Small Dense LDL Particles in Relation to LDL Oxidation in Normolipidemic CAD Patients

摘要

Aims: Lipid and lipoprotein cholesterol levels are not predictive of coronary artery disease (CAD) risk in all the subjects. The heterogeneity of lipoprotein particles plays an important role in this respect. This fact needs to be studied in normolipidemic CAD patients. The aim of the present study was to evaluate the role of small dense LDL particles in relation to LDL oxidation in normolipidemic coronary artery disease patients. Methods and Results: One hundred and twenty eight CAD patients and 200 age and sex matched normal individuals were studied. Subjects were screened for various biochemical investigations such as lipid profile, serum apoB, LDL apoB carbonyl content, MDA-LDL levels. Log (TG/HDL-C) ratio was taken as an index of LDL particle size. In the present study, lipid levels could not discriminate well between patients and normal subjects. However normolipidemic CAD patients had increased positive values of log (TG/HDL-C) as compared to controls indicating the predominance of small dense LDL particles. This was further supported from the raised serum apoB levels. LDL apoB carbonyl content (LDL protein oxidation) and MDA-LDL levels (LDL lipid peroxidation) were raised in normolipidemic CAD patients as compared to normal subjects. Conclusions: Assessment of LDL particle size and LDL oxidation status might be more predictive of CAD risk even in subjects with normal lipid and lipoprotein cholesterol levels. Introduction The relationship between plasma LDL cholesterol levels and atherosclerosis has evolved over the past fifty years. The National Cholesterol Education Programme Adult Treatment Panel formulated recommendations for therapy to prevent CAD on the basis of LDL cholesterol levels 1. However, with subsequent research it was revealed that LDL particles are heterogeneous in nature. LDL particles containing less cholesterol and increased triglyceride content are small and dense in nature. Small dense LDL particles are highly atherogenic. These particles possess an increased readiness for oxidation due to their lower antioxidant content, stimulate the endothelial dysfunction and are easily recognized by scavenger receptors leading to foam cell formation 2. Several studies reported heterogeneity of LDL particles with apoB enrichment in hypertriglyceridemic individuals 3, 4. Elevated apoB levels together with predominance of small dense LDL particles have been reported in patients suffering from coronary artery disease 5, 6. In the Quebec study (13 year follow-up study), small dense LDL particles were observed to be a strong independent predictor of CAD 7. The available data clearly suggests that small dense LDL particles increase the risk of coronary artery disease. Many of the studies reported the importance of small dense LDL particles in certain conditions associated with CAD such as hypertriglyceridemia, diabetes mellitus, metabolic syndrome 3,4,6. The significance of small dense LDL particles in CAD patients with normal lipid and lipoprotein cholesterol levels is not well covered in the literature even though many individuals suffering from coronary artery disease do have a normal lipid profile. Hence, it becomes important to look for the heterogeneity of LDL particles and their relationship with LDL oxidation in such individuals. In the light of these facts, the present study was aimed to investigate the role of small dense LDL particles in relation to LDL oxidation in normolipidemic CAD patients. Methods The present study was conducted on 128 CAD patients and 200 age and sex matched normal subjects. Diagnosis of CAD was carried out by the clinician on the basis of clinical symptoms, ECG changes and/or stress test and angiography (if required). The clinical condition of the normal subjects was confirmed by physical examination, ECG and/or stress test. The selection of CAD patients was framed on the basis of their lipid profile. CAD patients having normal lipid and lipoprotein cholesterol levels as per ATP III