Patients with mild or moderate chronic kidney disease (CKD) are know to have a significant increase in cardiovascular morbidity in which alterations in large arterial as well as endothelial function may play a role. In the present study, we investigated the relationship between glomerular filtration rate (GFR), augmentation index and endothelial function. Cross sectional study with healthy controls (CONT, n =16), patients with essential hypertension (EH, n = 14), and those with essential hypertension and peripheral artery disease (EH+PAD, n = 26). The effect of postocclusive reactive hyperemia (PORH; 220 mmHg, 3 min,

Objective: To develop an integrated central pressure-stiffness (ICPS) score to predict cardiovascular events. Design and method: One hundred chronic kidney disease (CKD) patients on conservative therapy were included in our study. Pulse wave velocity (PWV), central systolic blood pressure (cSBP) and central pulse pressure (cPP) were measured. A score was assigned to tertiles of PWV (0 to 2), cSBP (0 to 2) and cPP (0 to the first and second and 1 to the third tertile) based on each parameter's ability to individually predict cardiovascular events. The sum of these scores (ICPS) and three ICPS risk categories as predictors were studied. Finally, we compared discrimination of the ICPS risk categories with that of the Framingham CVD score. Results: High (ICPS 3 to 4; n = 37) and very high risk ICPS risk categories (ICPS 5; n = 12) had an increased cardiovascular risk (HR: 4.95, 95%CI: 1.97–12.42, HR: 9.73, 95%CI: 3.06–20.23, respectively) compared to the average risk group (ICPS 0 to 2; n = 51). The very high ICPS risk category remained an independent predictor (HR: 4.87, 95%CI: 1.81–13.08) in a model further adjusted for the Framingham CVD score (HR: 1.66, 95%CI: 1.13–2.43 per 1 SD increase). When comparing discrimination of the Framingham score (Harrell's C: 0.704, 95%CI: 0.625–0.784) and with ICPS added to the Framingham score (C: 0.729, 95%CI: 0.647–0–810), the difference was not significant probably due to the limited power of our study. Conclusions: The ICPS score may clinically importantly improve the identification of CKD patients with elevated cardiovascular risk, but larger studies are required.

BACKGROUND AND AIMS:The aim of this study was to develop an integrated central blood pressure-aortic stiffness (ICPS) risk score to predict cardiovascular events.METHODS:It was a retrospective cohort study. A total of 100 chronic kidney disease (CKD) patients on conservative therapy were included. Pulse wave velocity (PWV), central systolic blood pressure (cSBP), and central pulse pressure (cPP) were measured. A score was assigned to tertiles of PWV (0-2), cPP (0-2), and cSBP (0 to the first and second and 1 to the third tertile) based on each parameter's ability to individually predict cardiovascular outcome. The sum of these scores and three ICPS risk categories as predictors were studied. Finally, we compared discrimination of the ICPS risk categories with PWV, cSBP, and cPP.RESULTS:Adjusted for age and sex, patients in high and very high ICPS risk categories had increased cardiovascular risk (HR: 3.52, 95% CI: 1.65-7.49; HR: 7.56, 95% CI: 3.20-17.85, respectively). High and very high ICPS risk categories remained independent predictors in a model adjusted for multiple CV risk factors (HR: 4.58, 95% CI: 1.65-7.49; HR: 8.56, 95% CI: 3.09-23.76, respectively). ICPS risk categories (Harrell's C: 0.723, 95% CI: 0.652-0.795) showed better discrimination than PWV (Harrell's C: 0.659, 95% CI: 0.586-0.732, p = 0.028) and cSBP (Harrell's C: 0.660, 95% CI: 0.584-0.735, p = 0.008) and there has been a tendency of significance in case of cPP (Harrell's C: 0.691, 95% CI: 0.621-0.761, p = 0.170).CONCLUSION:The ICPS score may clinically importantly improve the identification of CKD patients with elevated cardiovascular risk.

