ascorbic-acid and Coronary-Artery-Disease

Percutaneous coronary intervention (PCI) is the preferred treatment for acute coronary syndrome (ACS) secondary to atherosclerotic coronary artery disease. This nonsurgical procedure is also used for selective patients with stable angina. Although the procedure is essential for restoring blood flow, reperfusion can increase oxidative stress as a side effect. We address whether intravenous infusion of vitamin C (VC) prior to PCI provides a benefit for cardioprotection. A total of eight randomized controlled trials (RCT) reported in the literature were selected from 371 publications through systematic literature searches in six electronic databases. The data of VC effect on cardiac injury biomarkers and cardiac function were extracted from these trials adding up to a total of 1185 patients. VC administration reduced cardiac injury as measured by troponin and CK-MB elevations, along with increased antioxidant reservoir, reduced reactive oxygen species (ROS) and decreased inflammatory markers. Improvement of the left ventricular ejection fraction (LVEF) and telediastolic left ventricular volume (TLVV) showed a trend but inconclusive association with VC. Intravenous infusion of VC before PCI may serve as an effective method for cardioprotection against reperfusion injury.

Topics: Acute Coronary Syndrome; Antioxidants; Ascorbic Acid; Biomarkers; Coronary Artery Disease; Creatine Kinase, MB Form; Databases, Factual; Heart; Humans; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Stroke Volume; Troponin; Ventricular Function, Left

Oxidative stress is involved in the pathogenesis of atherosclerosis. A variety of antioxidants has been used in clinical studies, during the past few years, for the prevention and treatment of atherosclerosis. In small clinical studies it was found that both vitamins C and E may improve endothelial function in high risk patients. However, interventional trials have been controversial, with some positive findings, many null findings, and some suggestion of harm in certain high-risk populations. Therefore, treatment with antioxidant vitamins C and E should not be recommended for the prevention or treatment of coronary atherosclerosis. New antioxidant strategies are needed to clarify the exact role of antioxidant treatment in coronary atherosclerosis.

Topics: Animals; Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Coronary Artery Disease; Endothelium, Vascular; Humans; Oxidative Stress; Risk Factors; Vitamin E

Laboratory and observational studies suggest that antioxidant and B vitamin supplementation may prevent atherosclerosis. Although trials have not shown a benefit of these supplements on clinical cardiovascular events, it is unknown whether they affect the progression of atherosclerosis as measured by imaging techniques.. The objective was to perform a meta-analysis of randomized controlled trials of the effect of vitamin-mineral supplementation on atherosclerosis progression.. We searched the MEDLINE, EMBASE, and CENTRAL databases for relevant studies. No language restrictions were applied. We separately analyzed trials using antioxidants (vitamins E and C, beta-carotene, or selenium) and trials using B vitamins (folate, vitamin B-6, or vitamin B-12). The progression of atherosclerosis was evaluated by B-mode ultrasound, intravascular ultrasound, or angiography. Effect sizes were calculated for the difference in slope of atherosclerosis progression between participants assigned to supplements and those assigned to the control group.. In trials not involving percutaneous transluminal coronary angioplasty, the pooled effect size was -0.06 (95% CI: -0.20, 0.09; 7 trials) for antioxidants and -0.93 (95% CI: -2.11, 0.26; 4 trials) for B vitamins. In trials involving percutaneous transluminal coronary angioplasty, the pooled relative risk of restenosis was 0.82 (95% CI: 0.54, 1.26; 3 trials) for antioxidants and 0.84 (95% CI: 0.34, 2.07; 2 trials) for B vitamins.. Our meta-analysis showed no evidence of a protective effect of antioxidant or B vitamin supplements on the progression of atherosclerosis, thus providing a mechanistic explanation for their lack of effect on clinical cardiovascular events.

Topics: Adult; Aged; Angiography; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Atherosclerosis; beta Carotene; Coronary Artery Disease; Dietary Supplements; Disease Progression; Female; Folic Acid; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Selenium; Trace Elements; Ultrasonography, Interventional; Vitamin B 12; Vitamin B 6; Vitamin E; Vitamins

The vascular endothelium plays a crucial role in the physiology of blood vessels and the pathological processes of atherosclerotic disease and acute coronary syndromes. Endothelial dysfunction is the core problem; it is an impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide activity in the vessel wall, which results in impairment in the regulation of vascular homeostasis. Further understanding of its mechanisms of action and possible therapeutic targets will be of great importance. The group of antioxidant vitamins, A, C and E, would seem uniquely situated to reduce cardiovascular events by improving endothelial function by reducing the concentration of reactive oxygen species in the vessel wall and by preventing oxidative modification of low-density lipoprotein. Unfortunately, despite extensive studies in both observational and randomized trials, the weight of evidence points to little or no benefit from antioxidant therapy.

Topics: Antioxidants; Ascorbic Acid; Coronary Artery Disease; Endothelium, Vascular; Humans; Nitric Oxide; Vitamin A; Vitamin E

The current evidence does not support the indiscriminate use of vitamins A, C, or E or beta carotene to prevent or reduce cardiovascular disease. Despite a plausible theory that antioxidants can prevent diseases caused by oxidative damage, trials thus far have not proven this. In fact, some studies found antioxidants may be harmful in some people. We review important studies of the effects of four antioxidants (vitamins A, C, and E, and beta carotene) and analyze whether the current evidence supports or confirms or rejects the presumed protective role.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Coronary Artery Disease; Dietary Supplements; Female; Humans; Lipid Peroxidation; Male; Oxidation-Reduction; Oxidative Stress; Patient Education as Topic; Prognosis; Risk Assessment; Treatment Outcome; Vitamin A; Vitamin E

Research into the oxidation of lipoproteins has yielded many new insights into the pathogenesis of atherosclerosis. However, despite lipoprotein oxidation's biologically plausible role in atherogenesis, several studies have reported inconsistent effects of antioxidants on clinical coronary end points, in sharp contrast with the studies of lipid modification with the 3-hydroxy-3-methylglutaryl coenzyme A inhibitors, or statins. There appears to be little support for the use of antioxidants in coronary prevention. However, the picture remains incomplete. What are the limitations of available antioxidant studies and the agents used? Until the picture can be clarified, lipid modification with strategies proved to reduce the risk for coronary events, such as statins or dietary changes in the style of the Mediterranean diet, should be better implemented in clinical practice.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Probucol; Rabbits; Vitamin E

Oxidative stress is involved in the pathogenesis of atherosclerosis, while a variety of antioxidants has been used in clinical studies, during the past few years, for the prevention and treatment of atherosclerosis. In small clinical studies it was found that both vitamins C and E may improve endothelial function in patients with risk factors for atherosclerosis such as diabetes mellitus, smoking, hypertension, or hypercholesterolemia. However, the initial, hopeful reports regarding the beneficial role of antioxidant vitamins against atherosclerosis, derived from purely observational studies, were followed by the negative results of almost all large randomized trials. Therefore, treatment with antioxidant vitamins C and E should not be recommended for the prevention or treatment of coronary atherosclerosis. New antioxidant strategies are needed to clarify the exact role of antioxidant treatment in coronary atherosclerosis.

Topics: Adult; Aged; Aged, 80 and over; Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Coronary Artery Disease; Diabetes Complications; Diet; Endothelium, Vascular; Female; Follow-Up Studies; Free Radicals; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Oxidative Stress; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Risk Factors; Smoking; Time Factors; Vitamin E

Oxidative stress occurs when there is an imbalance between free radical production and antioxidant capacity. This may be due to increased free radical formation in the body and/or loss of normal antioxidant defenses. Oxidative stress has been associated with the development of cardiovascular disease. The role of antioxidants in the primary and secondary prevention of coronary heart disease is currently under study. Although epidemiologic evidence indicates that antioxidants may decrease cardiovascular risk, clinical trial data are not conclusive. Information regarding the use and benefits of antioxidants in persons with diabetes is limited. Persons with diabetes may be more prone to oxidative stress because hyperglycemia depletes natural antioxidants and facilitates the production of free radicals. In addition, other factors such as homocysteine, insulin resistance, and aging may be contributory. This article highlights landmark clinical trials that have examined the cardioprotective effect of antioxidants. Because these trials have not been designed to study persons with diabetes, and clinical trial data for this group are not available, correlational studies are also presented. Finally, the concept of oxidative stress, the antioxidant and pro-oxidant factors that may contribute to oxidative stress, and the consequences of oxidative stress in persons with type 2 diabetes are presented. Key words: antioxidants, clinical trials,

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Blood Glucose; Clinical Trials as Topic; Coronary Artery Disease; Diabetes Mellitus, Type 2; Ferritins; Homocysteine; Humans; Oxidative Stress; Reactive Oxygen Species; Vitamin E

This presentation reviews data from epidemiologic and clinical trials on antioxidant vitamins, angiotensin-converting enzyme inhibitors, and homocysteine and their effect on atherosclerotic cardiovascular disease. Each of these areas seems promising, but the results of large, on-going studies must be determined before definitive conclusions can be made as to the effectiveness of these therapies.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid; beta Carotene; Cohort Studies; Coronary Artery Disease; Female; Homocysteine; Humans; Male; Middle Aged; Oxidative Stress; Randomized Controlled Trials as Topic; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Coronary Artery Disease; Coronary Disease; Diet; Dietary Fats; Food, Fortified; Humans; Vitamin E

The oxidative modification of low density lipoprotein (LDL) may be an early step in atherogenesis. Furthermore, evidence of oxidized LDL has been found in vivo. The most persuasive evidence shows that supplementation of some animal models with antioxidants slows atherosclerosis. The purpose of this review is to examine the roles that vitamin E, vitamin C and beta-carotene may play in reducing LDL oxidation.. English language articles published since 1980, particularly from groups active in this field of research.. In vitro, animal, and human studies on antioxidants, LDL oxidation, and atherosclerosis were selected.. Vitamin E has shown the most consistent effects with regard to LDL oxidation. Beta-carotene appears to have only a mild or no effect on oxidizability. Ascorbate, although it is not lipophilic, can also reduce LDL oxidative susceptibility.. LDL oxidizability can be reduced by antioxidant nutrients. However, more research is needed to establish their utility in the prevention of coronary artery disease.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coronary Artery Disease; Humans; Lipoproteins, LDL; Oxidation-Reduction; Vitamin E

Some evidences have shown the role of antioxidant vitamins in preventing atrial fibrillation (AF) after coronary artery bypass grafting (CABG) surgery. We sought to determine the effect of oral vitamin C on the incidence of postoperative AF in patients undergoing elective isolated on-pump CABG surgery.. One-hundred patients who underwent isolated CABG surgery were prospectively assigned into two groups: Group 1 - 50 patients received 2 g of oral vitamin C before and 500 mg twice daily lasting for 5 days after surgery; Group 2 - 50 patients as the control group did not receive any. All patients were continuously monitored after surgery in the intensive careunit (ICU), and then Holter monitoring was implemented for 72 h.. The mean of patients' age was 61.31 ± 6.42 years. Postoperative AF occurred in 16 and 4 patients in control and treatment groups, respectively (32% vs. 8%, p = 0.003). The ICU stay was 1.79 ± 0.313 and 2.10 ± 0.61 days for vitamin C and control groups, respectively (p = 0.002). The hospital stay was significantly lower in vitamin C group compared with that of the control group (5.32 ± 0.59 vs. 5.74 ± 1.30 days, respectively, p = 0.041). Baseline erythrocyte sedimentation rate (OR 1.030, 95% CI 1.003-1.058, p = 0.030) and taking vitamin C (OR 8.068, 95% CI 1.783-36.517, p = 0.007) were the independent predictors of postoperative AF.. Oral vitamin C can be safely used to decrease the incidence of postoperative AF in patients undergoing elective isolated on-pump CABG surgery.

