Paraoxonase 1 and atherosclerosis-related diseases.

A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high-density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis-related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end-stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features.

Capillary Electrophoresis of Free Amino Acids in Physiological Fluids Without Derivatization Employing Direct or Indirect Absorbance Detection.

Whole blood and/or plasma amino acids are useful for monitoring whole-body protein and amino acid metabolism in an organism under various physiological and pathophysiological conditions. Various methodological procedures are in use for their measurement in biological fluids. From the time when capillary electrophoresis was introduced as a technology offering rapid separation of various ionic and/or ionizable compounds with low sample and solvent consumption, there were many attempts to use it for the measurement of amino acids present in physiological fluids. As a rule, these methods require derivatization procedures for detection purposes.Here, we present two protocols for the analysis of free amino acids employing free zone capillary electrophoresis. Main advantage of both methods is an absence of any derivatization procedures that permits the analysis of free amino acid in physiological fluids. The method using direct detection and carrier electrolyte consisting of disodium monophosphate (10 mM at pH 2.90) permits determination of compounds that absorb in UV region (aromatic and sulfur containing amino acids, as well as some peptides such as carnosine, reduced, and oxidized glutathione). The other method use indirect absorbance detection, employing 8 mM p-amino salicylic acid buffered with sodium carbonate at pH 10.2 as running electrolyte. It permits quantification of 30 underivatized physiological amino acids and peptides. In our experience factorial design represents a useful tool for final optimization of the electrophoretic conditions if it is necessary.

Associations of lipoprotein subclasses and oxidative stress status in pulmonary and pulmonary plus extrapulmonary sarcoidosis.

Background: Sarcoidosis is an inflammatory disease with pulmonary and extrapulmonary manifestations. In such pathologic conditions, increased oxidative stress and rearrangement of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) may occur. Objective: This study evaluated association of oxidative stress and lipoprotein subclasses in severe forms of pulmonary and pulmonary plus extrapulmonary sarcoidosis. Methods: Lipid parameters, LDL and HDL subclass distributions, high-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), paraoxonase 1 (PON1), malondialdehyde (MDA), total-oxidant status (TOS), sulfhydryl (SH) groups, pro-oxidant anti-oxidant balance (PAB) were determined in 77 patients (53 isolated pulmonary and 24 pulmonary plus extrapulmonary) and 139 controls. Results: Both pulmonary and extrapulmonary sarcoidosis patients had significantly higher levels of triglycerides and TOS (P<0.05) and more LDL II, LDL III, LDL IVA particles (P<0.01), but lower HDL size, SH groups (P<0.001), PON1 activity and less LDL I subclasses (P<0.05) than controls. In isolated pulmonary disease, HDL-cholesterol (P<0.01) was significantly lower whereas proportions of HDL 3a and PAB were significantly higher (P<0.05) when compared with the control group. PON1 was significantly higher in pulmonary than in combined pulmonary-extrapulmonary disease (P<0.05). In pulmonary sarcoidosis, TOS and PON1 correlated significantly with small-sized HDL particles (P<0.05). Conclusions: Both patient groups were characterized by adverse lipoprotein profile and elevated oxidative stress. In isolated pulmonary group significant associations of oxidative stress and HDL particles distribution was demonstrated. Pulmonary sarcoidosis was associated with higher PON1 activity and rearrangement of LDL particles did not depend on disease localization. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 198-205).

Association of serum amyloid A and oxidative stress with paraoxonase 1 in sarcoidosis patients.

