Lipoprotein-associated phospholipase A2 predicts progression of cardiac allograft vasculopathy and increased risk of cardiovascular events in heart transplant patients

Abstract

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor for coronary artery disease (CAD) in nontransplant patients. We evaluated the association between Lp-PLA2, cardiac allograft vasculopathy (CAV) assessed by 3D intravascular ultrasound, and incidence of cardiac adverse events in heart transplant recipients.

Materials and methods: Fasting blood samples were obtained and stored from a cross-section of 112 cardiac transplant recipients attending the Mayo cardiac transplant clinic in 2000 to 2001, mean of 4.7 years after transplant. Lp-PLA2 was measured in plasma aliquots using an enzyme-linked immunoassay. Fifty-six of these patients subsequently underwent two 3D intravascular ultrasound studies in 2004 to 2006 12 months apart. Cardiovascular (CV) events included percutaneous coronary intervention, coronary artery bypass grafting (CABG), reduction in left ventricular ejection fraction (LVEF) < or =45% secondary to CAV and CV death.

Results: High Lp-PLA2 level was associated with increase in plaque volume (r=0.43, P=0.0026) and percent plaque volume (r=0.45, P=0.0004). The association remained significant after adjusting for clinical and lipid variables. During follow-up of 5.1+/-1.6 years, 24 CV adverse events occurred in 15 of 112 (13%) heart transplant patients. Lp-PLA2 level>236 ng/mL (higher tertile) identified a subgroup of patients having a 2.4-fold increase of relative risk for combined endpoint of CV events (percutaneous coronary intervention, CABG, LVEF<45%, and CV death; 95% CI 1.16-5.19, P=0.012) compared with patients with Lp-PLA2< or =236 ng/mL.

Conclusions: Lp-PLA2 is independently associated with progression of CAV and predicts a higher incidence of CV events and CV death in transplant patients. This finding supports the concept that systemic inflammation is an important mediator of CAV. Lp-PLA2 may be a useful marker for risk of CAV and a therapeutic target in posttransplant patients.

FIGURE 1

(A) X–Y scatterplot for the correlation between Lp-PLA2 and changes in plaque volume (r=0.43; P=0.0026). (B) X–Y scatterplot for the correlation between Lp-PLA2 and changes in percent plaque volume (r=0.45; P=0.0004).

FIGURE 2

Cardiovascular event—free survival according to Lp-PLA2 levels. Freedom from CV events 6 years after blood sample was 74% in patients with Lp-PLA2>236 ng/mL (higher tertile) compared with 92% in patients with Lp-PLA2≤236 ng/mL (P=0.02, log-rank test). One patient in the higher tertile had already undergone PCI before the blood sample; results remained significant if that event was excluded from the analysis.