Oxidation of LDL and extent of peripheral atherosclerosis (original) (raw)
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LDL Oxidation and Extent of Coronary Atherosclerosis
Arteriosclerosis, Thrombosis, and Vascular Biology, 1998
Accumulated evidence indicates that oxidative modification of LDL plays an important role in the atherogenic process. Therefore, we investigated the relation between coronary atherosclerosis and susceptibility of LDL to oxidation in a case-control study in men between 45 and 80 years of age. Case subjects and hospital control subjects were selected from subjects undergoing a first coronary angiography. Subjects with severe coronary stenosis (Ն85% stenosis in one and Ն50% stenosis in a second major coronary vessel) were classified as case subjects (nϭ91). Hospital control subjects with no or minor stenosis (Յ50% stenosis in no more than two of the three major coronary vessels, nϭ94) and population control subjects free of plaques in the carotid artery (nϭ85) were pooled for the statistical analysis into one control category. Enrollment procedures allowed for similar distributions in age and smoking habits. Case subjects had higher levels of total and LDL cholesterol and triglycerides and lower levels of HDL cholesterol. Resistance time, maximum rate of oxidation, and maximum diene production were measured ex vivo using copper-induced LDL oxidation. A borderline significant inverse trend was observed for coronary atherosclerosis risk at increasing resistance time. Odds ratios (95% confidence interval) for the successive quartiles were 1.0 (reference), 0.77 (0.39 to 1.53), 0.67 (0.33 to 1.34), and 0.55 (0.27 to 1.15) (p trend ϭ0.07). No relation with maximum rate of oxidation was found, and higher maximum diene levels were found in control subjects (PϽ.01). The main determinant of oxidation was the fatty acid composition of LDL. No effect of smoking or use of medication was observed. We conclude that although LDL resistance to oxidation may be a factor in atherogenesis, the ex vivo measure is not a strong predictor of severity of coronary atherosclerosis.
Atherosclerosis, 2014
Objectives: To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population. Methods: Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants. End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intimamedia thickness (IMT) in the highest quintile and ankle-brachial index <0.9 were considered indicators of subclinical atherosclerosis. Results: Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR ¼ 1.70; 95% Confidence Interval: 1.02e2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI ¼ 14.67% [4.90; 24.45], P ¼ 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles). Conclusions: OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions.
Lipoprotein oxidation and atherosclerosis
Biochemical Society Transactions, 2001
Lipoprotein oxidation is a key early stage in the development of atherosclerosis. Oxidation of lowdensity lipoprotein (LDL) is initiated by both enzyme-mediated and non-enzymic mechanisms in vivo, and oxidized LDL has many atherogenic properties. Oxidation of LDL in vivo is likely to be influenced by local environmental factors, such as pH. The composition of LDL is also important, including such factors as antioxidant content, fatty acid composition and particle size.
Role of oxidized low-density lipoprotein cholesterol concentration in atherosclerosis
Experimental and clinical cardiology
It is assumed that oxidized LDL (ox-LDL) plays a key role in the inflammatory response in the arterial vessel wall. This study aimed to investigate the association between oxidized low density lipoprotein cholesterol and carotid intima-media thickness, a measure used to diagnose the extent of carotid atherosclerotic vascular disease. Four groups of subjects were included in the study: a control group that included 15 normocholesterolemic healthy subjects (82% males, 18% females), 30 subjects with clinical signs of coronary artery disease (68% males, 32% females), 15 patients with arterial hypertension (66% males, 34% females), and 17dyslipidemic patients (64% males, 36% females). Lipid profiles of the patients were measured by enzymatic methods. Carotid IMT was measured by high-resolution Bmode ultrasound and ox-LDL by a commercially available sandwich ELISA (Mercodia AB, Uppsala, Sweden). Serum ox-LDL levels were higher in coronary artery disease patients (93.9 ± 7.35 U/L) and dyslipidemic patients (72 ± 14.34 U/L) compared with hypertensive (54 ± 12.03 U/L) and control subjects (55 ± 6.79 U/L). A positive, moderate correlation between ox-LDL and carotid IMT was found only in coronary artery disease group (r=0.56, p<0.001). No significant correlation was found between ox-LDL and carotid IMT in control (r=0.48, p<0.001), hypertensive (r=0.12, p<0.001) and dyslipidemic groups (r=0.14, p=0.05).
Clinical Chemistry, 2001
Background: Convincing evidence points to oxidative modification of LDL as an important trigger in a complex chain of events leading to atherosclerosis. We investigated the occurrence of enhanced susceptibility of LDL to oxidation and decreased vitamin E concentration in LDL as additional risk factors promoting atherosclerosis among patients with established coronary artery disease (CAD).Methods: We examined 132 patients with angiographically confirmed CAD and compared them with 111 healthy control individuals. We measured conjugated diene production to assess susceptibility of LDL to copper-mediated oxidation. Vitamin E content of LDL was measured by HPLC.Results: The mean lag time of LDL oxidation and LDL α-tocopherol/LDL-cholesterol ratio were lower in the patients with CAD (55 ± 14 min and 2.4 ± 1.0 mmol/mmol) than in the controls (63 ± 13 min and 2.9 ± 1.1 mmol/mmol; P <0.0001 and <0.001, respectively). Multiple stepwise regression analysis demonstrated the lag time (odds...
1998
Coronary heart disease (CHD) is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM) and the oxidation of low-density lipoprotein (LDL) may be an essential factor in the development of atherosclerotic lesions. Therefore, we studied the in vitro susceptibility of LDL to copper-induced oxidation in 72 NIDDM patients and 94 well-matched non-diabetic control subjects. There was no significant difference in the lagtime of LDL oxidation between NIDDM patients and control subjects (68.168.8 vs. 66.769.2 min, respectively, P 5 0.29). The plasma a-tocopherol / LDL-ratio was the most significant determinant of the lagtime in multiple regression analysis. High level of serum triglycerides was associated with decreased lagtime in control subjects, but not in NIDDM patients. Blood glucose balance was not associated with LDL susceptibility to oxidation in NIDDM patients. Subjects with CHD did not have LDL
Ex vivo measures of LDL oxidative susceptibility predict carotid artery disease
Atherosclerosis, 2005
Aim: The purpose of the study was to assess whether ex vivo measures of low-density lipoprotein (LDL) oxidation improved prediction of carotid artery disease (CAAD) case-control status compared to standard lipid and smoking measures. Methods: One hundred and forty cases with a high degree of carotid artery stenosis aged 40-83 years and an equal number of controls without stenosis or other vascular disease were matched by censored age within 2 years. Matched logistic regression evaluated the significance of copper-induced oxidative measures with and without covariates. The relationship of LDL oxidation measures with statin use and current smoking was also evaluated. Results: Logistic regression demonstrated a significant effect of the three correlated measures of oxidative susceptibility (lag time, oxidation rate and maximal rate of oxidation) separately on disease prediction (all p < 0.05). These oxidative measures remained significant predictors of case-control status when other cardiovascular disease predictors (age; LDL-C, HDL-C and ApoAI levels; current smoking, ever smoking and pack-years smoked) were jointly considered. This relationship was not attributable to the effects of statin use on LDL oxidation. Conclusions: Ex vivo measures of oxidation improved the prediction of carotid artery disease status, suggesting that this is an important determinant of atherosclerotic risk in this older population.