Insights From the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study

Abstract

Coronary heart disease is the leading cause of death and disability in the U.S., but recent advances have not led to declines in case fatality rates for women. The current review highlights gender-specific issues in ischemic heart disease (IHD) presentation, evaluation, and outcomes with a special focus on the results derived from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. In the second part of this review, we will assess new evidence on gender-based differences in vascular wall or metabolic alterations, atherosclerotic plaque deposition, and functional expression on worsening outcomes of women. Additionally, innovative cardiovascular imaging techniques will be discussed. Finally, we identify critical areas of further inquiry needed to advance this new gender-specific IHD understanding into improved outcomes for women.

Sex‐Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction

“…Healthy women have been shown to have higher endothelium‐dependent dilation when compared to their male counterparts, and the presence of cardiovascular risk factors has been associated with sex‐specific effects on endothelium‐dependent dilation 8. The Women's Ischemic Syndrome Evaluation study also suggested that sex plays a role in development of atherosclerosis, reporting increased likelihood of diffuse plaque formation in women when compared to men who developed discrete coronary lesions 9. Moreover, men have been shown to have a greater atheroma burden with more eccentric atheroma and diffuse epicardial endothelial dysfunction than women, suggesting increased structural and functional epicardial abnormalities when compared to their female counterparts 10.…”

Sex Differences in Clinical Characteristics, Psychosocial Factors, and Outcomes Among Patients With Stable Coronary Heart Disease: Insights from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial

“…It has been hypothesized that estrogens have protective effects on the vascular endothelium, thus women require more time and risk factor load to develop coronary disease 1. Compared with men, women also have less atherosclerotic burden, with lower prevalence of obstructive lesions, and more often have MI with no obstructive CAD 16, 17.…”

“…Similarly, a study in 988 women referred for coronary angiography observed that women with a history of depression were hospitalized more often over 2.3 years of follow‐up than those without a history of depression. In addition, the risk of death increased with increasing depression severity, even after adjusting for cardiovascular risk factors 1. The possible explanations for this relationship include both biological pathways and health behaviors, such as medication adherence, dietary habits, and physical activity.…”

“…Sex differences in the prevalence, presentation, management, and prognosis of coronary heart disease (CHD) have been described frequently 1, 2, 3. Female patients have more complex signs and symptoms of ischemia, and the variation in reproductive hormone levels may play a role in CHD pathophysiology and response to treatment.…”

Integration of Quantitative Positron Emission Tomography Absolute Myocardial Blood Flow Measurements in the Clinical Management of Coronary Artery Disease

“…Thus, the Women's Ischemia Syndrome Evaluation (WISE) study 94 and a more recent review 95 96 The cause of ischemia in these patients often is unclear and may be multifactorial. 95 Microvascular dysfunction, however, is thought to play an important pathophysiological role, 94,95 which clinically is very similar, if not identical, to syndrome X (angina with objective evidence of myocardial ischemia notwithstanding normal or only minimally diseased conduit coronary vessels [97][98][99] ). Quantitative PET measurements of absolute MBF are playing an increasingly important role in the evaluation and management of such patients, in whom qualitative SPECT MPI commonly is uninformative, if not misleading.…”