What is the clinical question being addressed?
What is the scope of COVID-19 and cardiovascular disease-related death in the United States?
What is the main finding?
Concomitant COVID-19 and cardiovascular disease is associated with high mortality and persistent racial disparities.
COVID-19 is associated with higher risk of acute coronary syndrome, venous thromboembolism, cerebrovascular accidents, and arrhythmias, especially after 30 days of incident infection.1 Moreover, preexisting cardiovascular disease (CVD) is associated with increased morbidity and mortality with acute COVID-19 illness. We sought to assess the COVID-19–related and CVD-related deaths and how they compare with deaths attributed to both COVID-19 and CVD.
We analyzed data from the Centers for Disease Control and Prevention WONDER (Wide-Ranging Online Data for Epidemiologic Research) database from January 1, 2020, to December 31, 2021. All deaths related to COVID-19 and CVD in adults aged ≥25 years were included. Data for deaths related to COVID-19 and CVD were obtained by querying “COVID-19” using International Classification of Diseases-10th Revision code U07.1 and “diseases of circulatory system” using International Classification of Diseases-10th Revision code I00-I99 as contributing or underlying causes of death. The 2 terms were then queried together to ascertain patients who had both COVID-19 and CVD, including pulmonary circulatory disorders and pulmonary embolism, as contributing or underlying causes of death. Sociodemographic data including age, sex, race/ethnicity, and region of residence across the United States were acquired for all 3 patient subgroups. Age-adjusted mortality rates (AAMR) per 100,000 population were determined. AAMRs were calculated by standardizing the deaths to the year 2000 U.S. population.
Between 2020 and 2021, there were a total of 6,715,183 deaths. Of the total deaths, 3,732,440 were CVD related only, and 843,894 were COVID-19 related only. A total of 385,462 deaths were related to both COVID-19 and CVD. The AAMR was 709.2 (95% CI: 708.5-710.0) in CVD only, 161.0 (95% CI: 160.7-161.4.7) in COVID-19 only, and 73.2 (95% CI: 73.0-73.4) in both COVID-19 and CVD (Table 1 ). The elderly age group (age ≥65 years) had the highest AAMR for both COVID-19–related and CVD-related deaths of 284.8 (95% CI: 283.8-285.9), followed by middle-aged adults (45-64 years) (AAMR: 41.7; 95% CI: 41.4-42.0) and young adults (25-44 years) (AAMR: 7.0; 95% CI: 6.8-7.1). When stratified by race/ethnicity, the AAMR of both COVID-19–related and CVD-related deaths was highest in Hispanic patients (AAMR: 117.7; 95% CI: 116.7-118.6) followed by non-Hispanic (NH) Black patients (AAMR: 114.5; 95% CI: 113.6-115.5) compared with NH White patients (AAMR: 61.6; 95% CI: 61.4-61.9) and NH Asian patients (AAMR: 51.5; 95% CI: 50.7-52.4). The AAMR stratified by census region revealed a higher rate of both COVID-19 and CVD-related deaths in the South (AAMR: 77.4; 95% CI: 77.0-77.8) followed by the Northeast (AAMR: 72.7; 95% CI: 72.2-73.3), the Midwest (AAMR: 71.0; 95% CI: 70.5-71.5), and the West (AAMR: 67.9; 95% CI: 67.4-68.4). The highest AAMR in the Northeast (127.3 vs 117.2), Midwest (118.0 vs 106.0), and South (111.6 vs 108.8) was observed among NH Black patients followed by Hispanic patients. However, the highest AAMR in the West was observed in Hispanic followed by NH Black patients (129.4 vs 100.3). The highest proportion of deaths occurred in a medical facility (266,333; 70.6%).
Table 1.
