Positron Emission Tomography for Risk Assessment of Women Investigated for Coronary Artery Disease

celerates atheroma formation leading to endothelial dysfunction, impaired vasoreactivity, and clinical instability. Focal epicardial disease can therefore be a later manifestation of atherosclerosis that follows the aforementioned pathophysiological alterations [8] . Unmasking them is challenging for the conventional noninvasive cardiac imaging tests and this is manifested by the often negative results for myocardial ischemia in women presenting with chest pain. Taken together these data suggest that accurate assessment of the atherosclerosis burden, endothelial function, and health of the microcirculation is very important for timely risk stratification and this has implications for the noninvasive approaches used to investigate women with chest pain. The goal of such stratification is to identify patients at risk for specific adverse events (cardiac death or nonfatal MI) and to develop posttest management strategies which might reduce patients’ risk of these outcomes. A variety of tests have been employed and these include exercise ECG, functional imaging with SPECT myocardial perfusion imaging (MPI) or stress echocardiography; more recently, CT coronary angiography and even cardiac magnetic resonance (CMR) imaging and positron emission tomography (PET) have been utilized for risk stratification. Hybrid imaging in the form of SPECT/CT or PET/CT has also been proposed as a comprehensive tool for assessing prognosis because it has the ability to provide concurrent quantitative information on myocardial perfusion, coronary anatomy, and plaque morphology [9] . Coronary heart disease remains the leading cause of death of women in the USA and is responsible for more deaths in women than all forms of cancer combined [1] . Moreover, recent data from the National Health and Nutrition Examination Survey (NHANES) looking at trends in midlife coronary heart disease risk show that over the past 2 decades the prevalence of myocardial infarction (MI) has increased in women aged 35–54 years while declining in men of the same age [2] . For Europe, data from the World Health Organization (WHO) demonstrate that cardiovascular disease accounts for 55% of deaths in women compared to just 43% of deaths in men [3] . In addition, there is evidence that symptomatic women with angiographically normal or nonobstructive coronary lesions have increased rates of MI, stroke, hospitalization for congestive heart failure, and cardiac mortality compared with a similarly matched cohort of asymptomatic community-based women [4] . Along with the knowledge on sex differences regarding clinical outcomes, results from the Women’s Ischemia Syndrome Evaluation (WISE) study and related studies implicate abnormal coronary reactivity [5] , microvascular dysfunction [6] , and plaque erosion/distal microembolization as important pathophysiological determinants of adverse outcomes [7] . Dysfunction of microcirculation is more common in women than men, presumably as a consequence of hormonal variations that result in vascular inflammation and subsequent remodeling. In the presence of risk factors for coronary artery disease (CAD), this process acReceived and accepted: March 25, 2011 Published online: June 1, 2011