Effects of initiation and acute withdrawal of statins on the neurovascular coupling mechanism in healthy, normocholesterolemic humans.
OBJECTIVE
Recent clinical trials imply increased risk of vascular events after statin withdrawal. There is evidence that this observation relates to an impaired nitric oxide system. The present analysis investigates the effect of initiation and withdrawal of statin therapy on resting and functionally activated cerebral hemodynamics in healthy young volunteers.


METHODS
Sixteen healthy students (aged 23.7+/-3.3 years, 10 male) were subjected to a placebo-controlled, double-blind crossover study with a washout phase between blocks of 4 weeks. In the verum group, 20 mg pravastatin was taken for 2 weeks followed by 40 mg for 4 weeks. Withdrawal effects were investigated the day after discontinuation. Total cholesterol levels, blood pressure, resting and evoked hemodynamic responses due to a visual stimulation task in the posterior cerebral artery were obtained at baseline and then weekly and the day after discontinuation.


RESULTS
In the verum group, cholesterol levels significantly decreased after 2 weeks (from 183+/-30 to 150+/-28 mg/dL; P<0.001) and then remained nearly stable (147+/-21 mg/dL after 6 weeks). Blood pressure, resting and evoked hemodynamic responses remained constant throughout the study. The day after statin withdrawal, evoked flow velocity responses were significantly lower (11+/-4% versus 13+/-5% at baseline; P<0.01) indicating inappropriate blood supply of active neurons.


CONCLUSIONS
Reduction in evoked flow velocity responses reflects reduced nitric oxide bioavailability and therefore supports molecular findings of acute statin withdrawal. Questions arise if the present data might give a link to reports of increased vascular events in patients at vascular risk after acute statin withdrawal.
Rosengarten
Bernhard
B
Department of Neurology, University Clinics of Giessen and Marburg, Am Steg 14, 35392 Giessen, Germany. bernhard.rosengarten@neuro.med.uni-giessen.de
Auch
Dieter
D
Kaps
Manfred
M
D000208:Acute Disease; D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D010919:Placebos; D017035:Pravastatin / Q000494:pharmacology
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D009569:Nitric Oxide; D002784:Cholesterol; D017035:Pravastatin