PEACE: Data Demonstrate Benefits of Plaque Identification in High-Risk Patients

MIAMI BEACH, FLA.—In a scientific presentation at TCT 2012 on likely genetic identifiers of coronary disease in patients with vulnerable plaque, researchers discussed new CAD markers and ischemia-guided PCI.

Jozef Bartunek, MD, PhD, of the Cardiovascular Center at the OLV Hospital in Aalst, Belgium, said that locus 9p21 is emerging as a CAD risk factor. In addition to its current status as a risk factor for three-vessel disease, left main disease and coronary artery grafting, previous research has also shown locus 9p21 to be associated with a risk of MI independent of family history, with a risk increase of 30% in the presence of family history.

Bartunek also discussed the PEACE study, which looked at 3,766 patients with stable CAD. Patients in the higher quartiles of lipoprotein-associated phospholipase A2 (Lp-PLA-2) remained at significantly greater risk for the composite of CV death, MI, coronary revascularization, unstable angina, or stroke (P<.001 for trend, adjusted HR 1.41, 95% CI 1.17-1.70, for patients in fourth vs. first quartile). When examined collectively, high-sensitivity CRP and Lp-PLA-2 were both effective predictors of ACS (CV death, MI, or UA) (P for trend <.001 for hsCR, P and .005 for Lp-PLA2), while Lp-PLA-2 alone was a significant predictor of coronary revascularization (P=.01 for trend).

According to Bartunek, identification of biomarkers of vulnerable plaque remains a work in progress; however, it should help to identify high-risk patients who require further imaging-guided work-up. While chromosome 9p21 represents a new genetic CV risk factor, a multimarker strategy needs to be refined to identify the combination of markers involved in the critical stages of plaque growth and rupture.

“Clinical and imaging-based phenotyping, coupled with multisite biosampling and unbiased high-throughput analyses, may yield novel markers of vulnerable [plaque]. I would submit that maybe it is time to … modify our approach to vulnerable patients … as we acknowledge the use of biomarkers,” Bartunek said.

Ischemia as early warning system

In a presentation of the FAME 2 trial data, Bernard De Bruyne, MD, PhD, of the Cardiovascular Center Aalst in Aalst, Belgium, discussed some of the contributing hemodynamic factors leading to abrupt coronary occlusion, including plaque stress, venturi effect, vasa vasorum and cholesterol crystals.

De Bruyne and colleagues enrolled 888 patients with stable CAD with at least one functionally significant stenosis assessed by FFR. The patients were randomly assigned to best-available medical therapy with or without FFR-guided PCI. Results demonstrated that the PCI group had a lower rate of primary endpoint events (death, MI, or urgent revascularization), at 4.3% vs. 12.7% (P<.001), driven primarily by a difference in urgent revascularization (0.7% vs. 9.5%; P<.001). The component endpoint rates of death from any cause or MI did not differ significantly between groups.

Only four patients in the PCI group underwent urgent revascularization triggered by MI or unstable angina with evidence of ischemia on an ECG compared with 23 patients in the medical therapy group.

 “Ischemia is definitely a marker of abnormal physical forces that take place at the level of epicardial stenosis,” De Bruyne said. “Ischemia is probably not the culprit by itself, but rather a marker, a surrogate of the physical forces that take place at the epicardial vessel.”

 De Bruyne added that pressure gradient should be considered as a focal contributor to plaque. Without pressure gradient, and the resulting absence of hemodynamic forces, plaque rupture would be highly unlikely.

“Even though plaque composition is critically important, plaque rupture will occur when there is an imbalance or when hemodynamic forces exceed the material strength of the plaque. This highlights the importance of these physical forces which have been largely neglected in studies over the last few years,” said De Bruyne.