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

Abstract

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 thyroid is intricately related to the cardiovascular system, sharing a common embryological origin, and having possible direct and indirect effects in the heart and vasculature (1). If moderate or severe thyroid dysfunction is usually detected and treated, then there may be little long-term cardiovascular consequence; however, this requires formal evaluation. With respect to mild dysfunction, attempts to clarify the net clinical significance and need for intervention have resulted in longstanding uncertainty and concern for overtreatment (2–4).

There is a need to better delineate the potential cross-sectional relationships with cardiovascular disease (CVD) risk factors as possible intermediaries between thyroid dysfunction and cardiovascular risk. In investigating this, triiodothyronine (T3) has been unavailable in most epidemiologic studies to date. T3 is considered the bioactive form of thyroid hormone that mediates peripheral effects and therefore of specific interest with respect to risk for CVD events.

Prior meta-analyses examining the association of thyroid function with atherosclerotic CVD events have reported major inconsistencies between studies. Higher-quality studies provided more conservative risk estimates than lower-quality studies (5). A single cohort study with standardized procedures, long-term follow-up, and a comprehensive thyroid panel (inclusive of T3), would be highly informative. Only one such study has been done that examined thyroid function and adverse outcomes in 2843 adults enrolled in the Cardiovascular Health Study, with thyrotropin (TSH), free thyroxine (FT4), and T3 concentrations in the euthyroid range (6).

Therefore, we conducted an analysis of data from the Atherosclerosis Risk in Communities (ARIC) study to extend knowledge of the cross-sectional and prospective associations of thyroid function with cardiovascular risk factors and outcomes.

Subjects and Methods

Study design and population

The original ARIC Study design was previously reported in detail (7). In brief, the ARIC Study is a prospective cohort of atherosclerosis risk in predominantly black and white men and women from four communities in the United States (Forsyth County, NC; suburban Minneapolis, MN; Washington County, MD; Jackson, MS). The current study was a cross-sectional and prospective analysis of thyroid measures, cardiovascular risk factors, and cardiovascular events. Thyroid tests were performed on serum samples originally obtained at the second (1990–1992) and fifth (2011–2013) ARIC examinations, and use of thyroid replacement hormone therapy was also recorded at these visits. ARIC visit 2 was considered the baseline for this study. Institutional review boards at each study center approved the study protocol, and written informed consent was obtained from all study participants.

We included all ARIC participants who attended visit 2 and had thyroid measurements performed on stored serum. We excluded those missing data on baseline covariates and those with a history of myocardial infarction (MI), stroke, or heart failure present at or before visit 2 (see Supplemental Fig. 1 for flow diagram of study population selection).

Exposures

Thyroid tests were conducted in 2011–2013 at the Advanced Research Diagnostics Laboratory (University of Minnesota) in serum samples that had been in storage at −70°C since collection. Clinical grade assays from Roche Diagnostics were used on an Elecsys 2010 Analyzer using a sandwich immunoassay method for TSH and competition immunoassay methods for FT4 and total T3. All interassay coefficients of variation were ≤10%. We considered thyroid function according to five common clinical categories: moderate or severe chemical hypothyroidism, mild chemical hypothyroidism, euthyroidism, mild chemical hyperthyroidism, and moderate or severe chemical hyperthyroidism (Table 1) (8, 9). In addition, we considered thyroid measures continuously using log-transformed TSH, FT4, and T3 concentrations. Log-transformations were in base 2, yielding estimates for a twofold increase in the marker.

Other measurements and definitions

Blood pressure was measured at rest via a standardized protocol with hypertension defined as taking antihypertensive therapy or having an untreated blood pressure of ≥140 systolic or ≥90 mm Hg diastolic (mean of the second and third of three readings). Serum glucose was measured using the hexokinase method. Hemoglobin A1c was measured in whole blood using high-performance liquid chromatography with instruments standardized to the Diabetes Control and Complications Trial assay (Tosoh A1c 2.2. Plus Glycohemoglobin and Tosoh G7 analyzers). Diabetes was considered present if a participant self-reported physician diagnosis or taking antidiabetic therapies, or had fasting glucose ≥126 mg/dL, a nonfasting glucose ≥200 mg/dL, or an hemoglobin A1c value of ≥6.5%. We examined fasting lipid concentrations including low-density lipoprotein cholesterol (LDL-C) [calculated as described (10)], high-density lipoprotein cholesterol (HDL-C), triglycerides, non-HDL-C, and total cholesterol/HDL-C. Body mass index was measured as weight in kilograms divided by the square of height in meters. Alcohol use and smoking status were self-reported.

