Trends in Cardiovascular Mortality Among Women with Uterine Corpus Cancer in the United States: Racial Disparities and Pandemic-Era Increases, 1999–2023

Trends in Cardiovascular Mortality Among Women with Uterine Corpus Cancer in the United States: Racial Disparities and Pandemic-Era Increases, 1999–2023 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Trends in Cardiovascular Mortality Among Women with Uterine Corpus Cancer in the United States: Racial Disparities and Pandemic-Era Increases, 1999–2023 Beibei Du, Lan Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8955332/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background: Cardiovascular disease (CVD) has emerged as an important competing cause of death among survivors of uterine corpus cancer (UCC). We aimed to characterize 25-year trends in CVD mortality burden among women with UCC and to assess whether racial disparities changed during the COVID-19 period. Methods : Using the CDC WONDER Multiple Cause of Death database (1999–2023), we identified 10,321 female decedents (9,261 White; 1,060 Black) aged ≥45 years with UCC recorded and CVD as the underlying cause. To address changes in U.S. race classification, analyses were conducted within two predefined eras (Era 1: 1999–2020; Era 2: 2018–2023). Primary measures included indexed mortality burden (stabilized to a 3-year mean baseline), Black-to-White ratios, premature CVD deaths (<65 years), and pandemic-era excess deaths. Results: In Era 1, the indexed mortality burden declined among White women to 0.75 by 2020, whereas the Black index increased to a peak of 1.47. In Era 2, the Black index reached 2.26 in 2022—more than doubling the era-specific baseline—while the White index increased to 1.36 by 2023. The Black-to-White disparity ratio peaked at 1.84 in 2022. By 2023, premature CVD deaths accounted for 29.8% of deaths among Black women compared with 10.9% among White women. Black women experienced 60 excess deaths in 2022 relative to the 2018–2019 mean. Conclusions : Racial disparities in CVD mortality among women with UCC persisted over time and widened during the COVID-19 period. A substantially higher proportion of premature cardiovascular deaths was observed among Black women. These findings highlight the importance of integrating cardiovascular risk assessment into cancer survivorship care, particularly for populations experiencing disproportionate mortality burden. Uterine Corpus Cancer Cardiovascular Mortality Racial Disparities Mortality Trends Population-Based Study Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Uterine corpus cancer (UCC) represents a growing public health challenge in the United States, (1–4) as one of the few malignancies with increasing incidence and mortality, particularly among minoritized populations. (2,5–7) As therapeutic advances extend survival, cardiovascular disease (CVD) has emerged as a major competing cause of death, often rivaling cancer recurrence.(8,9) Racial inequities in this cardio-oncology intersection are substantial: (10–12) Black women with UCC experience a higher burden of cardiometabolic comorbidities and are more likely to receive intensive, potentially cardiotoxic treatments for aggressive disease. (13–16) Despite these recognized risks, national trends in racial disparities in CVD mortality among UCC decedents remain incompletely characterized. Longitudinal assessment is complicated by an institutional shift in U.S. race classification from bridged-race to single-race systems, which introduces structural discontinuities in mortality surveillance. (17–19) Naïve aggregation across these regimes may generate misleading inferences, particularly in sparse strata affected by disclosure suppression and small annual counts. Moreover, distinguishing disease-specific inequities from background population risk remains an unresolved interpretive challenge. To address these limitations, we conducted a prespecified national analysis using a Dual-Era framework that treats the race-classification transition as a structural boundary. By examining cardiovascular mortality burden, Black-to-White disparity metrics, and premature CVD death across two classification systems, we evaluate the persistence of racial inequities over time and assess whether these disparities were exacerbated during the COVID-19 period. 2. Methods 2.1 Data Source and Study Design We utilized the CDC WONDER Multiple Cause of Death (MCOD) database, which aggregates U.S. death certificate information, including the underlying cause of death (UCOD), multiple causes of death (MCOD), and demographic characteristics. To address the structural discontinuity in U.S. race classification, we pre-specified a Dual-Era framework: Era 1 (1999–2020): Bridged Race reporting regime. Era 2 (2018–2023) : Single Race reporting regime. Methodological Rigor : Era separation was treated as an a priori structural boundary. We intentionally avoided pooling estimates across regimes to prevent regime-mixing artifacts and ensure the integrity of the longitudinal analysis. 2.2 Study Population and Cohort Definition The analytic cohort included female decedents aged ≥45 years meeting the following criteria: Uterine corpus cancer (UCC) recorded as a multiple cause of death (ICD-10 codes C54–C55). Cardiovascular disease (CVD) identified as the underlying cause of death (ICD-10 codes I00–I99). Analysis was restricted to Black and White women to maximize interpretability and reduce instability in sparse strata. I nterpretation Safeguard : As CDC WONDER MCOD does not provide survivor person-time or time since diagnosis, this study characterizes population-level mortality burden patterns among UCC-identified decedents rather than individual-level longitudinal risk. 2.3 Key Outco mes and Operational Definitions 2.3.1 Indexed Mortality Burden To stabilize baseline noise in sparse strata and mitigate the “baseline trap” (single-year volatility), we defined the annual mortality burden index as follows:Index(t) = Deaths(t) / Mean Deaths(baseline) The baseline was defined as the mean of the first three years in each era (1999–2001 for Era 1; 2018–2020 for Era 2). 2.3.2 Black-to-White Disparity Ratio Within each era and year, the racialized gap in mortality burden was quantified as: Ratio(BW,t) = Index(Black,t) / Index(White,t) A ratio >1 indicates a disproportionately higher indexed mortality burden in Black women relative to White women. 