Nigella sativa might be mediated by its effects on nitric oxide, angiotensin-converting enzyme, heme oxygenase and oxidative stress markers.This study was conducted to determine whether the blood pressure-lowering effect of Nigella sativa oil at a dose of 2.5 mg/kg for 8 weeks, respectively, concomitantly with L-NAME administration.Twenty-four adult male Sprague-Dawley rats were divided equally into 4 groups. One group served as the control (group 1), whereas the other three groups (groups 2-4) were administered L-NAME . Groups 3 and 4 were given oral nicardipine daily at a dose of 3 mg/kg and Nigella sativa oil prevented the increase in systolic blood pressure in the L-NAME-treated rats. The blood pressure reduction was associated with a reduction in cardiac lipid peroxidation product, NADPH oxidase, angiotensin-converting enzyme activity and plasma nitric oxide, as well as with an increase in heme oxygenase-1 activity in the heart. The effects of Nigella sativa on blood pressure, lipid peroxidation product, nicotinamide adenine dinucleotide phosphate oxidase and angiotensin-converting enzyme were similar to those of nicardipine. In contrast, L-NAME had opposite effects on lipid peroxidation, angiotensin-converting enzyme and NO.Nigella sativa oil appears to be mediated by a reduction in cardiac oxidative stress and angiotensin-converting enzyme activity, an increase in cardiac heme oxygenase-1 activity and a prevention of plasma nitric oxide loss. Thus, Nigella sativa oil might be beneficial for controlling hypertension.The antihypertensive effect of  Hypertension is defined as a persistent elevation of systolic blood pressure of 140 mmHg or greater and/or diastolic blood pressure of 90 mmHg or greater. Hypertension is a major risk factor for cardiovascular, cerebrovascular and renal diseases Oxidative stress is important in the pathogenesis of essential hypertension or in arterial damage related to essential hypertension Many factors are involved in blood pressure control, including angiotensin-converting enzyme (ACE), heme oxygenase (HO-1) and the endothelial-derived relaxing factor (EDRF) NO. ACE promotes the production of angiotensin II (Ang II) from angiotensin I (Ang I), which has a direct vasoconstrictor effect on the vessels that increase blood pressure. Ang II has been reported to increase vascular superoxide anion production via membrane NADPH oxidase activation, which will then lead to an increase in lipid peroxidation, inflammation and vascular injury Nigella sativa, which is also known as black cumin, has been shown to possess blood pressure-lowering effects in both animals and humans N. sativa was found to be rich in thymoquinone and polyphenols The use of medicinal plants for the prevention of cardiovascular diseases has been increasing recently. N. sativa remains uncertain. The antihypertensive effects of N. sativa may involve several mechanisms. El Tahir et al. N. sativa likely reduces blood pressure via a reduction in myocardial contractility and heart rate and that N. sativa might activate muscarinic receptors on blood vessels. However, Magyar et al. N. sativa might have calcium channel-blocking properties. To the best of our knowledge, the effects of N. sativa on ACE, HO-1, NADPH oxidase and NO have not been thoroughly explored. Therefore, the present study was designed to determine the effects of N. sativa oil on ACE, HO-1 and cardiac redox status  in Nω-nitro-L-arginine methyl ester (L-NAME)-treated rats. Nicardipine was used in the study as a positive control because it has antioxidant effects and calcium channel-blocking properties.However, the exact mechanism of the blood pressure-lowering effects of N. sativa oil (2.5 mg/kg) After a week of adaptation, twenty-four male Sprague-Dawley rats (180-220 g) obtained from the Laboratory Animal Resource Unit, Faculty of Medicine, Universiti Kebangsaan Malaysia were divided into four experimental groups. One group served as a control whereas the other three groups were administered L-NAME intraperitoneally (25 mg/kg) A non-invasive method was used to measure systolic blood pressure as described by Jaarin et al. Lipid peroxidation determined as malondialdehyde (MDA) was measured in the cardiac samples following a method by Ledwozyw et al. −1cm−1.NADPH oxidase activity measured as superoxide production in the cardiac samples was based on a reduction of ferricytochrome c in ferrocytochrome at pH 7.8 as described by Mustapha et al. ACE  and HO-1  activities were analyzed in cardiac samples using commercially available kits following the manufacturer's instructions. The colored end products of these enzymes were measured by a microplate reader  at 450 nm.2-) metabolite content in the samples. Plasma and cardiac NO content were estimated based on a previously described method The production of NO was indirectly detected by measuring the nitrite . The normality of the data was evaluated using a Kolmogorov–Smirnov test. Differences between the groups for each parameter were compared using a one-way analysis of variance (ANOVA) with Tukey's Honestly Significant Differences post-hoc test. Statistical significance was defined as N. sativa and nicardipine resulted in a significantly lower blood pressure  (Nigella sativa groups.The L-NAME-treated group displayed a significant increase in cardiac MDA content compared to the control. L-NAME+nicardipine and L-NAME+(p<0.05) . There wN. sativa-treated groups displayed lower enzyme activity. No significant difference was noted among the control, nicardipine- and N. sativa-treated groups  (N. sativa-treated group than in the control (p<0.005) and nicardipine (p<0.05) groups  . No sign) groups . The NO . sativa .p<0.001). The NO level was significantly higher in the N. sativa-treated group compared to the L-NAME and nicardipine-treated groups (p<0.001) (There was a significant reduction in plasma NO levels in the L-NAME and nicardipine-treated groups compared to the control (p<0.001) .In this study, we demonstrated that the intraperitoneal administration of an NO synthase inhibitor (L-NAME) at a dose of 25 mg/kg increased blood pressure in rats. This finding was similar to previous studies, which reported that L-NAME at a dose of 40-55 mg/kg per day increased blood pressure N. sativa oil a dose of 2.5 mg/kg for 8 weeks attenuated the systolic blood pressure increase in the rats that were co-treated with L-NAME. The effect of the oil on blood pressure in this study was in agreement with other studies N. sativa in this study was accompanied by significant reductions in MDA, ACE and NADPH oxidase activities and by an increase in HO-1 activity in cardiac tissue, in addition to an increase in plasma NO. Khattab and Nagi The administration of N. sativa oil in this study indicate that the oil has an antioxidant effect and may contribute to blood pressure reduction. The antioxidant effects of N. sativa have been reported previously N. sativa contributed towards its antihypertensive effect. The seed oil that contains thymoquinone, dithymoquinone and thymol might contribute to this effect N. sativa may be attributed to its diuretic properties Reductions in L-NAME-induced MDA content and NADPH oxidase activity by the N. sativa. The effect of thymoquinone on the overexpression of HO-1 expression was also reported by Kundu et al. The activation of HO-1 plays an important role in reducing blood pressure by reducing Ang II-induced inflammation and NADPH oxidase-mediated oxidative stress via the production of anion superoxide N. sativa oil reduced cardiac ACE activity in rats receiving L-NAME. This result suggests that the antioxidant properties of N. sativa oil contributed to the reduction of the enzyme activity. We are unsure of how the reduction in cardiac ACE reduced blood pressure because our study did not measure serum ACE and aldosterone levels. Further study of serum ACE and aldosterone must be performed in the future. However, a previous study by Zeggwagh et al. N. sativa aqueous extract had no effect on plasma ACE activity in spontaneously hypertensive rats.ACE converts Ang I to Ang II. The reduction of ACE activity leads to a reduction in blood pressure because of the reduction in Ang II synthesis. Ang II acts as a potent vasoconstrictor. Ang II exacerbates oxidative stress by increasing the production of superoxide N. sativa prevented the loss of plasma NO caused by L-NAME. The mechanism on how N. sativa reversed the reduction in NO levels in spite of L-NAME was unclear. We postulated that the effect is most likely attributable to the high antioxidant content of N. sativa, which helps prevent oxidative stress, vascular inflammation and dysfunction induced by L-NAME. A similar antioxidant effect on NO was reported by Nurul-Iman et al. EDRF, better known as NO, causes vasodilation, which subsequently reduces total peripheral resistance and hence reduces blood pressure. The inhibition of eNOS reduces NO production, whereas eNOS stimulation increases NO production. Our study showed that treatment with N. sativa in this study was comparable to that of nicardipine, which is a short-acting calcium antagonist. We chose nicardipine for this study because it has antioxidant effects and N. sativa was reported to possess calcium channel-blocking properties N. sativa, nicardipine reduced cardiac ACE. The effect of nicardipine on ACE in this study was in accordance with Kataoka et al. N. sativa, nicardipine had no effect on HO-1. In conclusion, N. sativa oil at a dose of 2.5 mg/kg attenuates the L-NAME-induced increase in blood pressure and was associated with a reduction in cardiac redox status and angiotensin-converting enzyme activity and an increase in HO-1 activity. N. sativa oil also prevented plasma NO loss. Notably, the blood pressure-lowering effect was comparable to that of nicardipine.The effect of


