Subclinical Thyroid Dysfunction and Cardiovascular Outcomes among Prospective Cohort Studies

Abstract

The association between subclinical thyroid dysfunction and cardiovascular outcomes has been recently clarified with the publication of three individual participant data (IPD) analyses from the Thyroid Studies Collaboration. We identified original cohort studies with a systematic review and pooled individual data from over 70'000 participants to obtain a more precise estimate of the risks of cardiovascular outcomes associated with subclinical thyroid dysfunction. Subclinical hypothyroidism and subclinical hyperthyroidism, defined as normal thyroxine (FT4) levels with increased or decreased Thyroid-Stimulating Hormones (TSH or thyrotropin) respectively, are associated with increased risk of cardiovascular outcomes compared to euthyroid state, particularly in those with a more pronounced thyroid dysfunction. Specifically, subclinical hypothyroidism is associated with an increased risk of coronary heart disease (CHD) events, CHD mortality and heart failure (HF) events in individuals with higher TSH levels, particularly in those with TSH levels ≥10.0 mIU/L. Conversely, subclinical hyperthyroidism is associated with an increased risk of total mortality, CHD mortality, HF and atrial fibrillation, particularly in those with suppressed TSH levels <0.10 mIU/L. Pending ongoing randomized controlled trials, these observational findings allow identifying potential TSH thresholds for thyroid medication initiation based on risk of clinical outcomes, although clinical decision based solely on observational data need caution. The impact of thyroid replacement among the elderly with subclinical hypothyroidism is currently studied in a multicenter international randomized controlled trial (Thyroid Hormone Replacement for Subclinical Hypothyroidism Trial, TRUST trial).

Thyroid Hormone Therapy and Risk of Thyrotoxicosis in Community-Resident Older Adults: Findings from the Baltimore Longitudinal Study of Aging

“…An emerging consensus in the literature suggests that mild subclinical hypothyroidism (elevated TSH levels <7-10 mIU/L with normal thyroid hormone levels) is not associated with a statistically significant increased risk of mortality or morbidity (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Consistent with this perspective, results of randomized trials of levothyroxine treatment have generally failed to show a benefit for symptoms, and have had mixed results regarding favorable impact on serum lipids, cardiac function, and survival, with positive effects observed for those with more severe hypothyroidism (reviewed in Cooper and Biondi (6)).…”

Subclinical hypothyroidism represents an additional risk factor for coronary artery calcification, especially in subjects with intermediate and high cardiovascular risk scores

“…SCH may be graded as mild (serum TSH, 4.5-9 mU/l) or moderate/severe (serum replacement (7,8,9,10). Previous studies have also suggested an association between SCH and coronary artery disease (CAD) (11,12,13,14). However, whether this association is related to SCH-induced changes in the serum lipid profile or other classical cardiovascular (CV) risk factors remains unclear (15,16).…”

Role of Thyroid Hormones in Different Aspects of Cardiovascular System

“…Specifically, SHypo is associated with an increased risk of CHD events, CHD mortality and heart failure events in individuals with higher TSH levels, particularly in those with TSH levels ≥10 μIU/mL. Conversely, SHyper is associated with an increased risk of total mortality, CHD mortality, heart failure and AF, particularly in those with suppressed TSH levels <0.10 μIU/ mL [57,58].…”