ASSOCIATION BETWEEN ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM AND LEFT VENTRICULAR REMODELING AFTER MYOCARDIAL INFARCTION

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 07670821
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: KANSAI MEDICAL UNIVERSITY
• Principal Investigator: IWASAKA Toshiji MEDICAL DEPARTMENT,KANSAI MEDICAL UNIVERSITY PROFESSOR, 医学部, 教授 (00098120)
• Co-Investigator(Kenkyū-buntansha): MATSUBARA Hiroaki MEDICAL DEPARTMENT,KANSAI MEDICAL UNIVERSITY ASSISTANT PROFESSOR, 医学部, 講師 (10239072) ; TSUJI Hisako MEDICAL DEPARTMENT,KANSAI MEDICAL UNIVERSITY ASSISTANT PROFESSOR, 医学部, 講師 (60201638)
• Project Period (FY): 1995 – 1997
• Keywords: renin-angiotensin system / angiotensin-converting enzyme / gene polymorphism / myocardiaol infarction / left ventricular remodeling / mortality

Research Abstract

Angiotensin-converting enzyme (ACE) gene insertion / deletion (I/D) polymorphism has been demonstrated to be associated with serum and cardiac ACE activity. To evaluate the association of the ACE gene I/D polymorphism with left ventricular remodeling and in-hospital mortality, we studied 290 consecutive patients with a first myocardial infarction who were admitted to our cardiovascular center.
There were 82 patients who received echocardiography 2 weeks and 1 year after onset of myocardial infaction. Left ventricular remodeling was defined as the increase in left ventricular end-diastolic volume index * 20% at the recording of echocardiogram 1 year after onset compared to that of 2 weeks after onset. There were 11 patients with the DD genotype, 38 patients with the ID genotype, and 33 patients with the II genotype. Left ventricular remodeling was found in 4 patients (36%) of the DD genotype, 9 patients (24%) of the ID genotype, and 6 patients (18%) of the II genotype. Biological gradien t was observed among these 3 groups, but did not reach statistical significance (p=0.1591). Logistic regression analysis was used to evaluate the association of the ACE gene genotype (DD v.s.ID/II) with left ventricular remodeling. After adjustment for age, site of myocardial infarction, reperfusion therapy during acute phase, ACE inhibitor use, history of hypertension, and ejection fraction 2 weeks after onset, the DD genotype had a tendency to be associated with left ventricular remodeling (odds ratio=2.486, p=0.1722). Our sample size might be too small to detect a 15% difference in the incidence of left ventricular remodeling between the DD and the ID/II genotypes.
On the other hand, in-hospital mortality was compared between the DD genotype and the ID/II genotypes in 290 consecutive patients using the logistic regression analysis adjusted for age, sex, site of myocardial infarction, Killip functional class, reperfusion therapy during acute phase, ACE inhibitor use, and beta-blocker use. There were 45 patients with the DD genotype, 128 patients with the ID genotype, and 117 patients with the II genotype. Twenty-eight patients died during hospitalization (1 with the DD,18 with the ID,and 9 with the II genotype). The DD genotype was significantly associated with lower in-hospital mortality (p=0.0227) after adjustment for the clinical variables. Our results clinically supported preconditioning effect of angiotensin II observed in experimental studies.