Study Highlights Clinical Risk of Nonobstructive CAD

Patients diagnosed with nonobstructive coronary artery disease (CAD) are at increased risk of myocardial infarction (MI) and mortality over the next year compared with those classified as having no apparent disease, according to results of a retrospective study published in the November 5, 2014, issue of the Journal of the American Medical Association. In general, the risk rises along with the number of diseased vessels.

According to lead author Thomas M. Maddox, MD, MSc, of the VA Eastern Colorado Health Care System (Denver, CO), the finding undercuts the traditional dichotomous classification of CAD and suggests that patients with nonobstructive disease may benefit from preventive therapy.

Investigators analyzed data on 37,674 patients who underwent elective coronary angiography at 79 VA centers between October 2007 and September 2012.
Results were categorized according to the severity of CAD. Overall, 22.3% of the cohort had no apparent CAD (no stenosis > 20%), 22.3% had nonobstructive disease (at least 1 stenosis ≥ 20% but none ≥ 70%), and 55.4% had obstructive CAD (any stenosis ≥ 70% or left main stenosis ≥ 50%). The extent of disease in the nonobstructive and obstructive CAD categories was also characterized by the number of diseased vessels.
Approximately two-thirds of patients underwent angiography for chest pain. Age, cardiovascular risk factors, and Framingham risk scores all increased with increasing CAD extent. The frequency of postangiography prescriptions for cardiovascular medications and the rates of revascularization also increased with CAD extent.

Risk Rises With Number of Diseased Vessels

In a Cox regression model, 1-year risk of hospitalization for MI rose progressively along with disease extent across the continuum of nonobstructive CAD (except for 2-vessel disease) relative to no apparent disease. The same relationships held true for mortality and the composite of MI and mortality (table 1).

Table 1. One-Year Risk: Nonobstructive CAD vs No Apparent Disease

After adjustment, all outcomes significantly increased with increasing CAD extent regardless of whether nonobstructive disease was mild or moderate, the only exception being the absence of a link between mild nonobstructive CAD and 1-year mortality. Similarly, the relationship between event risk and CAD extent showed no interaction with diabetes or symptom status.

The authors observe that the study—which is based on the predominant method of CAD diagnosis, namely, angiography—complements the findings of cardiac CT studies in showing a link between nonobstructive CAD and adverse outcomes.

They acknowledge, however, that because the study patients were referred for angiography, they are unlikely to reflect the prevalence of nonobstructive CAD in the population not undergoing catheterization. Moreover, patients’ classification as symptomatic or asymptomatic relied on angiographic results rather than direct clinical assessment.

Paradigm Shift Needed

In a video statement on the JAMA website, Dr. Maddox said the study highlights that the paradigm of dividing CAD into obstructive vs nonobstructive disease, “even though it’s helpful for establishing the cause of chest pain symptoms, is not as relevant for understanding patients’ risk for heart attack and death.

“Rather, we should recognize that the presence of any coronary disease, be it nonobstructive or obstructive, does portend a significant risk of 1-year heart attack and death,” he continued. “And as a result, all of these patients would probably benefit from preventative therapy.”

Dr. Maddox identified 3 next steps for researchers:

  • Verifying the findings in other populations, including those that are less predominantly male
  • Developing a better approach to categorizing CAD that considers risk of MI
  • Performing prevention studies among patients with nonobstructive CAD

“Nonobstructive patients were systematically excluded from all prevention trials we have to date, so it’s going to be important to understand the impact that our pharmacotherapies and lifestyle modifications can have on this population in reducing the risk of heart attack,” he emphasized.


Maddox TM, Stanislawski MA, Grunwald GK, et al. Nonobstructive coronary artery disease and risk of myocardial infarction. JAMA. 2014;312:1754-1763.

Related Stories:

Study Highlights Clinical Risk of Nonobstructive CAD

  • Dr. Maddox reports no relevant conflicts of interest.