Lausanne, Switzerland - A new study has found that older adults with severe subclinical hypothyroidism had almost double the risk of developing heart failure (HF) compared with those with normal thyroid function over a 12-year follow-up period [1]. Dr Nicolas Rodondi (University of Lausanne, Switzerland) and colleagues report their findings in the September 30, 2008 issue of the Journal of the American College of Cardiology.

Rodondi told heartwire that these results were in line with those of the only other study to have looked at subclinical hypothyroidism and HF incidence, which also found an increased HF risk only in those with high levels of thyroid-stimulating hormone (TSH).

The findings are important to inform the debate about subclinical hypothyroidism, he says. "There is a big controversy about whether we should screen and treat people with subclinical hypothyroidism. We know that people with overt hypothyroidism with symptoms need to get treated, but about those with no symptoms and just subclinical disease, there is debate. And within this debate about whether to treat or not is another controversy about the threshold at which you should treat."

These and other results from prior studies support the recommendations of several guidelines that those with subclinical hypothyroidism and no symptoms should be treated with thyroxine only if their TSH is 10.0 mU/L or more, Rodondi says. However, he points out that some endocrinologists disagree and advocate treating such patients at lower TSH levels. The debate is important, he says, because it is has been shown that monitoring of TSH levels under thyroxine is not always accurate in clinical practice, with overtreatment having its own attendant risks.

Rodondi and colleagues studied 3044 adults who were 65 or older participating in the Cardiovascular Health Study, all of whom were free of HF at baseline. They compared adjudicated HF events over a mean of 12 years of follow-up and changes in cardiac function over the course of five years among those with normal thyroid function (euthyroid; TSH 0.45-4.5 mU/L), those with subclinical hypothyroidism (divided into moderate, TSH 4.5-9.9 mU/L, and severe, >10.0 mU/L), and those with subclinical hyperthyroidism (TSH <0.45 mU/L) .

Over the follow-up period, 736 people developed HF events. Those with TSH 10.0 mU/L or more had a greater incidence of HF compared with euthyroid participants (adjusted HR 1.88, p=0.01). No such increased risk was seen in those with TSH 4.5-9.9 mU/L or in those with subclinical hyperthyroidism compared with euthyroid participants.

Baseline peak E velocity—an echocardiographic measure of diastolic function associated with incident heart failure in the cohort—was also greater in those with TSH 10.0 mU/L or more compared with euthyroid participants (0.80 m/s vs 0.72 m/s; p=0.002). And over the course of five years, left ventricular mass increased among those with TSH 10.0 mU/L or more, although other echocardiographic measures were unchanged.

In a further exploratory analysis, the researchers stratified people with TSH 10.0 mU/L or more into those who received thyroxine replacement therapy and those who didn't. They found that those who got thyroxine did not have an increased risk of HF, "providing indirect evidence that [thyroxine] might work to prevent development of HF in those with TSH 10.0 mU/L or more," said Rodondi.

He stressed, however, that "to definitively prove a link between subclinical thyroid dysfunction and HF, a randomized clinical trial would be needed in which one group is treated with thyroxine vs placebo to see if the former reduces the risk. That would be proof of concept, but it has not been done as yet."

Rodondi said their findings—that those with less severe subclinical hypothyroidism do not seem to be at risk of HF—are "important," because a high proportion of older adults fit into this category and are treated with thyroxine in clinical practice, without consistent evidence that this is of benefit.

Monitoring of TSH levels under thyroxine is not always accurate in clinical practice, he explains, and it is estimated that around 20% to 30% of people receiving thyroxine are overtreated. This in itself has risks, as subclinical hyperthyroidism has been associated with atrial fibrillation and increased fracture risk.

"In aggregate, our findings might help refine a treatment threshold at which clinical benefit would be expected and demonstrate a subpopulation at risk for a life-threatening condition," he and his colleagues say in their paper.

"Clinical trials should examine the efficacy of screening for and treating subclinical thyroid dysfunction and assess whether the risk of HF might be ameliorated by thyroxine replacement in individuals with TSH levels above 10 mU/L," they conclude.