Effect of Half-Marathon Running on Arterial Stiffness and Blood Biomarkers in High-Level and Recreational Male Athletes.

There is no clear understanding about the effect of intensive physical load on arterial stiffness and related biomarkers. The aim of this study was to evaluate the effect of half-marathon running on arterial stiffness and blood biomarkers during post-competitive recovery period in competitive and recreational male athletes. Eleven high-level long-distance runners (27.1 ± 4.8 yrs) and seven recreational athletes (34.3 ± 6.1 yrs), who participated in a half-marathon run were examined. Blood biomarkers and arterial stiffness (SphygmoCor 7.1) were measured at baseline and at 18 to 22 hours after the competition. There were no statistically significant changes between the groups in augmentation index (AIx, AIx@75) or pulse wave velocities at carotid-femoral segment (cfPWV) during recovery period. Between-group comparison did not reveal significant differences in blood pressure and arterial stiffness values at baseline and during recovery period. The change of cfPWV (difference between cfPWV at baseline and cfPWV during post-competitive recovery period) was significantly dependent on race time and sports level of the athlete (high-level or recreational). A significant increase was found in hsCRP, creatine kinase and LDH activity during the post-race period in both groups. No significant changes were found in oxidative stress markers in the groups after the race except for higher diene conjugates level in recreational athletes in comparison with the high-level group during recovery period. Our study results showed that half-marathon competition did not cause any significant changes in arterial stiffness parameters during the recovery period. However, the change in cfPWV was independently associated with half-marathon race time and the athlete's level of training revealing a mild increase of arterial stiffness in high-level athletes and athletes with a faster race time.

Oxidative Stress Parameters and Its Associations With Arterial Stiffness in Competitive Powerlifting Athletes After 12-Week Supervised Strength Training.

Jürgenson, J, Serg, M, Kampus, P, Kals, J, Zagura, M, Viru, M, Zilmer, K, Zilmer, M, Eha, J, and Unt, E. Oxidative stress parameters and its associations with arterial stiffness in competitive powerlifting athletes after 12-week supervised strength training. J Strength Cond Res 33(7): 1816-1822, 2019-Available studies have not revealed a clear understanding of the impact of intensive strength training on arterial stiffness and oxidative stress (OxS) parameters, which may have a significant impact on further cardiovascular health of an athlete. The purpose of this study was to evaluate the effect of a 12-week supervised strength training program (SSTP) on oxidative stress indices and its relationship with arterial stiffness in powerlifting athletes. A total of 19 men (28 ± 6 years) exercised for 12 weeks (4 days per week with intensity 60-90% assessed from 1 repetition maximum, 90-120 minutes per session). Oxidative stress parameters and arterial stiffness (SphygmoCor 7.1) were measured before and after SSTP. The study results showed that total peroxide concentration increased and total antioxidant capacity decreased significantly after SSTP. There were no significant changes in carotid-femoral pulse wave velocity (cfPWV) or in the augmentation index. Correlation analysis revealed that the magnitude of the increase of cfPWV was significantly related to the increase of OxS. The current study demonstrated that a 12-week SSTP in powerlifting athletes produced significant changes in OxS indices, which were positively related to increased aortic stiffness. This novel finding may have significant implications about the effect of OxS on cardiovascular health after high-intensity strength training. Furthermore, strength and conditioningcoaches may have to consider the long-term exercise-induced changes in OxS on an individual level, where increased OxS leads to impaired arterial stiffness and cardiovascular health.

The use of probiotic L. fermentum ME-3 containing Reg'Activ Cholesterol supplement for 4 weeks has a positive influence on blood lipoprotein profiles and inflammatory cytokines: an open-label preliminary study.

