Commentary based on Sidney S, Lee C, Liu J, Khan SS, Lloyd-Jones DM, Rana JS. Age-adjusted mortality rates and age and risk–associated contributions to change in heart disease and stroke mortality, 2011-2019 and 2019-2020. JAMA Netw Open 2022;5:e223872.

Introduction
COVID-19's impact has been felt across the entire healthcare system. Sidney et al. evaluated the pandemic's influence on cardiovascular-related mortality, and they examined the relative contributions of aging versus underlying disease risk in the total population and in major race/ethnicity groups.

Methods
The study calculated the age-associated and risk-associated deaths for each year between 2011 and 2020. The calculations were then compared from 2011-2019 and 2019-2020.¹

The mortality data used in this study was sourced from the Centers for Disease Control and Prevention (CDC) Wide-Ranging OnLine Data for Epidemiologic Research (WONDER) database, which relies on reported cause of death coding.¹ In 2020, only 5.5% of death certificates had COVID-19 without any other conditions listed in patients that died with COVID.² Confirmation by autopsy is not reflected in these numbers, which is a limitation.

Race and ethnicity data was traced from the United States (US) Census and was self-reported.¹

Results and Conclusion
The cohort study by Sidney et al. found an increase in risk-associated and age-adjusted deaths from heart disease and stroke between 2019 and 2020. There was a 4.1% increase in heart disease deaths and 5.2% in stroke deaths when compared to 2011-2019. This contrasts with a decrease in risk-associated deaths from heart disease by 7.1% and stroke by 1.8% from 2011 to 2019. There was also a 17.6% increase in total age-associated heart disease mortality and a 18.1% increase in deaths from stroke from 2019 to 2020. Racial/ethnic minority groups, particularly non-Hispanic Blacks, saw the greatest increases in risk-associated mortality.¹

Risk-associated increases in mortality were highest in non-Hispanic Black individuals, followed by Hispanic individuals, non-Hispanic Asian or Pacific Islander individuals, and non-Hispanic White individuals. There was more than a five-fold higher percentage increase in non-Hispanic Black individuals compared with non-Hispanic White individuals for heart disease and a two-fold higher percent.¹ The racial disparities seen in the mortality from heart disease and stroke are consistent with the disparities seen with COVID-19. Both the non-Hispanic Blacks and Hispanic populations had experienced disproportionately higher rates of COVID-19 infection and mortality. Access to healthcare and risk of exposure are thought to be driving factors.³

Discussion
While evaluating the results of this study, it is important to consider the methodology of the sourced data. The WONDER database relies on reported cause of death coding.¹ In 2020, only 5.5% of death certificates had COVID-19 without any other conditions listed in patients that died with COVID.² While COVID can be a systemic illness, the methodology of having only COVID as the cause of death in absence of other conditions is highly unlikely. Confirmation by autopsy is not reflected in these numbers, which is a limitation. The calculations rely on the accuracy and completeness of those that coded the causes of death.

A mechanistic explanation for this increase in mortality could be related to delays in timely care. Many patients missed scheduled appointments for fear of exposure to the SARS-CoV2 virus or provider office closures. Additionally, overcrowding in hospitals and fear delayed emergency room visits. There was also limited resources and staffing. For example, one case report highlights "what would have been a standard ST-elevation myocardial infarction treated with timely and successful stenting of a dominant right coronary artery occlusion, became a much more dangerous postinfarction ventricular septal defect".⁴

Health behaviors were greatly impacted during the pandemic. A survey that assessed lifestyle changes during COVID-19 found that weight gain was reported in 27.5% of the participants.⁵ This was likely a result of the reported increase in sedentary leisure coupled with a decrease in time spent engaging in physical activity. The same survey also showed an increase in anxiety scores,⁵ which led to fears of venturing out to gyms. The survey did uncover an increase in home-cooking.⁵ Another study found that significantly higher average adult body mass indexes (BMIs) and obesity prevalence rates during the COVID-19 pandemic coincided with observed higher rates of alcohol consumption and lower smoking rates.⁶

There may also be an underlying link between the increased stress and anxiety experienced during the pandemic and epigenetic changes. One study assessed the relationship between psychosocial stress and inflammation. Stress-driven FK506 binding protein 5 nuclear factor-kappa light-chain enhancer of activated B cells (FKBP5-NF-κB) signaling mediates the inflammatory process. An epigenetic change where aging and stress enhanced FK506-NF-κB through a positive feedback loop results in increased inflammation. This epigenetic response was found in those with a history of acute myocardial infarction.⁷ These findings depict a connection between psychosocial stress, inflammation, and cardiovascular risk on an epigenetic level.

