Abstract 14175: Cytotoxin-associated Gene-A-seropositivity and Interleukin-1 Polymorphisms Influence the Development and Recurrence of Acute Coronary Syndrome

BackgroundCytotoxin-accociated Gene-A (CagA)-seropositivity produced by Helicobacter pylori (HP) is associated vascular atherosclerosis as well as carcinogenesis. Pro-inflammatory interleukin-1 (IL-1) polymorphisms are reported to influence HP-related diseases activity. We examined the effect of CagA-seropositivity and IL-1 polymorphisms on the development and recurrence of HP-related acute coronary syndrome (ACS).MethodsWe enrolled 223 ACS and 129 control subjects. Immunoglobulin G antibodies against HP and CagA were measured, and IL-1 polymorphism analyses were performed for single nucleotide polymorphism in IL-1 beta-511 and the variable number of tandem repeats polymorphism in the IL-1 receptor antagonist by polymerase chain reaction. We assessed peripheral endothelial function by reactive hyperemia-peripheral arterial tonometry (RH-PAT) using the EndoPAT2000 system. Clinical outcome after ACS included all cause death, non-fatal MI, stroke, unstable angina, and revascularization.ResultsThe rates of MI between HP(-)CagA(-) (n=126), HP(+)CagA(-) (n=32), and CagA(+) (n=72) groups were 36.5%, 50.0%, and 54.2%, respectively (P=0.042). The rates of the simultaneous presence of CagA-seropositivity and IL-1 polymorphisms between control and MI groups were 16.3% and 29.7%, respectively (P=0.017). Multivariate logistic regression analysis for MI found CagA/IL-1 polymorphisms were significantly associated with MI (OR, 2.04; 95% CI, 1.02-4.09; P=0.043) with a significant net reclassification improvement of 26.9% (95% CI, 4.9-48.8%; P=0.016). Natural logarithm of RH-PAT index was significantly lower in patients with CagA seropositivity and IL-1 polymorphisms (0.55 ± 0.28 versus 0.66 ± 0.26; P=0.01). Kaplan-Meier analysis showed that CagA positive patients with IL-1 polymorphisms had worse prognosis (log-rank testP=0.037), and multivariate cox proportional hazards analysis identified CagA/IL-1 polymorphisms as a significant and independent predictor of clinical outcome (HR2.26, 95% CI1.13-4.53, P=0.021).ConclusionsOur study results revealed that bacterial virulence factor CagA and host genetic IL-1 polymorphisms might influence the development and recurrence of ACS.