EFFECT OF ANTIOXIDANT VITAMINS ON LOW-DENSITY-LIPOPROTEIN OXIDATION AND IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH HYPERCHOLESTEROLEMIA

Objectives. The aims of this study were to determine whether antioxida nt vitamins could reduce the susceptibility of low density lipoprotein (LDL) to oxidation and improve endothelium-dependent vasodilator resp onsiveness in patients with hypercholesterolemia. Background. Animals and humans with hypercholesterolemia have exhibited impaired endotheli um-dependent vasodilation. In vitro studies suggest that oxidatively m odified LDL can impair nitric oxide production. Methods. Forearm blood flow was measured with strain gauge plethysmography and brachial arte ry drug infusions in 19 patients, aged 52 +/- 9 sears, with hyperchole sterolemia (mean +/- SD total cholesterol 283 +/- 22 mg/dl, LDL 197 +/ - 31 mg/dl) and in 14 subjects, aged 48 +/- 8 years, with normal chole sterol levels (total cholesterol 169 +/- 20 mg/dl, LDL 102 +/- 25 mg/d l). Acetylcholine (7.5, 15 and 30 mu g/min) was utilized as an endothe lium-dependent vasodilator, and sodium nitroprusside (0.8, 1.6 and 3.2 mu g/min) was used to test endothelium-independent vasodilation. Oxid ative susceptibility of LDL was measured by a spectrophotometric assay of conjugated diene production after the addition of copper chloride. Hypercholesterolemic patients then received daily anti-oxidant vitami n supplements (beta carotene [30 mg], ascorbic acid [vitamin C] [1,000 mg], vitamin E [800 IU]) for 1 month, with repeat measurement of both forearm blood flow responsiveness to the same agonists and LDL oxidiz ability. Results. The maximal flow in response to acetylcholine was im paired in patients compared with that in normal subjects (9.8 +/- 7.8 vs. 15.9 +/- 8.1 ml/min per 100 ml, p = 0.03), with similar maximal fl ow responses to sodium nitroprusside (9.5 +/- 4.2 vs. 9.0 +/- 2.8 ml/m in per 100 ml, p = 0.72). After 1 month of vitamin therapy, the onset of LDL oxidation was prolonged over baseline measurements by 71 +/- 67 %, and the maximal rate of oxidation was decreased by 26 +/- 25% (both p < 0.001). However, the maximal forearm blood flow response to acety lcholine remained unchanged horn baseline values (maximal how after ac etylcholine 9.0 +/- 6.2 vs. 9.8 +/- 7.8 ml/min per 100 ml, p = 0.57). This study had 80% power (alpha 0.05) to exclude a 45% increase over b aseline value in acetylcholine-stimulated flow during vitamin therapy. Conclusions. Although 1 month of administration of antioxidant vitami n supplements in hypercholesterolemic patients reduced the susceptibil ity of LDL to oxidation, impairment in endothelial function tion remai ned unaltered. The use of nonvitamin antioxidants or concomitant reduc tion in LDL levels, as well as more sensitive techniques for measuring vascular responsiveness, may be required to show a beneficial effect on endothelial vasodilator function.