BACKGROUND: It has been reported that high-density lipoprotein (HDL) particles have anti-inflammatory and antioxidant roles thanks to different enzymes such as paraoxonase 1 (PON1). Under inflammatory and oxidative stress conditions, HDL particles may lose their protective properties. Sarcoidosis is an inflammatory disease characterized by excessive oxidative stress. Serum amyloid A (SAA) is produced in liver and in granulomas, and its concentration increases in inflammatory conditions contributing to increased catabolism of HDL particles. The aim of our study was to determine PON1 activity, SAA concentration and their associations in patients with sarcoidosis. MATERIALS AND METHODS: Inflammatory [high-sensitive C-reactive protein (hsCRP), angiotensin-converting enzyme (ACE), SAA], lipid [total cholesterol (TC), HDL-cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG)] oxidative stress status parameters [total oxidant status (TOS), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), sulfhydryl (SH) groups] and PON1 activities were determined in serum of 72 patients with sarcoidosis and 62 healthy subjects. RESULTS: HsCRP (P < 0·05), TC, LDL-c, TG, SAA, TOS, MDA and PAB (P < 0·001) were significantly higher, whereas HDL-c, SH groups and PON1 activity (P < 0·001) were significantly lower in patients with sarcoidosis when compared with controls. PON1 showed significant association with SAA, MDA and PAB. It was shown that 71% of decrease in PON1 activity may be explained by increase in TOS, PAB and SAA concentration. CONCLUSIONS: We found decreased PON1 activity and increased SAA concentration in patients with sarcoidosis. Inflammatory condition presented by high SAA was implicated in impaired HDL functionality evident through dysregulated PON1 activity. Excessive oxidative stress was also involved in dysregulation of PON1 activity.

Cardiovascular Risk Factors in 7-13 Years Old Children from Vojvodina (Serbia).

BACKGROUND: Atherosclerosis is a chronic inflammatory disease which starts early in life and depends on many factors, an important one being dyslipoproteinemia. According to several studies, atherosclerotic plaques or their precursors could be seen in children younger than 10 years. During later life, interaction with a sedentary way of life, as well as unhealthy nutrition, smoking, alcohol consumption, obesity and family history of cardiovascular disease cause the burden of atherosclerotic disease. METHODS: Study included 624 children (316 boys, 308 girls), aged from 7-13 years. We analysed socio-demographic data (BMI, blood pressure, cardiovascular family history, smoking status), as well as lipid status with lipoprotein little a-Lp(a), and apolipoproteins: Apo AI, Apo B-100 for all children. This enabled us to calculate new atherogenic indices Tg/HDL-c, lipid tetrad index (LTI) and lipid pentad index (LPI). Cardiovascular risk for later life was estimated by using modified Risk Score for Young Individuals (RS), which divided the subjects according to the score level: low, medium and higher risk. RESULTS: The older children (13 y) had better lipid status than the younger children, i.e. significantly lower total cholesterol, LDL-C, triglycerides and non-HDL-C concentration and significantly higher HDL-C concentration than the younger children and this was in accordance with the RS level. Children with a positive family history of CV disease had significantly higher Lp(a) concentration and blood pressure. LPI was significantly higher in children with a higher RS. CONCLUSIONS: The results of our work could be used for cardiovascular risk assessment in apparently healthy children to provide preventive measures which could control the changeable risk factors.

Beneficial Effects of Polyphenol-Rich Chokeberry Juice Consumption on Blood Pressure Level and Lipid Status in Hypertensive Subjects.

Epidemiological studies have shown a positive association between intake of foods rich in antioxidants and lower incidence of cardiovascular disease development. Polyphenols are considered the most abundant and important dietary antioxidants. The aim of this study was to evaluate effects of polyphenol-rich chokeberry juice consumption on 24-h ambulatory monitored blood pressure (BP) level in subjects with no pharmacologically treated high normal BP or grade I hypertension. Twenty-three subjects (12 men and 11 women) aged 33-67 were enrolled and instructed to consume 200 mL of juice daily for 4 weeks. Participants were divided in two groups, based on prevalence of sympathetic or parasympathetic activity. Measurements of biochemical parameters and heart rate variability analysis were also applied. At the end of the intervention period, average 24-h and awake systolic and diastolic BP were significantly decreased (P<.05). This was more pronounced in the group with prevalence of sympathetic activity. Significant reduction in triglyceride level (P<.05) and a reducing effect on total and low-density lipoprotein cholesterol were also found. Obtained results indicate a positive impact of regular chokeberry juice consumption on BP and lipid status in pharmacologically untreated hypertensive subjects.

