title: Blood pressure-lowering response to amlodipine as a determinant of the antioxidative activity of small, dense HDL3.
abstract: OBJECTIVE
  High-density lipoproteins (HDLs) exert multiple antiatherogenic activities including protection of low-density lipoproteins (LDLs) from oxidative stress. Beneficial effects of calcium channel blockers on cardiovascular disease may in part be related to the reduction of oxidative stress, potentially enhancing the antioxidative activity (AOX) of HDLs. This study aimed to assess the effect of 1 month's treatment with amlodipine on HDL AOX in hypertensive subjects.
  
  
  METHODS
  This was a prospective trial of amlodipine 10 mg/day administered for 1 month in primary-care patients with hypertension (n = 28), 46% of whom were obese and 57% of whom displayed the metabolic syndrome. The main outcome measure was HDL AOX, assessed as the capacity of small, dense HDL3c particles to attenuate LDL oxidation induced in vitro by an azo initiator (AAPH).
  
  
  RESULTS
  Mean (± SD) systolic (SBP) and diastolic (DBP) BP were reduced by amlodipine by 22.1 mmHg (± 13.2) and 10.4 mmHg (± 7.5), respectively (p < 0.001). Body mass index, waist circumference, and plasma levels of triglycerides, cholesterol, and fasting blood glucose did not change significantly. Amlodipine treatment did not modify HDL3c AOX in the whole study population; changes in AOX were, however, positively correlated with SBP (r = 0.37, p = 0.05 for maximal diene concentration; r = 0.34, p = 0.08 for LDL oxidation rate). When the population was divided into two subgroups according to the BP response to amlodipine (change in SBP below or above the median), HDL3c AOX was significantly improved in hyper-responders (BP-lowering response >22/10 mmHg) as compared with hypo-responders (BP-lowering response <22/10 mmHg: mean [± SD] change in the LDL oxidation rate in the presence of HDL3c, -6.8% [± 11.2] vs +1.9% [± 5.2], respectively, p = 0.04; maximal diene concentration, -8.6% [± 13.0] vs +1.9% [± 8.2], respectively, p < 0.05). By contrast, neither plasma concentrations of oxidized LDL, a marker of systemic oxidative stress, nor the chemical composition of HDL3c were modified between the subgroups.
  
  
  CONCLUSIONS
  In hypertensive patients, amlodipine treatment enhanced HDL AOX in subjects who had a BP reduction that exceeded the median response. This effect appears to be secondary to the hypotensive effect, rather than to the direct antioxidant properties, of the drug.
authors.affiliation: Service d'Endocrinologie-Métabolisme, Hôpital de la Pitié, Paris, France. boris.hansel@psl.aphp.fr
authors.forename: Boris
authors.initials: B
authors.lastname: Hansel
authors.forename: Xavier
authors.initials: X
authors.lastname: Girerd
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.forename: Randa
authors.initials: R
authors.lastname: Bittar
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chantepie
authors.forename: Alexina
authors.initials: A
authors.lastname: Orsoni
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000975:Antioxidants / Q000032:analysis* / Q000737:chemistry; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D053440:Lipoproteins, HDL3 / Q000097:blood* / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000032:analysis / Q000097:blood / Q000737:chemistry; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology; D008875:Middle Aged; D009765:Obesity / Q000503:physiopathology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D002121:Calcium Channel Blockers; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D017311:Amlodipine