Cardiovascular-Related and COVID-19–Related Mortality, 2020-2021
| Age-Adjusted Death Rate per 100,000 and Frequency for Both Cardiovascular Disease and COVID-19 | |||
|---|---|---|---|
| Deaths, n | Population, n | Overall Age-Adjusted Death Rate per 100,000 (95% CI) | |
| Entire cohort | 385,462 | 454,873,425 | 73.2 (73.0-73.4) |
| Sex | |||
| Men | 216,391 (56.1%) | 221,125,676 | 93.6 (93.2-94.0) |
| Women | 169,071 | 233,747,749 | 56.7 (56.5-57.0) |
| Race | |||
| Asian | 13,506 | 27,756,974 | 51.5 (50.7-52.4) |
| Black or African American | 59,364 | 54,752,155 | 114.5 (113.6-115.5) |
| White | 241,198 | 289,387,384 | 61.6 (61.4-61.9) |
| Hispanic | 64,064 | 72,446,135 | 117.7 (116.7-118.6) |
| Census region of United States | |||
| Northeast | 71,893 | 79,758,107 | 72.7 (72.2-73.3) |
| Midwest | 79,748 | 93,753,771 | 71.0 (70.5-71.5) |
| South | 153,412 | 173,573,832 | 77.4 (77.0-77.8) |
| West | 80,409 | 107,823,715 | 67.9 (67.4-68.4) |
| Age groups | |||
| Young adults (25-44 y) | 11,598 | 177,104,797 | 7.0 (6.8-7.1) |
| Middle age (45-64 y) | 76,263 | 166,261,310 | 41.7 (41.4-42.0) |
| Elderly (65+ y) | 297,601 | 111,507,318 | 284.8 (283.8-285.9) |
| Age-Adjusted Death Rate per 100,000 According to Race by Region (95% CI) | ||||
|---|---|---|---|---|
| Northeast | Midwest | South | West | |
| Asian | 66.4 (64.1-68.7) | 58.1 (55.0-61.3) | 38.9 (37.2-40.7) | 50.0 (48.8-51.2) |
| Black or African American | 127.3 (124.9-129.7) | 118.0 (115.7-120.3) | 111.6 (110.4-112.8) | 100.3 (97.3-103.2) |
| White | 60.6 (60.0-61.1) | 65.0 (64.5-65.5) | 66.2 (65.8-66.7) | 49.7 (49.1-50.2) |
| Hispanic | 117.2 (114.8-119.6) | 106.0 (102.6-109.4) | 108.8 (107.4-110.3) | 129.4 (127.8-131.0) |
| Age-Adjusted Death Rate per 100,000 According to Race for Cardiovascular Disease Only and COVID-19 Only (95% CI) | ||
|---|---|---|
| Cardiovascular Disease Only | COVID-19 Only | |
| Asian | 965.7 (963.0-968.5) | 235.9 (234.6-237.3) |
| Black or African American | 411.7 (409.2-414.2) | 103.2 (102.0-104.4) |
| White | 704.7 (703.8-705.5) | 138.2 (137.8-138.6) |
| Hispanic | 612.2 (610.0-614.4) | 251.7 (250.4-253.1) |
The study reveals several key findings. Deaths attributed to both COVID-19 and CVD were estimated at ∼70 per 100,000 persons in the United States, a figure higher than several common malignancies and many independent causes of CVD death. Hispanic and NH Black populations had higher AAMR related to both COVID-19 and CVD. Racial differences are determined to be a major determinant of outcomes with COVID-19, with minoritized populations experiencing higher risk of hospitalizations and mortality in several large-scale retrospective studies.2 , 3 Previous data revealed a much higher proportion of NH Black adults affected by COVID-19 compared with the proportion of NH Black adults in the total population.4 Data regarding vaccination were not available, which would have provided further insight if socioeconomic and racial inequities are confounded by vaccination rates in these populations.
Limitations of this analysis include a lack of individual-level data on baseline comorbidities, lack of statistical assessment for confounding variables, and the inability to ascertain the temporal association of CVD with COVID-19 infection, that is, if CVD occurred as a consequence of COVID-19 vs exacerbation of existing CVD related to COVID-19. Moreover, cause of death from out-of-hospital reported deaths is known to be less reliable. Therefore, it is important to emphasize that we cannot draw causal conclusions from these results.
In conclusion, mortality rates of concomitant COVID-19 and CVD in the United States are high, with persistent racial disparities. Efforts are needed to further delineate the reasons responsible for these differences that have an impact on clinical outcomes and mortality in the socially vulnerable strata of society.
Footnotes
Athena Poppas, MD, served as Guest Editor-in-Chief for this paper.
Dr Fudim has received grants from the National Heart, Lung, and Blood Institute (K23HL151744), the American Heart Association (20IPA35310955), Bayer, Bodyport, BTG Specialty Pharmaceuticals, and Verily; and has received consulting fees from Abbott, Alleviant, Audicor, AxonTherapies, Bayer, Bodyguide, Bodyport, Boston Scientific, Coridea, CVRx, Daxor, Deerfield Catalyst, Edwards Lifesciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, Medtronic, NXT Biomedical, Pharmacosmos, PreHealth, Shifamed, Splendo, Vironix, Viscardia, and Zoll. Dr Butler has received consulting fees from BI, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Ltd, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
References
- 1.Xie Y., Xu E., Bowe B., Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583–590. doi: 10.1038/s41591-022-01689-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Escobar G.J., Adams A.S., Liu V.X., et al. Racial disparities in COVID-19 testing and outcomes: retrospective cohort study in an integrated health system. Ann Intern Med. 2021;174:786–793. doi: 10.7326/M20-6979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Magesh S., John D., Li W.T., et al. Disparities in COVID-19 outcomes by race, ethnicity, and socioeconomic status: a systematic review and meta-analysis. JAMA Netw Open. 2021;4 doi: 10.1001/jamanetworkopen.2021.34147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Chowkwanyun M., Reed A.L. Racial health disparities and covid-19—caution and context. N Engl J Med. 2020;383:201–203. doi: 10.1056/NEJMp2012910. [DOI] [PubMed] [Google Scholar]