Association of Serum Pentraxin-3 and High-Sensitivity C-Reactive Protein with the Extent of Coronary Stenosis in Patients Undergoing Coronary Angiography.

BACKGROUND: We compared factors of inflammation - high sensitivity C-reactive protein (hsCRP) and pentraxin-3 (PTX3), and we explored their relationship with coronary artery disease (CAD). Also, we tested the usefulness of hsCRP and PTX3 in the risk assessment of coronary stenosis development and the diagnostic ability of these biomarkers to detect disease severity. METHODS: The study group consisted of 93 CAD patients undergoing coronary angiography. Patients were divided into CAD(0), representing subclinical stenosis, and CAD (1-3), representing significant stenosis in one, two or three vessels. RESULTS: We determined the concentration of lipid status parameters, hsCRP and PTX3. We found significantly lower PTX3 and hsCRP concentrations in CAD(0) than in CAD(1-3) group. Concentration of PTX3 showed an increasing trend with the increasing number of vessels affected. The area under ROC curve (AUC) for the combinations of hsCRP and PTX3 with lipid parameters had useful accuracy for detecting CAD(1-3) patients (AUC=0.770, p<0.001). CONCLUSION: PTX3 is a promising independent diagnostic marker for identifying patients with CAD, and a useful indicator of disease progression. In all the analyses PTX3 showed better performance than hsCRP. A combination of PTX3, hsCRP with the lipid status parameters provides risk stratification of the development of coronary stenosis and better classification than their individual application.

Renal transplantation promptly restores excretory function but disturbed L-arginine metabolism persists in patients during the early period after surgery.

The synthesis and whole body metabolism of L-arginine (Arg) are disturbed in renal diseases. Renal transplantation represents the best therapy in the end-stage of these diseases. In the present we compared alterations of plasma Arg and related compounds with renal excretory function in patients with end-stage renal disease, before and after kidney transplantation. Arg, asymmetric dimethylarginine (ADMA), citrulline (Cit), glutamine (Gln), ornithine (Orn), phenylalanine (Phe), tyrosine (Tyr), urea, creatinine, albumin, and nitrate were analyzed in patients before, immediately after (0-time) and 1, 2, 3, 7 and 14 days following living donors kidney transplantation. Healthy subjects were controls. Glomerular filtration rate (GFR) and amino acid molar ratios were calculated. Before transplantation creatinine, urea, Cit, Gln, ADMA, and nitrate were above, while GFR and Arg were below controls, confirming disturbed excretory and metabolic renal functions in patients with renal disease. Renal transplantation promptly normalized creatinine, urea, GFR, Cit, and nitrate. However, regardless of increased molar Phe/Tyr ratios, indicating increased net protein catabolism in peripheral tissues, low Arg and elevated ADMA concentrations persisted throughout the examined period. Alterations of other amino acids also suggest similarly disturbed Arg metabolism in patients after kidney transplantation. In conclusion, renal transplant promptly restored its excretory function, but increased net protein catabolism, disturbed Arg metabolism and endothelial dysfunction in entire body of these patients were not improved throughout the early period after the operation. That has to be considered in their therapy.

Effect of alpha-lipoic acid supplementation on oxidative stress markers and antioxidative defense in patients with schizophrenia.

