The effect of amlodipine on endothelial function in young adults with a strong family history of premature coronary artery disease: a randomised double blind study.
Endothelial dysfunction, an early event in atherogenesis, has been demonstrated in young asymptomatic subjects with a strong family history of premature coronary artery disease (CAD). In these subjects, preventive measures involving risk factor modification are not appropriate, and strategies employing novel antiatherogenic agents, such as the dihydropyridine calcium channel blocker, amlodipine, may be useful. Ninety-one subjects (mean age, 28.6 years; range, 18-40) with a strong family history of premature CAD and no other identified vascular risk factors were randomised to either 5 mg amlodipine (49 subjects) or placebo (42 subjects). Brachial artery flow mediated dilatation (FMD) (endothelium-dependent response) and response to glyceryltrinitrate (GTN) (direct smooth muscle dilator) were assessed non-invasively at baseline, and after 12 and 24 weeks using high-resolution vascular ultrasound. In those treated with amlodipine, mean FMD increased from 2.32+/-2.23% at baseline to 3.52+/-3.1% at 24 weeks (P<0.005). However, FMD also increased in the placebo group from 1.64+/-2.12 to 3.37+/-2.68% (P<0.002), and the difference between the FMD response in the amlodipine and placebo groups was not significant. Dilatation to GTN did not change in either group. Therefore, impaired endothelial function improved in family history subjects taking both amlodipine and placebo, but there is no difference between the groups.
Clarkson
P
P
Cardiothoracic Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, WC1N 3JH, London, UK. peterclarkson1@compuserve.com
Mullen
M J
MJ
Donald
A E
AE
Powe
A J
AJ
Thomson
H
H
Thorne
S A
SA
Bull
T
T
Deanfield
J E
JE
D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003327:Coronary Disease / Q000235:genetics*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D005996:Nitroglycerin; D012039:Regional Blood Flow / Q000187:drug effects; D014463:Ultrasonography; D014665:Vasodilator Agents
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D017311:Amlodipine; D005996:Nitroglycerin