Effect of cilazapril with or without low dose thiazide on LDL peroxidation in [correction of peroxidationin] hypertensive patients.
BACKGROUND
This study aims to address the question, "Does equivalent blood pressure (BP) reduction by cilazapril alone or in combination with low dose of both cilazapril and hydrochlorothiazide have an equal effect on lowering oxidation of plasma LDL?"


METHODS
Fifteen patients with untreated arterial hypertension were enrolled. Patients received 5 mg/d cilazapril (C5) for 6 weeks and were treated with a combination of 2.5 mg/d cilazapril and 12.5 mg/d hydrochlorothiazide (C2.5,HCTz) for an additional 2 months to achieve the same BP reduction as in the initial period. Treatment with a combination of 5 mg/d cilazapril and 12.5 mg/d hydrochlorothiazide (C5,HCTz) was administered for an additional 6 weeks.


RESULTS
Treatment with C5 or in combination with C2.5,HCTz lowered systolic BP by the same magnitude (P <.05). Treatment with C5,HCTz decreased systolic BP an additional 7% and diastolic BP by 6% (P <.05). The LDL of 15 hypertensive patients demonstrated a 16.7% shorter lag time to initiation of peroxidation and 8.5% higher malonyldialdehyde levels at point of maximal peroxidation than LDL from 10 healthy controls (P <.05). Treatment with C5 decreased LDL tendency to peroxidation (lag time was prolonged by 43%, P <.05; malonyldialdehyde levels decreased by 8.3%). The combined treatment of C2.5,HCTz achieved the same BP reduction, but did not increase LDL resistance to peroxidation. Treatment with C5,HCTz achieved the same reduction in malonyldialdehyde levels in LDL than C5 therapy, but prolonged lag time by 17% (P <.05).


CONCLUSIONS
The decreased tendency of LDL to peroxidation in hypertensive patients treated by cilazapril is due to the inherent effect of cilazapril, and not to a reduction in BP.
Hussein
Osamah
O
Lipid Research Laboratory, Internal Medicine Department A, Sieff Government Hospital, PO Box 1008, Safed 13100, Israel. husseinosamah@newmail.net
Radan
Arman
A
Reuven
Viskoper
V
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D008078:Cholesterol, LDL / Q000187:drug effects* / Q000378:metabolism*; D017315:Cilazapril / Q000008:administration & dosage*; D003404:Creatinine / Q000097:blood; D003971:Diastole / Q000187:drug effects; D004232:Diuretics; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005951:Glucose Tolerance Test; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage*; D013599:Systole / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D001786:Blood Glucose; D008078:Cholesterol, LDL; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D006852:Hydrochlorothiazide; D017315:Cilazapril; D014527:Uric Acid; D003404:Creatinine