Use of cardiovascular age for assessing risks and benefits of menopausal hormone therapy

The Women's Health Initiative studies and others have suggested that menopausal hormone therapy may enhance the risk of new cardiovascular (CV) events in older women and diminish the development of coronary atherosclerosis in younger women. The underlying mechanisms to explain these findings are encapsulated in the term "Timing Hypothesis." Extensive pathophysiologic studies have provided mechanistic evidence for the dichotomous effects of estrogen on coronary artery vasculature. Early in the atherosclerotic disease process, estrogen exerts protective effects on the endothelium and retards plaque formation. Late in the process, estrogen causes plaque erosion or rupture with subsequent thrombosis and acute coronary events. Analysis of the Timing Hypothesis in women examined in the Women's Health Initiative primarily used chronologic age to assess divergent effects of estrogen. The complexity of the data underlying coronary pathophysiology has resulted in controversy whether MHT can be used in older women or those with prior CV disease. In a debate of this issue at a recent International Menopause Society meeting, the concept of using CV age rather than chronologic age was discussed as a practical method of resolving this issue and facilitating therapeutic decisions in older women. This "Personal Perspective" will review the concepts underlying CV age, describe how it is determined, provide support for its utility, and propose future studies using this parameter.