Myeloperoxidase level and inflammatory markers and lipid and lipoprotein parameters in stable coronary artery disease.

BACKGROUND: Myeloperoxidase (MPO) impairing endothelial functions. We investigated whether increasing concentration of myeloperoxidase (MPO) and inflammatory markers induce progression and incident acute coronary syndrome (ACS) in stable coronary artery disease (SCAD) patients. Therefore, the concentration of MPO, lipids, lipoproteins (apo(apolipoprotein) AI, apoB, lipoprotein associated phospholipase A2 (LpPLA2) level), inflammatory markers (high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) concentration) were examined. METHODS: This study concerned 67 SCAD patients divided into groups: all patients, patients with MPO < 200 ng/ml, MPO 200-300 ng/ml, MPO > 300 ng/ml concentration and 15 controls. ApoAI, apoB and hsCRP levels were examined using the immunonephelometric method, and MPO, LpPLA2, IL-6, TNF-α concentration was performed by using Quantikine ELISA kit R&D Systems. RESULTS: In the all patients, and in group with MPO 200-300 ng/ml TC, LDL-C, nonHDL-C, LpPLA2 concentration and TC/HDL-C, LDL-C/HDL-C ratios were insignificant, and significantly higher concentration of TG, apoB, MPO, inflammatory markers and TG/HDL-C, MPO/apoAI, MPO/HDL-C ratios but HDL-C, apoAI level and HDL-C/apoAI ratio were significantly reduced. In the group of patients with MPO < 200 ng/ml, level of TC, LDL-C, nonHDL-C, apoAI, apoAII, LpPLA2 and MPO and LDL-C/HDL-C ratio were in-significant, HDL-C was decreased but apoB, TG, inflammatory markers, apoB/apoAI, TG/HDL-C, MPO/apoAI, MPO/HDL-C ratio were significantly increased. In the group of patients with MPO > 300 ng/ml concentration of TC, LDL-C, nonHDL-C, apoAII, LpPLA2 and LDL-C/HDL-C ratios were not significant, but HDL-C and apoAI concentrations were significantly decreased. The concentrations of TG, apoB, MPO and inflammatory markers and TG/HDL-C, MPO/apoAI, MPO/HDL-C ratios were significantly increased compared to the controls. The apoAI concentration was significantly decreased and the concentration of MPO and hsCRP as well as MPO/apoAI and MPO/HDL-C ratios were significantly higher as compared to the group of patients with MPO < 200 ng/ml. Spearman's correlation test showed a positive correlation between MPO concentration and MPO/apoAI and MPO/HDL-C ratios in all patients and MPO < 200 ng/ml, MPO 200-300 ng/ml. The patients with MPO > 300 ng/ml showed a positive correlation between the concentration of MPO and the level of hsCRP and IL-6, and a negative correlation between MPO/apoAI ratio and the concentration of HDL-C, apoAI and apoAII. CONCLUSION: The results suggest that moderate dyslipidemia and dyslipoproteinemia deepening of inflammation, and inflammation slowly induce increase MPO concentration which decrease apoAI and HDL-C level and disturb HDLs function. The increasing MPO level and MPO/HDL-C, MPO/apoAI ratios can differentiate the SCAD patients at the risk of acute coronary syndrome (ACAD) and stroke.

Lipids and lipoproteins and inflammatory markers in patients with chronic apical periodontitis.