BACKGROUND: Cardiovascular diseases continue to be a challenge and burden to heath. The incidence of type 2 diabetes is increasing. Modifying the (common) risk factors of them is the key of longterm success. The aim of the study was to establish if the special composition of innovative food supplement Reg'Activ Cholesterol (RAC) has a positive influence to the human body cardiovascular-inflammatory and diabetic parameters. METHODS: Forty-five clinically asymptomatic participants consumed an RAC containing an antioxidative and antiatherogenic probiotic Lactobacillus fermentum ME-3 (LFME-3) for 4 weeks. The parameters measured were total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, oxLDL, hsCRP, IL-6 and glycosylated haemoglobin (HbA1c%). RESULTS: The cardiovascular and diabetes risk profile of the participants improved significantly after 4 weeks of the intervention. The reduction of total cholesterol (from 6.5 ± 1.0 to 5.7 ± 0.9 mmol/l, p = 9.90806E-11) was on the account of LDL cholesterol as the HDL cholesterol level rose from 1.60 ± 0.31to 1.67 ± 0.34mml/l, p = 0.01. HbA1c% was reduced from 5.85 ± 0.28 to 5.66 ± 0.25 p = 4.64E-05 and oxLDL decreased from 84 ± 20 to 71 ± 15 U/l, p = 4.66292E-08. CONCLUSIONS: The consumption of RAC in clinically asymptomatic volunteers with borderline-high values of risk factors for cardiovascular disease (BMI, HbA1c%, LDL cholesterol) for 4 weeks had a positive effect on blood lipoprotein, oxidative stress and inflammatory profile. There are no human trials published before with RAC. TRIAL REGISTRATION: The trial described here isa n open label pilot study within the framework of a larger special clinical trial ( ISRCTN55339917 ) [Accessed 20 Feb 2016].

Antipsychotic Treatment Reduces Indices of Oxidative Stress in First-Episode Psychosis Patients.

38 first-episode psychosis (FEP) patients and 37 control subjects were recruited for the study of indices of oxidative stress (OxS). The main purpose of the study was to compare the OxS statuses (serum total antioxidant capacity (TAC), total level of peroxides (TPX), oxidative stress index (OSI), and ratio oxidized methionine (Met-SO) to methionine (Met)) between antipsychotic-naïve FEP patients and individuals without a history of psychiatric disorders. Subsequently, the impact of 7-month antipsychotic treatment was evaluated on the OxS status in FEP patients. An attempt was made to assess links between OxS signature and inflammation markers. The oxidative stress indices remained generally unchanged in antipsychotic-naïve FEP patients compared to control subjects. Despite that, there was a significant correlation between the levels of TPX and EGF (endothelial growth factor) in FEP patients. This correlation disappeared after antipsychotic treatment of FEP patients. Moreover, antipsychotic treatment was associated with a significant reduction in OxS indices, including TPX, OSI, and ratio between Met-SO and Met. By contrast, in chronic SCZ patients we established a significant high-grade OxS. In conclusion, the markers of total antioxidative capacity, lipid peroxidation, and protein oxidation revealed no high-grade OxS in FEP patients. Nevertheless, antipsychotic treatment induced a considerable anti-inflammatory effect. OxS levels were also significantly decreased if compared in FEP patients before and after antipsychotic treatment.

Antipsychotic treatment reduces psychotic symptoms and markers of low-grade inflammation in first episode psychosis patients, but increases their body mass index.

OBJECTIVE: The main goal of the present study was to analyze levels of cytokines of the interleukin family (IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8 and IL-10), interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP1), tumor necrosis factor-alpha (TNF-α), and vascular endothelial and endothelial growth factors (VEGF and EGF), in the blood samples of first-episode psychosis (FEP) patients before and seven months after the start of antipsychotic medication use. METHOD: 38 anti-psychotic medication-naïve FEP patients and 37 healthy controls (HC) were recruited. Biochip array technology was used to measure cytokines and growth factors. RESULTS: The comparison of these markers in FEP patients and HC revealed significantly higher levels of EGF, IL-4 and IL-6 and significantly lower level of IL-1ß in FEP patients before the antipsychotic treatment. Multiple regression analysis demonstrated significant correlations between FEP and EGF, IL-1ß and smoking. Treatment with antipsychotic drugs resulted in a statistically significant amelioration of the symptoms of psychosis, but caused a significant increase in the body mass index (BMI) of patients. Levels of EGF, IL-2, VEGF, IL-6, IFN-γ, IL-4, IL-8 and IL-1α were significantly lower in treated FEP patients compared to premedication levels. CONCLUSIONS: According to the present study, EGF and IL-1ß are markers of FEP. Antipsychotic drug treatment resulted in a significant clinical improvement of FEP patients and the suppression of positive symptoms was correlated with the decreased levels of EGF, IL-2 and IL-4. EGF was the strongest marker of FEP and treatment efficiency among the measured cytokines and growth factors.

