Emergence of Nonobstructive Coronary Artery Disease
Why the study?
Recognition of ischemic heart disease is often delayed or deferred in women due to sex-specific pathophysiology differing from traditional male-derived obstructive models, leaving at-risk women without specific strategies.
Key Points
- To synthesize current clinical evidence on nonobstructive coronary artery disease as a primary cause of ischemic heart disease and major adverse cardiovascular outcomes, particularly among symptomatic women.
- Reviewed observational registry and cohort studies, including the prospective WISE cohort (N=936 symptomatic women referred for coronary angiography) followed for up to 10 years.
- Evaluated diagnostic findings across international cohorts and clinical trial meta-analyses comparing angiography, coronary computed tomography angiography, and vascular stiffness markers.
- No obstructive coronary artery disease (<50% stenosis) was present in 40% to 70% of symptomatic women undergoing angiography compared to 14% to 32% of men.
- In a Danish registry of stable angina, diffuse nonobstructive disease carried an adjusted HR of 1.85 (95% CI: 1.51 to 2.28) for major adverse cardiovascular events and an adjusted HR of 1.52 (95% CI: 1.24 to 1.88) for all-cause mortality compared with asymptomatic reference controls.
- Among women in the WISE cohort with nonobstructive disease, the 10-year incidence of cardiovascular death or myocardial infarction reached 12.8% for narrowings >20% but <50%, compared to 6.7% for those with ≤20% diameter reduction.
Structured PICO
P
Population
Patients, predominantly women, with symptoms and signs of ischemic heart disease but nonobstructive coronary artery disease.
Limitations
- Lack of guideline-directed care for nonobstructive CAD
- Gaps in knowledge regarding pathophysiology and optimal treatment strategies
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“We have focused on the obstructive lesions for over 50 years, and now what we are beginning to recognize that arteries without obstruction still can convey some obstruction to blood flow, cause ischemia and cause adverse events. It is particularly a problem in women.”
LSLeandro SlipczukCardiologist, Montefiore Medical Center
“Cardiology is undergoing a transition now from a pure focus on identifying patients with obstructive CAD and treating them aggressively, [sometimes] after they've had an MI, to moving sooner [due to] realizing that nonobstructive CAD is not benign—and that it is heterogeneous and that it is common and undertreated.”
“Thus far patients, in particular women, with non-obstructive coronary arteries have perhaps been told 'they have nothing wrong with them' despite the fact they continue to have symptoms. We hope that our document will raise the much needed awareness of this condition both among patients and the treating clinicians so that these patients will now receive the right care.”
Implication
Nonobstructive coronary artery disease is a significant cause of ischemic heart disease and adverse outcomes, particularly in women, and should not be considered a benign condition.
Abstract
Recognition of ischemic heart disease (IHD) is often delayed or deferred in women. Thus, many at risk for adverse outcomes are not provided specific diagnostic, preventive, and/or treatment strategies. This lack of recognition is related to sex-specific IHD pathophysiology that differs from traditional models using data from men with flow-limiting coronary artery disease (CAD) obstructions. Symptomatic women are less likely to have obstructive CAD than men with similar symptoms, and tend to have coronary microvascular dysfunction, plaque erosion, and thrombus formation. Emerging data document that more extensive, nonobstructive CAD involvement, hypertension, and diabetes are associated with major adverse events similar to those with obstructive CAD. A central emerging paradigm is the concept of nonobstructive CAD as a cause of IHD and related adverse outcomes among women. This position paper summarizes currently available knowledge and gaps in that knowledge, and recommends management options that could be useful until additional evidence emerges.
Discussion
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Cite This Study
Pepine et al. (2015) conducted a review in Ischemic heart disease with nonobstructive coronary artery disease. Nonobstructive coronary artery disease vs. Obstructive coronary artery disease or normal coronary arteries was evaluated. Nonobstructive coronary artery disease is a highly prevalent cause of ischemic heart disease, particularly in women, and is associated with major adverse cardiovascular events similar to obstructive CAD.