OBJECTIVES We sought to investigate the effects of intensive cholesterol reduction on large artery, stiffness and blood pressure in normolipidemic patients with isolated systolic hypertension (ISH). BACKGROUND Isolated systolic hypertension is associated with elevated cardiovascular morbidity and mortality, and is primarily, due to large artery stiffening, which has been independently related to cardiovascular mortality. Cholesterol-lowering therapy, has been efficacious in reducing arterial stiffness in patients with hypercholesterolemia, and thus may, be beneficial in ISH. METHODS In a randomized, double-blinded, cross-over study, design, 22 patients with stage I ISH received three months of atorvastatin therapy, (80 mg/day) and three months of placebo treatment. Systemic arterial compliance was measured noninvasively using carotid applanation tonometry and Doppler velocimetry of the ascending aorta. RESULTS Atorvastatin treatment reduced total and low-density lipoprotein cholesterol and triglyceride levels by 36 +/- 2% (p < 0.001), 48 +/- 3% (p < 0.001) and 23 +/- 5% (p = 0.003), respectively, and increased high density, lipoprotein cholesterol by 7 +/- 3% (p = 0.03). Systemic arterial compliance was higher after treatment (placebo vs. atorvastatin: 0.36 +/- 0.03 vs. 0.43 +/- 0.05 ml/mm Hg, p = 0.03). Brachial systolic blood pressure was lower after atorvastatin treatment (154 3 vs. 148 2 mm Hg, p = 0.03), as were mean (111 +/- 2 vs. 107 +/- 2 mm Hg, p = 0.04) and diastolic blood pressures (83 +/- 1 vs. 81 +/- 2 mm Hg, p = 0.04), There was a trend toward a reduction in pulse pressure (71 +/- 3 vs. 67 +/- 2 mm Hg, p = 0.08). CONCLUSIONS Intensive cholesterol reduction may be beneficial in the treatment of patients with ISH and normal lipid levels, through a reduction in large artery, stiffness. (J Am Coll Cardiol 2002; 39:1020-5) (C) 2002 by the American College of Cardiology Foundation.