Increased carotid artery intima-media thickness and myeloperoxidase level in children with newly diagnosed juvenile idiopathic arthritis.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a frequent childhood rheumatic disease characterized by chronic inflammation. The latter has been related to impairment of arterial functional-structural properties, atherogenesis and later cardiovascular events. The objective of this study was to examine intima-media thickness (IMT) and the parameters of arterial stiffness in children with JIA at diagnosis and their correlation with JIA subtype and markers of inflammation and atherosclerosis. METHODS: Thirty-nine newly diagnosed patients with JIA (26 girls; mean age, 13.2 ± 2.6 years) and 27 healthy controls (9 girls; mean age, 13.6 ± 3.4 years) were included in the study. Twelve patients had oligoarthritis, fifteen had extended oligoarthritis and twelve had rheumatoid factor-negative polyarthritis. IMT of the common carotid artery was determined by ultrasonography, carotid-femoral pulse wave velocity (cfPWV) and augmentation index adjusted to a heart rate of 75 beats/min (AIx@75) were determined by applanation tonometry. The serum levels of atherosclerosis-related biomarkers, such as asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and adiponectin, were measured by enzyme-linked immunosorbent assay. RESULTS: Mean IMT (0.46 ± 0.04 vs. 0.42 ± 0.04 mm; p = 0.0003) and MPO concentration (115.2 [95% confidence interval {95% CI}, 97.4-136.3] vs. 57.6 [95% CI, 47.1-70.3] ng/ml; p < 0.0001) were higher in the patients with JIA than in the control subjects. The cfPWV, AIx@75 and serum ADMA and adiponectin levels did not significantly differ between the groups and JIA subtypes. Serum adiponectin level correlated negatively with AIx@75 in patients with JIA (r = -0.38; p < 0.05). CONCLUSIONS: Patients with JIA have increased mean IMT and elevated MPO levels at early stages of the disease. AIx@75 was inversely independently associated with adiponectin level in the patients, suggesting that lower adiponectin levels might influence arterial subclinical stiffening in patients with newly diagnosed JIA.

Effects of heat acclimation on changes in oxidative stress and inflammation caused by endurance capacity test in the heat.

BACKGROUND: The aim was to determine the effect of heat acclimation (HA) on oxidative stress (OxS) and inflammation in resting conditions and on the response pattern of these parameters to exhausting endurance exercise. METHODS: Parameters of OxS and inflammation were measured in non-heat-acclimated status (NHAS) and after a 10-day HA program (i.e., in heat-acclimated status; HAS) both at baseline and after an endurance capacity (EC) test in the heat. RESULTS: As a result of HA, EC increased from 88.62 ± 27.51 to 161.95 ± 47.80 minutes (P < 0.001). HA increased OxS level: total peroxide concentration rose from 219.38 ± 105.18 to 272.57 ± 133.39 µmol/L (P < 0.05) and oxidative stress index (OSI) from 14.97 ± 8.24 to 20.46 ± 11.13% (P < 0.05). In NHAS, the EC test increased OxS level: total peroxide concentration rose from 219.38 ± 105.18 to 278.51 ± 125.76 µmol/L (P < 0.001) and OSI from 14.97 ± 8.24 to 19.31 ± 9.37% (P < 0.01). However, in HAS, the EC test reduced OSI from 20.46 ± 11.13 to 16.83 ± 8.89% (P < 0.05). The value of log high-sensitive C-reactive protein increased from -0.32 ± 0.32 to -0.12 ± 0.34 mg/L (P < 0.05) in NHAS and from -0.31 ± 0.47 to 0.28 ± 0.46 mg/L (P < 0.001) in HAS. CONCLUSION: HA increases OxS level. However, beneficial adaptive effects of HA on acute exhaustive exercise-induced changes in OxS and inflammation parameters occur in a hot environment.

Growth factors serum levels in coronary artery disease patients scheduled for bypass surgery: perioperative dynamics and comparisons with healthy volunteers.

