Trends and Disparities in Ischemic Heart Disease and Pneumonia Associated Mortality in the United States: A Population-Based Retrospective Analysis of Death Records From 1999 to 2023

Abstract

Background

Ischemic Heart Disease (IHD) disrupts the cardiopulmonary reserve, while pneumonia exacerbates cardiac ischemia, with both being the leading causes of morbidity and mortality in older adults. Our study aimed to determine the long-term mortality trends and demographic disparities associated with IHD and pneumonia in the U.S. population.

Methods

A retrospective analysis of death certificates listing both IHD and pneumonia as underlying or contributing causes of death was done from 1999 to 2023 using the CDC WONDER database. Age-adjusted mortality rates (AAMRs) were computed per 100,000 individuals and standardized to the 2000 U.S. population. Temporal changes were assessed using Joinpoint regression analysis.

Results

Our findings revealed a V-shaped trend showing a significant decline in AAMR from 1999 to 2018, followed by a sharp rise until 2021 (COVID-19) before decreasing again through 2023. Men, older adults, and non-Hispanic (NH) African Americans had a higher mortality burden compared to their demographic counterparts. Geographically, residents of rural regions experienced higher AAMR than those in metropolitan areas.

Conclusions

Despite progress in reducing comorbid IHD and pneumonia mortality in the recent two decades, the COVID-19 pandemic caused a significant reversal in these trends. Persistent disparities across racial, gender, and geographic lines highlight the need for targeted public health interventions and improved access to cardiopulmonary care in high-risk populations.

Supplementary Information

The online version contains supplementary material available at 10.1007/s44197-026-00530-1.

Introduction

Ischemic heart disease (IHD) is the most common cause of mortality, causing over 9 million deaths in 2016 alone, and it has become one of the priorities in global health concerns [1]. In the United States (U.S.) IHD accounts 30% of overall mortality, having a significant impact on overall population health [2]. Also, the older adult (≥ 65 years) population in this country poses a higher risk of community-acquired pneumonia (CAP), with an annual incidence of hospitalizations of 2,093 per 100,000, implying that nearly one million Americans are admitted due to pneumonia every year [3]. However, both IHD and pneumonia are among the leading causes of healthcare utilization, disability, and deaths among aged individuals.

The clinical and pathophysiology between IHD and pneumonia could be explained by their shared risk factors such as old age, cigarette smoking, diabetes, and high blood pressure [4]. Pneumonia might worsen underlying IHD through mechanisms like systemic inflammation, which can destabilize coronary plaques, fever, and tachycardia, leading to elevated myocardial oxygen demand and potentially causing ischemia [4]. Furthermore, myocardial ischemia can be caused by hypoxia secondary to pneumonia, which can also trigger arrhythmias. Conversely, IHD alters the prognosis of pneumonia by reducing the cardiopulmonary reserve and lowering the ability of the patient to withstand hypoxic stress, thereby increasing the risk of complications and mortality. Such a bidirectional association develops a vicious cycle that is associated with worse prognosis and increased short-term mortality [5].

Current evidence supports the association between pneumonia and adverse cardiac outcomes. Hospital-based studies and cohorts have consistently demonstrated increased mortality among patients with pneumonia and underlying heart disease. Pneumonia is also considered to increase the risk of acute coronary syndrome through mechanisms likely related to systemic inflammation and prothrombotic states. Furthermore, IHD has been linked to more serious outcomes of pneumonia, including a higher risk of respiratory failure and sepsis. However, the current studies are either clinical or regional and remain without parallel in national-level, long-term investigations [6–7]. Further, these studies are often limited by small sample sizes and single-center designs despite evaluating the pathophysiological association between IHD and Pneumonia, and cannot capture the population-level burden, long-term temporal trends, or demographic disparities, which are necessary to inform national public health policy.