2.3.3 Premature CVD Deaths Premature deaths were defined as those occurring at age <65 years. The premature proportion was calculated as:Premature Proportion(t) = Deaths(<65,t) / Deaths(total,t) Suppression Handling : Cells suppressed under CDC WONDER disclosure rules were retained as missing (NA) rather than imputed as zeros to maintain the transparency of the reported data. 2.3.4 Excess Deaths During the COVID-19 Period To avoid regime-mixing, excess deaths were evaluated exclusively in Era 2. Using the 2018–2019 mean as the pre-pandemic baseline, annual excess deaths for 2020–2023 were calculated as: Excess(t) = Observed Deaths(t) - Mean Deaths(2018-2019) 2.3.5 Sensitivity Analysis: Population-Normalized Indexing To address potential denominator-driven artifacts, we computed population-normalized indexed crude rates:RateIndex(t) = Crude Rate(t) / Mean Crude Rate(baseline) This contextual normalization confirms whether observed trends reflect genuine mortality shifts rather than population scaling. 2.4 Statistical Analysis Analyses were primarily descriptive and pre-specified. We intentionally avoided smoothing techniques (e.g., LOESS) to preserve the transparency of annual fluctuations and suppression-related gaps. All analyses were performed using R (version 4.4.2) within the tidyverse and ggplot2 ecosystems. 3. Results 3.1 Baseline Characteristics and Temporal Trends From 1999 to 2023, a total of 10,321 female decedents with uterine corpus cancer (UCC) who died from cardiovascular disease (CVD) were identified, comprising 9,261 White and 1,060 Black women (Table 1). Across the study period, CVD mortality burden varied by era. In Era 1 (1999–2020), there were 7,231 CVD deaths among White decedents and 747 among Black decedents. In Era 2 (2018–2023), 2,030 deaths were recorded for White women and 313 for Black women. Although the majority of CVD deaths occurred in the ≥65 age group for both races (White: n=8,514; Black: n=957), distinct racial disparities were observed in premature mortality (<65 years). In Era 1, the proportion of premature deaths was 7.8% in White women and 6.7% in Black women. However, in Era 2, this proportion increased substantially to 16.9% in Black women, compared to 9.1% in White women. A temporal shift was particularly evident among Black women aged 45–64, with 51.5% of deaths in this subgroup occurring during the 6-year span of Era 2, whereas the burden for White women of the same age remained concentrated in Era 1 (75.2%). Geographic distribution and place of death also differed significantly by race. Nearly half of Black decedents (49.8%) were located in the Southern United States, while White decedents were distributed more evenly across the Northeast (25.7%), Midwest (27.7%), and South (24.9%). Regarding the place of death, Black women were more likely to die in medical facilities (51.2% vs. 33.7% for White women). Conversely, White women were more frequently reported to die at home (57.5% vs. 44.1%) or in nursing/hospice care facilities (34.3% vs. 22.9%). 3.2 Temporal Trends in Cardiovas cular Mortality Burden Longitudinal CVD mortality patterns among women with uterine corpus cancer (UCC) revealed divergent racial trajectories across both eras (Figure 1). In Era 1 (1999–2001 baseline: mean deaths/year, Black=43; White=439.7), White mortality burden remained stable before declining to a nadir of 0.56 in 2011, eventually concluding at 0.75 in 2020. Conversely, Black women exhibited marked annual volatility, surging from a 2015 low (0.26) to a peak of 1.47 in 2020—a 47% increase relative to baseline. In Era 2 (reporting based on "Single Race"，2018–2020 baseline: mean deaths/year, Black=38; White=303), racial divergence intensified during the pandemic period. While the indexed burden for White women rose steadily to 1.36 by 2023, Black women experienced a dramatic mid-pandemic surge, with the index climbing from 1.63 in 2020 to a peak of 2.26 in 2022—effectively more than doubling the baseline burden. Notably, this was followed by an abrupt decline to 1.24 in 2023, while the upward trajectory for White women persisted. 3.3 Black-to-White Disparity in Indexed Mortality Burden The Black-to-White indexed mortality ratio demonstrated a marked escalation during the pandemic period (Figure 2). While the ratio fluctuated near parity throughout much of Era 1, it surged to 1.96 in 2020. In Era 2, a sustained disproportionate burden was observed in Black women, with ratios of 1.52 in 2020, 1.56 in 2021, and a peak of 1.84 in 2022. This widening gap underscores the intensified racial disparities in cardiovascular mortality during the COVID-19 pandemic, followed by an attenuation of the ratio to 0.91 in 2023. 3.4 Premature CVD Deaths (<65 years) A persistent racial gap in premature CVD mortality (<65 years) was observed, with Black women exhibiting consistently higher proportions in years where CDC WONDER reporting was permitted (Figure 3). In Era 2, the proportion of premature deaths among Black women remained markedly elevated at 0.21 (2020), 0.23 (2021), 0.13 (2022), and peaking at 0.30 in 2023. Conversely, proportions for White women were significantly lower and more stable, ranging from 0.06 to 0.11. Notably, missing data points for Black women—particularly in earlier years—reflect CDC WONDER disclosure suppression in sparse strata and must not be misinterpreted as an absence of mortality. 3.5 Excess Cardiovascular Mortality During the COVID-19 Period (Era 2) In Era 2, significant excess cardiovascular mortality was observed in both racial groups relative to the 2018–2019 pre-pandemic baseline (Figure 4). Among Black women, excess deaths progressively increased from 2020 (+36) to a peak in 2022 (+60), before declining to +21 in 2023. For White women, excess mortality followed a monotonic upward trajectory, rising from +34.5 in 2020 to a maximum of +120.5 in 2023. To maintain methodological rigor and avoid interpretive ambiguity arising from the racial reporting transition, excess mortality analysis was strictly restricted to Era 2 (2018–2023). 3.6 Sensitivity Analysis: Population-Normalized Indexed Crude Rates Sensitivity analysis using population-normalized indexed crude rates confirmed directionally consistent trends with the primary analysis(Supplementary Figure S1). In Era 2, the normalized index for Black women exhibited a distinct pandemic-era elevation, peaking at 1.40 in 2022. This validates that the observed mortality surge was not merely an artifact of raw-count scaling. Notably, this normalization utilizes population denominators as contextual scaling and does not represent individual-level survivor person-time risk. 4. Discussion 4.1 Principal findings In this prespecified Dual-Era analysis, we characterized the 25-year trajectory of cardiovascular mortality burden among women with uterine corpus cancer and identified two principal findings. First, racial disparities in CVD mortality burden persisted across two institutional race-classification eras and widened during the COVID-19 period, with the Black-to-White indexed ratio reaching 1.84 in 2022. Second, a marked shift toward earlier cardiovascular death was observed among Black women, with the proportion of premature CVD deaths (<65 years) approaching three times that of White women by 2023. Together, these findings indicate that cardiovascular mortality among Black women with uterine cancer is disproportionately elevated and occurs at younger ages within the survivorship continuum. 