Density Lipoprotein In Patients Research Articles

Gamma-background environment during magnetic storms and the content of high density lipoprotein in patients with arterial hypertension depending on the temperament and variant of antihypertensive therapy

Gamma-background environment during magnetic storms and the content of high density lipoprotein in patients with arterial hypertension depending on the temperament and variant of antihypertensive therapy

Effects of supervised structured aerobic exercise training program on high and low density lipoprotein in patients with type II diabetes mellitus.

Background and Objective:Hyperlipidemia and dyslipidemia are very common conditions among patients with Type-2 diabetes mellitus (T2DM) and associated with increased risk of coronary heart diseases. Physical activity and exercises along with medical management and dietary plan are common strategies to use for the management of deranged lipid profile in patients with T2DM. We aimed to determine the effects of supervised structured aerobic exercise training (SSAET) program on high and low density lipoprotein in patients with T2DM.Methods:This randomized control trial study was conducted at Riphah Rehabilitation Research Centre (RRRC), Pakistan Railway General Hospital (PRGH) Rawalpindi from 1st January 2015 to 30th March 2016. The inclusion criteria was Type-2 diabetes patients of both gender aged between 40 to 70 years. Patients with severe complications like coronary artery diseases (CAD), and other serious complications like diabetic foot, and severe knee and hip osteoarthritis (OA) were excluded from the study. A total of 195 patients diagnosed with T2DM were screened out and 102 were selected for the study as per the inclusion criteria. All participants were randomly assigned into two groups, experimental ‘A’ (n=51) and control ‘B’ (n=51). Patients in group A were treated with SSAET program of 25 weeks at 3 days a week in addition to routine medical management, while patients in Group-B were on their routine medications and dietary plan. Serum LDL, and HDL were tested at baseline and after 25 weeks. The data was analysed through SPSS 20.Results:Mean and standard deviation of LDL in group A (n=51) was 118.56±19.17 (pre) and 102.64±13.33 (post), while the mean and standard deviation for Group-B (n=51) was 116.50±18.45 (Pre) and 109.88±17.13 (post). Both groups showed improvement but, Group-A treated with SSAET along with RMM showed significantly higher (P Value ≤ 0.05) improvement as compared with group B treated with RMM alone. Mean and standard deviation of HDL in Group-A was 42.70±8.06 (pre) and 47.47±7.16 (post), while the mean and standard deviation of group B is 43.37±8.15 (Pre) and 44.41±7.91 (post). Both groups showed improvement but Group-A treated with SSAET program along with RMM showed significantly higher (P Value ≤ 0.05) improvement than group B treated with RMM alone.Conclusion:SSAET program along with RMM is more effective strategy for the management of deranged lipid profile in patients with T2DM.

PHARMACOLOGICAL EFFECTS OF GEMFIBROZIL ON SOME CARDIOVASCULAR PREPARATIONS OF EXPERIMENTAL ANIMALS

Gemfibrozil (member of fibrates) is Peroxisome proliferator activated receptors (PPAR-α) agonist which improves lipid profiles particulary very low density lipoprotein and high density lipoprotein in patients with dyslipidemia.Objective: Studying the pharmacological effects of Gemfibrozil on some cardiovascular preparations of experimental animals. Materials and Methods: The experiments were conducted to study the effect of different doses of gemfibrozil on isolated perfused rabbit heart & coronary flow, isolated rabbit aortic spiral strip and mean arterial blood pressure of anaesthetized cats. Each experiment was done on six preparations. Results: In-vitro study: onisolated perfused rabbit heart, gemfibrozil (25-800µg/ml) produced a dose-dependent reduction on the amplitude of myocardial contractions. The inhibitory effect of gemfibrozil (100µg/ml) was not abolished after complete blockade of nicotinic and muscarinic receptors while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of calcium gluconate, isoprenaline, histamine and serotonin were not abolished after administration of gemfibrozil (100µg/ml). On coronary flow of isolated perfused rabbit heart, gemfibrozil (25-800μg/ml) produced also a dose-dependent reduction of coronary flow. On isolated spiral aortic strips of rabbit , gemfibrozil produced dose-dependent significant reduction on nor-epinpherine (NE) induced contraction. In-vivo study gemfibrozil produced a dose-dependent significant reduction in mean arterial blood pressure (MABP) of anaesthetized cats. Conclusion: Gemfibrozil produced a negative inotropic effect through nitric oxide release with a decrease in coronary flow. It also reduced NE- induced contractions of aortic spiral strips with reduction in mean arterial blood pressure. So it must me used cauciously in cases of heart failure, but it could be beneficial in hypertensive patient with atherosclerosis.

