The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis
Authors' conclusion
There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes.
Study context
- Population
- Adults (≥18 years) in prospective cohorts with thyroid-stimulating hormone (TSH) or free thyroxine (FT4) and CV outcomes or mortality, excluding solely pregnant women, overt thyroid disease and CVD; median age 59 years (range 18–106)
- Participants
- 134,346 adults26 cohorts
- Comparison
- FT4 and TSH percentile categories vs lowest-risk percentiles
- Outcome
- Composite of:
- CVD events (coronary heart disease, stroke, HF)
- All-cause mortality
Methodological detailsone-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses, adjusted for age, sex, smoking, systolic blood pressure, diabetes and total cholesterol, 3935 studies identified; 53 cohorts eligible; 26 cohorts agreed to participate
- One-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses
- Adjusted for age, sex, smoking, systolic blood pressure, diabetes and total cholesterol
- 3935 studies identified; 53 cohorts eligible; 26 cohorts agreed to participate
Pooled result
As reported in the abstract
Further pooled results
| Outcome | HR (95% CI) | |
|---|---|---|
| All-cause mortalityFT4 80–100th percentilesvs FT4 20–40th percentilesAge-adjusted and sex-adjusted | 1.34 (1.20–1.49) | |
| All-cause mortalityTSH 0–20th percentilesvs TSH 60–80th percentilesAge-adjusted and sex-adjusted | 1.09 (1.05–1.14) | |
| CVD mortalityFT4 80–100th percentilesvs FT4 20–40th percentilesAge-adjusted and sex-adjusted | 1.57 (1.31–1.89) | |
| CVD mortalityTSH 0–20th percentilesvs TSH 60–80th percentilesAge-adjusted and sex-adjusted | 1.07 (0.99–1.16) | |
| CVD eventsFT4 80–100th percentilesvs FT4 20–40th percentilesAge-adjusted and sex-adjusted | 1.22 (1.11–1.33) | |
| 0.512Hazard ratio (log scale) |
10-year absolute risk of composite outcome, age ≥70 years
- Increased over 5% for women with FT4 >85th percentile (median 17.6 pmol/L [IQR 15.0-18.3])
- Increased over 5% for men with FT4 >75th percentile (16.7 pmol/L [14.0-17.4])
Original publication
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