Effect of Lipid-Lowering Therapy with Pravastatin on Myocardial Blood Flow in Young Mildly Hypercholesterolemic Adults

Serum low-density lipoprotein cholesterol concentration is an important regulator of vascular reactivity. This double-blinded study examined the effect of lipid-lowering therapy on myocardial vasodilatory function in young hypercholesterolemic but otherwise healthy men. Fifty-one men (age 35 ± 4 years) with mild hypercholesterolemia (total cholesterol, 5.6 ± 0.8 m M) were randomly assigned to receive pravastatin, 40 mg/day, or placebo for 6 months. Myocardial blood flow was measured at rest and during adenosine-induced hyperemia using positron emission tomography and oxygen-15-labeled water at baseline and after treatment. Pravastatin lowered low-density-lipoprotein cholesterol by 33% from 3.77 ± 0.76 m M (p < 0.001), whereas placebo had no effect. At baseline, resting and adenosine-induced flow values were 0.85 ± 0.27 and 3.61 ± 1.00 ml/min per gram in the pravastatin group and 0.83 ± 0.18 and 3.17 ± 0.69 ml/min per gram in the placebo group. Despite significant low-density-lipoprotein cholesterol lowering, resting and adenosine-stimulated blood flow values remained similar at follow-up0.86 ± 0.23 and 3.79 ± 1.31 vs. 0.78 ± 0.20 and 3.20 ± 0.86 ml/min per gram, in the pravastatin and placebo groups, respectively. An improvement in adenosine-induced flow after pravastatin, but not after placebo, was seen only in a subgroup of subjects (n = 15) with relatively low adenosine flow (