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

Disclosures

Clin Endocrinol. 2022;96(1):70-81.

Conclusions

The preoperative TSH levels and the changes in thyroid hormone levels during follow-up after PCI in NSTE-ACS patients are clinically crucial. It was noted in this study that an increase in TSH level was associated with a poor clinical outcome. For such patients, it is more important to monitor changes in thyroid function and recurrence of cardiovascular events. Our results suggest that persistent SCH is associated with increased severity of coronary artery lesions and MACCE, and may be a prognostic predictor in patients with NSTE-ACS treated with PCI.

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Funding information
Tianjin Science and Technology Committee, Tianjin, China, Grant/Award Number: 17ZXMFSY00020

Acknowledgements
This study was supported by Tianjin Science and Technology Committee, Tianjin, China (Grant number: 17ZXMFSY00020).

Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.

Table 1. Baseline patient demographic, clinical, angiographic and procedural data according to TSH level
Variables	Euthyroidism (n = 1472)	Subclinical hypothyroidism (n = 170)	p value
Clinical characteristics
Age	62.4 ± 9.7	62.9 ± 9.1	.516
Age ≥65 years	622 (42.3%)	79 (46.5%)	.293
Female gender	490 (33.3%)	82 (48.2%)	<.001
BMI (kg/m²)	24.5 ± 2.6	24.3 ± 2.9	.485
Diabetes mellitus	438 (29.8%)	58 (34.1%)	.241
Hypertension	997 (67.7%)	115 (67.6%)	.300
Dyslipidaemia	950 (64.5%)	118 (69.4%)	.207
Family history of CAD	151 (10.3%)	21 (12.4%)	.398
Current smoking	557 (37.8%)	65 (38.2%)	.920
Prior smoking	741 (50.3%)	86 (50.6%)	.951
Prior myocardial infarction	203 (13.8%)	28 (16.5%)	.341
Prior PCI	353 (24.0%)	42 (24.7%)	.834
Prior stroke	237 (16.1%)	27 (15.9%)	.942
Prior peripheral vascular disease	8 (0.5%)	3 (1.8%)	.065
Prior chronic kidney disease	37 (2.5%)	22 (12.9%)	<.001
Initial systolic blood pressure (mmHg)	127.6 ± 15.6	127.7 ± 15.7	.910
Initial diastolic blood pressure (mmHg)	72.6 ± 9.9	72.2 ± 10.1	.590
Initial heart rate (bpm)	70.9 ± 9.1	70.1 ± 8.6	.264
LVEF (%)	58.9 ± 6.7	57.6 ± 8.2	.039
LVEF ≤ 50 (%)	163 (11.1%)	25 (14.7%)	.159
UA on admission	1051 (71.4%)	123 (72.4%)	.794
NSTEMI on admission	412 (28%)	47 (27.6%)	.925
Laboratory data
Interval of the follow-up (months)	28.5 (21.6, 33.5)	26.5 (17.1, 33.1)	.001
White blood cells	6.8 (5.7, 8.2)	6.6 (5.7, 7.9)	.152
Haemoglobin (g/L)	138 (128, 148)	134 (124.8, 142)	<.001
Platelet	220 (186.3, 258)	229.5 (184, 267.3)	.166
Creatinine (μmol/L), median (Q1, Q3)	72 (61, 83.8)	80 (66, 95.3)	<.001
FBG (mmol/L)	5.6 (5, 6.8)	5.9 (5.4, 7.1)	<.001