4.2 Mechanistic Interpretation: Structural Factors and Care Pathways The persistent and pandemic-amplified racial disparity in cardiovascular mortality burden among uterine corpus cancer (UCC) decedents reflects a synergistic interaction between biological phenotypes and structural care barriers. Structural Determinants and Cumulative Risk : Black women in the U.S. face an earlier onset of cardiometabolic comorbidities—including hypertension and diabetes—patterned by structural conditions such as neighborhood environments and food insecurity. (20,21) This "weathering" effect is manifested in our data by the alarming 30% premature CVD death rate (<65 years) observed in Black women in 2023, nearly triple that of White women. Cancer Phenotype and Treatment Stressors : Black women are disproportionately diagnosed with aggressive, non-endometrioid UCC subtypes requiring intensive treatment regimens. (22–24) Treatment-related physiological stress may interact with pre-existing metabolic vulnerability. The excess cardiovascular deaths observed in 2022 among Black decedents are consistent with the possibility that systemic health disruptions may disproportionately affect individuals with higher baseline cardiometabolic burden. Care Fragmentation and Inequitable Integration : Differences in place-of-death patterns may further suggest variation in survivorship care pathways. The higher proportion of facility-based deaths (51.2%) among Black women, compared with higher home or hospice deaths among White women (57.5% and 34.3%, respectively), may reflect disparities in longitudinal monitoring, primary care integration, or end-of-life transitions. Pandemic-related disruptions in transportation, insurance stability, and healthcare access may have contributed to these patterns, (21,25,26) particularly in the Southern U.S., where 49.8% of the Black decedent cohort was concentrated. 4.3 Clinic al and Health-System Implications Our findings support a fundamental reframing of uterine corpus cancer (UCC) survivorship care to prioritize cardiovascular prevention through an equity lens: Integrated Risk Assessment: Integration of cardiovascular risk assessment into oncology follow-up may be particularly relevant for populations experiencing disproportionate mortality burden. (27–29) Standardized referral pathways for cardiology evaluation could be considered, especially in settings with high facility-based mortality. (30) Early Intervention for Younger Survivors: Earlier cardiovascular risk evaluation among younger Black survivors may warrant consideration, given the elevated proportion of premature deaths observed in this study. (27) Low-Friction Care Pathways: Regional concentration of mortality burden suggests that high-prevalence areas, including parts of the Southern U.S., may benefit from improved coordination between oncology and primary care services, including structured transitions across care settings. (31) Crisis Resilience Planning: The pandemic-associated surge in cardiovascular mortality highlights the importance of maintaining continuity of cardiometabolic monitoring and medication access during periods of healthcare disruption. (32) 4.4 Strengths and Limitations The credibility of our findings is reinforced by several rigorous methodological choices designed to mitigate artifacts inherent in vital statistics. Key strengths include:1)Institutional Contextualization: By treating race-classification changes as a structural boundary (Dual-Era framework), we avoided the systematic bias common in studies that pool "bridged" and "single" race data.2)Noise Reduction: The use of a three-year stabilized baseline effectively filtered out annual volatility in sparse strata, ensuring that observed peaks reflected true epidemiological shifts rather than statistical noise.3)Sensitivity Validation: The population-normalized sensitivity analysis confirmed that the pandemic-era surge was a genuine increase in mortality rates rather than an artifact of raw-count scaling.4)Transparent Data Handling: Our commitment to preserving suppression-related gaps as missing values, rather than imputing zeros, maintained the integrity of the 25-year trend analysis. This study has several limitations inherent to population-level surveillance data:1)Burden vs. Individual Risk: CDC WONDER MCOD data do not provide survivor denominators, time since diagnosis, cancer stage, or treatment history. Thus, our findings characterize population-level mortality burden among decedents rather than individual-level causal risk.2)Disclosure Suppression: Reporting gaps in sparse strata for Black women reflect mandatory CDC privacy rules; while we avoided artificial trends by preserving these as missing, they limit continuous longitudinal characterization.3)Measurement Error: Potential misclassification of race or the underlying cause of death on certificates may introduce residual bias.4)Unobserved Confounding: We cannot fully disentangle whether the observed disparities arise from racial differences in cancer incidence, treatment intensity, or access to preventive care, as these mechanisms likely co-occur. 5. Conclusion In conclusion, our 25-year analysis across two distinct U.S. race-classification systems reveals that racial inequities in cardiovascular mortality among women with uterine corpus cancer are persistent, structural, and acutely intensified by public health crises. The COVID-19 pandemic acted as a catalyst, driving the Black-to-White indexed mortality ratio to a historical peak of 1.84 in 2022. Furthermore, the nearly three-fold higher proportion of premature CVD deaths among Black women underscores a profound "mortality front-loading" effect. These findings necessitate an equity-centered reframing of cardio-oncology care, advocating for explicit cardiovascular prevention embedded within survivorship pathways—prioritizing younger Black women and ensuring system resilience during periods of healthcare disruption. Declarations Ethics approval and consent to participate This study utilized publicly available, de-identified aggregate data from the Centers for Disease Control and Prevention (CDC) WONDER database. According to the U.S. Department of Health and Human Services regulations (45 CFR 46.102), this study does not classify as human subjects research and is therefore exempt from Institutional Review Board (IRB) review and approval. Requirement for informed consent was waived as the data are anonymized and aggregated. Consent for publication Not applicable. Availability of data and materials The raw mortality data analyzed during the current study are available in the CDC WONDER Multiple Cause of Death database repository, [https://wonder.cdc.gov/mcd.html]. The processed datasets generated and analyzed during the current study are included in this published article and its additional files. Competing interests The authors declare that they have no competing interests. