Abstract
Recent evidence suggests a strong relationship between angiotensin 1 (AT1) receptor gene expression and low-density lipoprotein cholesterol (LDL-C) plasma level. This article comparatively evaluates blood pressure-modulating effects and metabolic and haemodynamic actions of an antihypertensive treatment directly interacting (telmisartan) versus non-interacting (bisoprolol) with the AT1 receptor in statin-treated hypercholesterolaemic patients. Sixteen untreated hypertensive hypercholesterolaemic patients (aged 57.4 ± 7 years) were enrolled according to a randomized, single-blind, crossover design with a prospective randomized, open-label, blinded evaluation of the primary endpoint. All of the patients were allocated to treatment with simvastatin 20 mg/day for 2 weeks, and then randomly assigned to treatment with either telmisartan (40–80 mg/day) or bisoprolol (5–10 mg/day) whose daily dose was doubled after 2 weeks if blood pressure control was unsatisfactory. After a cumulative period of 4 weeks, the antihypertensive drugs were withdrawn for a washout period of 2 weeks when the patients were treated with simvastatin alone. They were then allocated to the alternative antihypertensive treatment (bisoprolol or telmisartan) for a cumulative period of 4 additional weeks with a dosage adjustment at week 2. The following were measured in each patient: lying and standing systolic blood pressure (SBP) and diastolic blood pressure (DBP); heart rate; 24-hour SBP and DBP by ambulatory blood pressure measurement; baseline forearm blood flow (FBF); and forearm vascular resistance (FVR), post-ischaemic FBF and FVR, lipid profile and fasting plasma glucose. After 2 weeks of treatment with simvastatin, baseline and post-ischaemic FBF increased (both p < 0.05), while baseline and post-ischaemic FVR decreased (both p < 0.05). Both antihypertensive treatments were associated with a significant reduction in SBP (p < 0.005), DBP (p < 0.05) and mean blood pressure (MBP) [p < 0.05]. Standing DBP and MBP were reduced more in the telmisartan than in the bisoprolol group (p < 0.05). Basal and post-ischaemic FBF were significantly increased (p < 0.05 and p < 0.005, respectively) and basal and post-ischaemic FVR were significantly decreased (both p < 0.005) only in the telmisartan-treated group. LDL-C plasma level significantly improved in both treatment groups (p < 0.05), while plasma triglycerides significantly decreased only in the telmisartan-treated group (p < 0.05). From the result of this preliminary study carried out on a small sample of hypercholesterolaemic hypertensive patients, it appears that the association with telmisartan and simvastatin could exert positive effects on a large quantity of vascular functionality parameters, after just a short treatment. This observation has not been confirmed in bisoprolol-treated patients.
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