Little is known about the association between the free triiodothyronine/free thyroxine (FT3/FT4) ratio and clinical outcomes in euthyroid patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). A total of 1448 euthyroid patients with NSTE-ACS who underwent PCI were included in this prospective study. Multivariate Cox regression analysis revealed that there was a significantly increased risk of stroke (hazard ratio [HR] 11.380, 95% confidence interval [CI]: 1.386–93.410, P = .024) and major adverse cardiovascular and cerebrovascular events (MACCEs) (HR 3.364, 95% CI: 1.595–7.098, P = .001) in patients in lower FT3/FT4 tertiles. The combined model of FT3/FT4 ratio and the Global Registry of Acute Coronary Events (GRACE) score provided the added value of risk assessment by improving C-statistics, integrated discrimination improvement (IDI), and the net reclassification index (NRI) (all P < .05). Thus, in euthyroid patients with NSTE-ACS undergoing PCI, the FT3/FT4 ratio was not only an independent prognostic indicator of long-term MACCE but also enhanced risk discrimination when combined with the GRACE risk score, which suggests that the calculation of FT3/FT4 before and after PCI may contribute to risk stratification in this particular patient group.
MachFBaigentCCatapanoAL, et al.2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111-88.
2.
RodriguezFMahaffeyKW. Management of patients with NSTE-ACS: a comparison of the recent AHA/ACC and ESC guidelines. J Am Coll Cardiol. 2016;68:313-21.
3.
ColletJPThieleHBarbatoE, et al.2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42:1289-367.
4.
Cavusoglu TurkerBTurkerFAhbabSHocaETahmazMAtaoğluHE. Serum albumin and FT3/FT4 ratio as additional co-morbidity parameters to predict mortality as a new approach: the Haseki scoring index (updated Charlson comorbidity index). PLoS One. 2022;17:e0264724.
5.
LiLCaiGLuWLiFYuLXiaoJ. The ratio of HDL-C to apoA-I interacts with free triiodothyronine to modulate coronary artery disease risk. BMC Cardiovasc Disord. 2021;21:504.
6.
KlingenbergRAghlmandiSRäberL, et al.Improved risk stratification of patients with acute coronary syndromes using a combination of hsTnT, NT-proBNP and hsCRP with the GRACE score. Eur Heart J Acute Cardiovasc Care. 2018;7:129-38.
7.
BrozaitieneJMickuvieneNPodlipskyteABurkauskasJBuneviciusR. Relationship and prognostic importance of thyroid hormone and N-terminal pro-B-Type natriuretic peptide for patients after acute coronary syndromes: a longitudinal observational study. BMC Cardiovasc Disord. 2016;16:45.
8.
CappolaARDesaiASMediciM, et al.Thyroid and cardiovascular disease research agenda for enhancing knowledge, prevention, and treatment. Thyroid. 2019;29:760-77.
9.
AhmadiNAhmadiFSadiqiMZiemnickaKMinczykowskiA. Thyroid gland dysfunction and its effect on the cardiovascular system: a comprehensive review of the literature. Endokrynol Pol. 2020;71:466-78.
10.
KimDHChoiDHKimHW, et al.Prediction of infarct severity from triiodothyronine levels in patients with ST-elevation myocardial infarction. Korean J Intern Med. 2014;29:454-65.
11.
LamprouVVarvarousisDPolytarchouKVarvarousiGXanthosT. The role of thyroid hormones in acute coronary syndromes: Prognostic value of alterations in thyroid hormones. Clin Cardiol. 2017;40:528-33.
12.
TarozaSRastenytėDPodlipskytėAKazlauskasHMickuvienėN. Nonthyroidal illness syndrome in ischaemic stroke patients is associated with increased mortality. Exp Clin Endocrinol Diabetes. 2020; 128:811-8.
13.
SatoYYoshihisaAKimishimaY, et al.Low T3 syndrome is associated with high mortality in hospitalized patients with heart failure. J Card Fail. 2019;25:195-3.
14.
KumarRMehtaVPrabhakarRDivyaSolankiPKMallickRK. To study the association between sick euthyroid state and the incidence of ACS. J Assoc Physicians India. 2022;70:11-2.