Measures of small and large artery dysfunction have not been investigated in a single cohort for the prediction of cardiovascular (CV) events in patients with nondialysed (ND) chronic kidney disease (CKD). This prospective cohort study aimed to determine whether central pulse wave velocity (cPWV), central pulse pressure (CPP) or microvascular post-occlusive reactive hyperaemia area (PORH HA ) independently predict CV events and mortality in CKD-ND. A total of 94 stage 1–5 CKD-ND (65.3±13.1 years; estimated glomerular filtration rate 35.3 (22.8–49.4) ml min −1 per 1.73 m 2 ) patients were followed-up for a median of 52 (36–65) months and had baseline cPWV and CPP measured by applanation tonometry and PORH HA by laser Doppler flowmetry. Multiple failure time Cox regression models were used to determine the predictive role of vascular parameters on CV mortality and events. Based on multiple linear regressions, baseline age, diabetes, CV disease, and systolic blood pressure (SBP) were independently related to cPWV ( R 2 =0.3), SBP and PORH HA to CPP ( R 2 =0.45), whereas CPP was the only parameter independently related to PORH HA ( R 2 =0.16, all P <0.05). During follow-up, 41 CV events occurred (14 CV deaths). In univariate analyses, cPWV (1.07 (1.02–1.13) per m s −1 ), CPP (1.04 (1.01–1.07) per mm Hg) and lnPORH HA (0.70 (0.58–0.85) per ln(PU × s)) were all related to the outcome. Baseline diabetes (HR 3.07 (1.65–5.68)), lnFGF23 (fibroblast growth factor-23; 1.86 (1.13–3.06) per RU ml −1 ) and CPP (1.04 (1.01–1.07) per mm Hg) were independent predictors of CV events. The impaired pulsatile component of large arteries (CPP) independently of other vascular markers (cPWV, PORH HA ) predicted CV outcomes in CKD-ND. CPP may integrate the information provided by cPWV and PORH HA .

Vascular calcification and hemodynamical abnormalities lead to reduced arterial elasticity in end stage renal disease. Fibroblast growth factor-23 (FGF23) predicts cardiovascular mortality in advance stages of renal failure possibly indicating more advanced vascular calcification. The relation of FGF23 to arterial stiffness in chronic kidney disease is currently under investigations. The aim of our cross sectional study was to assess the potential associations between FGF23 and arterial distensibility. FGF23 (ELISA), pulse wave velocity (PWV), augmentation index (AI) and central pulse pressure (CPP) (PulsePen), were measured in patients with different stages of renal insufficiency (n = 103, 64.8±13.3 years, 50 males, eGFR 40±21 mL/min/1.73m 2 ). Univariate and multiple linear regression models were used for the statistical analysis. According to our results, logFGF23 showed significant relation with serum phosphate, PTH levels and renal function. There were no significant correlations between FGF23 and PWV or CPP. AI, however, correlated negatively with logFGF23 (r = -0.24, p<0.05). By multiple regressions, serum phosphate, logFGF23, systolic blood pressure and heart rate proved to be the individual predictors of AI. (R 2 = 0.31, ß = 0.31, -0.33, 0.21, -0.27, p<0.05). In the subgroup of patients with <45 mL/min/1.73m 2 eGFR, serum phosphate and logFGF23 remained the significant predictors (R 2 0.21, ß = 0.31, -0.39, p<0.05) FGF23 may be a determinant of peripheral arterial elasticity independently of serum phosphate level especially in advanced stages of chronic kidney disease. (Supported by the Hungarian Kidney Foundation and the Hungarian Society of Hypertension)

Endothelial dysfunction, as assessed by laser-Doppler flowmetry (LDF) is an accepted method to measure microvascular reactivity, which correlates with cardiovascular risk factors in several patient populations. The aim of our prospective cohort study was to assess determinants of LDF parameters and to evaluate their prognostic values in patients with chronic kidney disease (CKD). Ninety four hypertensive, stage 1–5 non-dialysis CKD patients had LDF measurements (iontophoresis of acethylcoline and sodium nitropusside in different doses and postocclusive reactive hyperaemia (PORH)). Baseline associations of these parameters with clinical, hemodynamic and laboratory characteristics were determined by linear regression models. Patients were followed for a median of 43 (37–55) months and the prognostic value of LDF parameters for cardiovascular (CV) events were evaluated by log-rank tests and Cox proportional hazard models. The different LDF parameters did show strong correlation with each other. All iontophoresis parameters were strongly and negatively related to the presence of diabetes or antidiabetic treatment. All PORH parameters were strongly and negatively associated to central pulse pressure and the use of calcium channel blockers. During follow-up 26 CV events occurred. In multivariate analysis, only the presence of diabetes was found to be an independent predictor of CV events (RR: 3.85 (1.66–8.89), p=0.0012). None of the LDF parameters predicted CV outcome. According to our results only the presence of diabetes, but not parameters of microvascular reactivity measured by iontophoresis or PORH have prognostic value for CV events in patients with CKD on conservative therapy. (Supported by Hungarian Kidney Foundation and Hungarian Society of Hypertension).