Given these gaps, no comprehensive long-term epidemiologic mortality assessment was done involving both IHD and pneumonia in the U.S., and studies lack data on demographic or geographic disparities. Thus, understanding these temporal trends and identifying high-risk subgroups is important for targeted prevention, efficient resource allocation, and strategic public health planning. This study examined national mortality trends involving both IHD and pneumonia in adults aged ≥ 55 years in the U.S. from 1999 to 2023 using the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) Multiple Causes of Death database. Mortality patterns were also stratified by sex, race/ethnicity, age group, place of death, urbanization category, census region, and individual U.S. states to identify the populations at risk.

Methods

Data Source

We utilized the CDC WONDER database to analyze deaths occurring within the U.S. from 1999 to 2023. Death records listing both IHD and pneumonia as either an underlying or contributing cause of death were retrieved from the Multiple Cause-of‐Death Public Use Record section of the database [8]. This database has also been utilized in many studies to analyze mortality trends related to chronic diseases at the national level [9, 10]. Pneumonia and IHD-related deaths were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes J12-J18 and I20-I25, respectively. We utilized STROBE guidelines to ensure clarity and transparency in this analysis. Local institutional review board approval was not obtained for this study, as its primary data source was the CDC WONDER database, which comprises de-identified publicly available data. Further, our study identifies the cases based on the simultaneous presence of ICD-10 codes for both IHD and pneumonia on the same death certificate. This methodology reflects administrative co-listing at the time of death and does not confirm temporal sequencing or specific clinical pathophysiology.

Data Extraction

Pneumonia and IHD-related deaths and population sizes were extracted and analyzed from 1999 to 2023. Demographic (sex, race and ethnicity, and age) and geographic (urban-rural and state) data were also extracted as identified on the death certificates. Racial demographic characteristics were defined as NH African American, Hispanic, NH American Indian, NH Asian, and NH White individuals. Racial and ethnic characteristics were used as categories in CDC WONDER data analyses, depending largely on the information collected from death certificates [9, 10]. We included individuals aged ≥ 55 years in our study, and age group categories were defined as 55–64, 65–74, 75–84, and ≥ 85 years. This age group restriction was selected because adults aged ≥ 55 years represent the primary target population for pneumococcal vaccination and cardiovascular prevention guidelines [11, 12]. Furthermore, deaths in individuals aged < 55 years comprised < 3% of the total mortality burden and often yielded unreliable estimates due to low counts. The National Center for Health Statistics Urban-Rural Classification Scheme was used to classify the study population into large metropolitan areas, medium metropolitan areas, small metropolitan areas, and micropolitan (nonmetropolitan) areas, per the 2013 US Census classification [13].

Statistical Analysis

We determined crude and age-adjusted mortality (AAMR) rates per 100,000 individuals. The crude mortality rate (CMR) for a given year was calculated by dividing the total number of pneumonia and IHD-related deaths by the corresponding U.S. population for that year. AAMRs were determined by direct standardization of pneumonia and IHD-related deaths to the U.S. population for the corresponding year 2000, as already explained [14]. For trend description concerning CMR and AAMR for pneumonia and IHD-related mortality, the Joinpoint regression software package (V 5.2) was used [15]. The number of joinpoints (inflection points) was selected using the Grid Search method, which determines the optimal model fit by minimizing the Bayesian Information Criterion (BIC) while controlling for the overall significance level (permutation test, P < .05). Given the existing temporal trends in AAMR, log-linear regression models were established to estimate the annual percent change (APC) and the associated 95% confidence intervals (CIs).

Results

Absolute Mortality Distribution Across Demographic and Geographic Subgroups

Both IHD and pneumonia-related mortalities were listed on a total of 613,854 death certificates. Males (55.85%) experienced higher mortalities than females (44.15%). NH Whites (83.01%) contributed to most deaths, followed by NH African Americans (7.30%), Hispanics (6.19%), NH Asians (2.71%), and NH American Indians (0.50%). Mortalities were highest in medical facilities (68.9%), with lower frequencies in nursing homes (19.4%), decedents’ homes (7.1%), hospice facilities (2.8%), and other places (1.7%), respectively. Deaths were more prevalent in metropolitan areas (78.46%) than in non-metropolitan areas (21.54%). The region of the South (35.32%) had the highest deaths compared to the Midwest (23.03%), West (20.93%), and Northeast (20.72%) regions (Supplementary Fig. 1; Supplemental Table 1).

