Background
Methods
Literature search
Inclusion and exclusion criteria
Study selection
Data extraction
Quality assessment
Statistical analysis
Results
Search results
Summary of included studies
Author (year) | Study population | Country | No. of patients Nor/Hypo/Hyper | Defnition of Hypo/Hyper | Mean follow-up | Mean age (year) | Male % | Outcome | Adjusted variables | Quality score |
---|---|---|---|---|---|---|---|---|---|---|
Iacoviello 2008 [28] | prospective | Italy | 304/34/NA | TSH > 5.5mIU/l/ NA | 15 mo | 64 | 77 | All-cause mortality | Age, sex, BMI, DM, NYHA, HR, hypertension, LVEF, GFR, NT-proBNP, medication | 4 |
Frey 2013 [27] | INH study | Germany | 628/34/69 | TSH > 4.0 mIU/l/ TSH < 0.3 mIU/l | 37 mo | 68 | 71 | All-cause mortality | Age | 5 |
Rhee 2013 [26] | NHANES III | United States | 410/54/NA | TSH > 4.7 mIU/l | 14.3 mo | 52.3 | 42.6 | All-cause mortality | Age, sex, race, DM, hypertention, hypercholesterolemia, stroke, MI, BMI, GFR, medication | 4 |
Mitchell 2013 [25] | SCD-HeFT | United States | 1930/275/23 | TSH > 5.0 mIU/l/ THS < 0.3 mIU/l | 45.5 mo | 61.3 | 65 | All-cause mortality | Age, sex, DM, renal insufficiency, hypertension, LVEF, time since HF diagnosis, 6-min walk distance, medication | 6 |
Azemi 2013 [24] | Clinical setting | United States | 243/102/26 | TSH > 5 mIU/l/ TSH < 0.4 mIU/l | 27.2 mo | 67 | 77.9 | All-cause mortality | Age, sex, TSH, LVEF, DM, primary indication for ICD implantation, medication | 5 |
Deursen 2014 [23] | Observational survey | Italy | 2839/290/97 | NA/NA | 12.1 mo | 66 | 70 | All-cause mortality, hospilization | Age, sex, etiology, hypertension, AF, HR, body surface area, systolic blood pressure | 4 |
Chen 2014 [22] | HMO cohort | Israel | 4490/916/193 | TSH > 4.5 mIU/l/ TSH < 0.45 mIU/l | 14.5 mo | 75 | 49 | All-cause mortality, cardiac death and hospitalization | Age, sex, DM, ischemic heart disease, hyperlipdaemia, hypertension, AF, BMI, log transformed pulse, log transformed serum urea levels, GFR, hemoglobin, serum sodium, medication | 7 |
Perez 2014 [21] | CORONA | Europe | 4338/237/176 | TSH > 5.0 mIU/l/ TSH < 0.3 mIU/l | 32.8 mo | 72 | 77 | All-cause mortality, cardiac death and /or hospitalization | Age, sex, NYHA, LVEF, BMI, BP, HR, MI, smoking, angina pectoris, CABG, PCI, AA, hypertension, BM, AF, ICD, stroke, CPR, medication | 6 |
Li 2014 [20] | Clinical setting | China | 816/79/68 | TSH > 5.5 mIU/l/ TSH < 0.35 mIU/l | 42 mo | 52.1 | 73.7 | All-cause mortality | Age, sex, hypertension, AF, drinking and smoking history, QRS duration, LVEF, FT3, T3, T4, NT-Pro-BNP, medication | 6 |
Sharma 2015 [19] | Clinical setting | United States | 427/84/NA | TSH > 5.0 mIU/l | 36 mo | 68 | 77 | All-cause mortality, hospitalization | Sex, creatinine, DM, medication | 3 |