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Authors' contributions Conceptualization: B.D. and L.W.; Methodology: B.D. and L.W.; Software: B.D.; Validation: B.D. and L.W.; Formal Analysis: B.D.; Investigation: B.D.; Resources: L.W.; Data Curation: B.D.; Writing – Original Draft: B.D.; Writing – Review & Editing: B.D. and L.W.; Visualization: B.D.; Supervision: L.W.; Project Administration: L.W. All authors have read and agreed to the published version of the manuscript. Acknowledgements The authors thank the Centers for Disease Control and Prevention (CDC) for providing public access to the WONDER Multiple Cause of Death database, which made this study possible. References Abu-Rustum N, Yashar C, Arend R, Barber E, Bradley K, Brooks R, et al. Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology. 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Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYBACNvaG9B8fDCTs+NkbiNTCx3PggeSMAotkyZ4DRGqRk3B8IM3xoYJxw40EYh0mwZxgzGAgwWxw8/HGGww1NtGEtUi3JSQXGEjwSd5OK7ZgOJaW20BQi8yZhMMzgLbw3c4xk2BsOEyEFon8j808BkDFN88QrSUhmRmkZcINHmK18BxIYwQ6DBjIQL8kEOMX+faGNIYPf+qAUXl4440PNTaEtSADA4kEUpRDtJCqYxSMglEwCkYGAACyaz0o23jS3gAAAABJRU5ErkJggg==","orcid":"","institution":"Huai'an 82 hospital,China RongTong Medical Healthcare Group Co.Ltd","correspondingAuthor":true,"prefix":"","firstName":"Lan","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2026-02-24 09:23:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8955332/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8955332/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104507467,"identity":"ffd78ae8-c674-4ec9-8cbc-b646f0832713","added_by":"auto","created_at":"2026-03-12 15:11:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":42462,"visible":true,"origin":"","legend":"\u003cp\u003eIndexed cardiovascular mortality among uterine cancer decedents.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8955332/v1/c57d4b6fed7fb220b441f24f.png"},{"id":104507462,"identity":"4adee9e7-f6c7-418e-919a-34484139ca0c","added_by":"auto","created_at":"2026-03-12 15:11:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":82386,"visible":true,"origin":"","legend":"\u003cp\u003eRacial disparity in cardiovascular mortality.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8955332/v1/ef6bdf1b2715f753440bf227.png"},{"id":104507460,"identity":"e678ae4a-c2a1-495f-b6b0-545144ac387a","added_by":"auto","created_at":"2026-03-12 15:11:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":105081,"visible":true,"origin":"","legend":"\u003cp\u003eProportion of premature cardiovascular deaths (\u0026lt;65 Years).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8955332/v1/ac881079efdfc35a879bd0e4.png"},{"id":104507455,"identity":"c093c610-7922-48c8-92e8-34c0ccad4746","added_by":"auto","created_at":"2026-03-12 15:11:26","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":97654,"visible":true,"origin":"","legend":"\u003cp\u003eExcess cardiovascular deaths during the CoViD-19 period.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8955332/v1/3e200fe7d2526d2916fcf33d.png"},{"id":104507497,"identity":"f30729e1-60d8-43ce-b3dc-f4c0caf7ddb3","added_by":"auto","created_at":"2026-03-12 15:11:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1198718,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8955332/v1/6f044652-c59d-407b-b718-fc0c99d9e1b0.pdf"},{"id":104507458,"identity":"7d2af5e1-98ea-49c3-a677-3b8b09f27198","added_by":"auto","created_at":"2026-03-12 15:11:26","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":916992,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureS1.doc","url":"https://assets-eu.researchsquare.com/files/rs-8955332/v1/5756133189b2c36195939627.doc"},{"id":104507470,"identity":"4a357fdc-fa35-41b3-817e-0d1404356eee","added_by":"auto","created_at":"2026-03-12 15:11:32","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":16405,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8955332/v1/b970bf1afd7497acaa010edc.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Trends in Cardiovascular Mortality Among Women with Uterine Corpus Cancer in the United States: Racial Disparities and Pandemic-Era Increases, 1999–2023","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eUterine corpus cancer (UCC) represents a growing public health challenge in the United States, (1\u0026ndash;4) as one of the few malignancies with increasing incidence and mortality, particularly among minoritized populations. (2,5\u0026ndash;7) As therapeutic advances extend survival, cardiovascular disease (CVD) has emerged as a major competing cause of death, often rivaling cancer recurrence.(8,9)\u0026nbsp;Racial inequities in this cardio-oncology intersection are substantial:\u0026nbsp;(10\u0026ndash;12)\u0026nbsp;Black women with UCC experience a higher burden of cardiometabolic comorbidities and are more likely to receive intensive, potentially cardiotoxic treatments for aggressive disease.\u0026nbsp;(13\u0026ndash;16)\u003c/p\u003e\n\u003cp\u003eDespite these recognized risks, national trends in racial disparities in CVD mortality among UCC decedents remain incompletely characterized. Longitudinal assessment is complicated by an institutional shift in U.S. race classification from bridged-race to single-race systems, which introduces structural discontinuities in mortality surveillance. (17\u0026ndash;19) Na\u0026iuml;ve aggregation across these regimes may generate misleading inferences, particularly in sparse strata affected by disclosure suppression and small annual counts. Moreover, distinguishing disease-specific inequities from background population risk remains an unresolved interpretive challenge.