Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Narrative Review

Vol. 20 No. 2 (2022): New Horizons: Innovation in Medicine

The Interplay Between COVID-19 and Cardiovascular Disease

DOI
https://doi.org/10.26443/mjm.v20i2.880
Submitted
April 12, 2021
Published
2022-04-19

Abstract

Introduction: The emergence of the global COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus, SARS-CoV-2, has created a substantial burden on healthcare systems worldwide. The systemic impacts of COVID-19 infection are severe and broad in their implications, and the cardiovascular system is no exception. Discussion: Patients with a history of cardiovascular disease are at an increased risk for hospitalization and mortality, and COVID-19 infection has now been demonstrated to initiate acute, but serious, episodes of cardiovascular events such as stroke. Considering the rapid spread of COVID-19 across the globe and the inability of healthcare systems to address and adequately respond to the pandemic, therein lies an increased need for understanding the interplay between COVID-19 infection and cardiovascular disease. SARS-CoV-2 relies on binding the angiotensin-converting enzyme-2 (ACE2) receptor to infect host cells, with ACE2 representing a critical regulator of blood pressure homeostasis and proper cardiovascular functioning. Conclusion: Identifying the exact role of ACE2 in COVID-19 infection will have major implications for understanding the disease; therefore, here we have reviewed ACE2’s involvement in the pathogenesis of COVID-19 infection and the resulting end-organ damage. In addition, we have summarized how COVID-19 affects cardiovascular physiology, and how COVID-19 infection can manifest in acute cardiovascular events. Finally, we examine why patients with cardiovascular disease are at an increased risk of succumbing to COVID-19 and what the long-term cardiovascular implications of COVID-19 infection could mean. Relevance: This paper discusses the cardiovascular consequences of the global COVID-19 pandemic.

