Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease: An Individual Participant Data Analysis of 14 Cohorts

TY - JOUR

T1 - Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease

T2 - An Individual Participant Data Analysis of 14 Cohorts

AU - Åsvold, Bjørn O

AU - Vatten, Lars J

AU - Bjøro, Trine

AU - Bauer, Douglas C

AU - Bremner, Alexandra

AU - Cappola, Anne R

AU - Ceresini, Graziano

AU - den Elzen, Wendy P J

AU - Ferrucci, Luigi

AU - Franco, Oscar H

AU - Franklyn, Jayne A

AU - Gussekloo, Jacobijn

AU - Iervasi, Giorgio

AU - Imaizumi, Misa

AU - Kearney, Patricia M

AU - Khaw, Kay-Tee

AU - Maciel, Rui M B

AU - Newman, Anne B

AU - Peeters, Robin P

AU - Psaty, Bruce M

AU - Razvi, Salman

AU - Sgarbi, José A

AU - Stott, David J

AU - Trompet, Stella

AU - Vanderpump, Mark P J

AU - Völzke, Henry

AU - Walsh, John P

AU - Westendorp, Rudi G J

AU - Rodondi, Nicolas

AU - Thyroid Studies Collaboration

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

U2 - 10.1001/jamainternmed.2015.0930

DO - 10.1001/jamainternmed.2015.0930

M3 - Journal article

C2 - 25893284

SN - 2168-6106

VL - 175

SP - 1037

EP - 1047

JO - JAMA Internal Medicine

JF - JAMA Internal Medicine

IS - 6

ER -