BACKGROUND: Vascular endothelial growth factors are important mediators for neovascularization of chronically ischemic adult heart, but their elevated values have also been connected with acute ischemia. Coronary artery bypass grafting (CABG) is associated with activation of inflammatory processes. We aimed to clarify whether the latter is also accompanied with acute changes in concentrations of vascular growth factors. METHODS: Concentrations of growth factors VEGF and EGF, monocyte chemoattractant protein-1 (MCP-1), and a set of cytokines of 39 patients with stable coronary artery disease (CAD) were evaluated before and after CABG. Preoperative values were compared with data of healthy volunteers. RESULTS: In comparison with CAD patients, healthy controls had significantly higher values of VEGF (15.5 (10.05-35.3) and 119.4 (55.7-136.9) pg/mL, resp.), EGF (1.70 (1.14-3.18) and 37.3 (27.1-51.9) pg/mL, resp.), and MCP-1 (111.6 (81.75-171.9) and 156.9 (134.7-241.3) pg/mL, resp.). MCP-1, but not others, demonstrated a significant rise throughout the postoperative period. Proinflammatory interleukin-6 was significantly higher and anti-inflammatory IL-4 and IL-10 lower in patients with CAD. CONCLUSIONS: Patients with stable CAD have lower serum levels of growth factors than healthy volunteers. MCP-1, but not VEGF and EGF, becomes elevated immediately after CABG. Inflammatory status of CAD patients was drifted towards proinflammatory state.

Serum methylglyoxal level and its association with oxidative stress and disease severity in patients with psoriasis.

Psoriasis vulgaris (PV), a chronic inflammatory skin disease, is a condition of increased oxidative stress (OxS). However, interest related to oxidative and carbonyl stress damages to proteins, such as the formation of advanced glycation end products (AGEs) and their precursor molecule methylglyoxal (MG) has been modest. The objective of this study was to compare the systemic levels of OxS markers in patients with PV and healthy controls (Co) and to investigate their correlation with the serum level of MG. Total peroxide concentration (TPX) and total antioxidant capacity (TAC) were estimated by means of spectrophotometry. The TPX and TAC ratio was regarded as OxS index (OSI). MG level was determined using ELISA. Compared to Co, patients with PV had significantly increased blood levels of TPX (P < 0.0001), OSI (P < 0.0001), and MG (P = 0.01), and lower TAC levels (P < 0.0001). Increase in body mass index (BMI) appeared to contribute to this imbalance as TAC levels decreased with increasing BMI (r = -0.252, P < 0.01). Increased TPX concentration was associated with higher serum level of MG (r = 0.610, P = 0.004), the latter being positively correlated with psoriasis area and severity index (r = 0.577, P = 0.008). In performed multivariate regression analysis, TPX, TAC, and OSI were all significant predictors of MG level. Our study gave further proof of increased systemic psoriasis-related OxS. MG serum level, reflecting simultaneously OxS as well as carbonyl stress status, could be used as a marker of disease activity in clinical trials while looking for new systemic therapies for psoriasis.

Vitamin D reduces deposition of advanced glycation end-products in the aortic wall and systemic oxidative stress in diabetic rats.

