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. 2026 Jan 30;39(3):388–395. doi: 10.1080/08998280.2026.2620340

National mortality trends in mood affective disorders and hypertensive/ischemic heart diseases in the United States, 1999 to 2020: a CDC WONDER analysis

Muhammad Hamza Dawood a,✉, Ravi Kumar b, Mohammad Shahid Aman a, Syed Muhammad Hameez Qadri c, Lama Qadri d
PMCID: PMC13174849  PMID: 42148006

Abstract

Objective

This study assessed demographic and geographic trends in mortality linked to mood affective disorders (MAD) and hypertensive/ischemic heart diseases (HHD/IHD) in the United States.

Methods

Death certificate data from CDC WONDER (1999–2020) were analyzed to identify individuals (≥15 years) with MAD and HHD/IHD listed as underlying or contributing causes of death. Age-adjusted mortality rates (AAMRs) per 100,000 and annual percent change (APC) were calculated by year, sex, race/ethnicity, and region.

Results

From 1999 to 2020, 198,332 MAD–HHD/IHD–related deaths were recorded. The overall AAMR rose from 2.53 in 1999 to 5.05 in 2020. Women had consistently higher AAMRs than men (2.65 vs 2.30 in 1999; 5.36 vs 4.53 in 2020). Non-Hispanic Whites had the highest AAMR (3.57), followed by American Indian/Alaska Natives (2.31). North Dakota (7.51) and the Midwest (4.45) recorded the highest regional rates. Nonmetropolitan areas (6.73) showed higher mortality than metropolitan ones (3.29).

Conclusion

MAD–HHD/IHD mortality has steadily increased, with notable sex, racial, and geographic disparities, highlighting the need for targeted preventive strategies, such as improved mental health screening, cardiovascular risk assessment, and integrated care, as well as policy measures aimed at expanding access to mental health and cardiovascular services.

Keywords: Adult, CDC WONDER, hypertensive diseases, ischemic heart diseases, mood affective disorders, mortality trends

Mood affective disorder (MAD), among psychiatric disorders, represents a significant public health challenge, profoundly impacting morbidity, mortality, and healthcare financial burden.1,2 This has been particularly concerning in the United States, in part due to its substantial and ethnically diverse population. Approximately 57.8 million adults in the US (22.8%) were reported to have a psychiatric disorder in 2021,3 a significant increase from 43.6 million adults (18.1%) less than a decade earlier in 2014.4 MAD, including major depressive disorders, anxiety disorders, and bipolar disorders, constitutes a significant portion due to their high prevalence and substantial impact on individuals’ daily routines. According to the National Institute of Mental Health, in 2021 approximately 8.3% of US adults experienced major depressive episodes, affecting an estimated 21 million individuals.3 An estimated 2.8% of the US population is affected by bipolar disorders annually, while approximately 19% of US adults experience an anxiety disorder annually.5 Additionally, these disorders are clinically heterogeneous, with distinct symptomatology, natural histories, and therapeutic approaches, particularly within the broad spectrum of anxiety disorders. However, they share several pathophysiological and behavioral mechanisms that are relevant to cardiovascular diseases (CVDs). These include sustained activation of the hypothalamic-pituitary-adrenal (HPA) axis, autonomic dysregulation, systemic inflammatory responses, adverse lifestyle behaviors, and metabolic effects associated with certain psychotropic medications.6–15 Collectively, these shared mechanisms provide a biologically plausible rationale for examining MAD as a unified construct in relation to CVDs.

