Chronic kidney disease related mortality trends with and without valvular heart disease among adults in the United States: A retrospective analysis

Abstract

Background

Chronic kidney disease (CKD) and valvular heart disease (VHD) represent a significant global public health challenge. CKD is a major, independent risk factor for the development and progression of VHD. We aimed to examine the long-term mortality trends associated with VHD in individuals with and without CKD in the United States.

Methods

We obtained death certificate data for individuals aged ≥ 25 from the CDC WONDER, identifying deaths with VHD (International Classification of Diseases, 10th Revision [ICD-10] codes I05–I08) and CKD (ICD-10 N18). We calculated age-adjusted mortality rates (AAMRs) and crude mortality rates per 100,000 people. Annual percentage changes (APCs), average APC, and average differences in APCs through Joinpoint Regression.

Results

From 1999 to 2023, Concurrent VHD and CKD were attributed with 71,412 fatalities. AAMR rose from 0.81 in 1999 to 1.62 in 2023, reflecting an overall AAPC of 3.22 (95% CI: 2.20–4.26; p < 0.001). Males consistently exhibited higher AAMRs compared to females, but females showed a steeper rise (AAPC: 3.31 vs. 2.94). The highest AAMR was noted among non-Hispanic (NH) Black or African American individuals with an AAPC of 1.48. Mortality rates were elevated in the Midwest and among rural demographics when contrasted with urban populations. Mortality trends for concurrent VHD and CKD surpassed those for VHD or CKD alone.

Conclusion

Importantly, the increase in mortality associated with concurrent VHD and CKD occurred at a faster rate than that of VHD alone or CKD alone. These findings underscore the need for targeted interventions to address these disparities.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12872-026-06224-7.

Introduction

Chronic kidney disease (CKD) constitutes a significant global public health burden, impacting more than one-tenth of the worldwide population. It is defined by a sustained reduction in the estimated glomerular filtration rate to below 60 mL/min per 1.73 m² for a period of at least three months [1]. In the United States, the prevalence among the medicare population over 65 years is 13.5%, reflecting its role as a major driver of healthcare costs [2]. The global burden of CKD escalated markedly from 1990 to 2023, with the number of affected adults nearly doubling from 378 million to 788 million [3]. The major risk factors for CKD are anchored by the traditional systemic drivers of hypertension, diabetes mellitus, and a characteristic dyslipidaemia (elevated triglycerides, low High-density lipoprotein), which directly inflict vascular and glomerular injury [4].

Valvular heart disease (VHD), a structural or functional cardiac valve disorder, is a major global public health concern primarily resulting from rheumatic heart disease (RHD) or degenerative aging. It significantly contributes to rising cardiovascular morbidity and mortality worldwide [5]. Driven by an aging national population, the prevalence of VHD is rising steadily in the United States, with current estimates suggesting it affects 2.5% of the total U.S. population and over 13% of those aged 75 and older [6]. CKD is a major, independent risk factor for the accelerated development and progression of valvular heart disease, particularly degenerative calcific aortic and mitral stenosis [7]. The prevalence of VHD is approximately 14% in patients with chronic kidney disease, which is double the baseline rate of 7% observed in the general population [8].

The pathophysiological link between CKD and VHD is driven by a convergence of CKD-specific factors, including abnormal mineral metabolism such as hyperphosphatemia and secondary hyperparathyroidism, the accumulation of uremic toxins, and chronic inflammation [9]. The accelerated, active calcification process in CKD directly causes valvular stenosis. This structural valve dysfunction impairs cardiac hemodynamics, increases ventricular afterload, and often necessitates intervention, establishing a direct pathophysiological link between CKD and adverse cardiac outcomes [10].

