title: Two-week treatment with pravastatin improves ventriculo-vascular haemodynamic interactions in young men with type 1 diabetes.
abstract: Young patients with diabetes but without established vascular disease have altered conduit and resistance artery reactivity. Early endothelial dysfunction is an initial step in atherogenesis: reductions in nitric oxide (NO) production in these vascular beds are implicated. The study aim was two-fold: first, to detect baseline abnormalities in cardiac function, conduit vessels and the microcirculation using applanation tonometry, brachial artery ultrasound and laser Doppler fluximetry, respectively; and second, to investigate any modification in these parameters with the use of pravastatin. Nine young men with diabetes and normoalbuminuria were randomised in a double-blind cross-over fashion to placebo or pravastatin (40 mg) treatment for two weeks. They underwent scans on three separate occasions. Control patients (n=12) underwent a baseline scan but were not given any drug treatment. It was found that patients with diabetes had significantly higher systolic and diastolic blood pressures, heart rate and Buckberg index (propensity to myocardial ischaemia). Brachial artery reactivity and microcirculatory dilation were both reduced. Levels of von Willebrand Factor, a marker of endothelial damage, were also elevated. Pravastatin treatment restored these sub-clinical abnormalities towards normal levels. In conclusion, pravastatin improves vascular abnormalities in young male patients with diabetes through alterations in microcirculation and conduit vessel function, with secondary myocardial effects. This may be of benefit in preventing end-organ injury.
authors.affiliation: Department of Surgery, Beaumont Hospital, Dublin, Ireland. rowcasey@rcsi.ie
authors.forename: Rowan G
authors.initials: RG
authors.lastname: Casey
authors.forename: Myles
authors.initials: M
authors.lastname: Joyce
authors.forename: Kevin
authors.initials: K
authors.lastname: Moore
authors.forename: Chris
authors.initials: C
authors.lastname: Thompson
authors.forename: Patricia
authors.initials: P
authors.lastname: Fitzgerald
authors.forename: David J
authors.initials: DJ
authors.lastname: Bouchier-Hayes
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D010865:Pilot Projects; D017035:Pravastatin / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin