Abstract 11228: The Endothelial Nitric Oxide Synthase Gene -786T/C Polymorphism is a Significant Predictive Factor for Myocardial Lactate Production During Acetylcholine-Provoked Coronary Spasm
Myocardial lactate production (MLP) in the coronary circulation is a supporting diagnostic marker useful in the evaluation of coronary spasm-induced myocardial ischemia during acetylcholine (ACh)-provocation test. We previously found a -786T/C polymorphism in the 5’-flanking region of the endothelial nitric oxide synthase (eNOS) gene and reported that this polymorphism is strongly associated with coronary spasm. However, there is no report showing the relation between MLP induced by ACh-provocation test and eNOS gene -786T/C polymorphism in the large study population. We examined 712 consecutive patients who underwent myocardial lactate measurement during ACh-provocation test and agreed with genetic screening test of eNOS gene -786T/C polymorphism between January 1991 and December 2010. ACh-provoked MLP was observed in 252 out of 712 patients included in the present analysis [252 MLP-positive and 460 MLP-negative patients]. MLP-positive patients were more likely to be female, diabetic, non-smokers, had epicardial, multivessel and diffuse spasm pattern, with eNOS-786T/C polymorphism (60% vs. 44%, p<0.001, 25% vs. 19%, p=0.047, 61% vs. 46%, p<0.001, 83% vs. 36%, p<0.001, 37% vs. 11%, p<0.001, 39% vs. 12%, p<0.001, and 23% vs. 15%, p=0.011, respectively). Multiple logistic regression analysis identified female gender, epicardial spasm and -786T/C polymorphism to correlate with the MLP-positive finding (OR: 0.327; 95% CI: 0.226-0.475; p<0.001, OR: 10.137; 95% CI: 6.767-15.187; p<0.001, and OR: 1.621; 95% CI: 1.025-2.564; p= 0.039). In the analysis of patients with epicardial coronary spasm, Kaplan-Meier survival curve showed no difference in 5-year survival rates free from major adverse cardiac events between MLP-positive and MLP-negative patients with epicardial coronary spasm (p=NS). In conclusion, multiple predictors including female gender and eNOS gene -786T/C polymorphism were the significant predictors for the MLP induced by ACh-provocation test, highlighting the close relation between the genetic factors and ACh-induced myocardial ischemia in Japanese patients with coronary vasospastic angina.
Author Disclosures: K. Kaikita: Honoraria; Modest; Daiichi Sankyo, Bayer, Novartis, AstraZeneca, Dainippon Sumitomo Pharma, Otsuka, MSD. K. Sato: None. M. Nakayama: None. K. Tsujita: None. S. Kojima: None. S. Hokimoto: None. H. Ogawa: Other Research Support; Modest; AstraZeneca, Astellas, Boehringer lngelheim, Bristol-Myers Squibb, Daiichi Sankyo, Dainippon Sumitomo Pharma, Kowa, MSD, Novartis, Pfizer, Sanofi, Takeda. Other Research Support; Significant; Bayer, Chugai, Otsuka. Honoraria; Modest; AstraZeneca, Bayer, Pfizer, Sanofi, Takeda. Honoraria; Significant; Daiichi Sankyo, MSD.
- © 2014 by American Heart Association, Inc.