VHD is a significant but frequently overlooked complication of chronic kidney disease. Individuals with CKD have nearly twice the risk of VHD compared with the general population, largely due to accelerated calcification, chronic inflammation, and mineral bone abnormalities, leading to higher rates of heart failure and mortality [8, 9]. However, national-level data on the burden and mortality trends of concurrent VHD and CKD remain scarce, underscoring the need for targeted assessment to support CDC surveillance, resource planning, and preventive strategies. The objective of this study is to systematically examine long-term mortality trends of VHD within the national CKD population, also to compare mortality with VHD or CKD alone (CKD + VHD vs. CKD; CKD + VHD vs. VHD), to inform targeted public health strategies, optimize care pathways, and reduce cardiovascular morbidity and mortality in this high-risk group.

Methodology

Study setting, population, and case identification

Mortality data within the United States pertaining to the co-occurrence of VHD and CKD were obtained from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database [11]. This database constitutes a comprehensive national repository of mortality records derived from death certificates from all U.S. states and the District of Columbia. Analysis was conducted using the publicly available Multiple Cause-of-Death files to identify death certificates in which VHD and CKD were documented as either the underlying cause of death or contributing causes. The CDC WONDER database has been extensively utilized in prior investigations to characterize mortality patterns associated with VHD and CKD as independent disease entities [12, 13].

Case identification utilized the International Classification of Diseases, Tenth Revision [14], Clinical Modification (ICD-10-CM) codes, with both CKD and VHD were placed under underlying or multiple causes of death. CKD was classified using code N18, while VHD was recognized with codes I05–I08 and I34–I37. In line with the Multiple Cause of Death framework, this definition reflects the concurrent reporting of disease presence instead of a clinically determined or causal link between CKD and VHD. Our study targeted adults aged 25 years and older, since CKD-related death patterns in younger ages are rare and less reliably documented in the CDC WONDER registry. The age threshold of 25 and above is in accordance with the National Center for Health Statistics (NCHS) guidelines for adult mortality studies and guarantees consistency with earlier national studies [15]. Exclusion criteria were established for deaths with incomplete demographic information (e.g., any variables with missing values, especially patient demographics) or unreliable reported data (i.e., data given by patients/participants that was inaccurate or untrustworthy). This method guaranteed that the analysis centered on dependable and pertinent data, thus improving the precision of the study results. Due to the study’s multiple cause of death design, having other cardiovascular diseases mentioned on the death certificate did not constitute exclusion criteria. Death records that included ICD-10 codes for valvular heart disease (I05–I08, I34–I37) were accepted regardless of the presence of any other cardiovascular conditions on the death certificate.

Potential biases and limitations of the CDC WONDER database include inconsistent reporting across states, dependence on death certificate accuracy, and possible underestimation due to variability in coding practices. These factors were considered when interpreting the findings and are further discussed in the limitations section. Institutional review board approval was not required for this study, as the analysis relied exclusively on a publicly accessible, de-identified, and anonymized dataset provided by a governmental source and adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting [16].

Data abstraction and variables

Concurrent VHD and CKD-related deaths, population sizes, and location of death (including medical facilities [outpatient, emergency room, inpatient, death on arrival, or status unknown], home, hospice, and nursing home/long-term care facility) were extracted. In addition, mortality data for CKD alone and VHD alone were separately extracted to enable comparative analyses. Demographics (sex, race/ethnicity, and age), and regional information (census region, urban-rural, and state) were extracted from 1999 to 2023. Race and ethnic groups were classified as non-Hispanic White, non-Hispanic Black, Hispanic or Latino, non-Hispanic American Indian or Alaskan Native, and non-Hispanic Asian or Pacific Islander patients. The data on race and ethnicity collected from death certificates differ from that of self-reported information since they are reported by proxies instead of being self-identified. These racial/ethnic categories have been utilized in previous analyses of the CDC WONDER database and are based on the details provided on death certificates. Age groups were defined as younger adults (25–44 years), middle-aged adults (45–64 years), and older adults (≥ 65 years). For urban-rural classifications, the 2013 NCHS Urban-Rural Classification Scheme was used to categorize counties as urban (large metropolitan area; population ≥ 1 million), medium/small metropolitan area (population 50,000–999,999), and rural (population < 50,000) [17]. Regions were classified into Northeast, Midwest, South, and West according to the U.S. Census Bureau definitions [18].

