ascorbic-acid and Arterial-Occlusive-Diseases

Patients with peripheral arterial disease (PAD) have high rates of cardiovascular morbidity and mortality, including that caused by associated coronary heart disease and cerebrovascular disease. Previous studies have shown that coagulation parameters are altered in PAD and that altered coagulation may play a critical role in the susceptibility to cardiovascular complications in PAD. It is therefore important to assess the effect of secondary prevention measures on coagulation in patients with PAD. The Arterial Disease Multiple Intervention Trial (ADMIT), a multicenter, randomized, placebo-controlled trial, was conducted to determine the feasibility of a combined lipid-modifying, antioxidant, and antithrombotic treatment regimen in patients with PAD. The objective of this study was to assess the effect of the ADMIT interventions on coagulation.. ADMIT participants were randomly assigned to low-dose warfarin, niacin, and antioxidant vitamin cocktail or corresponding placebos in a 2 x 2 x 2 factorial design. Specialized coagulation studies were performed in a subset of 80 ADMIT participants at baseline and after 12 months of treatment.. Low-dose warfarin (1 to 4 mg/d) resulted in a significant decrease in factor VIIc (P <.001) and in plasma F1.2 (P =.001). Unexpectedly, niacin treatment also resulted in significant decrease in both fibrinogen (48 mg/dL; P <.001) and F1.2 (P =.04). von Willebrand factor increased after antioxidant vitamin treatment (P =.04).. A regimen of low-dose warfarin effectively modifies coagulation in patients with PAD. Niacin also favorably modifies fibrinogen and plasma F1.2. Niacin, in addition to its lipid effects, modifies abnormal coagulation factors that accompany PAD.

Topics: Aged; Anticoagulants; Antioxidants; Arterial Occlusive Diseases; Ascorbic Acid; beta Carotene; Blood Coagulation; Disease Progression; Drug Therapy, Combination; Feasibility Studies; Female; Fibrinogen; Humans; Male; Niacin; Vitamin E; von Willebrand Factor; Warfarin

We prospectively evaluated the relationship between dietary fiber and peripheral arterial disease risk (PAD) among 46,032 men, aged 40 to 75 y, in 1986. Subjects answered a vascular disease questionnaire and completed a validated 131-item food frequency questionnaire, and were free of PAD, cardiovascular disease and diabetes. During 12 y of follow-up 308 incident PAD cases were documented. After adjusting for age, smoking, hypertension, hypercholesterolemia, family history of early coronary heart disease, alcohol consumption, BMI, physical activity and energy intake, PAD risk in each quintile of cereal fiber intake compared with the lowest quintile was 0.69, 95% CI 0.49-0.97 for quintile 2; 0.65, 95% CI 0.45-0.94 for quintile 3; 0.68, 95% CI 0.47-0.98 for quintile 4; and 0.67, 95% CI 0.47-0.97 for quintile 5. In a nonlinear model the overall inverse association (P = 0.02) and nonlinear components (P = 0.03) were significant. Fruit, vegetable and total fiber intakes were not associated with PAD risk. These results suggest an inverse association between cereal fiber intake and PAD risk in men. Increasing cereal fiber intake may prevent PAD.

Topics: Adult; Aged; Arterial Occlusive Diseases; Ascorbic Acid; Body Mass Index; Boston; Dietary Fiber; Dietary Supplements; Feeding Behavior; Humans; Male; Middle Aged; Myocardial Infarction; Patient Selection; Reproducibility of Results; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin E

This study examined cross-sectionally the association of dietary beta-carotene, vitamin C, and vitamin E with peripheral arterial disease in Rotterdam, the Netherlands (1990--1993). The 4,367 subjects from the Rotterdam Study were aged 55--94 years and had no previous cardiovascular disease at baseline. Diet was assessed with a food frequency questionnaire. Peripheral arterial disease was defined as an ankle-arm systolic blood pressure index (AAI) of < or = 0.9 and was present in 204 men and 370 women. In multivariate-adjusted logistic regression analyses, vitamin C intake was significantly inversely associated with peripheral arterial disease in women (highest vs. lowest quartile: relative risk = 0.64, 95% confidence interval (CI): 0.48, 0.89; p(trend) = 0.006), and a 100-mg increase in intake was associated with a 0.013 AAI increase (95% CI: 0.001, 0.025). In men, vitamin E intake was inversely associated with peripheral arterial disease (relative risk = 0.67, 95% CI: 0.44, 1.03; p(trend) = 0.067); a 10-mg increase in intake was associated with a 0.015 AAI increase (95% CI: 0.001, 0.031). Whether these differences in antioxidant intake and the risk of a low AAI and of peripheral arterial disease between sexes are attributable to a different food pattern for men compared with women remains to be elucidated.