References

  1. Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. The Lancet Infectious Diseases. 2020;20(5):533-4. DOI:10.1016/s1473-3099(20)30120-1
  2. Mafham MM, Spata E, Goldacre R, Gair D, Curnow P, Bray M, et al. COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England. Lancet. 2020;396(10248):381-9. DOI:10.1016/S0140-6736(20)31356-8
  3. Bainton D, Jones GR, Hole D. Influenza and Ischaemic Heart Disease-a Possible Trigger for Acute Myocardial Infarction? Int J Epidemiol. 1978;7(3):231-9. DOI:10.1093/ije/7.3.231
  4. Spodick DH, Flessas AP, Johnson MM. Association of acute respiratory symptoms with onset of acute myocardial infarction: Prospective investigation of 150 consecutive patients and matched control patients. The American Journal of Cardiology. 1984;53(4):481-2. DOI:10.1016/0002-9149(84)90016-X
  5. Kwong JC, Schwartz KL, Campitelli MA, Chung H, Crowcroft NS, Karnauchow T, et al. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med. 2018;378(4):345-53. DOI:10.1056/NEJMoa1702090
  6. Madjid M, Miller CC, Zarubaev VV, Marinich IG, Kiselev OI, Lobzin YV, et al. Influenza epidemics and acute respiratory disease activity are associated with a surge in autopsy-confirmed coronary heart disease death: results from 8 years of autopsies in 34 892 subjects. European Heart Journal. 2007;28(10):1205-10. DOI:10.1093/eurheartj/ehm035
  7. Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med. 2004;351(25):2611-8. DOI:10.1056/NEJMoa041747
  8. Guzik TJ, Mohiddin SA, Dimarco A, Patel V, Savvatis K, Marelli-Berg FM, et al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovascular Research. 2020;116(10):1666-87. DOI:10.1093/cvr/cvaa106
  9. Bourgonje AR, Abdulle AE, Timens W, Hillebrands JL, Navis GJ, Gordijn SJ, et al. Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol. 2020;251(3):228-48. DOI:10.1002/path.5471
  10. Paz Ocaranza M, Riquelme JA, García L, Jalil JE, Chiong M, Santos RAS, et al. Counter-regulatory renin–angiotensin system in cardiovascular disease. Nature Reviews Cardiology. 2020;17(2):116-29. DOI:10.1038/s41569-019-0244-8
  11. Ferreira NS, Tostes RC, Paradis P, Schiffrin EL. Aldosterone, Inflammation, Immune System and Hypertension. Am J Hypertens. 2020. DOI:10.1093/ajh/hpaa137
  12. Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Engl J Med. 2020;382(17):1653-9. DOI:10.1056/NEJMsr2005760
  13. Ronco C, Reis T, Husain-Syed F. Management of acute kidney injury in patients with COVID-19. Lancet Respir Med. 2020;8(7):738-42. DOI:10.1016/S2213-2600(20)30229-0
  14. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 2020;395(10234):1417-8. DOI:10.1016/s0140-6736(20)30937-5
  15. Batlle D, Soler MJ, Sparks MA, Hiremath S, South AM, Welling PA, et al. Acute Kidney Injury in COVID-19: Emerging Evidence of a Distinct Pathophysiology. J Am Soc Nephrol. 2020;31(7):1380-3. DOI:10.1681/ASN.2020040419
  16. Nadim MK, Forni LG, Mehta RL, Connor MJ, Jr., Liu KD, Ostermann M, et al. COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup. Nat Rev Nephrol. 2020;16(12):747-64. DOI:10.1038/s41581-020-00356-5
  17. Romero-Sanchez CM, Diaz-Maroto I, Fernandez-Diaz E, Sanchez-Larsen A, Layos-Romero A, Garcia-Garcia J, et al. Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry. Neurology. 2020;95(8):e1060-e70. DOI:10.1212/WNL.0000000000009937
  18. Needham EJ, Chou SH, Coles AJ, Menon DK. Neurological Implications of COVID-19 Infections. Neurocrit Care. 2020;32(3):667-71. DOI:10.1007/s12028-020-00978-4
  19. Zhou M, Wong C-K, Un K-C, Lau Y-M, Lee JC-Y, Tam FC-C, et al. Cardiovascular sequalae in uncomplicated COVID-19 survivors. PLOS ONE. 2021;16(2):e0246732. DOI:10.1371/journal.pone.0246732
  20. Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(23):2950-73. DOI:10.1016/j.jacc.2020.04.031
  21. Klok FA, Kruip MJHA, Van Der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis Research. 2020;191:145-7. DOI:10.1016/j.thromres.2020.04.013