AIMS: Vitamin D may have an important role in reducing the risk of cardiovascular disease. Advanced glycation end-products (AGEs) such as Nε-(carboxymethyl)lysine (CML), have been implicated in diabetic vascular complications via oxidative stress-mediated pathways. We investigated the potential protective effect of vitamin D on CML accumulation in the diabetic aortic wall. To test the effects of vitamin D on systemic oxidative stress we also assessed liver oxidative stress index (OSI) and serum total antioxidant capacity (TAC). METHODS: Male Wistar rats were assigned to three groups: control, untreated diabetes, and diabetes+cholecalciferol. Diabetes was induced by streptozotocin, followed by oral administration of cholecalciferol (500 IU/kg) for 10 weeks in the treatment group. Aortic CML accumulation was determined by ELISA and immunohistochemical assays. OSI was assessed by measuring TAC and the level of total peroxides in the liver and serum using colorimetric assays. RESULTS: Untreated diabetes was associated with significantly elevated CML levels in the aortic wall (19.5 ± 3.3 vs 10.2 ± 4.7 ng/mL), increased liver OSI (6.8 ± 1.9 vs 3.1 ± 0.7), and reduced serum TAC (0.4 ± 0.1 vs 0.8 ± 0.3 mmol Trolox/L), in comparison with the control group. Cholecalciferol significantly blocked the accumulation of CML in the aortic wall (10.4 ± 8.4 vs 19.5 ± 3.3 ng/mL), decreased liver OSI (4.2 ± 1.4 vs 6.8 ± 1.9), and improved serum TAC (1.0 ± 0.2 vs 0.4 ± 0.1 mmol Trolox/L), compared with the untreated diabetic group. CONCLUSIONS: Streptozotocin-diabetes resulted in increased deposition of AGEs and increased oxidative stress in the serum and liver. Vitamin D supplementation may provide significant protection against oxidative stress-mediated vascular complications in diabetes.

Elevated blood plasma antioxidant status is favourable for achieving IVF/ICSI pregnancy.

The aim of the study was to determine the roles of intrafollicular and systemic oxidative stress and antioxidant response in ovarian stimulation and intracytoplasmic sperm injection (ICSI) outcomes. For this purpose, 102 ICSI patients undergoing controlled ovarian stimulation were enrolled and samples were collected on the day of follicle puncture. Total peroxide (TPX) concentrations and total antioxidant response (TAR) were measured in follicular fluid and blood plasma, and an oxidative stress index (OSI) was calculated based on these two parameters. Urinary concentrations of 8-iso-prostaglandin F2a (F2IsoP) were measured. Elevated intrafollicular oxidative stress was positively correlated with ovarian stimulation outcome: less FSH per retrieved oocyte was used, more oocytes were collected and higher serum oestradiol concentrations were measured in patients with higher follicular OSI. However, high urinary F2IsoP related to lower embryo quality and F2IsoP was also elevated in smoking patients. Patients with endometriosis had lower follicular antioxidant status. Most importantly, higher systemic blood TAR was significantly favourable for achieving clinical pregnancy (P=0.03). In conclusion, the findings suggest clear associations between oxidative stress, antioxidant status and several aspects of ovarian stimulation and IVF/ICSI outcome, including pregnancy rate. Several oxygen-dependent biochemical reactions produce reactive oxygen species as by-products that may eventually lead to oxidative stress, which is detrimental to cells and tissues. Total antioxidant status, on the other hand, comprises several agents that balance the excess of these reactive oxygen species and reduce potential damage to the body. The aim of the current work was to study this balance in 102 patients participating in an ICSI programme and to examine the degree to which total peroxide content and antioxidant status influence infertility and pregnancy outcome. During the study, several tests were performed to characterize oxidative stress levels in ovarian follicular fluid, blood plasma and urine. We found a significantly higher oxidative stress environment in the ovary when compared with blood plasma. This suggests a prominent role of oxidative stress in the ovaries of these patients. The elevated oxidative stress levels were correlated to a higher number of oocytes that could be obtained via the procedure and to a lower amount of FSH needed to mature the oocytes, suggesting that oxidative stress, to some degree, is favourable for hormone stimulation outcome. A high level of lipid peroxidation products in the urine, another marker of oxidative stress, was observed in smokers and this marker was elevated in patients with embryos that had lower developmental potential. A higher overall antioxidant status in blood plasma was advantageous for achieving pregnancy.

Mitochondrial oxidative stress index, activity of redox-sensitive aconitase and effects of endogenous anti- and pro-oxidants on its activity in control, Alzheimer's disease and Swedish Familial Alzheimer's disease brain.