Topics: Administration, Oral; Ascorbic Acid; Atrial Fibrillation; Coronary Artery Bypass; Coronary Artery Disease; Dose-Response Relationship, Drug; Elective Surgical Procedures; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Treatment Outcome; Vitamins

This small study has determined the effect of vitamin C on myocardial reperfusion in patients undergoing elective percutaneous coronary intervention (PCI). This study was to explore whether antioxidant vitamin C infusion before the procedure is able to affect the incidence of periprocedural myocardial injury (PMI) in patients undergoing PCI.. In this prospective single-centre randomized study, 532 patients were randomized into 2 groups: the vitamin C group, which received a 3-g vitamin C infusion within 6 hours before PCI, and a control group, which received normal saline. The primary end point was the troponin I-defined PMI, and the second end point was the creatine kinase (CK)-MB-defined PMI. Separate analyses using both end points were performed. PMI was defined as an elevation of cardiac biomarker values (CK-MB or troponin I) > 5 times the upper limit of normal (ULN), alone or associated with chest pain or ST-segment or T-wave changes.. After PCI, the incidence of PMI was reduced, whether defined by troponin or by CK-MB, compared with the control group (troponin I, 10.9% vs 18.4%; P = 0.016; CK-MB, 4.2% vs 8.6%; P = 0.035). Logistic multivariate analysis showed that preprocedure use of vitamin C is an independent predictor of PMI either defined by troponin I (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.33-0.97; P = 0.037) or by CK-MB (OR, 0.37; 95% CI, 0.14-0.99; P = 0.048).. In patients undergoing elective PCI, preprocedure intravenous treatment with vitamin C is associated with less myocardial injury.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Coronary Angiography; Coronary Artery Disease; Creatine Kinase, MB Form; Elective Surgical Procedures; Electrocardiography; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Reperfusion Injury; Oxidative Stress; Percutaneous Coronary Intervention; Preoperative Care; Prospective Studies; Treatment Outcome; Troponin

We evaluated the vasodilatory effects of two antioxidants, vitamins C (ascorbic acid) and E (α-tocopherol), on radial artery and endothelium-dependent responses in patients awaiting coronary artery bypass surgery.. The study was performed in three groups. The first group took 2 g of vitamin C orally (n = 31, vitamin C group), the second group took 2 g of vitamin C with 600 mg of vitamin E orally (n = 31, vitamins C + E group), and the third group took no medication (n = 31, control group). After baseline measurements were taken of the radial artery lumen diameter, flow volume and lumen area in the non-dominant radial artery, occlusion was maintained for five minutes with a pressure cuff placed around the arm. The measurements were taken again at the time of deflating the cuff, and 60 seconds later. The measurements were repeated after medication in two of the groups and after placebo in the third group.. We compared values of the vitamin C group with those of the vitamins C + E group, and found that the latter were higher than those of the vitamin C group but not statistically significant. In the control group, there was no statistical difference.. Vitamin C or its combination with vitamin E significantly enhanced endothelium-dependent vasodilatation in the radial circulation of patients with coronary artery disease. Its combination with vitamin E was superior to vitamin C administration alone for endothelial enhancement but this difference was not statistically significant. We hypothesised that vitamin C or its combination with vitamin E may be used as antioxidants for arterial graft patency in patients undergoing coronary artery surgery.

Topics: Administration, Oral; Adult; Aged; Antioxidants; Ascorbic Acid; Coronary Artery Bypass; Coronary Artery Disease; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Radial Artery; Time Factors; Tissue and Organ Harvesting; Treatment Outcome; Turkey; Ultrasonography; Vascular Patency; Vasodilation; Vitamin E; Waiting Lists

To reduce the increase of oxidative stress and the upregulation of CD40L during stenting procedure using ascorbic acid infusion.. CD40L upregulation occurring after coronary percutaneous coronary intervention predicts vascular events but the underlying mechanism is still unclear.. Fifty-six patients undergoing elective coronary stenting were randomly allocated to intravenous infusion of the antioxidant ascorbic acid or placebo. Platelet CD40L and plasma levels of soluble CD40L and of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, were measured before and after coronary stenting. In vitro study was also done to measure reactive oxidant species and CD40L expression in platelets exposed to anoxia-reoxygenation.. Placebo-treated patients showed a significant increase of platelet CD40L, soluble CD40L and 8-hydroxy-2'-deoxyguanosine compared to baseline values. Patients given ascorbic acid showed no change of soluble CD40L and platelet CD40L but a significant decrease of 8-hydroxy-2'-deoxyguanosine. After 60 and 120 min, soluble CD40L, platelet CD40L and 8-hydroxy-2'-deoxyguanosine were significantly lower in the ascorbic acid-treated group compared to the placebo-treated one. A significant correlation between platelet CD40L and soluble CD40L and between soluble CD40L and 8-hydroxy-2'-deoxyguanosine was observed. Platelets, in vitro exposed to anoxia-reoxygenation, had a burst of ROS and an upregulation of CD40L that were inhibited by ascorbic acid or apocynin, an inhibitor of NADPH oxidase.. This study shows that in patients undergoing coronary stenting CD40L is upregulated with a mechanism which is likely mediated by oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetophenones; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Biomarkers; Blood Platelets; CD40 Ligand; Coronary Artery Disease; Deoxyguanosine; Enzyme Inhibitors; Female; Flow Cytometry; Humans; Infusions, Intravenous; Italy; Linear Models; Male; Middle Aged; NADPH Oxidases; Oxidative Stress; Pilot Projects; Placebos; Prospective Studies; Reactive Oxygen Species; Stents; Time Factors; Treatment Outcome; Up-Regulation

The aim of this study was to evaluate the effect of high-dose allopurinol on vascular oxidative stress (OS) and endothelial function in subjects with stable coronary artery disease (CAD).. Allopurinol, a xanthine oxidase inhibitor, prolongs the time to chest pain during exercise in angina. We sought to ascertain whether allopurinol also improves endothelial dysfunction in optimally treated CAD patients, because such an effect might be of value to reduce future cardiovascular mortality. The mechanism of the anti-ischemic effect of allopurinol could be related to its reducing xanthine oxidase-induced OS, and our second aim was to see whether allopurinol really does reduce vascular tissue OS in CAD patients.. A randomized, double-blind, placebo-controlled, crossover study was conducted in 80 patients with CAD, comparing allopurinol (600 mg/day) with placebo. Endothelial function was assessed by forearm venous occlusion plethysmography, flow-mediated dilation, and pulse wave analysis. Vascular OS was assessed by intra-arterial co-infusion of vitamin C and acetylcholine.. Compared with placebo, allopurinol significantly improved endothelium-dependent vasodilation, by both forearm venous occlusion plethysmography (93 ± 67% vs. 145 ± 106%, p = 0.006) and flow-mediated dilation (4.2 ± 1.8% vs. 5.4 ± 1.7%, p < 0.001). Vascular oxidative stress was completely abolished by allopurinol. Central augmentation index improved significantly with allopurinol (2.6 ± 7.0%, p < 0.001) but not with placebo.. Our study demonstrates that, in optimally treated CAD patients, high-dose allopurinol profoundly reduces vascular tissue OS and improves 3 different measures of vascular/endothelial dysfunction. The former effect on OS might underpin the anti-ischemic effect of allopurinol in CAD. Both effects (on OS and endothelial dysfunction) increase the likelihood that high-dose allopurinol might reduce future cardiovascular mortality in CAD, over and above existing optimum therapy. (Exploring the therapeutic potential of xanthine oxidase inhibitor allopurinol in angina; ISRCTN15253766).

Topics: Aged; Allopurinol; Angina Pectoris; Antioxidants; Ascorbic Acid; Blood Flow Velocity; Brachial Artery; Coronary Artery Disease; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Endothelium, Vascular; Enzyme Inhibitors; F2-Isoprostanes; Female; Humans; Lipoproteins, LDL; Male; Natriuretic Peptide, Brain; Oxidative Stress; Plethysmography; Regional Blood Flow; Ultrasonography

Topics: Angioplasty, Balloon, Coronary; Ascorbic Acid; Coronary Artery Disease; Disease Progression; Follow-Up Studies; Heart Transplantation; Humans; Immunosuppressive Agents; Intention to Treat Analysis; Tunica Intima; Vascular Diseases; Vitamin E

An imbalance between the lipid peroxidation process and antioxidative protection is associated with the pathophysiology of coronary artery disease (CAD). The authors aimed to determine the relationship between the contributors of antioxidant protection, such as paraoxonase-1 (PON1) activity, albumin, vitamin C and ceruloplasmin (CP) levels, and lipid peroxidation indicators.. In the present study, the activity of PON1 was measured, together with serum concentrations of a variety of lipid constituents, albumin, vitamin C and CP levels, and lipid peroxidation indicators (conjugated dienes [CDs] and thiobarbituric acid-reactive substances [TBARS]). Data were gathered from 26 nondiabetic, angiographically proven, Turkish CAD patients and 26 healthy controls living in the Antalya region (Turkey).. CAD patients had significantly lower PON1 activity, high-density lipoprotein cholesterol, vitamin C and albumin concentrations, and higher CP, CD and TBARS concentrations than the controls. In the entire study population (n=52), serum CP levels were positively correlated with TBARS and CD levels, and negatively correlated with albumin and vitamin C levels, as well as with PON1 activity. On multiple logistic regression analysis, risk factors associated with CAD included high CP and low albumin levels.. CAD patients and controls were matched for age and sex, and high CP and low albumin levels were found to be independent risk factors for CAD. The present data gathered from the study group living in the Antalya region verifies that in CAD patients, CP impairs the oxidant-antioxidant balance in favour of the oxidants.

Topics: Albumins; Aryldialkylphosphatase; Ascorbic Acid; Case-Control Studies; Ceruloplasmin; Coronary Artery Disease; Female; Humans; Lipid Peroxidation; Lipoproteins, HDL; Male; Middle Aged; Risk Factors; Turkey

We measured flow-mediated dilation (FMD) by high-resolution brachial ultrasound in 61 women who participated in the Women's Angiographic Vitamin and Estrogen (WAVE) trial, a randomized controlled trial. There were no significant differences in the baseline demographics of women receiving hormone therapy (0.625 mg/day of conjugated equine estrogen plus 2.5mg of medroxyprogesterone acetate for women who had not had a hysterectomy) or placebo; or vitamins (400 IU of Vitamin E and 500 mg of Vitamin C twice daily) or placebo. Baseline FMD was impaired in all subjects (3.3+/-7.6%). Neither hormone therapy (4.1+/-5.2% at baseline, 4.2+/-5.0% at 3 months, and 4.1+/-6.5% at 34 months) nor antioxidant vitamins (3.0+/-8.3% at baseline; 3.5+/-4.6% at 3 months; 3.1+/-7.6% at 34 months) improved FMD (all p-values=NS). Endothelium-independent vasodilation, induced by nitroglycerin (NTG) was similar at baseline and was not affected by either therapy. In univariate and multivariate analysis, neither hormone therapy nor antioxidant vitamins were associated with FMD. Women with established coronary artery disease have impaired flow-mediated vasodilation of the brachial artery that does not improve after 3 months or up to 34 months of treatment with postmenopausal hormone therapy or antioxidant vitamins.

