Iranian Heart Journal

Iranian Heart Journal

Prognostic Implications of Subclinical Hypothyroidism in ST-Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Document Type : Original Article

Authors
Osama Ahmed Amin 1
Hazem Shalaby 2
Haidy Khattab 3
Ahmed Hamam 4
Ahmed Farouk Alaarag 2
1 Department of Cardiology, Beni-Suef University, Egypt.
2 Department of Cardiology, Tanta University, Egypt.
3 Department of Medical Physiology, Tanta University, Egypt.
4 Department of Endocrinology and Metabolism, Armed Forces College of Medicine, Egypt.
Abstract
Background: Subclinical hypothyroidism (SCH), characterized by elevated thyroid-stimulating hormone with normal free thyroxine (FT4), is a potential cardiovascular risk factor. The effect of SCH on outcomes in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) has received limited investigation. We aimed to evaluate the association between SCH and anti–thyroid peroxidase antibody (anti-TPO) positivity with no-reflow and acute heart failure (HF) in patients with STEMI after PCI.

Methods: This prospective cohort study enrolled 303 patients with STEMI undergoing primary PCI at 2 tertiary centers. SCH was defined as thyroid-stimulating hormone levels greater than 4.5 mIU/L with normal FT4 (0.8–1.8 ng/dL). Outcomes included no-reflow (Thrombolysis in Myocardial Infarction [TIMI] flow ≤ 2 or corrected TIMI frame count > 27) and acute HF (Killip class > II). Multivariate logistic regression was used to assess SCH and anti-TPO positivity as predictors of no-reflow and acute HF, adjusting for age, sex, diabetes, hypertension, smoking, Gensini score, thrombus burden, preprocedural TIMI flow, ischemic time, and anti-TPO status.

Results: Patients with SCH (n = 37, 12.2%) were more likely to be female (51.4% vs 32.0% in euthyroid patients; P = .02) and anti-TPO positive (83.8% vs 6.4%; P < .001). SCH was associated with higher Gensini scores (P = .02), increased no-reflow, and acute HF with Killip class greater than II. SCH and left ventricular ejection fraction could predict the occurrence of acute HF (P = .04 and P < .001, respectively). SCH and anti-TPO positivity (P = .03 and P = .01, respectively) could be associated with increased no-reflow.

