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


Baseline and Angiographic Characteristics

In this study, 1642 patients with NSTE-ACS who underwent PCI were selected and followed up. One thousand and seventy were men (65.2%) and 572 were women (34.8%), aged 27–88 years, with an average age of 62.5 ± 9.6 years. The median observation duration was 28.3 months. The median TSH, FT3 and FT4 were 1.79 mIU/L, 4.46 pmol/L, and 16.29 pmol/L, respectively. According to the serum thyroid hormone levels, 1642 patients were divided into the ET (n = 1472) and SCH groups (n = 170). The detection rate of SCH in this study was 10.4%. Nine hundred and sixty-seven patients completed thyroid function tests 6 months after PCI, and there were 48 SCH patients with normalisation of thyroid function, accounting for 35.3% of the 136 SCH patients who underwent reexamination. SCH was reported to show association with female sex, prior history of chronic kidney disease, higher serum creatinine, fasting blood glucose (FBG), N-terminal pro-B-type natriuretic peptide (NT-proBNP), triglyceride (TG), lipoprotein(a), triglyceride/HDL cholesterol (TG/HDL-C) ratio, homocysteine levels, lower left ventricular ejection fraction (LVEF) and low haemoglobin levels. Compared with patients in ET group, SCH patients had a wider range and higher number of diseased vessels. Gensini scores in SCH group were significantly higher than those in ET group. There were no significant differences in the frequency of antiplatelet drugs, anti-angina drugs, and lipid-lowering drugs between the two groups. Baseline clinical, angiographic, and PCI data are shown in Table 1. Sixteen patients (1.0%) progressed to overt hypothyroidism at 1 month after PCI, and eight patients (0.5%) progressed to overt hypothyroidism at 6 months after PCI. Patients who developed overt hypothyroidism received levothyroxine therapy, and some patients with serum TSH > 10 also received levothyroxine therapy after assessment patients' condition.

Relationship Between SCH and Severity of Coronary Artery Lesion

Table 2 shows the results of the multiple logistic regression analysis between TSH levels and the severity of coronary artery lesions. According to Table 1, we screened out the statistically significant variables and incorporated clinically significant indicators into the model. Gensini group 1 was regarded as the reference category. Because the sample size of this study was relatively small and the difference in sample size between the two groups was large, multiple logistic regression was performed in the three models. The results showed that TSH was significantly associated with the degree of coronary artery lesions in models 1 to 3. TSH level was an independent risk factor for Gensini group 2 (OR = 1.144, 95% CI: 1.057–1.237, p = .001) and Gensini group 3 (OR = 1.131, 95% CI: 1.043–1.226, p = .003).

Association Between SCH and MACCE

Among the 1642 patients, 141 patients had MACCE during follow-up, including 49 patients with SCH and 92 patients with ET. The cumulative incidence of terminal events in the SCH and ET groups during the follow-up period was 28.8% and 6.3%, respectively. During follow-up, the Kaplan–Meier method was used to evaluate the relationship between SCH and MACCE. In patients with SCH, unadjusted Kaplan–Meier estimates for MACCE (28.8% vs. 6.3%, log-rank p < .0001), nonfatal MI (1.8% vs. 0.1%, log-rank p = .0001), heart failure (5.3% vs. 0.2%, log-rank p < .0001), unplanned PCI (14.7% vs. 3.3%, log-rank p < .0001), unplanned CABG (2.9% vs. 0.9%, log-rank p = .0085) and cardiac death (2.4% vs. 0.5%, log-rank p = .0014) were significantly higher than those of patients with ET. However, there were no significant differences in the incidence of nonfatal stroke (1.8% vs. 1.3%, log-rank p = .4402) between the two groups (Figure 2). After adjusting for covariates, the risk of MACCE (HR: 4.067, p < .001), nonfatal MI (HR: 14.724, p = .003) and unplanned PCI (HR: 5.028, p < .001) were higher in the SCH group than in the ET group. Differences in the incidence of heart failure (HR: 6.012, p = .175), nonfatal stroke (HR: 2.039, p = .302), unplanned CABG (HR: 1.541, p = .57) or cardiac death (HR: 2.704, p = .375) between the two groups were not significant (Table 3).

Figure 2.

Kaplan–meier curve for survival of patients with subclinical hypothyroidism versus euthyroidism. CABG, coronary artery bypass grafting; ET, euthyroidism, MACCE, major adverse cardiovascular and cerebral events; MI, myocardial infarction; PCI, percutaneous coronary intervention; SCH, subclinical hypothyroidism

Subgroup Analysis

Figure 3 summarizes the relative risk of MACCE in patients with SCH and ET in each subgroup. Compared with ET, SCH group was associated with a higher risk of MACCE. SCH group after adjustment for age, sex, body mass index, diabetes mellitus, hypertension, hyperlipidemia and so forth, was found to be associated with a higher risk of MACCE compared to ET group in subgroups of different ages, genders, and Gensini groups 2 and 3.

Figure 3.

The relative risk of MACCE in patients with SCH and ET in each subgroup. Adjusted HR: age, gender, body mass index, diabetes mellitus, hypertension, dyslipidaemia, family history of coronary artery disease, current smoking, history of myocardial infarction, percutaneous coronary intervention, prior stroke, peripheral vascular disease, chronic kidney disease, left ventricle ejection fraction, admission diagnosis, haemoglobin, creatinine, fasting blood glucose, high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, lipid index, homocysteine, aspirin, clopidogrel, β-Blocker, angiotensin II coenzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker, statins, PCSK9 inhibitors, glycoprotein IIb-IIIa inhibitor, bivalirudin, multi-vessel disease, left main, left anterior descending, left circumflex artery, right coronary artery and Gensini score. CI, confidence interval; ET, euthyroidism; HR, hazard ratio; MACCE, major adverse cardiovascular and cerebral events; RR, relative risk; SCH, subclinical hypothyroidism