Topics: Aged; Antioxidants; Ascorbic Acid; Coronary Artery Disease; Endothelium, Vascular; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Humans; Medroxyprogesterone Acetate; Middle Aged; Multivariate Analysis; Postmenopause; Treatment Failure; Vasodilation; Vitamin E

Lipid lowering with statins prevents adverse cardiac events. Both lipid-lowering and antioxidant therapies may favorably affect vasomotor function and thereby improve ischemia.. In a randomized, double-blind, placebo-controlled trial, 300 patients with stable coronary disease, a positive exercise treadmill test, 48-hour ambulatory ECG with > or =1 episode of ischemia, and fasting total cholesterol of 180 to 250 mg/dL were assigned to 1-year treatment with intensive atorvastatin to reduce LDL to <80 mg/dL (n=96), intensive atorvastatin to reduce LDL to <80 mg/dL plus antioxidant vitamins C (1000 mg/d) and E (800 mg/d) (n=101), or diet and low-dose lovastatin, if needed, to reduce LDL to <130 mg/dL (n=103; control group). Ischemia end points, including ambulatory ECG monitoring and exercise treadmill testing, and endothelial assessment using brachial artery flow-mediated dilation were obtained at baseline and at 6 and 12 months. Baseline characteristics were similar in all groups. LDL decreased from approximately 153 mg/dL at baseline in the 2 atorvastatin groups to approximately 83 mg/dL at 12 months (each P<0.0001) and from 147 to 120 mg/dL in the control group (P<0.0001). During ambulatory ECG monitoring, mean number of ischemic episodes per 48 hours decreased 31% to 61% in each group (each P<0.001; P=0.15 across groups), without a change in daily heart rate activity. Mean duration of ischemia for 48 hours decreased 26% to 62% in each group (each P<0.001; P=0.06 across groups). Mean exercise duration to 1-mm ST-segment depression significantly increased in each group, but total exercise duration and mean sum of maximum ST depression were unchanged. Angina frequency decreased in each group. There was no incremental effect of supplemental vitamins C and E on any ischemia outcome. Flow-mediated dilation studies indicated no meaningful changes.. Intensive lipid lowering with atorvastatin to an LDL level of 80 mg/dL, with or without antioxidant vitamins, does not provide any further benefits in ambulatory ischemia, exercise time to onset of ischemia, and angina frequency than moderate lipid lowering with diet and low-dose lovastatin to an LDL level of <120 mg/dL.

Topics: Angina Pectoris; Antioxidants; Ascorbic Acid; Atorvastatin; Coronary Artery Disease; Diet Therapy; Dose-Response Relationship, Drug; Exercise Test; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipid Metabolism; Lipids; Lipoproteins, LDL; Male; Myocardial Ischemia; Pyrroles; Vasomotor System; Vitamin E

We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease (ASCVD) events.. The electron beam computed tomography-derived coronary calcium score predicts coronary disease events. Small, uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events, but controlled, scientific demonstration of these effects is lacking.. We conducted a double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg daily, vitamin C 1 g daily, and vitamin E (alpha-tocopherol) 1,000 U daily, versus matching placebos in 1,005 asymptomatic, apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender. All study participants also received aspirin 81 mg daily. Mean duration of treatment was 4.3 years.. Treatment reduced total cholesterol by 26.5% to 30.4% (p < 0.0001), low-density lipoprotein cholesterol by 39.1% to 43.4% (p < 0.0001), and triglycerides by 11.2% to 17.0% (p < or = 0.02) but had no effect (p = 0.80) on progression of coronary calcium score (Agatston method). Treatment also failed to significantly reduce the primary end point, a composite of all ASCVD events (6.9% vs. 9.9%, p = 0.08). Event rates were related to baseline calcium score (pre-specified analysis) and may have been reduced in a subgroup of participants with baseline calcium score >400 (8.7% vs. 15.0%, p = 0.046 [not a pre-specified analysis]).. Treatment with alpha-tocopherol, vitamin C, and low doses of atorvastatin (20 mg once daily) did not affect the progression of coronary calcification. Treatment may have reduced ASCVD events, especially in subjects with calcium scores >400, but these effects did not achieve conventional levels of statistical significance.

Topics: Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Aspirin; Atorvastatin; Calcinosis; Coronary Artery Disease; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyrroles; Tomography, X-Ray Computed

We investigated the effects of oral L-arginine on endothelial function, intravascular oxidative stress, and circulating inflammatory markers in patients with stable coronary artery disease (CAD).. Thirty-one stable CAD patients were randomly assigned to oral L-arginine (10 g) or vitamin C (500 mg, an antioxidant, as active control) daily for 4 weeks, with crossover to the alternate therapy after 2 weeks off therapy, in this study. Brachial artery endothelial function studies were performed and serum concentrations of lipids and inflammatory markers were measured at baseline, at the end of each 4-week treatment period and at the 2-week wash-out period. Susceptibility of low-density lipoprotein (LDL) particles to oxidation, a marker of oxidative stress, was determined in 11 patients at random before and after 4-week treatment of oral L-arginine.. We demonstrates that consumption of either L-arginine or vitamin C significantly increased brachial artery flow-mediated dilatation (mean diameter change from baseline of 4.87%, P<0.0001 and of 3.17%, P=0.0003, respectively). Neither oral L-arginine nor vitamin C affected lipid profiles and circulating levels of inflammatory markers. However, in the 11 patients whose LDL susceptibility to oxidation was determined, lag time significantly increased by 27.1% (P=0.045) after consumption of L-arginine for 4 weeks.. Oral L-arginine supplement improved endothelial function and reduced LDL oxidation in stable CAD patients.

Topics: Administration, Oral; Arginine; Ascorbic Acid; Cohort Studies; Coronary Artery Disease; Cross-Over Studies; Endothelium, Vascular; Female; Humans; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Safety

To assess the effects of intravenous vitamin C administration on the vasomotor responses to intracoronary L-arginine infusion in epicardial coronary arteries.. 28 patients with coronary artery disease and stable angina were enrolled in the study. Eight patients received intracoronary infusions of 150 micromol/min L-arginine before and after intravenous infusion of vitamin C, 10 patients received intracoronary infusions of 150 micromol/min L-arginine before and after intravenous infusion of normal saline, and 10 patients received intracoronary normal saline before and after intravenous infusion of vitamin C. The diameter of proximal and distal coronary artery segments was measured by quantitative angiography.. Infusion of L-arginine caused significant dilatation of both proximal (4.87 (0.96)%, p < 0.01 v normal saline) and distal (6.33 (1.38)%, p < 0.01 v normal saline) coronary segments. Co-infusion of vitamin C and L-arginine dilated proximal coronary segments by 8.68 (1.40)% (p < 0.01 v normal saline, p < 0.01 v L-arginine) and distal segments by 13.07 (2.15)% (p < 0.01 v normal saline, p < 0.01 v L-arginine). Intravenous infusion of vitamin C caused a borderline increase in proximal and distal coronary segment diameters (1.93 (0.76)% and 2.09 (1.28)%, respectively, not significant).. L-arginine dependent coronary segment vasodilatation was augmented by the antioxidant vitamin C in patients with coronary artery disease. Thus, vitamin C may have beneficial effects on nitric oxide bioavailability induced by L-arginine.

Topics: Angina Pectoris; Antioxidants; Arginine; Ascorbic Acid; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug Combinations; Drug Interactions; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Nitric Oxide; Vasodilation

Nitric oxide (NO)- and prostacyclin-independent vasodilatation in several vascular beds has been linked to the activation of cytochrome P450 (CYP) epoxygenases expressed in endothelial cells. However, these enzymes, which generate vasodilator epoxyeicosatrienoic acids, may also produce oxygen-derived free radicals, which attenuate the bioavailability of NO. Here, we studied the involvement of CYP 2C9 in modulating endothelium-dependent and -independent changes in forearm blood flow (FBF) in healthy volunteers and in patients with manifest coronary artery disease.. The effects of sulfaphenazole, a selective inhibitor of CYP 2C9, on endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside, SNP) FBF responses were measured by venous occlusion plethysmography in 5 healthy subjects and in 16 patients with angiographically documented stable coronary artery disease. Sulfaphenazole did not modify FBF responses to acetylcholine or SNP in healthy subjects. In contrast, sulfaphenazole markedly and dose-dependently enhanced the FBF response to acetylcholine without affecting the response to SNP. Vitamin C also increased the FBF response to acetylcholine, but this effect was further potentiated by sulfaphenazole. In the presence of N(omega)-monomethyl-l-arginine, sulfaphenazole failed to significantly improve acetylcholine-induced vasodilatation. The oxidation of serum proteins was enhanced in patients with coronary artery disease, and this effect was significantly attenuated by sulfaphenazole.. The CYP 2C9 inhibitor sulfaphenazole enhances endothelium-dependent vasodilator responses in patients with manifest coronary artery disease. This effect seems to be related to an increase in the bioavailability of NO, probably as a consequence of an attenuated generation of reactive oxygen species by CYP 2C9 in endothelial cells.

Topics: Acetylcholine; Adult; Aryl Hydrocarbon Hydroxylases; Ascorbic Acid; Blood Proteins; Coronary Artery Disease; Cytochrome P-450 CYP2C9; Endothelium, Vascular; Enzyme Inhibitors; Forearm; Humans; Male; Middle Aged; Nitric Oxide; omega-N-Methylarginine; Oxidation-Reduction; Regional Blood Flow; Sulfaphenazole; Vasodilation; Vasodilator Agents

Antioxidant trials have not demonstrated efficacy in slowing cardiovascular disease but could not rule out benefit for specific patient subgroups. Antioxidant therapy reduces LDL oxidizability in haptoglobin 1 allele homozygotes (Hp 1-1), but not in individuals with the haptoglobin 2 allele (Hp 2-1 or Hp 2-2). We therefore hypothesized that haptoglobin type would be predictive of the effect of vitamin therapy on coronary atherosclerosis as assessed by angiography.. We tested this hypothesis in the Women's Angiographic Vitamin and Estrogen (WAVE) trial, a prospective angiographic study of vitamins C and E with or without hormone replacement therapy (HRT) in postmenopausal women. Haptoglobin type was determined in 299 women who underwent baseline and follow-up angiography. The annualized change in the minimum luminal diameter (MLD) was examined in analyses stratified by vitamin use, haptoglobin type, and diabetes status.. We found a significant benefit on the change in MLD with vitamin therapy as compared with placebo in Hp 1-1 subjects (0.079 +/- 0.040 mm, P = 0.049). This benefit was more marked in diabetic subjects (0.149 +/- 0.064 mm, P = 0.021). On the other hand, there was a trend toward a more rapid decrease in MLD with vitamin therapy in Hp 2-2 subjects, which was more marked in diabetic subjects (0.128 +/- 0.057 mm, P = 0.027). HRT had no effect on these outcomes.. The relative benefit or harm of vitamin therapy on the progression of coronary artery stenoses in women in the WAVE study was dependent on haptoglobin type. This influence of haptoglobin type seemed to be stronger in women with diabetes.

Topics: Aged; Antioxidants; Ascorbic Acid; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Disease Progression; Double-Blind Method; Female; Haptoglobins; Humans; Lipids; Male; Middle Aged; Phenotype; Postmenopause; Prospective Studies; Vitamin E

Plasma vitamin A, C and E levels and erythrocyte antioxidant enzyme activities were investigated in type I and type II diabetic subjects with and without complications, i.e., hypertension, coronary artery disease and renal failure. Reverse phase HPLC was used to quantify vitamin A and E levels. We observed that the vitamin C levels were not significantly different between control and diabetic subjects. However, vitamin A and E levels were significantly lower in type I and type II diabetic subjects compared to controls. Superoxide dismutase (SOD) activity was significantly lower in type II, but not in type I, diabetic patients compared to controls. Interestingly, glutathione reductase and peroxidase activities were diminished in type I, but not in type II, diabetic subjects as compared to controls. Catalase activity was lower in both types of diabetic patients in comparison with their respective controls. Altogether these results suggest that diabetes mellitus may be associated with altered antioxidant status regardless to various complications.

Topics: Adult; Antioxidants; Ascorbic Acid; Catalase; Chromatography, High Pressure Liquid; Coronary Artery Disease; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Erythrocytes; Female; Glutathione Peroxidase; Glutathione Reductase; Humans; Hypertension; Male; Middle Aged; Renal Insufficiency; Superoxide Dismutase; Vitamin A; Vitamin E; Vitamins

Endothelial dysfunction has been described in patients with coronary artery disease (CAD) or chronic heart failure (CHF). Vitamin C administration leads to an improvement of endothelial function by reducing elevated levels of reactive oxygen species. It remains unclear, however, whether the degree of endothelial dysfunction caused by oxidative stress differs between CAD and CHF because of ischemic (ICM) or dilated cardiomyopathy (DCM).. In patients with CAD (n = 9; left ventricular ejection fraction [LVEF], 64% +/- 3%), ICM (n = 9; LVEF, 25% +/- 4%), DCM (n = 9; LVEF, 25% +/- 3%), and healthy subjects (HS; n = 5; LVEF, 66% +/- 5%) a change in internal radial artery diameter in response to acetylcholine (Ach; 15 and 30 microg/min) was measured with high-resolution ultrasound scanning during a co-infusion of normal saline or vitamin C (25 mg/min).. Ach-mediated vasodilation was blunted in patients with CHF (DCM, 90 +/- 20 microm; ICM, 86 +/- 20 microm) and patients with CAD (336 +/- 20 microm) as compared with HS (496 +/- 43 microm; P <.05 vs patients with DCM, ICM, CAD). Vitamin C co-infusion increased Ach-mediated vasodilation by 180 +/- 35 microm (to 270 +/- 30 microm) in DCM (P <.05 vs CAD, HS) and by 294 +/- 40 microm (to 380 +/- 20 microm) in ICM (P <.05 vs DCM, CAD, HS). In patients with CAD, vitamin C increased Ach-mediated vasodilation by 146 +/- 35 microm to normal values, whereas vascular diameter remained unchanged in HS (14 +/- 20 microm; P = not significant).. Acute vitamin C administration restored peripheral endothelial function in patients with CAD to normal values, whereas endothelial function remained attenuated in CHF, in particular in patients with DCM. These results suggest that in patients with CHF, factors other than oxidative stress (eg, cytokines) contribute to the pathologic endothelial function.

Topics: Acetylcholine; Aged; Ascorbic Acid; Cardiomyopathy, Dilated; Chronic Disease; Coronary Artery Disease; Drug Therapy, Combination; Endothelium, Vascular; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Nitroprusside; Oxidative Stress; Vasodilation; Vasodilator Agents

To examine the effect of vitamin C on forearm vasodilatory response to reactive hyperemia and on plasma level of plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA), antithrombin III (ATIII), proteins C and S, and factors V (fV) and VII (fVII) in patients with both type 2 diabetes and CAD.. A total of 39 patients with type 2 diabetes and CAD were divided into two groups and received vitamin C (2 g/day) or no antioxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge-strain plethysmography at baseline and after treatment. Forearm vasodilatory response to reactive hyperemia (RH%) or nitrate (NTG%) was defined as the percent change of flow from baseline to the maximum flow during reactive hyperemia or after administration of nitrate, respectively. Biochemical markers were determined by enzyme-linked immunosorbent assay (ELISA) or other standard methods.. RH% was significantly increased after treatment with vitamin C (from 62.4 +/- 7.2 to 83.1 +/- 9.3%, P = 0.024) but remained unaffected in the control group. Vitamin C decreased plasma levels of fV (from 143 +/- 5.4 to 123 +/- 6.03%, P = 0.038), vWF (from 133.5 +/- 14.5 to 109.5 +/- 11.4%, P = 0.016), and tPA (from 12.3 +/- 0.99 to 8.40 +/- 0.60 ng/ml, P = 0.001), whereas these levels remained unaffected in the control group. The changes in RH%, vWF, and tPA were significantly greater (P = 0.028, 0.036, and 0.007, respectively) in the vitamin C-treated group than in the control group. Levels of ATIII, proteins S and C, fVII, and PAI-1 remained unchanged in all groups.. Short-term treatment with high doses of vitamin C improved RH% and decreased plasma levels of tPA and vWF in patients with type 2 diabetes and CAD.

Topics: Administration, Oral; Aged; Antioxidants; Antithrombin III; Ascorbic Acid; Coronary Artery Disease; Diabetes Mellitus, Type 2; Factor V; Factor VII; Female; Fibrinolysis; Forearm; Humans; Hyperemia; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Protein C; Protein S; Regional Blood Flow; Thrombosis; Tissue Plasminogen Activator; Vasodilation; von Willebrand Factor

Anti-ischemic effect of angiotensin-converting enzyme inhibitor--chinapril was examined by exercise tolerance test [ETT] in randomised, cross-over double blind comparison in 20 pts with coronary artery disease treated with beta-blockers and nitrates. After 8 weeks of chinapril treatment maximal work capacity and exercise duration were significantly greater in comparison with baseline values, respectively: 7,8 vs 6,7 METs (p < 0,05) and 416 vs 335 s (p < 0,05). Time to ST segment depression was significantly longer after chinapril treatment: 394 vs 298 s (placebo) p = 0,01) vs 277 s (baseline), p = 0,008. The number of patients with exercise ST depression was significantly lower (63% vs 100%). Rate pressure product wasn't changed after chinapril treatment. Vitamin C therapy did not have influence on ischemia signs in exercise tolerance test.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid; Brain Ischemia; Coronary Artery Disease; Cross-Over Studies; Double-Blind Method; Exercise Test; Female; Humans; Male; Middle Aged; Nitrates

Hormone replacement therapy (HRT) and antioxidant vitamins are widely used for secondary prevention in postmenopausal women with coronary disease, but no clinical trials have demonstrated benefit to support their use.. To determine whether HRT or antioxidant vitamin supplements, alone or in combination, influence the progression of coronary artery disease in postmenopausal women, as measured by serial quantitative coronary angiography.. The Women's Angiographic Vitamin and Estrogen (WAVE) Trial, a randomized, double-blind trial of 423 postmenopausal women with at least one 15% to 75% coronary stenosis at baseline coronary angiography. The trial was conducted from July 1997 to January 2002 in 7 clinical centers in the United States and Canada.. Patients were randomly assigned in a 2 x 2 factorial design to receive either 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of medroxyprogesterone acetate for women who had not had a hysterectomy), or matching placebo, and 400 IU of vitamin E twice daily plus 500 mg of vitamin C twice daily, or placebo.. Annualized mean (SD) change in minimum lumen diameter (MLD) from baseline to concluding angiogram of all qualifying coronary lesions averaged for each patient. Patients with intercurrent death or myocardial infarction (MI) were imputed the worst rank of angiographic outcome.. The mean (SD) interval between angiograms was 2.8 (0.9) years. Coronary progression, measured in mean (SD) change, worsened with HRT by 0.047 (0.15) mm/y and by 0.024 (0.15) mm/y with HRT placebo (P =.17); and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo by 0.028 (0.15) mm/y (P =.32). When patients with intercurrent death or MI were included, the primary outcome showed an increased risk for women in the active HRT group (P =.045), and suggested an increased risk in the active vitamin group (P =.09). Fourteen patients died in the HRT group and 8 in the HRT placebo group (hazard ratio [HR], 1.8; 95% confidence interval [CI], 0.75-4.3), and 16 in the vitamin group and 6 in the vitamin placebo group (HR, 2.8; 95% CI, 1.1-7.2). Death, nonfatal MI, or stroke occurred in 26 HRT patients vs 15 HRT controls (HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and 18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction between the 2 treatment interventions.. In postmenopausal women with coronary disease, neither HRT nor antioxidant vitamin supplements provide cardiovascular benefit. Instead, a potential for harm was suggested with each treatment.

Topics: Aged; Antioxidants; Ascorbic Acid; Coronary Angiography; Coronary Artery Disease; Dietary Supplements; Double-Blind Method; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Humans; Lipoproteins; Medroxyprogesterone Acetate; Middle Aged; Postmenopause; Risk; Statistics, Nonparametric; Vitamin E

Cardiac transplantation is associated with oxidant stress, which may contribute to the development of accelerated coronary arteriosclerosis. We postulated that treatment with antioxidant vitamins C and E would retard the progression of transplant-associated arteriosclerosis.. In a double-blind prospective study, 40 patients (0-2 years after cardiac transplantation) were randomly assigned vitamin C 500 mg plus vitamin E 400 IU, each twice daily (n=19), or placebo (n=21) for 1 year. The primary endpoint was the change in average intimal index (plaque area divided by vessel area) measured by intravascular ultrasonography (IVUS). Coronary endothelium-dependent vasoreactivity was assessed with intracoronary acetylcholine infusions. IVUS, coronary vasoreactivity, and vitamin C and E plasma concentrations were assessed at baseline and at 1 year follow-up. All patients received pravastatin. Analyses were by intention to treat.. Vitamin C and E concentrations increased in the vitamin group (vitamin C 43 [SD 21] to 103 [43] mmol/L; vitamin E 24 [14] to 65 [27] mmol/L) but did not change in the placebo group (vitamin C 45 [15] vs 43 [16] mmol/L; vitamin E 27 [14] vs 27 [9] mmol/L; p<0.0001 for difference between groups). During 1 year of treatment, the intimal index increased in the placebo group by 8% (SE 2) but did not change significantly in the treatment group (0.8% [1]; p=0.008). Coronary endothelial function remained stable in both groups.. Supplementation with antioxidant vitamins C and E retards the early progression of transplant-associated coronary arteriosclerosis.

Topics: Antioxidants; Ascorbic Acid; Coronary Artery Disease; Coronary Vessels; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Female; Heart Transplantation; Humans; Male; Middle Aged; Prospective Studies; Tunica Intima; Ultrasonography, Interventional; Vasodilation; Vitamin E

Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations. Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events. This study was designed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease.. Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. The effect of the coadministration of vitamin C (24 mg/min) was assessed in a subgroup of 179 patients. Cardiovascular events, including death from cardiovascular causes, myocardial infarction, ischemic stroke, coronary angioplasty, and coronary or peripheral bypass operation, were studied during a mean follow-up period of 4.5 years. Patients experiencing cardiovascular events (n=91) had lower vasodilator responses to acetylcholine (P<0.001) and sodium nitroprusside (P<0.05), but greater benefit from vitamin C (P<0.01). The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation (P=0.001), the effect of vitamin C (P=0.001), and age (P=0.016) remained independent predictors of cardiovascular events.. Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease. These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity.

Topics: Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Coronary Artery Disease; Disease Progression; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Follow-Up Studies; Forearm; Humans; Male; Middle Aged; Oxidative Stress; Plethysmography; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Regional Blood Flow; Risk Assessment; Survival Rate; Vasodilation; Vasodilator Agents

This study was undertaken to evaluate the effects of alpha-tocopherol and ascorbic acid on markers of myocardial reperfusion injury and myocardial contractile function after coronary artery surgery. Forty-eight patients were divided into 4 groups; 300 mg/day alpha-tocopherol was given orally to the patients in group I for 14 days. In groups II and III, 4g of ascorbic acid was administered intravenously prior to induction and in the cardioplegic solution, respectively. Group IV was the control group. Blood samples were taken to determine the concentrations of creatine phosphokinase MB isoenzyme, malondialdehyde, uric acid, ascorbic acid and alpha-tocopherol in the perioperative period. Left ventricular functions were determined by means of MUGA scans and echocardiography preoperatively and on the 3rd and 7th days, postoperatively. The changes in serum creatine phosphokinase MB and malondialdehyde were significantly lower in study groups. when compared with the control group. We observed no significant changes in ventricular function, requirement for (+) inotropic agents and the incidence of ventricular arrhythmias among the groups, postoperatively. Biochemical findings are consistent with the free radical hypothesis. But we could not confirm these data with hemodynamic findings. This is probably due to the population of low-risk elective coronary surgery patients in this study.

