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Meta-Analysis
. 2015 Jun;175(6):1037-47.
doi: 10.1001/jamainternmed.2015.0930.

Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts

Bjørn O Åsvold  1 , Lars J Vatten  2 , Trine Bjøro  3 , Douglas C Bauer  4 , Alexandra Bremner  5 , Anne R Cappola  6 , Graziano Ceresini  7 , Wendy P J den Elzen  8 , Luigi Ferrucci  9 , Oscar H Franco  10 , Jayne A Franklyn  11 , Jacobijn Gussekloo  8 , Giorgio Iervasi  12 , Misa Imaizumi  13 , Patricia M Kearney  14 , Kay-Tee Khaw  15 , Rui M B Maciel  16 , Anne B Newman  17 , Robin P Peeters  18 , Bruce M Psaty  19 , Salman Razvi  20 , José A Sgarbi  21 , David J Stott  22 , Stella Trompet  23 , Mark P J Vanderpump  24 , Henry Völzke  25 , John P Walsh  26 , Rudi G J Westendorp  27 , Nicolas Rodondi  28 ; Thyroid Studies Collaboration
Collaborators, Affiliations
Meta-Analysis

Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts

Bjørn O Åsvold et al. JAMA Intern Med. 2015 Jun.

Abstract

Importance: Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD).

Objective: To assess the association between differences in thyroid function within the reference range and CHD risk.

Design, setting, and participants: Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline.

Exposures: Thyroid function as expressed by serum thyrotropin levels at baseline.

Main outcomes and measures: Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status.

Results: Among 55,412 individuals, 1813 people (3.3%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results.

Conclusions and relevance: Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Peeters has received lecture and consultancy fees from Genzyme Europe. No other disclosures were reported.

Figures

Figure
Figure. Hazard Ratios (HRs) of Coronary Heart Disease (CHD) Mortality, a First-Time CHD Event, and a First-Time Hard CHD Event per 1-mIU/L Higher Thyrotropin Level at Baseline, Adjusted for Age, Sex, and Smoking at Baseline
The squares represent HRs from each cohort, and the lines represent 95% CIs. The diamonds represent pooled HRs (with 95% CIs) from random-effects (DerSimonian and Laird [D+L] Overall) and fixed-effect (inverse variance [I-V] Overall) meta-analysis. EPIC-Norfolk indicates European Prospective Investigation of Cancer–Norfolk; HUNT, Nord-Trøndelag Health Study; InCHIANTI, Invecchiare in Chianti; and PROSPER, Prospective Study of Pravastatin in the Elderly at Risk. aWeights are from random-effects analysis.
See this image and copyright information in PMC

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