Demographic and Regional Trends of Heart Failure–Related Mortality in Young Adults in the US, 1999-2019

Vardhman Jain; Abdul Mannan Khan Minhas; Alanna A Morris; Stephen J Greene; Ambarish Pandey; Sadiya S Khan; Gregg C Fonarow; Robert J Mentz; Javed Butler; Muhammad Shahzeb Khan

doi:10.1001/jamacardio.2022.2213

. 2022 Jul 27;7(9):900–904. doi: 10.1001/jamacardio.2022.2213

Demographic and Regional Trends of Heart Failure–Related Mortality in Young Adults in the US, 1999-2019

Vardhman Jain ¹, Abdul Mannan Khan Minhas ², Alanna A Morris ³, Stephen J Greene ^4,⁵, Ambarish Pandey ⁶, Sadiya S Khan ^7,⁸, Gregg C Fonarow ^9,¹⁰, Robert J Mentz ^4,⁵, Javed Butler ^11,¹², Muhammad Shahzeb Khan ^4,^✉

¹Department of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio

²Department of Medicine, Forrest General Hospital, Hattiesburg, Mississippi

³Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia

⁴Division of Cardiology, Duke University School of Medicine, Durham, North Carolina

⁵Duke Clinical Research Institute, Durham, North Carolina

⁶Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas

⁷Division of Cardiology, Northwestern University, Chicago, Illinois

⁸Web Editor, JAMA Cardiology

⁹Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles Medical Center, Los Angeles

¹⁰Section Editor, JAMA Cardiology

¹¹Department of Medicine, University of Mississippi Medical Center, Jackson

¹²Baylor Scott and White Research Institute, Dallas, Texas

Accepted for Publication: May 26, 2022.

Published Online: July 27, 2022. doi:10.1001/jamacardio.2022.2213

^✉

Corresponding Author: Muhammad Shahzeb Khan, MD, MSc, Division of Cardiology, Duke University School of Medicine, 2301 Erwin Rd, Durham, NC 27710 (shahzeb.khan@duke.edu).

Author Contributions: Dr M. Khan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Jain, Minhas, Fonarow, Butler, M. Khan.

Acquisition, analysis, or interpretation of data: Jain, Minhas, Morris, Greene, Pandey, S. Khan, Fonarow, Mentz, Butler.

Drafting of the manuscript: Jain, M. Khan.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Jain, Minhas.

Administrative, technical, or material support: Jain, Minhas, S. Khan, M. Khan.

Supervision: Mentz, Butler, M. Khan.

Conflict of Interest Disclosures: Dr Morris reported grants from National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; Woodruff Foundation; and Association of Black Cardiologists outside the submitted work. Dr Greene reported nonfinancial support from Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinentics, Merck, Novartis, and Pfizer; personal fees from Boehringer Ingelheim, Cytokinetics, AstraZeneca, Merck, Bayer, Roche Diagnostics, Vifor, Sanofi, Urovant Pharmaceuticals, Bristol Myers Squibb; research support from the American Heart Association; grants from Novartis; has served on advisory boards for Amgen, AstraZeneca, Bristol Myers Squibb, and Cytokinetics; and has served as a consultant for Amgen, Bayer, Bristol Myers Squibb, Merck and Vifor outside the submitted work. Dr Pandey reported grants from National Institute on Aging during the conduct of the study; has served on the advisory board for Roche Diagnostics and Eli Lilly; has served as a consultant for Tricog Health; nonfinancial support from Pfizer and Merck; grants from Applied Theraputics and Myovista outside the submitted work; and is supported by the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute of Aging GEMSSTAR grant, and Applied Therapeutics. Dr S. Khan reported grants from American Heart Association and the National Institutes of Health outside the submitted work. Dr Fonarow reported research funding from the National Institutes of Health and personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis outside the submitted work. Dr Mentz reported personal fees from Bayer, Boehringer Ingelheim/Eli Lilly, Merck, Novartis, AstraZeneca, Vifor, Zoll, and Windtree; grants from American Regent; and research support and honoraria from Abbott, Amgen, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Medtronic, Roche, and Sanofi during the conduct of the study. Dr Butler reported personal fees from Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, V-Wave Limited, and Vifor outside the submitted work. No other disclosures were reported.

Disclaimer: Dr S. Khan is Web Editor of JAMA Cardiology and Dr Fonarow is Section Editor of JAMA Cardiology, but they were not involved in any of the decisions regarding review of the manuscript or its acceptance.