Outcomes

Cardiovascular risk factors were assessed as cross-sectional outcomes in a continuous fashion: blood pressure, glycemic measures, and blood lipids. Additional cross-sectional outcomes included high-sensitivity C-reactive protein (hsCRP) (continuous), as a measure of systemic inflammation, and heart rate (continuous).

Prospective outcomes were adjudicated fatal and nonfatal MI and stroke, consistent with the focus of recent clinical guidelines (11). Ascertainment and adjudication of cardiovascular events have been detailed previously (12, 13). Briefly, potential cardiovascular hospitalizations were reported annually by participants (or proxy) and identified through community-wide hospital surveillance and linkage to state and national death indexes. Trained personnel abstracted hospital records related to possible cardiovascular events, with outcomes adjudicated by a panel of experts. Incident MI was defined as definite or probable MI, death from coronary heart disease, or electrocardiographic evidence of a silent MI detected at one of the follow-up visits. We also examined definite or probable stroke (adjudicated). Follow-up data for all cardiovascular events were available up to 31 December 2014.

Statistical analysis

We examined age, sex, and race-center adjusted covariates as frequencies (percentage) for categorical variables and mean (standard deviation) for continuous variables according to thyroid status at baseline. We compared baseline characteristics of study participants using χ² and t tests for categorical and continuous variables, as appropriate. In individuals who were categorized as having mild or moderate–severe chemical hypothyroidism at baseline, we assessed use of thyroid hormone replacement therapy and thyroid function status during follow-up; similarly, we assessed follow-up thyroid function status in those with mild or moderate–severe chemical hyperthyroidism at baseline.

To characterize the associations of thyroid dysfunction and the individual hormones with cross-sectional outcomes, we used linear and logistic regression models. For prospective associations with incident cardiovascular events, we used Cox proportional hazards models, with censoring of noncardiovascular deaths and individuals lost to follow-up, to estimate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). We verified that the proportional hazards assumption was met using log–log plots.

We used restricted cubic spline models to investigate the continuous associations between T3 and blood pressure, glycemic markers, and lipids, as well as to investigate the continuous association between T3, FT4, and TSH and risk of MI and stroke. Knots were specified at the 20th, 40th, 60th, and 80th percentiles (110.3, 121.3, 131.4, and 144.3 ng/dL, respectively, for T3; 0.99, 1.08, 1.15, and 1.24 ng/dL, respectively, for FT4; and 1.10, 1.55, 2.07, and 2.98 mIU/L, respectively, for TSH). Thyroid test values were truncated at the 1st and 99th centiles to minimize the influence of extreme values at either tail of the distribution.

We constructed three models for each of the outcomes. Model 1 was unadjusted. Model 2 was adjusted for age (years), sex (men, women), race-field center (white participants, MN, MD, and NC; black participants, MS and NC), HDL-C (mg/dL), alcohol use (current, former, never), and tobacco use (current, former, never). Model 3 was adjusted for all variables in Model 2 plus systolic blood pressure (mm Hg), diastolic blood pressure (mm Hg), current antihypertensive medication use (yes, no), non-HDL-C (mg/dL), current lipid-lowering therapy (yes, no), diabetes (yes/no), body mass index (kg/m²), and heart rate. When modeling stroke, we also included atrial fibrillation (baseline or incident) as a mediator. We tested for multiplicative interactions by age, sex, race, and diabetes status, and stratified analyses where appropriate.

We conducted two sensitivity analyses. First, we excluded those on thyroid medication at baseline, reasoning that there may be a difference in the outcomes related to endogenous vs exogenous thyroid dysfunction. Second, in our cross-sectional analysis of risk factors, we excluded participants on treatment of the relevant risk factors (i.e., excluded those on antihypertensives when examining systolic blood pressure or those on lipid-modifying drugs when examining lipids, and so forth), to probe the natural associations unaltered by exposure to medications.

Results

Baseline characteristics

The mean age was 57 ± 6 years with 58% women and 76% white participants, with 4.8% of participants taking thyroid replacement therapy at baseline. Table 1 shows baseline characteristics by thyroid function group. Among 11,359 participants, 1381 (12%) had thyroid dysfunction at baseline, including moderate or severe chemical hypothyroidism (n = 255; 2.2%), mild chemical hypothyroidism (n = 542; 4.8%), mild chemical hyperthyroidism (n = 378; 3.3%), and moderate or severe chemical hyperthyroidism (n = 206; 1.8%).