BACKGROUND: Since chronic apical periodontitis (CAP) appears to be a risk factor for coronary heart disease, the aim of the study was to determine the relationship between the size of CAP lesion and inflammatory markers (hsCRP, IL-6, TNF-α), as well as lipids and lipoproteins (LpPLA2, apoAI, apoB level) in blood serum of patients with CAP. METHODS: The patients studied (n = 43) were divided into groups: patients under 50 and over 50 years of age, and a separate subgroup of the oldest age with the largest size of CAP lesions. Apolipoprotein AI (apoAI) above 150 mg/dL and below 150 mg/dL was used as an important criterion for the division of patients into groups. The CAP lesion size was measured using the Kodak digital imaging system software. The control group consisted of clinically healthy volunteers (n = 20) without CAP. Lipids were measured on a Siemens analyzer (Germany), apoAI, apoB, hsCRP levels were determined by immunonephelometric method, using the Health Care Diagnostic Product (Siemens GmbH, Germany), and IL-6, TNF-α and LpPLAG7 assay kits (ELISA, R&D Systems) were used. RESULTS: The findings suggested that in patients with CAP and their age increase, the CAP lesion size, the concentration of inflammatory markers and LpPLA2 mass increased. Correlations between the CAP lesion size and LpPLA2 mass and between the CAP lesion size and TG level in patients with apoAI 150 ≤ mg/dL showed increase TG in atherogenic apoB-containing triglyceride-rich lipoprotein and TC in cholesterol-rich lipoprotein. The patients with a low apoAI and high LpPLA2 level can have a higher risk of odontogenic disease and progression of atherosclerosis and coronary heart disease. CONCLUSION: We have found a positive correlation between apoAI level and the CAP lesion size and a negative correlation between LpPLA2 level and the CAP lesion size. The results suggest that apoAI and LpPLA2 in HDL particles have antiinflammatory action and together can limit the CAP lesion size in patient with a higher apoAI level. The literature data on the distribution of lipoprotein particles in subjects are still insufficient, so this problem requires further studies.

Alteration in diurnal and nocturnal melatonin serum level in patients with chronic heart failure.

INTRODUCTION: Melatonin is best known for its influence on circardian physiology. The circulating levels of the hormone vary in a daily cycle, allowing the regulation of the circadian rhythms of several biological functions. Melatonin is now considered as a cardioprotective factor and its secretion might be influenced by the clinical course of CHF. OBJECTIVE: Assessment of the alteration in diurnal and nocturnal melatonin serum levels in patients with chronic heart failure. MATERIAL AND METHODS: The study group consisted of 32 patients diagnosed with CHF according to ESC criteria. The study group was divided into two subgroups: patients in NYHA class II (n=21, 8 women) and patients in NYHA class III (n=11, 6 women). In all patients, serum melatonin levels at 02:00 and at 07:00 were determined using competitive enzyme immunoassay technique. High-sensitive C-reactive protein (HsCRP) was determined with nephelometric method. RESULTS: Mean hsCRP level was 0.368 (0.195; 0.794) mg/l and 0.54 (0.128; 1.04) mg/l in the group NYHA II and NYHA III patients, respectively; the difference was not statistically significant. NTproBNP levels were higher in NYHA III group than in the group NYHA II [2300 (1509;6317) pg/ml vs 7157 (4155; 13339) pg/ml]; the difference was substantial and approached the level of statistical significance (p=0.057). In both subgroups, higher levels of melatonin at 02:00 than at 07:00 was noticed; however, the differences were not statistically significant (p>0.05). In NYHA III subgroup lower levels of melatonin were observed at both time points; the difference was not statistically significant. CONCLUSION: The study results suggest that in patients with advanced heart failure (NYHA III but not NYHA II), nocturnal melatonin secretion is negatively correlated with NTproBNP.

Association between lipids, lipoproteins composition of HDL particles and triglyceride-rich lipoproteins, and LCAT and CETP activity in post-renal transplant patients.