Over the past decade (2010–2020), the relationship between MAD and CVD has garnered increased attention.6–9 Evidence from both US and international studies has shown that MAD is associated with higher risks of cardiovascular morbidity and mortality, particularly among middle-aged and older adults.6,8–11 These risks arise from a combination of physiological dysregulation (heightened inflammation, neuroendocrine disturbances, and autonomic imbalance), and behavioral factors including reduced physical activity, poor diet, and increased likelihood of substance use, a known contributor to hypertensive heart diseases (HHD) and ischemic heart diseases (IHD).8,9,12,13 Multiple studies in both the US and internationally have demonstrated that individuals with MAD have a higher incidence of HHD and IHD, with an associated increase in mortality rates among middle-aged and older adults.8–15 This is particularly concerning given that, as of 2021, HHD and IHD remain the leading causes of morbidity and mortality in the US, affecting almost half of its middle- to old-aged population.16–18 Despite advancements in the understanding, treatment, and awareness of both MAD and CVD, the mortality rates associated with these conditions remain concerning.10,11,18–23

The intersection of MAD and HHD/IHD presents a critical area for public health intervention, as individuals with these comorbid conditions face a substantially higher risk of mortality.10,11,14 This risk is often compounded by underdiagnosis due to symptom overlap, patient-clinician communication barriers, diagnostic overshadowing, medication side effects, and healthcare access.6,24,25 In recent years, major cardiology and psychiatry guidelines have emphasized the integrated management of MAD and CVD, including routine screening for depression and anxiety in patients with CVD, preferential use of selective serotonin reuptake inhibitors and cognitive behavioral therapy when appropriate, and the selection of psychotropic agents with more favorable cardiovascular risk profiles.7,12,25 While evidence that treating MADs alone directly reduces incident IHD- or HHD-specific events is still evolving, several studies have indicated that effective management of depressive and anxiety symptoms in patients with CVD is associated with better adherence to cardioprotective therapy, improved control of blood pressure and other risk factors, and reduced rehospitalization rates, which may collectively contribute to improved clinical outcomes.10,11,14 Consequently, evaluating the current demographic and regional trends of mortality related to MAD, particularly in the context of HHD and IHD in the US, is warranted to identify populations at highest risk so that timely targeted interventions can be provided. The frequent co-occurrence of these conditions reflects a clinically meaningful interaction, as MAD is consistently associated with poorer cardiovascular prognosis, delayed recognition of cardiac disease, suboptimal risk-factor control, and increased mortality among individuals with HHD and IHD. Therefore, we aimed to evaluate demographic and regional differences of MAD and HHD/IHD-related mortality from 1999 to 2020 within the US.

METHODS

We utilized mortality data sourced from death certificates accessible via the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. Our analysis covered the period from 1999 to 2020, focusing on mortality associated with MAD and HHD/IHD among individuals aged ≥15 years in the US. We employed the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) coding system using the codes of F30–F39 (mood [affective] disorders), I10-15 (hypertensive diseases), and I20-I25 (ischemic heart diseases). These ICD codes have been previously used to identify disorders related to mental health and CVDs in administrative databases.10,11 The dataset encompassed mortality determinants from death certificates across all 50 states and the District of Columbia. Methodologically, we examined the CDC WONDER Multiple Cause-of-Death Public Use records to identify deaths in which both MAD and HHD/IHD were documented on the death certificate, either as the underlying (primary) cause of death or as contributing (secondary) causes, regardless of their ordering. Institutional review board approval was deemed unnecessary as the investigation employed deidentified datasets publicly disseminated by governmental authorities for general research purposes. The study adhered meticulously to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to ensure methodological transparency and comprehensive reporting of findings.26

Two independent authors conducted a systematic collection and analysis of data pertaining to several critical parameters, with validation by a third author. These parameters encompassed population size, year, demographic characteristics, urban-rural classification, and regional delineation. Demographic variables under scrutiny included sex (defined as male and female) and race/ethnicity, which comprised categories such as non-Hispanic (NH) American Indian or Alaska Native, NH Asian or Pacific Islander, NH Black or African American, NH White, and Hispanic or Latino. Urban-rural classification utilized the National Center for Health Statistics scheme, categorizing areas into large central metro, large fringe metro, medium metro, small metro, micropolitan (nonmetro), and non-core (nonmetro) regions.27 Regional divisions were structured according to Northeast, Midwest, South, and West geographical designations based on US Census Bureau criteria.28 It is essential to emphasize that the data utilized in this investigation originated from death certificates obtained through the CDC WONDER database.29