According to previous studies different parameters characterize arterial stiffness relate to cardiovascular mortality in patients on haemodialysis. However, its relative prognostic value and the optimal time of measurement have not previously been examined in one cohort. The carotid-femoral pulse wave velocity (PWV), the carotid augmentation index (AI), the carotid pulse pressure (CPP) and the carotid-brachial pulse pressure amplification (AMP) were determined in 98 patients before and after haemodialysis procedure. Patients were followed for 29 months (median; range 1–34) and the association of these parameters with the risk of cardiovascular mortality was assessed using log-rank tests and Cox proportional hazards regression. During follow-up, 25 patients died of cardiovascular causes. Increasing pre-and postdialysis PWV tertiles and decreasing predialysis AMP tertiles were significantly related to cardiovascular mortality (p = 0.012 and 0.011 for PWV, respectively; and <0.001 for AMP). Neither the AI nor CPP was related to cardiovascular mortality. The adjusted hazard ratios for 1 m/s higher pre-and postdialysis PWV were 1.24 (1.07–1.44) and 1.17 (1.06–1.28), respectively. The hazard ratio for 10

BACKGROUNDThe method of estimating distance traveled by the pulse wave, used in the calculation of pulse wave velocity (PWV), is not standardized. Our objective was to assess whether different methods of distance measurement influenced the association of PWV to cardiovascular mortality in hemodialysis (HD) patients.METHODSNinety-eight chronic HD patients had their PWV measured using three methods for distance estimation; PWV1: suprasternal notch-to-femoral site minus suprasternal notch-to-carotid site, PWV2: carotid-to-femoral site, PWV3: carotid-to-femoral site minus suprasternal notch-to-carotid site. Carotid-to-femoral distance was used to approximate torso length. Patients were followed for a median of 30 months and the association of PWV and cardiovascular mortality was assessed using survival analysis before and after stratification for torso length.RESULTSThe three methods resulted in significantly different PWV values. During follow-up 50 patients died, 32 of cardiovascular causes. In log-rank tests, only tertiles of PWV1 was significantly related to outcome (P values 0.017, 0.257, 0.137, for PWV1, PWV2, and PWV3, respectively). In adjusted Cox, proportional hazards regression only PWV1 was related to cardiovascular mortality. In stratified analysis, however, among patients with below median torso length all PWV values were related to outcome, whereas in patients with above median torso length none of the PWV methods resulted in significant relationship to outcome.CONCLUSIONSPWV calculated using suprasternal notch-to-femoral distance minus suprasternal notch-to-carotid distance provides the strongest relationship to cardiovascular mortality. Longer torso weakens the predictive value of PWV, possibly due to more tortuosity of the aorta hence, more error introduced when using surface tape measurements.

AIM Corona phlebectatica paraplantaris (CPP) is a typical sign of chronic venous insufficiency (CVI). The aim of our study was to obtain information about the basic microcirculation and microvascular reactivity in CPP. METHODS Microcirculation of the skin was investigated on the surface of CPPs and as a control in a nearby vessel-free skin region of the foot. The resting flow was recorded in a supine position, then different provocation tests were performed such as local heating (44 ˚C, 2 min), postocclusive reactive hyperemia (PORH, 220 mmHg, 3 min) and venoarterial response (VAR). RESULTS There were significant differences between the circulation of CPPs and control skin: resting flux and amplitude values were higher in CPPs. Spectral analysis showed higher endothelial, sympathetic, myogenic, breathing and heart activities in CPPs. At the beginning of the PORH test, compression of the leg increased the flow in CPPs. Other PORH parameters, the response to local heating and VAR were not different in the two areas studied. CONCLUSION High resting flux values and large amplitudes in CPPs suggest more the presence of open AV shunts in the ankle region than the role of calibre differences. Pathological responses to different provocation tests can be a consequence of the CVI.

