title: High dose treatment with angiotensin II receptor blocker in patients with hypertension: differential effect of tissue protection versus blood pressure lowering.
abstract: Aggressive inhibition of renin-angiotensin-aldosterone system may provide the best cardiovascular protection. We examined the effect of different doses of angiotensin II receptor blocker, Candesartan, on arterial elasticity, inflammatory and metabolic parameters in hypertensive patients with multiple cardiovascular risk factors. 69 hypertensive patients were randomized into three groups: group 1 included patients treated with high doses of Candesartan (32 mg), group 2 included patients treated with conventional doses of Candesartan (16 mg), group 3 included patients that received antihypertensive treatment other that angiotensin II type-1 receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs). Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, hs-CRP, aldosterone, renin and Homeostasis model assessment-insulin resistance (HOMA-IR). Arterial elasticity was evaluated using pulse wave contour analysis method (HDI CR 2000, Eagan, Minnesota). In patients treated with high doses of Candesartan: large artery elasticity index (LAEI) increased from 8.6+/-2.8 to 16.6+/-5.1 ml/mm Hg x 100 after 6 months of treatment (p<0.0001). Small artery elasticity index (SAEI) increased from 2.7+/-1.3 to 5.9+/-2.8 ml/mm Hg x 100 (p<0.0001). Systemic vascular resistance (SVR) decreased from 1881.5+/-527.5 to 1520.9+/-271.8 (p<0.0006). In patients treated with conventional doses of Candesartan: LAEI index increased from 11.0+/-3.5 to 14.4+/-3.2 ml/mm Hg x 100 (p<0.0001). SAEI increased during the study from 3.7+/-1.4 to 5.4+/-2.1 ml/mm Hg x 100 (p<0.0001). SVR decreased from 1699.8+/-327.6 to 1400.7+/-241 (p<0.0001). In the control group: neither LAE nor SAE improved during the treatment period. Although similar reduction in blood pressure was observed in all three groups, both LAE and SAE improved only in patients treated by ARBs. Treatment with high doses of Candesartan improves arterial stiffness to a greater extent than conventional doses of Candesartan, despite comparable changes in blood pressure.
authors.affiliation: Department of Endocrinology, Wolfson Medical Center, Holon and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Shargorodsky
authors.forename: E
authors.initials: E
authors.lastname: Hass
authors.forename: M
authors.initials: M
authors.lastname: Boaz
authors.forename: D
authors.initials: D
authors.lastname: Gavish
authors.forename: R
authors.initials: R
authors.lastname: Zimlichman
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D003187:Compliance / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004548:Elasticity / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011673:Pulsatile Flow / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan