Effect of lipid-lowering therapy with pravastatin on myocardial blood flowin young mildly hypercholesterolemic adults

Serum low-density lipoprotein cholesterol concentration is an important reg ulator of vascular reactivity. This double-blinded study examined the effec t of lipid-lowering therapy on myocardial vasodilatory function in young hy percholesterolemic but otherwise healthy men. Fifty-one men (age 35 +/- 4 y ears) with mild hypercholesterolemia (total cholesterol, 5.6 +/- 0.8 mM) we re randomly assigned to receive pravastatin, 40 mg/day, or placebo for 6 mo nths. Myocardial blood flow was measured at rest and during adenosine-induc ed hyperemia using positron emission tomography and oxygen-15-labeled water at baseline and after treatment. Pravastatin lowered low-density-lipoprote in cholesterol by 33% from 3.77 +/- 0.76 mM (p < 0.001), whereas placebo ha d 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. Despi te significant low-density-lipoprotein cholesterol lowering, resting and ad enosine-stimulated blood flow values remained similar at follow-up: 0.86 +/ - 0.23 and 3.79 +/- 1.31 vs. 0.78 +/- 0.20 and 3.20 +/- 0.86 ml/min per gra m, in the pravastatin and placebo groups, respectively. An improvement in a denosine-induced flow after pravastatin, but not after placebo, was seen on ly in a subgroup of subjects (n = 15) with relatively low adenosine flow (< 4.0 ml/min per gram) at baseline. Six months of cholesterol-lowering therap y with statin treatment has no overall significant effect on coronary vasod ilator capacity in healthy subjects with mildly elevated cholesterol levels . A controlled study is needed to further test whether improvement in coron ary function is obtained in subjects with initially reduced hyperemic flow response.