Does treating subclinical hypothyroidism improve markers of cardiovascular risk?

Abstract

Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level in the face of normal free thyroid hormone values. The overall prevalence of subclinical hypothyroidism is 4-10% in the general population and up to 20% in women aged >60 years. The potential benefits and risks of therapy for subclinical hypothyroidism have been debated for 2 decades, and a consensus is still lacking. Besides avoiding the progression to overt hypothyroidism, the decision to treat patients with subclinical hypothyroidism relies mainly on the risk of metabolic and cardiovascular alterations. Subclinical hypothyroidism causes changes in cardiovascular function similar to, but less marked than, those occurring in patients with overt hypothyroidism. Diastolic dysfunction both at rest and upon effort is the most consistent cardiac abnormality in patients with subclinical hypothyroidism, and also in those with slightly elevated TSH levels (>6 mIU/L). Moreover, mild thyroid failure may increase diastolic blood pressure as a result of increased systemic vascular resistance. Restoration of euthyroidism by levothyroxine replacement is generally able to improve all these abnormalities. Early clinical and autopsy studies had suggested an association between subclinical hypothyroidism and coronary heart disease, which has been subsequently confirmed by some, but not all, large cross-sectional and prospective studies. Altered coagulation parameters, elevated lipoprotein (a) levels, and low-grade chronic inflammation are regarded to coalesce with the hypercholesterolemia of untreated patients with subclinical hypothyroidism to enhance the ischemic cardiovascular risk. Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement on markers of cardiovascular risk is the substantial demonstration that restoration of euthyroidism can lower both total and low-density lipoprotein-cholesterol levels in most patients with subclinical hypothyroidism. However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. On the other hand, levothyroxine replacement therapy can always be discontinued if there is no apparent benefit. Levothyroxine replacement therapy is usually safe providing that excessive administration is avoided by monitoring serum TSH levels. However, the possibility that restoring euthyroidism may be harmful in the oldest of the elderly population of hypothyroid patients has been recently raised, and should be taken into account in making the decision to treat patients with subclinical hypothyroidism who are aged >85 years.