Overall and Gender Associated Trends

The overall AAMR decreased from 62.8 (1999) to 18.6 (2023) during the study period. However, a marked decrease was observed in AAMR from 1999 to 2018 (APC: -6.85*; 95% CI: − 8.02 to -6.12) followed by a sharp increase until 2021 (APC: 30.09*; 95% CI: 18.48 to 37.99) coinciding with the COVID-19 pandemic before decreasing again through 2023 (APC: -30.32*; 95% CI: -39.85 to -20.55). The total average AAMR in males (50.2) was approximately double that of females (25.1). However, both genders showed a significant decline in rates from 1999 to 2018 followed by a stark rise until 2021 before declining again through 2023 with associated APCs of -6.73* (95% CI: -7.60 to -6.08), 33.64* (95% CI: 20.24 to 41.02), -32.81* (95% CI: -42.35 to -23.43) in males and − 7.30* (95% CI: -8.06 to -6.78), 25.64* (95% CI: 13.77 to 32.22) and − 30.15* (95% CI: -40.85 to -19.85) in females (Figs. 1 and 2; Supplemental Tables 2, 3).

Fig. 1.

Ischemic heart disease and Pneumonia related age-adjusted mortality rates per 100,000, stratified by Overall among older adults in the United States, 1999 to 2023. APC = Annual Percentage Change, CI = Confidence Interval

Fig. 2.

Ischemic heart disease and Pneumonia related age-adjusted mortality rates per 100,000, stratified by Sex among older adults in the United States, 1999 to 2023. APC = Annual Percentage Change, CI = Confidence Interval

Sensitivity Analysis: Underlying vs. Contributing Causes

We performed sensitivity analysis stratifying the data by the underlying cause of death. Significant declining trends were observed in AAMR from 1999 to 2017 among individuals listing IHD as the underlying cause and pneumonia as the contributing cause of mortality (n = 249,232). Following 2017 trends remain stable through 2023 (APC − 3.15; 95% CI: -5.56 to 2.84). Similarly, when pneumonia was the underlying cause and IHD as a contributing cause (n = 106,202), the AAMR declined from 9.3 in 1999 to 3.0 in 2023. This subgroup also did not exhibit the prominent V-shaped trend reversal seen in the overall aggregated data, showing sharp decreases from 2002 to 2023. However, this suggests that the mortality surge that is observed in the overall analysis was largely driven by deaths where neither IHD nor pneumonia was the underlying cause (e.g., COVID-19) (Supplementary Fig. 2; Supplemental Tables 3, 4).

Race and Ethnicity Mortality Analysis

NH American Indians exhibited the highest total average AAMR (36.3), followed by NH Whites (35.5), Hispanics (33.1), NH African Americans (30.2), and NH Asians (28.9). Significant declines were observed across all racial and ethnic groups between 1999 and 2023. However, a stark increase in rates were observed between 2018 and 2021 in NH American Indians (APC: 36.80*; 95% CI: 15.57 to 51.67), NH Asians (APC: 23.21*; 95% CI: 10.76 to 31.91), NH African Americans (APC: 39.87*; 95% CI: 23.33 to 50.67), NH Whites (APC: 26.25*; 95% CI: 17.81 to 31.66) while Hispanics showed significant surges from 2017 to 2020 (APC: 49.23*; 95% CI: 20.90 to 65.16) (Fig. 3; Supplemental Tables 3, 5).

Fig. 3.

