Trends and dynamics of changes in aortic pulse wave velocity over one-year observation period in patients treated with peritoneal dialysis.
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Biomedical subjects
Publications and source records attributed to A Zdzienicka.
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Increased aortic pulse wave velocity (AoPWV) has been identified as a risk factor for cardiovascular morbidity in the general population and in patients on dialysis. Most of the studies in ESRD patients refer to subjects on hemodialysis. Influence of the inflammatory process on aortic stiffening remains largely unknown. The aim of the present study was to evaluate potential relationships between AoPWV and blood pressure, basic anthropometric parameters, selected growth factors and markers of the inflammatory process in ESRD patients treated with peritoneal dialysis. The study population consisted of 43 patients (19 F, 24 M) with a mean age of 50.6 +/- 13.4 years on PD for a mean period of 21.9 +/- 20.7 months. AoPWV was measured using two pressure transducers placed on the carotid and femoral arteries and connected to an automatic processor (Complion Colson AS, Paris, France). Serum levels of Tumor Necrosis Factor alpha (TNFalpha), interleukin 6 (IL-6) and plasma basic Fibroblast Growth Factor (bFGF) were measured with ELISA; C-reactive protein and fibrinogen with nephelometry. Serum lipid profile was also assessed. Blood pressure was measured in an outpatient department under standardized conditions. Mean aortic pulse wave velocity in the study population was 10.7 +/- 2.1 m/s. No difference in AoPWV was found between men and women. AoPWV correlated significantly with age (R = 0.41; p < 0.01) but not with time on dialysis. Positive relationship between AoPWV and body weight and BMI was shown (R = 0.31; p < 0.05 and R = 0.35; p < 0.05, respectively). AoPWV correlated significantly with systolic blood pressure (SBP), mean arterial pressure (MAP) and pulse pressure (PP) (R = 0.46, p < 0.005, R = 0.46, p < 0.005 and R = 0.43, p < 0.01, respectively). AoPWV correlated with serum IL-6 and plasma bFGF (R = 0.32, p < 0.05 and R = 0.4, p < 0.01; respectively). The correlation with serum CRP was borderline significant (p < 0.53). In multiple regression analysis age (beta 0.38; p < 0.005), plasma bFGF level (beta 0.3; p < 0.05), and systolic blood pressure (beta 0.29; p < 0.05) were independently associated with pulse wave velocity. Our results suggest that AoPWV values in patients on PD are associated with factors similar to those encountered in the general population. We suggest that increased aortic stiffening may also be related to the chronic inflammatory process in PD patients.
BACKGROUND: Deterioration of left ventricular function during follow-up was reported in some patients with syndrome X and concomitant left bundle branch block. The patients with syndrome X and left bundle branch block has been frequently presented with elevated Endothelin-1 (ET-1) level while brain natriuretic peptide (BNP) (a sensitive marker of left ventricular dysfunction) has not been measured in patients with syndrome X. METHODS: The purpose of the present study was to assess left ventricular diastolic function, levels of N-terminal Brain Natriuretic Peptide (NT-proBNP) precursor and biochemical parameters of endothelial function in patients with syndrome X complicated by left bundle branch block but preserved left ventricular systolic function (group A, n=8). The echocardiographic and neurohormonal measures in these patients were compared to those in patients with syndrome X without left bundle branch block (group B, n=13), and controls (group C, n=15). RESULTS: At rest and after exercise the serum concentration of NT-proBNP was significantly higher in group A than in the controls (at rest: 232+/-96 vs. 133+/-23 fmol/ml, P=0.03; after exercise: 313+/-96 vs. 180+/-33 fmol/ml, P=0.02). The highest concentration of endothelin-1 was also found in group A, being significantly higher than in the controls (6.81 vs. 4.52 pg/ml, P<0.05). Mitral flow abnormalities were detected in left bundle branch block patients. Accordingly, the lowest E/A ratio was in group A and it differed significantly from that in group C (0.85 vs. 1.1, P<0.05). E/A ratio inversely correlated with plasma NT-proBNP concentration in patients with left bundle branch block (r=-0.48, P=0.02). CONCLUSIONS: Elevated NT-proBNP and endothelin-1 plasma concentrations were demonstrated in patients with syndrome X complicated by left bundle branch block even when left ventricular systolic function was still preserved. In this subgroup the magnitude of left ventricular diastolic dysfunction correlated with the increase of BNP level which reflects neurohormonal activation.