Data synthesis and analysis

Crude and age-adjusted mortality rates attributable to VHD among individuals with CKD were calculated and expressed per 100,000 population. Crude mortality rates were calculated by dividing the yearly count of deaths where both VHD and CKD were recorded by the accompanying United States population for that specific year. Age-adjusted mortality rates (AAMRs) were computed by standardizing deaths related to VHD and CKD against the 2000 U.S. standard population, following previously established methodologies [18]. Temporal trends in age-adjusted mortality rates were analyzed using the Joinpoint Regression Program (Joinpoint version 5.2.0.0; National Cancer Institute), with the annual percent change (APC) being the key metric for estimating trends [19]. This method employs log-linear regression models to identify significant changes in AAMR over time. For datasets containing 17–21 time points, the guidelines suggest identifying no more than three inflection points within the study period. Since this analysis spans 25 years, the Joinpoint regression software was configured to find up to four joinpoints where notable temporal variations in the trend occurred. Nonetheless, across many variables, including overall, gender, race, and census region, fewer inflection points than the maximum allowable were found, as the degree of variation between trends was more pronounced with fewer inflection points. Consequently, the analysis permitted the identification of between 0 and 4 joinpoints. The Grid Search method [0,2,2], along with the Monte Carlo permutation test with an overall significance level of 0.05 and 4,499 permutation tests, and the parametric method, were used to estimate the annual percent change (APC) and 95% confidence intervals (CIs). This methodology identifies statistically significant inflection points over time by applying log-linear regression models to segments of the mortality data that show temporal variation. Trends were categorized as either increasing or decreasing if the regression slope significantly deviated from zero, as assessed by a two-tailed t-test. This methodological approach has been applied in various previous studies [20–23]. To evaluate differences in mortality trends, nonparallel pairwise comparisons were performed comparing the cohort with concurrent VHD and CKD to cohorts with VHD alone or CKD alone. These comparisons were quantified using the Average Annual Percentage Change Difference (AAPCD), with 95% CIs reported. A two-sided p-value of less than 0.05 was considered indicative of statistical significance. To tackle data suppression and ensure reliability of rates in CDC WONDER, any deaths with counts between 1 and 9 were categorized as “suppressed” and left out of the rate calculations. Furthermore, rates derived from fewer than 20 deaths, which the CDC has identified as “unreliable,” were also omitted from our study to reduce statistical instability and avoid misinterpretation due to random fluctuations.

Sensitivity analysis

Sensitivity analyses were conducted based on three different criteria. Three analytical situations were explored: (1) the entire study timeframe (1999–2023), (2) the entire study timeframe without the years 2010–2011 due to an unexpected increase in AAMR and death counts, (3) excluding the pandemic years (1999–2023, minus 2020–2021), and (4) using VHD as the underlying cause of death (UCOD) and CKD as the contributing cause of death (MCOD) as a validation approach, since the data was entirely dependent on death certificate information.

Results

Overall

A total of 71,412 deaths were attributed to VHD in CKD patients aged 25 and above in the US from 1999 to 2023. Out of which 34,794 deaths were recorded in females, and 36,618 deaths were recorded in males (Table S1).

Information on deaths across care settings revealed that the majority occurred in medical facilities, with inpatient deaths accounting for 50.48%, outpatient deaths for 3.92%, those dead-on-arrival for 0.24%, and status unknown for 0.07%. Deaths at home represented 21.36%, while nursing homes or long-term care facilities contributed 16.21%. Hospice facilities accounted for 4.27% of deaths, and 3.29% occurred in other locations (Table S2).

The overall AAMR exhibited a steady rise between 1999 and 2023, increasing markedly from 0.82 to 1.62 (AAPC: 3.22; 95% CI: 2.20–4.26; p < 0.001), increasing by two-fold, indicating a substantial long-term increase in mortality burden. (Fig. 1; Table S3-S4).

Fig. 1.

