poisoning (ICD-10: X40-X44) was documented as a contributory cause on death certificates. Age-adjusted mortality rates (AAMR) were calculated, and trends were assessed using Joinpoint regression analysis.This study is explicitly framed as an ecological population-level surveillance analysis of death certificate co-coding patterns, rather than an assessment of individual-level drug user cardiovascular mortality risk, given the inherent general-population denominator limitation of CDC WONDER aggregate data. We identified 33,536 deaths nationwide meeting these criteria. The AAMR nearly doubled from 0.500 to 0.979 per 100,000 population (annual percent change: +3.64%, P < 0.001). Three distinct phases emerged: rapid increase (1999–2003, + 9.746%, P < 0.001), plateau (2003–2014, + 0.843%, P = 0.188), and second increase (2014–2020, + 4.887%, P < 0.001). Significant disparities existed: mortality was 2.48 times higher in men than women, and highest among non-Hispanic Black individuals (AAMR = 1.451, 2.25 times that of non-Hispanic Whites). The West region had the highest regional mortality (AAMR = 1.165), with Nevada recording the highest state-level rate (AAMR = 3.341). Middle-aged adults(45–64 years) accounted for 60.02% of all deaths. Cardiovascular deaths with concurrent drug poisoning coding rose significantly from 1999 to 2020 in the United States, with the age-adjusted mortality rate (AAMR) increasing from 0.50 to 0.98 per 100,000 population. The trend followed three phases: a rapid rise from 1999 to 2003, a period of relative stabilization from 2003 to 2014, and another rapid increase from 2014 to 2020. Disparities were substantial and uneven: in 2020, mortality in men was approximately 2.5 times higher than in women; the highest AAMR was among non-Hispanic Black or African American individuals, and the West region carried a significantly higher risk than other regions; the 45–64 age group had the highest mortality rate, while the 25–44 age group showed a fluctuating pattern. These findings underscore the need for strengthened cardiovascular assessment and monitoring within substance-use-disorder interventions and for tailored public health strategies targeting high-risk populations and regions. At the same time, interpretations should consider limitations of death certificate coding, including potential differences in surveillance intensity and misclassification across demographic and geographic groups.All population-level trends reflect coded mortality patterns and cannot be extrapolated to individual drug-user risk, consistent with modern CDC multi-cause surveillance standards.