High density lipoprotein in patients with liver failure; relation to sepsis, adrenal function and outcome of illness

High density lipoprotein (HDL) plays an important role in the transport of cholesterol to the adrenal gland for steroidogenesis and may have actions that modulate response to infection and critical illness. The clinical relevance of HDL level in patients with liver failure remains poorly characterised. In 164 critically-ill patients with acute (ALF) and acute on chronic liver failure (AOCLF) we evaluated the relationship between HDL levels measured on admission to intensive care unit (ICU) and survival, predisposition to sepsis and adrenocortical function assessed through the cortisol response to short synacthen testing (SST). In acute liver failure and acute on chronic liver failure, high density lipoprotein levels were significantly lower in non-survivors (P<0.01). Levels correlated closely with biochemical markers of liver function and the duration of liver failure. However, predictive accuracy was not superior to conventional markers and on multi-variate analysis did not show independent association with survival. Low HDL concentration was not associated with an increased incidence of sepsis either precipitating or complicating ICU admission. Evidence of adrenocortical insufficiency was present in more than half of patients undergoing SST and HDL level but not other lipid parameters correlated closely with cortisol increment after SST (r=0.364, P<0.0001). High density lipoprotein levels are low in patients with liver failure and reflect its severity. Levels are lower in non-survivors but do not offer an advantage as early indicators of prognosis over conventional markers. No evidence of a major predisposing role for infection was found, but findings suggest a close link to adrenal function.

The Causes and Consequences of Low Levels of High Density Lipoproteins in Patients with Diabetes

Type 2 diabetes is commonly accompanied by a low level of high density lipoprotein cholesterol (HDL-C) that contributes to the increased cardiovascular risk associated with this condition. Given that HDLs have the ability to improve increase the uptake of glucose by skeletal muscle and to stimulate the secretion of insulin from pancreatic beta cells the possibility arises that a low HDL concentration in type 2 diabetes may also contribute to a worsening of diabetic control. Thus, there is a double case for raising the level of HDL-C in patients with type 2 diabetes: to reduce cardiovascular risk and to improve glycemic control. Approaches to raising HDL-C include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. Of currently available drugs, the most effective is niacin. Newer formulations of niacin are reasonably well tolerated and have the ability to increase HDL-C by up to 30%. The effect of niacin on cardiovascular events in type 2 diabetes is currently being tested in a large-scale clinical outcome trial.

The role of dysfunctional HDL in atherosclerosis

This review focuses on HDL function in modulating LDL oxidation and LDL-induced inflammation. Dysfunctional HDL has been identified in animal models and humans with chronic inflammatory diseases including atherosclerosis. The loss of antiinflammatory function correlated with a loss of function in reverse cholesterol transport. In animal models and perhaps in humans, dysfunctional HDL can be improved by apoA-I mimetic peptides that bind oxidized lipids with high affinity.

Effect of Combination Nicotinic Acid and Gemfibrozil Treatment on Intermediate Density Lipoprotein, and Subclasses of Low Density Lipoprotein and High Density Lipoprotein in Patients With Combined Hyperlipidemia

