Another Piece of the Hormone and Heart Disease Puzzle

From the WebMD Archives

April 11, 2000 (Lake Tahoe, Calif.) -- The decision of whether to take hormone replacement therapy remains a riddle for women, particularly those concerned about heart disease.

Researchers hope to offer another clue in a report released in this week's issue of the Journal of the American Medical Association. They found that a substance in the blood stream called lipoprotein(a) appears to be the most significant cholesterol-related risk factor for a second heart attack. This lipoprotein -- also called Lp(a) -- is affected by estrogen in postmenopausal women, but the result of hormone therapy in women who don't have abnormally high Lp(a) may not be beneficial.

The study set out to see the effect of hormone replacement therapy, using estrogen and progestin, on the rate of new heart attacks in almost 2,800 postmenopausal women with heart disease over four years.

"In [the study], there was an increase in the rate of heart attacks in the first year and later a decrease. But overall, for four years the rate of heart attack was identical in the hormone-treated group and the placebo group," lead investigator Stephen B. Hulley, MD, MPH, tells WebMD. "We wondered whether Lp(a) might offer a clue to that."

According to Hulley, Lp(a) tends to increase blood clotting. Even though Lp(a) resembles LDL, or "bad" cholesterol, drugs commonly used to lower unusually high bad cholesterol levels have no effect on Lp(a).

The researchers found that the estrogen and progestin therapy had a more favorable effect than placebo on women with high levels of Lp(a) but a more adverse effect in women with low levels of Lp(a). In fact, those women had a slightly higher risk of heart attack than the placebo group.

Michael Criqui, MD, tells WebMD, "This might influence [which women] have a higher potential for benefit from estrogen and women that don't have as much potential for benefit, but we can't say that yet." Criqui is a professor of family medicine and prevention at the University of California, San Diego, and was not involved in the study.


Alan Altman, MD, an advisor to the National Women's Health Resource Center (, tells WebMD, "What's interesting is that lipoprotein(a) seems to be involved in cardiac risk. The higher it is, the greater the risk. They've shown pretty well that the women on estrogen and progestin diminished their level of Lp(a) ? but the women who really got benefit were the women who were worse off to begin with. We knew before that the greater the cardiac risk, the greater the benefit that you could potentially get from hormone replacement therapy." Altman is assistant clinical professor of obstetrics, gynecology, and reproductive medicine at Harvard University Medical School in Boston.

"We can draw nothing from this paper that would change anything I would say to a patient when I talk with her about her decision of whether or not to take HRT based on her unique situation," Altman adds.

Hulley acknowledged to WebMD that the findings of this study are preliminary and need to be confirmed in other studies. "Our general recommendation is that women should not start taking hormones to prevent heart attacks until there's evidence that it's beneficial, and we don't have that yet."

Vital Information:

  • Lipoprotein(a), or Lp(a), is a molecule in the blood stream similar to LDL, or "bad" cholesterol, and is a risk factor for heart disease.
  • In this study of postmenopausal women who have high levels of Lp(a), hormone replacement therapy was shown to lower it and decrease the risk of a heart attack, but the therapy showed an increased risk of heart attack in women who don't have high levels of Lp(a).
  • Experts recommend that women should not start taking hormones to prevent heart attacks until there is sound scientific evidence that it's beneficial.
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