Association with CVD risk factors

The association of thyroid function group with CVD risk factors, adjusted for age, sex, and race-center, is shown in Table 2. Compared with euthyroid participants, the group with moderate or severe chemical hypothyroidism had heart rates that were lower, on average, by 1.7 beats per minute and those with moderate or severe chemical hyperthyroidism had heart rates that were an average of 3.2 beats per minute higher. The two mild thyroid dysfunction groups did not significantly differ in heart rate relative to euthyroid participants.

The mild thyroid dysfunction groups also did not differ significantly in prevalence of diabetes, A1c, or glucose concentrations. A higher A1c was noted in the moderate or severe chemical hypothyroidism group, but it was modest and confined to individuals without diabetes. Hypertension was not more prevalent in thyroid dysfunction groups as compared with the euthyroid group. A modestly higher diastolic blood pressure was seen in the moderate or severe chemical hypothyroidism group.

Regarding blood lipids, in the setting of a low prevalence of lipid-lowering medication use (5.2%), mean adjusted differences in LDL-C were +15.1 (95% CI: 10.5 to 19.7) and +3.2 (0.0 to 6.4) mg/dL in those with moderate or severe and mild chemical hypothyroidism relative to euthyroidism; an opposite pattern was seen in moderate or severe and mild chemical hyperthyroidism [−10.8 (−15.9 to −5.7) and −3.9 (−7.7 to −0.1) mg/dL, respectively]. A similar pattern in mean adjusted differences were seen in non-HDL-C and triglycerides [non-HDL-C: +18.8 (95% CI: 13.7 to 24.0) and +4.0 (0.4 to 7.6) mg/dL in those with moderate or severe and mild chemical hypothyroidism and −11.3 (−17.1 to −5.6) and −4.8 (−9.0 to −0.5) mg/dL in those with moderate or severe and mild chemical hyperthyroidism, respectively, relative to euthyroidism; triglycerides: +24.5 (95% CI: 13.7 to 35.2) and +4.6 (−2.9 to 12.1) mg/dL in those with moderate or severe and mild chemical hypothyroidism, respectively, and −4.5 (−16.4 to 7.4) and −6.0 (−14.9 to 2.8) mg/dL in those with moderate or severe and mild chemical hyperthyroidism, respectively, relative to euthyroidism]. hsCRP did not differ between groups.

T3 concentrations appeared to have an inverse linear association with non-HDL-C concentrations, whereas the associations appeared nonlinear for other risk factor outcomes including blood pressure and A1c (Fig. 1). For each doubling in T3, non-HDL-C was lower by 18.0 mg/dL (95% CI: 15.2 to 20.8; P < 0.001) and LDL-C by 18.7 mg/dL (95% CI: 16.2 to 21.2; P < 0.001).

Thyroid-related outcomes in individuals with moderate or severe thyroid disease at baseline

Assessing whether moderate or severe thyroid disease was treated over the course of follow-up, as one may expect, we found that 111 individuals with baseline moderate or severe chemical hypothyroidism had follow-up data at visit 5 (2011–2013), at which time 94 (84.7%) were on thyroid replacement hormone therapy. Moreover, 76 individuals had follow-up thyroid hormone data, among whom 63 (82.9%) had resolution of moderate or severe chemical hypothyroidism. A total of 57 (90.5%) of the 63 participants who had resolution of moderate or severe chemical hypothyroidism were on thyroid replacement therapy at visit 5. Further, 29 (50.9%) of these 57 participants on thyroid replacement therapy were well controlled at visit 5 (i.e., TSH levels between 0.56 and 5.1 mIU/L). Among those 245 individuals with baseline mild hypothyroidism who had follow-up data at visit 5, 156 (63.7%) were on thyroid replacement hormone therapy. Considering the 61 participants with moderate or severe chemical hyperthyroidism at baseline and follow-up thyroid hormone data at follow-up at visit 5, 48 (78.7%) were no longer moderate or severely hyperthyroid.

Incident CVD events

During a median follow-up of 22.5 years, 1102 MIs and 838 strokes occurred. Although there was suggestion of increased MI risk at TSH levels >15 mIU/L, and increased stroke risk at FT4 levels ∼1.2 ng/dL, overall we did not observe any significant association between baseline TSH, FT4, or T3 with MI or stroke (Fig. 2). Unadjusted and adjusted Cox models of baseline thyroid function groups or by log-transformed concentration of T3 are shown in Table 3 and were also largely null (with the exception of moderate or severe chemical hypothyroidism in model 2 for MI risk). In models of continuous log2-transformed T3, the fully adjusted HR for MI was 0.88 (95% CI: 0.70 to 1.11) and for stroke it was 0.80 (0.61 to 1.06).