To investigate national trends in MAD and HHD/IHD-related mortality, we computed both crude and age-adjusted mortality rates (AAMRs) per 100,000 population spanning from 1999 to 2020. These rates were stratified by year, sex, race/ethnicity, census region, state and urban-rural status, accompanied by 95% confidence intervals (CI). Crude mortality rates were determined by dividing the number of deaths attributed to MAD and HHD/IHD by the corresponding US population for each year. AAMRs were calculated by standardizing deaths from these causes against the US population in the year 2000.30 To assess annual national trends in MAD and HHD/IHD related mortality, we utilized the Joinpoint Regression Program (Joinpoint V 5.0).31 This tool allowed us to calculate the annual percentage change (APC) in AAMRs with a 95% CI. The Joinpoint Regression Program employs log-linear regression models to identify significant changes in AAMRs over time, thereby aiding in the detection of temporal variations. APC values were classified as increasing or decreasing based on whether the slope of mortality change significantly deviated from zero, as determined through two-tailed t tests. Statistical significance was established at a threshold of P < 0.05.

RESULTS

Annual trends for MAD and HHD/IHD-related AAMR

Between 1999 and 2020, a total of 198,332 deaths attributable to MAD and HHD/IHD were recorded among individuals aged ≥ 15 years (Supplementary Table 1). In 1999, the AAMR for MAD and HHD/IHD-related adult deaths was 2.53, rising to 5.05 in 2020. The overall AAMR showed an increment from 1999 to 2001 (APC: 8.82, 95% CI: 3.04–13.87), followed by a slight incline from 2001 to 2014 (APC: 0.63, CI: −1.61–1.00), and a subsequent incline from 2014 to 2018 (APC: 3.99, CI: 0.92–5.98), followed by a more significant incline until 2020 (APC: 13.30, CI: 8.65–16.82) (Figure 1, Supplementary Tables 2 and 3).

Figure 1.

Figure 1.

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Overall and sex-stratified mood affective disorders and hypertensive/ischemic heart diseases-related age-adjusted mortality rates per 100,000 in individuals ≥15 years in the United States, 1999 to 2020. Men: 1999–2016 annual percentage change (APC), 1.17* (95% CI, 0.68–1.65); 2016–2020 APC, 9.26* (95% CI, 6.61–13.63). Women: 1999–2001 APC, 9.23* (95% CI, 1.74–16.38); 2001–2016 APC, 0.74 (95% CI, −2.03 to 1.20); 2016–2020 APC, 9.26* (95% CI, 6.40–15.48). Overall: 1999–2001 APC, 8.82* (95% CI, 3.04–13.87); 2001–2014 APC, 0.63 (95% CI, −1.61 to 1); 2014–2018 APC, 3.99* (95% CI, 0.92–5.98); 2018–2020 APC, 13.30* (95% CI, 8.65–16.82). *The APC is significantly different from zero at alpha = 0.05.

MAD and HHD/IHD-related AAMR stratified by sex

Throughout the study period, women consistently exhibited higher AAMRs than men (AAMR women: 3.55; 95% CI: 3.45–3.64; men: 2.97; 95% CI: 2.86–3.07). In 1999, the AAMR for women was 2.65 (95% CI: 2.56–2.74), which increased to 3.26 in 2001 (APC: 9.23, CI: 1.74–16.38), followed by a gradual increase to 3.65 in 2016 (APC: 0.74, CI: −2.03–1.20) and then a steeper incline to 5.36 in 2020 (APC: 9.26, CI: 6.40–15.48). Similarly, the AAMR for men in 1999 was 2.30 (95% CI: 2.19–2.41), which increased to 3.14 in 2016 (APC: 1.17; 95% CI: 0.68–1.65), followed by a steeper incline to 4.53 until 2020 (APC: 9.26; 95% CI: 6.61–13.63) (Figure 1, Supplementary Tables 2 and 3).