\u003c/p\u003e\n\u003cp\u003eTo address these limitations, we conducted a prespecified national analysis using a Dual-Era framework that treats the race-classification transition as a structural boundary. By examining cardiovascular mortality burden, Black-to-White disparity metrics, and premature CVD death across two classification systems, we evaluate the persistence of racial inequities over time and assess whether these disparities were exacerbated during the COVID-19 period.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1 Data\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Source and Study Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe utilized the CDC WONDER Multiple Cause of Death (MCOD) database, which aggregates U.S. death certificate information, including the underlying cause of death (UCOD), multiple causes of death (MCOD), and demographic characteristics. To address the structural discontinuity in U.S. race classification, we pre-specified a Dual-Era framework:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEra 1 (1999\u0026ndash;2020):\u0026nbsp;\u003c/strong\u003eBridged Race reporting regime.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEra 2 (2018\u0026ndash;2023)\u003c/strong\u003e: Single Race reporting regime.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodological Rigor\u003c/strong\u003e: Era separation was treated as an a priori structural boundary. We intentionally avoided pooling estimates across regimes to prevent regime-mixing artifacts and ensure the integrity of the longitudinal analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Study Population and Cohort Definition\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe analytic cohort included female decedents aged \u0026ge;45 years meeting the following criteria:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUterine corpus cancer (UCC)\u003c/strong\u003e recorded as a multiple cause of death (ICD-10 codes C54\u0026ndash;C55).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCardiovascular disease (CVD)\u003c/strong\u003e identified as the underlying cause of death (ICD-10 codes I00\u0026ndash;I99).\u003c/p\u003e\n\u003cp\u003eAnalysis was restricted to Black and White women to maximize interpretability and reduce instability in sparse strata.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eI\u003c/strong\u003e\u003cstrong\u003enterpretation Safeguard\u003c/strong\u003e: As CDC WONDER MCOD does not provide survivor person-time or time since diagnosis, this study characterizes population-level mortality burden patterns among UCC-identified decedents rather than individual-level longitudinal risk.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Key Outco\u003c/strong\u003e\u003cstrong\u003emes and Operational Definitions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.1 Indexed\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eMortality Burden\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo stabilize baseline noise in sparse strata and mitigate the \u0026ldquo;baseline trap\u0026rdquo; (single-year volatility), we defined the annual mortality burden index as follows:Index(t) = Deaths(t) / Mean Deaths(baseline)\u003c/p\u003e\n\u003cp\u003eThe baseline was defined as the mean of the first three years in each era (1999\u0026ndash;2001 for Era 1; 2018\u0026ndash;2020 for Era 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.2 Black-to-White Disparity Ratio\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWithin each era and year, the racialized gap in mortality burden was quantified as:\u003c/p\u003e\n\u003cp\u003eRatio(BW,t) = Index(Black,t) / Index(White,t)\u003c/p\u003e\n\u003cp\u003eA ratio \u0026gt;1 indicates a disproportionately higher indexed mortality burden in Black women relative to White women.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.3 Premature CVD Deaths\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePremature deaths were defined as those occurring at age \u0026lt;65 years. The premature proportion was calculated as:Premature Proportion(t) = Deaths(\u0026lt;65,t) / Deaths(total,t)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSuppression Handling\u003c/strong\u003e: Cells suppressed under CDC WONDER disclosure rules were retained as missing (NA) rather than imputed as zeros to maintain the transparency of the reported data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.4 Excess Deaths During the COVID-19 Period\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo avoid regime-mixing, excess deaths were evaluated exclusively in Era 2. Using the 2018\u0026ndash;2019 mean as the pre-pandemic baseline, annual excess deaths for 2020\u0026ndash;2023 were calculated as:\u003c/p\u003e\n\u003cp\u003eExcess(t) = Observed Deaths(t) - Mean Deaths(2018-2019)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.5 Sensitivity Analysis: Population-Normalized Indexing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo address potential denominator-driven artifacts, we computed population-normalized indexed crude rates:RateIndex(t) = Crude Rate(t) / Mean Crude Rate(baseline)\u003c/p\u003e\n\u003cp\u003eThis contextual normalization confirms whether observed trends reflect genuine mortality shifts rather than population scaling.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4 Statistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnalyses were primarily descriptive and pre-specified. We intentionally avoided smoothing techniques (e.g., LOESS) to preserve the transparency of annual fluctuations and suppression-related gaps. All analyses were performed using R (version 4.4.2) within the tidyverse and ggplot2 ecosystems.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Baseline Characteristics and Temporal Trends\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom 1999 to 2023, a total of 10,321 female decedents with uterine corpus cancer (UCC) who died from cardiovascular disease (CVD) were identified, comprising 9,261 White and 1,060 Black women (Table 1). Across the study period, CVD mortality burden varied by era. In Era 1 (1999\u0026ndash;2020), there were 7,231 CVD deaths among White decedents and 747 among Black decedents. In Era 2 (2018\u0026ndash;2023), 2,030 deaths were recorded for White women and 313 for Black women.\u003c/p\u003e\n\u003cp\u003eAlthough the majority of CVD deaths occurred in the\u0026nbsp;\u0026ge;65 age group for both races (White: n=8,514; Black: n=957), distinct racial disparities were observed in premature mortality (\u0026lt;65 years). In Era 1, the proportion of premature deaths was 7.8% in White women and 6.7% in Black women. However, in Era 2, this proportion increased substantially to 16.9% in Black women, compared to 9.1% in White women. A temporal shift was particularly evident among Black women aged 45\u0026ndash;64, with 51.5% of deaths in this subgroup occurring during the 6-year span of Era 2, whereas the burden for White women of the same age remained concentrated in Era 1 (75.2%).