Topics: Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Biomarkers; Cardioplegic Solutions; Cardiopulmonary Bypass; Coronary Artery Disease; Creatine Kinase; Creatine Kinase, MB Form; Female; Humans; Injections, Intravenous; Isoenzymes; Male; Malondialdehyde; Middle Aged; Myocardial Reperfusion Injury

To explore the association of supplementary and dietary vitamin E and C intake with the progression of coronary artery disease.. A subgroup analysis of the on-trial antioxidant vitamin intake database acquired in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled, serial angiographic clinical trial evaluating the risk and benefit of colestipol-niacin on coronary artery disease progression.. Community- and university-based cardiac catheterization laboratories.. A total of 156 men aged 40 to 59 years with previous coronary artery bypass graft surgery.. Supplementary and dietary vitamin E and C intake (nonrandomized) in association with cholesterol-lowering diet and either colestipol-niacin or placebo (randomized).. Change per subject in the percentage of vessel diameter obstructed because of stenosis (%S) determined by quantitative coronary angiography after 2 years of randomized therapy on all lesions, mild/moderate lesions (< 50%S), and severe lesions (> or = 50%S).. Overall, subjects with supplementary vitamin E intake of 100 IU per day or greater demonstrated less coronary artery lesion progression than did subjects with supplementary vitamin E intake less than 100 IU per day for all lesions (P = .04) and for mild/moderate lesions (P = .01). Within the drug group, benefit of supplementary vitamin E intake was found for all lesions (P = .02) and mild/moderate lesions (P = .01). Within the placebo group, benefit of supplementary vitamin E intake was not found. No benefit was found for use of supplementary vitamin C exclusively or in conjunction with supplementary vitamin E, use of multivitamins, or increased dietary intake of vitamin E or vitamin C.. These results indicate an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression. Verification from carefully designed, randomized, serial arterial imaging end point trials is needed.

Topics: Adult; Analysis of Variance; Antioxidants; Ascorbic Acid; Colestipol; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Diet, Atherogenic; Food, Fortified; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Vitamin E

Topics: Ascorbic Acid; Coronary Artery Bypass; Coronary Artery Disease; Female; Graft Occlusion, Vascular; Humans; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Time Factors; Vitamin E

Vitamin C remains an important, yet frequently unassessed, component of a healthy immune system though it may prove useful in alleviating the chronic inflammatory processes underlying chronic diseases such as coronary artery disease (CAD). Recent research identified a sizeable proportion of the United States population with insufficient vitamin C plasma levels and significant associations to both acute and chronic inflammation. This cross-sectional study used the 2003-2006 NHANES surveys data to extrapolate associations between plasma vitamin C levels (deficiency, hypovitaminosis, inadequate, adequate, and saturating) and CAD through inflammation (C-reactive protein and red cell distribution width). Increased reports of CAD diagnosis were identified in participants with vitamin C deficiency (OR: 2.31, CI: 1.49-3.58) and inadequate plasma levels (OR: 1.39, CI: 1.03-1.87). No significant correlation was identified between any other plasma vitamin C quintiles and CAD. When inflammation was controlled, previous associations in the deficient level of plasma vitamin C were no longer significant in association with CAD and participants with inadequate plasma vitamin C showed a reduced association to CAD diagnoses (OR: 0.33, CI: 0.13-0.86). Most chronic inflammation and vitamin C plasma statuses do not demonstrate specific signs or symptoms until the deficient level of vitamin C and/or disease. Thus, increased surveillance of both, and healthy nutritional habits remain crucial modifiable risk factors for disease prevention.

Topics: Ascorbic Acid; Coronary Artery Disease; Cross-Sectional Studies; Humans; Inflammation; Nutrition Surveys; Risk Factors; Vitamins

The purpose of this study was to evaluate the performance of biodegradable polymer sirolimus and ascorbic acid eluting stent systems with four commercially available drug-eluting stents (DES). We investigated the characterization of mechanical properties by dimension, foreshortening, recoil, radial force, crossing profile, folding shape, trackability, and dislodgement force. Additionally, we identify the safety and efficacy evaluation through registry experiments. Each foreshortening and recoil of D + Storm® DES is 1.3 and 3.70%, which has better performance than other products. A post-marketing clinical study to evaluate the performance and safety of D + Storm® DES is ongoing in real-world clinical settings. Two hundred one patients were enrolled in this study and have now completed follow-up for up to 1 month. No major adverse cardiovascular event (MACE) occurred in any subjects, confirming the safety of D + Storm® DES in the clinical setting. An additional approximately 100 subjects will be enrolled in the study and the final safety profile will be assessed in 300 patients. In conclusion, this study reported the objective evaluation of DES performance and compared the mechanical responses of four types of DES available in the market. There is little difference between the four cardiovascular stents in terms of mechanical features, and it can help choose the most suitable stent in a specific clinical situation if those features are understood. Graphical abstract.

Topics: Absorbable Implants; Ascorbic Acid; Coronary Artery Disease; Drug-Eluting Stents; Humans; Polymers; Prosthesis Design; Sirolimus; Treatment Outcome

This study was designed to evaluate the serum malondialdehyde (MDA), non-enzymatic antioxidants (vitamin A and C), macro-minerals (magnesium and calcium), and trace elements (zinc, copper, and iron) levels in patients with coronary artery disease (CAD) and to explore their role in disease progression.. This prospective case-control study was comprised of 40 CAD patients and 40 healthy volunteers as cases and control subjects, respectively. The level of lipid peroxidation was assessed by measuring the serum MDA level using a UV spectrophotometer. The levels of vitamins A and C were determined by high-performance liquid chromatography (HPLC) and UV spectrophotometric method, respectively. Atomic absorption spectroscopy (AAS) was used to measure serum macro-minerals (Mg and Ca) and trace elements (Zn, Cu, and Fe) concentrations.. The mean age of CAD patients and control subjects was 53.90 ± 2.22 and 37.03 ± 1.50 years, respectively. This study revealed significantly higher concentrations of MDA (p < 0.01) and lower concentrations of vitamin A (p < 0.01), and vitamin C (p < 0.05) in the CAD patients than in control subjects. The mean values of Mg, Cu, Zn, Ca, and Fe were 11.67 ± 0.64, 1.17 ± 0.03, 0.43 ± 0.02, 107.38 ± 1.81, and 1.66 ± 0.04 μg/mL, respectively for the CAD patients and 19.38 ± 0.65, 1.07 ± 0.02, 0.87 ± 0.02, 94.29 ± 1.89, and 1.52 ± 0.05 μg/mL, respectively for the controls and the differences were significant (p < 0.05) between the patients and controls.. From these findings, we can suggest that there is a strong association of CAD with an elevated level of MDA, depleted levels of antioxidants, and altered macro-minerals and trace elements concentrations.

Topics: Adult; Ascorbic Acid; Case-Control Studies; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Minerals; Oxidative Stress; Trace Elements; Vitamin A

Dietary nutrients have significant effects on the risk of cardiovascular diseases. However, the results were not uniform across different countries. The study aims to determine the relative importance of dietary nutrients associated with coronary artery disease (CAD) among the Nepalese population. A hospital-based matched case-control study was carried out at Shahid Gangalal National Heart Center in Nepal. In the present study, patients with more than seventy percent stenosis in any main coronary artery branch in angiography were defined as cases, while those presenting normal coronary angiography or negative for stressed exercise test were considered controls. Dietary intakes of 612 respondents over the past 12 months were evaluated using a semi-quantitative customized food frequency questionnaire. In conditional regression model, the daily average dietary intake of β-carotene (OR: 0.54; 95%CI: 0.34, 0.87), and vitamin C (OR: 0.96; 95%CI: 0.93, 0.99) were inversely, whereas dietary carbohydrate (OR: 1.16; 95%CI: 1.1, 1.24), total fat/oil (OR: 1.47; 95%CI: 1.27, 1.69), saturated fatty acid (SFA) (OR: 1.2; 95%CI: 1.11, 1.3), cholesterol (OR: 1.01; 95%CI: 1.001, 1.014), and iron intakes (OR: 1.11; 95%CI: 1.03, 1.19) were positively linked with CAD. Moreover, in random forest analysis, the daily average dietary intakes of SFA, vitamin A, total fat/oil, β-carotene, and cholesterol were among the top five nutrients (out of 12 nutrients variables) of relative importance associated with CAD. The nutrients of relative importance imply a reasonable preventive measure in public health nutrients specific intervention to prevent CAD in a resource-poor country like Nepal. The findings are at best suggestive of a possible relationship between these nutrients and the development of CAD, but prospective cohort studies and randomized control trials will need to be performed in the Nepalese population.

Topics: Aged; Ascorbic Acid; beta Carotene; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Dietary Carbohydrates; Dietary Fats; Fatty Acids; Female; Humans; Iron; Male; Middle Aged; Models, Theoretical; Nepal; Nutrients; Nutrition Surveys; Prospective Studies; Public Health

Nutritional intervention targeting dietary intake modification is a major component of treatment for chronic kidney disease; however, little is known about the relationship between dietary intake and kidney function decline in individuals with preserved kidney function.. During the 5-year follow-up, 290 participants (13.5%) experienced rapid kidney function decline. Relative to individuals in the lowest quartile of serum carotenoids, those in the highest quartile had significantly lower odds of rapid kidney function decline in the fully adjusted model (odds ratio, 0.51; 95% confidence interval [CI], 0.32-0.80; P trend, .02). No association of levels of serum tocopherols, ascorbic acid, or lycopene with kidney function decline was found. There was no evidence that results differed for individuals with hypertension or diabetes.. These results demonstrate that higher serum carotenoid levels, reflective of a fruit- and vegetable-rich dietary pattern, inversely associate with rapid kidney function decline in early middle adulthood and provide insight into how diet might play a role in chronic kidney disease prevention.