BACKGROUND: The purpose of this study was to examine the effects of alpha-lipoic acid (LA) supplementation on oxidative stress markers in patients with schizophrenia. SUBJECTS AND METHODS: Eighteen (18) medicated patients with schizophrenia and 38 healthy controls received daily supplements of LA (500 mg/day) for three months. At baseline, 45th and 90th days of supplementation, venous blood collected for analysis of oxidative stress markers [superoxide anion (O2(•-)), thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPP)] and antioxidative defense markers [superoxide dismutase (SOD), total sulfhydryl groups (-SH) and total antioxidant status (TAS)]. RESULTS: Increased plasma TBARS, TAS, SH groups levels and SOD activity were found in schizophrenic patients compared to control group. LA supplementation significantly reduced TBARS, AOPP and improved TAS levels in healthy subjects, while there were no significant differences in patients group. SH groups increased after 45 days and decreased to baseline levels after 90 days of supplementation in the control group. SOD activity decreased significantly in patients group after 45 days and 90 days of supplementation. After initial rose SOD activity in control group, decreased to baseline levels found after 90 days. CONCLUSION: LA supplementation decreased lipid peroxidation and oxidative damage of proteins and improved non-enzymatic antioxidant capacity in healthy controls. No significant changes were observed on oxidative damage in patients with schizophrenia.

The influence of maternal smoking habits before pregnancy and antioxidative supplementation during pregnancy on oxidative stress status in a non-complicated pregnancy.

BACKGROUND: As a physiological condition closely linked with increased susceptibility to oxidative stress, pregnancy can be further compromised by cigarette smoking. Inadequate nutrition and reduced intake of antioxidants can also disrupt the prooxidant/antioxidant relationship and contribute to oxidative stress. Increased oxidative stress during pregnancy may be involved in several complications of pregnancy, such as preterm labor, fetal growth restriction, preeclampsia and miscarriage. OBJECTIVES: The aim of this study was to investigate the influence of maternal smoking habits before pregnancy on the parameters of oxidative stress and the antioxidative defense system, lipid profile parameters and paraoxonase-1 (PON1) activity during the third trimester of uncomplicated pregnancies. MATERIAL AND METHODS: Healthy pregnant women (n = 86) were divided into non-smoking and smoking groups, and into groups taking vitamin supplements and not taking them. Oxidative damage was measured through the levels of thiobarbituric acid-reacting substances (TBARS) and plasma antioxidant status was evaluated by measuring total antioxidant capacity (TAC). RESULTS: TBARS concetration was significantly higher (p < 0.05) and PON1 activity was significantly lower (p < 0.05) in the smokers' group. No significant differences were found in the investigated parameters in relation to vitamin supplement intake. CONCLUSIONS: Habitual smoking before pregnancy is associated with increased oxidative stress. Vitamin supplementation has no effect on the oxidative stress status of healthy pregnant women.

Association of small, dense low-density lipoprotein cholesterol and galectin-3 in patients with chronic kidney disease.

BACKGROUND: Dyslipidemia is a common feature of chronic kidney disease (CKD). Although it has been observed that the pattern of lipid abnormalities can vary according to the stage of CKD, there is lack of data concerning the distribution of lipoprotein subclasses at various stages of the disease. In addition, association of proatherogenic small, dense low-density lipoprotein (sdLDL) subclasses with markers of inflammation, such is galectin-3, is not sufficiently explored. The aim of this study was to analyze concentrations and relative proportions of sdLDL-cholesterol (sdLDL-C) and galectin-3 in patients with CKD, with respect to the stage of the disease. Also, we sought possible independent associations of galectin-3 and sdLDL-C. METHODS: The study involved 100 hemodialysis (HD) and 50 pre-dialysis patients, together with 94 healthy individuals. SdLDL-C was measured by heparin-magnesium precipitation method. Galectin-3 was measured by ELISA technique. RESULTS: Galectin-3 levels were higher in pre-dialysis and HD patients than in the control group (p < 0.01). The concentration of sdLDL-C was highest in the pre-dialysis group and lowest in HD patients (p < 0.01). CKD patients with increased galectin-3 concentrations had significantly higher relative proportions of cholesterol in sdLDL (% sdLDL-C) than their counterparts with lower galectin-3 levels (p < 0.05). Relative proportion of sdLDL-C was shown to be an independent determinant of galectin-3 concentration. CONCLUSIONS: Our results demonstrated alterations in concentrations and proportions of sdLDL-C according to the stages of CKD. The observed independent associations of % sdLDL-C and galectin-3 provide further insight into their complex interaction during the progression of atherosclerosis in CKD.