Efficient function of the mitochondrial respiratory chain and the citric acid cycle (CAC) enzymes is required for the maintenance of human brain function. A conception of oxidative stress (OxS) was recently advanced as a disruption of redox signalling and control. Mitochondrial OxS (MOxS) is implicated in the development of Alzheimer's disease (AD). Thus, both pro- and anti-oxidants of the human body and MOxS target primarily the redox-regulated CAC enzymes, like mitochondrial aconitase (MAc). We investigated the specific activity of the MAc and MOxS index (MOSI) in an age-matched control (Co), AD and Swedish Familial AD (SFAD) post-mortem autopsies collected from frontal cortex (FC) and occipital primary cortex (OC) regions of the brain. We also examined whether the mitochondrial neuroprotective signalling molecules glutathione, melatonin and 17-ß-estradiol (17ßE) and mitochondrially active pro-oxidant neurotoxic amyloid-ß peptide can modulate the activity of the MAc isolated from FC and OC regions similarly or differently in the case of Co, AD and SFAD. The activity of redox-sensitive MAc may directly depend on the mitochondrial oxidant/antioxidant balance in age-matched Co, AD and SFAD brain regions.

Effects of 60 minutes of hyperoxia followed by normoxia before coronary artery bypass grafting on the inflammatory response profile and myocardial injury.

BACKGROUND: Ischemic preconditioning induces tolerance against ischemia-reperfusion injury prior a sustained ischemic insult. In experimental studies, exposure to hyperoxia for a limited time before ischemia induces a low-grade systemic oxidative stress and evokes an (ischemic) preconditioning-like effect of the myocardium. We hypothesised that pre-treatment by hyperoxia favours enchanced myocardial protection described by decreased release of cTn T in the 1st postoperative morning and reduces the release of inflammatory cytokines. METHODS: Forty patients with stable coronary artery disease underwent coronary artery bypass grafting with cardiopulmonary bypass. They were ventilated with 40 or >96% oxygen for 60 minutes followed by by 33 (18-59) min normoxia before cardioplegia. RESULTS: In the 1st postoperative morning concentrations of cTnT did not differ between groups ((0.44 (0.26-0.55) ng/mL in control and 0.45 (0.37-0.71) ng/mL in hyperoxia group). Sixty minutes after declamping the aorta, ratios of IL-10/IL-6 (0.73 in controls and 1.47 in hyperoxia, p = 0.03) and IL-10/TNF-α (2.91 and 8.81, resp., p = 0.015) were significantly drifted towards anti-inflammatory, whereas interleukins 6, 8and TNF-α and interferon-γ showed marked postoperative rise, but no intergroup differences were found. CONCLUSIONS: Pre-treatment by 60 minutes of hyperoxia did not reduce postoperative leak of cTn T in patients undergoing coronary artery bypass surgery. In the hyperoxia group higher release of anti-inflammatory IL-10 caused drifting of IL-10/IL-6 and IL-10/TNF-α towards anti-inflammatory.

Nebivolol and metoprolol: long-term effects on inflammation and oxidative stress in essential hypertension.

Arterial hypertension is characterised by increased oxidative stress and inflammation, which are associated with further cardiovascular risk. The aim of our study was to investigate the long-term effects of nebivolol and metoprolol succinate on oxidative stress, and on inflammatory and pro-inflammatory markers in patients with hypertension. Eighty patients with never-treated mild-to-moderate essential hypertension, aged 30-65 years, were randomised to a 5 mg daily dose of nebivolol or a 50-100 mg daily dose of metoprolol succinate. Brachial blood pressure, plasma oxidized LDL (oxLDL), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen, intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA), and urine 8-isoprostane levels were measured before and after 1 year of treatment. Nebivolol and metoprolol reduced equally significantly brachial blood pressure. The oxLDL was significantly reduced in both groups (p < 0.01 and for both drugs), but only nebivolol reduced 8-isoprostanes (p = 0.01). In the metoprolol group, change in oxLDL levels correlated with change in systolic blood pressure (r = 0.45; p < 0.01) and pulse pressure (r = 0.47; p < 0.01). Both metoprolol and nebivolol reduced ICAM-1 (p < 0.01). There was no change in IL-6, hsCRP, fibrinogen, or ADMA levels in either group. These data suggest that in long-term antihypertensive treatment both the cardioselective beta blocker metoprolol succinate and the vasodilating beta blocker nebivolol have inflammation-related effects but only nebivolol has a favourable blood pressure-independent effect on oxidative stress.

ß2-microglobulin, a novel biomarker of peripheral arterial disease, independently predicts aortic stiffness in these patients.