Topics: Adult; Ascorbic Acid; Biomarkers; Carotenoids; Cohort Studies; Coronary Artery Disease; Diet; Female; Follow-Up Studies; Fruit; Humans; Kidney; Male; Prospective Studies; Renal Insufficiency; Risk; Tocopherols; Vegetables

Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61. Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61. Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Topics: Animals; Antioxidants; Apolipoprotein B-48; Ascorbic Acid; Cardiotonic Agents; Coronary Artery Disease; Cytokines; Diet, Atherogenic; Dietary Supplements; Enzyme-Linked Immunosorbent Assay; Female; Hyperlipidemias; Immunoblotting; Lipid Metabolism; Lipoproteins, HDL; Male; Mice, Inbred C57BL; Myocardial Ischemia; Phospholipid Transfer Proteins; Reference Values; Reproducibility of Results; Scavenger Receptors, Class B; Treatment Outcome; Vitamin E

Atrial fibrillation is one of the most frequent complications and a major risk of morbidity and mortality after cardiac surgery. Antioxidants such as vitamin C are used for prevention of this arrhythmia. Different results of studies have been reported, but most of them have shown efficiency of vitamin C in prophylaxis of postoperative AF. We tried to examine this efficacy with larger sample size.. Three hundred and fourteen on pump coronary artery bypass graft surgery alone. Patients were divided into two groups: The intervention group received vitamin C (N = 160) and the control group did not receive any (N = 154). Intervention group was administered two grams of vitamin C intravenously (IV) 24 hours preoperatively, 500 mg every 12 hours IV for 48 hours in ICU, and 500 mg every 12 hours PO for 48 hours in ward. Continuous monitoring in ICU and three times a day ECG was used for AF detection. The two groups were compared.. The two groups were matched in terms of age, sex, LA size, ejection fraction, functional class, and TSH level. Of the patients, 244 were male. Mean age was 62 years (40-84 years) in both groups. M/F ratio was four in both groups. Functional class and ejection fraction were the same in both groups. There was no mean TSH level difference. AF occurrence in vitamin C group was 7.6 % and in control group was 7.8 %. There was no difference in ICU or hospital stay.. Prophylactic use of vitamin C does not further reduce postoperative atrial fibrillation in on pump CABG patients.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Atrial Fibrillation; Coronary Artery Bypass; Coronary Artery Disease; Double-Blind Method; Female; Humans; Incidence; Iran; Length of Stay; Male; Middle Aged; Postoperative Care; Postoperative Complications; Prognosis; Survival Rate

The aim of this study was the simultaneous determination of levels of cadmium and l-ascorbic Acid (AA) in human saphenous vein (SV) used in coronary artery bypass grafting (CABG) and check whether there is a relationship between these levels.. Human SV were collected from 40 patients (20 men and 20 women; age, 40-75 years) at the time of routine coronary artery surgical revascularization. The concentration of cadmium in the tissue was determined according to the GF AAS-atomic absorption method. The concentration of AA was assayed in supernatant by FIA method with spectrophotometric detection.. AA concentration (mean±SD); men: 98,7±13,18μg/g tissue, women: 96,06±11,98μg/g tissue. Cadmium concentration(mean±SD); men: 309±103,71ng/g tissue, women: 348,5±255,71ng/g tissue. Correlations among concentrations of AA and cadmium were insignificant negative in the group of men (Pearson r=-0,1504, p=0,5269) and in the group women (Pearson r=-0339, p=0144).. Negative correlations among concentrations of AA and cadmium in human SV obtained in our study may indicate a protective effect of this vitamin in relation to toxic cadmium.

Topics: Adult; Aged; Ascorbic Acid; Cadmium; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Saphenous Vein

Topics: Ascorbic Acid; Coronary Artery Disease; Elective Surgical Procedures; Female; Humans; Male; Myocardial Reperfusion Injury; Oxidative Stress; Percutaneous Coronary Intervention; Preoperative Care

Coronary artery disease (CAD) is a multifactorial disease caused by the interplay of environmental risk factors with multiple predisposing genes. The present study was undertaken to evaluate the role of DNA repair efficiency and oxidative stress and antioxidant status in CAD patients. Malonaldehyde (MDA), which is an indicator of oxidative stress, and mean break per cell (b/c) values, which is an indicator of decreased DNA repair efficiency, were found to be significantly increased in patients compared to normal controls (P less than 0.05) whereas ascorbic acid and GSH were found to be lower among patients than the control group. It has been found that elevated oxidative stress decreased antioxidant level and decreased DNA repair efficiency can contribute to the development of CAD. This study also showed that high MDA, low ascorbic acid and GSH were significantly associated with high b/c value.

Topics: Antioxidants; Ascorbic Acid; Case-Control Studies; Cells, Cultured; Chromatids; Chromosome Breakage; Chromosomes, Human; Coronary Artery Disease; DNA Repair; Female; Glutathione; Humans; Male; Malondialdehyde; Metaphase; Oxidative Stress; Prognosis

Increased production of oxygen free radicals and decreased oxidant capacity occur in coronary artery diseases (CAD) This pro-oxidant shift in intracellular redox state may induce cell death by either direct cell membrane damage by lipic peroxidation or apoptosis through activation of transcription factors. These changes occur not only in cardiomyocytes, bu also in cardiac sympathetic nerves, which are very sensitive to oxidative damage. Patients with heart failure encountel reduced peripheralblood flow at rest, during exercise and in response to endothelium-dependentvasodilators. Current treatments of cardiomyopathy, a degenerative condition of the myocardium frequently associated with heart failure have done little to enhance patient survival. Decreased myocardial contractility and altered regulation of peripheral circulation along with oxidative conditions are important contributors to the symptoms and prognosis of the disease process. Nitric oxide formed from L-arginine (2-amino-5 guanidinovaleric acid) metabolism in endothelial cells contributes to regulation of blood flow under these conditions. L-Arginine is the precursor of nitric oxide, an endogenous messenger molecule involved in a variety of endothelium-mediated physiological effects in the vascular system. In the present study, we investigated the effect of oral administration of L-arginine (3 g/day) on the intracellular redox status of the patients of ischemic cardiomyopathy aged 45-60 yrs. The enzymatic and non-enzymatic antioxidant parameters like superoxide dismutase, catalase, total thiols (TSH) and ascorbic acid along with pro-oxidant parameters, such as xanthine oxidase, as well as index of oxidative stress as protein carbonyl content and malondialdehyde (a marker of lipid peroxidation) were investigated in the plasma and RBC lysate. L-Arginine (3 g/day) administration was found to improve the levels of these parameters in the patients and regulate the blood flow, as evident by the improved blood pressure of the patients. Thus, it is inferred that L-arginine attenuates the oxidative stress conditions along with maintaining the blood pressure rate of patients suffering from cardiomyopathy.

Topics: Antioxidants; Arginine; Ascorbic Acid; Cardiomyopathies; Catalase; Coronary Artery Disease; Female; Free Radicals; Humans; Male; Middle Aged; Models, Biological; Myocardial Ischemia; Oxidants; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Superoxide Dismutase; Thyrotropin; Xanthine Oxidase

Neopterin is released from human monocyte-derived macrophages upon stimulation with interferon-gamma and is a sensitive indicator for cellular immune activation. Furthermore, reactive oxygen species (ROS) are produced in case of immune activation and inflammation. In a cross-sectional approach, plasma concentrations of neopterin and of antioxidant compounds and vitamins were compared in 1463 patients investigated by coronary angiography, which were recruited within the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. Serum neopterin concentrations were higher in patients with coronary artery disease (CAD; mean+/-S.D.: 8.7+/-7.3 nmol/L) compared to controls (7.4+/-5.0 nmol/L; Welch's t-test: p<0.001). Mean concentrations of ascorbic acid (p<0.0001), gamma-tocopherol (p<0.05), lycopene (p<0.001), lutein+zeaxanthin (p<0.05), alpha-carotene (p<0.05) and beta-carotene (p<0.05) were lower in CAD than in controls. Neopterin concentrations correlated with CAD-score (r(s)=0.156; p<0.0001) and inversely with antioxidants lycopene (r(s)=-0.277; p<0.0001) and lutein+zeaxanthin (r(s)=-0.175; p<0.0001) levels and with vitamins ascorbic acid (r(s)=-0.207; p<0.0001) and alpha-tocopherol (r(s)=-0.105; p<0.0001). The study demonstrates that higher neopterin production is associated with lower concentrations of antioxidant compounds in patients at risk for atherosclerosis. Results suggest that lower concentrations of antioxidant compounds may relate to higher grade of chronic immune activation in patients.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coronary Angiography; Coronary Artery Disease; Female; Humans; Lutein; Lycopene; Male; Middle Aged; Neopterin; Oxidative Stress; Risk Factors; Vitamin E; Xanthophylls; Young Adult; Zeaxanthins

Topics: Ascorbic Acid; Biomarkers; Coronary Artery Disease; Counseling; Erythrocyte Membrane; Fatty Acids, Unsaturated; Feeding Behavior; Folic Acid; Health Knowledge, Attitudes, Practice; Humans; Lipids; Nutritional Status; Patient Compliance; Patient Education as Topic; Practice Guidelines as Topic; Risk Reduction Behavior; Time Factors; Treatment Outcome

Nutrition has a major influence after coronary events but long-term adherence to dietary advice is poorly evaluated.. To evaluate if a cardiovascular rehabilitation programme including dietary counselling has a positive impact on adherence to dietary recommendations.. Two groups of coronary patients were compared in an observational non-randomized study. Group I included 32 patients at the acute phase of a coronary syndrome and group II included 104 patients between six months and three years after completing a cardiovascular rehabilitation programme. The evaluation was performed with (1) a validated 14-item food frequency questionnaire (FFQ), which gives scores for the consumption of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), Omega-6 and Omega-3 polyunsaturated fatty acids (PUFA), fruits and vegetables, and a global cardiovascular protective dietary score; and (2) biological markers.. SFA score was higher in group I vs II (7.4+/-2.8 vs 4.4+/-2.1, p<0.001) whereas Omega-3 PUFA (2.2+/-2.0 vs 4.7+/-2.1, p<0.001), fruit and vegetables score (3.3+/-1.4 vs 4.3+/-1.7, p=0.001) and global dietary score (-1.1+/-4.5 to 7.0+/-4.9, p<0.001) were higher in group II. The Omega-6:Omega-3 PUFA ratio was higher in group I (14.2+/-12.7 vs 6.3+/-5.4, p<0.001). Biological markers showed higher plasma contents of Omega-3 PUFA (4.05+/-1.70% vs 2.80+/-1.07%, p<0.001), folate (19.7+/-12.2 nmol/L vs 13.0+/-5.0 nmol/L, p<0.001) and vitamin C (7.60+/-3.99 mg/L vs 4.18+/-3.46 mg/L, p<0.001), and a higher erythrocyte membrane Omega-3 PUFA content (6.60+/-2.19% vs 5.38+/-2.17%, p=0.016) in group II vs I.. Using a short FFQ, this study showed sustained improvement in dietary habits in patients with coronary heart disease who receive nutritional education during a cardiovascular rehabilitation programme.

Topics: Adult; Ascorbic Acid; Biomarkers; Coronary Artery Disease; Counseling; Erythrocyte Membrane; Fatty Acids, Unsaturated; Feeding Behavior; Folic Acid; Health Knowledge, Attitudes, Practice; Humans; Lipids; Male; Middle Aged; Nutrition Assessment; Nutritional Status; Patient Compliance; Patient Education as Topic; Practice Guidelines as Topic; Program Evaluation; Risk Reduction Behavior; Surveys and Questionnaires; Time Factors; Treatment Outcome

Topics: Antioxidants; Ascorbic Acid; Coronary Artery Disease; Female; Humans; Male; Vitamin E

Topics: Aged; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Atrial Fibrillation; Coronary Artery Disease; Humans; Male; Myocardial Revascularization; Postoperative Complications; Risk Factors

The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p < 0.001). This suggests that use of ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

Topics: Animals; Antioxidants; Aorta; Ascorbic Acid; Carotid Stenosis; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Diet, Atherogenic; Hypercholesterolemia; Lipid Peroxidation; Malondialdehyde; Rabbits

Excessive vascular oxidant stress has been implicated in cardiac transplant-associated arteriosclerosis (TxAA). In a recent placebo-controlled study of 40 cardiac transplant recipients, vitamin C 500 mg twice a day and vitamin E 400 IU twice a day for 1 year retarded the progression of TxAA, as assessed by intravascular ultrasound (IVUS). Endothelial dysfunction is a key feature of TxAA and reflects oxidant stress. We hypothesized that coronary endothelial dysfunction portends greater TxAA progression and a larger therapeutic response to anti-oxidant vitamins.. In this pre-specified analysis, the 40 cardiac transplant recipients were categorized according to normal or abnormal coronary endothelial vasomotor function at baseline, as assessed by acetylcholine (10(-8) to 10(-6) mol/liter). The effect of anti-oxidant vitamins within these two groups of patients was assessed by the change in intimal index over 1 year using IVUS.. With placebo (n = 21), the increase in intimal index was greater in the presence vs absence of endothelial dysfunction (11 +/- 3% vs 5 +/- 1%, p < 0.05). Among patients with endothelial dysfunction (n = 21), the intimal index increased 11 +/- 3% with placebo, but decreased -1 +/- 2% with vitamins (p = 0.002). Among patients with normal endothelial function (n = 14), the intimal index increased 5 +/- 1% with placebo and 1 +/- 1% with vitamins (p < 0.05).. Endothelial dysfunction indicates rapid TxAA progression, even in the statin era. Although anti-oxidant vitamins reduce disease progression in patients with normal or abnormal endothelial function, the magnitude of benefit is larger in patients with endothelial dysfunction.