HbA1c (%)	6.4 ± 1.3	6.6 ± 1.5	.057
Hs-CRP (mg/L)	1.7 (0.7, 4.8)	2.2 (0.8, 6)	.069
CK-MB (ng/mL)	16 (13, 23)	15 (13, 21)	.114
Hs-Troponin-I (ng/mL)	0.014 (0.008, 0.134)	0.017 (0.01, 0.123)	.083
NT-proBNP (pg/ml)	132.9 (55.2, 403.6)	214.7 (75.4, 818)	.001
Total cholesterol (mmol/L)	4.1 (3.5, 4.8)	4.2 (3.6, 5)	.081
Triglycerides (mmol/L)	1.6 (1.2, 2.2)	1.9 (1.6, 2.4)	<.001
Lipoprotein(a) (nmol/L)	29.7 (11.4, 70)	42.6 (20.2, 98)	<.001
HDL cholesterol (mmol/L)	1 (0.9, 1.2)	1 (0.8, 1.2)	.421
LDL cholesterol (mmol/L)	2.7 (2.1, 3.3)	2.8 (2.1, 3.4)	.333
TC/HDL-C ratio	4 (3.2, 5)	4.1 (3.1, 5.1)	.743
TG/HDL-C ratio	1.6 (1.1, 2.3)	1.9 (1.4, 2.6)	<.001
LDL-C/HDL-C ratio	2.6 (2, 3.5)	2.7 (1.8, 3.5)	.995
Uric acid (μmol/L)	320.5 (266, 377)	321.5 (261, 374.3)	.483
Homocysteine (μmol/L)	12.8 (10.6, 16.3)	14.1 (11.4, 17.5)	.014
TSH at admission (μIU/mL)	1.67 (1.16, 2.38)	5.44 (5.08, 6.23)	<.001
FT3 at admission (pmol/L)	4.5 (4.1, 4.9)	4.11 (3.83, 4.6)	<.001
FT4 at admission (pmol/L)	16.4 (14.9, 18)	15.1 (13, 16.8)	<.001
TSH 1 day after PCI (μIU/mL)	2.6 (1.82, 3.68)	6.24 (5.5, 7.56)	<.001
TSH 1 week after PCI (μIU/mL)	2.35 (1.68, 3.25)	6.03 (5.36, 6.98)	<.001
TSH 1 month after PCI (μIU/mL)	2.03 (1.43, 2.89)	5.52 (5.1, 6.23)	<.001
Angiographic and procedural data
Glycoprotein IIb-IIIa inhibitor	385 (26.2%)	35 (20.6%)	.115
Bivalirudin	186 (12.6%)	39 (22.9%)	<.001
Gensini score	37 (20, 60)	51 (34, 90)	<.001
Lesion site of vessels, n (%)
Left main	101 (6.9%)	27 (15.9%)	<.001
Left anterior descending artery	1271 (86.3%)	159 (93.5%)	.008
Left circumflex artery	996 (67.7%)	134 (78.8%)	.003
Right coronary artery	992 (67.4%)	137 (80.6%)	<.001
Involved vessels, n (%)			<.001
One vessel	382 (26%)	24 (14.1%)
Two vessels	393 (26.7%)	32 (18.8%)
Three vessels	697 (47.4%)	114 (67.1%)
Multi-vessel disease, n (%)	1090 (74.0%)	146 (85.9)	.001
Drug-eluting stent	1164 (79.1%)	140 (82.4%)	.317
Stent number			.191
≤1	1070 (72.7%)	116 (68.2%)
2	313 (21.3%)	40 (23.5%)
3	78 (5.3%)	12 (7.1%)
≥4	11 (0.8%)	2 (1.2%)
Discharge medication
Aspirin	1449 (98.4%)	169 (99.4%)	.316
Clopidogrel	1015 (69.0%)	120 (70.6%)	.662
Ticagrelor	456 (31.0%)	50 (29.4%)	.675
ACEI/ARBs	735 (49.9%)	88 (51.8%)	.651
Calcium channel blocker	383 (26.0%)	36 (21.2%)	.170
Beta-blockers	863 (58.6%)	102 (60%)	.731
Statin	1354 (92.0%)	162 (95.3%)	.125
PCSK9 inhibitors	65 (4.4%)	6 (3.5%)	.591
Proton pump inhibitor	1189 (80.8%)	141 (82.9%)	.495
Follow-up medication
Antiplatelet drugs	1444 (98.1%)	168 (98.8%)	.504
ACEI/ARBs	730 (49.6%)	85 (50.0%)	.920
Calcium channel blocker	379 (25.7%)	33 (19.4%)	.071
Beta-blockers	856 (58.2%)	97 (57.1%)	.784
Statin	1346 (91.4%)	159 (93.5%)	.351

