The research of C. Noel Bairey Merz, MD, focuses on heart disease in women, preventive cardiology, coronary physiology/pathophysiology and advanced cardiac imaging, as well as alternative and complementary medicine approaches to heart disease. Cardiovascular disease (CVD) is the leading cause of death in the US and on the planet, yet up to 70% of patients undergoing invasive angiography do not have obstructive coronary artery disease (CAD), more common in women than in men, as described by US and multi-national consensus documents. Although CMD has been documented over several decades, variability in symptom and stress testing characteristics lead to the widely held notion that these patients were “low risk”, very often receiving no specific therapy and dismissal from sub-specialty care. Evidence from the WISE original multicenter cohort, documented a higher risk of adverse events (e.g. death, myocardial infarction [MI], stroke, or hospitalization for heart failure [HF] or angina) emerging after 4-years of follow-up, comparable to patients with obstructive CAD, and higher in African American women25. Others have confirmed these findings and extended them to men (~20%). We have documented that most of these patients have coronary endothelial dysfunction, extensive but non-obstructive coronary atherosclerosis by intravascular ultrasound (IVUS), CMD, and myocardial ischemia. CMD, ischemia on stress testing, and angina persisting at 1-yr follow-up, identify patients at higher risk for adverse outcomes, most frequently hospitalization for HF, with preserved left ventricular (LV) ejection fraction (EF), i.e. HFpEF. Estimates from ACC/NCDR and WISE databases, indicate there are at least 3-4 million women and 1-2 million men in the US alone with INOCA who incur health-care costs similar to many with obstructive CAD. CMD may result from changes in function and/or structure of the coronary microcirculation, and in the absence of upstream obstructive CAD, is poorly understood mechanistically. Termed ischemia with no obstructive CAD (INOCA) and myocardial infarction with no obstructive CAD (MINOCA), these syndromes are increasingly observed in women, as well as men. Pharmacologic probe trials support anti-atherosclerotic and anti-ischemic therapies, and our ongoing clinical trial (WARRIOR NCT03417388) is testing high intensity statin, maximally-tolerated angiotensin-converting-enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) and low dose aspirin in women with INOCA for reduction of major adverse CV events (MACE); results are expected in 2025. For more information go to https://oir.nih.gov/wals