Key result
Cilazapril /d prolongs LDL peroxidation lag time ~43% versus low-dose cilazapril plus HCTZ.
Why the study?
It was unclear whether equivalent blood pressure reduction by cilazapril alone or combined with low-dose hydrochlorothiazide equally affects plasma LDL oxidation in hypertensive patients.
Does equivalent blood pressure reduction by cilazapril alone or in combination with hydrochlorothiazide have an equal effect on lowering oxidation of plasma LDL in patients with untreated arterial hypertension?
Does equivalent blood pressure reduction by cilazapril alone or in combination with hydrochlorothiazide have an equal effect on lowering oxidation of plasma LDL in patients with untreated arterial hypertension?
Cilazapril reduces LDL peroxidation in hypertensive patients through an inherent drug effect that is independent of its blood pressure-lowering effect.
Answers are grounded in this paper and cite their sources.
Cilazapril may exert BP-independent antioxidant effects on LDL; hypothesis-generating and should not change practice without randomized confirmation.
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.
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O. Hussein (2003) studied untreated arterial hypertension (n=25). Cilazapril with or without hydrochlorothiazide vs. Sequential treatment phases and healthy controls was evaluated on LDL tendency to peroxidation (lag time to initiation of peroxidation) (prolonged by 43%, p=<.05). Cilazapril /d prolonged the lag time to LDL peroxidation by 43%, an effect not seen with equivalent blood pressure reduction using low-dose cilazapril plus hydrochlorothiazide.
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