Ischemic heart disease and Pneumonia related age-adjusted mortality rates per 100,000, stratified by Race/Ethnicity among older adults in the United States, 1999 to 2023. APC = Annual Percentage Change, CI = Confidence Interval

Age-Associated Mortality Trends

Adults aged 85 + years (207.2) had triple the CMRs of adults aged 75–84 years (60.3), 65–74 (16.9), and 55–64 years (4.8). AAMR declined significantly across all age groups during the study period. However, from 2018 to 2021 significant increases were observed across all age groups being most prominent in those aged 55–64 years (APC: 48.05*; 95% CI: 38.04 to 55.38) followed by 65–74 (APC: 40.75*; 95% CI: 28.18 to 49.41), 75–84 (APC: 33.16*; 95% CI: 17.46 to 41.97) and 85 + years (APC: 19.12*; 95% CI: 9.16 to 24.87) respectively (Supplementary Fig. 3; Supplemental Tables 3, 6).

Regional Analysis

States in the top 90th percentile (Rhode Island, Oklahoma, Vermont, Kentucky, Ohio, and West Virginia) had an average AAMR of 50.8, which is approximately 2.5 times that of the AAMR (20.7) of states (Alaska, Nevada, Utah, Montana, Arizona, and Colorado) in the lower 10th percentile. On average, the highest AAMRs were observed in the Northeastern region (35.5), followed by the Western (35.2), Midwestern (34.9), and Southern (34.1). Non-metropolitan areas (41.3) consistently had higher IHD and pneumonia-related AAMRs than metropolitan areas (32.8) throughout the study period. However, both metropolitan and non- metropolitan areas experienced sharp declines from 1999 to 2018, followed by significant surges through 2020 (Non-metropolitan: APC: -6.20*; 95% CI: -7.30 to -5.47; APC: 32.31*; 95% CI: 9.04 to 45.00, Metropolitan: APC: − 7.3786*; 95% CI: -8.7056 to -6.4848; 38.29*; 95% CI: 8.31 to 52.98) (Figs. 4 and 5; Supplemental Tables 7–9).

Fig. 4.

Ischemic heart disease and Pneumonia related age-adjusted mortality rates per 100,000, stratified by Urbanization among older adults in the United States, 1999 to 2023. APC = Annual Percentage Change, CI = Confidence Interval

Fig. 5.

Ischemic heart disease and Pneumonia related age-adjusted mortality rates per 100,000, stratified by States among older adults in the United States, 1999 to 2023

Discussion

This retrospective analysis shows that the overall AAMR for IHD and pneumonia decreased from 1999 to 2019, and then increased till 2021, and then decreased from 2021 to 2023. Gender based disparities were observed in which males experienced higher AAMRs as compared to females. Second, the AAMR was higher in NH American Indians as compared to NH Whites. Third, the overall AAMR increased with age and reported the highest in adults aged 85+. Rates were high across non-metropolitan areas and the Northeast region.

Previous literature suggests that inflammation in pneumonia results is associated with cardiovascular events [16]. Heart-related complications are considered the main cause of mortality in patients with pneumonia [17]. A study reports that about 30% pneumonia cases were associated with major cardiovascular complications and mortality [18]. The association between pneumonia and IHD is well established and reported by many studies. It is hypothesized that acute infection in CAP increases metabolic demand and could result in myocardial ischemia [19]. Further, the vasoconstrictive effect of thromboxane A2 also increases the risk of myocardial infarction [20]. Moreover, oxygen imbalance and inflammation due to pneumonia can cause decreased myocardial activity and result in worsening of heart failure [21]. Though our death certificate data cannot confirm these mechanisms in individual decedents, the mortality trends that we observed align with these established clinical associations.

Our ecological data cannot establish direct causality; the decline in overall mortality observed in our study aligned with the findings of evidence-based therapy and evidence-based guideline therapy at the start of the 20th century, which showed that reductions in heart failure (HF) events were associated with the decline in pneumonia incidences [22]. This can be attributed to several factors, including vaccination for inflammation in pneumonia that may reduce HF incidence and related mortality, especially among older patients [23, 24]. Further, the early diagnosis of pneumonia and antibiotic therapy showed positive outcomes [25]. The introduction of receptor-nephrilysin inhibitors also helped to reduce the incidence of HF events in 2015 and onward [26]. This decrease in AAMR may also be attributed to a decrease in smoking status in the US at that time [27]. National public health policies helped individuals in quitting smoking, engaging in healthy activities, and consuming healthy diets [28, 29].