Notably, they also had a remarkably greater prevalence of mild and/or moderate LVDD compared with those without NAFLD . Age, hypertension, smoking, medication use, E/A ratio, LV volumes and mass were comparable between the two groups of patients. NAFLD was associated with a three-fold increased odds of mild and/or moderate LVDD after adjusting for age, sex, body mass index, hypertension, diabetes duration, hemoglobin A1c, eGFR, LV mass index and ejection fraction . In conclusion, NAFLD is independently associated with early LVDD in type 2 diabetic patients with preserved systolic function.Accumulating evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with left ventricular diastolic dysfunction (LVDD) in nondiabetic individuals. To date, there are very limited data on this topic in patients with type 2 diabetes and it remains uncertain whether NAFLD is independently associated with the presence of LVDD in this patient population. We performed a liver ultrasonography and trans-thoracic echocardiography  in 222 (156 men and 66 women) consecutive type 2 diabetic outpatients with no previous history of ischemic heart disease, chronic heart failure, valvular diseases and known hepatic diseases. Binary logistic regression analysis was used to examine the association between NAFLD and the presence/severity of LVDD graded according to the current criteria of the American Society of Echocardiography, and to identify the variables that were independently associated with LVDD, which was included as the dependent variable. Patients with ultrasound-diagnosed NAFLD ( Non-alcoholic fatty liver disease (NAFLD) is increasingly diagnosed worldwide and is the most common chronic liver disease in patients with type 2 diabetes (occurring in up to 70–75% of these patients) –3. In adTo date, there is ample evidence suggesting that NAFLD is associated not only with liver-related morbidity and mortality, but also with an increased risk of developing cardiovascular disease, which is the most common cause of death among patients with type 2 diabetes –8. In reTo our knowledge, very little information is currently available regarding the relationship between NAFLD and LVDD in people with type 2 diabetes, a group of individuals in whom structural and functional myocardial abnormalities may develop even in the absence of hypertension or ischemic heart disease (IHD) . In a smThus, the aim of the present study was to examine whether NAFLD is associated with LVDD  ,12 in a i.e., myocardial infarction, angina or coronary revascularization procedures), chronic heart failure, valvular diseases, atrial fibrillation, malignancy and end-stage renal disease; and (2) a prior history of cirrhosis of any etiology or other known causes of chronic liver diseases, including viral hepatitis, hemochromatosis and excessive alcohol intake . All women were postmenopausal and did not take hormonal replacement therapy.We studied 222 white consecutive outpatients with type 2 diabetes, who regularly attended our diabetes clinics of the University of Verona and the “Sacro Cuore” Hospital of Negrar. For the current study, we excluded patients with: (1) a prior history of IHD  approved the study protocol. All participants gave their written informed consent for participation in this medical research.Body mass index (BMI) was calculated by dividing weight in kilograms by height in meters squared. A physician measured blood pressure with a mercury sphygmomanometer (at the right upper arm using an appropriate cuff size) after patients had been seated quietly for at least 5 minutes. Patients were considered to have hypertension if their blood pressure was ≥140/90 mmHg or if they were taking any anti-hypertensive drugs. Pulse pressure was determined as the difference between the systolic pressure and diastolic pressure. Information on alcohol consumption, smoking history and use of medications was obtained from all patients via interviews during medical examinations.Venous blood samples were drawn in the morning after an overnight fast. Serum liver enzymes, creatinine (measured using a Jaffé rate-blanked and compensated assay) and other biochemical blood measurements were determined using standard laboratory procedures . Normal ranges for serum aspartate and alanine aminotransferases and gamma-glutamyltransferase in our laboratory were 10–40 U/l for women and 10–50 U/l for men, respectively. LDL-cholesterol was calculated using the Friedewald’s formula. Hemoglobin A1c (HbA1c) was measured by an automated high-performance liquid chromatography analyzer ; the upper limit of normal for our laboratory was 5.6%. Glomerular filtration rate (eGFR) was estimated by the 4-variable Modification of Diet in Renal Disease study equation . AlbuminPresence of either internal or common carotid artery stenoses was ascertained by echo-Doppler scanning. In all participants, the presence of microvascular diabetic complications, such as peripheral sensory neuropathy (by biothesiometer), nephropathy  and retinopathy (by fundoscopy after pupillary dilation) was also recorded.i.e., evidence of diffuse hyperechogenicity of the liver relative to the kidneys, ultrasound beam attenuation and poor visualization of intrahepatic vessel borders and diaphragm [Liver ultrasonography was performed in all participants by two experienced and trained radiologists, who were blinded to the subjects’ details, including echocardiographic data. Hepatic steatosis was diagnosed on the basis of characteristic ultrasonographic features, iaphragm . It is kiaphragm . No infoiaphragm .A 12-lead standard resting electrocardiogram and a transthoracic echocardiographic Doppler evaluation with spectral tissue Doppler analysis  were performed within approximately 1 month of liver ultrasonography in all patients by two experienced and trained cardiologists, who were blinded to the participants’ details, including liver ultrasound data. Conventional echocardiography was used to measure left ventricular (LV) diameters, wall thickness, and mass according to international standard criteria . LV end-tau), which is derived from the following formula: tau = (14.70–100 x e’)/0.15 [Pulsed-wave tissue Doppler echocardiography of the septal and lateral mitral annulus was used to measure the early (e’) and late (a’) annular diastolic and systolic (s’) tissue velocities, and the mean values of septal and lateral annulus measurements were used for analysis –19. The e’)/0.15 . LV end-e’)/0.15 .SYS) and global strain rate (SRSYS), respectively. Similarly, the global strain rate during the early (SRE) and late (SRL) phase of diastole was also calculated. The ratio of trans-mitral E-wave velocity to SRE as an index of LV filling pressure was calculated as previously proposed [P = NS for all differences). Similarly, when tissue Doppler imaging signals were re-measured by a second observer, the mean absolute differences in tissue velocities between the 2 observers were 0.11±0.09 cm/s for s’ velocity, 0.30±0.25 cm/s for e’ velocity, and 0.36±0.28 cm/s for a’ velocity . No significant differences were also found in the intra-observer and inter-observer variabilities for global longitudinal strain, SRSYS, and SRE [Myocardial deformation measurements were also performed off-line (by the same cardiologist who performed echocardiographic examinations) in a subgroup of patients with adequate apical windows with the use of a standard EchoPac PC workstation application  for 2-dimensional speckle-tracking myocardial strain analysis. Global longitudinal strain and strain rate curves were obtained in 156 patients, including all six LV myocardial segments from 4-chamber, 2-chamber, and long-axis apical views –23. The proposed . StandarIn all participants LV diastolic function was categorized as normal, mild, moderate or severe dysfunction using the echocardiographic criteria that have been proposed and validated by the American Society of Echocardiography (ASE). The individual criteria in the ASE algorithm used to grade LV diastolic function were mitral E/A ratio, Dte, e’ septal, e’ lateral, averaged E/e’ ratio, indexed left atrial volume, and mitral (A) and pulmonary vein (Ar)-wave durations ,24.t-test for normally distributed variables and the Mann-Whitney test for non-normally distributed variables; the X2 test with Yates’s correction for continuity was used to test differences in categorical variables between the groups. Binary logistic regression analysis was used to examine the association between NAFLD and the presence/severity of LVDD graded according to current ASE criteria , and to identify the variables that are independently associated with LVDD, which was included as the dependent variable. Four forced-entry multivariable logistic regression models were performed: an unadjusted model; a model adjusted for age and sex (model 1); a regression model further adjusted for BMI, diabetes duration, HbA1c, eGFR and hypertension (model 2); and, finally, a model adjusted for the same variables included in model 2 plus echocardiographic parameters, such as LV ejection fraction and indexed LV mass (model 3). The covariates for multivariable regression analyses were chosen as potential confounding factors based on their significance in univariate analyses or based on their biological plausibility . Interaction terms were also generated between NAFLD and sex, age and BMI in terms of LVDD. None of these interaction terms was statistically significant in the fully adjusted regression models. P-values <0.05 were considered statistically significant.Data are presented as means±SD, medians and inter-quartile ranges (IQR) or percentages. Differences in main clinical and biochemical characteristics and echocardiographic parameters among patients stratified by NAFLD status were tested with the unpaired Student’s i.e., hepatic steatosis on ultrasonography among patients who did not have excessive alcohol consumption, viral hepatitis, drug-induced liver disease or other known causes of liver disease) and 64 patients did not. Overall, 91 patients had normal diastolic function, whereas the remaining 131 (59%) patients had mild or moderate grades of LVDD; no patients had severe LVDD. No patients had clinical, biochemical characteristics  or ultrasonographic findings suggestive of cirrhosis or portal hypertension .Of the 