The goal of this study was to determine, using analytic ultracentrifugation, the effect of nicotinic acid alone or nicotinic acid added to gemfibrozil on lipoprotein subclass distribution, including intermediate-density lipoprotein (IDL; low-density to very low density flotation rate [S(f)] 12 to 20); low-density lipoprotein (LDL) subfractions LDL-I (S(f) 7 to 12), LDL-II (S(f) 5 to 7), LDL-III (S(f) 3 to 5), and LDL-IV (S(f) 0 to 3); and high-density lipoprotein (HDL) subfractions HDL(2) (high-density flotation rate 3.5 to 9.0) and HDL(3) (high-density flotation rate 0 to 3.5). Patients with combined hyperlipidemia were randomized to nicotinic acid (1,500 mg/day) plus placebo or nicotinic acid plus gemfibrozil (1,200 mg/d) for 12 weeks. Baseline characteristics were similar between the 2 groups, and mean LDL cholesterol (180 +/- 33 mg/dl) and triglycerides (310 +/- 126 mg/dl) were typical for patients with combined hyperlipidemia. Treatment with nicotinic acid resulted in a reduction in dense LDL (S(f) 5 to 7; p = 0.02), which was counterbalanced by an increase in buoyant LDL (S(f) 7 to 12; p = 0.03) that resulted in no significant LDL mass or LDL cholesterol change. IDL was reduced (p = 0.005) and HDL(2) increased by 143% (p = 0.004). The combination of nicotinic acid and gemfibrozil resulted in a further 17.8% reduction in apolipoprotein B (p = 0.06), a further 33.8% reduction in IDL (p = 0.06), and a greater reduction in the apolipoprotein B/apolipoprotein A-I ratio (p = 0.02). The combination of nicotinic acid and gemfibrozil reduced atherogenic by IDL 71%, dense LDL-III by 52%, and apolipoprotein B by 37% and increased protective HDL(2) by 90%. In conclusion, this investigation revealed that a combination of a fibric acid derivative and nicotinic acid offers greater improvement in detailed lipoprotein subclass distribution and apolipoprotein ratios than monotherapy.

Decreased oxidation susceptibility of plasma low density lipoproteins in patients with Gilbert's syndrome

The association of hyperbilirubinemia in Gilbert's syndrome (GS) with a decrease in prevalence of coronary artery disease is a well-known phenomenon. In this study, the state of low-density lipoprotein (LDL) oxidation which has been postulated to be a significant determinant at the etiopathogenesis of atherosclerotic disorders was investigated among individuals with GS. For this purpose, serum cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, apolipoprotein A and B, bilirubins, thiobarbituric acid-reactive substances, and the sensitivity of LDL oxidation levels, as well as serum alanine aminotransferase, aspartate aminotranserfase, gamma glutamyl transferase, and alkaline phosphatase activities, were determined in 17 patients with Gilbert's syndrome and 15 healthy adults. There was no significant difference between the groups except the indirect bilirubin parameter (P < 0.001). In comparison with the healthy individuals, LDL oxidation levels between 75 and 120 min were significantly lower (P < 0.005) along with prolonged lag-phase in GS patients, indicating a delay in oxidation susceptibility. It is suggested that the chronic hyperbilirubinemia leading to a lag-phase prolongation in LDL oxidation and a decrease in LDL oxidation may be reason for the low percentage of coronary artery disease.

Implications of Nε-(Carboxymethyl)lysine in Altered Metabolism of Low Density Lipoproteins in Patients with Type 2 Diabetes and Coronary Artery Disease

The aim of this study is to evaluate the role of the glycoxidation product, NIµ-(carboxymethyl)lysine (CML), on the metabolism of LDL which can give rise to increased risks of Coronary Artery Disease (CAD) in Type 2 Diabetes Mellitus (T2DM) patients. Polyclonal anti-CML antibodies, were used for measurement of serum CML. CML concentrations were measured by competitive enzyme-linked immunosorbent assay (ELISA) in the serum of 81 T2DM patients with CAD, 86 T2DM without CAD and 104 healthy subjects. LDLs from the study groups were isolated and labeled with the fluorescence dye, 1, 1â�²-dioctadecyl-3, 3, 3â�², 3â�²-tetramethylindo carbocyanine perchlorate (DiI). LDL from healthy subjects was subjected to oxidation and glycation. Receptor-mediated uptake of labeled native and modified-LDL was studied in human hepatocellular carcinoma (HepG2) cells. CML concentrations were significantly higher in T2DM with CAD patients than diabetic patients but without CAD (529.5±83.6 vs. 425.1±64.4 ng mL-1, p<0.001). The uptake of DiI-LDL from type 2 diabetes patients without CAD was significantly lower than that for LDL from diabetic patients without CAD or glycated-LDL in HepG2 cells. This study demonstrated that CML may be largely responsible for the defective uptake of LDL of T2DM with CAD. Thus, CML may be used as endogenous biomarker for early detection of CAD in type 2 diabetes patients and may be considered as a new goal for the glycemic control in those patients.