\u003c/p\u003e\n\u003cp\u003eGeographic distribution and place of death also differed significantly by race. Nearly half of Black decedents (49.8%) were located in the Southern United States, while White decedents were distributed more evenly across the Northeast (25.7%), Midwest (27.7%), and South (24.9%). Regarding the place of death, Black women were more likely to die in medical facilities (51.2% vs. 33.7% for White women). Conversely, White women were more frequently reported to die at home (57.5% vs. 44.1%) or in nursing/hospice care facilities (34.3% vs. 22.9%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTemporal Trends in Cardiovas\u003c/strong\u003e\u003cstrong\u003ecular Mortality Burden\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLongitudinal CVD mortality patterns among women with uterine corpus cancer (UCC) revealed divergent racial trajectories across both eras (Figure 1). In Era 1 (1999\u0026ndash;2001 baseline: mean deaths/year, Black=43; White=439.7), White mortality burden remained stable before declining to a nadir of 0.56 in 2011, eventually concluding at 0.75 in 2020. Conversely, Black women exhibited marked annual volatility, surging from a 2015 low (0.26) to a peak of 1.47 in 2020\u0026mdash;a 47% increase relative to baseline.\u003c/p\u003e\n\u003cp\u003eIn Era 2 (reporting based on \u0026quot;Single Race\u0026quot;，2018\u0026ndash;2020 baseline: mean deaths/year, Black=38; White=303), racial divergence intensified during the pandemic period. While the indexed burden for White women rose steadily to 1.36 by 2023, Black women experienced a dramatic mid-pandemic surge, with the index climbing from 1.63 in 2020 to a peak of 2.26 in 2022\u0026mdash;effectively more than doubling the baseline burden. Notably, this was followed by an abrupt decline to 1.24 in 2023, while the upward trajectory for White women persisted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Black-to-White Disparity in Indexed Mortality Burden\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Black-to-White indexed mortality ratio demonstrated a marked escalation during the pandemic period (Figure 2). While the ratio fluctuated near parity throughout much of Era 1, it surged to 1.96 in 2020. In Era 2, a sustained disproportionate burden was observed in Black women, with ratios of 1.52 in 2020, 1.56 in 2021, and a peak of 1.84 in 2022. This widening gap underscores the intensified racial disparities in cardiovascular mortality during the COVID-19 pandemic, followed by an attenuation of the ratio to 0.91 in 2023.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Premature CVD Deaths (\u0026lt;65 years)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA persistent racial gap in premature CVD mortality (\u0026lt;65 years) was observed, with Black women exhibiting consistently higher proportions in years where CDC WONDER reporting was permitted (Figure 3). In Era 2, the proportion of premature deaths among Black women remained markedly elevated at 0.21 (2020), 0.23 (2021), 0.13 (2022), and peaking at 0.30 in 2023. Conversely, proportions for White women were significantly lower and more stable, ranging from 0.06 to 0.11. Notably, missing data points for Black women\u0026mdash;particularly in earlier years\u0026mdash;reflect CDC WONDER disclosure suppression in sparse strata and must not be misinterpreted as an absence of mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5 Excess Cardiovascular Mortality During the COVID-19 Period (Era 2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn Era 2, significant excess cardiovascular mortality was observed in both racial groups relative to the 2018\u0026ndash;2019 pre-pandemic baseline (Figure 4). Among Black women, excess deaths progressively increased from 2020 (+36) to a peak in 2022 (+60), before declining to +21 in 2023. For White women, excess mortality followed a monotonic upward trajectory, rising from +34.5 in 2020 to a maximum of +120.5 in 2023. To maintain methodological rigor and avoid interpretive ambiguity arising from the racial reporting transition, excess mortality analysis was strictly restricted to Era 2 (2018\u0026ndash;2023).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.6 Sensitivity Analysis: Population-Normalized Indexed Crude Rates\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSensitivity analysis using population-normalized indexed crude rates confirmed directionally consistent trends with the primary analysis(Supplementary Figure S1). In Era 2, the normalized index for Black women exhibited a distinct pandemic-era elevation, peaking at 1.40 in 2022. This validates that the observed mortality surge was not merely an artifact of raw-count scaling. Notably, this normalization utilizes population denominators as contextual scaling and does not represent individual-level survivor person-time risk.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e\u003cstrong\u003e4.1 Principal findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this prespecified Dual-Era analysis, we characterized the 25-year trajectory of cardiovascular mortality burden among women with uterine corpus cancer and identified two principal findings. First, racial disparities in CVD mortality burden persisted across two institutional race-classification eras and widened during the COVID-19 period, with the Black-to-White indexed ratio reaching 1.84 in 2022. Second, a marked shift toward earlier cardiovascular death was observed among Black women, with the proportion of premature CVD deaths (\u0026lt;65 years) approaching three times that of White women by 2023. Together, these findings indicate that cardiovascular mortality among Black women with uterine cancer is disproportionately elevated and occurs at younger ages within the survivorship continuum.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.2 Mechanistic Interpretation: Structural Factors and Care Pathways\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe persistent and pandemic-amplified racial disparity in cardiovascular mortality burden among uterine corpus cancer (UCC) decedents reflects a synergistic interaction between biological phenotypes and structural care barriers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStructural Determinants and Cumulative Risk\u003c/strong\u003e: Black women in the U.S. face an earlier onset of cardiometabolic comorbidities\u0026mdash;including hypertension and diabetes\u0026mdash;patterned by structural conditions such as neighborhood environments and food insecurity. (20,21) This \u0026quot;weathering\u0026quot; effect is manifested in our data by the alarming 30% premature CVD death rate (\u0026lt;65 years) observed in Black women in 2023, nearly triple that of White women.