Table 3.
Sensitivity analyses of the effect of subclinical hypothyroidism on the risk of Heart Failure (HF) Events
| Euthyroidism | Subclinical Hypothyroidism
|
||||||||
|---|---|---|---|---|---|---|---|---|---|
| TSH 4.5–19.9 mIU/L | TSH 10–19.9 mIU/L | ||||||||
|
| |||||||||
| Events | Participants | Events | Participants | HR (95% CI) | Events | Participants | HR (95% CI) | ||
| All eligible studies | |||||||||
| Random-effects model | 1762 | 22,674 | 250 | 2068 | 1.26 (0.91, 1.74) | 40 | 224 | 1.86 (1.27, 2.72) | |
| Fixed-effects model | 1762 | 22,674 | 250 | 2068 | 1.10 (0.96, 1.26) | 40 | 224 | 1.81 (1.32, 2.49) | |
| Excluding those with thyroid medication use * | |||||||||
| At baseline | 1730 | 22,351 | 237 | 1937 | 1.28 (0.88, 1.87) | 33 | 192 | 1.36 (0.92, 1.99) | |
| At baseline and during follow-up† | 1696 | 22,238 | 197 | 1732 | 1.26 (0.93, 1.69) | 24 | 146 | 2.37 (1.59, 3.54) | |
| Excluding those with missing FT4 ‡ | 1762 | 22,674 | 208 | 1575 | 1.34 (0.93, 1.95) | 39 | 220 | 1.91 (1.26, 2.88) | |
| Outcomes | |||||||||
| Three studies with formal adjudication procedures§ | 1205 | 9943 | 186 | 1274 | 0.96 (0.82, 1.12) | 27 | 129 | 1.66 (0.95, 2.91) | |
| Further adjustments of multivariate models | |||||||||
| Plus body mass index, creatinin and atrial fibrillation at baseline|| | 1326 | 10,644 | 213 | 1342 | 1.13 (0.86, 1.48) | 36 | 144 | 1.51 (1.06, 2.15) | |
| Plus lipid-lowering and antihypertensive medications# | 1336 | 10,681 | 212 | 1347 | 1.14 (0.85, 1.53) | 35 | 143 | 1.55 (1.09, 2.19) | |
| Excluding study of cardiac patients (Bari) | 1709 | 22,385 | 229 | 2029 | 1.04 (0.88, 1.22) | 33 | 214 | 1.62 (1.15, 2.29) | |
| Excluding preexisting HF ** | 1630 | 22,234 | 217 | 2005 | 1.04 (0.87, 1.26) | 31 | 211 | 1.67 (1.12, 2.49) | |
| Excluding baseline Atrial Fibrillation*** | 1698 | 22,500 | 238 | 2043 | 1.26 (0.92, 1.72) | 37 | 220 | 1.81 (1.27, 2.58) | |
Abbreviations: CI, Confidence Interval; FT4, Free Thyroxine; HF, Heart Failure; HR, Hazard Ratio; NA, data not applicable; TSH, Thyroid-Stimulating Hormone. HR are all age and sex-adjusted unless stated otherwise.
The numbers of participants with thyroid medication appear in Table 1.
Leiden was excluded from this stratum because of zero participant with subclinical hypothyroidism.
493 participants with subclinical hypothyroidism and missing t4 were excluded: 21 participants excluded from CHS, 230 from Health ABC (T4 not measured in Health ABC when TSH ≤ 7.0), 241 from PROSPER and 1 from Leiden
Formal adjudication procedures with experts adjudicating each case were only performed in CHS, HABC and PROSPER. See eTable 1.
Data on creatinin and atrial fibrillation were not available at baseline for the EPIC-Norfolk study. 50 participants with missing data for body mass index, creatinine and atrial fibrillation: 9 in CHS, 24 in Health ABC and 17 in Leiden.
Data on lipid-lowering and antihypertensive medications were not available for the EPIC-Norfolk study. 8 participants with missing data for hypertensive and lipid-lowering treatment: 1 in CHS, and 7 in Health ABC.
503 excluded because of HF at baseline: 11 in CHS, 106 in Health ABC, 58 in Leiden (1missing value), 328 in Bari (all participants with pre-existing HF), 0 in PROSPER. Data on preexisting HF were not available for EPIC study (only preexisting overall CVD assessed); after excluding those with preexisting CVD from EPIC, HR was 1.62 (1.02, 2.58) for TSH 10–19.9 mIU/L.
199 participants were excluded because of AF at baseline. 58 in CHS, 49 in Health ABC, 45 in Leiden 43 in Bari. Data were not available for EPIC-Norfolk study. Baseline AF was an exclusion criteria from PROSPER trial (4 participants had AF at baseline) 1 missing in HABC, 2 missing in Leiden. After excluding EPIC-Norfolk study, HR was 1.92 (1.24, 2.96) for TSH 10.0–19.9 mIU/L. Prevalence of baseline AF across TSH categories: 170/5615 (3.0%) for TSH 0.45–4.49 mIU/L, 20/628 (3.2%) for TSH 4.5–6.9 mIU/L, 1/174 for TSH 7.0-9-9 mIU/L (0.6%) and 4/102 (3.9%) for TSH 10.0–19.9 mIU/ L.