Enhanced atherogenesis and altered high density lipoprotein in patients with Crohn's disease

A chronic inflammatory state is a risk factor for accelerated atherogenesis. The aim of our study was to explore whether Crohn's disease (CD), characterized by recurrent inflammatory episodes, is also associated with accelerated atherogenesis. In 60 CD patients and 122 matched controls, carotid intima media thickness (IMT), a validated marker for the burden and progression of atherosclerosis, was assessed ultrasonographically. Additional subgroup analyses, including plasma levels of acute phase reactants and HDL protein profiling, were performed in 11 consecutive patients with CD in remission, 10 patients with active CD, and 15 healthy controls. Carotid IMT in patients with CD was increased compared with healthy volunteers: 0.71 (0.17) versus 0.59 (0.14) mm (P < 0.0001), respectively. In the subgroup analysis, HDL levels in controls and patients in remission were identical [(1.45 (0.48) and 1.40 (0.46) mmol/l; P = 0.797], whereas HDL during exacerbation was profoundly reduced: 1.02 (0.33) (P = 0.022). HDL from patients with active CD and CD patients in remission was characterized by a reduced ability to attenuate oxidation compared with controls (P = 0.008 and P = 0.024 respectively). Patients with CD have increased IMT compared with matched controls, indicative of accelerated atherogenesis. The changes during CD exacerbation in terms of HDL concentration and composition imply a role for impaired HDL protection in these patients.

Abstract 1390: Composition Analysis of High Density Lipoproteins in Patients with extreme HDL-C Levels with or without Ischemic Heart Disease

Objective: We hypothesize that patients with high HDL-C levels and Ischemic Heart Disease (IHD) may have dysfunctional HDL or have unrecognized non-conventional risk factors. Methods: Individuals with verified IHD with either high HDL-C (n=53; female: ≥73.5mg/dL; male: ≥61.9mg/dL) or low HDL-C (n=42; female:≤38.7mg/dL; male: ≤34.1mg/dL) were compared with subjects without IHD and matched HDL-C levels (n=110). All subjects had normal LDL-C (&lt;160mg/dL) and triglyceride levels (&lt;150mg/dL) and none were treated with LDL-C-lowering medications. After removal of apoB lipoproteins, apoA-I, apoA-II, apoE, triglycerides, free cholesterol, cholesteryl ester, and phospholipids were analyzed (Cobas-Fara). HDL and LDL-subclasses were examined by linear gradient gel electrophoresis (Lipoprint®) and by Segmented Gradient Gel Electrophoresis (S-GGE). Cholesterol (RLP-C) and triglyceride (RLP-TG) content of remnant-like lipoprotein particles were measured by an immunoseparation technique. Results: Subjects with high HDL-C levels and IHD had lower apo-AI (p&lt;0.001) and cholesteryl ester (p&lt;0.01) levels compared to controls with high HDL and no IHD. Subjects with low HDL-C and IHD had lower triglyceride (p=0.01) levels compared to controls with matched HDL-C levels and no IHD. The HDL subclass, using S-GGE, with density 1.063–1.100g/ml and diameter 98 –130Å correlated with levels of HDL-C (r 2 =0.66, p&lt;0.0001). LDL subclasses using Lipoprint® exhibited higher fraction of Intermediate Density Lipoproteins (IDL-C) in patients with high HDL-C and IHD when compared with individuals with same HDL-C and no IHD (p=0.006). This was also true in the low HDL-C groups (p=0.01). This was further supported by higher levels of RLP-C and RLP-TG in individuals with high HDL and IHD (p=0.03 and p=0.03, respectively) when compared with respective controls. Conclusions: These results suggest that HDL composition rather than HDL-C levels is important in deciphering the protective role of HDL in IHD and that measurement of remnant-like lipoproteins may be useful for identifying patients with high HDL-C that are still at risk for developing IHD.