222 patients (156 men and 66 women) included in the study, 158 (71.2%) patients met the clinical criteria for a diagnosis of NAFLD , overweight/obese, and had a longer duration of diabetes compared with those without NAFLD. They also had significantly higher values of HbA1c and serum gamma-glutamyltransferase, had a greater prevalence of chronic kidney disease , and tended to have higher blood pressure values and to receive more anti-hypertensive medications. The two groups did not differ significantly in terms of age, smoking, pulse pressure, mean arterial pressure, heart rate, fasting glucose levels, lipids, serum aminotransferases, abnormal albuminuria, diabetic retinopathy, peripheral sensory neuropathy, carotid artery stenoses>50%, and current use of hypoglycemic, lipid-lowering and anti-hypertensive drugs . No patients were taking pioglitazone or glucagon-like peptide-1 receptor agonists.Table 2shows the echocardiographic characteristics of patients grouped according to NAFLD status. Compared with those without NAFLD, patients with NAFLD had echocardiographic features of early LVDD as detected by tissue Doppler imaging, i.e., lower e’ tissue velocity, higher E/e’ ratio, higher Tau, higher LV-EDP, higher EDP/EDV ratio. They also had a slightly larger left atrial volume and lower LV-ejection fraction. Again, when we performed global strain and strain rate measurements in a subgroup of these patients (n = 156), we confirmed that NAFLD patients had a significantly higher E/SRE ratio than those without NAFLD. As also shown in Table 2, no significant differences were found in LV volumes, E and A trans-mitral wave velocities, E/A ratio, Dte, s’ velocity, a’ velocity, IVRT, Ar-A duration, SVR index and SAC between the two groups of patients.n = 57) and male patients with NAFLD (n = 101) had lower e’ tissue velocity  and higher E/e’ ratio  compared with female (n = 9) and male (n = 55) patients without NAFLD.After stratifying participants by sex, both female patients with NAFLD .Notably, as shown in Table 3shows the effect of the adjustment for several potential confounders on the relationship between NAFLD and presence of mild and/or moderate LVDD. In univariable logistic regression analysis, NAFLD was associated with a ~five-fold increased odds of mild and/or moderate LVDD . When we analyzed men and women separately, the presence of NAFLD was associated with an increased odds of LVDD in both sexes: unadjusted odds ratio of 5.13, 95%CI 2.5–10.6 for men and unadjusted odds ratio of 2.47, 95%CI 0.7–10.4 for women, respectively . After adjustment for age and sex (model 1), NAFLD maintained a significant association with LVDD. Further adjustments for BMI, duration of diabetes, HbA1c, eGFR and hypertension (defined as blood pressure ≥140/90 mmHg or use of any anti-hypertensive medication) (model 2) did not appreciably weaken this association. Additional inclusion in this regression model of relevant echocardiographic parameters, such as LV-EF and indexed LV mass (model 3), did not weaken the strong association between NAFLD and LVDD. Of note, other independent predictors of LVDD were a longer duration of diabetes, male sex and lower LV-EF.i.e., an index of LV filling pressure) [To date, the data available regarding the association between NAFLD and LVDD in patients with type 2 diabetes mellitus are scarce. To our knowledge, the only study available in the literature is that published by our group on a small sample of 50 outpatients with type 2 diabetes, in which we had reported a positive association between NAFLD and early LVDD, defined as increased E/e’ ratio (ressure) . In thatressure) ,24.To our knowledge, this is the largest cross-sectional study aimed at examining the association between NAFLD and LVDD in an outpatient sample of type 2 diabetic individuals. In the present study, we confirm and extend the results of our previously published study showing that there was a strong, graded relationship between NAFLD and the severity of LVDD (according to the ASE diagnostic criteria). None of these participants were included in our previously published study. Notably, the association between NAFLD and LVDD remained statistically significant even after adjusting for a larger number of potential confounders, including diabetes-related variables, kidney function parameters, hypertension, and relevant echocardiographic parameters. Moreover, it is also important to note that the use of hypoglycemic, lipid-lowering and anti-hypertensive drugs was not significantly different between patients with and without NAFLD. Again, no patients were treated with pioglitazone or glucagon-like peptide-1 receptor agonists, which have been shown to reduce hepatic steatosis ,25 and ii.e., mean arterial pressure, SVR index, pulse pressure and SAC) were found between patients with and without NAFLD, our findings also suggest that the observed abnormalities in LV diastolic function could be not attributable to different LV afterload conditions. However, we assessed afterload only at rest and, therefore, we cannot exclude that the hemodynamic response to exercise might differ significantly between the two groups of patients despite similar resting conditions [Collectively, our results suggest that NAFLD may contribute to impairments of both active and passive LV diastolic properties that are most probably additive to the myocardial defects already present in type 2 diabetes. Since no significant differences in afterload conditions in terms of either “steady” or “pulsatile” components of the arterial load  in people at increased risk for cardiac abnormalities, or is an independent risk factor for the development and progression of cardiac function abnormalities.et al. [To date, a number of case-control studies have demonstrated that nondiabetic patients with NAFLD, both adults and children/adolescents, have echocardiographic features of early LVDD compared with their counterparts without NAFLD ,31–37. Tet al.  also repet al. .et al. [et al. [et al. reported that only intra-hepatic triglyceride content and visceral adipose tissue were independent predictors of LV diastolic function, whereas myocardial triglyceride content, epicardial and pericardial fat were not associated with diastolic function measures [In respect to mechanisms how NAFLD might adversely impact on cardiac function and structure, there is now increasing evidence suggesting that NAFLD is not simply an epiphenomenon of structural and functional myocardial abnormalities, but may also contribute to their pathogenesis ,9. Accoret al.  found thet al. . Emerginet al. ,39. Rijz [et al.  found thmeasures . This fui.e., some of our diabetic control patients could have underlying NAFLD despite fairly normal serum liver enzymes and negative ultrasonography examination), this limitation would serve to attenuate the magnitude of our effect measures toward null; thus, our data can probably be considered conservative estimates of the relationship between NAFLD and LVDD. Finally, because our sample comprised white type 2 diabetic individuals who were followed at an outpatient clinic, our results may not necessarily be generalizable to other non-white diabetic populations.Our study has some important limitations. Firstly, the cross-sectional design of the study limits our ability to establish both the temporality and the causality of the observed associations. Secondly, the diagnosis of NAFLD was based on ultrasound imaging and the exclusion of other known etiological factors of chronic liver diseases, but was not confirmed by liver biopsy. Although some non-differential misclassification of NAFLD on the basis of ultrasonography is likely , which is the most practical and reproducible method for diagnosing early LVDD, the completeness of the dataset, the ability to adjust for multiple risk factors and potential confounders and the exclusion of patients with cirrhosis; we believe that the inclusion of patients with such complication would possibly have confounded the interpretation of the data.In conclusion, these results indicate that NAFLD is independently associated with echocardiographic features of early LVDD in type 2 diabetic patients with preserved systolic function and without overt IHD. Further studies are needed to explore whether improvement in NAFLD (or future treatments for NAFLD) will ultimately delay or prevent the development of LVDD in patients with type 2 diabetes mellitus.


Background and Objective. Renal Doppler resistive index (RDRI) is a noninvasive index considered to reflect renal vascular perfusion. The aim of this study was to identify the independent hemodynamic determinants of RDRI in mechanically ventilated patients after cardiac surgery. Methods. RDRI was determined in 61 patients by color and pulse Doppler ultrasonography of the interlobar renal arteries. Intermittent thermodilution cardiac output measurements were obtained and blood samples taken from the tip of pulmonary artery catheter to measure hemodynamics and mixed venous oxygen saturation (SvO2). Results. By univariate analysis, RDRI was significantly correlated with SvO2, oxygen extraction ratio, left ventricular stroke work index, and cardiac index, but not heart rate, central venous pressure, mean artery pressure, pulmonary capillary wedge pressure, systemic vascular resistance index, oxygen delivery index, oxygen consumption index, arterial lactate concentration, and age. However, by multivariate analysis RDRI was significantly correlated with SvO2 only. Conclusions. The present data suggests that, in mechanically ventilated patients after cardiac surgery, RDRI increases proportionally to the decrease in SvO2, thus reflecting an early vascular response to tissue hypoxia. In humans and animals, various quantitative and semiquantitative Doppler parameters have been proposed to quantify renal blood flow. Among these, renal Doppler resistive index (RDRI) measured from intrarenal arteries is the one most widely used for clinical investigations since it does not require estimations of Doppler angle or vessel cross-sectional