A selegilinnek es N-proragyl szarmazekainak (dezmetil-deprenyl, deprenyl-N-oxid) neuroprotektiv hatasat tanulmanyoztuk A-2058 melanoma sejtkulturan. A sejtkarosodast BSO toxinnal valtottuk ki, mely gatolja a glutation szinteziset, valamint csokkenti az elősejtek szamat es a sejt mitozist, mikozben noveli az apoptotikus indexet. A selegiline es metabolitjai csokkentik a sejt veszteseget es az apoptotikus indexet. A leghatasosabb antiapoptotikus hatasu vegyuletnek a dezmetil-deprenyl bizonyult, mig a deprenyl-N-oxid kontroll szinten stabilizalta az elősejtek aranyat, novelve a mitotikus indexet a kontrollhoz viszonyitva. A deprenyl-N-oxid igeretes neuroprotektiv vegyuletnek tűnik. A selegiline ’first pass’ metabolizmusa jelentős. Jo hatasfoku, toleralhato parenteralis ut kimunkalasa novelhetne a vegyulet antidepressziv hatasat „sajtreakcio” nelkul. A selegiline novelte a magas zsirtartalmu tapon tartott patkanyok teljes scavanger kapacitasat es kivedte a maj elzsirosodasat. Az SSAO enzim exogen szubsztratja a benzilamin, gatolja az inzulinrezisztencia kialakulasat es a glukoz-toleranciat. Az elhizasos es diabeteszes ragcsalomodelleken kapott eredmenyeink megerősitettek az SSAO enzim szubsztratjanak, az oralisan adagolt benzilaminnak a kedvező hatasat a szenhidrat- es zsiranyagcserere. A kezeles nem rontotta, inkabb javitotta a nitrogen-monoxid hasznosithatosagat az aortaban. | The neuroprotective effect of selegiline and its N-propargyl derivatives (desmethyl-deprenyl, deprenyl-N-oxide) has been investigated on A-2058 melanoma cell culture. Cell damage was induced by BSO toxicity. BSO inhibits glutation synthesis, decreases viable cell number and mitotic rate, while increased the apoptotic index. Selegiline with its metabolites decreased cell loss and the apoptotic ratio. Desmethyl-deprenyl was the most effective compound decreasing apoptotic activity, while deprenyl-N-oxide stabilized cell number on control level and increased the ratio of mitotic cells above the serum deprived control. Desmethyl-deprenyl supposed to be promising neuroprotective agent. Selegiline has a high rate of ‘first pass’ metabolism. An efficient route of parenteral administration could establish antidepressive activity, without “cheese reaction”. Selegiline treatment of rats kept on high fat diet increased total scavenger capacity and decreased fat content of rat liver. Our results have confirmed the insulinomimetic effect of oral treatment with benzylamine, exogenous substrate of SSAO, using various rodent models of diabetes and obesity. The treatment also improved the bioavailability of nitric oxide in the aorta. Based on these results, further studies on the effect of SSAO substrate amines on carbohydrate and lipid metabolism is reasonable, especially as insulin resistance, obesity and their vascular complications are major health problems.