High-density lipoprotein (HDL) remodeling within the plasma compartment and the association between lecithin-cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) activity, and lipid, lipoprotein concentrations and composition were investigated. The aim was to examine the high sensitivity of C-reactive protein (hsCRP), lipid, apolipoprotein B (apoB), apoAI, total apoAII, apoAIInonB, apoB-containing apoAII (apoB:AII), total apoCIII, apoCIIInonB, apoB-containing apoCIII (apoB:CIII) concentration and LCAT and CETP activity to gain an insight into the association between them and LCAT and CETP, 57 post-renal transplant (Tx) patients with and without statin therapy and in 15 healthy subjects. Tx patients had moderate hypertriglyceridemia, hypercholesterolemia, and dyslipoproteinemia, disturbed triglyceride-rich lipoproteins (TRLs) and HDL composition, decreased LCAT, and slightly increased hsCRP but no CETP activity. Spearman's correlation test showed the association between lipids and lipoproteins and LCAT or CETP, and multiple ridge stepwise forward regression showed that immunosuppressive therapy in Tx patients can disturb HDL and TRLs composition. The results suggest that inhibition or activation of LCAT is due, in part, to HDL-associated lipoprotein. Lipoprotein composition of apoAI, apoAIInonB, and apoCIIInonB in HDL particle and apoB:AII TRLs can contribute to decrease LCAT mass in Tx patients. Tx patients without statin and with lower triglycerides but higher HDL cholesterol concentration and disturbed lipoprotein composition of ApoAI and apoAII in HDL particle can decrease LCAT, increase LDL cholesterol, aggravate renal graft, and accelerate atherosclerosis and chronic heart diseases.

Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients.

Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I (apoA-I) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-ß-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.

Relationships between serum lipid, lipoprotein, triglyceride-rich lipoprotein, and high-density lipoprotein particle concentrations in post-renal transplant patients.

OBJECTIVE: Disturbances in lipid and lipoprotein profiles in patients after kidney transplantation (Tx) are still not understood. METHODS: Serum levels of lipids, lipoprotein, triglyceride-rich lipoproteins (TRLs), and high-density lipoprotein (HDL) particles were determined, lipid and lipoprotein ratios were calculated, and their relationships in Tx patients with hypertriglyceridemia (HTG) and lower apolipoprotein AI (apoAI) concentration were examined. Serum lipid and lipoprotein levels were measured in 109 Tx patients and 89 healthy subjects. HDL particle levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Tx patients had disturbed concentration, composition, and metabolism of TRLs and HDL particles. Multivariance analysis showed significant and positive correlation between HDL cholesterol/apoAI (HDL-C/apoAI) and HDL-C/HDL ratios, which indicates that both ratios could sensitively reflect changes in the HDL subclasses and their distribution into smaller size particles. In Tx patients, the decreased HDL-C/apoAI ratio indicates that, along with the decreased apoAI concentration, the HDL-C level is decreased. However, a low HDL-C/HDL ratio indicates that HDL particles in Tx patients transport lesser content of HDL-C but more triglyceride (TG) (high TG/HDL ratio), and thus are hypercatabolized and removed; therefore, concentration of HDL particles in serum was decreased. CONCLUSION: The decrease of HDL-C/apoAI ratio seems to be a good marker of HDL subclass distribution into smaller size particles.

Disturbed lipids, lipoproteins and triglyceride-rich lipoproteins as well as fasting and nonfasting non-high-density lipoprotein cholesterol in post-renal transplant patients.

