Impact of Subclinical Hypothyroidism on Cardiometabolic Biomarkers in Women

Abstract

Context: Whether subclinical hypothyroidism (SCH) is associated with cardiometabolic abnormalities is uncertain.

Objective: To examine diverse cardiometabolic biomarkers across euthyroid, SCH, and overt hypothyroidism (HT) in women free of cardiovascular disease (CVD).

Design: Cross-sectional adjusted associations for lipids, lipoprotein subclasses, lipoprotein insulin resistance score, inflammatory, coagulation, and glycemic biomarkers by ANCOVA for thyroid categories or TSH quintiles on a Women's Health Study subcohort.

Setting: Outpatient.

Patients or other participants: Randomly sampled 3,914 middle-aged and older women for thyroid function analysis (thyroid-stimulating hormone [TSH], free T4), of whom 3,321 were not on lipid lowering therapy.

Intervention: None.

Main outcome measure: Associations of SCH and HT with cardiometabolic markers.

Results: Going from euthyroid to HT, the lipoprotein subclasse profiles were indicative of insulin resistance [respective values and p for trend]: larger VLDL size (nm)[51.5 (95%CI51.2, 51.8) to 52.9 (51.8, 54.1) p=0.001]; higher LDL particles concentration (nmol/L)[1283 (95%CI1267, 1299) to 1358 (1298, 1418) p=0.004] and smaller LDL size. There was worsening lipoprotein insulin resistance score from euthyroid 49.2 (95%CI 48.3, 50.2) to SCH 52.1 (95%CI 50.1, 54.0), and HT 52.1 (95%CI 48.6, 55.6), p for trend 0.008. Of the other biomarkers, SCH and HT were associated with higher hs-CRP and HbA1c. For increasing TSH quintiles results were overall similar.

Conclusions: In apparently healthy women, SCH cardiometabolic profiles indicated worsening insulin resistance and higher CVD risk markers compared with euthyroid individuals, despite similar LDL and total cholesterol. These findings suggest that cardiometabolic risk may increase early in the progression towards SCH and OH.

Keywords: Coagulation; Inflammation; Insulin Resistance; Lipoproteins; Metabolomics; Subclinical Hypothyroidism.

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.