Subclinical Thyroid Dysfunction and Cardiovascular Outcomes among Prospective Cohort Studies
Baris Gencer, Tinh-Hai Collet, Vanessa Virgini, Reto Auer and Nicolas Rodondi
Affiliation: Cardiology Division, Department of Medicine, Geneva University Hospital, Switzerland.
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).
Keywords: Cardiovascular epidemiology, coronary heart disease, heart failure, meta-analysis, subclinical thyroid dysfunction.
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