Factor analysis of risk variables associated with iron status in patients with coronary artery disease.

OBJECTIVES: Epidemiological evidence concerning the role of iron, a lipid peroxidation catalyst, in atherosclerosis and coronary artery disease (CAD) is inconsistent. DESIGN AND METHODS: Exploratory factor analysis was used to examine the potential clustering of variables known to be associated with CAD using data from 188 patients with angiographically-approved disease. The resulting factors were then tested for their association with serum ferritin and soluble transferrin receptor (sTfR) as indicators of body iron status. RESULTS: Factor analysis resulted in a reduction of a variable number from the original 15 to 5 composite clusters. These factors were interpreted as (1) "proatherogenic factor" with positive loadings of TC, LDL-C, apoB and TG; (2) "inflammatory factor" with positive loadings of hsCRP, fibrinogen and MDA; (3) "antiatherogenic factor" with positive loadings of HDL-C and apoA-I; (4) "obesity factor" with positive loadings of weight and waist; and (5) "antioxidative status factor" with positive loadings of SOD and age and negative loading of superoxide anion. "Inflammatory", "obesity" and "antiatherogenic" factors predicted high ferritin values and the "proatherogenic factor" predicted high sTfR values. We compared the ability of the "proatherogenic factor" with that of a multivariable logistic model that included the "proatherogenic factor" and sTfR values in predicting significant stenosis in patients. The area under the ROC curve was 0.692 vs. 0.821, respectively. CONCLUSIONS: "Inflammatory", "obesity", "antiatherogenic" and "proatherogenic" factors were associated with increased parameters of body iron status. The measurement of sTfR improves the prediction of CAD based on clustered cardiovascular risk factors.

Effects of polyphenol-rich chokeberry juice on antioxidant/pro-oxidant status in healthy subjects.

Berry fruits are a rich source of polyphenols, especially anthocyanins: well-known potent anti-oxidant phytochemicals. The purpose of this study was to evaluate beneficial effects of long-term consumption of polyphenol-rich organic chokeberry juice on different markers of antioxidant/pro-oxidant status in healthy female volunteers. Twenty-nine women, aged 25-49, were included in the study. Serological markers of oxidative stress and antioxidant defence, blood pressure, routine biochemical, and anthropometric parameters were analyzed at baseline and after twelve weeks of regular chokeberry juice consumption. Significant decrease in thiobarbituric acid-reactive substances level (TBARS; P<.001) and pro-oxidant-antioxidant balance (PAB; P<.05), as well as increase in paroxonase-1 activity toward diazoxon (P<.01) were found. Total oxidative status and sulphydryl groups levels were not significantly influenced by the intervention. Anthropometric, biochemical parameters, and blood pressure values were within the referent values for all subjects and were not influenced by the chokeberry juice consumption. However, we found positive correlation between age, body mass index, waist circumference, body fat percent, blood pressure, and analyzed marker of lipid peroxidation, which was influenced by the consumption. In conclusion, the fine modulation of several antioxidant/pro-oxidant status biomarkers observed in healthy subjects indicates putative prophylactic effects of polyphenol-rich chokeberry juice and supports its importance as part of an optimal diet.

Dietary supplementation with polyphenol-rich chokeberry juice improves skin morphology in cellulite.

The aim of our study was to investigate possible beneficial effects of organic chokeberry juice (OCJ) consumption in the treatment of cellulite. Twenty-nine women aged 25-48 with a cellulite grade 2 according to the Nurnberger-Muller scale were included. Anthropometric and biochemical parameters were measured. Skin structure was analyzed by ultrasonography. All subjects consumed 100 mL of OCJ per day, during 90 days. Measurements of investigated parameters were performed at 0, 45, and 90 days of the study. A marked reduction in the subcutaneous tissue thickness was observed in all subjects, with the average reduction of 1.9 mm. The length of subcutaneous tissue fascicles (ScTFL) was reduced in 97% (28 out of 29) of subjects, with the average value of 1.18 mm. After 45 days of chokeberry juice consumption, reduction of edema was observed in 55.2% of the subjects with edema at the baseline, while at the endpoint of the study, edemas were not observed in any of the subjects involved in the study. OCJ could have beneficial effects on the cellulite condition, including the length of ScTFL, subcutaneous tissue, and dermis thickness as well as on edema reduction.