Serum levels of lipids and lipoproteins were determined in 98 post-renal transplant fasting patients, and lipids and non-high density lipoprotein-cholesterol (non-HDL-C) and lipid ratios in the same post-renal transplant non-fasting patients were compared. The reference group was 87 healthy subjects. All patients were divided into two groups: patients with dyslipidemia (n = 69) and patients with normolipidemic (n = 29). The post-renal transplant patients (TX) with dyslipidemia had a significantly increased concentration of triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), non-HDL-C, apoB, and TRL and lipid ratios, and decreased HDL-C level and lipoprotein ratios. The lipids, lipoproteins, and lipoprotein ratios were significantly beneficial in TX patients with normolipidemic than in those with dyslipidemia. However, TRL concentration and lipid ratios were significantly increased and apoAI/apoCIII significantly decreased as compared to the reference group. The TX patients with dyslipidemia showed a significant correlation between TG and apoB:CIII (r = 0.562, p < 0.001) and apoCIII (r = 0.380, p < 0.004), but those with normolipidemic showed a significant correlation only between TG and apoCIII (r = 0.564, p < 0.008). Regression and Bland-Altman analyses showed excellent correlation between fasting and nonfasting non-HDL-C levels (r = 0.987, R(2) + 0.987) in TX patients both with dyslipidemia and normolipidemic. We think the finding that nonfasting labs that are reliable for non-HDL-C as well as total cholesterol is important, as fasting labs are not always available. Disturbances of lipids, lipoproteins, and TRLs depend not only on the kind of treatment, but due to multiple factors can accelerate cardiovascular complications in post-renal transplant patients with dyslipidemia and also with normolipidemic. Further studies concerning this problem should be completed.

A long-term study of dyslipidemia and dyslipoproteinemia in stable post-renal transplant patients.

BACKGROUND: Dyslipidemia is a major risk factor for atherosclerotic disease in renal transplant patients. METHODS: The serum levels of lipids and lipoproteins were determined in the same 12 post-renal transplant patients (TX) 10-29 and 73-122 months after transplantation. Thirteen healthy subjects--i.e., without diabetes, endocrine disease, liver disease, active inflammatory disease, glucose intolerance, malignancy, obesity, and urinary protein--were used as a reference group. TX patients had stable renal function. Twelve patients received cyclosporine A and prednisone, six received lovastatin, and one received rapa and prednisone. Lipids and lipoprotein (apo)AI and B were determined using Roche kits. An anti-apoB antibody was used to separate apoB-containing apoCIII and apoE lipoproteins as triglyceride-rich lipoproteins (TRLs) in the non-HDL fraction from apoCIIInonB and apoEnonB in the HDL fraction. RESULTS: In both groups of post-renal transplant patients, a statistically significant increase of TG, TC, and non-HDL-C levels was observed. Moreover, statistically significant changes were shown in total apoCIII and apoCIIInonB, as well as in TG/HDL-C and apoAI/apoCIII ratios, as compared to the reference group. On the other hand, in TX patients 73-122 months after transplantation, significantly higher concentrations of TC, LDL-C, and especially non-HDL-C were observed. It was shown that apoCIII, apoCIIInonB, apoB:CIII, and lipid and lipoprotein ratios as risk factors of atherosclerosis and renal risk factors were higher in these patients 73-122 months after transplantation. CONCLUSION: TX patients in a long-term study showed that they had disturbed lipoprotein composition, and its consequence was hyperlipidemia, perhaps partly due to the increased use of immunosuppressants and steroids.

Disturbed lipoprotein composition in non-dialyzed, hemodialysis, continuous ambulatory peritoneal dialysis and post-transplant patients with chronic renal failure.

Studies were carried out in 183 non-dialyzed, 123 hemodialysis, 81 continuous ambulatory peritoneal dialysis and 35 post-transplant patients and in 103 healthy subjects as a reference group. Lipids and apolipoprotein (apo)AI and apoB were determined using Roche kits. An anti-apoB antibody was used to separate apoB-containing apoCIII and apoE-triglyceride-rich lipoprotein (TRL) in the non-high-density lipoprotein (non-HDL) fraction from apoCIIInonB and apoEnonB in the HDL fraction in four groups of patients with chronic renal failure (CRF) and healthy subjects. Multivariate linear regression analysis was used to investigate the relationship between triglyceride (TG) or HDL-cholesterol (HDL-C) concentrations and lipoproteins. Dyslipidemia varied according to the degree of renal insufficiency, the type of dialysis and therapy regime in CRF patients. Lipoprotein disturbances were manifested by increased TG, non-HDL-C and TRL concentrations, and decreased HDL-C and apoAI concentrations, whereas post-renal transplant patients showed normalization of lipid and lipoprotein profiles, except for TG levels and total apoCIII and apoCIIInonB. The present study indicates that CRF patients have disturbed lipoprotein composition, and that hypertriglyceridemia and low HDL-C concentrations in these patients are multifactorial, being secondary to disturbed lipoproteins. The method using anti-apoB antibodies to separate apoB-containing lipoproteins in the non-HDL fraction from non-apoB-containing lipoproteins in HDL can be used in the diagnosis and treatment of patients with progression of renal failure or atherosclerosis. The variability of TG and HDL-C concentrations depends on the variability of TRL and cholesterol-rich lipoprotein concentrations, but the decreases in TG and increases in HDL-C concentrations are caused by apoAI concentration variability. These relationships, however, need to be confirmed in further studies.