High Dose Alpha Tocopherol therapy does not affect subfractions of High Density Lipoproteins in patients with Coronary Artery Disease on Statin therapy

Low levels of High density lipoprotein (HDL) are predictive of coronary heart disease (CHD). However, subfractions of HDL are implicated as better indicators of the disease process. The large HDL particles (HDL2) are inversely correlated to the severity of coronary artery disease (CAD). Alpha tocopherol (AT) is the main lipid soluble antioxidant in plasma and is anti-inflammatory. Previously, a small study (n=44) showed that the combination of an antioxidant cocktail (800 IU/d RRR-AT plus 1g Vitamin C, 25 mg β-carotene and 100 ug Se) with simvatstatin –niacin (S-N) therapy attenuated the protective increase in HDL2 seen with S-N alone. Thus, we tested the effect of high dose RRR-AT (1200 IU/d for 2 yrs) supplementation on HDL subfractions in a prospective randomized placebo-controlled study in a larger population of patients (n=90) with stable CAD on AT / placebo at 5 different time points (baseline, 6 months, 1 year, 1½ and 2 years). Importantly, 94% of the patients were on statin therapy. HDL subfractions were analyzed by NMR spectroscopy and divided into large (8.8 to 13.0nm), medium (8.2 to 8.8 nm), and small (7.3 to 8.2 nm) HDL particles. AT levels significantly increased (p<0.05) following therapy compared to placebo. There were no differences in the plasma total cholesterol, TG or LDL-C. AT therapy over 2 years had no significant effect on total (p=0.5), large (p=0.6), medium (p=0.8) and small (p=0.9) HDL particles compared to baseline or placebo. We conclude that high dose RRR-AT therapy over 2 years, in patients with CAD on statin therapy, does not negatively affect HDL subclasses. Thus the negative interaction previously proposed between antioxidant cocktail and statin therapy cannot be ascribed to AT. NIH RO1

The correlation between negative mood and serum oxidized low density lipoprotein in patients with coronary heart disease

目的 探讨不良心境对冠心病(CHD)患者血清氧化低密度脂蛋白(ox-LDL)浓度影响,及其相关性.方法110例住院冠心病患者和40名健康体检者(对照组)作为研究对象.用焦虑自评量表(SAS)、抑郁自评量表(SDS)、焦虑状态-特质问卷(STAI)制定不良心境标准.以不良心境标准为分组依据,将入组的CHD患者分为严重不良心境组(31例)、一般不良心境组(37例)、无明显不良心境组(42例).酶联免疫吸附试验(ELISA)法测CHD患者血清ox-LDL的水平.用f检验和Pearson直线相关分析法进行统计分析.结果1.严重不良心境组、一般不良心境组、无明显不良心境组CHD患者血清ox-LDL水平[分别为(0.63±0.20)mg/L,(0.52±0.14)mg/L,(0.51±0.11)mg/L]明显高于正常对照组[(0.44±0.19)mg/L],严重不良心境组CHD患者的血清ox-LDL浓度明显高于一般不良心境组、无明显不良心境组,差异有显著性(P＜0.05).一般不良心境组、无明显不良心境组血清ox-LDL差异无显著性(P＞0.05);2.严重不良心境组CHD患者血清ox-LDL浓度与不良心境显著正相关(r=0.398,P＜0.05).3.冠心病患者血清ox-LDL与总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)浓度呈显著正相关(r=0.395～0.459,P＜0.05),与高密度脂蛋白胆固醇(HDL-C)呈显著负相关(r=-4.07,P＜0.05).结论不良心境能促进CHD的发生发展,是诱发CHD的危险因素。

Mo-P5:357 Enhanced atherogenesis and altered high density lipoprotein in patients with Crohn's disease

Mo-P5:357 Enhanced atherogenesis and altered high density lipoprotein in patients with Crohn's disease