^✉

Corresponding author.

PMCID: PMC9330269 PMID: 35895048

This cohort study assesses trends in heart failure–related mortality in Black, Hispanic, and White young adults.

Key Points

Question

What are the trends in heart failure (HF)–related mortality in young adults?

Findings

In this cohort study, 61 729 HF-related deaths were identified in young adults between 1999 and 2019, and the overall age-adjusted mortality rate per 100 000 persons increased from 2.36 in 1999 to 3.16 in 2019. Black adults had a 3-fold higher mortality rate compared with White adults, and there were significant sex, race and ethnic, and geographic variations over the study period.

Meaning

There is a high burden of HF-related mortality in young adults that is increasing, and health policy measures are needed to address this concerning trend.

Abstract

Importance

There are limited data on mortality trends in young adults with heart failure (HF).

Objective

To study the trends in HF-related mortality among young adults.

Design, Setting, and Participants

This retrospective cohort analysis used mortality data of young adults aged 15 to 44 years with HF listed as a contributing or underlying cause of death in the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1999 to December 2019. Analysis took place in October 2021.

Exposures

Age 15 to 44 years with HF listed as a contributing or underlying cause of death.

Main Outcomes and Measures

HF-related age-adjusted mortality rates (AAMR) per 100 000 US population stratified by sex, race and ethnicity, and geographic areas.

Results

Between 1999 and 2019, a total of 61 729 HF-related deaths occurred in young adults. Of these, 38 629 (62.0%) were men and 23 460 (38.0%) were women, and 22 156 (35.9%) were Black, 6648 (10.8%) were Hispanic, and 30 145 (48.8%) were White. The overall AAMR per 100 000 persons for HF in young adults increased from 2.36 in 1999 to 3.16 in 2019. HF mortality increased in young men and women, with men having higher AAMRs throughout the study period. AAMR increased for all race and ethnicity groups, with Black adults having the highest AAMRs (6.41 in 1999 and 8.58 in 2019). AAMR for Hispanic adults and White adults increased from 1.62 to 2.04 and 1.83 to 2.45 over the same time period, respectively. Across most demographic and regional subgroups, HF-related mortality stayed stable or decreased between 1999 and 2012, followed by an increase between 2012 and 2019. There were significant regional differences in the burden of HF-related mortality, with states in the upper 90th percentile of HF-related mortality (Oklahoma, South Carolina, Louisiana, Arkansas, Alabama, and Mississippi) having a significantly higher mortality burden compared with those in the bottom tenth percentile.

Conclusions and Relevance

Following an initial period of stability, HF-related mortality in young adults increased from 2012 to 2019 in the United States. Black adults have a 3-fold higher AAMR compared with White adults, with significant geographic variation. Targeted health policy measures are needed to address the rising burden of HF in young adults, with a focus on prevention, early diagnosis, and reduction in disparities.

Introduction

The lifetime risk of developing heart failure (HF) ranges between 26% and 40% among adults who are alive at age 45 years.¹ Although most individuals who are diagnosed with HF are older adults, an increasing proportion of younger adults are being diagnosed in recent years.² These adverse patterns may be a reflection of the rising burden of cardiometabolic risk factors beginning in young adulthood.³ There are limited data surrounding HF-related mortality in young adults. Given the potential economic burden stemming from the loss of productivity years and health care utilization that may be associated with HF mortality at a young age, it is important to quantify the magnitude of the problem to inform health policy measures.

Methods

Deaths occurring within the Unites States related to HF were extracted from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database.⁴ The Multiple Cause-of-Death Public Use record death certificates were studied to select HF as a contributing or underlying cause of death on nationwide death certificates using International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes I11.0, I13.0, I13.2, and I50.x. Young adults were defined as those aged 15 to 44 years at the time of death. This study was exempt from institutional review board approval given the deidentified nature of the database.

HF-related deaths, population sizes, and location of death were extracted from January 1999 to December 2019. Race and ethnicity groups were defined as Hispanic, non-Hispanic Black/African American, or non-Hispanic White. Race and ethnicity were considered as reported on death certificates in accordance with standards from the US Office of Management and Budget.⁴ For urban-rural classifications, the National Center for Health Statistics Urban-Rural Classification Scheme was used to divide the population into urban (large metropolitan area [population, ≥1 million], medium/small metropolitan area [population, 50 000-999 999]), and rural (population, <50 000) counties per the 2013 US census classification.

