Impact of Subclinical Hypothyroidism on Cardiometabolic Biomarkers in Women

Paulo H. N. Harada; Julie E. Buring; Nancy R. Cook; Michael E. Cobble; Krishnaji R. Kulkarni; Samia Mora


J Endo Soc. 2017;1(2):113-123. 

In This Article


Compared with euthyroid women, those with SCH and HT were older and had higher BMI, greater prevalence of postmenopausal status, lower prevalence of current smoking, higher blood pressure, and greater prevalence of metabolic syndrome ( Table 1 ). Noticeably, metabolic syndrome prevalence (25.4% on euthyroid to 39.6% on HT) and smoking (18.2% on euthyroid to 11.3% on HT) were largely different across thyroid categories.

In analyses that adjusted for age, race, household income, current smoking, systolic blood pressure, antihypertensive treatment, menopause status, and hormone replacement therapy, across thyroid categories there were no significant contrasts for total cholesterol, LDL cholesterol, ApoA1, or Lp(a) ( Table 2 ). By contrast, going from euthyroid to SCH and HT, there was a pattern of increasing atherogenic dyslipidemia, namely, lower HDL cholesterol, higher triglycerides, higher ApoB concentrations, as well as higher triglyceride/HDL-c ratios and apoB/Apoa1 ratios. Additional adjustment for BMI did not change the results.

On examining the lipoprotein particle distributions, there was a trend toward increasing insulin resistance going from euthyroid to SCH and HT ( Table 3 ). In this order, there were increasing concentrations of large and medium VLDL particles, reflected by increasing VLDL size. Regarding LDL subclasses, from ET to HT there were increasing concentrations of total LDL particles and particularly of the small LDL (pattern B). This resulted in a smaller average LDL particle size. In contrast to differences seen in LDL particles, there were no HDL particle differences across thyroid categories. The LPIR score reflected the overall profile of the lipoprotein subclasses, as indicated by greater lipoprotein insulin resistance going from a euthyroid mean LPIR score of 49.2 (95% CI, 48.3, 50.2) to 52.1 in SCH (95% CI, 50.1, 54.0) and 52.1 in HT (95% CI, 48.6, 55.6)(P for trend of 0.008). Additional adjustment for BMI neutralized differences for LDL particle size and LPIR signaled ( Table 3 ).

For inflammatory and coagulation biomarkers, there were mixed results across thyroid categories ( Table 4 ). Mean hs-CRP levels increased from 2.0 mg/L (95% CI, 1.9, 2.1) in euthyroid to 2.1 mg/L (95% CI, 1.9, 2.3) in SCH and 2.4 mg/L (95% CI, 2.0, 2.8) in HT (P for trend of 0.028); however, it was null after BMI adjustment. In contrast, no significant differences were noted for the other inflammatory/coagulation biomarkers. HbA1c levels were all below the upper limit of normality across thyroid categories, although a small but statistically significant difference was noted comparing HT with euthyroid.

On analysis restricted to euthyroid and SCH women (Supplemental Tables 1–3), TSH quintile values were mostly within the normal range (i.e., euthyroid). Only the top TSH quintile had individuals in the SCH range, which comprised 91.0% (573 women) of the top quintile. Similar to the analyses for thyroid categories, across increasing TSH quintiles the overall profile was consistent with worsening dyslipidemia and dyslipoproteinemia. In contrast to the analysis according to thyroid categories, we noted that there were decreasing concentrations of large HDL particles and increasing concentrations of small HDL particles from the bottom to the top quintile, reflected in smaller HDL particles size. Of note, increasing TSH quintiles presented quite linear LPIR increments (Supplemental Table 2; Fig. 1).

Figure 1.

LPIR according to TSH quintiles. LPIR score differences for TSH quintiles (Q) vs the first TSH quintile along euthyroid and SCH are shown. For linear regression for median TSH across categories, adjustment covariates include age, income, current smoking, race, household income, systolic blood pressure, high blood pressure treatment, menopause status, and hormone replacement therapy. The P value for the trend for median TSH values within each quintile is shown. *Bonferroni adjusted P value = 0.010 for the fifth quintile vs the first quintile.

Regarding metabolic syndrome, there was increasing prevalence from ET to HT (P < 0.001). Compared with euthyroid, SCH and HT adjusted odds ratios for metabolic syndrome were, respectively, 1.37 (95% CI, 1.08, 1.73) and 1.88 (95% CI, 1.30, 2.72) (P for linear trend of <0.001). Increasing TSH within euthyroid and SCH range had higher odds ratios for metabolic syndrome in reference to the bottom quintile (P for trend of 0.001) (Supplemental Table 4), in which the top quintile had an odds of 1.49 (95% CI, 1.10, 2.01).