Associations of oxidative stress status parameters with traditional cardiovascular disease risk factors in patients with schizophrenia.

BACKGROUND: The purpose of this study was to assess oxidative stress status parameters and their possible associations with traditional cardiovascular risk factors in patients with schizophrenia, as well as their potential for patient-control discrimination. METHODS: Fasting glucose, lipid profile and oxidative stress status parameters were assessed in 30 schizophrenic patients with atypical antipsychotic therapy and 60 control subjects. RESULTS: Malondialdehyde (MDA), pro-oxidant/antioxidant balance (PAB) and total anti-oxidant status (TAS) were significantly higher whereas total sulfhydryl (SH) groups were significantly lower in schizophrenic patients vs. control group. Higher serum PAB values showed an independent association with schizophrenia. The addition of PAB to conventional risk factors improved discrimination between healthy control subjects and patients. CONCLUSION: Increased oxidative stress and changed lipid profile parameters are associated in schizophrenic patients and may indicate risk for atherosclerosis. The serum PAB level may reflect the levels of oxidative stress in schizophrenia and improve discrimination of patients from controls.

Association of glutathione-S-transferase gene polymorphism and lipoprotein subclasses in hemodialysis patients.

OBJECTIVES: End-stage renal disease (ESRD) is characterized by profound dyslipidemia and enhanced oxidative stress. The patients also show evidence of exhausted and/or deficient anti-oxidative defense enzymes, one of them being glutathione-S-transferase (GST). This study investigates relationship between GST gene polymorphism and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses in ESRD. DESIGN AND METHODS: GSTM1, T1, and P1 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 160 patients undergoing hemodialysis. LDL and HDL subclasses were separated by gradient gel electrophoresis and biochemical parameters were measured by routine laboratory methods. RESULTS: GSTM1-positive patients had higher proportion of small, dense LDL III particles than those with GSTM1-null genotype (P<0.05). Similarly, GSTP1-Ile/Ile patients had higher proportion of LDL III (P<0.05), but more HDL 2b and less HDL 3a particles than GSTP1-Ile/Val and Val/Val carriers (P<0.05). LDL subclass distribution in smokers with GSTM1-null genotype was shifted towards smaller particles, as compared to GSTM1-positive and GSTM1-null non-smokers. Smokers with GSTP1-Ile/Val and Val/Val genotypes had smaller LDL size than their non-smoking counterparts (P<0.05). Both smokers and non-smokers with GSTP1 Ile/Ile genotype had more LDL III particles than non-smokers carrying Val allele. Non-smokers with GSTP1 Ile/Ile genotype had more HDL 2b subclasses than non-smokers with GSTP1-Ile/Val and Val/Val (P<0.05), but less HDL 3a particles than smokers with GSTP1-Ile/Val and Val/Val genotypes (P<0.05). GSTT1 gene polymorphism had no effect on lipoprotein subclass distributions. CONCLUSIONS: Our results demonstrate significant associations between low activity GST genotypes and proatherogenic lipoprotein particles in hemodialysis patients which might further increase their cardiovascular disease risk.

Smaller HDL particles are associated with absence of obstructive coronary artery disease in stable angina pectoris patients.