HF-related crude and age-adjusted mortality rates (AAMR) per 100 000 persons were determined. Crude mortality rates were determined by dividing the number of HF-related deaths by the corresponding US population of that year. AAMRs were calculated by standardizing the HF-related deaths to 2000 US population as previously described.⁵ The Joinpoint regression program version 4.9.0.0 (National Cancer Institute) was used to determine trends in AAMR using annual percent change (APC). This method identifies significant changes in AAMR over time by fitting log-linear regression models where temporal variation occurred. APCs with 95% CIs for the AAMR were calculated at the identified line segments linking join points using the Monte Carlo permutation test. APCs were considered increasing or decreasing if the slope describing the change in mortality was significantly different than 0 using 2-tailed t testing. Significance was set at P < .05. Sensitivity analyses were performed to include only adults aged 25 to 44 years, as well as using HF only as an underlying cause of death. Analysis took place in October 2021.

Results

Between 1999 and 2019, a total of 61 729 HF-related deaths occurred in young adults (eTable 1 in the Supplement). Of these, 38 629 (62.0%) were men and 23 460 (38.0%) were women, and 22 156 (35.9%) were Black, 6648 (10.8%) were Hispanic, and 30 145 (48.8%) were White. Of 59 061 deaths that had information available on location of death, 40 820 (69.1%) occurred within medical facilities, 1725 (2.9%) occurred in nursing homes/long-term care facilities, 862 (1.5%) occurred in hospice, and 15 654 (26.5%) occurred at home (eTable 2 in the Supplement). The overall AAMR during the study duration was 2.47; AAMR was higher for men compared with women (3.04 vs 1.87) and higher for Black adults compared with Hispanic and White adults (6.77 vs 1.51 vs 1.91, respectively).

Overall, the AAMR for HF in young adults increased from 2.36 in 1999 to 3.16 in 2019 (Figure 1). AAMR was stable from 1999 to 2012 (APC, −0.3% [95% CI, −0.8 to 0.2]) followed by a rise between 2012 and 2019 (APC, 5.0% [95% CI, 3.6-6.3]) (Figure 1). HF mortality increased in young men and women. Specifically, the AAMR in men increased from 2.82 in 1999 to 3.98 in 2019, while the AAMR in women increased from 1.87 in 1999 to 2.33 in 2019 (Figure 1). AAMR increased for all race and ethnicity groups as well. Black adults had the highest AAMR that increased from 6.41 in 1999 to 8.58 in 2019, whereas that for Hispanic and White adults and increased from 1.62 to 2.04 and 1.83 to 2.45, respectively, over the same time period (Figure 2). Nonmetropolitan areas had the highest AAMR that increased from 3.22 in 1999 to 5.11 in 2019. Mortality rates similarly increased in large and medium/small metropolitan area during the study period (Figure 3A; eTable 3 in the Supplement). There were significant regional differences in the burden of HF-related mortality, with states in the upper 90th percentile of HF-related mortality (Oklahoma, South Carolina, Louisiana, Arkansas, Alabama, and Mississippi) having a significantly higher mortality burden compared with those in the bottom 10th percentile (Figure 3B; eTable 4 in the Supplement). Data regarding the underlying causes of death among patients who had HF listed as a cause of death, as well as the sensitivity analyses are presented in eTables 5 to 7 and eFigures 1 and 2 in the Supplement.

Figure 2. — APC indicates annual percent change.

^aP < .05.

Figure 3. — APC indicates annual percent change.

^aP < .05.

Discussion

In this 20-year analysis of mortality data from the Centers for Disease Control and Prevention, we report an increase in age-adjusted HF-related mortality rates in young adults. There was an initial period of relatively stable mortality rates between 1999 and 2012 followed by a rapid increase that was consistent across all sex and racial and ethnic groups. Young Black adults had a nearly 3-fold higher AAMR compared with Hispanic and White adults. Moreover, there were significant regional differences in the burden of HF-related mortality, with states in the upper 90th percentile of HF-related mortality (Oklahoma, South Carolina, Louisiana, Arkansas, Alabama, and Mississippi) having a significantly higher mortality burden compared with those in the bottom 10th percentile.