MAD and HHD/IHD-related AAMR stratified by race/ethnicity

When stratified by race/ethnicity, AAMRs were highest among NH White followed sequentially by NH American Indian or Alaska Native, NH Black or African American, Hispanic or Latino, and NH Asian or Pacific Islander populations (NH White: 3.57; 95% CI: 3.49–3.64; NH American Indian or Alaska Native: 2.31; 95% CI: 1.60–3.19; NH Black or African American: 2.18; 95% CI: 2.00–2.37; Hispanic or Latino: 1.83; 95% CI: 1.62–2.04; NH Asian or Pacific Islander: 1.01; 95% CI: 0.80–1.24). The AAMRs for NH American Indian or Alaska Native demonstrated an incline from 1999 until 2018 (APC: 1.65), followed by a steeper incline until 2020 (APC: 25.97). The AAMRs for NH Asian or Pacific Islander populations exhibited a steeper incline from 1999 to 2005 (APC: 9.61), followed by a slight decline from 2005 to 2016 (APC: −1.85) and then a steeper incline until 2020 (APC: 12.45). The AAMR for NH Black or African American (APC: 2.25) and Hispanic or Latino (APC: 3.43) populations increased from 1999 until 2018 followed by a steeper incline until 2020 (APC: 22.81 and 14.66). The AAMR for the NH White population exhibited a steep incline from 1999 to 2001 (APC: 8.70), followed by a gradual increase from 2001 to 2012 (APC: 0.50), with another incline until 2018 (APC: 3.19), followed by a steeper increment until 2020 (APC: 13.57). Overall, AAMRs for all racial/ethnic groups showed an upward trend until 2020, with the largest increment observed among the NH American Indian or Alaska Native population (APC: 1.65 to 25.97) (Figure 2, Supplementary Tables 2 and 4).

Figure 2.

Figure 2.

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Mood affective disorders and hypertensive/ischemic heart diseases-related age-adjusted mortality rates per 100,000 stratified by race in individuals ≥15 years in the United States, 1999 to 2020. Non-Hispanic (NH) American Indian or Alaska Native: 1999–2018 annual percentage change (APC), 1.65 (95% CI, −3.88 to 3.50); 2018–2020 APC, 25.97* (95% CI, 4.18–40.73). NH Asian or Pacific Islander: 1999–2005 APC, 9.61* (95% CI, 3.13–36.03); 2005–2016 APC −1.85 (95% CI, −11.94 to 0.17); 2016–2020 APC, 12.45* (95% CI, 5.29–27.41). NH Black or African American: 1999–2018 APC, 2.25* (95% CI, 1.37–2.99); 2018–2020 APC, 22.81* (95% CI, 10.80–29.37). NH White: 1999–2001 APC, 8.70* (95% CI, 2.33–15.44); 2001–2012 APC, 0.50 (95% CI, −2.71 to 0.95); 2012–2018 APC, 3.19* (95% CI, 1.33–5.53); 2012–2018 APC, 13.57* (95% CI, 8.90–16.86). Hispanic or Latino: 1999–2018 APC, 3.43* (95% CI, 0.77–4.45); 2018–2020 APC, 14.66* (95% CI, 4.55–20.32). *APC is significantly different from zero at alpha= 0.05.

MAD and HHD/IHD-related AAMR stratified by geographic region

Significant disparities in AAMRs were observed in different states, ranging from 1.11 (95% CI: 1.01–1.22) in Nevada to 7.51 (95% CI: 7.08–7.95) in North Dakota. States ranking in the top 90th percentile included North Dakota, Minnesota, Ohio, Vermont, and Nebraska, exhibiting approximately 6.8 times higher AAMRs compared to those in the bottom 10th percentile states such as Alabama, Utah, District of Columbia, Arizona, and Nevada (Figure 3, Supplementary Table 5). On average, the AAMRs were highest in the Midwest region at 4.45 (95% CI: 4.28–4.62), followed by the West at 3.11 (95% CI: 2.96–3.25). The Northeast and South had the lowest AAMR at 3.00 (95% CI: 2.85–3.14) and 2.96 (95% CI: 2.85–3.07), respectively. The AAMRs in the Northeast region declined from 1999 to 2007 (APC: −1.32), followed by an incline until 2017 (APC: 2.66) and a steeper incline until 2020 (APC: 12.65). The AAMRs in the South region gradually increased from 1999 to 2017 (APC: 2.10), followed by a steeper incline from 2017 to 2020 (APC: 15.33). The AAMRs in the West increased significantly from 1999 to 2003 (APC: 6.84), with a stable period until 2014 (APC: 0.66), followed by a significant rise until 2020 (APC: 4.12). The AAMRs in the Midwest region showed a steeper incline from 1999 to 2002 (APC: 8.81), followed by a period of slight decline until 2013 (APC: −0.93) and then a small increment until 2018 (APC: 2.42), followed by a period of sharp incline until 2020 (APC: 11.50) (Figure 4, Supplementary Tables 2 and 6).