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCancer Phenotype and Treatment Stressors\u003c/strong\u003e: Black women are disproportionately diagnosed with aggressive, non-endometrioid UCC subtypes requiring intensive treatment regimens. (22\u0026ndash;24) Treatment-related physiological stress may interact with pre-existing metabolic vulnerability. The excess cardiovascular deaths observed in 2022 among Black decedents are consistent with the possibility that systemic health disruptions may disproportionately affect individuals with higher baseline cardiometabolic burden.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCare Fragmentation and Inequitable Integration\u003c/strong\u003e: Differences in place-of-death patterns may further suggest variation in survivorship care pathways. The higher proportion of facility-based deaths (51.2%) among Black women, compared with higher home or hospice deaths among White women (57.5% and 34.3%, respectively), may reflect disparities in longitudinal monitoring, primary care integration, or end-of-life transitions. Pandemic-related disruptions in transportation, insurance stability, and healthcare access may have contributed to these patterns, (21,25,26) particularly in the Southern U.S., where 49.8% of the Black decedent cohort was concentrated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.3 Clinic\u003c/strong\u003e\u003cstrong\u003eal and Health-System Implications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur findings support a fundamental reframing of uterine corpus cancer (UCC) survivorship care to prioritize cardiovascular prevention through an equity lens:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntegrated Risk Assessment:\u0026nbsp;\u003c/strong\u003eIntegration of cardiovascular risk assessment into oncology follow-up may be particularly relevant for populations experiencing disproportionate mortality burden. (27\u0026ndash;29) Standardized referral pathways for cardiology evaluation could be considered, especially in settings with high facility-based mortality. (30)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEarly Intervention for Younger Survivors:\u0026nbsp;\u003c/strong\u003eEarlier cardiovascular risk evaluation among younger Black survivors may warrant consideration, given the elevated proportion of premature deaths observed in this study. (27)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLow-Friction Care Pathways:\u003c/strong\u003e Regional concentration of mortality burden suggests that high-prevalence areas, including parts of the Southern U.S., may benefit from improved coordination between oncology and primary care services, including structured transitions across care settings. (31)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCrisis Resilience Planning:\u0026nbsp;\u003c/strong\u003eThe pandemic-associated surge in cardiovascular mortality highlights the importance of maintaining continuity of cardiometabolic monitoring and medication access during periods of healthcare disruption. (32)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.4 Strengths and Limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe credibility of our findings is reinforced by several rigorous methodological choices designed to mitigate artifacts inherent in vital statistics. Key strengths include:1)Institutional Contextualization: By treating race-classification changes as a structural boundary (Dual-Era framework), we avoided the systematic bias common in studies that pool \u0026quot;bridged\u0026quot; and \u0026quot;single\u0026quot; race data.2)Noise Reduction: The use of a three-year stabilized baseline effectively filtered out annual volatility in sparse strata, ensuring that observed peaks reflected true epidemiological shifts rather than statistical noise.3)Sensitivity Validation: The population-normalized sensitivity analysis confirmed that the pandemic-era surge was a genuine increase in mortality rates rather than an artifact of raw-count scaling.4)Transparent Data Handling: Our commitment to preserving suppression-related gaps as missing values, rather than imputing zeros, maintained the integrity of the 25-year trend analysis.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations inherent to population-level surveillance data:1)Burden vs. Individual Risk: CDC WONDER MCOD data do not provide survivor denominators, time since diagnosis, cancer stage, or treatment history. Thus, our findings characterize population-level mortality burden among decedents rather than individual-level causal risk.2)Disclosure Suppression: Reporting gaps in sparse strata for Black women reflect mandatory CDC privacy rules; while we avoided artificial trends by preserving these as missing, they limit continuous longitudinal characterization.3)Measurement Error: Potential misclassification of race or the underlying cause of death on certificates may introduce residual bias.4)Unobserved Confounding: We cannot fully disentangle whether the observed disparities arise from racial differences in cancer incidence, treatment intensity, or access to preventive care, as these mechanisms likely co-occur.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn conclusion, our 25-year analysis across two distinct U.S. race-classification systems reveals that racial inequities in cardiovascular mortality among women with uterine corpus cancer are persistent, structural, and acutely intensified by public health crises. The COVID-19 pandemic acted as a catalyst, driving the Black-to-White indexed mortality ratio to a historical peak of 1.84 in 2022. Furthermore, the nearly three-fold higher proportion of premature CVD deaths among Black women underscores a profound \u0026quot;mortality front-loading\u0026quot; effect. These findings necessitate an equity-centered reframing of cardio-oncology care, advocating for explicit cardiovascular prevention embedded within survivorship pathways\u0026mdash;prioritizing younger Black women and ensuring system resilience during periods of healthcare disruption.