15.
YuanDJiaSZhuP, et al.Usefulness of FT3 to FT4 ratio to predict mortality in euthyroid patients with prior cardiovascular events undergoing PCI: five-year findings from a large single-center cohort study. Front Endocrinol2021;12:700349.
16.
FribergLWernerSEggertsenGAhnveS. Rapid down-regulation of thyroid hormones in acute myocardial infarction: is it cardioprotective in patients with angina?Arch Intern Med. 2002;162:1388-94.
17.
PasqualettiGCalsolaroVBernardiniS, et al.Degree of peripheral thyroxin deiodination, frailty, and long-term survival in hospitalized older patients. J Clin Endocrinol Metab. 2018;103:1867-76.
18.
YuTTianCSongJ, et al.Value of the fT3/fT4 ratio and its combination with the GRACE risk score in predicting the prognosis in euthyroid patients with acute myocardial infarction undergoing percutaneous coronary intervention: a prospective cohort study. BMC Cardiovasc Disord. 2018;18:181.
19.
FoxKAFitzgeraldGPuymiratE, et al.Should patients with acute coronary disease be stratified for management according to their risk? Derivation, external validation and outcomes using the updated GRACE risk score. BMJ Open. 2014;4:e004425.
20.
EggersKMBaronTHjortMNordenskjöldAMTornvallPLindahlB. GRACE 2.0 score for risk prediction in myocardial infarction with nonobstructive coronary arteries. J Am Heart Assoc. 2021;10:e021374.
21.
YuNWangLZengY, et al.The association of thyroid hormones with coronary atherosclerotic severity in euthyroid patients. Horm Metab Res. 2022;54:12-9.
22.
LeFevreML. Screening for thyroid dysfunction: U.S. preventive services task force recommendation statement. Ann Intern Med. 2015;162:641-50.
23.
FarooqVvan KlaverenDSteyerbergEW, et al.Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients: development and validation of SYNTAX score II. Lancet. 2013;381:639-50.
24.
LeveyASStevensLASchmidCHCKD-EPI Chronic Kidney Disease Epidemiology Collaboration, et al.A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604-12.
25.
RampidisGPBenetosGBenzDCGiannopoulosAABuechelRR. A guide for Gensini score calculation. Atherosclerosis. 2019;287:181-183.
26.
IbanezBJamesSAgewallSESC Scientific Document Group, et al.2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39:119-77.
27.
ThygesenKAlpertJSJaffeASExecutive 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, et al.Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018;72:2231-64.
28.
HicksKAMahaffeyKWMehranR, et al.2017 cardiovascular and stroke endpoint definitions for clinical trials. J Am Coll Cardiol. 2018;71:1021-34.
29.
DeLongERDeLongDMClarke-PearsonDL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837-45.
30.
LemeshowSHosmerDWJr. A review of goodness of fit statistics for use in the development of logistic regression models. Am J Epidemiol. 1982;115:92-6.
31.
RedelmeierDABlochDAHickamDH. Assessing predictive accuracy: how to compare Brier scores. J Clin Epidemiol. 1991;44:1141-6.
32.
PencinaMJD’AgostinoRBD’AgostinoRBJrVasanRSVasanRS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157-72; discussion 207-12.
33.
MerkeAMerkeJSilbernagelGMärzW. Free thyroid hormones and mortality in Caucasians undergoing angiography: the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Endocr Pract. 2017;23:288-98.
34.
HanCXuKWangL, et al.Impact of persistent subclinical hypothyroidism on clinical outcomes in non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention. Clin Endocrinol. 2022;96:70-1.
35.
NdrepepaGBraunSMayerK, et al.Prognostic value of thyroid-stimulating hormone within reference range in patients with coronary artery disease. Metabolism. 2015;64:1308-15.
36.
WangBLiuSLiL, et al.Non-thyroidal illness syndrome in patients with cardiovascular diseases: a systematic review and meta-analysis. Int J Cardiol. 2017;226:1-10.
37.
GaoSMaWHuangSLinXYuM. Predictive value of free triiodothyronine to free thyroxine ratio in euthyroid patients with myocardial infarction with nonobstructive coronary arteries. Front Endocrinol. 2021;12:708216.
