CHICAGO — Subclinical hyperthyroidism significantly increases the risks of both cardiovascular and all-cause mortality, according to findings from a prospective cohort study.
Subclinical hypothyroidism was similarly an independent risk factor for all-cause mortality in the study. But its association with increased cardiovascular mortality fell short of statistical significance, reported Dr. Jose Augusto Sgarbi of the University of Marilia (Brazil).
He added that there have been conflicting results in the few well-designed epidemiologic studies that have previously addressed the question of a possible increase in cardiovascular mortality in patients with subclinical thyroid dysfunction. As a result, there has been no consensus regarding screening and treatment of these abnormalities.
Thus, the findings of the longitudinal Japanese-Brazilian Thyroid Study have important clinical implications: “These data highlight the importance of a more aggressive strategy to identify and treat individuals with subclinical thyroid dysfunction,” the endocrinologist said at the annual meeting of the American Thyroid Association.
He reported on 1,100 adult Japanese Brazilians in the study. None were on thyroid medications at baseline.
At baseline, subclinical hypothyroidism—defined as a serum TSH level greater than 4.5 mU/L in the presence of normal serum free T4 and total or free T3—was identified in 6.2% of the study population. Subclinical hyperthyroidism—defined as a serum TSH level below 0.45 mU/L with a normal serum free T4— was detected in 8.9%. Overt hyperthyroidism was found in 1.8%, while 0.8% had overt hypothyroidism. The remaining subjects were euthyroid.
During a mean 7 years of follow-up, 76 participants died. The overall mortality rate was 5.1% in euthyroid individuals and significantly higher at 12.1% in those with subclinical hypothyroidism and 21.7% in participants with subclinical hyperthyroidism.
All-cause and cardiovascular mortality were higher in subjects with more pronounced subclinical thyroid dysfunction than in those with milder abnormalities. For example, the cardiovascular mortality rate was 2.8% in euthyroid subjects, 8.6% in those with relatively mild subclinical hyperthyroidism as defined by a TSH of 0.1–0.44 mU/L, and more than 27% in participants with a TSH below 0.1 mU/L. But even in individuals with only mildly increased or decreased TSH the increase in mortality was statistically significant.
Subjects with subclinical thyroid dysfunction tended to be older than euthyroid individuals. However, the populations had similar baseline rates of dyslipidemia, diabetes, hypertension, metabolic syndrome, smoking, and macrovascular disease.
In a multivariate Cox regression analysis that controlled for age and other potential confounders, subclinical hyperthyroidism was independently associated with a 3.4-fold increased risk of all-cause mortality compared with euthyroid status. Subclinical hypothyroidism conferred a 2.4-fold increased risk.
Individuals with subclinical hyperthyroidism were at 5.5-fold increased risk for cardiovascular mortality. The 1.9-fold increase in subclinically hypothyroid subjects was not statistically significant. The elevated all-cause mortality in this group was attributed to a combination of cardiovascular, cancer, and infectious disease deaths.
The Japanese-Brazilian Thyroid Study was funded by a federal agency.
FULL TEXT
