Predictors of stable coronary artery disease progression in the post-COVID period.

Aim. To evaluate the clinical course of stable coronary artery disease (CAD) depending on the timing of disease onset in relation to COVID-19 infection, and to identify predictors of disease progression during the post-COVID period. Materials and Methods. This study included 431 patients with stable CAD who had a confirmed history of COVID-19 between 2020 and 2023, with a minimum of 3 months between infection and enrollment. Patients were divided into two groups based on the timing of CAD diagnosis: patients diagnosed with CAD in the post-COVID period (n = 198, post-COVID-CAD) and patients diagnosed with CAD before their COVID-19 infection (n = 233, pre- COVID-CAD). We further evaluated clinical and laboratory parameters, including lipid profile (apolipoprotein A1, apolipoprotein B, lipoprotein( a)), N-terminal pro-brain natriuretic peptide (NT-proBNP), ST2, and coronary angiography. Logistic regression analysis was used to identify predictors of CAD progression. Results. Patients with pre- COVID-CAD were older (median age 62 vs. 61 years, p = 0.009), had a higher body mass index (BMI: 31.02 vs. 28.73 kg/m², p < 0.001), and a longer history of arterial hypertension (15 vs. 9.5 years, p < 0.001). COVID-19 was more severe in patients with pre-COVID-CAD, with a higher hospitalization rate (50.2% vs. 37.8%, p = 0.012) and more frequent moderate cases during the acute phase (58.7% vs. 45.9%, p < 0.009). Patients with pre-COVID-CAD also had a higher prevalence of prior myocardial infarction (51.0% vs. 26.7%, p < 0.001) and hemodynamically significant coronary artery lesions (86.2% vs. 67.6%, p < 0.001). Conversely, normal coronary arteries were more often observed in patients with post-COVID-CAD (8.5% vs. 7.2%, p = 0.003), possibly indicating microvascular involvement in post-COVID-CAD pathogenesis. Multifocal atherosclerosis was prevalent in both groups (75.7% vs. 79.8%, p = 0.351). Heart failure with mildly reduced ejection fraction (HFmrEF) was more common in patients with pre-COVID-CAD (10.7% vs. 5.0%, p = 0.034), whereas heart failure with preserved ejection fraction (HFpEF) predominated in patients with post-COVIDCAD (94.9% vs. 89.2%, p = 0.034). Left ventricular ejection fraction and glomerular filtration rate were significantly lower in patients with pre-COVID-CAD (60% vs. 62%, p = 0.007; 63.0 vs. 67.5 mL/min/1.73 m², p < 0.001, respectively). Laboratory indicators such as triglycerides, Lp(a), apoB, uric acid, and cystatin C were significantly elevated in patients with pre-COVID-CAD (p < 0.05). Multivariate analysis identified the following significant predictors of CAD progression in the post-COVID period: angina duration > 2.5 years, BMI > 29.66 kg/m², a history of moderate COVID-19, Lp(a) > 317.6 mg/dL, and NT-proBNP > 161.04 pg/mL. Conclusion. The timing of CAD onset in relation to COVID-19 significantly influences the disease course, emphasizing the need for a differentiated management strategy in post-COVID patients to predict CAD progression

1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirusinfected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–1069. https://doi.org/10.1001/jama.2020.1585

2. Shi S., Qin M., Cai Y., Liu T., Shen B., Yang F. et al. Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. Eur. Heart J. 2020;41(22):2070–2079. https://doi.org/10.1093/eurheartj/ehaa408

3. Shi S., Qin M., Shen B., Cai Y., Liu T., Yang F. et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5(7):802–810. https://doi.org/10.1001/jamacardio.2020.0950

4. Lala A., Johnson K.W., Januzzi J.L., Russak A.J., Paranjpe I., Richter F. et al. Prevalence and impact of myocardial injury in patients hospitalized with COVID-19 infection. J. Am. Coll. Cardiol. 2020;76(5):533–546. https://doi.org/10.1016/j.jacc.2020.06.007

5. Lombardi C.M., Carubelli V., Iorio A., Inciardi R.M., Bellasi A., Canale C. et al. Association of troponin levels with mortality in Italian patients hospitalized with coronavirus disease 2019: results of a multicenter study. JAMA Cardiol. 2020;5(11):1274–1280. https://doi.org/10.1001/jamacardio.2020.3538

6. Avanoglu Guler A., Tombul N., Aysert Yıldız P., Özger H.S., Hızel K., Gulbahar O. et al. The assessment of serum ACE activity in COVID-19 and its association with clinical features and severity of the disease. Scand. J. Clin. Lab. Invest. 2021;81(2):160–165. doi:10.1080/00365513.2021.1871641

7. Al-Aly Z., Xie Y., Bowe B. High-dimensional characterization of postacute sequelae of COVID-19. Nature. 2021;594(7862):259–264. https://doi.org/10.1038/s41586-021-03553-9

8. Ayoubkhani D., Khunti K., Nafilyan V., Maddox T., Humberstone B., Diamond I., et al. Post-COVID syndrome in individuals admitted to hospital with COVID-19: retrospective cohort study. BMJ. 2021;372:n693. https://doi.org/10.1136/bmj.n693

9. Drake T.M., Riad A.M., Fairfield C.J., Egan C., Knight S.R., Pius R. et al. Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study. Lancet. 2021;398(10296):223–237. https://doi.org/10.1016/S0140-6736(21)00799-6

10. 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. https://doi.org/10.1016/S0140-6736(20)30183-5