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study utilized publicly available, de-identified aggregate data from the Centers for Disease Control and Prevention (CDC) WONDER database. According to the U.S. Department of Health and Human Services regulations (45 CFR 46.102), this study does not classify as human subjects research and is therefore exempt from Institutional Review Board (IRB) review and approval. Requirement for informed consent was waived as the data are anonymized and aggregated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw mortality data analyzed during the current study are available in the CDC WONDER Multiple Cause of Death database repository, [https://wonder.cdc.gov/mcd.html]. The processed datasets generated and analyzed during the current study are included in this published article and its additional files.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: B.D. and L.W.; Methodology: B.D. and L.W.; Software: B.D.; Validation: B.D. and L.W.; Formal Analysis: B.D.; Investigation: B.D.; Resources: L.W.; Data Curation: B.D.; Writing \u0026ndash; Original Draft: B.D.; Writing \u0026ndash; Review \u0026amp; Editing: B.D. and L.W.; Visualization: B.D.; Supervision: L.W.; Project Administration: L.W. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the Centers for Disease Control and Prevention (CDC) for providing public access to the WONDER Multiple Cause of Death database, which made this study possible.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAbu-Rustum N, Yashar C, Arend R, Barber E, Bradley K, Brooks R, et al. Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw JNCCN. 2023 Feb;21(2):181\u0026ndash;209. doi:10.6004/jnccn.2023.0006 PubMed PMID: 36791750.\u003c/li\u003e\n\u003cli\u003eSiegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. 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BMJ Oncol. 2023 Oct 13;2(1). doi:10.1136/bmjonc-2023-000090 PubMed PMID: 10.1136/bmjonc-2023-000090.\u003c/li\u003e\n\u003cli\u003eMuhandiramge J, Zalcberg JR, van Londen GJ, Warner ET, Carr PR, Haydon A, et al. Cardiovascular Disease in Adult Cancer Survivors: a Review of Current Evidence, Strategies for Prevention and Management, and Future Directions for Cardio-oncology. Curr Oncol Rep. 2022 Nov 1;24(11):1579\u0026ndash;92. doi:10.1007/s11912-022-01309-w\u003c/li\u003e\n\u003cli\u003eSki CF, Cartledge S, Foldager D, Thompson DR, Fredericks S, Ekman I, et al. Integrated care in cardiovascular disease: a statement of the Association of Cardiovascular Nursing and Allied Professions of the European Society of Cardiology. Eur J Cardiovasc Nurs. 2023 Jul 1;22(5):e39\u0026ndash;46. doi:10.1093/eurjcn/zvad009\u003c/li\u003e\n\u003cli\u003eTurk J. Improving Warm Hand-Offs to Appropriate Levels of Care \u0026amp; Evidence Based Practices.\u003c/li\u003e\n\u003cli\u003eQuagliariello V, Berretta M, Maurea F, Barbato M, Paccone A, Iovine M, et al. Healthcare Management in Cardio-Oncology, Clinical Strategies and Future Perspectives: A Narrative Review. Healthcare. 2025 Oct 15;13(20). doi:10.3390/healthcare13202599\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Uterine Corpus Cancer, Cardiovascular Mortality, Racial Disparities, Mortality Trends, Population-Based Study","lastPublishedDoi":"10.21203/rs.3.rs-8955332/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8955332/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eCardiovascular disease (CVD) has emerged as an important competing cause of death among survivors of uterine corpus cancer (UCC). We aimed to characterize 25-year trends in CVD mortality burden among women with UCC and to assess whether racial disparities changed during the COVID-19 period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Using the CDC WONDER Multiple Cause of Death database (1999–2023), we identified 10,321 female decedents (9,261 White; 1,060 Black) aged ≥45 years with UCC recorded and CVD as the underlying cause. To address changes in U.S. race classification, analyses were conducted within two predefined eras (Era 1: 1999–2020; Era 2: 2018–2023). Primary measures included indexed mortality burden (stabilized to a 3-year mean baseline), Black-to-White ratios, premature CVD deaths (\u0026lt;65 years), and pandemic-era excess deaths.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eIn Era 1, the indexed mortality burden declined among White women to 0.75 by 2020, whereas the Black index increased to a peak of 1.47. In Era 2, the Black index reached 2.26 in 2022—more than doubling the era-specific baseline—while the White index increased to 1.36 by 2023. The Black-to-White disparity ratio peaked at 1.84 in 2022. By 2023, premature CVD deaths accounted for 29.8% of deaths among Black women compared with 10.9% among White women. Black women experienced 60 excess deaths in 2022 relative to the 2018–2019 mean.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Racial disparities in CVD mortality among women with UCC persisted over time and widened during the COVID-19 period. A substantially higher proportion of premature cardiovascular deaths was observed among Black women. These findings highlight the importance of integrating cardiovascular risk assessment into cancer survivorship care, particularly for populations experiencing disproportionate mortality burden.\u003c/p\u003e","manuscriptTitle":"Trends in Cardiovascular Mortality Among Women with Uterine Corpus Cancer in the United States: Racial Disparities and Pandemic-Era Increases, 1999–2023","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-12 15:11:04","doi":"10.21203/rs.3.rs-8955332/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-03T18:46:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-16T22:09:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"168218904670578395784575153704834459503","date":"2026-03-10T16:20:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"223428651941572225235530394652559277348","date":"2026-03-09T13:06:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97902130156581116680110295757346020019","date":"2026-03-09T07:06:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-09T00:59:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-27T13:11:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-25T01:48:07+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-25T01:47:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2026-02-24T09:07:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0349318d-5c6d-435e-9bdd-487a06a119c0","owner":[],"postedDate":"March 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-12T15:11:04+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-12 15:11:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8955332","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8955332","identity":"rs-8955332","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}