Prognosis in Women With Myocardial Ischemia in the Absence of Obstructive Coronary Disease

Abstract

Background-We previously reported that 20% of women with chest pain but without obstructive coronary artery disease (CAD) had stress-induced reduction in myocardial phosphocreatine-adenosine triphosphate ratio by phosphorus-31 nuclear magnetic resonance spectroscopy (abnormal MRS), consistent with myocardial ischemia. The prognostic implications of these findings are unknown. Methods and Results-Women referred for coronary angiography for suspected myocardial ischemia underwent MRS handgrip stress testing and follow-up evaluation. These included (1) nϭ60 with no CAD/normal MRS, (2) nϭ14 with no CAD/abnormal MRS, and (3) nϭ352 a reference group with CAD. Cardiovascular events were death, myocardial infarction, heart failure, stroke, other vascular events, and hospitalization for unstable angina. Cumulative freedom from events at 3 years was 87%, 57%, and 52% for women with no CAD/normal MRS, no CAD/abnormal MRS, and CAD, respectively (PϽ0.01). After adjusting for CAD and cardiac risk factors, a phosphocreatine-adenosine triphosphate ratio decrease of 1% increased the risk of a cardiovascular event by 4% (Pϭ0.02). The higher event rate in women with no CAD/abnormal MRS was primarily due to hospitalization for unstable angina, which is associated with repeat catheterization and higher healthcare costs. Conclusions-Among women without CAD, abnormal MRS consistent with myocardial ischemia predicted cardiovascular outcome, notably higher rates of anginal hospitalization, repeat catheterization, and greater treatment costs. Further evaluation into the underlying pathophysiology and possible treatment options for women with evidence of myocardial ischemia but without CAD is indicated.

Ischemia and No Obstructive Coronary Artery Disease (INOCA): What Is the Risk?

“…These stable patients typically have symptoms of chest pain suspected to be angina and/or abnormal stress testing, in the setting of no obstructive CAD at coronary angiography 1, 2. The definition of obstructive CAD varies between different guidelines or studies 3, 4, 5, 6, 7, 8, 9, 10. In general, “normal”‐appearing coronary arteries are defined as 0% luminal stenosis or <20%, and non–obstructive CAD (NOCAD) is defined as luminal stenosis >20% but <50% 3, 8, 9, 10.…”

“…The definition of obstructive CAD varies between different guidelines or studies 3, 4, 5, 6, 7, 8, 9, 10. In general, “normal”‐appearing coronary arteries are defined as 0% luminal stenosis or <20%, and non–obstructive CAD (NOCAD) is defined as luminal stenosis >20% but <50% 3, 8, 9, 10. However, some studies use a threshold of <70% for NOCAD,4 while anatomical scores consider a stenosis ≥50% as significant 5, 6, 11.…”

“…Overall estimates in women and men from the Veterans Administration Cardiovascular Assessment Reporting and Tracking System,16 the National Cardiac Data Registry, and the National Heart, Lung, and Blood Institute–sponsored Women's Ischemia Syndrome Evaluation (WISE)10 databases indicate that there are at least 3 to 4 million American women and men with stable INOCA. Incurred healthcare costs are similar to those for obstructive CAD.…”

“…Documented MACE rates in stable INOCA patients are summarized in Table 1 4, 10, 15, 26, 35, 36, 37, 38, 39, 40, 41. Additionally, many of these patients have an adverse quality of life, functional status, and exercise capacity with relatively frequent visits to healthcare providers for persistent or recurring disabling symptoms 42.…”

Local Production of Soluble Urokinase Plasminogen Activator Receptor and Plasminogen Activator Inhibitor‐1 in the Coronary Circulation Is Associated With Coronary Endothelial Dysfunction in Humans

“…Coronary microvascular dysfunction9, 36, 37 and elevated levels of systemic suPAR15, 16, 38 have both been associated with increased major adverse coronary outcomes. Elevated levels of suPAR have also been observed in advanced atherosclerotic disease in both the carotid39, 40 and renal arteries,41 which in turn has been associated with major adverse coronary outcomes.…”