  22. Naymagon L, Zubizarreta N, Feld J, Van Gerwen M, Alsen M, Thibaud S, et al. Admission D-dimer levels, D-dimer trends, and outcomes in COVID-19. Thrombosis Research. 2020;196:99-105. DOI:10.1016/j.thromres.2020.08.032
  23. Rostami M, Mansouritorghabeh H. D-dimer level in COVID-19 infection: a systematic review. Expert Review of Hematology. 2020;13(11):1265-75. DOI:10.1080/17474086.2020.1831383
  24. Mueller C, Giannitsis E, Jaffe AS, Huber K, Mair J, Cullen L, et al. Cardiovascular biomarkers in patients with COVID-19. European Heart Journal Acute Cardiovascular Care. 2021. DOI:10.1093/ehjacc/zuab009
  25. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. DOI:10.1016/S0140-6736(20)30566-3
  26. Grobler C, Maphumulo SC, Grobbelaar LM, Bredenkamp JC, Laubscher GJ, Lourens PJ, et al. Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes. International Journal of Molecular Sciences. 2020;21(14):5168. DOI:10.3390/ijms21145168
  27. Kidde J, Gorabi AM, Jamialahmadi T, Sahebkar A. COVID-19 Is an Endothelial Disease: Implications of Nitric Oxide. Springer International Publishing; 2021. p. 109-13.
  28. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. DOI:10.1016/S0140-6736(20)30183-5
  29. Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System. JAMA. 2020;324(8):799-801. DOI:10.1001/jama.2020.13372
  30. McFadyen JD, Stevens H, Peter K. The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications. Circ Res. 2020;127(4):571-87. DOI:10.1161/CIRCRESAHA.120.317447
  31. Li Y, Li M, Wang M, Zhou Y, Chang J, Xian Y, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke and Vascular Neurology. 2020;5(3):279-84. DOI:10.1136/svn-2020-000431
  32. Qin C, Zhou L, Hu Z, Yang S, Zhang S, Chen M, et al. Clinical Characteristics and Outcomes of COVID-19 Patients With a History of Stroke in Wuhan, China. Stroke. 2020;51(7):2219-23. DOI:10.1161/strokeaha.120.030365
  33. Katsanos AH, Palaiodimou L, Zand R, Yaghi S, Kamel H, Navi BB, et al. The Impact of SARS‐CoV ‐2 on Stroke Epidemiology and Care: A Meta‐Analysis. Annals of Neurology. 2021;89(2):380-8. DOI:10.1002/ana.25967
  34. Qureshi AI, Baskett WI, Huang W, Shyu D, Myers D, Raju M, et al. Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients. Stroke. 2021:STROKEAHA120031786. DOI:10.1161/STROKEAHA.120.031786
  35. Ramos-Araque ME, Siegler JE, Ribo M, Requena M, López C, De Lera M, et al. Stroke etiologies in patients with COVID-19: the SVIN COVID-19 multinational registry. BMC Neurology. 2021;21(1). DOI:10.1186/s12883-021-02075-1
  36. Beyrouti R, Adams ME, Benjamin L, Cohen H, Farmer SF, Goh YY, et al. Characteristics of ischaemic stroke associated with COVID-19. Journal of Neurology, Neurosurgery & Psychiatry. 2020;91(8):889-91. DOI:10.1136/jnnp-2020-323586
  37. Hernández-Fernández F, Sandoval Valencia H, Barbella-Aponte RA, Collado-Jiménez R, Ayo-Martín Ó, Barrena C, et al. Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description. Brain. 2020;143(10):3089-103. DOI:10.1093/brain/awaa239
  38. Benussi A, Pilotto A, Premi E, Libri I, Giunta M, Agosti C, et al. Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy. Neurology. 2020;95(7):e910-e20. DOI:10.1212/wnl.0000000000009848
  39. Coromilas EJ, Kochav S, Goldenthal I, Biviano A, Garan H, Goldbarg S, et al. Worldwide Survey of COVID-19 Associated Arrhythmias. Circulation: Arrhythmia and Electrophysiology. 2021. DOI:10.1161/circep.120.009458
  40. Luetkens JA, Isaak A, Zimmer S, Nattermann J, Sprinkart AM, Boesecke C, et al. Diffuse Myocardial Inflammation in COVID-19 Associated Myocarditis Detected by Multiparametric Cardiac Magnetic Resonance Imaging. Circulation: Cardiovascular Imaging. 2020;13(5). DOI:10.1161/circimaging.120.010897
  41. Bojkova D, Wagner JUG, Shumliakivska M, Aslan GS, Saleem U, Hansen A, et al. SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes. Cardiovascular Research. 2020;116(14):2207-15. DOI:10.1093/cvr/cvaa267