Topics: Antioxidants; Ascorbic Acid; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Disease Progression; Endothelium, Vascular; Female; Heart Transplantation; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Male; Middle Aged; Oxidative Stress; Ultrasonography, Interventional; Vitamin E

Numerous studies have evaluated the association between antioxidants and coronary atherosclerosis but have been limited by its study among individuals with advanced atherosclerosis. The authors studied 865 consecutive patients, 39-45 years of age, without known coronary artery disease and presenting for a periodic physical examination. Antioxidant intake was assessed with the Block Dietary Questionnaire, and coronary atherosclerosis was identified by measuring coronary artery calcification using electron beam computed tomography. The mean age was 42 (+/-2), 83% were male, and the prevalence of coronary artery calcification was 20%. Vitamin supplements were used by 56% of the participants, and the mean (+/-SD) daily intake (dietary plus supplemental) of vitamins A, C, and E were 1683 mg (+/-1245), 371 mg (+/-375), and 97 mg (+/-165), respectively. There was no significant correlation between coronary artery calcification score and individual vitamin or total antioxidant vitamin intake, even after adjusting for traditional cardiac risk factors. The highest quartile of vitamin E was positively associated with calcification (odds ratio=1.77; 95% confidence interval, 1.02-3.06). Antioxidant vitamin intake is not significantly related to coronary artery calcification, implying that there is no effect on the development of early coronary atherosclerosis. High doses of vitamin E may confer an increased risk of calcified atherosclerosis.

Topics: Adult; Antioxidants; Ascorbic Acid; Calcinosis; Case-Control Studies; Coronary Artery Disease; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Odds Ratio; Risk Factors; Surveys and Questionnaires; Tomography, X-Ray Computed; Vitamin A; Vitamin E; Vitamins

High plasma concentrations of ascorbic acid, a marker of fruit and vegetable intake, are associated with low risk of coronary artery disease. Whether this relationship is explained by a reduction in systemic inflammation is unclear. We investigated the relationship between ascorbic acid plasma concentration and coronary artery disease risk, and in addition whether this relationship depended on classical risk factors and C-reactive protein (CRP) concentration. We used a prospective nested case-control design. The study consisted of 979 cases and 1794 controls (1767 men and 1006 women). Increasing ascorbic acid quartiles were associated with lower age, BMI, systolic and diastolic blood pressure, and CRP concentration, but with higher HDL-cholesterol concentration. No associations existed between ascorbic acid concentration and total cholesterol concentration or LDL-cholesterol concentration. When data from men and women were pooled, the risk estimates decreased with increasing ascorbic acid quartiles such that people in the highest ascorbic acid quartile had an odds ratio for future coronary artery disease of 0.67 (95 % CI 0.52, 0.87) compared with those in the lowest quartile (P for linearity=0.001). This relationship was independent of sex, age, diabetes, smoking, BMI, LDL-cholesterol, HDL-cholesterol, systolic blood pressure and CRP level. These data suggest that the risk reduction associated with higher ascorbic acid plasma concentrations, a marker of fruit and vegetable intake, is independent of classical risk factors and also independent of CRP concentration.

Topics: Age Distribution; Aged; Ascorbic Acid; Blood Pressure; Body Mass Index; C-Reactive Protein; Case-Control Studies; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; England; Female; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Sex Distribution; Smoking

Ascorbic acid is a vitamin soluble in water and its deficiency in human body causes scurvy. Its symptoms in adults are gingivitis, susceptibility of blood vessels to damage and bleeding, changes in bones and cartilage and retarded wound healing. Ascorbic acid is necessary in redox processes taking place in cell. It is reversibly oxidized to dehydroascorbic acid and partially metabolized to inactive sulphide and oxalic acid, which is expelled in urine. It is well absorbed from the digestive system and easily reaches the tissues. Healthy organism contains 1.5 g of ascorbic acid and daily requirement for ascorbic acid is estimated for 30-100 mg. Ascorbic acid is not synthesized by humans, but it is an essential dietary vitamin for the species. Ascorbic acid is used in treatment deficiency in daily demand for vitamin C, caused by improper diet, poor absorption or cigarette smoking. It is used in large doses in general weakness, infectious diseases and during the recovery period. Positive results have been obtained after therapy with vitamin C of Mollera-Barlowa disease, Schonlein-Henoch disease, Werlhof disease, haemophilia and also in patients with stable coronary artery disease. Vitamin C is assumed to be a basic antioxidant, although its role in pathological conditions is controversial. However, it seems that the complexity of the oxidant-antioxidant system makes the question of participation of vitamin C (and other scavengers of free radicals) in pathogenesis of diseases still open.

Topics: Adult; Aged; Ascorbic Acid; Chromatography, High Pressure Liquid; Coronary Artery Bypass; Coronary Artery Disease; Dehydroascorbic Acid; Female; Humans; Male; Middle Aged; Preoperative Care; Smoking

Ascorbic acid is an antioxidant nutrient possibly related to the development of atherosclerosis. To examine the relation between ascorbic acid and coronary artery calcium, an indicator of subclinical coronary disease, the authors analyzed data from 2,637 African-American and White men and women aged 18-30 years at baseline who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1985-2001). Participants completed diet histories at enrollment and year 7, and plasma ascorbic acid levels were obtained at year 10. Coronary artery computed tomography was performed at year 15. The authors calculated odds ratios in four biologically relevant plasma ascorbic acid categories, adjusting for possible confounding variables. When compared with men with high plasma ascorbic acid levels, men with low levels to marginally low levels had an increased prevalence of coronary artery calcium (multivariate odds ratio = 2.68, 95% confidence interval: 1.31, 5.48). Among women, the association was attenuated and nonsignificant (multivariate odds ratio = 1.50, 95% confidence interval: 0.58, 3.85). Ascorbic acid intakes from diet alone and diet plus supplements were not associated with coronary artery calcium. Low to marginally low plasma ascorbic acid levels were associated with a higher prevalence of coronary artery calcium among men but not among women.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Black or African American; Calcinosis; Coronary Angiography; Coronary Artery Disease; Dietary Supplements; Feeding Behavior; Female; Humans; Male; Multivariate Analysis; Prevalence; Prospective Studies; Risk; Sex Distribution; United States; White People

Type 2 diabetes mellitus (DM) and coronary artery disease (CAD) are both associated with endothelial dysfunction and elevated oxidative and inflammatory state. We examined the effect of vitamin C on endothelial function and levels of soluble vascular cell adhesion molecule (sVCAM-1), interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha), in DM patients with or without CAD and in non-diabetic subjects.. Thirty-seven patients with DM + CAD, 17 patients with DM without CAD and 21 non-diabetic subjects were divided into groups receiving vitamin C 2 g/day or no anti-oxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia was considered as index of endothelium-dependent dilation.. Baseline levels of IL-6 and TNF-alpha were significantly higher in patients with DM + CAD compared with patients with DM (P < 0.01) or non-diabetic subjects (P < 0.01). IL-6 and TNF-alpha levels were also higher in DM compared with non-diabetic subjects (P < 0.05). sVCAM-1 levels were lower in non-diabetic controls compared with DM + CAD (P < 0.05) or DM (P < 0.05). Reactive hyperaemia was higher in non-diabetic controls compared with DM + CAD (P < 0.001) or DM (P < 0.001). Vitamin C significantly increased reactive hyperaemia only in the DM + CAD group, while it had no effect on serum levels of sVCAM-1, TNF-alpha and IL-6 in any of the groups.. Type 2 diabetes mellitus is associated with impaired endothelial function and increased levels of TNF-alpha, IL-6 and sVCAM-1, especially in patients with DM and CAD. Vitamin C significantly increased forearm vasodilatory response to reactive hyperaemia only in patients with combined DM and CAD.

Topics: Antioxidants; Ascorbic Acid; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Female; Forearm; Humans; Hyperemia; Interleukin-6; Male; Middle Aged; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Vasodilation

Previous studies in patients with a history of Kawasaki disease have focused on vascular endothelial function in coronary arteries, and the endothelial function of systemic arteries is not fully understood. Furthermore the effect of vitamin C on systemic endothelial function after Kawasaki disease has not been elucidated.. We attempted to analyze endothelium-dependent vasodilatation in the brachial artery after Kawasaki disease by using high resolution ultrasonography and to investigate whether the acute administration of vitamin C could restore such systemic endothelial dysfunction.. We compared 39 patients (7.1 +/- 2.7 years) 1.0 to 9.6 years after acute Kawasaki disease with 17 matched healthy subjects (7.0 +/- 3.1 years) as controls. Using high resolution vascular ultrasound, we measured brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilatation) and sublingual nitroglycerin (causing endothelium-independent dilatation).. The percent change in diameter of the brachial artery induced by reactive hyperemia in the patients with a history of Kawasaki disease (6.2 +/- 3.9%) was significantly lower than that in the control group (14.1 +/- 6.8%; P < 0.0001). No significant difference could be found in percent change in diameter induced by sublingual administration of nitroglycerin between the control (33.2 +/- 13.7%) and the patients with a history of Kawasaki disease (30.6 +/- 9.2%; P = 0.49). There was no significant difference in percent change in diameter of the brachial artery induced by reactive hyperemia between the patients who received gamma-globulin (6.0 +/- 4.0%) and those who did not receive gamma-globulin (7.9 +/- 3.3%; P = 0.33). Intravenous infusion of vitamin C significantly increased the percent change in diameter of brachial artery induced by reactive hyperemia in 19 patients with history of Kawasaki disease (6.6 +/- 3.5 to 13.0 +/- 5.5%; P < 0.0001), whereas no significant increase was seen in the percent change in diameter of brachial artery induced by reactive hyperemia in 20 patients with history of Kawasaki disease after placebo administration (6.5 +/- 4.5 to 7.3 +/- 4.9%; P = 0.20).. Our study showed decreased percent change in diameter of the brachial artery induced by reactive hyperemia in patients with history of Kawasaki disease compared with the healthy children, indicating that systemic endothelial dysfunction exits after Kawasaki disease. Although such systemic endothelial dysfunction after Kawasaki disease is not influenced by early treatment with high dose gamma-globulin in the acute stage of Kawasaki disease, it can be restored by the acute intravenous administration of vitamin C.

