Associations Between Subclinical Thyroid Dysfunction and Cardiovascular Risk Factors According to Age and Sex

Abstract

Context: Subclinical thyroid dysfunction (ScTD), comprising subclinical hypothyroidism (SHypo) and subclinical hyperthyroidism (SHyper), has been associated with increased risk for cardiovascular events.

Objective: To assess associations between ScTD and cardiovascular risk factors (cvRFs) according to age and sex.

Methods: This analysis of pooled participant data from large prospective cohort studies from the Thyroid Studies Collaboration assessed cvRFs (blood pressure [BP], lipid levels, high-sensitivity C-reactive protein [hs-CRP]) among participants aged 18 to 103 years with SHypo (thyroid-stimulating hormone [TSH] > 4.50 mU/L, normal fT4) and SHyper (TSH < 0.45 mU/L, normal fT4) vs euthyroid (TSH 0.45-4.50 mU/L).

Results: Of 69 006 participants (mean age 62 years, 55% women, 25% current smokers) from 16 international cohorts, 3748 (5.4%) had SHypo and 3428 (5.0%) had SHyper. In both women and men, systolic and diastolic BP were similar regardless of thyroid status. Exceptions were lower diastolic BP in women with SHyper compared to euthyroid participants (adjusted mean difference [aMD] -1.3 mmHg, 95% CI -2.0 to -0.5), and lower systolic BP in men with SHyper compared to euthyroid participants (aMD -3.1 mmHg, 95% CI -4.8 to -1.4). In both women and men, lipid levels (total, HDL, LDL-cholesterol, triglycerides) and hs-CRP were similar regardless of thyroid status. The only exception were women with SHyper who had lower LDL-cholesterol vs euthyroid (aMD -0.17 mmol/L, 95% CI -0.29 to -0.05).

Conclusion: Participants with ScTD and euthyroid participants have similar cvRFs and differences are arguably too small to explain the increased cardiovascular risk in ScTD observed in previous studies.

Keywords: LDL-cholesterol; arterial hypertension; dyslipidemia; high-sensitivity C-reactive protein; subclinical hyperthyroidism; subclinical hypothyroidism.

Figure 1.

(16 Cohorts, n = 45 819 participants): mean differences of blood pressure in subclinical thyroid dysfunction vs the euthyroid state. Top: SHyper, subclinical hyperthyroidism (TSH < 0.45 mU/L, normal fT4) with marked (TSH < 0.10 mU/L) dysfunction; Bottom: SHypo, subclinical hypothyroidism (TSH > 4.50 mU/L, normal fT4) with marked (TSH 10-20 mU/L) dysfunction; mean differences with 95% CI vs the euthyroid state (TSH 0.45 to 4.50 mU/L) for systolic and diastolic blood pressure (BP) in mmHg for women (left) and men (right). Numerical details are displayed in Supplementary Tables S1A and S3A (40).

Figure 2.

(13 Cohorts, n = 24 781 participants): mean differences of lipid parameters (top) and high-sensitivity C-reactive protein (bottom) in subclinical thyroid dysfunction vs the Euthyroid State. (A) Top: SHyper, subclinical hyperthyroidism (TSH <0.45 mU/L, fT4 within the reference range) with marked (TSH < 0.10 mU/L) dysfunction; Bottom: SHypo, subclinical hypothyroidism (TSH > 4.50 mU/L, fT4 within the reference range) with marked (TSH 10-20 mU/L) dysfunction; mean differences with 95% CI vs the euthyroid state (TSH 0.45 to 4.50 mU/L) for lipid parameters total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol in mmol/L for women (left) and men (right). Numerical details are displayed in Supplementary Tables S1B and S3B (40). (B) Top: SHyper, subclinical hyperthyroidism (TSH < 0.45 mU/L, fT4 within the reference range) with marked (TSH < 0.10 mU/L) dysfunction; Bottom: SHypo, subclinical hypothyroidism (TSH > 4.50 mU/L, fT4 within the reference range) with marked (TSH 10-20 mU/L) dysfunction; mean differences with 95% CI vs the euthyroid state (TSH 0.45 to 4.50 mU/L) for high-sensitivity C-reactive protein in mg/L for women (left) and men (right). Numerical details are displayed in Supplementary Tables S1B and S3B (40).