Th-P15:202 Transfer of lipids from a cholesterol-rich nanoemulsion to high density lipoprotein in patients with type 2 diabetes

Th-P15:202 Transfer of lipids from a cholesterol-rich nanoemulsion to high density lipoprotein in patients with type 2 diabetes

Inhibition of HMG-CoA Reductase with Cerivastatin Lowers Dense Low Density Lipoproteins in Patients with Elevated Fasting Glucose, Impaired Glucose Tolerance and Type 2 Diabetes Mellitus

While 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors effectively decrease LDL cholesterol, it remains controversial whether these agents also lower dense LDL, which are considered particularly atherogenic. We examined the effects of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin on lipids, lipoproteins, and apolipoproteins in 69 patients with elevated fasting glucose, impaired glucose tolerance, or type 2 diabetes, combined hyperlipoproteinemia and increased concentrations of dense LDL (apo B in LDL-5 plus LDL-6 > 25 mg/dl). The study was a multicenter, double-blind, randomized, parallel-group comparison of cerivastatin at 0.4 mg daily for 12 weeks (n = 34) and placebo (n = 35). Cerivastatin significantly reduced cholesterol (- 20 %, p < 0.001), IDL cholesterol - 37 %, p < 0.001), LDL cholesterol (- 26 %, p < 0.001), apolipoprotein B (- 25 %, p < 0.001), triglycerides (- 12 %, p < 0.05), and raised HDL cholesterol (+ 7.5 %, p < 0.05) and apolipoprotein AI (+ 7.2 %, p < 0.05). Cerivastatin signficantly lowered apolipoprotein B in all LDL subfractions (- 21 to - 28 %, p < 0.05). Absolute changes were greatest in dense LDL and the change in dense LDL made the largest contribution to the change of total LDL. The change of dense LDL was highly correlated with baseline values. There was no consistent relationship between the effect of cerivastatin on triglycerides and the decrease of dense LDL. The HMG CoA reductase inhibitor cerivastatin lowers total and LDL cholesterol and the concentration of dense LDL in patients with elevated fasting glucose, impaired glucose tolerance or type 2 diabetes.

Oxidized Low Density Lipoprotein in Patients with Kawasaki Disease

Background: Recently, more and more studies have demonstrated that oxidized low density lipoprotein (ox-LDL) played a key role in the pathogenesis of adult coronary artery disease. This study was to investigate the ox-LDL and general lipoprotein profiles in patients with Kawasaki disease.Methods: Forty consecutive patients with Kawasaki disease who underwent cardiac catheterization were studied prospectively. We classified the patients into two groups: Group A consisted of 12 patients with coronary artery disease, coronary stenosis or aneurysm. Group B consisted of 28 patients with normal coronary angiography. Blood sample was tested for the levels of ox-LDL autoantibody, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG).Results: There were no significant differences between two groups in gender, age of onset of disease, TG, cholesterol, HDL-C, LDL-C, and TC/HDL. There was significantly higher level of ox-LDL in group A than that in group B (p=0.008).Conclusions: There is significantly higher level of ox-LDL in patients of Kawasaki disease with coronary artery disease. The role of Ox-LDL needs further studies.

The autoantibody expression against different source of oxidized low density lipoprotein in patients with acute myocardial infarction

The aim of this study was to examine the expression of antibodies against two different sources of low density lipoprotein (LDL) that were oxidized by CuSO 4, in patients with early stage of acute myocardial infarction (AMI). When LDL purified from sera with high level of LDL was used as a modified antigen, the results indicated that the titers of antibodies against the oxidized LDL in 30 patients were increased by 135% compared to those in normal subjects; however, the titers of antibody against modified LDL purified from normal-range LDL in the same patients were only slightly increased by 52%. Comparing the levels of autoantibody expressed in the high LDL sera group, high triglyceride sera group, and AMI patients sera group (total of 41; in addition to 30 AMI patients, 11 more sera of AMI patients were collected), the amount of autoantibody against the oxLDL purified from high LDL sera in AMI patients sera group was significantly increased up to 195%. In contrast to AMI patients, the sera titers against the same antigen in two subject groups with either high LDL or high triglyceride are only 50% higher than normal subjects. Moreover, the ratio of thromboxane B 2 over 6-keto-prostaglandin F 1α (6-keto-PG F 1α) in the acute myocardial infarction patients was 1.79, which is much lower than the normal subjects, 4.19. Concluding from the above observations, we suggest that the expression level of anti-oxidized LDL antibody may play a role on the pathogenesis of acute myocardial infarction disease, but is independent with the levels of thromboxane A 2 and prostacyclin in the examined sera.