Korabbi vizsgalatok eredmenyei alapjan az erfali tagulekonysag parameterei osszefuggest mutatnak a cardiovascularis mortalitassal hemodializalt betegekben. A kulonboző parameterek relativ prognosztikus erteket ugyanakkor egy kozos kohorszban eddig nem vizsgaltak. Modszer: Dializis előtt es utan 98 betegnel mertuk a carotis-femoralis pulzushullam terjedesi sebesseget, a carotis augmentacios indexet, a carotis pulzusnyomasat es a carotis-brachialis pulzusnyomas amplifikaciojat. A betegeket 29 honapig (median) (tartomany 1–35) kovettuk, majd a cardiovascularis mortalitas es a kiindulaskor mert tagulekonysagi parameterek kozotti osszefuggest vizsgaltuk log-rank tesztek, illetve a korhoz, diabeteshez es korabban meglevő cardiovascularis megbetegedeshez illesztett Cox-fele regresszios modellek alkalmazasaval. Eredmenyek: A kovetes alatt 40 beteg halt meg (mortalitasi rata 20,7/100 betegev), koztuk 25-en cardiovascularis ok kovetkezteben. A dializis előtt es utan mert pulzushullam-terjedesi sebesseget tercilisei, illetve a dializis előtt mert pulzusnyomas-amplifikacio tercilise szignifikans osszefuggest mutattak a cardiovascularis mortalitassal (log-rank p-ertekek 0,012 es 0,011 a pre- es posztdializis pulzushullam-terjedesi sebesseg, illetve <0,001 es 0,321 a pre- es posztdializis pulzusnyomas-amplifikacio eseten). Az augmentacios indexek, illetve a carotispulzusnyomas-ertekek nem alltak osszefuggesben a cardiovascularis mortalitassal. Cox-modellben az 1 m/s-mal gyorsabb pre- es posztdializis pulzushullam-terjedesi sebessegehez tartozo relativ riziko 1,24 (1,07–1,44) es 1,17 (1,06–1,28) volt. 10%-kal kisebb predializispulzusnyomas-amplifikacioval jaro rizikonovekedes 41% (3–92%) volt. Egy kozos modellben vizsgalva mind a predializispulzushullam-terjedesi sebesseg, mind a pulzusnyomas-amplifikacio szignifikans osszefuggest mutatott a cardiovascularis tulelessel [relativ riziko: 1,23 (1,07–1,42) es 1,39 (1,02–1,89)]. Kovetkeztetes: Hemodializalt betegekben az erfali tagulekonysagot leiro kulonboző parameterek kozul a pulzushullam-terjedesi sebesseg a meres idejetől fuggetlen, konzekvens osszefuggest mutat a cardiovascularis mortalitassal. Ugyanakkor a predializispulzusnyomas-amplifikacios ertek tovabbi prognosztikus informaciot hordoz. | Previous studies demonstrated that different parameters of arterial stiffness are related to cardiovascular mortality in hemodialysis patients. The relative prognostic value of these parameters has not previously been evaluated in one cohort. Patients and Methods: : Carotid-femoral pulse wave velocity, carotid augmentation index, carotid pulse pressure and carotid-brachial pulse pressure amplification were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1–34) and the association of these parameters with cardiovascular mortality was assessed using log-rank tests and Cox proportional hazards regressions. Results: During follow-up, 40 patients died (mortality rate 20.7/100 patient-year), of which 25 died of cardiovascular causes. Increasing pre- and postdialysis pulse wave velocity tertiles and decreasing predialysis pulse pressure amplification tertiles were significantly related to cardiovascular mortality (p-values are 0.012 and 0.011 for pre- and postdialysis pulse wave velocity, and <0.001 and 0,321 for pre- and postdialysis pulse pressure amplification, respectively). Neither the carotid augmentation index nor carotid pulse pressure was related to cardiovascular mortality. In the Cox-regression, the adjusted hazard ratios for 1 m/s higher pre- and postdialysis pulse wave velocity were 1.24 (1.07–1.44) and 1.17 (1.06–1.28), respectively. The hazard ratio for 10% lower predialysis pulse pressure amplification was 1.41 (1.03–1.92). When included in the same model, both predialysis pulse wave velocity and pulse pressure amplification remained significantly associated with cardiovascular mortality (relative risk: 1.23 [1.07–1.42] and 1.39 [1.02–1.89]). Conclusion: Among different stiffness parameters, pulse wave velocity is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis pulse pressure amplification seems to provide additional prognostic information.

