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

Abstract and Introduction


Background: Data on the association of subclinical hypothyroidism (SCH) with the severity of coronary artery disease and major adverse cardiovascular and cerebral events (MACCE) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI) are limited and conflicting.

Objective: We established the baseline rate of SCH and followed the trajectory of thyroid-stimulating hormone (TSH) values during and after hospitalisation for PCI for up to six months and determined whether persistent SCH was associated with the severity of coronary artery disease and MACCE in patients with NSTE-ACS after PCI.

Design: Population-based prospective cohort study.

Patients: We included patients with NSTE-ACS who underwent PCI with simple balloon angioplasty or stent implantation for coronary heart disease.

Measurements: Thyroid function tests of patients before PCI and 1 day, 1 week, 1 and 6 months after PCI were performed. Cases showing transient SCH were excluded. Patients were divided into two groups based on the results of four TSH tests: 0.27–4.2 mIU/L (n = 1472, 89.7%) and >4.2 mIU/L (n = 170, 10.4%). The risk factors for the severity of coronary artery lesions were estimated using multinomial logistic regression analysis. Univariate and multivariate Cox regression analyses were used to study the relationship between TSH and MACCE.

Results: Among 1642 patients, there were 1070 males (65.2%) and 572 females (34.8%), with an average age of 62.5 ± 9.6 years. SCH patients had a wider range of diseased vessels and a higher number of diseased vessels (p < .05). TSH level was an independent risk factor for moderate [odds ratio (OR) = 1.144, 95% confidence interval (95% CI): 1.057–1.237, p = .001] and severe (OR = 1.131, 95% CI: 1.043–1.226, p = .003) coronary artery lesions. After adjusting for covariates, the risk of MACCE [hazard ratio (HR): 4.067, p < .001], nonfatal myocardial infarction (HR: 14.724, p = .003), and unplanned PCI (HR: 5.028, p < .001) were higher in the SCH group than in the euthyroidism group. There were no significant differences in the incidence of heart failure (HR: 6.012, p = .175), nonfatal stroke (HR: 2.039, p = .302), unplanned coronary artery bypass grafting (CABG) (HR: 1.541, p = .57), or cardiac death (HR: 2.704, p = .375) between the two groups.

Conclusions: Preoperative TSH levels and changes in thyroid hormone levels several months post-PCI in NSTE-ACS patients are highly significant in practice. Persistent SCH is associated with severe coronary artery lesions and MACCE, and may be a predictor for evaluating the prognosis of PCI-treated NSTE-ACS patients.


An early invasive management in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can improve clinical prognosis, especially in high-risk subgroups. To further improve the prognosis of NSTE-ACS patients after percutaneous coronary intervention (PCI), early recognition of modifiable risk factors to identify patients at the highest risk of out-of-hospital adverse events is paramount.

Hypothyroidism is closely related to the occurrence and development of coronary heart disease (CHD) and the poor prognosis of cardiovascular and cerebrovascular diseases.[1] Thus, the effects of even slight changes in thyroid function on the cardiovascular system cannot be ignored. There is growing evidence that subclinical hypothyroidism (SCH) is also closely related to poor short- and long-term prognosis in patients with CHD.[2–5] The increased levels of thyroid-stimulating hormone (TSH) are associated with cardiovascular risk.[6] This relationship may be mediated by dyslipidemia,[7–9] endothelial dysfunction,[8,10] inflammation,[11] insulin resistance[12] and cardiac systolic and diastolic dysfunction[13] in patients with CHD.

It is not clear whether persistent SCH is associated with the severity of coronary artery disease and major adverse cardiovascular and cerebral events (MACCE) in patients with NSTE-ACS after PCI, and the existing data on the association between SCH and MACCE is conflicting. We observed that previous studies on the long-term effects of SCH only evaluated baseline thyroid function, ignoring the natural history of the condition, in that SCH might naturally transition to normal thyroid function or significant hypothyroidism over time. Hyland et al.[14] in their study of thyroid function in a single cardiovascular heart study (CHS) cohort found that only 56% of the elderly patients diagnosed with SCH showed persistent hypothyroidism after 2 years, while 34% of the patients returned to normal thyroid function during this period. This suggests that a significant proportion of elderly patients with SCH may revert to a state of normal thyroid function.[6] These findings raised our concern that the analysis using a single time point to define SCH was weakened by patients with transient SCH, which potentially masks the effects of persistent SCH. To avoid physiological or transient increase in serum TSH levels, all patients should be re-examined for thyroid function 1 month after coronary angiography.[15] It is worth repeatedly monitoring thyroid hormone levels in NSTE-ACS patients at different time points, which will help identify patients at high risk for postoperative adverse events and mortality. Therefore, we analyzed the changes in TSH levels to investigate the differences in the severity of coronary artery lesions and clinical outcomes between NSTE-ACS patients with normal thyroid function and persistent SCH after PCI, and evaluated the predictive value of TSH in the occurrence of MACCE events in this population.