BACKGROUND: This study investigated the effects of comicronised fenofibrate in patients with dyslipidemia and polymetabolic syndrome X. DESIGN: After a 6-week dietary run-in phase, 37 male patients eligible on lipid criteria entered a 12-week treatment phase consisting of diet plus one capsule daily containing 200 mg of comicronised fenofibrate (Lipanthyl(R)). RESULTS: A significant reduction in plasma concentrations of total cholesterol, LDL cholesterol and triglyceride was observed after 4, 8 and 12 weeks of treatment with fenofibrate. The improvement in the atherogenic index LDL/HDL cholesterol from a pretreatment 3.8 to 3.0 after treatment was highly statistically significant and may be judged as satisfactory. Significant changes were also observed in haemostatic factors (fibrinogen reduced by 19%, factor VII activity reduced by 18%). Fasting serum insulin levels and insulin response (area under the curve) after oral glucose load were significantly reduced by 26.8% and 18.7%, respectively, indicating an improvement of insulin sensitivity. Systolic and diastolic blood pressure were significantly reduced. Uric acid was significantly reduced by 21.6%. CONCLUSION: These favourable effects of comicronised fenofibrate both on lipid and non lipid parameters, including insulin sensitivity, may confer to this product a particular interest in the treatment of patients with polymetabolic syndrome X.
Vascular endothelial growth factor (VEGF) is known to induce the release of nitric oxide (NO) from endothelial cells. However, the effect of NO on VEGF synthesis is not clear. Accordingly, the effect of endogenous and exogenous NO on VEGF synthesis by rat vascular smooth muscle cells (VSMCs) was investigated. Two in vitro models were used: (1) VSMCs stimulated to produce NO by treatment with interleukin (IL)-1beta (10 ng/mL) and (2) VSMCs lipotransfected with pKecNOS plasmid, containing the endothelial constitutive NO synthase (ecNOS) cDNA. The synthesis of NO was inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME, 2 to 5 mmol/L) or diaminohydroxypyrimidine (DAHP, 2.5 to 5 mmol/L), inhibitors of NOS and GTP cyclohydrolase I, respectively. Some cells treated with L-NAME or DAHP were supplemented with L-arginine (10 mmol/L) or tetrahydrobiopterin (BH(4); 100 micromol/L), respectively. In addition, we studied the effect of sodium nitroprusside (SNP; 10 and 100 micromol/L) and chemically related compounds, potassium ferrocyanide and ferricyanide, on VEGF generation. IL-1beta induced iNOS expression and NO generation and significantly upregulated VEGF mRNA expression and protein synthesis. L-NAME and DAHP totally inhibited NO generation and decreased the IL-1beta-upregulated VEGF synthesis by 30% to 40%. Supplementation with L-arginine or BH(4) increased NO generation by L-NAME- or DAHP-treated cells, and VEGF synthesis was augmented by addition of BH(4). The cells generating NO after pKecNOS transfection released significantly higher amounts of VEGF than cells transfected with control plasmids. Inhibition of NO generation by L-NAME decreased VEGF synthesis. In contrast to the effect of endogenous NO, we observed the inhibition of VEGF synthesis in the presence of high (10 or 100 micromol/L) concentrations of SNP. This effect was mimicked by chemically related ferricyanide and ferrocyanide compounds, suggesting that the inhibitory effect of sodium nitroprusside may be mediated by an NO-independent mechanism. The results indicate that endogenous NO enhances VEGF synthesis. The positive interaction between endogenous NO and VEGF may have implications for endothelial regeneration after balloon angioplasty and for angiogenesis.
BACKGROUND: The association between apo E isoforms and insulin output during the oral glucose test (OGTT) in 60 non-diabetic, non-obese patients with essential hypertension and in control subjects (non-obese, non-diabetic normotensive subjects) was estimated. METHODS: According to low or high insulin output during OGTT, the subjects were divided into the following groups: normotensive subjects with low (NLI) and high (NHI) and hypertensive subjects with low (HLI) and high (HHI) insulin output. RESULTS: The apo E 4/2 phenotype was detected in 32% of hypertensive subjects but not in control subjects. The frequency of apo E 3/2 phenotype in hypertensive subjects was 5% and in normotensive subjects 15%. An increased frequency of phenotype apo E 4/3 was noticed both in HHI (46%) and in NHI (50%) compared with HLI (22%) and NLI (17%) groups. CONCLUSION: The results suggest that the determination of phenotypes apo E and insulin output may contribute to an early detection of individuals at high risk of hypertension development.