Topics: Adolescent; Ascorbic Acid; Blood Flow Velocity; Brachial Artery; Child; Child, Preschool; Coronary Artery Disease; Endothelium, Vascular; Female; gamma-Globulins; Humans; Infusions, Intravenous; Male; Mucocutaneous Lymph Node Syndrome; Nitroglycerin; Ultrasonography; Vasodilation

Topics: Antioxidants; Ascorbic Acid; Coronary Angiography; Coronary Artery Disease; Dietary Supplements; Estrogen Replacement Therapy; Female; Humans; Postmenopause; Vitamin E

Coronary endothelial dysfunction is associated with an increase in cardiac events. Hypercholesterolemia (HC) and hypertension (HT) are both associated with endothelial dysfunction, and their coexistence is associated with an increased incidence of cardiac events in epidemiological studies. However, pathogenic mechanisms are poorly understood. Here we studied the effects of coexisting HC and HT on coronary endothelial function.. Four groups of pigs were studied after 12 weeks of a normal diet (n=9), a 2% HC diet (n=9), HT (achieved by unilateral renal artery stenosis, n=8), or HC+HT (n=6). Coronary endothelial function was tested, in epicardial arteries and arterioles, by using organ chamber techniques. Oxidative stress was measured in coronary artery tissue. Vasodilatory response to bradykinin and calcium ionophore was significantly impaired in animals with HC+HT compared with each risk factor alone (P<0.05 for both). In animals with coexistent HC and HT, the increase in oxidative stress was more pronounced compared with each risk factor alone (P<0.05). Furthermore, chronic antioxidant supplementation significantly improved coronary artery vasoreactivity.. These results suggest that HC and HT have a synergistic deleterious effect on coronary endothelial function, associated with increased oxidative stress. This interaction may contribute to the increased incidence of coronary heart disease and cardiac events seen when HC and HT coexist.

Topics: Animals; Antioxidants; Ascorbic Acid; Bradykinin; Calcimycin; Coronary Artery Disease; Coronary Vessels; Cyclic GMP; Diet, Atherogenic; Endothelin-1; Endothelium, Vascular; Female; Hemodynamics; Hypercholesterolemia; Hypertension, Renovascular; Lipids; Nitric Oxide; Nitroprusside; Oxidative Stress; Renal Artery Obstruction; Renin; Substance P; Swine; Vasodilator Agents; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Coronary Artery Disease; Disease Progression; Humans; Organ Transplantation; Vitamin E

Adequate vitamin C (AsA) intake may lower the risk of arteriosclerotic cardiovascular disease, but little is known about its influence on the progression of atherogenic disease in the elderly.. We examined whether AsA intake was associated with serum lipids, apolipoprotein A-1 (ApoA1) and apolipoprotein B (ApoB), in 680 Japanese elderly persons.. There were no significant gender differences among mean serum lipids and apolipoprotein concentrations and intakes of macronutrients. AsA intake had a significant positive association with serum concentrations of high-density cholesterol and ApoA1, but an inverse association with serum concentrations of low-density cholesterol and ApoB, after adjusting for age, body mass index, total energy, and macronutrients. AsA intake was strongly inversely related to ApoA1/ApoB.. Increased AsA intake could play an important role in lipid composition and could be of potential importance in the genesis and prevention of atherogenic disease in the elderly.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Apolipoproteins A; Apolipoproteins B; Ascorbic Acid; Coronary Artery Disease; Dietary Supplements; Female; Humans; Japan; Male; Nutrition Surveys; Primary Prevention; Probability; Risk Assessment; Sensitivity and Specificity; Urban Population

Topics: Ascorbic Acid; Coronary Artery Disease; Heart Transplantation; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin E

Topics: Ascorbic Acid; Carnitine; Coronary Artery Disease; Diet, Reducing; Estrogens; Exercise; Female; Humans; Hyperlipoproteinemia Type II; Lipoprotein(a); Mutation; Niacin; Receptors, LDL; Risk Factors; Tamoxifen

The possible involvement of oxidative damage in the progression of atherosclerosis has been suggested. There is some evidence that antioxidant therapy may be beneficial for the prevention of coronary heart disease. In this study, we investigated the relationship between coronary artery disease (CAD) and serum antioxidative status by measuring the total antioxidant status (TAS). Other relevant antioxidants, such as retinol, alpha, gamma-tocopherol, ascorbic acid, alpha, beta-carotenoids, erythrocyte glutathione peroxidase (GSH-Px) and oxidative products, were also determined in 31 male CAD patients with angiographically defined CAD and 66 male controls, aged 40-70 years, in a case-control study. The TAS levels, ratio and the concentrations of retinol, albumin, total protein and HDL cholesterol were significantly lower in the CAD patients than in the controls (p<0.01), and alpha-tocopherol and alpha/gamma-tocopherol were significantly higher in the CAD patients than in the controls. The TAS level correlated positively with gamma-GTP, GPT, GOT and uric acid (p<0.01). A multiple regression analysis in the CAD patients revealed that the TAS levels correlated most negatively with the number of diseased vessels. The concentrations of carotenoids and GSH-Px, as well as the alpha/gamma-tocopherol ratio were also significantly associated. Although conditional logistic regression analysis suggested low levels of HDL-cholesterol to be a significant coronary risk factor (OR=5.1, 95% CI=1.09-24.3), the TAS level showed no significant independent contribution to CAD. This study demonstrated an association of antioxidant parameters with the atherosclerosis progression, however, it did not confirm antioxidants as an independent risk factor for CAD event.

Topics: Adult; Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Carotenoids; Case-Control Studies; Coronary Artery Disease; Coronary Disease; gamma-Tocopherol; Glutathione Peroxidase; Humans; Middle Aged; Oxidative Stress; Regression Analysis; Vitamin A

Postmenopausal women who use estrogen appear to be protected from coronary heart disease (CHD). Studies have demonstrated that estrogen can lower low-density lipoprotein (LDL) levels and the antioxidant activity of 17 beta-estradiol can prevent the oxidation of this LDL. Ascorbic acid is regarded as a major hydrophylic antioxidant, however, its impact on the prevention of CHD has yet to be clearly demonstrated. Modified low density lipoprotein (LDL(-)) is an important marker of LDL oxidation in vivo, since it contributes to the oxidative susceptibility of low density lipoprotein, and at physiological levels displays pro-inflammatory and cytotoxic properties. Previously we showed that women taking estrogen replacement therapy have lower LDL(-) levels along with lower predisposition of the LDL to oxidize. In this study, we evaluated the potential action of 17 beta-estradiol (E(2)) in combination with ascorbic acid (AA) measured on the basis of LDL oxidative susceptibility in vitro and in the presence of cultured cells. High concentrations of E(2) were able to inhibit LDL oxidation, whereas in the presence of ascorbic acid nano- to picomolar levels of E(2) were sufficient to suppress LDL oxidation (P<0.05). Preconditioning male aortic endothelial cells (RAEC) with 5 ng/ml of E(2) (E(2)RAEC) reduced the formation of LDL(-) (P<0.005), and a more extensive inhibition was found in the presence of AA (P<0.0001). Interestingly, E(2) enhanced the uptake of LDL in the absence or presence of AA, however, this was not seen for the uptake of LDL(-). These results provide the first evidence that ascorbic acid can enhance the antioxidant effect of E(2) by preventing LDL oxidation by copper ions or cells. The cytoprotective and antiatherogenic effect of E(2) appears to involve a reduction in the extent of oxidized LDL formation and uptake. The enhanced activity of E(2) in the presence of ascorbate indicates that the antioxidant and antiatherosclerosis activity of E(2) may occur at concentrations within the physiological range.

Topics: Adult; Animals; Antioxidants; Aorta; Ascorbic Acid; Biomarkers; Cells, Cultured; Coronary Artery Disease; Drug Synergism; Endothelium, Vascular; Estradiol; Glutathione; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Progesterone; Rabbits; Vitamin E

Topics: Ascorbic Acid; Coronary Artery Disease; Coronary Vessels; Female; Humans; Middle Aged; Nitric Oxide; Vasodilation

In recent years it has been reported that free oxygen radicals play an important role in the pathogenesis of degenerative diseases and that antioxidant vitamins such as vitamins E or C prevent their harmful effects. In this study, we evaluated the following: Erythrocyte susceptibility to lipid peroxidation; the role of erythrocyte glutathione (GSH) as an antioxidant; plasma lipid fractions; and the relationship between plasma lipid peroxides and antioxidant vitamin levels. Thiobarbituric acid-reactive substance (TBARS) levels were measured to determine the levels of plasma lipid peroxides and the susceptibility to lipid peroxidation when erythrocytes were stressed by hydrogen peroxide for 2 h in vitro. Erythrocyte TBARS production was significantly higher in patients with coronary atherosclerosis than in the controls. On the other hand, the levels of plasma high-density lipoproteins, vitamin C, vitamin E and erythrocyte GSH were significantly lower, and the levels of plasma total cholesterol, triglycerides, low-density lipoproteins and TBARS were significantly higher in the patients with coronary atherosclerosis than in the controls. In conclusion, our results indicate that erythrocytes from patients with coronary atherosclerosis are more susceptible to oxidation than those of controls and that these patients have lowered antioxidant capacity as revealed by decreased plasma levels of vitamins C and E.

Topics: Ascorbic Acid; Coronary Artery Disease; Erythrocytes; Female; Glutathione; Humans; Lipid Peroxides; Lipoproteins, LDL; Male; Middle Aged; Thiobarbituric Acid Reactive Substances; Vitamin E

Diabetes is associated with increased oxidant stress. This may contribute to the development of diabetic macrovascular complications through increased oxidation of low-density lipoprotein (LDL), which is thought to be a crucial step in the development of atherosclerosis. The sulfonylurea gliclazide has been shown to have free radical-scavenging activity in vitro, but its effects on LDL oxidation, and these effects of other sulfonylureas, are unknown. To investigate this we studied the effects of in vitro supplementation with gliclazide 1 mumol/L on copper-induced oxidation of LDL isolated from 20 control subjects and 22 type II diabetic patients. The effects of 1 mumol/L vitamin C, a known water-soluble antioxidant, were studied simultaneously. The resistance to oxidation, expressed as the lag time between the addition of copper and commencement of oxidation, was significantly increased by both gliclazide and vitamin C, and the effect was similar for LDL from diabetic and control subjects. The baseline oxidation lag time was 63.4 +/- 2.1 minutes, and increased to 108 +/- 4.4 minutes with gliclazide and 88.7 +/- 5.6 minutes with vitamin C (P = .0001, baseline v either treatment). The increase in lag time with gliclazide of 70% +/- 3% was greater than the 30% +/- 5% increase with vitamin C (P < .0005). In a separate experiment, LDL isolated from eight control and 10 diabetic subjects was supplemented with 1 mumol/L gliclazide, glibenclamide, glipizide, and tolbutamide. For each LDL sample, all drugs were studied simultaneously and the oxidation lag time was compared against that of untreated LDL. Gliclazide increased the lag time from 53.7 +/- 2.4 minutes to 108.4 +/- 4.5 minutes (P = .0001). None of the other sulfonylureas had any effect on lag time. These findings demonstrate that gliclazide is an effective inhibitor of in vitro LDL oxidation, and in this respect, it is more potent on a molar basis than vitamin C. This antioxidant property of gliclazide was not shared by the other sulfonylureas studied.

Topics: Administration, Oral; Adult; Antioxidants; Ascorbic Acid; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Gliclazide; Glipizide; Glyburide; Humans; Hypoglycemic Agents; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Sulfonylurea Compounds; Tolbutamide

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Coronary Artery Disease; Female; Free Radicals; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Vitamin E

Topics: Ascorbic Acid; Capsules; Cholesterol; Coronary Artery Disease; Coronary Disease; Humans; Incidence; Vitamin A; Vitamin D; Vitamins

Topics: Ascorbic Acid; Coronary Artery Disease; Glutathione; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization

Topics: Ascorbic Acid; Coronary Artery Disease; Glutathione; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization