Predicting response to chronic antihypertensive treatment with fosinopril: the role of angiotensin-converting enzyme gene polymorphism.

Insertion (I)/deletion (D) polymorphism of the ACE gene has been reported to be involved in various cardiovascular diseases. We investigated prospectively whether the response to the ACE inhibitor fosinopril varied according to the ACE genotype in previously untreated Greek hypertensive patients. After a 4-week observation period, fosinopril was administered at a dose of 20 mg daily and blood pressure was measured weekly for 6 months. The study population consisted of 104 hypertensive patients (46 male, 58 female). There were no differences in age, gender, body mass index, and pretreatment blood pressure levels among patients with the DD, ID, and II genotypes (n= 42, 30, 32, respectively). The reduction in systolic blood pressure was significantly greater in patients carrying the DD compared to II or ID genotypes (5.6 +/- 3.1 vs. 3.1 +/- 1.1 or 3.6 +/- 2.2, respectively; ANOVA, p < 0.05). The reduction in diastolic blood pressure was also significantly greater in DD hypertensives compared with II or ID (8.9 +/- 6 vs. 5.5 +/- 3.4 or 5.8 +/- 4, respectively; ANOVA, p < 0.05). The age and BMI were not correlated with the changes in SBP or DBP that were observed after fosinopril administration. In conclusion, the ACE gene genotype was shown to influence the response to fosinopril in hypertensive patients.

Moxonidine effect on microalbuminuria, thrombomodulin, and plasminogen activator inhibitor-1 levels in patients with essential hypertension.

Increased sympathetic activity seems to play an important role in the pathogenesis and development of complications of atherosclerotic origin in patients with essential hypertension (EH). The aim of this study was to evaluate the effect of a new antihypertensive agent, moxonidine (M), on microalbuminuria (urine albumin excretion, UAE), plasma thrombomodulin (TM), and tissue plasminogen activator inhibitor (PAI-1) in patients with mild to moderate EH associated with increased UAE. Fifty-eight patients (32 M, 26 F) with EH and microalbuminuria, with a mean age of 56.6 +/- 8.2 years and a body mass index (BMI) of 23.8 +/- 3.1 kg/m2 who responded to M therapy (0.3-0.4 mg/daily) were studied before and after their blood pressure control. The 24-hour urine albumin excretion (RIA method), as well as TM and PAI-1 plasma levels (ELISA method), were determined before and 6 months after the initiation of treatment under moxonidine therapy. At the end of the 6-month period, all patients remained normotensive. The 24-hour urine albumin excretion had decreased to 24.5 +/- 6.4 vs. 32.3 +/- 7.2 ug/min before therapy (P < 0.001). The plasma TM levels had decreased to 44.0 +/- 7 vs. 51.0 +/- 9 ng/mL before therapy (P < 0.01), and PAI-1 levels had also decreased to 11.5 +/- 4.5 vs. 15.8 +/- 8 IU/mL before therapy (P < 0.05). The results of our study suggest that in hypertensive patients with microalbuminuria, moxonidine, an imidazoline I1-receptor agonist, a new centrally acting antihypertensive agent, significantly reduces urine albumin excretion as well as thrombomodulin and PAI-1 levels. These preliminary findings demonstrate a favorable effect on renal function and endothelial homeostatic mechanisms (maintenance of haemostatic balance).