Context: Cardiovascular outcomes in mild thyroid dysfunction (treatment controversial) and moderate or severe dysfunction (treatment standard) remain uncertain. Objective: To examine cross-sectional and prospective associations of thyroid function with cardiovascular risk factors and events. Design: In the Atherosclerosis Risk in Communities Study, we measured concentrations of thyrotropin, free thyroxine, and total triiodothyronine (T3) in stored serum samples originally collected in 1990-1992. We used multivariable linear regression to assess cross-sectional associations of thyroid function with cardiovascular risk factors and Cox regression to assess prospective associations with cardiovascular events. Follow-up occurred through 31 December 2014. Setting: General community. Participants: Black and white men and women from the United States, without prior myocardial infarction (MI), stroke, or heart failure. Main Outcomes and Measures: Cross-sectional outcomes were blood pressure, glycemic markers, and blood lipids. Prospective outcomes were adjudicated fatal and nonfatal MI and stroke. Results: Among 11,359 participants (5766 years, 58% women), thyroid function was more strongly associated with blood lipids than blood pressure or glycemic measures. Mean adjusted differences in low-density lipoprotein cholesterol were +15.1 (95% confidence interval: 10.5 to 19.7) and +3.2 (0.0 to 6.4) mg/dL in those with moderate/severe and mild chemical hypothyroidism, relative to euthyroidism; an opposite pattern was seen in hyperthyroidism. Similar differences were seen in triglycerides and non-high-density lipoprotein cholesterol. With a 22.5-year median follow-up, 1102 MIs and 838 strokes occurred, with similar outcomes among baseline thyroid function groups and by T3 concentrations. Conclusions: Hypothyroidism is associated with hyperlipidemia, but the magnitude is small in mild chemical hypothyroidism, and cardiovascular outcomes are similar between thyroid function groups.
Bibliographical noteFunding Information:
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) Contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C. S.S.M. was supported by National Institutes of Health (NIH)/NHLBI Grant T32HL007024 at the time of this research. This research was also supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grants 2R01DK089174 and K24DK106414 to E.S. Reagents for the thyroid function tests were donated by Roche Diagnostics. S.S.M., N.D., and E.S. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Disclosure Summary: S.S.M. is a co-inventor on a pending patent filed by Johns Hopkins University for the novel method of low-density lipoprotein cholesterol estimation. He has received research support from the PJ Schafer Cardiovascular Research Fund, American Heart Association, Aetna Foundation, CASCADE FH, Google, and Apple. He has served as a consultant to Quest Diagnostics, Sanofi/Regeneron, Amgen, and the Pew Research Center. S.S.M.’s grants and consultative work do not specifically relate to thyroid biomarkers. The remaining authors have nothing to disclose.
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