EFFECT OF ANTIOXIDANT VITAMINS ON LOW-DENSITY-LIPOPROTEIN OXIDATION AND IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH HYPERCHOLESTEROLEMIA
Dm. Gilligan et al., EFFECT OF ANTIOXIDANT VITAMINS ON LOW-DENSITY-LIPOPROTEIN OXIDATION AND IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH HYPERCHOLESTEROLEMIA, Journal of the American College of Cardiology, 24(7), 1994, pp. 1611-1617
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.