Biomarkers May Identify Risky Subcritical Lesions

Two biomarkers associated with rapid progression to critical stenoses in nonculprit lesions following percutaneous coronary intervention (PCI) may eventually help personalize therapy by identifying patients in need of prophylactic stenting or aggressive medical therapy, according to a subanalysis of patients enrolled in the PROSPECT study.

PROSPECT, originally published in 2011 in The New England Journal of Medicine, enrolled 700 patients with acute coronary syndromes (ACS) who had previously undergone successful PCI of 1 or 2 major coronary arteries. Once enrolled, patients underwent three-vessel coronary angiography and intravascular ultrasound (IVUS) for lesion characterization. Over 3.4 years of follow-up, major adverse cardiovascular events (MACE) were equally attributable to recurrence at both culprit and nonculprit (or subcritical) lesions.

For the new analysis, Martin Möckel, MD, of the Charité Hospital in Berlin, and colleagues sought to identify specific biomarker profiles in patients with nonculprit lesions that are prone to MACE events. The researchers measured 12 vascular and cardiovascular risk-related biomarkers in blood samples taken at baseline, 30 days and 180 days in 697 patients from PROSPECT. These biomarkers were then related to patient outcomes recorded during the follow-up period.

Biomarker analysis

The analysis indicated that biomarkers sFLT-1 and GDF-15 seem promising for identifying those patients at risk of MACE due to vulnerable and subcritical lesions, as well as for monitoring disease progression in patients with known subcritical lesions, Möckel said.

Median sFLT-1 levels were higher in patients without a nonculprit index event compared with patients with nonculprit lesion-related MACE (P=.03); at 6 months, sFLT-1 levels decreased and the difference had disappeared. Both cystatin C and beta-2-microglobulin values were slightly higher in patients with nonculprit MACE at baseline (P=.07 and P=.02, respectively), and they increased slightly and remained significant at 6 months.

GDF-15 values at baseline were higher in patients who had any MACE during the follow-up period (P=.02). These patients also had higher cystatin C and beta-2 microglobulin and lower HDL and ApoA1 levels. In multivariate analysis, only insulin-dependent diabetes (HR 3.43; 95% CI 1.38-8.58) and a history of angina remained significant predictors of nonculprit MACE.

Promising first step

“The results of our research are a first promising step because it suggests the possibility of using sFLT-1 and GDF-15 for identifying patients at risk of carrying vulnerable but yet subcritical lesions,” Möckel told TCT Daily. Once identified, he said, patients could then undergo IVUS, “which is too complex and costly to be performed in all subcritical lesions of every patient.”

Although biomarker identification is not yet ready for clinical practice, its eventual use could help determine whether prophylactic stenting of vulnerable lesions or intensified antithrombotic or statin therapy would be warranted for certain patients, Möckel added.

“Our results might offer a cost-effective, noninvasive, personalized solution to identify patients at risk. Importantly, with prophylactic stenting, we have a therapeutic strategy at hand that will most probably improve patient care and outcome,” he told TCT Daily.