Figure 3.

Figure 3.

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Mood affective disorders and hypertensive/ischemic heart diseases–related age-adjusted mortality rate per 100,000 stratified by state among individuals ≥15 years in the United States, 1999 to 2020.

Figure 4.

Figure 4.

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Mood affective disorders and hypertensive/ischemic heart diseases–related age-adjusted mortality rates per 100,000 stratified by census region in individuals ≥15 years in the United States, 1999 to 2020. Northeast: 1999–2007 annual percentage change (APC), −1.32 (95% CI, −8.73 to 1.14); 2007–2017 APC, 2.66* (95% CI, 0.18–5.58); 2017–2020 APC, 12.65* (95% CI, 6.28–21.48). Midwest: 1999–2002 APC 8.81* (95% CI, 4.53–17.09); 2002–2013 APC, −0.93* (95% CI, −3.61 to −0.24); 2013–2018 APC, 2.42 (95% CI, −0.87 to 4.80); 2018–2020 APC, 11.50* (95% CI, 5.59–15.41). South: 1999–2017 APC, 2.10* (95% CI, 1.62–2.59); 2017–2020 APC, 15.33* (95% CI, 10.51–23.96). West: 1999–2003 APC, 6.84* (95% CI, 3.67–13.49); 2003–2014 APC, 0.66 (95% CI, −1.69 to 1.34); 2014–2020 APC, 4.12* (95% CI, 2.76–6.82). *APC significantly differs from zero at alpha = 0.05.

When analyzing data by urbanization, AAMRs were highest in micropolitan (nonmetro) areas at 4.52 (95% CI: 4.25–4.78), followed closely by noncore (nonmetro) areas at 4.42 (95% CI: 4.13–4.71), small metro areas at 4.04 (95% CI: 3.79–4.29), medium metro areas at 3.55 (95% CI: 3.39–3.71), large fringe metro areas at 2.94 (95% CI: 2.80–3.07), and large central metro areas at 2.63 (95% CI: 2.51–2.75). The AAMRs in micropolitan (nonmetro) exhibited a substantial increment from 1999 to 2001, followed by a gradual increase until 2018 and then a steeper increment until 2020. The AAMRs in noncore (nonmetro) areas exhibited a gradual increase from 1999 until 2018, followed by a steeper incline until 2020. The AAMRs in small metro areas experienced a steeper incline until 2002, followed by a stable period until 2014 and then an increase until 2018, with a steeper incline until 2020. AAMRs in medium metro areas experienced an incline until 2001, followed by a steady period until 2015 and then a steeper incline until 2020. Large central metro and large fringe metro areas experienced a gradual increment with period of stability from 1999 to 2018 and 2016, respectively, followed by a substantial increment until 2020 (Figure 5, Supplementary Tables 2 and 7).

Figure 5.

Figure 5.