area . Moreove2) [During low-flow states, splanchnic hypoperfusion and blood flow-redistribution are part of the physiological response to oxygen supply and demand mismatch. In two previous studies, RDRI has been shown to be able to detect tissue hypoperfusion and oxygenation due to occult hemorrhagic shock in hemodynamically stable polytrauma patients  and to c2) . Based oThis hypothesis was tested in the present study by searching for independent hemodynamic correlates of RDRI in mechanically ventilated patients after cardiac surgery.The study was approved by institutional review board of our university hospital (protocol number 812/2014). Study protocol and aim were explained to patients before surgery and each of them gave a written informed consent.2O or FiO2 > 50%.Sixty-one consecutive patients admitted to the intensive care unit after elective cardiac surgery were included in the study . They we2O and FiO2 50%. They were sedated by continuously infused propofol. At the time of inclusion, no patient was receiving renal replacement therapy or had overt acute renal failure. RDRI measurements were performed immediately before hemodynamic measurements, at admission in intensive care unit (ICU), and within the first 12 hrs whenever needed per clinical condition.All patients were mechanically ventilated with tidal volume of 8–10 mL/kg of predicted body weight and positive end-expiratory pressure of 5 cm HArterial Leadercath 3F, Vygon, Ecouven, France) and a pulmonary artery catheter . Clinical data were collected from the bedside monitor . Intermittent thermodilution cardiac output (CO) measurements were performed using the pulmonary artery catheter by injecting 10 mL of normal saline into the superior vena cava at room temperature. Three consecutive injections were randomly made during the respiratory cycle. If measurements differed by >10%, the cardiac output was measured two more times and a mean was calculated after exclusion of the highest and lowest values. To avoid variation between operators, the injections were always performed by the same experienced operator. Washout curves were examined for stable baseline temperature, undisturbed rapid upstroke, and exponential decay without signs of early recirculation. Cardiac output was normalized for total body surface area to obtain the cardiac index (CI). Blood samples (2 mL per sample) were taken from the tip of pulmonary artery catheter to measure SvO2. The correct positioning of the catheter was confirmed by the waveform of the pressure curve, catheter length, and chest X-ray. SvO2 was measured .Patients were positioned 30° supine and all pressure transducers were referred to mid chest at the level of right atrium. All patients had a radial arterial catheter (2), mixed venous oxygen saturation (SvO2), oxygen delivery index (DO2I), oxygen consumption index (VO2I), oxygen extraction ratio (O2ER), central venous pressure (CVP), cardiac index (CI), left ventricular stroke work index (LVSWI), heart rate (HR), pulmonary capillary pressure (PCP), and mean arterial pressure (MAP).The following hemodynamic parameters were calculated: arterial oxygen saturation  with a S5-1 Sector Array transducer for kidney's examination with the patient in supine position. After a general preliminary examination of the abdominal cavity and organs, Doppler ultrasound measurements were obtained in the interlobar arteries of the renal cortex. The ultrasound examination was considered technically adequate if the following criteria were met: (a) a clear two-dimensional longitudinal scan with definition of renal parenchyma, (b) a good color Doppler image with representation of the intrarenal vascular blood flow, and (c) at least three consecutive Doppler time-velocity spectra for each renal area . Waveforms were recorded and renal Doppler resistive index was calculated according to Planiol and Pourcelot protocol [All ultrasonographic examinations were performed by a single expert operator using a Philips CX50 Echocardiography , GraphPad Prism 6.00 , and the R software/environment .A two-sided A power calculation carried out for a linear correlation coefficient of 0.4 with type-I error probability of 0.05 returned a statistical power of 0.90 with a sample size of 61.2 and SvO2, and larger O2 extraction ratio . The creatinine mean value at admission was 1.1 ± 0.1 mg/dL. RDRI was adequately measureable from both kidneys in 56 patients and from the right kidney alone in the remaining 5 patients, because of suboptimal visualization of left kidney due to overlying bowel gas. Thus 117 measurements were obtained in the 61 patients. Eleven patients had RDRI >0.70. When subjects were grouped on the basis of this cutoff, those with RDRI >0.7 had higher heart rate, lower SaOon ratio . No othe2 , O2-ER , CI , and LVSWI , but not with HR , CVP , MAP , PCP , SVRI , DO2I , VO2I , arterial lactate concentration , and age  , CI (P = 0.029), O2-ER (P < 0.001), and SvO2 (P < 0.001) , with SvO2 being the major contributor (P < 0.001). Even when age was forced in the multivariate analysis the overall significance of the model did not change , confirming SvO2 as the major contributor  . O2-ER atributor .2 < 55% had a RDRI significantly higher than those with SvO2 ≥ 55% .Patients with SvOP = 0.763), hospital length of stay , ICU mortality , number of red blood cell transfusion requirements , time of mechanical ventilation , intra-aortic counter pulsation , and number of patients requiring hemodialysis .The evolution of patients with high RDRI did not differ from that observed in patients with normal values in terms of ICU length of stay  calculated for each patient at each measurement.This study has some limitations. First, our critically ill patients were sedated and mechanically ventilated with standardized ventilation after cardiac surgery, and thus results cannot be extrapolated to either spontaneously breathing patients or other critical conditions requiring protective mechanical ventilation. Second, patients with increased creatinine levels were excluded from the study. Although this makes the results not applicable to patients with acute or chronic renal failure, it allowed us to avoid confounding factors influencing renal vasoconstriction. Third, the age and the use of vasoactive drugs were quite similar among patients, which may have prevented finding significant correlations. Nevertheless, the narrow range of age and the similar use of vasoactive drugs in all patients allowed us to describe the response of RDRI to tissue hypoxia independently of other confounding factors. Fourth, the study was not potentiated to find differences in terms of clinical outcomes.2, supposedly reflecting a vascular response to hypoxia.In conclusion, the results of the present study suggest that RDRI is sensitive to oxygen supply and changes in SvO


Background. The aim of study was to determine relationships between functional capacity (NYHA class), left ventricle ejection fraction (LVEF), hemodynamic parameters, and biomarkers of redox state and inflammation in patients with dilated cardiomyopathy (DCM). Methods. DCM patients , NYHA class IIV, and LVEF 2.94 ± 7.1% were studied. Controls comprised age-matched healthy volunteers (n = 28). Echocardiography and right heart catheterization were performed. Serum activities of superoxide dismutase isoenzymes (MnSOD and CuZnSOD), concentrations of uric acid (UA), malondialdehyde (MDA), and C-reactive protein (hs-CRP) were measured. Results. MnSOD, UA, hs-CRP, and MDA were significantly higher in DCM patients compared to controls. Except MDA concentration, above parameters were higher in patients in III-IV NYHA class or with lower LVEF. hsCRP correlated with of MnSOD (P < 0.05) and CuZnSOD activity (P < 0.01). Both isoenzymes positively correlated with mPAP and pulmonary capillary wedge pressure . UA positively correlated with MnSOD (P < 0.05), mPAP (P < 0.05), and PVRI (P < 0.05). The negative correlation between LVEF and UA (P < 0.01) was detected. Conclusion. There are relationships among the severity of symptoms of heart failure, echocardiographic hemodynamic parameters, oxidative stress, and inflammatory activation. Increased MnSOD activity indicates the mitochondrial source of ROS in patients with advanced heart failure. Dilated cardiomyopathy characterized by alteration in the structure and function of the myocardium with dilation and impaired contraction of the left ventricle (LV) or both ventricles (LV ejection fraction <40%) and is sometimes called nonischemic cardiomiopathy.hemodynamic parameters such as increased pulmonary capillary wedge pressure (PWP), pulmonary artery pressure (PAP), and pulmonary vascular resistance (PVR) ;the inspiratory and expiratory muscle weakness ;greater than normal phosphocreatine depletion and/or acidosis in the peripheral working muscle associated with impaired oxygen delivery ;mitochondrial dysfunction with impaired oxidative phosphorylation and defective electron transport chain at heart and skeletal muscles , 5.Deterioration of myocardial performance resulting in the development of exercise intolerance and sometimes limited daily activity as symptoms of heart failure (HF) mostly assessed according to New York Heart Association (NYHA) Functional Classification . There aOne of hemodynamic features of dilated cardiomyopathy is increase of the pulmonary capillary wedge pressure (PWP) as indicator of elevated left ventricular filling pressure (preload). Up to 60% of patients with severe left ventricular (LV) systolic dysfunction may also present elevated pulmonary artery pressure due to passive transmission of elevated end diastolic pressure .Left ventricle overload leads to a shift of fatty acid oxidation towards more efficient glucose oxidation. However, it also leads to reduction of maximal oxidative phosphorylation (OXPHOS) capacity with decreased activities of respiratory chain complexes and increase of electron leak .Besides mitochondrial leakage reactive oxygen species (ROS) may arise from many sources, including vascular nicotinamide adenine