We noted a surge in IHD and pneumonia-associated AAMR during the COVID-19 pandemic, which strongly aligns with the existing studies showing increased mortality among pneumonia patients, especially those having a history of HF, as these individuals were more prone to severe respiratory infections [30]. Studies have reported that there were fewer hospitalizations for cardiovascular conditions during COVID-19. This explains the observed increase in AAMRs in our study, as high cardiovascular disease (CVD) deaths during COVID required emergent treatment, but the large influx of COVID patients had disrupted the healthcare system, and CVD patients got less attention towards treatment, resulting in high deaths [31, 32]. Further, this pattern can be depicted by a 64% decline in diagnostic tests related to heart diseases in 2020 [33]. Moreover, health-seeking behavior declined significantly, which may be due to strict lockdown measures and fear of hospital-acquired infection, resulting in a 50% decline in cardiac hospitalization and worsening of cardiac outcomes [34, 35]. To mitigate these disruptions, the medical community rapidly adopted new clinical guidelines and telemedicine to maintain continuity of care [36–40]. However, the AAMRs declined significantly with the normalization of healthcare capacity and diagnostic testing volumes to pre-pandemic levels by late 2021 [33, 41]. So, the AAMR declined from 2021 onward. However, beyond the healthcare disruption brought by the COVID-19 pandemic, we should also acknowledge the significant influence of changing coding practices over time on mortality trends. Also, increased awareness of respiratory comorbidities during the pandemic might have also contributed to increased pneumonia reporting across death certificates, while misclassification of COVID-19 pneumonia as unspecified viral or bacterial pneumonia could also inflate the observed rates. Thus, the observed spike during the pandemic should be interpreted with caution as it might reflect a combination of excess mortality and variations in cause of death reporting during the study period.

The nature of the 2020–2021 mortality spike was further clarified after the sensitivity analysis based on the underlying cause of death. Trends remained relatively stable or continued to decrease during the pandemic among individuals when analyzing deaths where IHD or pneumonia was the specific underlying cause. This deviation between these stable subgroups and the sharp spike in overall aggregated mortality data suggests that the surge was significantly driven by deaths where a third condition, likely COVID-19, was the underlying cause, while IHD and pneumonia were listed as contributing comorbidities, highlighting the impact of coding practices during the pandemic where respiratory and cardiovascular conditions were frequently co-listed as complications of COVID-19 mortality.

Gender-based disparities were also prominent, with males reporting higher AAMR than women. It is noted that males are biologically more susceptible to having worse pneumonia-related outcomes compared to females, possibly due to testosterone-related immune suppression, lack of X-linked immune redundancy, exaggerated inflammatory response, and slower lung repair [42]. In contrast, estrogen provides immunity to the female body from infections and also helps in faster lung recovery in pneumonia [43]. Moreover, physiological factors and social behaviors of smoking and drinking are more common in men and are considered the major cause of cardiovascular disease [43]. Thus, these differences highlight the need for therapeutic measures in men with both IHD and pneumonia.

Racial disparities were also evident, with NH African Americans and NH American Indians experiencing a higher mortality burden. These disparities likely reflect systemic inequities rather than biological differences, including structural barriers like unequal access to primary care, lower rates of health insurance coverage, and disparities in cardiovascular risk factors management, all of which could contribute to worsening outcomes in these communities [44, 45]. Additionally, medical mistrust as a result of historical inequities could delay care-seeking behavior, especially during public health crises like the COVID-19 pandemic [46, 47]. To address these disparities, social health determinants and equitable cardiovascular and respiratory care access should be accounted for by healthcare policy under the broad category of targeted public health interventions.

