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.

Limitations

This study has some limitations. Patients in this study did not undergo anti-thyroid autoantibodies and thyroid ultrasound examination; therefore, some patients with a diagnosis of thyroiditis may have been missed. High calcium and phosphorus products are considered to be a risk factor for patients with CKD, and there was no routine measurement of calcium and phosphorus status in our study. Since the age-adjusted TSH reference range was not included in our study, the prevalence of SCH may have been overestimated. Patients included in the study were required to measure TSH levels before coronary angiography and 1 day and 1 month after coronary angiography. Although there were professionals in this study responsible for notifying patients by telephone and making appointments for reexamination, it was inevitable that some patients failed to complete TSH examination regularly, which may have affected the generalisability of the study. Lastly, the power of our study was calculated by estimating the occurrence of MACCEs and thus, comparisons of the occurrence of each component outcome may be underpowered.

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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.