Wang 2015 [18] | Clinical setting | China | 353/41/35 | TSH > 4.78 mIU/l/ TSH < 0.55 mIU/l | 17 mo | 51 | 71 | All-cause mortality | Age, sex, BP, NT-Pro BNP, LVEF, smoking, AF, DM, anemia, renal dysfuntion, NYHA, medication | 5 |
Hayashi 2016 [17] | Clinical setting | Japan | 188/5/NA | TSH > 4.5 mIU/l | 26 mo | 70 | 57 | Cardiac death and hospitalization | Age, sex, LVEF, NT-Pro BNP, eGFR | 3 |
Sato 2018 [16] | Clinical setting | Japan | 911/132/NA | TSH > 4.0 mIU/l | 36.6 mo | 68 | 57.4 | All-cause mortality, cardiac death and hospitalization | Age, sex, BMI, BP, HR, NYHA, DM, hypertension, anemia, chronic kidney disease, AF, smoking, LVEF, medication | 5 |
Ro 2018 [15] | Clinical setting | United States | 349/25/NA | TSH > 4.7 mIU/l | 67 mo | 54.5 | 35 | hospitalization | Age, sex, BMI, race, ethnicity, DM, hypertension, hyperlipidemia, CAD, CVD | 4 |
Subclinical thyroid dysfunction and HF outcome
Subgroup analysis and sensitive analysis
All-cause mortality | Cardiac death and/or hospitalization | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Heterogeneity | Meta-analysis | Heterogeneity | Meta-analysis | |||||||
Subgroup | Number of studies | I2% | P value | HR | 95% CI | Number of studies | I2% | P value | HR | 95% CI |
Age | ||||||||||
≤ 65 | 5 | 55.0 | 0.064 | 1.70 | 1.31–2.20 | 1 | 1.23 | 1.08–1.40 | ||
> 65 | 7 | 0.0 | 0.603 | 1.31 | 1.14–1.50 | 6 | 55.3 | 0.048 | 1.37 | 1.14–1.65 |
Ethnicity | ||||||||||
Europe | 6 | 20.9 | 0.276 | 1.31 | 1.09–1.58 | 4 | 32.0 | 0.220 | 1.25 | 1.06–1.47 |
United States | 3 | 0.0 | 0.901 | 1.53 | 1.31–1.80 | 1 | 1.23 | 1.08–1.40 | ||
Asian | 3 | 76.6 | 0.014 | 1.67 | 1.00–2.78 | 2 | 63.3 | 0.099 | 1.76 | 1.11–2.81 |
Follow-up | ||||||||||
≤ 24 | 5 | 51.4 | 0.083 | 1.70 | 1.30–2.23 | 2 | 0.0 | 0.343 | 1.28 | 1.09–1.50 |
> 24 | 7 | 17.8 | 0.294 | 1.35 | 1.17–1.56 | 5 | 62.8 | 0.030 | 1.36 | 1.11–1.66 |
Sample size | ||||||||||
≤ 1000 | 7 | 45.6 | 0.088 | 1.57 | 1.25–1.97 | 3 | 72.3 | 0.027 | 1.53 | 1.09–2.15 |
> 1000 | 5 | 33.1 | 0.201 | 1.36 | 1.15–1.61 | 4 | 24.7 | 0.263 | 1.24 | 1.07–1.44 |
Score | ||||||||||
≤4 | 4 | 0.0 | 0.688 | 1.51 | 1.22–1.86 | 4 | 60.6 | 0.054 | 1.48 | 1.17–1.87 |
> 4 | 8 | 58.2 | 0.019 | 1.43 | 1.18–1.73 | 3 | 25.5 | 0.261 | 1.32 | 1.15–1.51 |
Thyroid drug use | ||||||||||
Yes | 5 | 0.0 | 0.826 | 1.48 | 1.29–1.70 | 4 | 56.5 | 0.075 | 1.32 | 1.08–1.60 |
No | 7 | 64.0 | 0.011 | 1.48 | 1.14–1.94 | 7 | 71.8 | 0.002 | 1.36 | 1.12–1.66 |
Amidarone use | ||||||||||
Yes | 6 | 43.8 | 0.113 | 1.31 | 1.08–1.57 | 5 | 46.2 | 0.115 | 1.33 | 1.13–1.56 |
No | 6 | 19.1 | 0.289 | 1.57 | 1.30–1.90 | 6 | 73.7 | 0.002 | 1.36 | 1.09–1.70 |
Publication bias
Begg’s test | Egger’s test | |
---|---|---|
All cause mortality | ||
Hypothyroidism | 1.00 | 0.870 |
Hyperthyroidism | 1.00 | 0.504 |
Cardiac death and/or hospitalization | ||
Hypothyroidism | 0.119 | 0.005 |
Hyperthyroidism | 0.806 | 0.932 |