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Table 2 Subgroup and heterogeneity analyses of pooled RRs of primary outcomes

From: What is the association of hypothyroidism with risks of cardiovascular events and mortality? A meta-analysis of 55 cohort studies involving 1,898,314 participants

Factors IHD Cardiac mortality
N studies Events/participants RR (95% CI) I 2 P valuea N studies Events/participants RR (95% CI) I 2 P valuea
Degrees of hypothyroidism
 All hypothyroidism 4 13,444/593,499 1.13 (1.04–1.23) 0.0% Reference 2 282/2836 1.83 (0.72–4.62) 90.0% 0.75
 SCH 8 3400/21,623 1.12 (0.89–1.42) 55.8% 0.74 5 819/32,086 2.00 (1.34–2.97) 47.8% Reference
 OHypo 1 18/474 2.54 (0.87–7.41) - 0.30 - - - - -
Study population
 Convenience sample 4 1406/8946 1.08 (0.66–1.79) 58.2% 0.73 5 398/6595 2.33 (1.39–3.91) 70.7% Reference
  Cardiac patientsb 3 1277/8149 1.15 (0.68–1.94) 67.7% - 4 393/5596 2.22 (1.28–3.83) 76.5% -
 Population-based 9 15,456/606,650 1.12 (1.00–1.25) 36.8% Reference 2 703/28,327 1.43 (1.10–1.86) 0.0% 0.33
Mean age
 ≥80 years - - - -   - - - - -
 65–79 years 8 3417/20,298 1.06 (0.89–1.27) 37.4% 0.45 2 236/3077 1.91 (0.61–5.93) 82.3% 0.68
 <65 years 5 13,445/595,298 1.19 (1.02–1.39) 51.0% Reference 5 865/31,845 2.07 (1.39–3.07) 61.8% Reference
Location
 Europe 7 13,907/600,542 1.10 (0.95–1.26) 31.7% 0.23 4 814/31,087 1.91 (1.28–2.86) 52.8% 0.26
 North America 4 2675/12,727 1.08 (0.95–1.24) 15.2% 0.22 1 205/2430 1.14 (0.76–1.71) - Reference
 Asia 1 18/474 2.54 (0.87–7.41) - Reference 2 82/1405 3.02 (2.00–4.56) 0.0% 0.10
 Oceania 1 262/1853 1.80 (1.20–2.70) - 0.63 - - - - -
Female proportion
 ≥50% 9 15,773/610,042 1.07 (0.98–1.18) 19.9% 0.08 3 708/29,326 1.47 (1.12–1.94) 2.3% Reference
 <50% 4 1089/5554 1.47 (1.04–2.07) 40.9% Reference 4 393/5596 2.22 (1.28–3.83) 76.5% 0.52
Mean follow-up
 ≥10 years 5 3615/45,383 1.18 (0.98–1.42) 55.4% Reference 3 708/29,326 1.47 (1.12–1.94) 2.3% Reference
 5–10 years 2 11,491/557,482 1.13 (1.02–1.25) 0.0% 0.73 - - - - -
 <5 years 6 1756/12731 1.07 (0.75–1.53) 53.9% 0.59 4 393/5596 2.22 (1.28–3.83) 76.5% 0.52
Factors Cardiovascular mortality All-cause mortality
N studies Events/participants RR (95% CI) I 2 P valuea N studies Events/participants RR (95% CI) I 2 P valuea
Degrees of hypothyroidism
 All hypothyroidism 5 2724/20,707 0.99 (0.70–1.39) 42.0% 0.35 21 98,621c/876,811 1.21 (1.07–1.37) 87.6% 0.51
 SCH 12 2549/137,310 1.15 (1.00–1.32) 0.0% Reference 18 13,529/159,104 1.32 (1.13–1.54) 65.9% Reference
 OHypo - - - - - 1 6/474 1.78 (0.21–14.98) - 0.80
Study population
 Convenience sample 5 1454/12,229 1.15 (0.95–1.39) 0.0% 0.70 20 9004c/54,577 1.45 (1.27–1.66) 63.4% 0.009
  Cardiac patientsb 2 1333/9820 1.10 (0.83–1.45) 0.0% - 13 4643c/38,219 1.51 (1.26–1.81) 65.7% -
 Population-based 12 3819/145,788 1.08 (0.86–1.36) 33.3% Reference 20 103,152/981,812 1.10 (0.95–1.28) 91.7% Reference
Mean age
 ≥80 years 1 87/539 0.55 (0.33–0.93) - 0.004 3 6216/18,267 1.05 (0.55–1.98) 95.2% Reference
 65–79 years 11 2799/22,989 1.08 (0.94–1.23) 0.0% 0.04 20 9706/49,057 1.15 (1.03–1.29) 34.7% 0.73
 <65 years 5 2387/134,489 1.53 (1.16–2.01) 0.0% Reference 17 96,234c/969,065 1.38 (1.19–1.60) 89.3% 0.22
Location
 Europe 7 1807/13,446 0.96 (0.74–1.23) 33.4% 0.045 19 92,477/847,659 1.09 (0.95–1.26) 83.2% 0.92
 North America 5 2544/24,417 1.08 (0.90–1.29) 0.0% 0.097 10 8176c/40,891 1.26 (1.12–1.41) 54.5% 0.50
 Asia 4 731/118,301 1.72 (1.13–2.62) 0.0% Reference 10 10,671/143,981 1.75 (1.42–2.15) 60.1% 0.07
 Oceania 1 191/1853 1.50 (0.90–2.50) - 0.70 1 832/3858 1.06 (0.86–1.31) - Reference
Female proportion
 ≥50% 12 3814/149,254 1.06 (0.87–1.29) 29.5% Reference 22 103,550/990,510 1.13 (0.97–1.31) 91.1% Reference
 <50% 5 1459/8763 1.23 (0.96–1.58) 0.0% 0.35 18 8606c/45,879 1.42 (1.25–1.63) 65.8% 0.03
Mean follow-up
 ≥10 years 7 3338/139,867 1.21 (0.98–1.50) 16.2% 0.12 9 14,896/165,332 1.25 (0.98–1.59) 89.7% 0.44
 5–10 years 5 399/4517 1.19 (0.94–1.52) 0.0% 0.20 13 88,149c/822,913 1.10 (0.92–1.32) 85.8% Reference
 <5 years 5 1536/13,633 0.88 (0.63–1.23) 34.0% Reference 18 9111c/48,144 1.37 (1.19–1.58) 72.7% 0.09
  1. CI confidence interval, IHD ischemic heart disease, OHypo overt hypothyroidism, RR relative risk, SCH subclinical hypothyroidism
  2. aP values indicate whether the pooled estimate in each subgroup differs from a nominated reference subgroup
  3. bStudies with cardiac patients were included in convenience sample studies
  4. cTwo cohort studies by McQuade et al. [45] and Mitchell et al. [46] did not provide the number of all-cause mortality events; we contacted the authors by email but didn’t get a reply