Overall and sex stratified trends in Chronic Kidney Disease and Valvular Heart Disease related mortality, shown as age-adjusted mortality rates per 100,000 in the United States, 1999–2023. *Indicates that the annual percentage change is significantly different from zero at α = 0.05. APC = annual percent change; CI = confidence interval

VHD and CKD-related mortality trends stratified by sex

When stratified by gender, males consistently exhibited higher AAMRs than females throughout the study period, suggesting a persistent sex-based disparity in mortality burden.

Among males, the AAMR increased significantly from 1999 to 2023 (APC: 2.94; 95% CI: 1.88 to 4.01; p < 0.001) (Fig. 1; Table S3-S4). Similarly, females showed a notable rise between 1999 and 2023 (APC: 3.31; 95% CI: 2.24 to 4.38; p < 0.001) (Fig. 1; Table S3-S4).

VHD and CKD-related mortality trends stratified by race/ethnicity

Over the past two decades, the highest recorded AAMRs were observed among NH Black or African American individuals, followed by NH White individuals. Hispanic or Latino individuals and NH Asian or Pacific Islander individuals exhibited the lowest AAMR. While all racial and ethnic categories exhibited an upward trend, the degree of increase varied among the groups, revealing different patterns over time. The most significant relative rise in mortality was seen in NH White individuals, while NH Asian or Pacific Islanders experienced a relatively slower increase. The disparities in mortality based on race persisted throughout the entire study period, showing no evident signs of convergence or reduction.

In NH Black or African American individuals, the AAMR increased markedly from 1999 to 2023 (AAPC: 1.48; 95% CI: 0.62 to 2.34; p = 0.001) (Fig. 2; Table S3, S5).

Fig. 2.

Race-stratified trends in Chronic Kidney Disease and Valvular Heart Disease related mortality, shown as age-adjusted mortality rates per 100,000 in the United States, 1999–2023. *Indicates that the annual percentage change is significantly different from zero at α = 0.05. APC =annual percent change; CI = confidence interval

Among Hispanic or Latino individuals, the AAMR rose from 1999 to 2023 (AAPC: 1.58; 95% CI: 0.24 to 2.94; p < 0.022) (Fig. 2; Table S3, S5).

NH White individuals exhibited an upward trend for AAMR between 1999 and 2023, peaking in 2021 (AAPC: 3.90; 95% CI: 2.82 to 5.00; p < 0.001) (Fig. 2; Table S3, S5).

Among NH Asian or Pacific Islander individuals, the AAMR increased from 1999 to 2008, then rose sharply by 2011. It subsequently declined in 2014 before rising again until 2023 (Fig. 2; Table S3, S5).

VHD and CKD-related mortality trends stratified by state

Significant differences in mortality rates were noted among various U.S. states. These variations indicate the uneven distribution of mortality burden linked to co-reported VHD and CKD. No conclusions about changes over time within specific states were drawn, as analyses of state-specific trends were not performed. The findings from 1999 to 2020 revealed that Oregon had the highest AAMR (2.31), while Nevada had the lowest (0.64). States in the top 90th percentile included Oregon, Washington, Minnesota, Vermont, Wisconsin, and Alaska. Conversely, states in the lowest 10th percentile included Nevada, Utah, Louisiana, Georgia, Arizona, and Arkansas (Table S6).

While the findings from 2021 to 2023 revealed that Oregon had the highest AAMR (4.68) and Georgia had the lowest (0.72). States in the top 90th percentile included Oregon, Minnesota, Wisconsin, Washington, South Dakota, and Vermont. Conversely, states in the lowest 10th percentile included Georgia, New Mexico, Mississippi, Louisiana, New York, and Connecticut (Table S6).

VHD and CKD-related mortality trends stratified by urban-rural

In terms of urbanization, rural areas exhibited a higher AAMR than urban areas from 1999 to 2020; however, the rate of increase was more pronounced in urban areas.

In rural areas, the AAMR increased significantly from 1999 to 2020 (AAPC: 4.04; 95% CI: 2.60 to 5.49; p < 0.001) (Fig. 3; Table S3, S7).

Fig. 3.