Lipid and apolipoproteins (ApoAI, ApoB, Apo CIII, ApoE) disturbance in hemodialysis (HD) and renal transplant (Tx) patients.

The aim of the study was to evaluate the serum lipid and apolipoprotein profiles among patients after renal transplantation (Tx) and to compare them with the profiles obtained for permanently hemodialysed patients (HD). The investigations were performed at 15 Tx, 40 HD patients and the control group of 40 healthy subjects. There were significantly increased TG, ApoAIII, ApoE, TC/ HDL-C, ApoCIII non B, ApoCIII:B and decreased HDL-C, ApoAI, HDL-C/ApoAI, ApoAI/ApoCIII, ApoB/ApoCIII ratios comparing HD patients to the control group. There were increased TG, ApoCIII, ApoCIII non B, ApoB/ApoCIII ratios and decreased ApoAI/ApoCIII ratios in Tx patients as compared to the control subjects. Moreover, there were significantly higher HDL, ApoAI, HDL/ApoAI, ApoCIII non B and lower ApoE, ApoE/ApoB, ApoCIII:B ratios in Tx patients as compared to these of HD patients. Significant inverse correlation of the time which passed from executed Tx and ApoCIII:B ratio (r = -0.67; p < 0.01) at renal transplant patients were observed, which means the diminished risk of development of atherosclerosis.

Serum lipoprotein(a) concentrations and apolipoprotein(a) phenotypes in hemodialysis, chronic ambulatory peritoneal dialysis and post-transplant patients.

Serum lipoprotein(a) [Lp(a)] concentrations and apolipoprotein(a) apo(a) phenotypes were determined in 81 hemodialysis (HD) patients, 37 chronic ambulatory peritoneal dialysis (CAPD) patients, 25 post-transplant patients and 99 healthy subjects as the reference group. The CAPD patients had significantly higher serum Lp(a) concentration than HD patients, but both had significantly increased Lp(a) levels as compared with the reference group and post-transplant patients. When all studied groups were divided into two subgroups with at least one low molecular weight (LMW) isoform and with only one high molecular weight (HMW) isoform, they presented a similar distribution. (Pearson's chi-squared = 2,78; df = 3; p = NS). The median serum Lp(a) levels were significantly increased with HMW class versus the reference group and post-transplant patients. In CAPD patients, the LMW phenotypes showed significantly increased median serum Lp(a) concentrations versus the reference group, but they were not statistically elevated in HD patients. In the post-transplant patients, LMW and HMW phenotypes did not differ as compared to the reference group. The elevated Lp(a) levels in HD and CAPD groups were explained by apo(a) type-specific, but not by differences in, isoform frequencies. We conclude that HD and CAPD patients had increased Lp(a) levels compared with the reference group, whereas elevated Lp(a) concentrations were observed mainly in patients with HMW apo(a) phenotypes. Patients after renal transplantation showed a correction of Lp(a) levels mainly in HMW phenotypes. The LMW status corresponding to high Lp(a) levels and apo(a) isoforms could be used together with Lp(a) levels with other risk factors to assess in uremic patients the predisposition to coronary artery disease.