Arterial stiffness is a prominent feature of vascular ageing and strongly predicts cardiovascular and total mortality. The ß2-microglobulin, (ß2M) a newly identified biomarker of peripheral arterial disease (PAD), is related to renal insufficiency, inflammatory and neoplastic diseases, but may also play a role in vascular dysfunction. However, the relationship between arterial stiffness and ß2M has not been previously studied in patients with atherosclerosis. In the present study we examined a possible association between ß2M and arterial stiffness in patients with PAD and in healthy subjects. Plasma ß2M levels and parameters of arterial stiffness such as aortic pulse wave velocity (aPWV) and augmentation index (AIx) were measured in 66 patients with PAD and in 66 apparently healthy subjects. Plasma levels of ß2M, aPWV and AIx were significantly increased in patients with PAD compared with controls (1858.1 ± 472.8 vs 1554.5 ± 277.9 µg/L, p < 0.001; 9.9 ± 2.2 m/s vs 7.6 ± 1.6 m/s, p < 0.001; 28 ± 8 vs 14 ± 11%, p < 0.001; respectively). There existed significant correlation between aPWV and ß2M for the patient group (R = 0.47; p < 0.001), but not for the controls (R = 0.14; p = 0.26). In multivariate analysis, ß2M remained independently associated with aPWV, fetuin-A, age and glomerular filtration rate in patients (R(2) = 0.5, p < 0.001). We found no relationship between ß2M and AIx in either group. We demonstrated that among patients with PAD elevated plasma ß2M levels were associated with higher aortic stiffness irrespective of cardiovascular disease risk factors. These data suggest that ß2M may influence the pathogenesis of aortic stiffness in atherosclerosis.

Association between asymmetric dimethylarginine and indices of vascular function in patients with essential hypertension.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is associated with endothelial dysfunction. The aim of the present study was to investigate the relationship between ADMA, indices of arterial stiffness, endothelial function and carotid artery intima-media thickness (IMT) in hypertension patients. Eighty middle-aged (47 ± 10 years) untreated patients with mild to moderate essential hypertension underwent routine physical examination, pulse wave analysis (PWA), measurement of aortic pulse wave velocity (PWV) and IMT. In PWA, administration of salbutamol and nitroglycerine was used to assess endothelium-dependent (EDV) and endothelium-independent vasodilation, respectively. In univariate analysis, ADMA was correlated with EDV (r = -0.26; p = 0.02) and IMT (r = 0.32; p = 0.007). In multiple regression analysis, ADMA was independently associated with the female gender, EDV, IMT and total cholesterol (R(2) = 0.30; p < 0.001). No correlation was detected between ADMA and augmentation index, central/brachial blood pressure or aortic PWV. In hypertension patients, ADMA is independently correlated with IMT and EDV. Thus, ADMA is a marker of endothelial dysfunction and intima-media thickening in patients with hypertension.

Association of osteoprotegerin with aortic stiffness in patients with symptomatic peripheral artery disease and in healthy subjects.

BACKGROUND: Arterial stiffening is an independent predictor for cardiovascular mortality. Preliminary studies have shown that arterial calcification may have an impact on increased vascular stiffness. However, there are limited data about the role of calcification inhibitor osteoprotegerin (OPG) as an independent predictor for arterial stiffness in patients with peripheral arterial disease (PAD) and in healthy subjects. The aim of this study was to evaluate the association between OPG and arterial stiffness parameters in patients with PAD and in healthy subjects. METHODS: We studied 69 men with PAD (age 63 + or - 7 years) and 68 healthy subjects (age 54 + or - 8 years). Serum OPG and oxidized low-density lipoprotein (oxLDL) were measured using the enzyme-linked immunosorbent assay method. Radial and aortic pulse wave velocity (aPWV) and augmentation index (AIx) were determined by applanation tonometry. RESULTS: The OPG (5.4 + or - 1.7 vs. 4.4 + or - 1.1 pmol/l; P < 0.001) and aPWV (10.1 + or - 2.5 vs. 7.6 + or - 1.6 m/s; P < 0.001) were different for the patients and for the controls. There was a linear relationship between OPG and aPWV in patients with PAD (R = 0.37; P = 0.003) and in healthy individuals (R = 0.40; P = 0.001). In multiple regression models after adjustment for potential confounders, OPG was independently associated with aPWV in the patients (R(2) = 0.47; P < 0.0001) and in the controls (R(2) = 0.44; P < 0.0001). The AIx or radial PWV was not correlated with OPG for either group. CONCLUSION: The independent association between OPG and aPWV in patients with PAD and in controls suggests that the calcification inhibitor OPG may influence aortic stiffening in atherosclerosis and in clinically healthy subjects.