Urbanization-stratified trends in Chronic Kidney Disease and Valvular Heart Disease related mortality, shown as age-adjusted mortality rates per 100,000 in the United States, 1999–2023. *Indicates that the annual percentage change is significantly different from zero at α = 0.05. APC = annual percent change; CI = confidence interval

Similarly, urban areas experienced a notable increase between 1999 and 2020, (AAPC: 3.35; 95% CI: 2.02 to 4.70; p < 0.001) (Fig. 3; Table S3, S7).

VHD and CKD-related mortality trends stratified by census region

Mortality trends also showed disparities across US Census regions from 1999 to 2023. The highest AAMR was observed in the West region, while the lowest was recorded in the South region. Every region displayed a trend of growth over time, but the rate of increase varied, with the most significant surge noted in the Midwest. The regional variation observed suggests that the burden of mortality was not evenly spread across the primary geographic areas of the United States.

In the Northeast region, the AAMR rose from 1999 to 2023 (AAPC: 2.85; 95% CI: 1.94 to 3.77; p < 0.001) (Fig. 4; Table S3, S8).

Fig. 4.

Census region–stratified trends in Chronic Kidney Disease and Valvular Heart Disease related mortality, shown as age-adjusted mortality rates per 100,000 in the United States, 1999–2023. *Indicates that the annual percentage change is significantly different from zero at α = 0.05. APC = annual percent change; CI = confidence interval

In the Midwest region, this trend continued, increasing the AAMR by 2023 (AAPC: 4.06; 95% CI: 2.93 to 5.19; p < 0.001) (Fig. 4; Table S3, S8).

Similarly, the South region exhibited an increase in AAMR between 1999 and 2023 (AAPC: 2.75; 95% CI: 1.82 to 3.70; p < 0.001) (Fig. 4; Table S3, S8).

The AAMR climbed from 1999 to 2023 in the West region (AAPC: 3.52; 95% CI: 2.24 to 4.82; p < 0.001) (Fig. 4; Table S3, S8).

VHD and CKD-related mortality trends stratified by age group

CMRs revealed distinct patterns across various age groups from 1999 to 2023. The highest CMR was recorded in older adults aged 65–85 + years.

For the 25-44-year-old adults, the CMR exhibited an upward trend between 1999 and 2023 (AAPC: 1.65; 95% CI: 0.32 to 2.99; p = 0.016) (Fig. 5; Table S3, S9).

Fig. 5.

Age-stratified trends in Chronic Kidney Disease and Valvular Heart Disease related mortality, shown as crude mortality rates per 100,000 in the United States, 1999–2023. *Indicates that the annual percentage change is significantly different from zero at α = 0.05. APC = annual percent change; CI = confidence interval

Among adults aged 45–64 years, the CMR initially declined from 1999 to 2008 (APC: − 1.76; 95% CI: − 2.95 to − 0.55; p = 0.007), followed by a notable increase in 2011 (APC: 14.57; 95% CI: 1.53 to 29.29; p = 0.029). It then decreased slightly in 2014, before rising again by 2023 (APC: 5.96; 95% CI: 5.00 to 6.93; p < 0.001) (Fig. 5; Table S3, S9).

Among the 65-84-year-old adults, the CMR showed a continuous upward trend until 2023. (AAPC: 2.89; 95% CI: 1.71 to 4.09; p < 0.001) (Fig. 5; Table S3, S9).

Valvular heart disease versus combined mortality

Between 1999 and 2023, there were a total of 1,072,431 reported deaths associated with VHD in the United States (Table S10). The analysis revealed a decrease in the average annual mortality rate (AAMR) from 1999 to 2023 (AAPC: −0.24; 95% CI: −0.59 to 0.10) over the course of the study. There was a reduction from 1999 to 2007 (APC: −1.41; 95% CI: −2.04 to − 0.79), followed by a period of stability until 2018. However, rates rose from 2018 to 2023 (APC: 1.66; 95% CI: 0.52 to 2.81) (Fig. 6; Table S3, S11).

Fig. 6.