dinucleotide oxidases , xanthinElevated circulating levels of inflammatory cytokines have been reported in heart failure, but most initial studies have focused on patient with cachexia or end stage failure (III and IV NYHA class) . The furWe decided to assess potentially relationships between functional capacity, blood oxygenation, some echocardiographic parameters, invasive hemodynamic parameters, and serum biomarkers of reduction-oxidation reactions and inflammation in patient with heart failure due to dilated cardiomyopathy.We recruited 109 consecutive patients aged 18–80 years old with nonischemic dilated cardiomyopathy diagnosed according to the WHO criteria  who undeβ-blocker, mineralocorticoid receptor antagonist (MRA), digitalis, and diuretics for at least 1 month  and end-systolic volume (ESV) were obtained from the apical 4- and 2-chamber views by the modified Simpson's method. Left ventricular ejection fraction (LVEF) was calculated in a standard manner as follows: (EDV − ESV) × 100/EDV, to assess ventricular systolic function.2) were collected in order to determine its saturation. After twenty minutes of stabilization of circulation parameters pulmonary wedge pressure (PWP), systolic pulmonary artery pressure (sPAP), diastolic pulmonary artery pressure (dPAP), and right atrium pressure (RAP) were measured. Cardiac output was measured by thermodilution using rapid bolus injection of 10 cc of cold saline. Systolic (sABP) and diastolic (dABP) systemic arterial pressure were measured noninvasively. Hemodynamic parameters were acquired five times—mean values were used for final evaluation. Acquired data enabled calculation of mean pulmonary artery pressure (mPAP) and mean systemic arterial pressure (mABP), pulmonary vascular resistance index (PVRI), and systemic vascular resistance index (SVRI).mPAP [mm Hg] equals the sum of dPAP and one-third of a subtraction of sPAP and dPAP in pulmonary artery (mPAP = dPAP + [sPAP − dPAP]/3).mABP [mm Hg] equals the sum of diastolic arterial blood pressure (dABP) and one-third of a subtraction of systolic arterial blood pressure (sABP) and dABP (mABP = dABP + [sABP − dABP]/3).·s·cm−5/m2] equals quotient of subtraction mPAP, PWP, and CI (PVRI = [mPAP − PWP]/CI 79.9).PVRI [dyna·s·cm−5/m2] equals quotient of subtraction mABP, RAP, and CI (SVRI = [mABP − RAP]/CI 79.9).SVRI [dynaBlood pressure parameters were expressed in millimeters of mercury [mm Hg], CI as liters per minute [L/min/m2]. Resistance was expressed in dyna·s·cm−5/m2.Right heart catheterization (RHC) was performed by the use of Swan-Ganz catheter (Star Edwards Lifesciences) administered under local anesthesia (1% Lignocaine) via the right jugular vein into pulmonary artery. Then two samples of mixed venous blood . hs-CRP was determined in serum by ELISA method using commercially available kit. NT-proBNP was measured with the use of chemiluminescence method . Additionally, we also determined blood hemoglobin and serum creatinine concentrations using routine techniques.SOD isoenzymes activity was determined with the use of spectrophotometric method by Oyanagui with KCN as the inhibitor of the CuZnSOD isoenzyme. CuZnSOD activity was taken as difference between total SOD activity and MnSOD activity. SOD activity was calculated against blank probe (containing bidistilled water). Enzyme activity was expressed as nitrite units (NU) per mL serum. One NU exhibits 50% inhibition of formation of nitrite ion under the method's condition .Malondialdehyde was measured according to method described by Ohkawa using the reaction with thiobarbituric acid with spectrofluorimetric detection: excitation 515 nm and emission 552 nm. MDA concentration was calculated from the standard curve, prepared from 1,1,3,3-tetraethoxypropane .All dilated cardiomyopathy patients (group D), for purpose of this study, were divided into two groups depending on functional capacity . Additionally redox and inflammatory parameters were analyzed in subgroup of patients according to severity of left ventricle dysfunction . t-test. If the distribution was nonnormal the data were presented as median with the first and fourth quartiles and were compared using “U” Mann-Whitney test. Categorical data were presented as absolute numbers and percentage and were compared using χ2 test. Spearman correlation coefficient was counted for particular parameters. Results were considered statistically significant if P < 0.05. Lack of statistical significance was presented as NS (nonsignificant). Statistical analysis was performed with Statistica 10.0 software .Normality of the distribution of the continuous data was analysed by Shapiro-Wilk test. If the distribution was normal, the data were presented as mean ± standard deviation and were compared with Student'sβ-blockers (94.5%) and either an ACE (92.6%) (angiotensin-converting enzyme) inhibitor and/or an ARB (angiotensin receptor blocker). Most of the patients were treated with diuretics, spironolactone and digoxin  were finally enrolled into the study. All patients were clinically stable in the last one month. The twenty-eight healthy control subjects aged 38.1 ± 5.4  were not significantly younger than the patients. Of all the patients studied, 26.6% were hypertensive and 11% had type 2 diabetes. The majority of patients were treated with  digoxin . The mea2 was present  had significantly higher concentration of UA, hs-CRP and activity of both izoenzymes SOD in comparison to patients from group A1. MDA concentration was comparable . Except There were statistically significant positive correlations between uric acid concentration and mPAP  and PVRIhs-CRP concentration negatively correlated with LVEF. Positive correlations between hs-CRP and PVRI were found , Table 5Both isoenzymes' activities positively correlated with mPAP and PWP. The negative correlations between them and LVEF were detected. There were no correlations between MDA concentration with LVEF and examined hemodynamic parameters .2 negatively correlated with NT-proBNP concentration which is reflection of heart failure conditions. Additionally negative correlation between SvO2 and UA was detected. There is statistically significance positive correlation limit between MnSOD activity and NT-proBNP concentration . MnSOD positively correlated with CuZnSOD  we have found no significant differences in MDA level. There was no correlation between MDA level and severity of HF and echocardiographic and hemodynamic parameters. Our results are similar to previous reports which demonstrated increase in MDA level in patients with HF , 28. Opp2 as indicator of tissue hypoxia in our study [In our DCM group concentration of UA was markedly increased in comparison to the control. The highest value of UA was observed in patient with severe HF. Furthermore, UA level correlated with LVEF and examined hemodynamic parameter without systemic arterial pressure. Recently Borghi et al. also have found inverse relation of serum UA to LVEF in male elderly patients with HF. One of the potential mechanisms which may explain this result is lower cardiac index leading to hypoxemia. There was a slight correlation between UA and SvOur study . Leyva eur study . Previouur study , 35. Accur study . UA concur study . During Previous studies by Hill and Singal demonstrated that HF subsequent to myocardial infarct was associated with the antioxidant decrease as well as increased oxidative stress . In contOur study demonstrates the elevated plasma SOD activity, mainly MnSOD in NYHA III-IV patients comparing to the I-II NYHA patients and control group. There were no changes in Cu,Zn-SOD activity between studied groups divided depending on NYHA class and control. Both MnSOD and CuZnSOD activity were higher in patients with lower LVEF.For prevention the oxidative stress in heart failure patients we have seen adaptational increase of the enzymatic antioxidative defense represent by increase in MnSOD and CuZnSOD activity in group with LVEF <20% comparing to the group LVEF ≥20%. Comparing with the control group we have seen decrease of SOD activity in NYHA I, II and LVEF ≥20% group. This transition from decrease to increase in SOD activity in our HF patients may be the key factor providing a constant MDA level. Some different adaptational changes with increase of the antioxidative defense followed by the formation of a relative deficit were found by Schimke et al. in myocardial tissue of heart transplant recipients , 41.Our data do not show the tissue origins of the markers of increased lipid peroxidation or SOD; both poorly perfused peripheral muscles and the myocardium could have contributed . Lack ofThe function of antioxidant system is not to remove these oxidants entirely but instead to keep them at the level below which they will trigger the inflammatory cascade, a series of intracellular and intranuclear signaling that results in the release of destructive inflammatory cytokines . It has The positive correlation between CRP concentration and activities of superoxide isoenzymes suggests the existence of link between free radicals and inflammation in DCM. Rankinen observed additionally correlation between MDA and hs-CRP but we did not observe such correlation .In our study we have observed increase in CRP level according to the NYHA class and LVEF. It was the same as the results obtained by Alonso-Martínez et al. . An assoUnfortunately, we only have a number of pieces of the puzzle, but these pieces cannot yet be connected to provide final pathway of relationships between oxidative stress and inflammation. It would be valuable information to determine if examined parameters are capable of predicting prognosis in patients with chronic heart failure (CHF).The correlation between MnSOD and mPAP, PWP, LVEF combined with correlation between MnSOD and NT-proBNP, CRP, and UA may indicate a link among increased mitochondrial ROS generation, severity of HF, systemic and pulmonary hemodynamic, and the level of inflammation in DCM patients. Thus it is plausible to think that mitochondria are an important source of ROS in the HF.