  42. O’Shea CJ, Thomas G, Middeldorp ME, Harper C, Elliott AD, Ray N, et al. Ventricular arrhythmia burden during the coronavirus disease 2019 (COVID-19) pandemic. European Heart Journal. 2021;42(5):520-8. DOI:10.1093/eurheartj/ehaa893
  43. Bangalore S, Sharma A, Slotwiner A, Yatskar L, Harari R, Shah B, et al. ST-Segment Elevation in Patients with Covid-19 — A Case Series. N Engl J Med. 2020. DOI:10.1056/NEJMc2009020
  44. Modin D, Claggett B, Sindet-Pedersen C, Lassen MCH, Skaarup KG, Jensen JUS, et al. Acute COVID-19 and the Incidence of Ischemic Stroke and Acute Myocardial Infarction. Circulation. 2020;142(21):2080-2. DOI:10.1161/CIRCULATIONAHA.120.050809
  45. Sultanian P, Lundgren P, Stromsoe A, Aune S, Bergstrom G, Hagberg E, et al. Cardiac arrest in COVID-19: characteristics and outcomes of in- and out-of-hospital cardiac arrest. A report from the Swedish Registry for Cardiopulmonary Resuscitation. Eur Heart J. 2021. DOI:10.1093/eurheartj/ehaa1067
  46. De Rosa S, Spaccarotella C, Basso C, Calabrò MP, Curcio A, Filardi PP, et al. Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era. European Heart Journal. 2020. DOI:10.1093/eurheartj/ehaa409
  47. Metzler B, Siostrzonek P, Binder RK, Bauer A, Reinstadler SJ. Decline of acute coronary syndrome admissions in Austria since the outbreak of COVID-19: the pandemic response causes cardiac collateral damage. European Heart Journal. 2020. DOI:10.1093/eurheartj/ehaa314
  48. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth Universal Definition of Myocardial Infarction (2018). Journal of the American College of Cardiology. 2018;72(18):2231-64. DOI:10.1016/j.jacc.2018.08.1038
  49. Bonow RO, Fonarow GC, O’Gara PT, Yancy CW. Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality. JAMA Cardiology. 2020;5(7):751-3. DOI:10.1001/jamacardio.2020.1105
  50. Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091. DOI:10.1136/bmj.m1091
  51. Pareek M, Singh A, Vadlamani L, Eder M, Pacor J, Park J, et al. Relation of Cardiovascular Risk Factors to Mortality and Cardiovascular Events in Hospitalized Patients with Coronavirus Disease 2019 (From the Yale COVID-19 Cardiovascular Registry). Am J Cardiol. 2021. DOI:10.1016/j.amjcard.2021.01.029
  52. Botly LCP, Martin-Rhee M, Kasiban A, Swartz RH, Mulvagh SL, Lindsay MP, et al. COVID-19 Pandemic: Global Impact and Potential Implications for Cardiovascular Disease in Canada. CJC Open. 2020;2(4):265-72. DOI:10.1016/j.cjco.2020.06.003
  53. World Health Organization. Hypertension 2019 [Available from: https://www.who.int/news-room/fact-sheets/detail/hypertension.
  54. Garies S, Hao S, McBrien K, Williamson T, Peng M, Khan NA, et al. Prevalence of Hypertension, Treatment, and Blood Pressure Targets in Canada Associated With the 2017 American College of Cardiology and American Heart Association Blood Pressure Guidelines. JAMA Network Open. 2019;2(3):e190406. DOI:10.1001/jamanetworkopen.2019.0406
  55. Xia F, Zhang M, Cui B, An W, Chen M, Yang P, et al. COVID-19 patients with hypertension are at potential risk of worsened organ injury. Scientific Reports. 2021;11(1). DOI:10.1038/s41598-021-83295-w
  56. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020;323(20):2052. DOI:10.1001/jama.2020.6775
  57. Caillon A, Zhao K, Klein KO, Greenwood C, Lu Z, Paradis P, et al. High systolic blood pressure at hospital admission is an important risk factor in models predicting outcome of COVID-19 patients. Am J Hypertens. 2021. DOI:10.1093/ajh/hpaa225
  58. Nouri‐Vaskeh M, Kalami N, Zand R, Soroureddin Z, Varshochi M, Ansarin K, et al. Comparison of Losartan and Amlodipine Effects on the Outcomes of Patient with COVID‐19 and Primary Hypertension: A Randomized Clinical Trial. International Journal of Clinical Practice. 2021. DOI:10.1111/ijcp.14124