Topics: Aged; Aged, 80 and over; Antioxidants; Arterial Occlusive Diseases; Ascorbic Acid; beta Carotene; Cross-Sectional Studies; Diet; Diet Surveys; Energy Metabolism; Female; Humans; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Netherlands; Peripheral Vascular Diseases; Population Surveillance; Prospective Studies; Risk Factors; Sex Distribution; Surveys and Questionnaires; Urban Health; Vitamin E

Vascular endothelial growth factor (VEGF) has been implicated in the reendothelialization of the vascular wall after balloon injury. This study investigated whether thrombin, which is formed during activation of the coagulation cascade at sites of vascular injury, upregulates VEGF expression in vascular smooth muscle cells (VSMCs). VEGF expression was assessed in native and cultured VSMCs by Northern blot analysis and reverse transcription-polymerase chain reaction and the release of VEGF protein by immunoassay. alpha-Thrombin time- and concentration-dependently increased VEGF mRNA levels, mainly that mRNA coding for the soluble splice variant VEGF(164/165), and stimulated the release of VEGF protein. These effects required the proteolytic activity of thrombin and were mimicked by a thrombin receptor activating-peptide. Upregulation of VEGF expression was also induced by conditioned medium from alpha-thrombin-stimulated VSMCs. Both the early and the delayed alpha-thrombin-induced VEGF expressions were attenuated by antioxidants and by diphenyleneiodonium. alpha-Thrombin-induced VEGF release was significantly reduced by a platelet-derived growth factor (PDGF)-, a transforming growth factor (TGF)-beta-, and a basic fibroblast growth factor (bFGF)-neutralizing antibody. Thrombin caused a redox-sensitive upregulation of expression of VEGF in VSMCs through a direct and an indirect effect, which was dependent on the endogenous formation of PDGF, TGF-beta, and bFGF. Upregulation of VEGF expression may represent an important mechanism by which the coagulation cascade contributes to the regeneration of the endothelial lining at sites of balloon injury.

Topics: Acetylcysteine; Angioplasty, Balloon; Animals; Antioxidants; Arterial Occlusive Diseases; Ascorbic Acid; Cells, Cultured; Endothelial Growth Factors; Fibroblast Growth Factor 2; Humans; Kinetics; Lymphokines; Male; Muscle, Smooth, Vascular; Platelet-Derived Growth Factor; Rats; Rats, Wistar; Reactive Oxygen Species; RNA, Messenger; Thrombin; Transcriptional Activation; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

1. The ability of EPC-K1 to improve myocardial infarction was evaluated in a rat model with coronary artery occlusion and reperfusion. 2. The myocardial infarct size was 30.5 +/- 1.7% by intravenous (i.v.) administration and 28.8 +/- 2.7% by intraduodenal (i.d.) administration of the saline EPC-K1 at doses between 1 and 10 mg/kg, i.v. and at doses between 50 and 200 mg/kg, i.d., reduced myocardial infarct size dose dependently. Significant reduction in myocardial infarct size was found at a dose of 10 mg/kg, i.v., and 200 mg/kg, i.d.

Topics: Animals; Antioxidants; Arterial Occlusive Diseases; Ascorbic Acid; Combined Modality Therapy; Coronary Disease; Disease Models, Animal; Free Radical Scavengers; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Rats; Rats, Wistar; Vitamin E

Experience of treatment of 215 patients with obliterating diseases of the vessels in terminal stage using the method of transcatheter medicinal mixtures infusion was summarized. Use of original method permitted to avert the gangrene appearance in 65% of patients, to lower the amputation level--in 15%; in 20% of patients the result was unsatisfactory, high limb amputation was conducted to them.

Topics: Adult; Aged; Amputation, Surgical; Anti-Bacterial Agents; Arterial Occlusive Diseases; Ascorbic Acid; Combined Modality Therapy; Dextrans; Drug Combinations; Heparin; Humans; Infusions, Intra-Arterial; Ischemia; Leg; Middle Aged; Nicergoline; Papaverine; Pentoxifylline; Procaine; Vasodilator Agents; Vitamin B Complex

Altered trace elements and ascorbic acid metabolism have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, their role in the disease process, or the effect of atherosclerosis on their tissue levels within plaque, is poorly understood. The present study analyzes the concentrations of Fe, Cu, Zn, and Mn, and ascorbic acid and superoxide dismutase (SOD) activity in tissue samples from 29 patients with abdominal aortic aneurysms (AAA) and 14 patients with atherosclerotic occlusive disease (AOD). It was observed that the Fe and Mn concentrations in AAA and AOD tissue were higher than the levels in nondiseased control aorta, whereas Cu and Zn levels in AAA and AOD tissue were similar to the levels in controls. The Zn:Cu ratio was significantly lower in the AAA tissue in comparison to both AOD and control tissue. In addition, AAA and AOD tissue had low ascorbic acid levels and low Cu,Zn-SOD activity with Cu,Zn-SOD:Mn-SOD ratios of 0.27 and 0.19, respectively, compared to a ratio of 3.20 in control aorta. These data indicate that aorta affected by aneurysms and occlusive disease have altered trace element and ascorbic acid concentrations, as well as low Cu,Zn-SOD activity. Although these observations do not directly support the hypothesis that AAA is associated with aortic Cu deficiency they do suggest a role for oxygen radicals or increased lipid peroxidation in occlusive and aneurysmal disease of the aorta.

Topics: Adult; Aged; Aorta, Abdominal; Aortic Aneurysm; Arterial Occlusive Diseases; Ascorbic Acid; Humans; Middle Aged; Reference Values; Superoxide Dismutase; Trace Elements

Topics: Adrenal Cortex Hormones; Adult; Aged; Arterial Occlusive Diseases; Ascorbic Acid; Cerebrovascular Disorders; Child; Chorioretinitis; Edema; Female; Humans; Ketones; Male; Middle Aged; Retinal Artery; Retinal Degeneration; Retinal Diseases; Retinal Vessels; Rutin; Vitamin B Complex; Xanthines

Topics: Arterial Occlusive Diseases; Arteries; Ascorbic Acid; Blood; Ether; Histidine; Humans; Vitamins