A csontbiologia teren vegzett vizsgalatok vezettek a tumornekrozis-faktorok csaladjaba tartozo receptorok, igy az osteoprotegerin es a receptor activator of nuclear factor κB (RANK) szerepenek tisztazasahoz a csontatepules folyamatanak szabalyozasaban. A RANK receptor ligandja (RANKL) a csontreszorpcio stimulatora, mig az osteoprotegerin a csont keringő, szolubilis protektora. A csontatepules koros allapotai (igy az osteoporosis is) osszefuggnek az osteoprotegerin es a RANKL kozti egyensulyi allapot megbomlasaval. Az elmult evek eredmenyei ramutattak arra is, hogy az osteoprotegerin/RANKL/RANK rendszer fontos szerepet jatszik az immun- es a vascularis rendszer szabalyozasaban. Kozlemenyunkben az elsődlegesen „csontprotektor” hatasukent megismert osteoprotegerin funkciojat, szabalyozasat es patologias allapotokban – dontően a cardiovascularis megbetegedesekben – jatszott szerepet, rizikomarkerkent valo alkalmazhatosagat foglaljuk ossze. Vegul kronikus hemodializalt betegeink kozott vegzett prospektiv vizsgalatunkat ismertetjuk, amelyben az ezen betegek cardiovascularis mortalitasa, OPG-szerumszintje es erfali tagulekonysaga kozti osszefuggest vizsgaltuk – pozitiv eredmennyel. | Experimental and clinical trials in the field of bone biology helped to clarify the role of receptors, which belong to the tumor necrosis factor family, such as osteoprotegerin and receptor activator of nuclear factor κB (RANK), in the regulation of bone remodeling. The ligand of the receptor activator of nuclear factor κB (RANKL) is a stimulator of bone resorption, while osteoprotegerin is the soluble “decoy” receptor to RANKL, protecting thereby bone from resorption. Pathological states of bone remodeling (like osteoporosis) are associated with inbalance in the activity of osteoprotegerin and the receptor activator of nuclear factor κB. Recent studies, however, also indicate that the osteoprotegerin/RANKL/RANK system has important roles in the regulation of the immune and vascular system as well. In this review we summarize the function and regulation of osteoprotegerin, its role in pathological states – primarily in cardiovascular diseases – and its relevance as a marker of cardiovascular risk. Finally, we present our prospective trial performed among the chronic dialyzed patients, where we examined the association between the cardiovascular mortality, osteoprotegerin levels and the arterial stiffness.

Assessment of arterial stiffness in dialysis patients has prognostic significance. The TensioClinic device uses oscillometrically obtained wave forms to calculate pulse wave velocity (PWV) and augmentation index (AI). Our objective was assess the validity of measurements of TensioClinic (PWVT, AIT) compared to that of the validated PulsePen tonometer (PWVP, AIP). We measured PWV and AIx in duplicate, before and after hemodialysis, in 94 hemodialysis patients. Reliability of a given device was assessed by calculating the standard deviation of the difference (SDD) between the first and second measurement. Validity of TensioClinic was evaluated by comparing its results to that obtained by the PulsePen device, using correlation analysis and Bland-Altman plots. Predialysis SDD for PWVP and PWVT were –0.03±0.94 m/s and 0.51±1.35 m/s, postdialysis PWVP and PWVT SDD-s were 0.09±1.419 m/s and 0.07±1.81 m/s, respectively. Pre- and postdialysis SDD for AIP and AIT were 0.87±5.49

Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to survival in hemodialysis patients. The link between OPG and aortic stiffening - a consequence of arterial calcification - has not previously been evaluated in this population, and it is not known whether OPG related mortality risk is mediated by arterial stiffening. At baseline OPG and aortic pulse wave velocity (PWV) was measured in 98 hemodialysis patients who were then followed for a median of 18 months. The relationship between OPG and PWV was assessed by multivariate linear regression. The role of PWV in mediating OPG related mortality risk was evaluated by including both OPG and PWV in the same survival model. At baseline mean (SD) PWV was 11.2 (3,3) m/s and median OPG (interquartile range) was 11.1 (7.5–15.9) nmol/L. There was a strong positive linear relationship between PWV and lnOPG (beta = 1.48, p = 0.009), independent of other covariates. During follow-up 28 patients died (mortality rate 18.4/100 patient years). In separate survival models both PWV and lnOPG were related to all cause mortality (hazard ratios 1.21[1.07–1.38] and 5.39 [2.16–13.43], respectively). When both PWV and lnOPG were entered into the same model, only OPG remained significantly associated with mortality (hazard ratios 1.12 [0.97–1.28] and 4.37 [1.62–11.80], respectively). In hemodialysis patients OPG is strongly related to PWV and OPG related mortality risk may, in part, mediated by increased PWV.