ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension.

BACKGROUND: Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. METHODS: The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D-dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). RESULTS: Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =. 012), tPA antigen (P =.0001), fibrinogen (P =.0002), D-dimer (P =. 0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. CONCLUSIONS: Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension.

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.

Fibrinolytic/hemostatic variables in arterial hypertension: response to treatment with irbesartan or atenolol.

Essential hypertension is often accompanied by abnormalities of the coagulation/fibrinolytic system, predisposing to a procoagulant state. The aim of the present study was to compare the effects of atenolol (beta1-blocker agent) and irbesartan (angiotensin II type 1 receptor antagonist) on plasma levels of hemostatic/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensives. Fifty-four patients were randomly assigned to atenolol 25 to 150 mg (26 patients) or irbesartan 75 to 300 mg (28 patients). The plasma levels of plasminogen activator inhibitor-1 antigen, thrombomodulin, tissue factor pathway inhibitor antigen, fibrinogen, and factor XII were determined before and after 6 months of therapy. Age, gender distribution, body mass index, lipid profile, and baseline values of the measured markers were similar in both groups. Baseline values for systolic and diastolic blood pressure, as well as the reduction after treatment, were not significantly different between the two groups. Treatment with irbesartan was associated with a significant decrease in the levels of all the parameters. Similar findings were observed in the atenolol group, except for factor XII and tissue factor pathway inhibitor levels, which were not significantly decreased in this group. The reduction, however, of fibrinogen, plasminogen activator inhibitor-1, and thrombomodulin was significantly greater in the irbesartan than in the atenolol group. In conclusion, the results indicated that, despite an equally controlled blood pressure, 6-month therapy with irbesartan was associated with a more favorable modification of hemostatic/fibrinolytic status than atenolol.

Elevated plasma immunoreactive leptin levels preexist in healthy offspring of patients with essential hypertension.

BACKGROUND: Plasma leptin levels and plasma insulin levels have been found to be elevated in patients with essential hypertension (EH) and have been suggested to be components of the metabolic syndrome. Increased heart rate (HR) may predict the development of EH in normal or borderline-hypertensive individuals. The aim of our study was to test the hypothesis that elevated plasma leptin and insulin levels as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP) and increased resting HR preexist in the healthy offspring of patients with EH. METHODS AND RESULTS: Twenty-six (12 male, 14 female) healthy offspring of hypertensive patients, mean age 16 +/- 2.5 years and body mass index (BMI) of 21.5 +/- 2.8 kg/m(2) (group A), and 30 (14 male, 16 female) healthy offspring of normotensive patients, mean age 17 +/- 2.3 years and BMI of 21.9 +/- 2.4 kg/m(2) (group B), were studied. (The two groups were matched for sex, age, and BMI). Mean SBP, DBP, resting HR, plasma leptin, and plasma insulin levels (radioimmunoassay method) were determined in the whole study population. Mean SBP, DBP, and resting HR were significantly higher in group A than in group B (120 +/- 12 vs 112 +/- 9.5 mm Hg, 77 +/- 9 vs 72 +/- 7 mm Hg, 79 +/- 8 vs 75 +/- 5 beats/min, P <.01, P <.05, and P <.05, respectively). Plasma leptin and insulin levels were significantly higher in group A than in group B (9 +/- 5.06 vs 5.6 +/- 2.5 ng/mL and 20.11 +/- 11.3 vs 14.8 +/- 5.2 microIU/mL, P <.01 and P <.05, respectively). CONCLUSIONS: Our findings support the hypothesis that hyperleptinemia, hyperinsulinemia, and elevated blood pressure and resting HR preexist in the healthy offspring of patients with EH.