Non-obstructive coronary artery disease (CAD) is atherosclerotic coronary artery plaques that do not obstruct blood flow or result in anginal symptoms. Non-obstructive CAD occurs in 10% to 25% of patients undergoing coronary angiography, according to published research. Prior pre-clinical studies have noted that the majority of plaque ruptures and resultant myocardial infarctions (MIs) arise from non-obstructive plaques, yet non-obstructive CAD has generally not been recognized to confer significant risks. “The presence of these lesions has frequently been characterized in the medical literature as insignificant, but this perception may be incorrect,” explains Thomas M. Maddox, MD, MSc, FACC, FAHA.

While non-obstructive CAD can be identified by coronary angiography, little is known about its risk of adverse outcomes. The few studies assessing this link have typically focused on patients with MI, thus providing inadequate information about patients with stable non-obstructive CAD. Most coronary angiography registries only include patients with obstructive CAD, and the few that do include patients with non-obstructive CAD do not have longitudinal outcomes data.

“We need more data on non-obstructive CAD patients and their long-term outcomes to better understanding their risks for adverse cardiac outcomes and the implications of potential therapies to manage this patient population,” says Dr. Maddox. Fortunately, this data is now available via a VA cardiac catheterization laboratory database that is administered by the VA Clinical Assessment, Reporting, and Tracking (CART) program.

Important Comparisons

In a study published in JAMA, Dr. Maddox and colleagues compared MI and mortality rates between patients with non-obstructive CAD, obstructive CAD, and no apparent CAD. The study team used data from the CART program, which records anatomic data from all coronary angiograms performed in the VA healthcare system and tracks patients’ longitudinal outcomes. They then assessed the extent of non-obstructive and obstructive CAD and its association with 1-year hospitalization rates for non-fatal MIs and all-cause mortality rates.

After assessing more than 37,000 patients, researchers found that about one-quarter had non-obstructive CAD and more than half had obstructive CAD. Among patients with no apparent CAD, the 1-year MI rate was 0.11%. “However, the 1-year MI rate increased progressively among patients with non-obstructive CAD,” Dr. Maddox says. In patients with one-vessel non-obstructive CAD, the 1-year MI rate was 0.24%. In two-vessel non-obstructive CAD, the rate was 0.56%. In three-vessel non-obstructive CAD, the rate was 0.59%. Corresponding 1-year MI rates were 1.18%, 2.18%, and 2.47%, respectively.

The study team also found that 1-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with three-vessel or LM obstructive CAD (Table). After risk adjustment, there was no significant association between one- or two-vessel non-obstructive CAD and mortality, but significant associations with mortality were seen for three-vessel non-obstructive CAD (hazard ratio [HR], 1.6), one-vessel obstructive CAD (HR, 1.9), two-vessel obstructive CAD (HR, 2.8), and three-vessel or LM obstructive CAD (HR, 3.4). “The 1-year MI risk increased progressively by CAD extent,” says Dr. Maddox. “If patients have CAD—regardless of whether it’s obstructive or non-obstructive—then they’re at greater risk of having an MI.”

Significant Implications

Dr. Maddox says that the results highlight a need to recognize that non-obstructive CAD is associated with significantly higher risks for MI, a finding that is consistent with prior studies indicating that a majority of MIs are related to non-obstructive stenoses. The study complements these previous findings by demonstrating the association between non-obstructive CAD and adverse cardiac outcomes using coronary angiography, which is the predominant method of CAD diagnosis in current clinical practice.

Results of the study support the concept that non-obstructive CAD is not insignificant. Instead, it is associated with a significant and quantifiable risk for cardiovascular morbidity and mortality. “The presence of CAD, rather than its degree of obstruction, should be considered when making prognoses and managing these patients,” says Dr. Maddox. “Our study results also highlight the importance of preventive strategies like pharmacotherapy treatments and lifestyle modifications to mitigate these risks.”

In future research, investigations should focus on the best methods of quantifying the extent of CAD and correlating it with subsequent MI and mortality rates, according to Dr. Maddox. “We should also examine the effect of non-obstructive CAD in non-VA populations and in patients outside the United States,” he says. “The hope is we will collect more empirical evidence to assess whether these patients can benefit from the prevention therapies recommended for obstructive CAD. Studies of some therapies, such as antiplatelet agents and statins, are also needed in patients with clearly defined non-obstructive CAD.”