Abstract 5908: Impact of Secretory PLA2-IIa Gene Polymorphims on sPLA2 Activity and Cardiovascular Events Following an AMI: Results From the French Registry of Acute ST Elevation or Non-ST-elevation Myocardial Infarction (FAST-MI) Registry
Background: Increased levels of secretary phospholipase A2 (sPLA2) activity, which accounts for several types ofd sPLA2 including the group IIA, is associated with a higher risk of coronary artery disease and recurrent CV events.
Objectives and Methods: The FAST-MI registry included consecutive patients with ST-elevation (STEMI) or non-STEMI ≤ 48 hours of symptom onset in 223 French intensive care units in France. DNA and serum were available for 1029 patients. We assessed the relationship between the polymorphisms of PLA2IIA gene, serum tertiles of sPLA2 activity at the acute phase of MI, and their impact on the risk of death and recurrent MI during the first year of follow-up.
Results: Five single nucleotide polymorphisms (SNPs) in the PLA2G2A gene were identified and distinguished 6 common haplotypes (frequencies >5%) which accounted for 94% of the observed haplotypes. By single locus analysis, the C763 allele was associated with an increased level of sPLA2 activity (P<10 – 6)). Serum level of sPLA2 activity was associated with the risk of death and recurrent AMI which persisted after adjustment for known cardiovascular risk factors, CRP at entry, and treatments including statins: 1.66 (0.99 –2.80) and 2.00 (1.21–3.32) for second and third tertiles compared to first tertile (p trend < 0.03). The CGGAT haplotype, the only haplotype carrying the C763 allele was associated with an increase sPLA2 activity levels of up to 38.4% (1.73 nmol/ml/min) compared to the most frequent haplotypes (1.25 nmol/ml/min, P<0.0001). The same haplotype was also associated with the risk of death and recurrent MI during the first year of follow-up. After adjustment on age, gender, diabetes, hypertension, CRP and early use of statine, the association between CGGAT haplotype and outcome remained significant (RR=1.89, 95%CI=1.18 –3.04, p=0.009). Further adjustment for serum levels of sPLA2 activity markedly weakened the effect of CGGAT haplotype on death and recurrent MI (RR=1.67, 95%CI= 1.03 – 2.70 p=0.037.
Conclusion: The association of the sPLA2 group IIA gene polymorphisms with serum levels of sPLA2 activity and major one-year clinical outcome in AMI patients, suggest the hypothesis of a causal role of sPLA2 activity in atherosclerosis and its complications.