Table 1.
Most representative prospective or cross-sectional studies on subclinical hypothyroidism and cardiovascular risk.
| Reference | Study design | Study population | Participants (sHT) | Age (years) | TSH (mIU/l) | Follow-up (years) | Analyzed endpoint | Outcome |
|---|---|---|---|---|---|---|---|---|
| Hak et al. (84) | Cross-sectional | Postmenopausal women | 1149 (124) | 96.0 ± 7.9 | >4.00 | NA | CVE | OR 2.3 (CI 1.3–4.2) |
| Parle et al. (83) | Prospective | Community dwelling | 1120 (94) | >60 | >5.00 | 10 | CVM | HR 0.9 (CI 0.6–1.3) |
| Lindeman et al. (85) | Cross-sectional | Community dwelling | 755 (112) | 74.1 ± 8.2 | NA | NA | CVE | p = 0.0007 (TSH > 10.0) |
| Imaizumi et al. (78) | Prospective | Community dwelling | 2650 (257) | 62.7 ± 11.1 | 7.16 ± 4.82 | 12.2 | ACM, CVE | HR 1.9 (CI 1.1–3.2), in men only OR 2.5 (CI 1.1–5.5) |
| Gussekloo et al. (23) | Prospective | Community dwelling | 502 (30) | >85 | >4.8 | 4 | ACM | HR 0.76 (0.62–0.92) |
| van den Beld et al. (22) | Prospective | Community dwelling | 359 (6) | 77.8 (73–94) | >4.3 | 4 | Survival | NS |
| Cappola et al. (80) | Prospective | Community dwelling | 3135 (496) | 72.7 ± 5.6 | 6.67 ± 2.54 | 13 | CVM, CVE | HR 1.14 (CI 0.91–1.43), HR 1.04(CI 0.87–1.23) |
| Iervasi et al. (73) | Prospective | Hospitalized cardiac patients | 2113 (208) | 61.1 (60.7–61.5) | 6.7 (6.01–7.44) | 2.7 | ACM, CVM | HR 2.0 (CI 1.33–3.04), HR 2.4 (CI 1.36–4.21) |
| Bauer et al.(86) | Prospective | Community dwelling | 438 (37) | 71.5 ± 5.0 | >5.50 | 11.9 | Survival | HR 1.23 (CI 0.55–2.74) |
| Razvi et al.(5) | Prospective | Community dwelling | 2376 (97) | 49.9 ± 17.9 | 6.00–15.00 | 20 | CVE, CVM | HR 1.76 (CI 1.15–2.71), HR 1.79 (1.02–3.56) 1 |
| McQuade et al. (87) | Retrospective | Community dwelling | 6240 (1396) | EU: 54.6 ± 12.7, Mild sHT: 57.1 ± 13.3, Moderate sHT: 58.9 ± 13.6 | Mild sHT: 3.1–6.0, Moderate sHT: 6.1–10.0 | 8 | ACM | p = 0.026 in moderate sHT people aged > 65 years |
| de Jongh et al. (88) | Prospective | Community dwelling | 1219 (34) | >65 | 6.89 (5.65–9.59) | 10.7 | ACM, CVM | HR 0.9 (CI 0.58–1.42), HR 0.5 (CI 0.20–1.49) |
| Waring et al. (89) | Prospective | Community dwelling | 1503 (116) | 74 | 4.79–10.00 | 8.3 | ACM, CVM | HR 1.01 (CI 0.7–1.4), HR 1.28 (CI 0.8–2.1) |
| Hyland et al. (74) | Prospective | Community dwelling | 4863 (697) | 73.4 ± 5.7 | 6.7 ± 2.6 | 10 | CVE, CVM | HR 1.37 (CI 1.0–1.87), HR 0.89 (CI 0.64–1.48) |
| LeGrys et al. (90)a | Prospective | Postmenopausal women | 3663 (282) | 65–79 | > 4.69 | >5 | CVE: TSH 4.69–6.99, TSH > 7.00, TSH 4.69–6.99, TSH > 7.00 | Age 65–70: HR 0.99 (CI 0.42–2.35), HR 1.11 (CI 0.51–2.39); Age 71–79: HR 0.53 (CI 0.13–2.26), HR 1.27 (CI 0.44–3.69) |
| Rhee et al. (91) | Prospective | Community dwelling | 2570 (691) | sHT: 59.2 ± 19.2 | 6.3 (5.3–8.72) | 14.3 | ACM | Pre-existing HF: HR 1.77 (CI 1.19–2.64), No pre-existing HF: HR 0.97 (CI 0.84–1.12) |
| Ceresini et al. (92) | Prospective | Community dwelling | 951 (29) | > 65 | >4.68 | 6 | CVM | HR 0.50 (CI 0.10–2.55) |
| Yeap et al. (82) | Prospective | Community dwelling men | 3885 (416) | 70–89 | > 4.00 | 6.4 ± 1.5 | ACM | HR 1.06 (CI 0.86–1.32) |
| Frey et al. (69) | Prospective | Hospitalized cardiac patients | 1032 (34) | sHT 62 ± 12, EU 67 ± 13 | 5.29 (4.02–9.38) | 3.08 (1.5–3.58) | ACM | HR 0.96 (CI 0.52–1.77) |
| Perez et al. (75)b | Prospective | Community dwelling | 4987 (237) | >60 | 6.40 (5.60–8.00) | 2.73 | CVM, ACM | HR 1.46 (CI 1.16–1.84), HR 1.36 (CI 1.03–1.76) |
aFirst-time incident myocardial infarction.
bTSH value lower than 8.00 mIU/l but no distinction between sHT and overt hypothyroidism. Age and TSH value are reported as mean ± SD or median (confidence interval or range).
sHT, subclinical hypothyroidism; EU, euthyroidism; HR, hazard ratio; OR, odds ratio; ACM, all-cause mortality; CVM, cardiovascular mortality; CVE, cardiovascular events; NS, not significant; NA, not available.