Effects of losartan versus hydrochlorothiazide on indices of endothelial damage/dysfunction, angiogenesis and tissue factor in essential hypertension.

Background: Abnormalities in endothelial function, angiogenesis and thrombogenesis are found in essential hypertension. Angiotensin II has been postulated as an agent involved in these processes. We hypothesized that the treatment of essential hypertension with the angiotensin II receptor antagonist, losartan, would affect endothelial damage/dysfunction, angiogenesis and coagulation, when compared to treatment with a diuretic.

Methods: Forty hypertensive patients (28 male, mean age 56 +/- 11.8 years) were randomized to treatment with losartan 50-100 mg o.d. or hydrochlorothiazide 12.5-25 mg o.d. over a 12-week period. Patients were assessed at week 0, 4 and 12. Endothelial damage/dysfunction was assessed using plasma levels of von Willebrand factor (vWf) and changes in flow-mediated dilation of the brachial artery (FMD). Vascular endothelial growth factor (VEGF) and its soluble receptor Flt-1 (sFlt-1) were measured as indices of angiogenesis, and plasma tissue factor (TF) as an index of coagulation. Baseline results in hypertensives were compared to 20 healthy controls (13 male, mean age 61.1 +/- 10.1 years).

Results: Mean patient BP was 161/95 +/- 21/18 mmHg compared to 134/81 +/- 11/7 mmHg in controls (p<0.002). Plasma levels of TF (p=0.023) were significantly higher in patients compared to controls, and FMD was significantly lower (p<0.001). There were no significant differences in baseline blood pressures, plasma indices or FMD between patients randomized to losartan and hydrochlorothiazide. There were no significant changes in levels of plasma indices or FMD over 12 weeks of treatment in either patient group. Significant correlations between levels of VEGF with sFlt-1 (Spearman p<0.001) and TF (p=0.009) and sFlt-1 and TF (p=0.035) were seen in the untreated state, amongst the patient group only.

Conclusion: We have confirmed previous observations of increased levels of TF and decreased FMD in hypertensive patients compared to healthy controls. Contrary to previous observations in higher-risk hypertensive patient groups, the treatment of essential hypertension with either losartan or hydrochlorothiazide did not affect indices of endothelial damage/dysfunction, angiogenesis or coagulation.