In this cross-sectional cohort , 5.8% had CKD. At a cut-off SUDOSCAN-DKD score of 53, the test had sensitivity of 76.7%, specificity of 63.4% and positive likelihood ratio of 2.1 to detect CKD. The area under receiver operating characteristic curve for CKD was 0.75 . Patients without CKD but low score had worse risk factors and complications than those with high score. We conclude that SUDOSCAN may be used to detect patients at risk of impaired renal function as part of a screening program in Chinese population, especially in outreach or low resource settings.There are gaps between recommendations on regular screening for diabetic kidney disease (DKD) and clinical practice especially in busy and low resource settings. SUDOSCAN  is a non-invasive technology for assessing sudomotor function using reverse iontophoresis and chronoamperometry which detects abnormal sweat gland function. Vasculopathy and neuropathy share common risk factors and we hypothesized that SUDOSCAN may be used to detect chronic kidney disease (CKD). Between 2012 and 2013, SUDOSCAN was performed in a consecutive cohort of 2833 Hong Kong Chinese adults with type 2 diabetes. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min/1.73m Diabetic kidney disease (DKD), indicated by albuminuria and/or reduced glomerular filtration rate (GFR) predict end-stage renal disease, cardiovascular disease and all-cause mortality ,2. Due t1c), fasting plasma glucose and 2-hour plasma glucose during oral glucose tolerance test  -1.154 × [age] -0.203 × [0.742 if female] ×1.233, where SCR was serum creatinine in μmol/l and 1.233 was the adjusting coefficient for Chinese [2. Microalbuminuria was defined as urine ACR ≥2.5–25.0 mg/mmol in men and ≥3.5–25 in women, and macroalbuminuria, urine ACR ≥25.0 mg/mmol.Blood and urine samples were collected for plasma glucose, HbAThe objectives of our initiative to evaluate the efficacy of SUDOSCAN in detecting and predicting CKD were set to firstly examine the association of SUDOSCAN-DKD score with estimated GFR in a cross-sectional cohort, and at the next stage, to determine whether baseline SUDOSCAN-DKD score is associated with incident CKD in patients with normal renal function at baseline. We estimated the sample size based on expected incidence of CKD to enable future prospective analysis. Assuming a correlation r value of 0.4 between estimated GFR and SUDOSCAN-DKD score, 63 cases with CKD will give more than 95% power to confirm this correlation. Assuming an annual incidence of CKD of 6.0%, 1900 patients would confirm this incidence with 95% confidence interval of 5.0–7.2%. Assuming 30% of patients will not be returning for repeat GFR at 1 year, we recruited over 2800 patients in the present cohort.1c, LDL-cholesterol, use of RAS blockers and use of other anti-hypertensive drugs. We did not adjust for age as age was already included in the built-in calculation of the SUDOSCAN-DKD score. We constructed receiver operating characteristic (ROC) curve to estimate the sensitivity and specificity of SUDOSCAN-DKD score for detecting CKD. The area under the ROC curve was calculated and the optimal cut-point was the peak of the curve where the sum of sensitivity and specificity was greatest. A 2-sided p-value <0.05 was considered significant. Statistical analysis was performed using Statistical Package for Social Science software .All data were expressed as mean±standard deviation (SD), median (inter-quartile range) or percentages as appropriate. We used multiple linear regression to estimate the independent correlation of SUDOSCAN-DKD score with estimated GFR adjusted for gender, disease duration, body mass index (BMI), systolic blood pressure (BP), HbA2 in the CKD group and 116.0±28.1 ml/min/1.73m2 in the non-CKD group (p = 0.001). Patients with CKD were older and had longer disease duration and worse metabolic profile with higher BMI, systolic BP, HbA1c but lower blood haemoglobin , 5.7% had CKD, 26.1% had microalbuminuria and 9.9% had macroalbuminuria. The mean estimated GFR was 42.1±14.0 ml/min/1.73mmoglobin . They weElectrochemical skin conductance was lower in the CKD group than the non-CKD group at both hands  and feet . The mean SUDOSCAN-DKD score were 45.5±12.3 and 58.6±15.1 in the CKD and non-CKD groups, respectively.1c, low LDL-cholesterol, and use of anti-hypertensive drugs  of the total square . At SUDO1c, blood haemoglobin, estimated GFR but higher systolic BP and were more likely to have microalbuminuria, retinopathy, sensory neuropathy and cardiovascular disease than those with high score.Among patients with no CKD (n = 2670), 36.7% were scored ≤53 on SUDOSCAN. Patients with low score were older and more likely to be female with longer duration of diabetes than those with score>53 . These pDiabetic kidney disease is prevalent and requires periodic laboratory assessments to allow timely intervention for cardiovascular-renal protection. In this large cross-sectional sample of community-dwelling Chinese patients with type 2 diabetes, patients with a low SUDOSCAN-DKD score (≤53) had 2-fold increased likelihood of having CKD than those with higher scores. Based on our findings, we conclude that SUDOSCAN may be useful in detecting patients at risk of having CKD. The worse risk factor and complications profiles in patients with normal GFR but low SUDOSCAN-score suggested that the device might also have a utility in detecting early renal involvement although prospective evaluation will be needed. Given the non-invasive and portable nature of SUDOSCAN, it can be a used in outreach programs or low resource setting as part of a CKD screening program.1c in patients with diabetes [Sudomotor function is a subtype of autonomic function which reflects the integrity of sympathetic nerve fibers innervating the sweat glands . Sudomotdiabetes . Moreovediabetes –13,22.per se, however, is rarely measured in routine clinical practice as its precise assessment is both time- and labor-consuming [Sudomotor function onsuming . SUDOSCAonsuming –13, otheonsuming –15.Graded relationships between low electrochemical skin conductance measured by SUDOSCAN and severity of peripheral sensory neuropathy have been reported in people with diabetes ,25. The The natural progression of DKD involves the gradual transition from hyperfiltration to albuminuria, to decline in GFR. While microalbuminuria is traditionally viewed as an early indicator of diabetic renal involvement, its predictive value for advance renal disease is recently challenged by poor sensitivity and specificity . On the In this analysis, the optimal SUDOSCAN-DKD score for detecting CKD was 53 with 77% sensitivity and 63% specificity. In our previous case-control cohort, the cutoff value of 55 had 94% sensitivity and 78% specificity. The better performance might be due to greater case dichotomization in our previous study . While tWe acknowledge the following limitations. One, despite the relatively large sample size of this cross-sectional cohort, prospective evaluation is needed to confirm the clinical utility of SUDOSCAN for risk stratification and prognostication in CKD. Two, only Chinese patients were studied and our results might not be generalizable to other ethnic groups which might have different patterns of risk attributes. Three, SUDOSCAN is a screening instrument only and cannot replace blood and urine sampling for quantification of renal function.In conclusion, SUDOSCAN may detect patients at high risk of CKD. Given its non-invasive, portable and easy-to-use features, it may be used in outreach programs or low resource settings as part of a detection program to identify high risk subjects for further assessments.


There is no clear consensus regarding optimal indications or timing of initial or repeat kidney biopsy in the management of pediatric systemic lupus erythematosus (pSLE).A web-based survey was designed to assess current practice patterns among pediatric nephrologists and pediatric rheumatologists and distributed to members of Midwest Pediatric Nephrology Consortium (MWPNC) and Childhood Arthritis and Rheumatology Research Alliance (CARRA).Respondents included 111 rheumatologists and 71 nephrologists from 65 and 34 centers, respectively. Numbers of years in sub-specialty practice were comparable. Rheumatologists and nephrologists frequently collaborate in the care of children with lupus nephritis (LN). More than 90 % of respondents refer patients to each either other after diagnosing LN. Over 60 % describe shared decision making regarding when to perform kidney biopsy and how to interpret biopsy findings. Many pediatric nephrologists consider biopsy to be of higher risk for complication in pSLE and alter their standard pre-or post-biopsy management.vice versa. Consensus exists between specialties in general, and practice differences that exist occur between individual physicians rather than between specialties. A systematic approach to biopsy may result in improved health related outcomes in pSLE.It is uncommon for pediatric nephrologists to manage LN without input from pediatric rheumatologists and The online version of this article (doi:10.1186/s12969-015-0024-x) contains supplementary material, which is available to authorized users. Approximately 50 % of patients with pediatric-onset systemic lupus erythematosus (pSLE) will develop some form of lupus nephritis (LN) . This reet al. and refined by Austin et al. [Although classification of LN according to renal histopathology is essential in guiding appropriate therapy, there remains disagreement over the classification system that best predicts prognosis or response to therapy . The Worn et al.  for proln et al. , 8 and Tn et al. , but addThe Joint European League Against Rheumatism (EULAR) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) recommend repeat kidney biopsy 6-months after induction therapy for LN in children and adults , but thiThere is considerable variation in pre-biopsy preparation and biopsy technique utilized in children undergoing biopsy for LN , 19. PedRoutine post-biopsy care also varies tremendously among pediatric nephrologists , 23, 25.In this study, we describe practice patterns related to kidney biopsy of children with LN, compare the variations in practice among and between pediatric nephrologists and rheumatologists, and assess how these two sub-specialties interact in clinical decision making. We present and discuss the results of a survey addressing specifically in pSLE the approach to first biopsy, approach to repeat biopsy, mechanisms for obtaining biopsies, and methods for interpretation of results.Practice patterns were assessed with an online survey sent to 300 members of the CARRA and 160 members of the MWPNC via SurveyMonkey in January 2014. The survey included 26 questions designed to delineate current clinical practice in the approach to renal biopsy in pSLE. Respondents had the option of disclosing their institution. Respondents were uniquely identified by IP address and date of response. Nineteen questions were directed towards both pediatric rheumatologists and pediatric nephrologists, two specifically directed towards pediatric rheumatologists, and 5 specifically towards pediatric nephrologists  and 34 of the 51 pediatric nephrology centers (67 %) with membership in the MWPNC were represented. Some institutions were represented by more than one respondent in one or both sub-specialty. Respondents were evenly distributed across the range of years in practice, with about a quarter each practicing 0–5, 6–10, 11–20, or >20years in their specialty  have their patients’ biopsies read by a dedicated renal pathologist at their primary institution, although 21.2 % use a local general pathologist. The remaining 12.3 % have their biopsies sent out to a renal pathologist at another institution. Pathologists utilize the WHO grading system (33.2 %), the ISN/RPS grading system (22.4 %), or both (33.0 %). A total of 9.5 % of respondents were unsure of which grading system their pathologists were using (11.6 % of nephrologists vs. 8.2 % of rheumatologists). For diffuse proliferative GN, the activity and chronicity indices were provided routinely to 80.9 % of respondents, whereas 2.3 % received only the activity index, 1.1 % received only the chronicity index, and 15.2 % worked with pathologists who did not provide either.n = 3), and 2 of those 3 have an internal medicine rheumatologist at their institution who care for children. Similarly, only 3.6 % of pediatric rheumatologists (n = 4) do