Autoantibody against, malondialdehyde-modified low density lipoprotein in patients with non-diabetic unstable angina: a potential role in immunologic reaction of plaque instability.

The role of autoantibody against oxidized low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis is still unknown. The purpose of this study was to determine whether autoantibodies against malondialdehyde (MDA)-modified LDL are associated with coronary artery disease (CAD) and clinical presentations of CAD in non-diabetic patients without acute myocardial infarction (AMI). We determined the serum levels of autoantibody against MDA-modified LDL by ELISA in 71 patients with angiographically significant CAD (> or = 50% diameter stenosis in at least 1 vessel) and 80 controls without angiographically significant CAD. Among the total 151 subjects, 30 subjects did not have any clinical ischemic event, 90 subjects had stable angina symptoms, and 31 subjects had unstable angina symptoms. The autoantibody titer, expressed mean optical density units, was significantly higher in patients with CAD than in controls (0.177 +/- 0.014 versus 0.127 +/- 0.011, respectively; p=0.006) and higher in unstable angina group than in stable angina group (0.240 +/- 0.025 versus 0.145 +/- 0.007, respectively; p < 0.001). By logistic regression analysis, the high autoantibody titer was associated significantly with CAD (P=0.008), independent of age, gender, body mass index, triglyceride concentration, and the ratio of total cholesterol-high density lipoprotein (HDL) cholesterol. In multiple regression analysis, presence of CAD, smoking history and low HDL-cholesterol level were independent factors associated with a increased anti-oxLDL Ab titer. The autoantibody titer was significantly lower in nonsmoker than smoker (p=0.019) and higher in low HDL- cholesterol (< or = 35 mg/dl) group than in high HDL-cholesterol group (p=0.012). Elevated autoantibody titer was associated with CAD and the unstable clinical presentation of CAD. Our results suggest that immune response to oxidized LDL may play a role in the pathogenesis of atherosclerosis and plaque instability.

Autoantibodies against oxidized low density lipoproteins in patients with stable angina, unstable angina or peripheral vascular disease; pathophysiological implications.

Antibody antioxidized low density lipoproteins (oxLDL) might play a role both in atherogenesis and in the pathogenesis of acute coronary syndromes. Antibody titres to oxLDL and levels of C-reactive protein were compared in unstable angina, stable angina or peripheral artery disease. Antibody titres to LDL oxidated by CuSO(4)for 2, 4 and 18 h (Cu-oxLDL-Ab(2-4-18)) or by peroxidase (HRP-oxLDL-Ab) were assessed by ELISA. Cu-oxLDL-Ab(2-4-18)were consistently higher in peripheral artery disease than in unstable angina (P<0.001, P<0.001, P=0.01, respectively) or in stable angina (P<0.001, P=0.01, P=ns) but similar in unstable and stable angina. Accordingly, HRP-oxLDL-Ab were higher in peripheral artery disease than in unstable angina (P<0.001) or stable angina (P=0.04) but similar in unstable and stable angina. The number of arterial stenoses was higher in peripheral artery disease than unstable and stable angina (P<0.01). Cu-oxLDL-Ab and HRP-oxLDL-Ab correlated with the severity of atherosclerosis (P<0.01, R=0.4;P=0.02, R=0.3 respectively). Conversely, C-reactive protein levels were higher in unstable than in stable angina (P<0.001) or in peripheral artery disease (P<0.03) but similar in stable angina and peripheral artery disease and did not correlate with the severity of atherosclerosis. The autoimmune response to oxLDL is likely to play an important role in atherogenesis but not in precipitating acute coronary syndromes.