Hormone Therapy's Heart Risks May Hang on Cholesterol
By Crystal Phend
PHILADELPHIA, 23 may 2008-- Lipid levels may be enough to help women decide whether hormone replacement therapy is worth the heart risk, researchers said.
Women with an LDL-to-HDL cholesterol ratio less than 2.5 were not at elevated risk of coronary heart disease while using hormone therapy, said Paul F. Bray, M.D., of Thomas Jefferson University here, and colleagues.
Those who had higher ratios were more likely to develop heart disease when they took hormone therapy, the researchers reported in the June 1 issue of the American Journal of Cardiology.
Their analysis of the larger Women's Heath Initiative (WHI) trials may provide a simple tool for clinicians and patients to determine individual risk, they said.
The WHI studies showed no benefit in the primary endpoint of reduction in coronary events with estrogen in women who had a hysterectomy or with estrogen plus progesterone in postmenopausal women. In other studies, hormone therapy actually increased heart attack and stroke risk.
"Despite increasing information and understanding of clinical benefits and risks of hormone therapy, practitioners are still challenged in making management choices for individual postmenopausal women," they said, noting that the Framingham risk prediction model excludes hormone therapy as a factor.
However, lipids aren't the whole story, Dr. Bray's group cautioned. "The decision to use postmenopausal hormones must consider the totality of health risks and benefits, including stroke, thrombosis, and gall bladder disease."
The researchers analyzed biomarker findings from the trials in a nested case-control study of 271 patients with incident coronary heart disease and 707 healthy controls.
Among the findings in the combined trial results, the researchers reported that hormone therapy increased risks of coronary heart disease in association with:
LDL cholesterol levels of 130 mg/dl and above (odds ratio 1.46, 95% confidence interval 1.02 to 2.10) but not lower levels (OR 0.66, 95% CI 0.34 to 1.27, P=0.03 for interaction).
Non-HDL cholesterol at or above 169 mg/dl (OR 1.64, 95% CI 1.11 to 2.42) but not lower levels (OR 0.88, 95% CI 0.53 to 1.47, P=0.04 for interaction).
Total-to-HDL cholesterol ratios at or above 4.182 (OR 1.69, 95% CI 1.15 to 2.49) but not lower ratios (OR 0.76, 95% CI 0.44 to 1.29, P=0.01 for interaction).
LDL-to-HDL cholesterol ratios at or above 2.5 (OR 1.73, 95% CI 1.18 to 2.53) but not lower ratios (OR 0.60, 95% CI 0.34 to 1.06, P=0.002 for interaction).
The results remained the same when women who used lipid-lowering drugs were excluded.
High sensitivity C-reactive protein at or above 2.0 mg/dl was also associated with elevated heart disease risk (OR 1.58, 95% CI 1.05 to 2.39). However, the interaction with hormone therapy use was not significant (P=0.16).
Low C-reactive protein added little to the value of the best predictor, LDL-to-HDL ratio, the researchers said. Women with low baseline LDL-to-HDL cholesterol ratios were not at elevated risk of coronary heart disease events on hormone therapy regardless of C-reactive protein, they added.
"Importantly, we found no clear evidence that either form of hormone therapy posed a risk of coronary heart disease events" for women with favorable baseline cholesterol levels and ratios, Dr. Bray and colleagues said.
Based on animal studies, the link between hormone therapy and lipids may be that the cholesterol metabolite 27-hydroxycholesterol competes with estrogen to block the vascular benefits of estrogen for nitric oxide production and endothelial cell migration, they said.
The researchers cautioned that the subgroup analysis of the WHI study had relatively small numbers of patients without sufficient sample size to stratify by age.
"Women considering the use of postmenopausal hormone therapy should determine their overall cardiac risk and specifically their lipid profile," the investigators concluded.
The Women's Health Initiative program was supported by the National Heart, Lung, and Blood Institute. The researchers provided no information on conflicts of interest.
Primary source: American Journal of CardiologySource reference:Bray PF, et al "Usefulness of baseline lipids and c-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events" Am J Cardiol 2008; 101: 1599-1605.
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