  59. Khera R, Clark C, Lu Y, Guo Y, Ren S, Truax B, et al. Association of Angiotensin‐Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease‐19. Journal of the American Heart Association. 2021. DOI:10.1161/jaha.120.018086
  60. Armstrong K, Soltoff A, Rieu-Werden M, Metlay J, Haas J. Use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers associated with lower risk of COVID-19 in household contacts. PLOS ONE. 2021;16(3):e0247548. DOI:10.1371/journal.pone.0247548
  61. HFSA/ACC/AHA Statement Addresses Concerns Re: Using RAAS Antagonists in COVID-19 [press release]. 2020.
  62. Garcia S, Albaghdadi Mazen S, Meraj Perwaiz M, Schmidt C, Garberich R, Jaffer Farouc A, et al. Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States During COVID-19 Pandemic. Journal of the American College of Cardiology. 2020;75(22):2871-2. DOI:10.1016/j.jacc.2020.04.011
  63. Hammad TA, Parikh M, Tashtish N, Lowry CM, Gorbey D, Forouzandeh F, et al. Impact of COVID-19 pandemic on ST-elevation myocardial infarction in a non-COVID-19 epicenter. Catheterization and Cardiovascular Interventions. 2021;97(2):208-14. DOI:https://doi.org/10.1002/ccd.28997
  64. Gluckman TJ, Wilson MA, Chiu S-T, Penny BW, Chepuri VB, Waggoner JW, et al. Case Rates, Treatment Approaches, and Outcomes in Acute Myocardial Infarction During the Coronavirus Disease 2019 Pandemic. JAMA Cardiology. 2020;5(12):1419. DOI:10.1001/jamacardio.2020.3629
  65. Becker RC. Anticipating the long-term cardiovascular effects of COVID-19. J Thromb Thrombolysis. 2020:1-13. DOI:10.1007/s11239-020-02266-6
  66. Zheng C, Huang WY, Sheridan S, Sit CH-P, Chen X-K, Wong SH-S. COVID-19 Pandemic Brings a Sedentary Lifestyle in Young Adults: A Cross-Sectional and Longitudinal Study. Int J Environ Res Public Health. 2020;17(17). DOI:10.3390/ijerph17176035
  67. Rossen LM, Branum AM, Ahmad FB, Sutton P, Anderson RN. Excess Deaths Associated with COVID-19, by Age and Race and Ethnicity — United States, January 26–October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(42):1522-7. DOI:10.15585/mmwr.mm6942e2
  68. Badreldin HA, Atallah B. Global drug shortages due to COVID-19: Impact on patient care and mitigation strategies. Res Social Adm Pharm. 2021;17(1):1946-9. DOI:10.1016/j.sapharm.2020.05.017
  69. Toh DJW, Rowe E, Nelson R, O'Connell A, Lim K, Fielke L, et al. Outcomes for the first wave of hospitalised patients with COVID‐19 in the South Australian context: a retrospective audit. Internal Medicine Journal. 2021;51(2):189-98. DOI:10.1111/imj.15106
  70. Murthy S, Archambault PM, Atique A, Carrier FM, Cheng MP, Codan C, et al. Characteristics and outcomes of patients with COVID-19 admitted to hospital and intensive care in the first phase of the pandemic in Canada: a national cohort study. CMAJ Open. 2021;9(1):E181-E8. DOI:10.9778/cmajo.20200250
  71. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-20. DOI:10.1056/NEJMoa2002032
  72. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-81. DOI:10.1001/jama.2020.5394
  73. Pouw N, Van De Maat J, Veerman K, Ten Oever J, Janssen N, Abbink E, et al. Clinical characteristics and outcomes of 952 hospitalized COVID-19 patients in The Netherlands: A retrospective cohort study. PLOS ONE. 2021;16(3):e0248713. DOI:10.1371/journal.pone.0248713
  74. Velasco-Rodríguez D, Alonso-Dominguez J-M, Vidal Laso R, Lainez-González D, García-Raso A, Martín-Herrero S, et al. Development and validation of a predictive model of in-hospital mortality in COVID-19 patients. PLOS ONE. 2021;16(3):e0247676. DOI:10.1371/journal.pone.0247676
  75. Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, et al. Clinical Characteristics of Covid-19 in New York City. N Engl J Med. 2020;382(24):2372-4. DOI:10.1056/NEJMc2010419

Downloads

Download data is not yet available.

Similar Articles

You may also start an advanced similarity search for this article.