not have access to a pediatric nephrologist at their primary institution. The decision to perform a kidney biopsy in a patient with pSLE is made by 62.5 % of respondents only after discussions are held between nephrology and rheumatology. Only 29.6 % of respondents stated that the decision was made by the pediatric nephrologists alone; and only 7.8 %, by the pediatric rheumatologist alone.More than 90 % of pediatric rheumatologists and nephrologists refer their patients with pSLE to the other provider after a diagnosis of nephritis is made. There are very few pediatric nephrologists who do not have access to a pediatric rheumatologist at their primary institution  who obtain true “protocol” biopsies in order to guide the dosing of induction therapy, and 5 % who re-biopsy patients in remission in order to guide withdrawal of immunosuppression. However, 41.7 % would obtain repeat kidney biopsy after induction therapy in patients with no response and 25 % would in patients with only partial response. For patients in renal remission from a proliferative nephritis who develop a renal flare, 69 % would obtain another biopsy to guide therapy. Only 2.7 % (n = 5) obtain repeat biopsy for non-renal lupus flares.There were no significant differences in the proportion of pediatric rheumatologists or nephrologists that would recommend/perform repeat renal biopsies under specific instances Table . For proThere were 29 % of respondents who stated that they do not routinely repeat kidney biopsy after an initial pathologic diagnosis of proliferative LN. Of these 17 were nephrologists and 35 were rheumatologists. Of the nephrologists who do not re-biopsy, most stated that they made biopsy decisions alone without consultation of their rheumatology colleagues. Of the rheumatologists who do not re-biopsy, only 2 stated that they made biopsy decisions alone, and most did so in consultation with their local pediatric nephrologists. The pediatric rheumatologists who do not recommend routine repeat biopsy tended to have been practicing longer, whereas the pediatric nephrologists who do not perform routine repeat kidney biopsy tended to have been practicing for < 10 years. All 16 pediatric nephrologists practicing their specialty >20 years stated that they will routinely re-biopsy patients with proliferative LN for specific indications.Repeat biopsy after initial diagnosis of membranous LN (class V) differed very little from the practice following initial diagnosis of proliferative LN Table . Only 32The majority (71.3 %) of respondents reported that at their institutions, renal biopsies on pSLE patients with nephritis were primarily performed by pediatric nephrologists. There were 19.9 % of respondents from institutions where interventional radiology primarily performed the biopsies, and respondents from the remaining 8.8 % of institutions had both pediatric nephrologists and radiologists performing proportionate numbers of biopsies.Pediatric nephrologists were also questioned about their preferences regarding the biopsy procedure itself. When asked about pre-procedural laboratory testing, complete blood count (CBC) is usually performed by 96 % of nephrologists, partial thromboplastin time (PTT) by 94 %, prothrombin time (PT) by 90 %, and INR by 76 %. Less common laboratory testing included: type and screen (36 %), platelet function testing (15 %), lupus anticoagulant (12.6 %), serum chemistries (2.8 %), urine beta-HCG (2.8 %), urinalysis (1.4 %), and bleeding time (1.4 %). Significant anemia (<7 g/dL) is thought to be a contraindication to kidney biopsy by 35.4 % of nephrologists, whereas 5.4 % delay biopsy for Hgb < 8 g/dL and 1.4 % delay biopsy for Hgb < 9 g/dL until anemia can be corrected. For significant thrombocytopenia (<50x10^3/mcL) 58 % of nephrologists will defer biopsy. A few specifically commented that they would transfuse PRBC, platelets, or FFP in order to perform kidney biopsy without delay. Other contraindications to renal biopsy included active infection (58 %), uncontrolled hypertension (59 %), and solitary kidney (17 %).Non-steroidal anti-inflammatories (NSAIDs), including aspirin, are routinely held by 85 % of pediatric nephrologists prior to biopsy. Most recommended holding these drugs for 3–7 days prior to kidney biopsy (54.4 %), whereas 1.5 % held for 1 day, 11.8 % held for 2 days, 11.8 % held 8–14 days, and 5.9 % held >14 days. NSAID use shortly before kidney biopsy is considered an absolute contra-indication by 27 % of nephrologists. However, 14.7 % of pediatric nephrologists would proceed with biopsy despite NSAID use even for routine non-emergent kidney biopsies. Some pediatric nephrologists consider recent NSAID use a higher risk procedure warranting referral to interventional radiology. Others start immunosuppressive therapy and delay biopsy because of the NSAID use.Of 68 pediatric nephrologists, 54.4 % routinely observe patients overnight after kidney biopsy, whereas 38.2 % routinely send patients without complications home on the same day. Some nephrologists have particular concerns about pSLE patients after biopsy, as suggested by the fact that 7.4 % routinely observed their pSLE patients, but not patients with non-SLE kidney disease, overnight before discharge Fig. .Fig. 1A Results of this survey of North American pediatric subspecialists clearly indicate that rheumatologists and nephrologists do frequently work together in the care of patients with pSLE and nephritis. Most pediatric nephrologists and rheumatologists routinely review biopsy results together as well. However there is a wide variation in approaches to performing and interpreting biopsies in pSLE among both sub-specialties.p-value = 0.114). The only significant correlation between years in practice and practice patterns was between the proportion of individuals who had been practicing 11–20 years and adherence to ACR guidelines .Pediatric rheumatologists and nephrologists appear to value guidelines such as those published by the ACR, based on the high proportion who stated that they use them. However, the number of respondents who deviated based on pediatric definitions of proteinuria suggests that pediatric guidelines might be useful. The numbers of respondents who deviated were comparable between specialties. The differences in opinion on when to biopsy relate to number of years in practice in a more complex manner. There were approximately equal proportions of both pediatric nephrologists and pediatric rheumatologists in each of the 4 groups   who manage nephritis in pSLE without routinely seeking the input of pediatric nephrologyOf these 6 rheumatologists, 3 make the decision to biopsy without other consultation, but the other 3 seek guidance from their nephrologist when deciding to order a kidney biopsy, and 5 have their nephrologist perform the biopsy once the decision is made. In addition, 5 of the 6 review renal biopsy results with their local pediatric nephrologist.There is clearly no consensus regarding the indications for repeat kidney biopsy in the management of proliferative or membranous LN. Just under one third of respondents do not routinely recommend repeat biopsy in any instance. Alternatively, 1.7 % routinely recommend repeat biopsies for any lupus flare, regardless of kidney involvement. The most common practice is to repeat kidney biopsy in patients who have an exacerbation of their lupus which results in worsening of the urinary sediment (2/3rds of respondents). The second most common is to repeat biopsy at some time point during induction therapy in non-responders (32 % for membranous LN and 42 % for proliferative LN). Only a few programs use “protocol” biopsies to guide duration of induction or maintenance therapies in patients regardless of response. Interestingly, there were no significant differences in the proportion of rheumatologists or nephrologists that engaged in the practice of recommending/performing routine “protocol” repeat biopsy. This suggests that in general pediatric rheumatologists and nephrologists are similar in their approach to repeat biopsy, and that differences that exist are more common between individual physicians than between sub-specialties.Despite the ongoing role of pediatric nephrologists in medical management of nephritis in pSLE, there might be a shift in who is actually performing the biopsies. Many nephrologists appear to consider pSLE to be a risk factor for complications after kidney biopsy, and 12 (17 %) are primarily referring their pSLE patients to interventional radiology to perform the biopsy. It was not asked whether these nephrologists perform kidney biopsies routinely on their other patients. Of rheumatologists who completed the survey, referral rates to nephrology and interventional radiology are comparable. Therefore only 70 % of pediatric nephrologists are choosing to perform biopsies of patients with pSLE and only 70 % of pediatric rheumatologists are having their local pediatric nephrologist performing the biopsies.Finally, there is great variability in the perceived safety of kidney biopsies in pSLE. Most of this variability is likely to reflect differences in perceived safety of kidney biopsy in general. There are 38 % of pediatric nephrologists who discharge their pSLE patients the same day as the procedure, similar to their practice with non-SLE patients. Conversely, 54 % observe both their pSLE and non-SLE patients overnight. However, 8 % of pediatric nephrologists do send most patients home on the day of biopsy, but specifically observe pSLE patients overnight, due to perceived risk of complications. Identifying sources of perceived increased risk of kidney biopsy in children with lupus nephritis was beyond the scope of this study, but hypotheses can be drawn from nephrologist responses to survey questions on biopsy procedure. Possibilities include higher rates of anemia, thrombocytopenia, hypertension, NSAID use, or anticoagulant use in pSLE patients than in non-SLE patients, as well as a perceived need for performing biopsy more urgently and less electively when relative contraindications exist,Limitations of our study include the possibility of selection bias, recall bias, or reporting bias. Results of survey-based studies can be inherently subject to significant bias, and the strategies for survey distribution as well as the response rates should always be taken into account when interpreting survey data. Questions were written by pediatric nephrologists and rheumatologists together in order to minimize leading questions or error due to differences in terminology. By surveying specialists participating in either CARRA or MWPNC, we may have biased the results towards particular types of pediatric centers. We chose to survey providers as opposed to centers, as differences in practice patterns amongst providers in the same center are often encountered. There were no restrictions on how many providers could respond to the survey from any one center, which could allow for bias. However, the large degree of voluntary reporting of the respondents’ institution allowed us to compare practice patterns within centers with the highest degree of survey participation. The degree of collaboration between sub-specialties may not be applicable to primary care pediatric centers or centers outside of the United States or Canada. However, the strengths of the survey include the >40 % response rate, the large number of institutions represented, and the high proportion of completed surveys without missing responses. Aside from reports of transplant kidney biopsy, this study represents one of the only surveys to assess approach to kidney biopsy for a particular kidney disease, lupus nephritis, and the only survey to date that compares the approaches between pediatric rheumatologists and nephrologists.The results of this survey support the need for developing a pSLE-specific approach to kidney biopsy. Agreement between pediatric nephrology and rheumatology should not be an impediment. We support the formation of a collaborative group consisting of both pediatric nephrologists and pediatric rheumatologists to find ways to improve the diagnosis and treatment of LN and promote more collaborative research . Studies on the effect of different strategies for performing repeat biopsy on the outcomes of proliferative and membranous nephritis in pSLE are warranted. Variability around practice remains significant and it is becoming clear in medicine that standardization can greatly improve outcomes.


