Impact of Persistent Subclinical Hypothyroidism on Clinical Outcomes in Non-ST-Segment Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Chuyi Han; Kaihang Xu; Le Wang; Yingyi Zhang; Rui Zhang; Ao Wei; Lijie Dong; Yuecheng Hu; Jinghan Xu; Wenyu Li; Tingting Li; Chunwei Liu; Wei Qi; Dongxia Jin; Jingxia Zhang; Hongliang Cong


Clin Endocrinol. 2022;96(1):70-81. 

In This Article

Design and Methods

Study Population

This was a single-centre, observational, prospective cohort study. The original cohort included 2035 NSTE-ACS patients who underwent PCI with simple balloon angioplasty or stent implantation, for CHD without planned PCI or coronary artery bypass grafting (CABG) within 1 month from April 2018 to May 2020 in the Eighth Department of Cardiology, Tianjin Chest Hospital. The flow chart of the entire selection process and the exclusion criteria is shown in Figure 1. Initially, we excluded 85 patients through the medical record system and selected 1825 eligible patients. Next, we excluded 52 patients who did not have at least one thyroid function test performed within one month after PCI because of COVID-19 or other reasons. Forty-six patients who had elevated TSH before PCI and where thyroid function returned to normal during postoperative reexamination or follow-up within 1 month were also excluded, and 85 patients were lost to follow-up. Thus, the final cohort included 1642 patients. All patient information was obtained by independent reviewers who were blinded to the purpose of the study. All participants signed the informed consent form. This study was approved by the Institutional Review Committee.

Figure 1.

The flow chart of the entire selection process and the exclusion criteria

Thyroid Function Tests and the Definition of SCH

We measured serum TSH, FT3 and FT4 levels in patients before PCI and 1 day after PCI. The doctors who were in charge of the follow-up advised the patients or their families to get the thyroid function tests redone at 1 week, 1 and 6 months postoperatively in the outpatient clinics of our hospital. The serum FT3 (normal, 3.10–6.80 pmol/L), FT4 (12.00–22.00 pmol/L) and TSH (0.27–4.20 mIU/L) were determined by electrochemical luminescence immunoassay, using Roche COBAS E602 automatic electrochemical luminescence analyzer, using the Roche kit and calibrator (Roche). Thyroid function tests all measured using the same assay.

Euthyroidism (ET) or normal thyroid function was defined as TSH levels of 0.27–4.2 mIU/L, FT3 levels of 3.1–6.8 pmol/L and FT4 levels of 12.0–22.0 pmol/L, without documented history of hypothyroidism. SCH was defined as TSH > 4.2 mIU/L and FT3 and FT4 levels within the normal range with either a history of SCH recorded in the patients' clinical records before coronary angiography or 1 day, 1 week and 1 month after coronary angiography with no symptoms or signs of hypothyroidism.

Study Definitions

Clinical data were collected from medical records by trained clinicians, including patients' basic information, medical history, laboratory indicators, basic medication information and reports on past surgeries. Peripheral venous blood samples from all patients were collected in the morning after overnight fasting before coronary angiography. Blood analysis, lipid profile and renal function tests were carried out using an automatic biochemical analyzer and supporting reagents. Transthoracic echocardiography and other laboratory examinations were performed within 48 h after admission.

The definition of NSTE-ACS is in line with the current guidelines of the European Society of Cardiology[16] which includes patients diagnosed with unstable angina pectoris or non-ST elevation myocardial infarction (NSTEMI) at discharge. The Cockcroft-Gault formula was used to calculate the creatinine clearance.[17] The estimated glomerular filtration rate (eGFR) was calculated using the eGFR formula recommended by the 2012 Chronic Kidney Disease Epidemiology Collaboration Group.[18] Chronic kidney disease (CKD) is defined as an eGFR of ≤60 ml/min/1.73 m2.

PCI Procedure

Before PCI, all patients received loading doses of dual antiplatelet agents, including 300 mg aspirin and 300 mg clopidogrel or 180 mg ticagrelor. Antiplatelet therapy after PCI consisted of 100 mg aspirin combined with 75 mg clopidogrel or 90 mg ticagrelor twice a day for 1 year and then continuing only one of these drugs after 1 year. Angiographic data were obtained from catheter room records. We used the Gensini score to evaluate the severity of the coronary artery lesions. According to the Gensini score,[19] the coronary artery lesions were divided into three grades: Gensini group 1 (score 0–26), Gensini group 2 (score 26.5–52) and Gensini group 3 (score >52). Gensini scores were obtained by experienced interventional cardiologists based on the Gensini scoring guidelines after analyzing the characteristics of coronary angiographic lesions.

Clinical Follow-up

Independent researchers who oversaw the follow-up informed the patients or their families to go to the outpatient clinic of our hospital to review their thyroid function and recorded their expected reexamination time as 1 week, 1 and 6 months after PCI. Follow-up doctors reviewed 1642 patients in outpatient department or over telephone calls every 6 or 12 months, depending on each patient's medical and social situation.

The primary outcome was defined as a composite of MACCE, including cardiac death, heart failure, nonfatal myocardial infarction (MI), nonfatal stroke and unplanned revascularization (including any unplanned PCI and surgical bypass of target or nontarget vessels). The secondary outcomes were the individual components of the primary endpoint: cardiac death, heart failure, MI, nonfatal stroke and unplanned revascularization. Cardiac death refers to death caused by myocardial infarction, heart failure, malignant arrhythmia (including sudden cardiac death) or other structural or functional heart diseases. Although patients could experience more than one component of the composite primary endpoint, each patient was evaluated until the occurrence of their first event and only once during the analysis.

Statistical Analysis

Statistical analysis was performed using IBM SPSS Statistics (version 22.0). Continuous variables conforming to the normal distribution were presented as mean ± standard deviation, and the patients' baseline characteristics between groups were analyzed using Student's t test. Non-normally distributed continuous variables were presented as medians and interquartile ranges, and the Mann–Whitney U test was used for comparison between groups. Categorical variables were presented as frequencies, and the comparison between groups was carried out using the chi-square test or Fisher's exact test, as appropriate. For the ordered rank variables of the three categories, the Kruskal–Wallis H test was used for comparison between groups. Risk factors for the severity of coronary artery lesions were estimated using multinomial logistic regression analysis.

The survival rate was calculated using the Kaplan–Meier method, and comparisons between groups were performed using the Log-rank χ 2 test. We used univariate and multivariate Cox regression to analyze the relationship between TSH and MACCE and estimated MACCE hazard ratio (HR) by incorporating baseline variables of clinical significance and univariate correlation with prognosis into a multivariate Cox proportional hazard regression model. In addition, although some variables showed no statistical difference in univariate analysis, their high clinical significance and close relation to the risk of adverse cardiovascular events may have been masked by other confounding factors, so they were also included in the multivariate Cox risk model for adjustment. A two-tailed p < .05, was considered to indicate statistical significance.