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Mood affective disorders and hypertensive/ischemic heart diseases–related related age-adjusted mortality rates per 100,000 stratified by urban/rural classification in individuals ≥15 years in the United States, 1999 to 2020. Large central metro 1999–2018 annual percentage change (APC), 0.68 (95% CI, −0.78 to 1.32); 2018–2020 APC, 14.62* (95% CI, 2.58–20.56). Large fringe metro 1999–2016 APC, 0.33 (95% CI, −0.44 to 1.00); 2016–2020 APC, 10.05* (95% CI, 6.10–19.61). Medium metro: 1999–2001 APC, 7.69* (95% CI, 2.19–11.82); 2001–2015 APC, 0.98* (95% CI, 0.38–1.29); 2015–2020 APC, 9.30* (95% CI, 8.03–11.04). Small metro: 1999–2002 APC, 8.78* (95% CI, 3.87–17.93); 2002–2014 APC, 0.73 (95% CI, −2.42 to 1.37); 2014–2018 APC, 4.69* (95% CI, 0.34–7.05); 2018–2020 APC, 15.46* (95% CI, 9.45–19.88). Micropolitan (nonmetro): 1999–2001 APC, 15.57* (95% CI, 4.15–26.89); 2001–2018 APC, 1.23* (95% CI, 0.27–1.62); 2018–2020 APC, 17.47* (95% CI, 8.39–21.96). Noncore (nonmetro): 1999–2018 APC, 2.90* (95% CI, 2.38–3.30); 2018–2020 APC, 14.39* (95% CI, 6.77–18.15). *APC is significantly different from zero at alpha = 0.05.

DISCUSSION

In this comprehensive 22-year retrospective analysis of mortality data from the CDC WONDER database, significant findings were identified, bearing substantial implications for public health policy. Initially, there was a marked increase in mortality between 1999 and 2001, followed by a plateau persisting until 2016, after which a more notable rise occurred through 2018, culminating in a sharper escalation by 2020. This temporal pattern demonstrated remarkable consistency for both men and women. Moreover, a demographic analysis indicated that individuals of the NH White racial group exhibited the highest mortality related to MAD and HHD/IHD-related AAMR. Additionally, significant regional disparities were identified, with the North Dakota and Midwest region displaying the highest MAD and HHD/IHD-related AAMR. Furthermore, nonmetropolitan areas consistently exhibited elevated mortality rates compared to metropolitan areas (Supplementary Figure 1).

Literature has indicated a general decline in cardiovascular and all-cause mortality rates since the 1990s, primarily ascribed to intensified efforts in modifying risk factors and implementing guideline-directed medical therapies.32,33 This decline in overall CVD mortality represents a significant achievement in public health. However, it is noteworthy that despite these advances, HHD and IHD have shown a consistent annual increase and remain among the leading causes of mortality in adults globally and in the United States.34–37 MAD often coexists with other chronic conditions, including CVDs such as HHD and IHD, exacerbating overall morbidity and mortality risks.8,9,12,13,15 Similarly to trends noted in diabetes mellitus–related cardiovascular mortality,22 adults with MAD-related cardiovascular mortality continued to demonstrate higher mortality rates annually, as corroborated by our findings, consistent with the studies of Ebert et al, Lambert et al, and Correll et al.10,11,14 Various factors have been posited to account for the heightened mortality rates observed in adults, including adverse effects of pharmacological interventions, suboptimal dietary practices, elevated rates of tobacco consumption, and inadequate physical activity.8,9,13,24,25 Additionally, individuals with MAD often face barriers to accessing healthcare, stemming from both socioeconomic limitations38 and negative perceptions among non–mental health clinicians toward patients with mental illness, compounded by societal stigmatization.39,40 Furthermore, the notable increase in 2020 aligns with well-documented disruptions caused by the COVID-19 pandemic, which intensified mental health symptoms, increased psychosocial stressors, and reduced access to timely cardiovascular care. Because these factors substantially influenced both MAD and cardiovascular outcomes nationwide, the 2020 data provide important epidemiologic context and reflect genuine changes in population health during this period.

