What dictates prognosis in myocardial ischemic syndromes: myocardial ischemia or coronary atherosclerosis?

Myocardial ischemic syndromes are the main cause of death worldwide, with a rising incidence in developing countries. But why and how people with myocardial ischemic syndromes die or suffer major adverse cardiovascular events, namely myocardial infarction and sudden cardiac death, is still an incompletely resolved question. The intricacy of the issue arises at least somewhat from the relationship between angina pectoris, coronary atherosclerosis, and transient myocardial ischemia on the one hand and subsequent myocardial infarction, ischemic heart failure, and death on the other; a cause-effect relationship is not necessarily implied. The question has important prognostic and therapeutic implications because a proper identification of causes and mechanisms allows us to optimize the workup of patients and the therapeutic targets. Studies of conditions of myocardial infarction with normal coronary arteries (MINOCA) and angina with normal coronary arteries can be instrumental to resolving some of these unknowns. Such analyses convey the concept that coronary atherosclerosis, even when subclinical and usually considered prognostically irrelevant, has, conversely, important adverse prognostic implications. They also highlight, however, an important role for myocardial ischemia, which—when appropriately detected—alters prognosis unfavorably on top of coronary atherosclerosis. L