The effect of Irbesartan antihypertensive treatment on the fibrinolysis-thrombosis system

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Coagulation and fibrinolysis disorders are considered independent risk factors for cardiovascular events in hypertension. The effects of antihypertensive agents in this system have not been fully clarified. Moreover, the AT1 receptors inhibitors effects are unknown. The study population comprised 285 consecutive, untreated patients with uncomplicated essential hypertension, who normalized their blood pressure with 150mg Irbesartan, daily monotherapy. Plasma fibrinogen and plasminogen activator inhibitor 1 (PAI-1) levels were determined before and 6 months after treatment. Fibrinogen plasma levels decreased from 316 to 303 mg/dl (-2.7% p=0.00001), more in diadetics and glucose intolerants than normoglycemics ( -8,4 vs -4.8 vs 0.7% p=0.00003), in patients with high waist/hips ratio (-5.7 vs -0.6% p=0.0001), dyslipidaemia (-5.8 vs -0.8% p=0.006), highplasma aldosterone levels ( -6.7 vs -0.5% p=0.00005), high initial fibrinogen levels (-10.3 vs -0.9% p<0.00001) and left ventricular hypertrophy (-4,5 vs -0.1% p=0,005). Irbesartan -induced plasma fibrinogen changes correlated to baseline fibrinogen and PAI-1 initial levels (r=-0.498 p=0.00001 and r=-0.204 p=0.0004 respectively), blood sugar (r=-0.218 p<0.0001), waist/hips ratio (r= - 0.157 p=0.007), plasma aldosterone (r= - 0.226 p=0,0001) and plasma aldosterone difference after therapy (r=0.235 p=0.00004), left ventricular mass index reduction(r=0.249 p=0.00001) and baseline value(r= -0.212 p=0.0002). Furthermore, significant correlations were detected with baseline total cholesterol value(r= -0.155 p= 0.007 ), triglycerides (r=-0.178 p=0.002 ),and LDL levels (r= -0.133 p=0.02 ). Plasminogen activator inhibitor (PAI-1) plasma levels decreased from 3.08 to 2.89 IU/ml (-4.4 % p<0.0001), ), more in diadetics and glucose intolerants than normoglycemics( -7.4 vs -6.5 vs 3.4% p=0.0002), in patients with high waist/hips ratio (-5.2 vs -3.6% p=0.0001), dyslipidaemia (-5.7 vs -3.6% p=0.05), high plasma renin activity ( -8.4 vs -3.4% p=0.04) and high PAI-1 pre-treatment levels (-8.7 vs -2.4% p=0.00004). Irbesartan -induced plasma PAI-1 changes correlated to baseline PAI-1 levels (r=-0.362 p<0.00001 ), blood sugar (r=-0.196 p=0.001) and plasma aldosterone (r= - 0.152 p=0,008) . Significant correlations were found, as well, with baseline HDL (r= 0.147 p= 0.01 ), triglycerides (r=-0.184 p=0.001 ) and especially with their changes (r= -0.216 p=0.0002 and r= 0.208 p=0.0003 respectively ). It is concluded that Irbesartan antihypertensive treatment improves selected factors of coagulation/fibrinolysis system, especially in patients with risk factors for coronary artery disease.