Long-Term Major Adverse Cardiovascular Events in Patients with Moderate and Severe Covid-19: Focused on Early Statin Use and Previous CVD
-
Arezoo Khosravi
,
Saeed Ghodsi
,
Mohammadreza Memarjafari
,
Alireza Nematollahi
,
Reza Sheikh Sharbafan
,
Seyed-Ali Sadre-Bafghi
,
Seyed-Vahid Moosavi
,
Mansour Abdollahzadeh
,
Arash Jalali
,
Maryam Moshkani Farahani
Abstract
Background: Limited data exist regarding the status of long-term cardiovascular disease (CVD) outcomes of hospitalized COVID-19 patients. We aimed to examine the efficacy of early statin use after SARS‑CoV‑2 pneumonia and the impact of prior CVD on the incidence of cardiovascular events.
Methods: A prospective cohort study was performed on hospitalized COVID-19 patients. The primary endpoint was major adverse cardiovascular events (MACE) as a composite of cardiovascular mortality, stroke, heart failure, venous thromboembolism (VTE), revascularization, and nonfatal myocardial infarction (MI). The secondary endpoints comprised MACE components, all-cause mortality, readmission for COVID-19, and impaired functional classes.
Results: The mean age of the 858 participants was 55.52±13.97 years, and the median follow-up time was 13 months (11.5-15). Men comprised 63.9% of the patients. Overall, MACE occurred in 84 subjects (9.8%), and 98 patients (11.4%) received ventilation. A multivariate Cox regression model was employed to explore the association between statin use and outcomes, and the following hazard ratios were obtained: MACE (0.831 [0.529 to 0.981]; P=0.044), All-cause mortality (1.098 [0.935 to 1.294]; P=0.255), stroke (0.118 [0.029 to 0.48]; P=0.003), revascularization (0.103 [0.029 to 0.367]; P<0.0001), poor functional capacity (0.827 [0.673 to 1.018]; P=0.073), nonfatal MI (0.599 [0.257 to 1.394]; P=0.234), VTE (0.376 [0.119 to 1.190]; P=0.096), and decompensated heart failure (0.137 [0.040 to 0.472]; P=0.002). Prior CVD predicted MACE (2.953 [1.393 to 6.271]; P=0.005), all-cause death (1.170 [0.960 to 1.412]; P=0.102), and VTE (2.770 [0.957 to 8.955]; P=0.051).
Conclusion: Previous CVD is a robust predictor of long-term MACE and VTE. Early statin use might decrease the incidence rates of MACE, ischemic stroke, revascularization, and readmission for heart failure.
1. Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol 2020;17:259-260.
2. Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail 2020;26:470-475.
3. Creel-Bulos C, Hockstein M, Amin N, Melhem S, Truong A, Sharifpour M. Acute Cor Pulmonale in Critically Ill Patients with COVID-19. N Engl J Med 2020;382:e70.
4. Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association? Eur Heart J 2020;41:1858.
5. Fox SE, Lameira FS, Rinker EB, Vander Heide RS. Cardiac Endotheliitis and Multisystem Inflammatory Syndrome after COVID-19. Ann Intern Med 2020;173:1025-1027.
6. Figliozzi S, Masci PG, Ahmadi N, Tondi L, Koutli E, Aimo A, Stamatelopoulos K, Dimopoulos MA, Caforio ALP, Georgiopoulos G. Predictors of adverse prognosis in COVID-19: A systematic review and meta-analysis. Eur J Clin Invest 2020;50:e13362.
7. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, Gong W, Liu X, Liang J, Zhao Q, Huang H, Yang B, Huang C. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol 2020;5:802-810.
8. Katsoularis I, Fonseca-Rodríguez O, Farrington P, Lindmark K, Fors Connolly AM. Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study. Lancet 2021;398(10300):599-607.
9. Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med 2022;28:583-590.
10. Wang W, Wang CY, Wang SI, Wei JC. Long-term cardiovascular outcomes in COVID-19 survivors among non-vaccinated population: A retrospective cohort study from the TriNetX US collaborative networks. EClinicalMedicine 2022;53:101619.
11. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation 2018;138:e618-e651.
12. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale. Circulation 1981;64:1227-1234.
13. Writing Committee; Gluckman TJ, Bhave NM, Allen LA, Chung EH, Spatz ES, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2022;79:1717-1756.
14. Ayoubkhani D, Khunti K, Nafilyan V, Maddox T, Humberstone B, Diamond I, Banerjee A. Post-covid syndrome in individuals admitted to hospital with COVID-19: retrospective cohort study. BMJ 2021;372:n693.
15. Günster C, Busse R, Spoden M, Rombey T, Schillinger G, Hoffmann W, Weber-Carstens S, Schuppert A, Karagiannidis C. 6-month mortality and readmissions of hospitalized COVID-19 patients: A nationwide cohort study of 8,679 patients in Germany. PLoS One 2021;16:e0255427.
16. Leijte WT, Wagemaker NMM, van Kraaij TDA, de Kruif MD, Mostard GJM, Leers MPG, Mostard RLM, Buijs J, van Twist DJL. Sterfte en heropname na ziekenhuisopname met COVID-19 [Mortality and re-admission after hospitalization with COVID-19]. Ned Tijdschr Geneeskd 2020;164:D5423.
17. Ballin M, Bergman J, Kivipelto M, Nordström A, Nordström P. Excess Mortality After COVID-19 in Swedish Long-Term Care Facilities. J Am Med Dir Assoc 2021;22:1574-1580.e8.
18. Rezel-Potts E, Douiri A, Sun X, Chowienczyk PJ, Shah AM, Gulliford MC. Cardiometabolic outcomes up to 12 months after COVID-19 infection. A matched cohort study in the UK. PLoS Med 2022;19:e1004052.
19. Katsoularis I, Fonseca-Rodríguez O, Farrington P, Lindmark K, Fors Connolly AM. Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study. Lancet 2021;398(10300):599-607.
20. Sung JG, Sobieszczyk PS, Bhatt DL. Acute Myocardial Infarction Within 24 Hours After COVID-19 Vaccination. Am J Cardiol 2021;156:129-131.
21. Kim YE, Huh K, Park YJ, Peck KR, Jung J. Association Between Vaccination and Acute Myocardial Infarction and Ischemic Stroke After COVID-19 Infection. JAMA 2022;328:887-889.
22. Ye X, Ma T, Blais JE, Yan VKC, Kang W, Chui CSL, Lai FTT, Li X, Wan EYF, Wong CKH, Tse HF, Siu CW, Wong ICK, Chan EW. Association between BNT162b2 or CoronaVac COVID-19 vaccines and major adverse cardiovascular events among individuals with cardiovascular disease. Cardiovasc Res 2022;118:2329-2338.
23. Driggin E, Maddox TM, Ferdinand KC, Kirkpatrick JN, Ky B, Morris AA, Mullen JB, Parikh SA, Philbin DM Jr, Vaduganathan M. ACC Health Policy Statement on Cardiovascular Disease Considerations for COVID-19 Vaccine Prioritization: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2021;77:1938-1948.
24. Harrison SL, Buckley BJR, Rivera-Caravaca JM, Zhang J, Lip GYH. Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews. Eur Heart J Qual Care Clin Outcomes 2021;7:330-339.
25. Zein AFMZ, Sulistiyana CS, Khasanah U, Wibowo A, Lim MA, Pranata R. Statin and mortality in COVID-19: a systematic review and meta-analysis of pooled adjusted effect estimates from propensity-matched cohorts. Postgrad Med J 2022;98:503-508.
26. Ayeh SK, Abbey EJ, Khalifa BAA, Nudotor RD, Osei AD, Chidambaram V, Osuji N, Khan S, Salia EL, Oduwole MO, Yusuf HE, Lasisi O, Nosakhare E, Karakousis PC. Statins use and COVID-19 outcomes in hospitalized patients. PLoS One 2021;16:e0256899.