From our analysis, we observed that the AAMR increases with the age of individuals, which can be attributed to age-associated physiological changes in the body and in the cardiovascular system, like arteriosclerosis and diminished myocardial activity that leads to the worsening of outcomes in older patients with IHD [48, 49]. Also, an increased pneumonia-related mortality is observed among aged individuals compared to younger populations [50, 51].

Discrepancies in AAMRs were evident across different geographic regions. The AAMR was highest in West Virginia and lowest in Alaska. Differences in access to hospitals and the different socioeconomic status of individuals in these regions might have contributed to these observed variations in mortality [44]. Further, non-metropolitan areas had consistently higher AAMR than metropolitan areas. Residents of non-metropolitan regions have limited access to the healthcare system; they have low socioeconomic levels and have to travel long distances to get medical access [52]. Smoking is also more common in non-metropolitan areas as compared to metropolitan areas [53]. Thus, all of these factors might have resulted in increased mortality and therefore need special attention to facilitate the rural residents with health care facilities and provide them with equal health care opportunities. Also, public health authorities should work on the prevention of smoking in such areas.

Limitations

This study has several limitations. First, it relies on death certificate data from the CDC WONDER database, and it is subject to misclassification bias, underreporting, and inconsistencies in ICD-10 coding that may vary across regions. Because both ischemic heart disease and pneumonia are listed as causes of death, it is difficult to determine whether the observed increases in mortality are primarily driven by IHD, pneumonia, or their combined effects. Second, as a descriptive ecological observational study, causality cannot be established; the findings reflect associations and temporal trends rather than direct cause-and-effect relationships. Third, the lack of individual-level data and clinical details, such as disease severity, medication adherence, vaccination status, healthcare access, and hospital care, limits the ability to adjust for or assess the role of these important factors. Fourth, comprehensive subgroup analyses were performed by age, sex, race, and geography, which can increase the risk of Type I error due to multiple comparisons, and therefore, subgroup-specific APCs should be interpreted as exploratory and hypothesis-generating. Fifth, excluding non-resident deaths may slightly underestimate the overall mortality burden. Despite these limitations, the study provides meaningful insights into evolving patterns and disparities in IHD and pneumonia mortality and highlights areas for future research.

Conclusions

This study highlights the significant mortality burden and disparities associated with co-existing IHD and pneumonia in the U.S. adult population. Mortality rates declined over the past two decades, with persistent demographic and geographic disparities. Further, a reversal of these trends was noted during the COVID-19 pandemic, depicting a sharp rise in rates, emphasizing the need for continued public health surveillance. Future research should evaluate the mechanistic pathways driving these disparities and population-level trends using clinical datasets.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Author Syed Tawassul Hassan contributed to Conceptualization, Writing - Original Draft, Writing - Review & Editing, Supervision, Data curation, Visualization, Formal Analysis, Software, and Project administration. Author Arooj Ihsan Ullah contributed to Writing - Original Draft, Writing - Review & Editing, Validation, Visualization, Formal Analysis, Software, and Resources. Author Naveed Ahmad contributed to Software, Data Curation, Validation, Formal Analysis, and Visualization. Author Muhammad Shaheer Bin Faheem contributed to Supervision, Investigation, Validation, Resources, and Writing - Review & Editing. Author Ali Jan Yaqubi contributed to Data curation, Project administration, and Resources. Author Muhammad Liaquat Raza contributed to Validation and Project administration.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data Availability

The datasets generated during and/or analyzed during the current study are publicly available.

Declarations

Ethics Approval and Consent to Participate

This study used publicly available, de-identified data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database and did not involve human participants or identifiable private information. As such, institutional ethics approval and informed consent were not required, in accordance with national regulations and institutional policies. The study complies with the ethical standards of the Declaration of Helsinki.

Consent for Publication

Not applicable.

Competing interests

The authors declare no competing interests.

Clinical Trial Number

Not applicable.