Alcohol use also increased during the pandemic. An Alcohol Use Disorders Identification Test (AUDIT) survey revealed that AUDIT scores increased. An analysis of the survey results showed greater alcohol consumption was associated with a younger age, male sex, and primary job loss due to COVID-19. The greatest increase in high-risk drinking was observed largely among individuals who were under stay-at-home restrictions. Working from home also presented opportunities to consume alcohol during the day that would not have been present in the traditional office setting.⁸

With COVID-19 vaccines and risk-reduction measures in place, clinicians should address these potential changes in health behaviors and emphasize the importance of regular follow-up with their patients. Psychosocial stress, alcohol, weight gain, vascular inflammation, and sedentary lifestyles are risk enhancing factors of stroke and heart disease. Additionally, we must address social determinants of health to promote health equity and narrow health disparities in the community.

Table 1

Factors Leading to Observed Increase CV Mortality from 2019-2020

Delayed emergent and routine care

Limited healthcare resources

Increases in BMI

Increased alcohol consumption

Less physical activity

Increase in stress and anxiety levels

Increase in negative coping behaviors

Increased vascular inflammation secondary to increased stress and anxiety

Underlying health disparities intensified

Data limitation: coding cause of death

References

1. Sidney S, Lee C, Liu J, Khan SS, Lloyd-Jones DM, Rana JS. Age-adjusted mortality rates and age and risk–associated contributions to change in heart disease and stroke mortality, 2011-2019 and 2019-2020. JAMA Netw Open 2022;5:e223872.
2. Gundlapalli AV, Lavery AM, Boehmer TK, et al. Death certificate–based ICD-10 diagnosis codes for COVID-19 mortality surveillance — United States, January–December 2020. MMWR Morb Mortal Wkly Rep 2021;70:523–27.
3. Mackey K, Ayers CK, Kondo KK, et al. Racial and ethnic disparities in COVID-19-related infections, hospitalizations, and deaths: a systematic review. Ann Intern Med 2021;174:362-73.
4. Masroor S. Collateral damage of COVID-19 pandemic: delayed medical care. J Card Surg 2020;35:1345-47.
5. Flanagan EW, Beyl RA, Fearnbach SN, Altazan AD, Martin CK, Redman LM. The impact of COVID-19 stay-at-home orders on health behaviors in adults. Obesity (Silver Spring) 2021;29:438-45.
6. Restrepo BJ. Obesity prevalence among U.S. adults during the COVID-19 pandemic. Am J Prev Med 2022;Apr 04:[Epub ahead of print].
7. Zannas AS, Jia M, Hafner K, et al. Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-κB-driven inflammation and cardiovascular risk. Proc Natl Acad Sci U S A 2019;116:11370-79.
8. Killgore WDS, Cloonan SA, Taylor EC, Lucas DA, Dailey NS. Alcohol dependence during COVID-19 lockdowns. Psychiatry Res 2021;296:113676.

Clinical Topics: Cardiac Surgery, Cardiovascular Care Team, Congenital Heart Disease and Pediatric Cardiology, COVID-19 Hub, Diabetes and Cardiometabolic Disease, Prevention, Stable Ischemic Heart Disease, Vascular Medicine, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and SIHD, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Exercise, Smoking, Stress, Chronic Angina, Dyslipidemia

Keywords: COVID-19, COVID-19 Vaccines, SARS-CoV-2, Pandemics, Cardiovascular Diseases, Cohort Studies, Ethnic Groups, African Americans, Cause of Death, Death Certificates, Tacrolimus, Coronary Vessels, Follow-Up Studies, Health Promotion, Prevalence, ST Elevation Myocardial Infarction, Sedentary Behavior, Self Report, Social Determinants of Health, Minority Groups, Risk Factors, Heart Disease Risk Factors, Aging, Stroke, Obesity, Centers for Disease Control and Prevention, U.S., Heart Septal Defects, Ventricular, Stress, Psychological, Alcohol Drinking, Delivery of Health Care, Exercise, Health Behavior, Emergency Service, Hospital, Risk Reduction Behavior, Weight Gain, Epigenesis, Genetic, Hospitals, Workforce, Anxiety, Smoking, Primary Prevention

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