Intestinal Lactobacillus sp. is associated with some cellular and metabolic characteristics of blood in elderly people.

The higher counts or particular groups (Firmicutes/Bacteroidetes) of intestinal microbiota are related to host metabolic reactions, supporting a balance of human ecosystem. We further explored whether intestinal lactobacilli were associated with some principal cellular and metabolic markers of blood in 38 healthy >65-year-old persons. The questionnaire, routine clinical and laboratory data of blood indices as much as the oxidized low-density lipoprotein (ox-LDL) and baseline diene conjugates in low-density lipoprotein (BDC-LDL) of blood sera were explored. The PCR-based intestinal Lactobacillus sp. composition and counts of cultivable lactobacilli (LAB) were tested. The facultative heterofermentative lactobacilli (Lactobacillus casei and Lactobacillus paracasei) were the most frequent (89 and 97%, respectively) species found, while Lactobacillus acidophilus, Lactobacillus plantarum and Lactobacillus reuteri were present in almost half of the elderly persons. The number of species simultaneously colonizing the individuals ranged from 1 to 7 (median 4). In elderly consuming probiotics the LAB counts were significantly higher than in these not consuming (median 7.8, range 4.2-10.8 vs. median 6.3, range 3.3-9.7 log cfu/g; p=0.005), adjusted (OR=1.71, CI95 1.04-2.82; p=0.035) for age and body mass index (BMI). The colonization by L. acidophilus was negatively related (r=-0.367, p=0.0275) to L. reuteri, staying significant after adjusting for age, sex and BMI (OR=0.16, CI95 0.04-0.73; p=0.018). However, the blood glucose concentration showed a tendency for a negative correlation for colonization with Lactobacillus fermentum (r=-0.309, p=0.062) adjusted for BMI (Adj. R(2)=0.181; p=0.013) but not for age and sex. The higher white blood cells (WBC) count was positively related (r=0.434, p=0.007) to presence of Lactobacillus reuteri adjusted for age, sex and BMI (Adj. R(2)=0.193, p=0.027). The lower values of ox-LDL were predicted by higher counts of cultivable lactobacilli adjusted by sex, age and BMI (r = -0.389, p = 0.016; Adj. R(2)=0.184 p=0.029). In conclusion, the pilot study of elderly persons shows that the intestinal lactobacilli are tightly associated with WBC count, blood glucose and content of ox-LDL which all serve as risk markers in pathogenesis of inflammation, metabolic syndrome and cardiovascular disease (CVD).

Inflammatory/oxidative stress during the first week after different types of cardiac surgery.

OBJECTIVES: To compare inflammatory and oxidative stress time course during the first week after different types of cardiac surgery. DESIGN: In patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CABG) or on the working heart (OPCAB) and aortic valve replacement (VALVE) blood samples for high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), myeloperoxidase (MPO), asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) were taken preoperatively and for six consecutive postoperative days. RESULTS: Exploitation of cardiopulmonary bypass (CABG, VALVE groups), but not OPCAB, resulted in significant rise of MPO for two postoperative days. ADMA and Hcy changed in parallel fashion, being significantly decreased in the first postoperative morning and rising to the preoperative levels thereafter. In comparison with coronary artery disease patients, VALVE group had lower preoperative levels of ADMA and different postoperative time course. Postoperative concentrations of IL-6 and hsCRP were increased significantly in all groups and remained elevated during the first postoperative week. CONCLUSIONS: Cardiac surgery results in extensive and complex inflammatory/oxidative stress response regardless of the method or type of surgical procedure used. Myeloperoxidase could be one of the parameters to evaluate the cardiopulmonary bypass-associated inflammatory and oxidative stress response.