Our results are consistent with recent findings suggesting that HF-related mortality stayed relatively stable between 2006 and 2014.⁶ However, our current findings highlight that subsequent HF-related mortality among young adults in a more contemporary cohort has been on the rise since 2012, with consistent patterns by sex and race and ethnicity. This is in the backdrop of an increase in HF incidence and hospitalization rates in younger adults, as shown by a recent 15-year retrospective analysis.⁷ While this recent increase in HF mortality is likely in part driven by the rising incidence of cardiometabolic risk factors and HF incidence among young adults, other factors such as the implementation of the Hospital Readmission Reduction Program and increased electronic health record diagnosis of HF may have also played a part in increased reporting of HF on death certificates.⁸ Thus, although declines in cardiovascular mortality between the 1970s to 2010s could signal success of targeted health policy interventions, use of guideline-directed medical therapy, and better mitigation of clinical risk, these data from recent years suggest challenges with the continued successful implementation of these strategies. Additionally, young adults may be more susceptible to the health effects of being uninsured or underinsured because the US lacks a safety net health coverage for adults younger than 65 years.

We also report significant racial and ethnic disparities, with Black adults having approximately 3 times higher AAMR compared with Hispanic and White adults. This adverse trend may be secondary to adverse socioeconomic determinants of health and underlying bias in treatment.⁹ Among patients with HF, there is evidence of structural racism and care disparities that disproportionately impact Black patients; they are less likely to receive accessible ambulatory care that could decrease the need for hospitalization; be admitted under the care of a cardiologist; or be admitted to a cardiac intensive care unit.¹⁰ Black adults may also face challenges in getting connected with outpatient HF clinics, starting to receive and adhere to guideline-directed medical therapy, and are more likely to use emergency departments for acute HF care compared with Hispanic and White adults, which may be secondary to systemic factors, like structural racism in care delivery.¹¹

Our results also show that there are significant geographic variations in HF-related mortality in young adults. While individual risk factors are pertinent to assess the risk of incident and fatal HF events, the impact of health policy measures are better understood with a geospatial lens. The large geographic variation in HF mortality could, in part, be explained by differences in outpatient cardiology practice, the impact of state legislature such as Medicaid expansion, and comorbidity burden. Data suggest that the burden of comorbidities such as diabetes, hypertension, and obesity, and behavioral risk factors follow a similar geographical trend,¹² and better public health awareness about these adverse health behaviors could help decrease the regional disparity in HF mortality among young adults.

Limitations

There are several limitations in this study. The use of International Statistical Classification of Diseases codes and reliance on death certificates may have resulted in some misclassification of HF as a cause of death.^13,14 Further, the increase in electronic health record diagnosis of HF could translate to increased reporting on death certificates, leading to an increase in death certificate trends for HF mortality, which may or may not be a solid proxy for actual HF mortality trends in young adults. The database does not provide data on disease characteristics to further characterize the HF phenotype, such as vital signs, laboratory values, echocardiographic data, or genetic testing.

Conclusions

In conclusion, our results show that after an initial period of stability, HF-related mortality in young adults has overall increased from 2012 to 2019 in the United States. Black adults have a 3-fold higher age-adjusted mortality rate compared with White adults, with significant geographic variation. Targeted health policy measures to address the rising burden of HF in young adults is needed, with a focus on prevention, early diagnosis, and reduction in disparities.

Supplement.

eTable 1. Absolute Number of Heart failure Related Deaths Stratified by Sex and Race and Ethnicity in the United States, 1999-2019

eTable 2. Trends in Heart Failure Related Mortality Stratified by Place of Death in the United States, 1999-2019

eTable 3. Heart failure Related Mortality Stratified by Region in the United States,1999-2019

eTable 4. Heart failure Related Mortality Stratified by States in the United States, 1999-2019

eTable 5. Conditions listed as underlying causes of death from the records listing heart failure among causes of death (contributing or underlying) in the United States, 1999 to 2019

eTable 6. Heart failure Related Mortality for age group 25-44 years in the United States, 1999-2019

eTable 7. Heart failure Mortality (listed as underlying cause), among young adults in the United States, 1999-2019

eFigure 1. Trends in Heart failure related age adjusted mortality rates for age group 25-44 years in the United States, 1999-2019

eFigure 2. Trends in Heart failure Mortality (listed as underlying cause), among young adults in the United States, 1999-2019

Click here for additional data file.^{(265.5KB, pdf)}

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