Abbreviations: ACEI/ARB, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker; BMI, body mass index; CABG, coronary artery bypass graft; CAD, coronary artery disease; CK-MB, creatine kinase-MB fraction; FBG, fasting blood glucose; FT3, free triiodothyronine; FT4, free thyroxine; HbA1c, haemoglobin A1c; HDL, high-density lipoprotein; HDL-C, high-density lipoprotein cholesterol; Hs-CRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; NSTEMI, non-ST-segment elevation myocardial infarction; NT-pro-BNP, N-terminal pro-B-type natriuretic peptide; PCI, percutaneous coronary intervention; PCSK9, proprotein convertase subtilisin/kexin type 9; TC, total cholesterol; TG, triglyceride; TSH, thyroid-stimulating hormone.

Table 2. The analysis of multinomial logistic regression about the severity of coronary artery lesions
	b	p value	95% CI for OR
Model 1: Age, female gender
Gensini group 1			1.000 (reference)
Gensini group 2	0.151	<.001	1.163 (1.079–1.253)
Gensini group 3	0.153	<.001	1.165 (1.080–1.256)
Model 2: Model 1 + HTN, DM, current smoking, CKD
Gensini group 1			1.000 (reference)
Gensini group 2	0.157	<.001	1.170 (1.083–1.264)
Gensini group 3	0.161	<.001	1.174 (1.086–1.269)
Model 3: Model 2 + TG, TC, LDL-C, Lp(a), NT-proBNP
Gensini group 1			1.000 (reference)
Gensini group 2	0.120	.003	1.128 (1.043–1.219)
Gensini group 3	0.120	.003	1.127 (1.042–1.220)

Abbreviations: CKD, chronic kidney disease; DM, diabetes mellitus; HTN, hypertension; LDL-C, low-density lipoprotein cholesterol; Lp(a), Lipoprotein(a); NT-pro-BNP, N-terminal pro-B-typenatriuretic peptide; TC, total cholesterol; TG, triglyceride.

Table 3. Hazard ratios for major adverse cardiovascular and cerebral events in patients with subclinical hypothyroidism versus euthyroidism
Variable	Euthyroidism (n = 1472)	Subclinical hypothyroidism (n = 170)	Unadjusted HR (95% CI)	p value	Adjusted HR (95% CI)	P value
Cardiac death	7 (0.5%)	4 (2.4%)	5.824 (1.71–19.90)	.005	2.704 (0.300–24.362)	.375
Nonfatal myocardial infarction	2 (0.1%)	3 (1.8%)	14.54 (2.43–87.05)	.003	14.724 (2.459–88.176)	.003
Heart failure	3 (0.2%)	9 (5.3%)	29.87 (8.08–110.35)	<.001	6.012 (0.449–80.465)	.175
Revascularization with PCI	48 (3.3%)	25 (14.7%)	5.19 (3.20–8.41)	<.001	5.028 (2.883–8.768)	<.001
Revascularization with CABG	13 (0.9%)	5 (2.9%)	3.64 (1.30–10.22)	.014	1.541 (0.347–6.850)	.57
Stroke	19 (1.3%)	3 (1.8%)	1.61 (0.48–5.43)	.446	2.039 (0.528–7.876)	.302
MACCE	92 (6.3%)	49 (28.8%)	5.29 (3.74–7.49)	<.001	4.067 (2.756–6.003)	<.001

Note: 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, priorstroke, 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.
Abbreviations: CABG, coronary artery bypass grafting; HR, hazard ratio; PCI, percutaneous coronary intervention.