Association Between Subclinical Thyroid Dysfunction and Fracture Risk.

Importance: Clinical hyperthyroidism accelerates bone resorption without compensatory bone formation, reducing bone density and increasing the risk of fracture. The association between subclinical hyperthyroidism and fracture risk is less clear. Objective: To investigate the association of endogenous subclinical thyroid dysfunction and fracture risk, independent of clinical confounders. Design, Setting, and Participants: This cohort study included 10 946 participants from the Atherosclerosis Risk in Communities Study, an ongoing prospective cohort study of community-dwelling individuals conducted from 1987-1989 through December 31, 2019, in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis, Minnesota. Participants were not taking thyroid medications and had no history of fractures. Exposures: Thyrotropin and free thyroxine levels were measured at visit 2 (1990-1992). Subclinical hyperthyroidism was defined as a thyrotropin level lower than 0.56 mIU/L, subclinical hypothyroidism as a thyrotropin level higher than 5.1 mIU/L, and euthyroidism as a thyrotropin level of 0.56 to 5.1 mIU/L, with normal free thyroxine levels from 0.85 to 1.4 ng/dL. Main Outcomes and Measures: Incident fracture was ascertained using hospitalization discharge codes through 2019 and linkage to inpatient and outpatient Medicare claims through 2018. Results: Of 10 946 participants (54.3% women; mean [SD] age, 57 [5.7] years), 93.0% had euthyroidism, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism. During a median follow-up of 21 years (IQR, 13.0-27.3 years), there were 3556 incident fractures (167.1 per 10 000 person-years). The adjusted hazard ratios of fracture were 1.34 (95% CI, 1.09-1.65) for those with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism compared with individuals with euthyroidism. Among those with normal free thyroxine levels, thyrotropin levels in the lower-than-normal range were significantly associated with higher fracture-related hospitalization risk; fracture risk was greater among individuals with thyrotropin concentrations below 0.56 mIU/L. Conclusions and Relevance: This community-based cohort study suggests that subclinical hyperthyroidism was an independent risk factor associated with fracture. The increased risk for fracture among individuals with a thyrotropin level lower than 0.56 mIU/L highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease.

Relation of Lifestyle Factors and Life's Simple 7 Score to Temporal Reduction in Troponin Levels Measured by a High-Sensitivity Assay (from the Atherosclerosis Risk in Communities Study).

The impact of lifestyle-related factors on temporal decreases in high-sensitivity cardiac troponin T (hs-cTnT), possibly reflecting reversal of subclinical myocardial damage, has not been evaluated in a community-based setting. We measured hs-cTnT twice, 6 years apart, in 9,256 participants from the Atherosclerosis Risk in Communities (ARIC) Study who were free from baseline cardiovascular disease. We used Poisson and multinomial regression to evaluate the associations of cigarette smoking, alcohol consumption, body mass index, healthy diet score, physical activity, and Life's Simple 7 (LS7) score (a composite measure of lifestyle-related health factors) with 6-year decreases in hs-cTnT. Of the 3,017 patients with detectable baseline hs-cTnT (≥5 ng/L), 2,418 (80%) remained detectable, whereas 599 (20%) had undetectable levels (<5 ng/L) at the 6-year follow-up visit. Patients with a body mass index of <30 kg/m2, adherence to American Heart Association's physical activity guidelines, and average or optimal LS7 scores were more likely to improve from a detectable to an undetectable hs-cTnT level during follow-up. There was a robust association between optimal LS7 score and temporal hs-cTnT reduction (relative risk 1.64, 95% confidence interval 1.11 to 2.42, for baseline ≥5 ng/L and for follow-up <5 ng/L). A greater duration of exposure to average or optimal LS7 score was also associated with increased likelihood of temporal hs-cTnT reduction (p-trend <0.001). In conclusion, we found that lifestyle factors and the LS7 score were associated with reversal of subclinical myocardial damage. In conclusion, our results support the growing evidence that hs-cTnT levels change in response to lifestyle modifications and hs-cTnT may serve as a useful dynamic surrogate for monitoring cardiovascular risk.

Thyroid Function, Cardiovascular Risk Factors, and Incident Atherosclerotic Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study.

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 (57 ± 6 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.

The Association of Socioeconomic Status With Subclinical Myocardial Damage, Incident Cardiovascular Events, and Mortality in the ARIC Study.

The association between socioeconomic status (SES) and subclinical cardiovascular disease is not well understood. Using data from the Atherosclerosis Risk in Communities Study, we sought to evaluate the cross-sectional and prospective associations of SES, measured by annual income and educational level, with elevated high-sensitivity cardiac troponin T (hs-cTnT) concentrations (≥14 ng/L) using Poisson and multinomial logistic regressions, respectively. We used Cox proportional hazard models to compare the risks of coronary heart disease, heart failure, and mortality according to SES, stratified by baseline hs-cTnT concentration. Our study baseline was 1990-1992, with follow-up through 2011. We found an independent association between SES and hs-cTnT. When comparing participants in the lowest educational level group to those in the highest, the adjusted prevalence ratios for elevated hs-cTnT were 1.36 (95% confidence interval: 1.05, 1.75) overall, 1.83 (95% confidence interval: 1.23, 2.71) in blacks, and 1.05 (95% confidence interval: 0.73, 1.52) in whites (P for interaction = 0.08). Among participants with nonelevated hs-cTnT concentrations, when comparing those in the lowest income groups to those in the highest, the adjusted hazard ratios were strongest for heart failure and death. Having elevated baseline hs-cTnT doubled the risk of heart failure and death. Persons with low SES and elevated hs-cTnT concentrations have the greatest risk of cardiovascular events, which suggests that this group should be aggressively targeted for cardiovascular risk reduction.