Chronic kidney disease Alone and Valvular Heart Disease Alone-Related mortality in the United States, 1999 to 2023. *Indicates that the annual percentage change is significantly different from zero at α = 0.05. APC = annual percent change; CI = confidence interval

In comparison, mortality rates for patients with both VHD and CKD showed a consistent increase throughout the entire period (AAPC: 3.22; 95% CI: 2.20 to 4.26). The rise in mortality related to VHD combined with CKD from 1999 to 2023 was significantly higher than that of VHD alone, as demonstrated by the AAPCD between the two groups (AAPCD: 3.47%; 95% CI: 2.43 to 4.50; p < 0.001) (Table S3).

Chronic kidney disease versus combined mortality

Between 1999 and 2023, the United States recorded a total of 2,322,109 deaths associated with chronic kidney disease (CKD) (Table S10). The mortality rates for CKD increased significantly during this timeframe (AAPC: 1.42; 95% CI: 0.52 to 2.34) (Fig. 6; Table S3, S11).

In contrast, the mortality rates for individuals suffering from both valvular heart disease (VHD) and CKD saw an even steeper rise over the same period (AAPC: 3.22; 95% CI: 2.20 to 4.26). From 1999 to 2023, the growth in mortality related to combined VHD and CKD was significantly higher than that of CKD alone, as shown by the AAPCD between the two groups (AAPCD: 1.80%; 95% CI: 0.50 to 3.10; p = 0.007) (Table S3).

Sensitivity analysis

When evaluating the long-term mortality trends from 1999 to 2023 for individuals with both VHD and CKD, the baseline overall analysis reveals a steep, steady rise with an AAPC of 3.22 (95% CI: 2.03 to 4.43). Interestingly, completely excluding the surge years of 2011 and 2012 yields a slightly less aggressive but much more complex narrative; rather than a single continuous trajectory, the Joinpoint reveals four distinct trend segments, showing a significant initial increase (APC: 3.03), a brief plateau from 2005 to 2008, an accelerated rise between 2008 and 2021 (APC: 5.20), and a final slight decline after 2021, concluding a slightly lower overall AAPC of 2.85 (95% CI: 1.20 to 4.52). By contrast, when isolating the data to exclude the COVID-19 pandemic years (2020–2021), the trend smooths back out into a single linear segment across the full range, matching the baseline overall AAPC at 3.15 (95% CI: 1.99 to 4.32). Finally, designating VHD as UCD and CKD as MCD reveals the steepest overall escalation of all three variations, producing a single upward trajectory with a notably higher AAPC and APC of 3.77 (95% CI: 2.85 to 4.70). (Supplementary Fig. 1, 2 &3)

Discussion

Our 25-year analysis of mortality data for VHD and CKD in adults from the Centers for Disease Control and Prevention yielded considerable insights. We observed that the overall AAMR exhibited an increase throughout the study period.

The increase in AAMR can be explained by a multitude of reasons. This bi-directional interplay between VHD and CKD has been well documented in prior literature and is associated with adverse clinical outcomes [8, 24]. Concurrently, the prevalence of CKD has increased in the United States [25], and metabolic risk factors such as obesity and diabetes, which may drive CKD and worsen cardiovascular outcomes (including VHD), elevating the risk of death [26, 27]. Moreover, complications related to cardiovascular issues stemming from COVID-19 might have played a role in the increasing trend of mortality observed in recent years [28]. Whether these population-level trends directly drive the increase in the observed mortality cannot be determined from death certificate data alone; prospective studies with granular clinical detail are needed to establish causative mechanisms.

