title: Angiotensin converting enzyme genotype influences the response to the angiotensin II receptor antagonist losartan in patients with hypertension.
abstract: To examine whether the response to the angiotensin II receptor antagonist losartan varies depending on the angiotensin converting enzyme (ACE) genotype, we prospectively studied the effect of losartan in 42 hypertensive patients (20 men, 22 women; mean age: 60.4 years). After a 4-week observation period, losartan was administered at 50 mg/day and blood pressure was measured every 2 to 4 weeks for 12 weeks. Among the 42 patients, 19, 11, and 12, respectively, had the II, ID, and DD ACE genotypes. The baseline plasma ACE activity in patients with the ID or DD genotype was significantly higher than that in patients with the II genotype (13.8 +/- 4.2 vs. 9.6 +/- 2.3 IU/l; p = 0.0002). However, age, gender, baseline systolic and diastolic blood pressure (SBP/DBP), and body mass index (BMI) were not different among the groups. After 12 weeks of treatment with losartan alone, DBP in the ID+DD group was significantly higher than that in the II group (85.0 +/- 9.0 vs. 77.8 +/- 9.6 mmHg, p = 0.018), while the percent reduction in DBP in the ID+DD group was significantly smaller than that in the II group (7.9 +/- 8.8 vs. 14.3 +/- 10.1%, p = 0.035). Multiple regression analysis showed that the significant predictors of the DBP at 12 weeks were age (p = 0.030), ACE genotype (p = 0.029) and baseline DBP (p = 0.0001). The ACE genotype may be a determinant of the response to losartan in hypertensive patients.
authors.affiliation: Division of Cardiology, Department of Medicine, Shiga University of Medical Science, Setatsukinowa-cho, Otsu 520-2192, Japan. nakamura@belle.shiga-med.ac.jp
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Shinji
authors.initials: S
authors.lastname: Tamaki
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Uchida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ohmichi
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaoka
authors.forename: Nobuo
authors.initials: N
authors.lastname: Miyauchi
authors.forename: Takehisa
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Harumi
authors.initials: H
authors.lastname: Sayama
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Shinro
authors.initials: S
authors.lastname: Matsuo
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D003971:Diastole; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007703:Peptidyl-Dipeptidase A; D019808:Losartan