Subclinical Hyperthyroidism Raised CHD Mortality, AF Risks

Endogenous subclinical hyperthyroidism increased the risks of coronary heart disease mortality, total mortality, and atrial fibrillation, a study published online April 23 in the Archives of Internal Medicine has shown.

The excess risk was most pronounced in patients who had the lowest thyrotropin levels – below 0.10 mIU/L – said Dr. Tinh-Hai Collet of the department of ambulatory care and community medicine, University of Lausanne (Switzerland), and associates (Arch. Intern. Med. 2012 April 23 [doi:10.1001/archinternmed.2012.402]).

Researchers have long suspected an association between subclinical hyperthyroidism and adverse cardiovascular effects, but prospective cohort studies and study-level meta-analyses alike have reached conflicting conclusions about such a link.

Dr. Collet and colleagues conducted a patient-level meta-analysis of the issue, reasoning that examining individual participant data from large cohort studies might resolve the question.

The researchers included all 10 prospective longitudinal cohorts in the literature that reported baseline thyrotropin and free thyroxine levels, included euthyroid control groups, and specifically tracked coronary heart disease (CHD) and mortality outcomes. They excluded studies that used first-generation thyrotropin assays, because those tests are not sensitive enough to detect subclinical hyperthyroidism reliably.

The 10 cohorts comprised 52,674 patients with a median age of 59 years. The median follow-up was 8.8 years, and the total follow-up was 501,922 person-years. A total of 2,188 (4.2%) of those patients had endogenous subclinical hyperthyroidism.

Overall, 8,527 patients died during follow-up. There were 1,896 CHD deaths, 3,653 CHD events, and 785 cases of incident atrial fibrillation (AF).

For patients with subclinical hyperthyroidism, the overall hazard ratio compared with euthyroid control patients for all-cause mortality was 1.24, for CHD mortality was 1.29, for CHD events was 1.21, and for incident AF was 1.68.

Both CHD mortality and AF rates – but not the other outcomes – were significantly higher among patients with the very lowest thyrotropin levels, the investigators said.

Those increased risks did not change materially when the data were analyzed according to patient age or the presence of preexisting cardiovascular disease. The results also remained the same in sensitivity analyses, even after the data were adjusted to account for body mass index and the use of lipid-lowering or antihypertensive medication.

In contrast, cancer mortality and stroke mortality were no higher in patients with subclinical hyperthyroidism than in control patients.

"Our results, based on individual participant data, demonstrate that there is indeed an increased risk of total and CHD mortality associated with subclinical hyperthyroidism," Dr. Collet and associates said.

Their findings support recent guidelines stating that the treatment of subclinical hyperthyroidism "should be strongly considered" in all patients aged 65 and older whose thyrotropin level is lower than 0.10 mIU/L.

The study could not address whether such therapy decreases the elevated risk of death, CHD events, or AF, the authors said, and no large randomized controlled trial has yet attempted to do so. Such a trial would be "challenging" to perform because of the low prevalence of subclinical hyperthyroidism in the general population, they added.

The Swiss National Science Foundation supported the study. The investigators reported no relevant financial conflicts of interest.