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


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.
Fogari
Roberto
R
Department of Internal Medicine and Therapeutics, Clinica Medica II, IRCCS Policlinico S.Matteo, University of Pavia, Piazzale Golgi 19, 27100, Pavia, Italy. r.fogari@smatteo.pv.it
Preti
Paola
P
Zoppi
Annalisa
A
Lazzari
Pierangelo
P
Corradi
Luca
L
Fogari
Elena
E
Ciccarelli
Leonardina
L
Derosa
Giuseppe
G
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007249:Inflammation / Q000097:blood* / Q000473:pathology; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D013607:Tablets; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D002121:Calcium Channel Blockers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D011758:Pyrroles; D013607:Tablets; D014409:Tumor Necrosis Factor-alpha; D017311:Amlodipine; D002784:Cholesterol; D000069059:Atorvastatin