The interaction of vascular stiffness and cardiovascular events in women: insights from The Heart and Estrogen/Progestin Replacement Study.

Hormone Replacement Therapy and Cardiovascular Events T he matter regarding hormone replacement therapy and cardiovascular events has been the subject of multiple publications. While observational studies depicted a protection from coronary events in patients receiving hormone replacement therapy, recent randomized trials have failed to show that promising evidence.1 The Heart and Estrogen/Progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled trial of 4.1 years in duration, and a subsequent, open-label, observational follow-up for 2.7 years (HERS II) enrolled 2,763 women with documented coronary artery disease to receive either conjugated equine estrogens (0.625 mg) and progestin medroxyprogesterone (2.5 mg) or placebo.2–4 The results of HERS demonstrated that hormone replacement therapy did not have a positive overall effect on cardiovascular outcomes, such as nonfatal infarction and mortality from coronary heart disease. A more detailed analysis of this trial demonstrated that during the first year of treatment, there was a significant increase in adverse coronary heart disease events (52% excess cardiovascular events); and during the follow-up period, including an additional 2.7 years, hormone replacement therapy did not confer any protective effects. Although the underlying mechanisms by which this may occur are speculative, a prothrombotic, proarrhythmic, or proischemic effect of hormonal replacement therapy could account for the early increased risk of coronary heart disease. These early detrimental effects, however, are steadily offset by the favorable changes in lowand high-density lipoprotein cholesterol of hormone replacement therapy, thus delaying the progression of underlying atherosclerosis. The large cohort of postmenopausal women included in HERS and the long-term follow-up have allowed the investigation of other issues that are relevant to women cardiovascular disease. Recently, a prospective substudy form the HERS cohort5 demonstrated that although randomization to hormone replacement did not increase the risk of heart failure, the presence of diabetes, myocardial infarction, atrial fibrillation, creatinine clearance of 40 mL/min, systolic BP of 120 mm Hg, current smoking, body mass index of 35, left bundle-branch block, and left ventricular hypertrophy were identified as strong risk factors for the development of heart failure in women. Of all the predictors, diabetes was the strongest risk factor (adjusted hazard ratio, 3.1; 95% confidence interval, 2.3 to 4.2). In the issue of CHEST (see page 1498), Nair et al report another very interesting observation from the HERS cohort. The authors examined the potential role of pulse pressure in the development of cardiovascular events in the HERS cohort. In addition, the authors explore another interesting and controversial issue: the effects of hormone replacement therapy on pulse pressure and vascular stiffness.