BACKGROUND: A research on novel cardiovascular risk factors is mainly focused on patients with clinically verified coronary artery disease (CAD), while less is known about their presence in symptomatic patients, but without angiographically proven occlusion of coronary arteries. The aim of this study was to compare plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) size and subclasses in stable angina patients with and without significant obstructive CAD. METHODS: LDL and HDL subclasses were analysed in 100 stable angina patients with ≥50% of obstruction and 40 patients with less than 50% of luminal narrowing, as assessed by coronary angiography. RESULTS: Patients with <50% of obstruction had reduced mean HDL size and higher proportion of small HDL particles (P < 0.05). HDL size and proportion of small HDL particles were significant and independent predictors of obstructive CAD (P < 0.05, respectively). CONCLUSIONS: Stable angina patients with <50% of coronary obstruction have more favourable HDL subclasses distribution than patients with significant coronary stenosis.

Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients?

BACKGROUND: The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. METHODS: We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. RESULTS: Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. CONCLUSIONS: NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor.

Distribution of low-density lipoprotein and high-density lipoprotein subclasses in patients with sarcoidosis.

CONTEXT: Systemic inflammatory diseases are associated with proatherogenic lipoprotein profile, but there is a lack of information regarding overall distributions of lipoprotein subclasses in sarcoidosis. OBJECTIVE: To investigate whether patients with sarcoidosis have altered distributions of plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles. DESIGN: Seventy-seven patients with biopsy-proven sarcoidosis (29 with acute and 48 with chronic sarcoidosis) treated with corticosteroids and 77 age- and sex-matched controls were included in the study. Low-density lipoprotein and HDL subclasses were determined by gradient gel electrophoresis, while inflammatory markers and lipid parameters were measured by standard laboratory methods. RESULTS: Compared to controls, patients had fewer LDL I subclasses (P < .001), but more LDL II and III (P < .001) subclasses. This pattern was evident in both acute and chronic disease groups. Patients also had smaller HDL size (P < .001) and higher proportions of HDL 2a (P = .006) and 3a particles (P = .004). Patients with chronic sarcoidosis had smaller LDL size than those with acute disease (P = .02) and higher proportions of HDL 3a subclasses (P = .04) than controls. In acute sarcoidosis, relative proportions of LDL and HDL particles were associated with levels of inflammatory markers, whereas in chronic disease an association with concentrations of serum lipid parameters was found. CONCLUSIONS: The obtained results demonstrate adverse lipoprotein subfraction profile in sarcoidosis with sustained alterations during disease course. Evaluation of LDL and HDL particles may be helpful in identifying patients with higher cardiovascular risk, at least for prolonged corticosteroid therapy due to chronic disease course.

Assessment of endothelial dysfunction: the role of symmetrical dimethylarginine and proinflammatory markers in chronic kidney disease and renal transplant recipients.

OBJECTIVES: The study was designed to evaluate associations between symmetric dimethylarginine (SDMA), inflammation, and superoxide anion (O2∙-) with endothelial function and to determine their potential for screening of endothelial dysfunction in patients with chronic kidney disease (CKD) and renal transplant (RT) recipients. MATERIALS AND METHODS: We included 64 CKD and 52 RT patients. Patients were stratified according to brachial artery flow-mediated dilation (FMD). RESULTS: Logistic regression analysis showed that high SDMA and high sensitive C-reactive protein (hs-CRP) were associated with impaired FMD in CKD and RT patients, after adjustment for glomerular filtration rate. The ability of inflammation, SDMA, and O2∙- to detect impaired FMD was investigated by receiving operative characteristic analysis. Hs-CRP (area under the curves (AUC) = 0.754, P < 0.001), IL-6 (AUC = 0.699, P = 0.002), and SDMA (AUC = 0.689, P = 0.007) had the highest ability to detect impaired FMD. SDMA in combination with inflammatory parameters and/or O2∙- had better screening performance than SDMA alone. CONCLUSIONS: Our results indicate a strong predictable association between hs-CRP, SDMA, and endothelial dysfunction in CKD patients and RT recipients. The individual marker that showed the strongest discriminative ability for endothelial dysfunction is hs-CRP, but its usefulness as a discriminatory marker for efficient diagnosis of endothelial dysfunction should be examined in prospective studies.