BACKGROUND: The role of nitric oxide (NO) in regulation of systemic blood pressure both in normotensives and in hypertensives remains unknown. OBJECTIVE: To investigate the influence of L-arginine (the substrate for generation of NO) on blood pressure in 30 men (aged 51.5 +/- 7.3 years) with established primary arterial hypertension that was not well controlled. METHODS: The antihypertensive therapy was not discontinued and the patients were administered beta-blockers and calcium antagonists only. On day '0' the patients were administered 250 ml 0.9% NaCl during 180 min intravenously. Then we infused 250 mg/kg L-arginine diluted in 250 ml 0.9% NaCl over 180 min into the antecubital vein for four consecutive days (days 'I'-'IV'). Conventional blood pressure and heart rate measurementws were performed before infusion and every 30 min during infusion. Twenty-four-hour ambulatory blood pressure monitoring (with a SpaceLabs 90207 device) with half-hourly recordings during the daytime and during the night-time was performed on the day of NaCl infusion ('0') and repeated on the day of L-arginine infusion ('II') for all patients. As indicators of generation of NO, blood level of cyclic GMP and urinary concentration of nitrite/nitrate were measured. RESULTS: On all days of L-arginine infusion we found significant falls in systolic and diastolic blood pressures (P < 0.0001) with an accompanying significant increase in heart rate (P < 0.001). The most potent hypertensive effect during infusion of L-arginine was observed on day 'I'. Mean systolic blood pressure decreawsed from 152.1 +/- 20.0 mmHg to a minimum of 123.3 +/- 16.2 mmHg after 60 min of the infusion (by about 19%). The maximal percentage fall in systolic blood pressure was consecutively lower on each day oif L-arginine infusion. It was 14.3% on day 'II', 11.9% on day 'III' and 10.1% on day 'IV'. Similarly, the greatest reduction of diastolic blood pressure was observed during infusion of L-arginine on day 'I'. Mean diastolic blood pressure decreased from 95.9 +/- 13.6 to 80 +/- 9.7 mmHg after 120 min of infusion (by about 17%). On the consecutive days maximal falls in diastolic blood pressure compared with its initial value were 13.5% on day 'II', 10.4% on day 'III' and 9.8% on day 'IV'. Twenty-four-hour ambulatory blood pressure monitoring revealed a significant decrease in diastolic blood pressure during infusion of L-arginine compared with day 0 when 0.9% NaCl was infused. Systolic and diastolic blood pressure variabilities were significantly decreased and the day-night differences in systolic and diastolic blood pressures were increased after infusion of L-arginine. We found a significant correlation between heart rate and systolic blood pressure both during the daytime and during night-time on the day of infusion of L-arginine. An increase in urinary concentration of nitrite/nitrate was observed after administration of L-arginine.CONCLUSION: The present results demonstrate that infusion of L-arginine can influence the systemic blood pressure in hypertensives through NO synthesis. By using ambulatory blood pressure monitoring we documented that the hypotensive effect of L-arginine seems to be limited to the infusion period itself. A decrease in blood pressure variability might imply an increase in sensitivity of baroreceptors or an improvement of autonomic functioning.
We compared the high-density lipoprotein (HDL) composition and particle heterogeneity in 60 nonobese (normal body mass index, BMI) men suffering from coronary artery disease (CAD) with normolipemia and normoinsulinemia with lower and higher insulin output during the oral glucose tolerance test (silent hyperinsulinemia). The apolipoprotein apoAI, apoAII, and apoE levels were higher in the high insulin response (HI) group than in low insulin response (LI) group. The ratio of apoAI versus total protein and the ratio of apoAI versus total cholesterol were increased in HI compared with LI. The lipid components in HDL were higher in LI than in HI, while for HDL2 they were higher in HI. The fractioning of HDL by gradient gel electrophoresis revealed a different pattern of HDL particles in both groups. The larger particles, HDL2b and HDL2a (mean particle diameters 10.6 and 9.2 nm, respectively), occur more frequently in HI patients (up to 60%) than in LI patients, whereas the smaller particles, HDL3a and HDL3b (mean particle diameters 8.6 and 7.8 nm, respectively), predominate in LI patients. Our results demonstrate that even in the normoglycemic, normocholesterolemic CAD patients, a high insulin output observed during the oral glucose tolerance test may be connected with a different HDL particle pattern, which suggests changes in the reverse cholesterol transport.