27. INSPIRATION-S Investigators. Atorvastatin versus placebo in patients with COVID-19 in intensive care: randomized controlled trial. BMJ 2022;376:e068407.
28. Castiglione V, Chiriacò M, Emdin M, Taddei S, Vergaro G. Statin therapy in COVID-19 infection. Eur Heart J Cardiovasc Pharmacother 2020;6:258-259.
29. Correale M, Tricarico L, Fortunato M, Dattilo G, Iacoviello M, Brunetti ND. Infection, atherothrombosis and thromboembolism beyond the COVID-19 disease: what similar in physiopathology and researches. Aging Clin Exp Res 2021;33:273-278.
30. Lim MA, Pranata R, Huang I, Yonas E, Soeroto AY, Supriyadi R. Multiorgan Failure With Emphasis on Acute Kidney Injury and Severity of COVID-19: Systematic Review and Meta-Analysis. Can J Kidney Health Dis 2020;7:2054358120938573.
2. Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail 2020;26:470-475.
3. Creel-Bulos C, Hockstein M, Amin N, Melhem S, Truong A, Sharifpour M. Acute Cor Pulmonale in Critically Ill Patients with COVID-19. N Engl J Med 2020;382:e70.
4. Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association? Eur Heart J 2020;41:1858.
5. Fox SE, Lameira FS, Rinker EB, Vander Heide RS. Cardiac Endotheliitis and Multisystem Inflammatory Syndrome after COVID-19. Ann Intern Med 2020;173:1025-1027.
6. Figliozzi S, Masci PG, Ahmadi N, Tondi L, Koutli E, Aimo A, Stamatelopoulos K, Dimopoulos MA, Caforio ALP, Georgiopoulos G. Predictors of adverse prognosis in COVID-19: A systematic review and meta-analysis. Eur J Clin Invest 2020;50:e13362.
7. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, Gong W, Liu X, Liang J, Zhao Q, Huang H, Yang B, Huang C. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol 2020;5:802-810.
8. Katsoularis I, Fonseca-Rodríguez O, Farrington P, Lindmark K, Fors Connolly AM. Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study. Lancet 2021;398(10300):599-607.
9. Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med 2022;28:583-590.
10. Wang W, Wang CY, Wang SI, Wei JC. Long-term cardiovascular outcomes in COVID-19 survivors among non-vaccinated population: A retrospective cohort study from the TriNetX US collaborative networks. EClinicalMedicine 2022;53:101619.
11. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation 2018;138:e618-e651.
12. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale. Circulation 1981;64:1227-1234.
13. Writing Committee; Gluckman TJ, Bhave NM, Allen LA, Chung EH, Spatz ES, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2022;79:1717-1756.
14. Ayoubkhani D, Khunti K, Nafilyan V, Maddox T, Humberstone B, Diamond I, Banerjee A. Post-covid syndrome in individuals admitted to hospital with COVID-19: retrospective cohort study. BMJ 2021;372:n693.
15. Günster C, Busse R, Spoden M, Rombey T, Schillinger G, Hoffmann W, Weber-Carstens S, Schuppert A, Karagiannidis C. 6-month mortality and readmissions of hospitalized COVID-19 patients: A nationwide cohort study of 8,679 patients in Germany. PLoS One 2021;16:e0255427.
16. Leijte WT, Wagemaker NMM, van Kraaij TDA, de Kruif MD, Mostard GJM, Leers MPG, Mostard RLM, Buijs J, van Twist DJL. Sterfte en heropname na ziekenhuisopname met COVID-19 [Mortality and re-admission after hospitalization with COVID-19]. Ned Tijdschr Geneeskd 2020;164:D5423.
17. Ballin M, Bergman J, Kivipelto M, Nordström A, Nordström P. Excess Mortality After COVID-19 in Swedish Long-Term Care Facilities. J Am Med Dir Assoc 2021;22:1574-1580.e8.
18. Rezel-Potts E, Douiri A, Sun X, Chowienczyk PJ, Shah AM, Gulliford MC. Cardiometabolic outcomes up to 12 months after COVID-19 infection. A matched cohort study in the UK. PLoS Med 2022;19:e1004052.
