High oxidative stress in patients with stable coronary heart disease

doi:10.1016/S0021-9150(03)00053-4

Atherosclerosis

Volume 168, Issue 1, May 2003, Pages 99-106

https://doi.org/10.1016/S0021-9150(03)00053-4 Get rights and content

Abstract

Oxidized low density lipoprotein (oxLDL) plays a pivotal role in the development of atherosclerosis. The aim of the study was to investigate the relationship between oxLDL and other oxidative stress biomarkers with stable coronary heart disease (CHD). We compared the degree of oxidative stress in patients with CHD and sex-matched healthy control subjects in a case-control study. The study included 64 male subjects: 32 patients with stable CHD and 32 normal control subjects. Levels of circulating oxLDL were measured by a monoclonal antibody 4E6-based competition ELISA. Comparison of oxidative stress marker levels between cases and controls, adjusted for age, revealed significantly higher plasma oxLDL levels (63.32±25.49 vs. 37.73±20.58 U/l, P=0.001), lower serum levels of autoantibodies against oxLDL (341.53±350.46 vs. 796.45±1034.2 mU/ml, P=0.021), higher activities of the antioxidant enzymes superoxide dismutase in erythrocytes (951±70.2 vs. 771.6±191.2 U/g, P=0.032) and glutathione peroxidase in whole blood (GSH-Px: 10 714.4±3705.4 vs. 5512.2±1498.1 U/l, P<0.001). The risk of having CHD was 20.6-fold greater (95% CI, 1.86–228.44, P=0.014) in the highest tertile of the oxLDL distribution than in the lowest, determined by logistic regression analysis on the combined study population after adjustment for age and other potential confounding factors. When the risk associated with GSH-Px levels was calculated, the odds ratio was 305.3 (95% CI, 5.07–18369.95, P=0.006) in the highest tertile compared with the lowest. Our results showed that an oxidative stress occurs in patients with CHD despite being clinically stable and under medical treatment. The combination of oxLDL levels and GSH-Px activity may be useful for the identification of patients with stable CHD.

Introduction

Oxidative stress produced by free radicals has been linked to the development of several diseases such as atherosclerosis, cancer, and neurodegenerative diseases [1]. The biological oxidative effects of free radicals on lipids, DNA, and proteins are controlled by a spectrum of exogenous dietary antioxidants, including vitamin E, C, and phenolic compounds, and by endogenous antioxidants including the scavenger enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) [2]. Furthermore, serum paraoxonase1 (PON1), a high density lipoprotein (HDL) linked enzyme, appears to have antioxidative properties [3]. The balance between free radical generation and antioxidant activity is critical to the pathogenesis of oxidative stress related disorders [1], [2]. Elevated oxidative stress and superoxide anion formation in vascular cells could promote conversion of low density lipoprotein (LDL) to atherogenic oxidized LDL (oxLDL). One of the earliest steps in the generation of oxidatively modified LDL is the peroxidation of its polyunsaturated fatty acids. The oxidative breakdown of these fatty acids, such as malondialdehyde (MDA) and 4-hydroxynonenal, form covalent bands with lysine residues of apolipoprotein B (apoB). The modified apoB has immunogenic properties [4]. Several studies have been conducted to investigate the role of autoantibodies against oxLDL (OLAB), suggesting that OLAB reflect the degree of oxidative modification of LDL, but the results are controversial [5], [6].

High levels of oxLDL are found in patients with different acute coronary syndromes, indicating that oxLDL might be a marker for atherosclerosis [7], [8], [9]. However, controversial data have been obtained in patients with stable coronary heart disease (CHD) [7], [8]. The aim of this study was to compare the degree of oxidative stress in patients with stable CHD and healthy subjects, and to study the association between oxLDL and other oxidative stress biomarkers with stable CHD.

Section snippets

Subjects

The present case-control study was nested within the Spanish Olive Oil Study (SOLOS) which is aimed at evaluating the antioxidant effect of olive oil in healthy volunteers and CHD patients. The study was conducted in 32 healthy non-smoking male volunteers aged from 23 to 92 years (mean, 57 years) and in 32 male patients aged from 42 to 82 years (mean, 68 years) with stable CHD and angiographically documented coronary stenosis. For the present study, serum samples drawn at entry (basal level)

Patient characteristics

CHD patients were older than the control group (P<0.01). The clinical characteristics of the study group are presented in Table 1. CHD patients had a higher BMI than the control group. Plasma levels of TC, LDL-C, TG, and Lp(a) were similar, while the CHD patients had significantly lower HDL-C levels than the control group. Coronary angiograms of patients showed at least 50% stenosis of 1 (n=14 patients), 2 (n=11 patients), or 3 (n=7 patients) vessels. Nine patients had CHD complicated by

Discussion

In the present study, we have determined several oxidative stress biomarkers in stable CHD patients and healthy volunteers. Our results showed oxidative stress to be high in CHD patients despite being clinically stable and under medical treatment. This oxidative stress was reflected by the increase of oxLDL levels together with high levels of the antioxidant enzymes SOD and GSH-Px.

Free radical production induces antioxidant enzyme activity as a protective mechanism against free radical injury.

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High oxidative stress in patients with stable coronary heart disease

Abstract

Introduction

Section snippets

Subjects

Patient characteristics

Discussion

Lancet

Free Radic. Biol. Med.

Lancet

J. Biol. Chem.

Clin. Chim. Acta

Lancet

Atherosclerosis

Free Radic. Biol. Med.

Clin. Immunol.

Atherosclerosis

Atherosclerosis

Lipid peroxidation and antioxidants as biomarkers of tissue damage

Clin. Chem.

Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity

N. Engl. J. Med.

Antibodies to oxidized LDL in relation to carotid atherosclerosis, cell adhesion molecules, and phospholipase A(2)

Arterioscler. Thromb. Vasc. Biol.

Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease

Circulation

Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes

Circulation

Circulating oxidized low density lipoprotein levels. A biochemical risk marker for coronary heart disease

Arterioscler. Thromb. Vasc. Biol.