Chicago, IL - Two population-based studies aimed at clarifying a longstanding clinical puzzle, whether subclinical hypothyroidism (SH) may heighten cardiovascular risk, have come up with results that conflict with earlier similar investigations. One showed that elevated levels of thyrotropin (thyroid-stimulating hormone [TSH]) among septuagenarians with SH predicted development of new or recurrent heart failure but not other cardiovascular disease (CVD) [1]. In the other study, SH among adults in the community was independently associated with an increased risk of hospitalization or death from coronary heart disease (CHD) [2].

"Taken together, these studies suggest that the incidence of some cardiovascular disorders may be increased in patients with SH, particularly those patients with TSH levels greater than 10 mIU/L," according to an accompanying editorial by Dr Lawrence M Crapo (Santa Clara Valley Medical Center, San Jose, CA) [3]. All three papers were published in the November 28, 2005 issue of the Annals of Internal Medicine.

Both studies are noteworthy for having stratified risk by degree of TSH elevation, according to Crapo, who notes that "both SH and CVD are quite prevalent in the general population and become more so with advancing age. If an association exists between the degree of SH and subsequent CVD, then it is important to define the TSH level above which it is reasonable to initiate levothyroxine sodium therapy."

No one, however, is proposing that such therapy will prevent CVD. On the contrary, the Annals reports follow a long line of observational studies that for the most part have found no such strong ties between SH and CVD, Dr Martin I Surks (Montefiore Medical Center, New York, NY) told heartwire. So the new research, he said, serves mostly to increase an already murky knowledge base without really clarifying whether SH actually promotes heart disease. "But hopefully they will stimulate more investigation," said Surks, an endocrinologist and coauthor of recent SH-management guidelines [4].

Of 2730 randomly selected persons aged 70 to 79 years participating in the Health, Aging and Body Composition Study conducted in two US metropolitan areas, 12.4% had SH, reported Dr Nicolas Rodondi (University of California, San Francisco) and colleagues. The condition is typically defined as an elevated TSH (>4.5 mIU/L in this study) coincident with normal serum thyroxine levels.

Over a four-year follow-up, baseline SH was associated with an increased risk of new or recurrent HF, one that rose significantly with ascending TSH concentrations. Neither thyroid status nor stratified TSH levels were predictive of all-cause mortality or other cardiovascular or peripheral vascular outcomes.

In addition, subjects with a TSH level >7.0 mIU/L, both with and without a baseline HF history, had a significantly elevated risk of HF over the follow-up. And a TSH >10.0 mIU/L was a significant predictor of all-cause mortality, but solely among patients with a history of CVD—defined as stroke, peripheral vascular disease, or HF.

The other study comprised both cross-sectional and longitudinal analyses of participants in the Busselton Health Study, conducted in a rural Australian community. They consisted of 2108 persons with baseline TSH measurements for cross-sectional assessment and a subgroup of those who were initially CHD-free and followed for 20 years.

Subclinical hypothyroidism (partly defined by TSH >4.0 mIU/L) was independently associated with CHD events (death from or hospitalization with CHD) both at the time of TSH measurement and over the long term, reported Dr John P Walsh (University of Western Australia, Perth) and associates. The risk was most pronounced when TSH exceeded 10.0 mIU/L in both analyses.

As neither of the Rodondi and Walsh studies saw increased cardiovascular risk among persons with SH and TSH below 7 mIU/L, Crapo writes in his editorial, "treatment of subjects with mild SH or high-normal TSH levels would probably not be beneficial in the prevention of CVD."