The purpose of the study was to evaluate a relationship between HDL, triglyceride levels and insulinaemia in primary arterial hypertension. The study population consisted of 60 men aged 32-68 years (mean age 50.87 years, s.d. 8.4) with hypertension duration of 11.1 years (s.d. 6.4 years) who were compared with 60 normotensives matched for sex, age and BMI. We examined blood pressure, plasma lipoprotein content, sum of glucose and sum of insulinaemia (sum ins) during OGTT (oral glucose tolerance test). OGTT revealed insulin secretion almost twice as high in hypertensives (P < 0.001 sum ins 11002 microU min/ml, s.d. 4846) than in normotensives (sum ins 6662 microU min/ml, s.d. 3099). Comparison of concentration of selected VLDL components shows that hypertensives were characterised by markedly higher concentration of triglycerides (1.46 mmol/L, s.d. 0.87 in hypertensives and 1.04 mmol/L, s.d. 0.54 in normotensives), free and esterified cholesterol and protein, including apolipoprotein B than normotensives. It was also found that hypertensives had higher levels of apo CIII0 and lower levels of CIII1 VLDL than normotensives. Hypertensive patients showed also a higher frequency of apo E2 isoforms (three-fold) and apo E4 isoforms (two-fold) than healthy subjects. No changes were detected in the composition of LDL and HDL between the groups. Analysing the discriminating ability of biochemical parameters chosen in a step-wise manner it was found that sum ins and HDL, protein and cholesterol concentrations were the factors most powerfully differentiating men with hypertension from healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Inversive association between concentration of plasma high density lipoprotein (HDL) components and endogenous insulin response to oral glucose uptake was observed in 89 healthy, normolipidaemic, non obese, non diabetic male subjects. Inversive correlation between sum of insulin released during oral glucose tolerance test and HDL free and esterified cholesterol as well as apolipoprotein A1 concentration were confirmed. Coexistence of increased insulin secretion and low ratio of free cholesterol concentration to esterified cholesterol and to proteins in HDL was also observed. In separate group of subjects with normal glucose tolerance in high insulin response subgroup the cholesterol (free and esterified) and protein concentrations were lower than in subgroup with low insulin response. The free cholesterol/esterified cholesterol and free cholesterol/protein (apoA1) ratios were decreased in high insulin response subgroup. It is concluded that low concentration of free cholesterol is a most significant change of HDL composition in hyperinsulinemic, healthy men.
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The study was performed in cooperation of the Department of Neurotraumatology and the Department of Clinical Biochemistry Jagiellonian University in Cracow. In patients with central nervous system injury, diagnosed upon computerized tomography scan, melatonin levels were measured. The most frequent reason of damage was severe craniocerebral trauma. Consciousness, assessed according to Glasgow Coma Scale, was between 3 to 13 points. Melatonin levels were measured at 8 a.m. The investigation could not demonstrate any correlations between consciousness disturbances after head injury and serum melatonin levels in the morning. To draw a final conclusion further experiments are necessary. They will help to explain the role of endogenous melatonin in patients after craniocerebral injury.
The aim of the study was to assess the relation between urinary excretion of epinephrine and norepinephrine, and stroke severity, prognosis and standard biochemical investigations in acute phase of ischaemic stroke. The study was done on the material of 36 patients (17 women and 19 men, aged 41-89 years, mean: 69 +/- 13 years) admitted to the stroke unit of the Neurology Department within 24 hours (mean: 7.7 hours), after the first ever ischaemic stroke affecting the territory of the internal carotid artery circulation, confirmed by CT. Patients with the history of diabetes mellitus, cardiac insufficiency and infection on admission were excluded from the study. The 24-hour urine collection for catecholamines (epinephrine and norepinephrine) was done on the first and third day of hospitalization. An even single increased daily excretion of epinephrine (> 10 micrograms/24 hr) was found in 21 and norepinephrine (> 50 micrograms/24 hr) in 10 of 36 patients. No correlation between daily excretion of epinephrine and norepinephrine was found. Statistical analysis revealed a significant relation between norepinephrine, but not epinephrine, and neurological deficit, prognosis and some biochemical parameters of investigated patients. Patients with increased daily excretion of norepinephrine showed worse neurological deficit (p < 0.01), greater mortality assessed on the 30-th and 90-th day of stroke (p < 0.05) and increased plasma glucose, sedimentation rate, white blood cells count, creatinine kinase activity as well as microalbuminuria and decreased plasma kalium concentration.