Gene polymorphisms in APOE, NOS3, and LIPC genes may be risk factors for cardiac adverse events after primary CABG

Abstract

Introduction: Coronary artery disease progression after primary coronary artery bypass grafting may, beside classical atherosclerosis risk factors, be depending on genetic predisposition.

Methods: We investigated 192 CABG patients (18% female, age: 60.9 +/- 7.4 years). Clinically cardiac adverse events were defined as need for reoperation (n = 88; 46%), reintervention (n = 58; 30%), or angina (n = 89; 46%). Mean follow-up time measured 10.1 +/- 5.1 years. Gene polymorphisms (ApoE, NOS3, LIPC, CETP, SERPINE-1, Prothrombin) were investigated separately and combined (gene risk profile).

Results: Among classical risk factors, arterial hypertension and hypercholesterinemia significantly influenced CAD progression. Single ApoE, NOS3 and LIPC polymorphisms provided limited information. Patients missing the most common ApoE epsilon 3 allele (5,2%), showed recurrent symptoms (p = 0,077) and had more frequently reintervention (p = 0,001). NOS3 a allele was associated with a significant increase for reintervention (p = 0,041) and recurrent symptoms (p = 0,042). Homozygous LIPC patients had a higher reoperation rate (p = 0.049). A gene risk profile enabled us to discriminate between faster and slower occurrence of cardiac adverse events (p = 0.0012).

Conclusion: Single APOE, LIPC and NOS3 polymorphisms permitted limited prognosis of cardiac adverse events in patients after CABG. Risk profile, in contrast, allowed for risk stratification.

Figure 1

Risk profile and occurrence of cardiac adverse events. Out of the seven investigated gene polymorphisms, six were combined for a risk profile (see text). Patients with the risk profile had significantly more reoperations (0.012) and were more likely to have recurrent symptoms (0.0012). The incidence of interventions (PTCA, stent) were not different among the groups (p = 0.38). However, multivariate Cox regression analysis revealed that only the risk profile had significant impact on the incidence of cardiac adverse events (p = 0.004).