Throughout the study, males exhibited a higher mortality rate than females. It has been documented that estrogen and its receptors provide a protective effect against CKD and also have anti-inflammatory and vasoprotective effects [29, 30], though whether this mechanism underlies the sex difference observed in our population-level data cannot be confirmed from death certificates. Differences in health-seeking behavior and treatment utilization by sex may also be relevant and warrant investigation in future linked administrative data studies [31]. NH Black or African American individuals had the highest AAMR throughout the study period. This is consistent with documented higher prevalence of CKD and faster progression to end-stage renal disease (ESRD) among African Americans, meaning that African Americans are three times more likely to require renal replacement therapy than their non-Hispanic White counterparts [32]. Additionally, black people are less likely to be covered by health insurance despite the implementation of the Patient Protection and Affordable Care Act (ACA) [33]. This means that these individuals are less likely to have access to preferential treatment, resulting in delayed access to screening and treatment, though our dataset does not include insurance or socioeconomic variables and cannot directly test this hypothesis. Hypertension, which disproportionately affects Black Americans [34], predisposes them to accelerated CKD progression, promotion of left ventricular hypertrophy, and worsening of VHD outcomes; however, we cannot isolate its contribution from our data.

Geographically, the Western US had the highest AAMR by Census region. One plausible contextual factor is that the western region has several states in it with the highest life expectancy, meaning large older adult populations that survive long enough to develop advanced CKD and calcific VHD [35]. In the Midwest, these issues are intensified by industrial and agricultural influences, including increased exposure to environmental toxins, which could lead to kidney damage [36]. State-wise trends were more or less consistent with broader census-region trends, with Oregon topping the table across both periods. In contrast, Nevada, which recorded the lowest AAMR during 1999–2020, also lies within the Western region, highlighting substantial future in mortality patterns even within the same census region. Similarly, Georgia, which demonstrated the lowest AAMR during 2020–2023, is located in the Southern United States, a region that exhibited comparatively lower AAMR during the latter study period. These findings suggest that state-level mortality patterns may partially reflect broader regional trends while also underscoring meaningful intra-regional variation. Notably, the rural areas exhibited a consistently higher overall mortality rate compared to urban areas, consistent with prior reports of elevated cardiovascular mortality in rural populations [22, 23, 37]. These disparities may be attributable to differences in healthcare access, specialist availability, diagnostic resources, and cardiovascular risk factor burden, although causal inferences cannot be drawn from this ecological analysis.

Adults aged 65–85 + years accounted for the greatest mortality burden. Frailty is defined as vulnerability to endogenous and exogenous stressors. This means that these individuals are at a higher risk of developing negative health events, which may explain the higher mortality in this subgroup [38]. Similarly, this age group suffers from multiple chronic comorbidities and poor organ functions, and low compensatory capabilities [39]. These comorbidities, such as hypertension, diabetes, heart failure, and coronary artery disease, limit therapeutic options and are associated with worse outcomes.

The divergent trends experienced by VHD, CKD, and VHD-CKD can be explained on the basis of disease management. This trend indicates that VHD alone benefited from major advances in diagnosis and treatment, whereas CKD and especially CKD coexisting with VHD represent a population in whom these gains are blunted or reversed. For VHD, the advances in non-invasive imaging and transcatheter therapies allow earlier diagnosis and offer treatment for a wider range of patients [40]. Meanwhile, the rise in mortality from CKD likely reflects the rise of comorbidities and the higher prevalence of CKD in the general population, as discussed before. Most importantly, the increase in mortality in coexisting VHD-CKD may be explained based on risk amplification i.e. the cumulative burden of these conditions and their shared cardiovascular risk profile; however, the ecological design of this study precludes causal inference regarding the drivers of the observed trends. Whether therapeutic advances in VHD meaningfully benefit individuals with concurrent CKD, who are often excluded from or underrepresented in clinical trials, remains an important unanswered question.

These findings underscore the need for strengthened prevention and care strategies for CKD and VHD, including improved early diagnostic approaches, timely clinical intervention, and enhanced risk stratification using validated biomarkers. Optimizing supportive therapies for advanced disease, such as renal replacement strategies in appropriate populations, may also help mitigate adverse outcomes. Furthermore, policy initiatives aimed at reducing healthcare disparities, such as expanding access to primary and specialty care, supporting community-based prevention programs, and delivering culturally appropriate health education, may contribute to narrowing observed racial and regional differences in mortality.

