Blood substances linked to heart risk.

Although women do get heart disease, they often start developing it later in life, about a decade after their male counterparts.

Researchers had long postulated that this advantage was due to estrongen, the hormone that is plentiful during a woman's youth but declines sharply as she experiences menopause.

A new study puts a twist on that theory. The findings suggest that the body's blood-clotting system may also play a role in the heart protection enjoyed by premenopausal women.

Otavio C.E. Gebara of the Harvard Medical School in Boston and his colleagues focused on a substance in the blood called plasminogen activator inhibitor (PAI). One of PAI's main duties in the blood stream is to block the action of the clot-buster tissue blood vessel cells. A synthetic form of TPA is now used as a drug to dissolve clots. Such clots can block the heart's blood supply and cause heart attacks and strokes.

The researchers studied blood samples taken from 766 women and 682 men who were part of the Framingham Heart Study, a long-running investigation of cardiovascular disease. The team discovered that concentration of PAI in the blood were lower in premenopausal women than in men of the same age. The scientists believe that lower PAI concentrations translate into blood that is less likely to form clots. With less PAI around, TPA is freer to exert its clot-busting talent, they note.

After menopause, however, PAI concentrations in women start to look like those in age-matched men, Gebara says. Even more important women getting estrogen-replacement therapy after menopause had decreased amounts of PAI, more like those of premenopausal women. The researchers suspect that estrogen may regulate how much PAI gets into the bloodstream. "The correlation between PAI levels and estrogen status points to a possible mechanism through which estrogen may exert its protective effect," Gebra says. The team plans a new study to prove that estrogen has a direct effect on PAI.