Interaction and sensitivity analyses

There was no significant interaction of thyroid markers with age, sex, or race-center with respect to cross-sectional or prospective outcomes. Our findings were robust in sensitivity analyses excluding the 4.8% of participants on thyroid medication at baseline (Supplemental Table 1) and excluding participants on treatment of the relevant risk factors (Supplemental Table 2).

Discussion

In this study of community-dwelling US adults without prior CVD, we observed the following major findings: (1) thyroid function was most strongly associated with blood lipids among modifiable risk factors; (2) as opposed to moderate or severe thyroid disease, the association of mild thyroid disease with lipids was small in magnitude; (3) most individuals with moderate or severe thyroid disease were detected and treated; and (4) cardiovascular prognosis was generally similar between thyroid function groups.

Although cardiovascular outcomes were generally similar between thyroid function groups, our results are fully compatible with the most robust observational evidence to date on these associations finding relatively modest associations between thyroid dysfunction and increased risk of CVD outcomes (6, 14–16). In a 2010 Thyroid Studies Collaboration, individual participant data analysis of seven cohort studies, including 4470 coronary heart disease events and 2168 coronary heart disease deaths, found that TSH levels >7 to 10 mIU/L were associated with increased coronary heart disease risk (16). Our study results (Fig. 2; Table 3) are compatible with these findings; however, we do not have sufficient statistical power to determine whether similar associations are present in the ARIC study.

Consistent with blood lipids being most strongly associated with thyroid dysfunction among the cardiovascular risk factors explored in our study, the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Cholesterol Guideline recognizes hypothyroidism as one of the most commonly encountered secondary causes of elevated LDL-C and triglycerides (11). The atherogenic lipid changes in thyroid dysfunction appear to occur quickly, as seen in individuals with a hypothyroid state 3 weeks after thyroidectomy (17). Even low normal free T4 concentrations have been associated with a more atherogenic lipid profile (18). However, in ARIC participants with mild but not moderate or severe chemical hypothyroidism, alterations in the lipid profile were small in magnitude, generally compatible with the modest effects previously seen in randomized trials of l-thyroxine in such individuals (19, 20).

As compared with blood lipids, any associations of thyroid dysfunction with blood pressure and glycemic measures were more modest. Even in the moderate or severe thyroid dysfunction groups, differences in blood pressure were only ∼2 mm Hg relative to the euthyroid group, and 0.1% for A1c. No significant association was seen between mild thyroid dysfunction and blood pressure or glycemic measures. Moreover, T3 concentrations did not have a continuous linear relationship to these risk factors, in contrast to blood lipids. Therefore, the net relationship of thyroid dysfunction to blood pressure and glycemia may not be of major clinical significance. This is seemingly inconsistent with some previous research reporting a linear relationship between serum TSH levels and blood pressure and argues for further research on the association between thyroid function and blood pressure (21, 22).

Regarding coronary risk, Collet et al. (14) previously reported that endogenous mild chemical hyperthyroidism was associated with coronary heart disease mortality, especially when the TSH concentration was <0.10 mIU/L. In analyses of mild chemical hypothyroidism by Hyland et al. (23) of the Cardiovascular Health Study, no association was observed with incident coronary heart disease, regardless of stratification by degree of TSH elevation. Within the reference range, TSH concentrations were also not associated with risk of coronary heart disease in an analysis by Asvold et al. (15). In a pooled analysis of 15 studies by Razvi et al. (20), mild chemical hypothyroidism was associated with both prevalent and incident ischemic heart disease; however, the risk was confined to individuals <65 years of age. Walsh et al. (24) reported that mild chemical hypothyroidism was an independent risk factor for coronary heart disease, without modification by age, whereas Hak et al. (25) reported that mild chemical hypothyroidism was associated with MI in elderly women. Thus, prior studies have been inconsistent; importantly, those studies considered higher quality on the basis of methods of outcome ascertainment and adjudication, accounting for confounders, and completeness of follow-up, have provided risk estimates close to 1.0 (5). The present analysis, examining the end point of MI, the coronary end point of the 2013 ACC/AHA guidelines, is in agreement with those higher quality studies.