19. Katsoularis I, Fonseca-Rodríguez O, Farrington P, Lindmark K, Fors Connolly AM. Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study. Lancet 2021;398(10300):599-607.
20. Sung JG, Sobieszczyk PS, Bhatt DL. Acute Myocardial Infarction Within 24 Hours After COVID-19 Vaccination. Am J Cardiol 2021;156:129-131.
21. Kim YE, Huh K, Park YJ, Peck KR, Jung J. Association Between Vaccination and Acute Myocardial Infarction and Ischemic Stroke After COVID-19 Infection. JAMA 2022;328:887-889.
22. Ye X, Ma T, Blais JE, Yan VKC, Kang W, Chui CSL, Lai FTT, Li X, Wan EYF, Wong CKH, Tse HF, Siu CW, Wong ICK, Chan EW. Association between BNT162b2 or CoronaVac COVID-19 vaccines and major adverse cardiovascular events among individuals with cardiovascular disease. Cardiovasc Res 2022;118:2329-2338.
23. Driggin E, Maddox TM, Ferdinand KC, Kirkpatrick JN, Ky B, Morris AA, Mullen JB, Parikh SA, Philbin DM Jr, Vaduganathan M. ACC Health Policy Statement on Cardiovascular Disease Considerations for COVID-19 Vaccine Prioritization: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2021;77:1938-1948.
24. Harrison SL, Buckley BJR, Rivera-Caravaca JM, Zhang J, Lip GYH. Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews. Eur Heart J Qual Care Clin Outcomes 2021;7:330-339.
25. Zein AFMZ, Sulistiyana CS, Khasanah U, Wibowo A, Lim MA, Pranata R. Statin and mortality in COVID-19: a systematic review and meta-analysis of pooled adjusted effect estimates from propensity-matched cohorts. Postgrad Med J 2022;98:503-508.
26. Ayeh SK, Abbey EJ, Khalifa BAA, Nudotor RD, Osei AD, Chidambaram V, Osuji N, Khan S, Salia EL, Oduwole MO, Yusuf HE, Lasisi O, Nosakhare E, Karakousis PC. Statins use and COVID-19 outcomes in hospitalized patients. PLoS One 2021;16:e0256899.
27. INSPIRATION-S Investigators. Atorvastatin versus placebo in patients with COVID-19 in intensive care: randomized controlled trial. BMJ 2022;376:e068407.
28. Castiglione V, Chiriacò M, Emdin M, Taddei S, Vergaro G. Statin therapy in COVID-19 infection. Eur Heart J Cardiovasc Pharmacother 2020;6:258-259.
29. Correale M, Tricarico L, Fortunato M, Dattilo G, Iacoviello M, Brunetti ND. Infection, atherothrombosis and thromboembolism beyond the COVID-19 disease: what similar in physiopathology and researches. Aging Clin Exp Res 2021;33:273-278.
30. Lim MA, Pranata R, Huang I, Yonas E, Soeroto AY, Supriyadi R. Multiorgan Failure With Emphasis on Acute Kidney Injury and Severity of COVID-19: Systematic Review and Meta-Analysis. Can J Kidney Health Dis 2020;7:2054358120938573.
| Files | ||
| Issue | Vol 18 No 3 (2023): J Teh Univ Heart Ctr | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jthc.v18i3.14113 | |
| Keywords | ||
| COVID-19 SARS-CoV2 MACE statin cardiovascular disease outcome mortality | ||
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How to Cite
1.
Khosravi A, Ghodsi S, Memarjafari M, Nematollahi A, Sharbafan R, Sadre-Bafghi S-A, Moosavi S-V, Abdollahzadeh M, Jalali A, Moshkani Farahani M. Long-Term Major Adverse Cardiovascular Events in Patients with Moderate and Severe Covid-19: Focused on Early Statin Use and Previous CVD. J Tehran Heart Cent. 2023;18(3):183-195.
