Effects of amlodipine-atorvastatin combination on inflammation markers and insulin sensitivity in normocholesterolemic obese hypertensive patients.

Eur J Clin Pharmacol

Department of Internal Medicine and Therapeutics, Clinica Medica II, IRCCS Policlinico S.Matteo, University of Pavia, Piazzale Golgi 19, 27100, Pavia, Italy.

Published: October 2006

Objective: The objective of this study was to assess the effect of amlodipine-atorvastatin combination on plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and insulin sensitivity in normocholesterolemic obese hypertensive patients.

Materials And Methods: After a 4-week placebo wash-out period, 50 normocholesterolemic [total cholesterol (TC) <5.2 mmol/L], obese (BMI >/=30 kg/m(2)) hypertensive patients (DBP >90 and <105 mm Hg and SBP >140 and <180 mm Hg) were randomly treated with amlodipine (10 mg) or with amlodipine (10 mg) plus atorvastatin (20 mg) according to a cross-over design; each treatment had a 12-week duration. At the end of the placebo and of each treatment period, blood pressure (BP), TNF-alpha, IL-6, insulin resistance (IR) by homeostasis model assessment of IR index (HOMA-IR) and TC were evaluated.

Results: Amlodipine monotherapy decreased both SBP (-17.1 mm Hg, p=0.008 vs. placebo) and DBP (-14.3 mm Hg, p=0.008) as well as TNF-alpha (from 3.66+/-1.6 to 3.09+/-1.1 pg/ml, p=0.045) and HOMA-IR (from 4.58+/-0.7 to 3.88+/-0.6, p=0.007). The amlodipine-atorvastatin combination produced a decrease in SBP (-22.5 mm Hg, p=0.0007 vs. placebo, p=0.039 vs. amlodipine), DBP (-17.7 mm Hg, p=0.0007 vs. placebo; p=0.04 vs. amlodipine), TNF-alpha (2.59+/-0.9 pg/mL, p=0.007 vs. placebo and p=0.038 vs. amlodipine) and HOMA-IR (2.86+/-0.4, p=0.0008 vs. placebo and p=0.007 vs. amlodipine). The combination reduced IL-6 (from 7.93+/-1.9 to 5.59+/-1.2 pg/mL, p=0.008 vs. placebo and p=0.007 vs. amlodipine) and TC (from 4.3+/-0.5 to 3.6+/-0.4 mmol/L, p=0.008 vs. placebo and vs. amlodipine). HOMA-IR changes significantly correlated with TNF-alpha changes (r=0.38, p<0.05) during combination but not during amlodipine monotherapy. In normocholesterolemic, obese hypertensive patients, the amlodipine-atorvastatin combination decreased inflammatory markers and IR more than amlodipine monotherapy and produced a greater SBP and DBP reduction.

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http://dx.doi.org/10.1007/s00228-006-0176-1DOI Listing

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