Stroke is another major form of atherosclerotic CVD that was added as an end point to cardiovascular risk assessment in the 2013 ACC/AHA prevention guidelines. In addition to atherosclerosis, stroke can occur due to thromboembolism, with atrial fibrillation representing a common underlying cause. A systematic review and meta-analysis in 2014 showed no association between either mild chemical hypothyroidism or hyperthyroidism with risk of stroke (26). A subsequent pooled analysis of individual participant data in 2015 also reported no overall association of mild chemical hypothyroidism with stroke (6). However, there was suggestion of increased risk in individuals <65 years and with higher TSH. Our analysis did not reproduce these latter findings and is consistent with a lack of excess stroke risk related to thyroid dysfunction in individuals free of pre-existing CVD who are diagnosed and treated.

The lack of a difference in clinical events likely reflects a lack of clinically significant alterations in risk factors in mild chemical thyroid dysfunction and in the case of moderate or severe thyroid dysfunction suggests that existing clinical care negates any long-term cardiovascular risk that might otherwise occur in this group without treatment. Regarding treatment of persons with moderate or severe chemical hypothyroidism, 85% of those in our study reported being on thyroid hormone replacement therapy at a later study visit. Though we did not record treatments of those with moderate or severe chemical hyperthyroidism, we documented subsequent resolution by thyroid function testing in 79% of individuals. The finding that ∼15% to 20% of individuals had persistent moderate or severe thyroid disease at a 23-year follow-up suggests a need for greater attention to treatment and follow-up in a portion of the population.

Some limitations of our study must be considered. A key limitation of our cross-sectional analysis is the lack of ability to infer temporality of the observed associations between thyroid function and cardiovascular risk factors. Furthermore, clinical thyroid status was not ascertained at ARIC visit 2, so it is possible that mild thyroid dysfunction in ARIC may be more moderate than mild thyroid dysfunction in the clinic, yielding a group that is closer to euthyroidism than studies with clinic-based populations. Indeed, there was no significant alteration in heart rate in the mild thyroid dysfunction groups. To more powerfully assess any potential relationships, we explored the continuous associations of the individual thyroid biomarkers with outcomes. Furthermore, it warrants consideration that our analysis was limited to individuals without pre-existing CVD, whereas it has been suggested that hypothyroidism is associated with higher cardiovascular risk in patients with coronary artery disease undergoing percutaneous coronary intervention (27). An additional study limitation is that mild chemical hyperthyroidism is often transient, and only a single baseline assessment of thyroid status was performed. A final limitation of our study is that modern TSH assays may better identify persons with mild TSH abnormalities. Thyroid experts debate the thresholds at which the clinician should treat the TSH levels, but once a patient has a borderline value they are now typically followed with serial TSH levels at 6- or 12-month intervals or more often if clinical signs of thyroid dysfunction manifest.

Our study has five important strengths. First, we used a comprehensive panel of thyroid tests, including T3 along with TSH and FT4. T3 showed the closest relationship with heart rate, consistent with known biologic effects and the importance of its measurement. Second, we had follow-up data on thyroid medication use and thyroid function tests, which allowed confirmation that the vast majority of individuals with moderate or severe thyroid disease at baseline were subsequently treated. A third strength of our study is that we used the same third generation TSH assay in all participants. Older studies generally used first or second generation TSH assays. Fourth, we included high quality fasting lipids. Lastly, a major strength of our study was its power in a single cohort. Although prior meta-analyses have also included large numbers of participants, long durations of follow-up time, and many clinical events, our study has the advantage of standardization in measurements and end point adjudication.

Conclusion

In a large prospective cohort study in the United States, inclusive of T3 concentrations, we addressed the longstanding clinical question of cardiovascular risk in individuals initially free of CVD but with thyroid dysfunction. Persons with various degrees of thyroid function, by clinical categories or concentrations of T3, had cardiovascular outcomes over two decades of follow-up that were similar to those with normal thyroid function. These results support existing guideline recommendations and provide reassurance that clinical management of moderate or severe thyroid disease in the United States is effectively mitigating any long-term cardiovascular consequences.

Abbreviations:

 
• ACC

  American College of Cardiology

 
• AHA

  American Heart Association

 
• ARIC

  Atherosclerosis Risk in Communities

 
• CI

  confidence interval

 
• CVD

  cardiovascular disease

 
• FT4

  free thyroxine

 
• HDL-C

  high-density lipoprotein cholesterol

 
• HR

  hazard ratio

 
• hsCRP

  high-sensitivity C-reactive protein

 
• LDL-C

  low-density lipoprotein cholesterol

 
• MI

  myocardial infarction

 
• T3

  triiodothyronine

 
• TSH

  thyrotropin.

Acknowledgments

The authors thank the staff and participants of the ARIC study for their important contributions.

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.

References