Limitations and strengths

This study has multiple limitations. First, it relies on national death certificate data, making it purely observational, which may introduce misclassification bias and limit the capacity to determine causal relationships between VHD and trends in CKD-related mortality. Second, the data may be subject to underreporting, potentially leading to the exclusion of CKD and VHD as causes of death. The dataset lacks clinical detail, such as comorbidities, which hampers the assessment of confounders or effect modifiers. These results should be understood in light of the limitations associated with analyses based on death certificates. Future investigations employing prospective or interventional study designs are essential to better understand causal mechanisms.

Third, the database is missing comprehensive clinical details, such as the severity of diseases, the presence of comorbid conditions, and treatment protocols, which hinders our capacity to evaluate how medications, disease progression, and multimorbidity influence mortality trends. Additionally, the lack of information on baseline factors, such as socioeconomic status and access to healthcare, limits a thorough analysis of disparities in both care delivery and outcomes. Although AAMRs help to reflect changes in the age distribution of the population, they may not fully capture other temporal shifts in risk factors or healthcare practices. Lastly, a discontinuity in AAMR for CKD between 2011 and 2012 may reflect changes in coding or certification standards rather than a true epidemiological shift, and warrants further investigation.

Finally, we noticed a discrepancy in AAMR values for CKD-related mortality between 2011 and 2012, which may be due to alterations in coding, certification practices, or reporting standards instead of a genuine epidemiological change. Further examination is required to determine if this difference is a result of a data artifact or changes in external policies.

This study also boasts notable strengths. Firstly, it is among the pioneering studies that evaluate simultaneous mortality rates associated with VHD and CKD in a high-risk older demographic in the US, filling a crucial void in existing research. Furthermore, the research reveals trends that can guide clinicians and help tackle disparities based on sex and ethnoracial backgrounds, ultimately aiding in the enhancement of healthcare delivery for all individuals. The analysis also highlights significant variations in healthcare access based on geography, especially the lack of skilled physicians in rural areas and certain states. This insight could lead to policy modifications aimed at boosting the physician workforce and improving healthcare accessibility in underserved locations.

Conclusion

This Study characterises significant disparities in concurrent CKD and VHD-related mortalities among the population of the US from 1999 to 2023. The overall AAMR increased throughout the study period, with a disproportionate burden among males, NH black or african american individuals, the western region of the US, non-metropolitan areas, and adults aged 65–85+. Rise in mortality for concurrent VHD and CKD was higher than for VHD or CKD alone, highlighting a high-risk cardiorenal subgroup in whom the benefits of advances in VHD management appear attenuated. These descriptive findings should motivate prospective, multi-disciplinary research to establish causal mechanisms and support evidence-based policy to reduce disparities in care access and outcomes.

Abbreviations

CKD

Chronic kidney disease

VHD

Valvular heart disease

RHD

Rheumatic heart disease

NRHVD

Non-rheumatic valvular heart disease

CDC WONDER

Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research

NCHS

National Center for Health Statistics

STROBE

Strengthening the Reporting of Observational Studies in Epidemiology

AAMR

Age-adjusted mortality rate

CMR

Crude Mortality rate

APC

Annual percent change

CI

Confidence interval

AAPCD

Average Annual Percentage Change Difference

ESRD

End stage renal disease

ACA

Affordable Care Act

Authors’ contributions

Conception & Design: SMData Extraction: VDAnalysis: VDMain Manuscript Writing: AH, FU, UM, HUManuscript - editing and revision: SM, KSFinal review and supervision: KS.

Funding

None.

Data availability

Data is provided within the manuscript or supplementary information files. Any extra data required will be provided on further request to the author.

Declarations

Ethics approval and consent to participate

Ethics approval is deemed unnecessary according to national regulations as our study did not involve any human/ animal test subject (http://nbcpakistan.org.pk/nbc-r.html). The need for consent to participate is deemed unnecessary according to national regulations as our study did not involve any human/ animal test subject (http://nbcpakistan.org.pk/nbc-r.html). We ensured adherence to the ethical principles outlined in the Declaration of Helsinki. This has been clearly stated under the Declarations section in the manuscript.

Competing interests

The authors declare no competing interests.