Conclusions: SCH and anti-TPO positivity could be associated with adverse outcomes in patients with STEMI post-PCI, suggesting a role for thyroid function screening in risk stratification. (Iranian Heart Journal 2026; 27(3): 49-59)
Keywords
hypothyroidism
no-reflow
acute heart failure
1.         Biondi B, Cappola AR, Cooper DS. Subclinical hypothyroidism: a review. JAMA. 2019; 322(2):153-60. doi:10.1001/jama.2019.9052
2.         Taylor PN, Albrecht D, Scholz A, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018; 14(5):301-16. doi:10.1038/nrendo. 2018.18
3.         Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017;390(10101):1550-62. doi:10.1016/S0140-6736(17)30703-1
4.         Razvi S, Jabbar A, Pingitore A, et al. Thyroid hormones and cardiovascular function and diseases. J Am Coll Cardiol. 2018;71(16):1781-96. doi:10.1016/j.jacc.2018.02.045
5.         Gencer B, Collet TH, Virgini V, et al. Subclinical thyroid dysfunction and cardiovascular outcomes among prospective cohort studies. Endocr Metab Immune Disord Drug Targets. 2020; 20(6):836-45. doi:10.2174/1871530320666200129115536
6.         Cappola AR, Desai AS, Medici M, et al. Thyroid and cardiovascular disease: research agenda for enhancing knowledge, prevention, and treatment. Circulation. 2019; 139(25):2892-909. doi:10.1161/CIRCULATIONAHA.118.036859
7.         Stott DJ, Rodondi N, Kearney PM, et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med. 2017; 376(26):2534-44. doi:10.1056/NEJMoa1603825
8.         Berta E, Lengyel I, Halmi S, et al. Dyslipidemia in subclinical hypothyroidism: a systematic review and meta-analysis. Endocr Pract. 2021;27(6):608-15. doi:10.1016/j.eprac.2021.02.011
9.         Qari FA. Thyroid hormone profile in patients with acute coronary syndrome. Iran Red Crescent Med J. 2015;17(7):e26919. doi:10.5812/ircmj.26919
10.      Jabbar A, Pingitore A, Pearce SHS, et al. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol. 2017;14(1):39-55. doi:10.1038/nrcardio.2016.174
11.      Jabbar A, Ingoe L, Junejo S, et al. Effect of levothyroxine on left ventricular ejection fraction in patients with subclinical hypothyroidism and acute myocardial infarction: a randomized clinical trial. JAMA. 2020; 324(3):249-58. doi:10.1001/jama.2020.9389
12.      Peeters RP. Subclinical hypothyroidism. N Engl J Med. 2017; 376(26):2556-65. doi:10.1056/NEJMcp1611144
13.      Izkhakov E, Zahler D, Rozenfeld KL, et al. Unknown subclinical hypothyroidism and in-hospital outcomes and short- and long-term all-cause mortality among ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention. J Clin Med. 2020; 9(12):3829. doi:10.3390/jcm9123829
14.      Collet TH, Bauer DC, Cappola AR, et al. Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis. J Clin Endocrinol Metab. 2014; 99(10):3353-62. doi:10.1210/jc.2014-1255
15.      Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J. 2019; 40(3):237-69. doi:10.1093/eurheartj/ehy462
16.      Birjandi B, Ramezani Tehrani F, Amouzegar A, Tohidi M, Bidhendi Yarandi R, Azizi F. The association between subclinical hypothyroidism and TPOAb positivity with infertility in a population-based study: Tehran thyroid study (TTS). BMC Endocr Disord. 2021; 21(1):108. doi:10.1186/s12902-021-00773-y
17.      Buske M, Feistritzer HJ, Jobs A, Thiele H. Management of acute coronary syndrome: ESC guidelines 2023. Herz. 2024; 49(1):5-14. doi:10.1007/s00059-023-05231-8
18.      Charach L, Blatt A, Jonas M, et al. The Gensini score was used to estimate the severity of STEMI, NSTEMI, unstable angina, and anginal syndrome. Medicine (Baltimore). 2021; 100(41):e27331. doi:10.1097/MD.0000000000027331
19.      Rezkalla SH, Stankowski RV, Hanna J, Kloner RA. Management of no-reflow phenomenon in the catheterization laboratory. JACC Cardiovasc Interv. 2017; 10(3):215-23. doi:10.1016/j.jcin.2016.11.059
20.      Sun B, Liu J, Yin H, et al. Delayed vs. immediate stenting in STEMI with a high thrombus burden: a systematic review and meta-analysis. Herz. 2019; 44(8):726-34. doi:10.1007/s00059-018-4731-x
21.      Khot UN, Jia G, Moliterno DJ, et al. Prognostic importance of Killip class in acute myocardial infarction: an updated meta-analysis. J Am Coll Cardiol. 2023; 81(8_Suppl):1873. doi:10.1016/S0735-1097(23)02217-6
22.      Han C, Xu K, Wang L, et al. Impact of persistent subclinical hypothyroidism on clinical outcomes in non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention. Clin Endocrinol (Oxf). 2022; 96(1):70-81. doi:10.1111/cen. 14613
23.      Arambam P, Kaul U, Gupta S, Alok A, Kumar S, Janardhanan R. Thyroid dysfunction in acute coronary syndrome and its prognostic implications. Int J Health Sci. 2022;6(S9):2235-48. doi:10.53730/ijhs.v6nS9.12915
24.      Jabbar A, Ingoe L, Thomas H, et al. Prevalence, predictors, and outcomes of thyroid dysfunction in patients with acute myocardial infarction: the ThyrAMI-1 study. J Endocrinol Invest. 2021; 44(6):1209-18. doi:10.1007/s40618-020-01408-0
25.      Mavai M, Bhandari B, Singhal A, Mathur SK. Cardiac autonomic modulation and anti-thyroid Peroxidase (TPO) antibodies in subclinical hypothyroidism: does a correlation exist? Cureus. 2021; 13(10):e18844. doi:10.7759/cureus. 18844
26.      Isailă OM, Stoian VE, Fulga I, Piraianu AI, Hostiuc S. The relationship between subclinical hypothyroidism and carotid intima-media thickness as a potential marker of cardiovascular risk: a systematic review and meta-analysis. J Cardiovasc Dev Dis. 2024; 11(4):98. doi:10.3390/jcdd11040098
27.      Tan Q, Chen M, Yang H, Guo Y, Zou X. Subclinical hypothyroidism predicted adverse cardiovascular events in patients with ejection fraction preserved heart failure. Ther Clin Risk Manag. 2024; 20:227-37. doi:10.2147/TCRM.S433489
28.      Kaushik A, Agrawal M. Relationship between subclinical hypothyroidism and the risk of cardiovascular complications. Cureus. 2023; 15(1):e33708. doi:10.7759/cureus. 33708
29.      Moon S, Kim MJ, Yu JM, et al. Subclinical hypothyroidism and the risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective cohort studies. Thyroid. 2018; 28(9):1101-10. doi:10.1089/thy. 2017.0414
30.      Al-Gburi AJ, Al-Obaidi SR, Abdullah WH. Short-term outcomes among patients with subclinical hypothyroidism undergoing primary percutaneous coronary intervention. Ghana Med J. 2023; 57(1):37-42. doi:10.4314/gmj.v57i1.6
31.      Xu C, Zhou L, Wu K, et al. Abnormal glucose metabolism and insulin resistance are induced via the IRE1α/XBP-1 pathway in subclinical hypothyroidism. Front Endocrinol (Lausanne). 2019; 10:303. doi:10.3389/fendo.2019.00303
32.      Liu J, Duan Y, Fu J, Wang G. Association between subclinical hypothyroidism and coronary heart disease: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2021; 12:642609. doi:10.3389/fendo.2021.642609
33.      Rotondi M, de Martinis L, Coperchini F, et al. Serum concentrations of acute-phase proteins in patients with autoimmune thyroiditis: a systematic review. Thyroid. 2020; 30(10):1413-20. doi:10.1089/thy. 2019.0788
34.      Ter Maaten JM, Damman K, Verhaar MC, et al. Connecting heart failure with preserved ejection fraction and renal dysfunction: the role of endothelial dysfunction and inflammation. Eur J Heart Fail. 2016; 18(6):588-98. doi:10.1002/ejhf.497
35.      Zhang H, Li X, Zhang N, Tian L. Effect of thyroid dysfunction on N-terminal pro-B-type natriuretic peptide levels: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023; 14:1083171. doi:10.3389/fendo.2023.1083171
Iranian Heart Journal
Volume 27, Issue 3
Summer 2026
Pages 49-59