YazıcıSKırışTCeylanUS, et al.Relation of low T3 to one-year mortality in non-ST-elevation acute coronary syndrome patients. J Clin Lab Anal. 2017;31:e22036.
40.
BiondiBCappolaARCooperDS. Subclinical hypothyroidism: a review. JAMA. 2019;322:153-60.
41.
KimurTKotajimaNKandaTKuwabaraAFukumuraYKobayashiI. Correlation of circulating interleukin-10 with thyroid hormone in acute myocardial infarction. Res Commun Mol Pathol Pharmacol. 2001;110:53-58.
42.
KahramanSCam KahramanFZencirkiran AgusH, et al.Perceived stress level is associated with coronary artery disease severity in patients with ST-segment elevation myocardial infarction. Turk Kardiyol Dernegi Arsivi. 2020;48:494-3.
43.
BurakCYesinMTanıkVO, et al.Prolonged P wave peak time is associated with the severity of coronary artery disease in patients with non-ST segment elevation myocardial infarction. J Electrocardiol. 2019;55:138-43.
44.
RencüzoğullarıİÇağdaşMKarakoyunS, et al.The association between electrocardiographic R wave peak time and coronary artery disease severity in patients with non-ST segment elevation myocardial infarction and unstable angina pectoris. J Electrocardiol. 2018;51:230-5.
45.
SmithSJBosGGerbrandyJDocterRVisserTJHennemannG. Lowering of serum 3,3′,5-triiodothyronine thyroxine ratio in patients with myocardial infarction; relationship with extent of tissue injury. Eur J Clin Invest. 1978;8:99-102.
46.
MaiaALGoemannIMMeyerELWajnerSM. Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease. J Endocrinol. 2011;209:283-97.
47.
WangCHanSLiYTongFLiZSunZ. Value of FT3/FT4 ratio in prognosis of patients with heart failure: a propensity-matched study. Front Cardiovasc Med. 2022;9:859608.
48.
YuanDZhangCJiaS, et al.Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease. Nutr Metabol Cardiovasc Dis. 2021;31:579-86.
49.
MakkiNBrennanTMGirotraS. Acute coronary syndrome. J Intensive Care Med. 2015;30:186-20.
50.
FliersEBiancoACLangoucheLBoelenA. Thyroid function in critically ill patients. Lancet Diabetes Endocrinol. 2015;3:816-825.
51.
PingitoreAChenYGerdesAMIervasiG. Acute myocardial infarction and thyroid function: new pathophysiological and therapeutic perspectives. Ann Med. 2012;44:745-57.
52.
RasoolRUnarAJafarTHChanihoonGQMubeenB. A role of thyroid hormones in acute myocardial infarction: an update. Curr Cardiol Rev. 2023;19:e280422204209, Online ahead of print.
53.
JabbarAPingitoreAPearceSHZamanAIervasiGRazviS. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol. 2017;14:39-55.
54.
VisserenFLJMachFSmuldersYMESC National Cardiac SocietiesESC Scientific Document Group, et al.2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42:3227-337.
55.
HungJRoosAKadesjöE, et al.Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction. Eur Heart J. 2021;42:2552-61.
56.
FabrisETen BergJMHermanidesRS, et al.NT-proBNP level before primary PCI and risk of poor myocardial reperfusion: insight from the on-TIME II trial. Am Heart J. 2021;233:78-5.
57.
NikorowitschJOjedaFLacknerKJ, et al.Head-to-head comparison of the incremental predictive value of the three established risk markers, Hs-troponin I, C-reactive protein, and NT-proBNP, in coronary artery disease. Biomolecules. 2020;10:394.
58.
EagleKALimMJDabbousOHGRACE Investigators, et al.A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA. 2004;291:2727-33.
59.
PencinaMJD’AgostinoRBPencinaKMJanssensACGreenlandP. Interpreting incremental value of markers added to risk prediction models. Am J Epidemiol. 2012;176:473-81.
60.
ÇınarTŞaylıkFAkbulutT, et al.Evaluation of intermountain risk score for short- and long-term mortality in ST elevation myocardial infarction patients. Angiology. 2022:74, 357-64.
