Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19

Abstract Background Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. Methods Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020. Results Of the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those ≤65 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74). Conclusions Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital.)

[1]  K. Harmon,et al.  Comorbid Medical Conditions in Young Athletes: Considerations for Preparticipation Guidance During the COVID-19 Pandemic , 2020, Sports health.

[2]  Christophe G. Lambert,et al.  Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study , 2020, medRxiv.

[3]  N. Soudani,et al.  Molecular Insights Into SARS COV-2 Interaction With Cardiovascular Disease: Role of RAAS and MAPK Signaling , 2020, Frontiers in Pharmacology.

[4]  M. Fralick,et al.  Good things come in threes (and sometimes fours): Update on renin–angiotensin–aldosterone system inhibitors and COVID-19 , 2020, Canadian Medical Association Journal.

[5]  A. Zhernakova,et al.  Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes , 2020, Frontiers in Genetics.

[6]  T. Walther,et al.  Cell type-specific expression of the putative SARS-CoV-2 receptor ACE2 in human hearts , 2020, European heart journal.

[7]  Tao Guo,et al.  Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19) , 2020, JAMA cardiology.

[8]  G. Oudit,et al.  Angiotensin Converting Enzyme 2: A Double-Edged Sword. , 2020, Circulation.

[9]  W. Gong,et al.  Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. , 2020, JAMA cardiology.

[10]  A. Verma,et al.  COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? , 2020, JAMA.

[11]  F. Ruschitzka,et al.  COVID-19 Illness and Heart Failure , 2020, JACC: Heart Failure.

[12]  Mandeep R. Mehra,et al.  COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal , 2020, The Journal of Heart and Lung Transplantation.

[13]  Sharukh Lokhandwala,et al.  Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. , 2020, JAMA.

[14]  Michael Roth,et al.  Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? , 2020, The Lancet Respiratory Medicine.

[15]  A. Walls,et al.  Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein , 2020, Cell.

[16]  G. Herrler,et al.  SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor , 2020, Cell.

[17]  Qiurong Ruan,et al.  Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China , 2020, Intensive Care Medicine.

[18]  Young-Jun Park,et al.  Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein , 2020, Cell.

[19]  X. Li,et al.  The vasoprotective axes of the renin‐angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases , 2017, Pharmacological research.

[20]  P. T. Ten Eyck,et al.  Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection , 2017, The Journal of Immunology.

[21]  S. Klein,et al.  Sex differences in immune responses , 2016, Nature Reviews Immunology.

[22]  Kazuhiko Ito,et al.  Seasonal Influenza Infections and Cardiovascular Disease Mortality. , 2016, JAMA cardiology.

[23]  D. Diz,et al.  Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Receptor Blockers on Cardiac Angiotensin-Converting Enzyme 2 , 2005, Circulation.

[24]  N. Hooper,et al.  Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. , 2004, The Biochemical journal.

[25]  D. Chong,et al.  Do Men Have a Higher Case Fatality Rate of Severe Acute Respiratory Syndrome than Women Do? , 2004, American journal of epidemiology.

[26]  World Health Organization Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected. Interim guidance , 2020 .