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CLINICAL STUDY: RISK FACTORS

The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia

^a University of Wisconsin Medical School, Madison, Wisconsin, USA

Manuscript received February 7, 2001; revised manuscript received July 31, 2001, accepted August 20, 2001.

^* Reprint requests and correspondence: Dr. James H. Stein, Section of Cardiovascular Medicine, University of Wisconsin Medical School, H6/315 Clinical Science Center (3248), 600 Highland Avenue, Madison, Wisconsin 53792 USA
jhs{at}medicine.wisc.edu

OBJECTIVES

The goal of this study was to determine the long-term effects of statins and antioxidant vitamins on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia.

BACKGROUND

Lipid-lowering therapy and antioxidant vitamins improve endothelium-dependent vasodilation in young and middle-aged adults with hypercholesterolemia, but their effects in older adults are not known.

METHODS

Two double-blind, placebo-controlled studies were performed in individuals 70 years old with low-density lipoprotein cholesterol (LDL-C) 140 mg/dl. In the first study, 37 subjects were randomized to receive (group 1) pravastatin for six months then pravastatin and vitamin E for six additional months or (group 2) vitamin E for six months, then pravastatin and vitamin E for six additional months. In the second study, additional 17 subjects sequentially received simvastatin for six months, then simvastatin and vitamins C and E for six additional months. Flow-mediated vasodilation of the brachial artery was measured by high-resolution ultrasound.

RESULTS

At baseline, subjects in both studies were similar in age (mean ± SD, 75.8 ± 4.2 years), gender, systolic blood pressure, total cholesterol (261.6 ± 37.4 mg/dl), LDL-C (180.3 ± 28.1 mg/dl), high-density lipoprotein cholesterol and triglycerides levels. Flow-mediated vasodilation was severely impaired (2.2 ± 3.9%). Both statins reduced total and LDL-C levels (p < 0.001); however, neither statin, antioxidant vitamin regimen nor the combination of statins and antioxidant vitamins improved flow-mediated vasodilation of the brachial artery. At baseline, nitroglycerin-mediated vasodilation also was impaired (10.7 ± 5.6%) and did not change in either study.

CONCLUSIONS

Older adults with hypercholesterolemia have impaired flow-mediated vasodilation of the brachial artery that does not improve after one year of therapy with statins and antioxidant vitamins, despite significant lipid-lowering.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   CHD = coronary heart disease   FMD = flow-mediated vasodilation   HDL-C = high-density lipoprotein cholesterol   LDL-C = low-density lipoprotein cholesterol   NTG = nitroglycerin   NTGMD = nitroglycerin-mediated vasodilation   PAVES = Pravastatin and Vitamin E in Seniors study   SAVES = Simvastatin, Ascorbate and Vitamin E in Seniors study

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