Recently, the Heart and Estrogen/progestin Replacement Study (HERS) found no effect of 4.1 years of estrogen plus progestin therapy in women with established coronary disease. Recent data showing elevated levels of C-reactive protein (CRP) in women taking hormone replacement (HRT) suggest that this null effect in HERS could be due to a previously unrecognized pro-inflammatory effect of HRT offsetting the other benefits of estrogen. However, there are several important questions remain concerning HRT, CRP, and atherosclerosis. First, do the estrogen-associated changes in CRP reflect a true increase in systemic vascular inflammation mediated through interleukin-6 (IL-6) and other inflammatory cytokines, or are they simply due to a direct effect of estrogen on hepatic synthesis of CRP? Second, are baseline measures of CRP and other inflammatory markers, or estrogen-associated change in these markers related to subsequent progression of angiographically defined coronary atherosclerosis? To answer these questions, the investigators propose to measure CRP and other inflammatory markers in stored serum from participants in the Estrogen Replacement and Atherosclerosis (ERA) trial, an NHLBI-sponsored angiographic trial to examine the effects of daily conjugated estrogen (0.625 mg) or estrogen plus medroxyprogesterone acetate (MPA) (2.5 mg) on progression of coronary disease in postmenopausal women. By examining the relationships between these measures, treatment assignment, and progression of coronary atherosclerosis, they hope to clarify the effects of estrogen use on vascular inflammation and the consequences of these effects for the pathogenesis of atherosclerosis. The investigators state that this information may help guide clinical decision-making and future research initiatives because of the fundamental role that estrogen therapy and vascular inflammation play in modulating risk for heart disease in women.
| Mellen, P B; Bittner, V; Herrington, D M (2007) Post-challenge glucose predicts coronary atherosclerotic progression in non-diabetic, post-menopausal women. Diabet Med 24:1156-9 |
| Mellen, Philip B; Cefalu, William T; Herrington, David M (2006) Diabetes, the metabolic syndrome, and angiographic progression of coronary arterial disease in postmenopausal women. Arterioscler Thromb Vasc Biol 26:189-93 |
| Herrington, David M; Howard, Timothy D; Brosnihan, K Bridget et al. (2002) Common estrogen receptor polymorphism augments effects of hormone replacement therapy on E-selectin but not C-reactive protein. Circulation 105:1879-82 |