11. Inciardi R.M., Adamo M., Lupi L., Cani D.S., Di Pasquale M., Tomasoni D. et al. Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy. Eur. Heart J. 2020;41(19):1821– 1829. https://doi.org/10.1093/eurheartj/ehaa388

12. Sandoval Y., Januzzi Jr J.L., Jaffe A.S. Cardiac troponin for the diagnosis and risk-stratification of myocardial injury in COVID-19: JACC review topic of the week. J. Am. Coll. Cardiol. 2020;76(10):1244–1258. https://doi.org/10.1016/j.jacc.2020.06.068

13. Daugherty S.E., Guo Y., Heath K., Dasmariñas M.C., Jubilo K.G., Samranvedhya J. et al. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ. 2021;373:n1098. https://doi.org/10.1136/bmj.n1098

14. Nalbandian A., Sehgal K., Gupta A., Madhavan M.V., McGroder C., Stevens J.S. et al. Post-acute COVID-19 syndrome. Nat. Med. 2021;27(4):601–615. https://doi.org/10.1038/s41591-021-01283-z

15. Varga Z., Flammer A.J., Steiger P., Haberecker M., Andermatt R., Zinkernagel A.S. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5

16. Evans P.C., Rainger G.E., Mason J.C., Guzik T.J., Osto E., Stamataki Z. et al. Endothelial dysfunction in COVID-19: a position paper of the ESC working group for atherosclerosis and vascular biology, and the ESC council of basic cardiovascular science. Cardiovasc. Res. 2020;116(14):2177–2184. https://doi.org/10.1093/cvr/cvaa230

17. Robbins-Juarez S.Y., Qian L., King K.L., Stevens J.S., Husain S.A., Radhakrishnan J. et al. Outcomes for patients with COVID-19 and acute kidney injury: a systematic review and meta-analysis. Kidney Int. Rep. 2020;5(8):1149–1160. https://doi.org/10.1016/j.ekir.2020.06.013

18. Ioannou G.N., Baraff A., Fox A., Shahoumian T., Hickok A., O’Hare A.M. et al. Rates and Factors Associated With Documentation of Diagnostic Codes for Long COVID in the National Veterans Affairs Health Care System. JAMA Netw. Open. 2022;5(7):e2224359. https://doi.org/10.1001/jamanetworkopen.2022.24359

19. Zhang T., Li Z., Mei Q., Walline J.H., Zhang Z., Liu Y. et al. Cardiovascular outcomes in long COVID-19: a systematic review and meta-analysis. Front. Cardiovasc. Med. 2025;12:1450470. https://doi.org/10.3389/fcvm.2025.1450470

20. Behnood S.A., Shafran R., Bennett S.D., Zhang A.X.D., O’Mahoney L.L., Stephenson T.J. et al. Persistent symptoms following SARSCoV-2 infection amongst children and young people: a meta-analysis of controlled and uncontrolled studies. J. Infect. 2022;84:158–170. https://doi.org/10.1016/j.jinf.2021.11.011

21. Nalbandian A., Sehgal K., Gupta A., Madhavan M.V., McGroder C., Stevens J.S. et al. Post-acute COVID-19 syndrome. Nat. Med. 2021;27:601–615. https://doi.org/10.1038/s41591-021-01283-z

22. Seitz A., Ong P. Endothelial dysfunction in COVID-19: a potential predictor of long-COVID? Int. J. Cardiol. 2022;349:155–156. https://doi.org/10.1016/j.ijcard.2021.11.051

23. Nannoni S., de Groot R., Bell S., Markus H.S. Stroke in COVID-19: a systematic review and meta-analysis. Int. J. Stroke. 2021;16(2):137–149. https://doi.org/10.1177/1747493020972922

24. Wang G., Zhang Q., Zhao X., Dong H., Wu C., Wu F. et al. Low highdensity lipoprotein level is correlated with the severity of COVID-19 patients: an observational study. Lipids Health Dis. 2020;19(1):204. https://doi.org/10.1186/s12944-020-01382-9

25. Nurmohamed N.S., Collard D., Reeskamp L.F., Kaiser Y., Kroon J., Tromp T.R. et al. Lipoprotein(a), venous thromboembolism and COVID-19: a pilot study. Atherosclerosis. 2021;341:43–49. https://doi.org/10.1016/j.atherosclerosis.2021.12.010

26. Vinciguerra M., Romiti S., Fattouch K., Bellis A., Greco E. Atherosclerosis as Pathogenetic Substrate for Sars-Cov2 Cytokine Storm. J. Clin. Med. 2020;9(7):2095. https://doi.org/10.3390/jcm9072095

27. Poznyak A.V., Bezsonov E.E., Eid A.H., Popkova T.V., Nedosugova L.V., Starodubova A.V. et al. ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis. Int. J. Mol Sci. 2021;22(9):4691. https://doi.org/10.3390/ijms22094691

28. Chidambaram V., Shanmugavel Geetha H., Kumar A., Majella M.G., Sivakumar R.K., Voruganti D. et al. Association of Lipid Levels With COVID-19 Infection, Disease Severity and Mortality: A Systematic Review and Meta-Analysis. Front. Cardiovasc. Med. 2022;9:862999. https://doi.org/10.3389/fcvm.2022.862999

29. Liu Y., Zhang H.-G. Vigilance on New-Onset Atherosclerosis Following SARS-CoV-2 Infection. Front. Med. 2021;7:629413. https://doi.org/10.3389/fmed.2020.629413

30.