Furthermore, our analysis revealed significant disparities by sex. Specifically, we observed that women with MAD and HHD/IHD exhibited higher mortality rates compared to men in the US. This contrasts with the findings of Ebert et al, who reported higher CVD mortality rates in men than in women among those with mental and behavioral disorders.10 This can be attributed to the fact that women tend to have mental disorders that affect the mood, such as depression and anxiety disorders,41 whereas men are more prone to substance use disorders, which are more related to behavioral disorders.10 Both types of disorders are associated with cardiovascular mortality; however, the mechanisms and associated risks differ, thus explaining the discrepancies in outcomes between the two studies. Another contributing factor is the increasing prevalence of HHD42 and IHD43 in women in recent years, which is further exacerbated by MAD,6,8,9 as one of the two, CVDs or psychiatric disorders, most often go underdiagnosed due to symptom overlap.6,24,25

Similarly, a significant racial/ethnic disparity in MAD and HHD/IHD–related mortality was observed, with NH White individuals exhibiting the highest mortality rates, approximately double those of any other race, in contrast to a prior study focusing on mental and behavioral disorders in which the highest mortality was in NH Black or African American individuals.10 This is influenced by several factors. Lifestyle choices, genetic predispositions, and the older age distribution of the White population,44 comorbidities,45 and access to healthcare compared to other races46 may reflect differences attributable to survival bias, further affecting the rise of mortality among Whites with MAD and HHD/IHD in the US. Nevertheless, assessing inequities within institutions and implementing culturally tailored, multidisciplinary interventions such as integrated primary care–mental health–cardiology models, community health worker–led programs, culturally adapted psychotherapeutic approaches, and faith- or community-based initiatives could help alleviate racial disparities.

In addition, significant geographical variations in MAD and HHD/IHD–related mortality in adults were observed, with the Midwestern region having the highest burden compared to other US regions, as supported by findings from Ebert et al.10 Our findings indicate that nonmetropolitan areas have the highest burden of MAD and HHD/IHD-related mortality in older adults compared with metropolitan areas. MAD and HHD/IHD–related AAMR has consistently increased for both metropolitan areas and nonmetropolitan areas over the past two decades, with nonmetropolitan areas observing a significantly higher rate than metropolitan areas. The notable regional disparities are likely attributable to variations in outpatient practices, including the degree of adherence to guideline-directed therapies, the impact of state regulations concerning Medicaid, restricted access to high-quality healthcare services, heightened prevalence of comorbid conditions, sedentary lifestyle patterns,44–48 availability of primary care physicians and cardiologists/psychiatrists practicing within the region to manage these conditions,49,50 and socioeconomic disadvantage in rural areas at times of massive inflation in the economy.51,52

Several limitations merit attention. First, dependence on ICD codes and death certificates entails the potential for misrepresentation or underrepresentation of MAD and HHD/IHD as causal factors in mortality.53 Second, the database is devoid of comprehensive clinical data such as severity levels, comorbid conditions, and specific treatment regimens, thereby restricting the exploration of factors influencing mortality outcomes. Third, socioeconomic determinants of health data were also unavailable, potentially influencing access to healthcare services. Lastly, the study spanned data from 1999 to 2020 without considering potential changes in diagnosis and reporting standards for MAD, HHD, and IHD over this period. Such changes could potentially impact the accuracy of observed mortality rates and trends.

In summary, following an initial incline in the AAMR for MAD and HHD/IHD–related mortality among individuals ≥15 years from 1999 to 2001, the AAMR stabilized until 2016 and then increased more significantly through 2018, with a steeper rise by 2020. The mortality patterns were associated with significant geographic and demographic disparities, with the highest AAMRs observed among women, NH Whites, and those residing in the Midwest region and in nonmetropolitan areas of the US. These findings emphasize the necessity for focused interventions aimed at preventing and effectively addressing MAD and HHD/IHD within the adult demographic of the United States. Moreover, further investigation is warranted to delve deeper into the underlying causes of these observed patterns and discrepancies, as indicated by existing literature and recent findings highlighting a resurgence in the prevalence and mortality rate of MAD and CVD.

Supplementary Material

Supplemental Material
UBMC_A_2620340_SM5364.docx (42KB, docx)
Supplemental Material
UBMC_A_2620340_SM5358.docx (3.4MB, docx)

ACKNOWLEDGMENTS

The authors would like to thank the Research Council of Pakistan for their support and assistance in the study.

Disclosure statement/Funding

The authors report no funding or conflicts of interest.

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