To describe the clinical, functional and quality of life characteristics in women with Stress Urinary Incontinence (SUI). In addition, to analyse the relationship between the variables reported by the patients and those informed by the clinicians, and the relationship between instrumented variables and the manual pelvic floor strength assessment.Two hundred and eighteen women participated in this observational, analytical study. An interview about Urinary Incontinence and the quality of life questionnaires (EuroQoL-5D and SF-12) were developed as outcomes reported by the patients. Manual muscle testing and perineometry as outcomes informed by the clinician were assessed. Descriptive and correlation analysis were carried out.p < .001). No correlation was found between outcomes of quality of life reported by the patients and outcomes of functional capacity informed by the physiotherapist.The average age of the subjects was (39.93 ± 12.27 years), (24.49 ± 3.54 BMI). The strength evaluated by manual testing of the right levator ani muscles was 7.79 ± 2.88, the strength of left levator ani muscles was 7.51 ± 2.91 and the strength assessed with the perineometer was 7.64 ± 2.55. A positive correlation was found between manual muscle testing and perineometry of the pelvic floor muscles  contains supplementary material, which is available to authorized users. The International Continence Society (ICS) defines Urinary Incontinence (IU) as “the complaint of involuntary leakage of urine.” Abrams P et al.  One of tThe etiology of UI is multifactorial ; there aThe strengthening of pelvic floor muscles is one of the first recommendations for the treatment of mild and moderate SUI. Different modalities include pelvic floor muscle training alone or in combination with biofeedback and vaginal cones or balls ,10. TraiManual palpation is a technique used today by most physiotherapists to assess the correct contraction of the pelvic floor muscles. It was first described by Kegel ,13 as a The aim of this study was to describe normal reference values of the strength of the pelvic floor muscles in women with SUI. Second, we analysed the relationship between the variables reported by the patients and those informed by the clinicians, and the relationship between instrumented variables and the manual pelvic floor strength assessment.Two hundred and eighteen women between 22 and 85 years of age participated in this observational, analytical study. The patients were recruited from the Community Physiotherapy and Sport Center  after confirming the diagnosis of urodynamic SUI  in speciThe Malaga University Ethics Committee, following the Helsinki declaration, gave ethical clearance for the study. All participants in this study signed an informed consent form before their inclusion.Questions were asked about gender, height and weight, and Body Mass Index (BMI) was calculated. A specific clinical interview was developed with the aim of analysing the principal components of pelvic floor dysfunction. A physiotherapist from the Consulting Unit of Physiotherapy of the Pelvic Floor conducted every question. The questionnaire consisted of 38 items, where items 1–11 referred to delivery conditions, items 12–23 presented information about faecal and urinary incontinence and items 24–38 were related to medical conditions and lifestyle  from which the physical and mental component of the SF-12 scores were constructed. The questionnaire has demonstrated a reliability score of 0.70 , and theκ =0.33, 95% confidence interval 0.09 to 0.57) [Laycock  developeto 0.57) .We used a vaginal pressure device connected to a pressure manometer that shows the air pressure through an arbitrary scale from 0 to 12  to assess the strength of pelvic floor muscles . The perp < 0.05. IBM SPSS Statistics (version 22.0) for Windows was used for this statistical analysis.The descriptive analysis was developed by calculating the means and standard deviations for quantitative variables. For the analysis of categorical variables, we calculated the absolute frequencies and quartiles. The normality of the variables was assessed by the Kolmogorov-Smirnov test. The Pearson correlation coefficient was calculated to test the association between the variables. All tests were interpreted as statistically significant when The study sample consisted of 218 women aged 28 to 85 years (35.42 ± 9.30). The main characteristics of the patients were presented together with the results concerning the study of quality of life in Table Regarding the gynaecological screening, the results were as follows. One hundred-thirteen (53.6%) patients had bladder prolapse, while the remaining 98 (46.4%) did not; 92 (43.6% ) women had womb prolapse, and 119 (56.4%) did not; the presence of rectum prolapse was evident in 41.2% (87 patients).The results concerning the manual muscle test were the following: the strength of the right levator ani muscles (SD 7.79 ± 2.88), the cut-off points were 6, 7 and 10 for percentile 25, 50 and 75, respectively. The distribution of four categories was 60 (27.9%) in the category very weak, 39 (17.8%) in the category weak, 37 (17.8%) in the category strong and 80 (37.5%) in the category very strong. The strength of left levator ani muscles was 7.51 ± 2.91. The cut-off points were 4, 7 and 10 for percentile 25, 50 and 75, respectively. The distribution of 4 categories was 64 (30.8%) in the category very weak, 41 (18%) in the category weak, 46 (20.3%) in the category strong and 64 (30.8%) in the category very strong.According to the assessment with the perineometer, the patient group showed strength (7.64 ± 2.55). The cut-off points were 6, 8 and 10 to percentile 25, 50 and 75, respectively. The distribution of the sample categories was 55 (26.1%) in the category very weak (quartile 4), 21 (1.4%) in the category weak, 69 (36.2%) in the category strong. Finally, 169 (82.4%) women had automation effort, versus 35 (17.1%) women who did not.The results concerning the SUI questionnaire about the deliveries, urinary and faecal incontinence and the information catalogued as heterogeneous, are presented in Tables Analysis of the relationship between different outcome variables reported by a clinical examination of the pelvic floor is shown in Table The analysis of the relationship between the different outcome variables reported by the patients and those reported by a clinical examination of the pelvic floor is shown in Table The main contribution of this study is the stratification of the strength of the pelvic floor muscle (PFM) in a normal distribution of a large sample of women with SUI, allowing reference baseline data for the clinic in order to have a preventive paper and to establish levels of severity. We also found significant relationships between the values obtained by evaluating the manual strength assessment by the therapist and the values found by the perineometer. Another important point is the absence of a significant relationship between muscle strength and informed quality of life values of patients.Most of the studied women had a muscular strength of three or lower on the Oxford Scale in both right and left levator ani muscles, which makes the average strength being in the moderate range. This fact is consistent with a previous epidemiological study developed in 1,732 Spanish women , where sMoreover, the average values of muscular strength reported by the perineometer were moderate  and most of the patients were allocated between quartiles 2 and 4. These findings agree with Isherwood and Rane  who showp < 0.01). Other previous work suggested a good correlation between the maximum pressure obtained using a perineometer and manual palpation with the Brink Scale [The current study shows a high correlation between values obtained with the “perineometer” and the manual evaluation of the PFM, matching with Isherwood and Rane  who usednk Scale ,28. Howenk Scale  found noThis study also has consistent values in terms of the quality of life measured by the SF-12 questionnaire with a previous study , which eThe mean age of the women studied was 39.93, as opposed to a previous study that established a mean age of 43.39 in the Spanish population of women with UI . HoweverThe average of 1.56 deliveries agrees with previous studies showing 1.29 deliveries in the Spanish population , but is Almost half of the sample suffered urine loss while exerting effort, and it was in situations such as coughing, laughing, jumping, hearing the sound of water or after coitus. These data are partially consistent with those reported in a previous study  developeAmong the limitations of this study is the fact that we do not have all the socio-demographic data of the study population. Other aspects, as pelvic floor dysfunction could be included in the interview and SUI specific questionnaires in future studies. This is due to the sample selection, which was made directly through the Consulting Unit of Physiotherapy of the Pelvic Floor, and which had to follow the dynamics posed for inclusion of patients in this service. However, the authors consider that the volume of descriptive data presented is very important since many aspects of previously validated questionnaires were collected and can be referenced by future studies looking to make more extensive comparisons regarding population subgroups. It would be necessary to recruit a stratified sample to export the results to the general population.This paper adds important findings in terms of establishing cut-off points of patient groups according to the strength of the PFM and the relationship of clinical variables obtained by the physiotherapist and those reported by the patients. Future studies should be carried out in order to analyse the strength of the PFM before and after an intervention and to determine the sensitivity to change of the strength of the pelvic floor muscles.The strength of PFM has been stratified in a normal distribution of a large sample of women with SUI creating a baseline for the clinic, to both prevent and establish levels of severity. There is a relationship between the strength of the pelvic muscles assessed manually and that obtained by a perineometer in women with SUI. There is no relationship between these values of strength and general health and quality of life perceived by them.


This will require increased clinical vigilance, more aggressive treatment and, of major importance, continued efforts in stressing healthy lifestyle choices. Moreover, as modern medicine embraces “personalized” or “precision” medicine, it needs to be stressed that it is essential to “personalize” care for patients with hypertension because comorbidities and risk factors such as diabetes, previous stroke, kidney disease, ethnic background, age, and frailty will influence clinical decisions on care and treatment. This is especially important because many of these factors are not necessarily accounted for in all clinical studies that form the basis of evidence-based hypertension guidelines. Better management of hypertensive patients aiming for a systolic blood pressure lower than the currently recommended level of 140 mm Hg, and striving for 120–130 mm Hg, should protect against hypertension-associated adverse events with less cardiovascular morbidity and mortality.


P > 0.05 for all variables). In multivariate analysis, platelet count and percentages of recording time spent at arterial oxygen saturation < 90% significant variables are associated with MPV  and . Consequently, our findings predominantly suggest that there is a casual and reciprocal interaction between MPV and autonomic activation.Some studies show increased mean platelet volume (MPV) in obstructive sleep apnea (OSA). The aim of this study was to evaluate MPV in OSA patients without cardiovascular risk factors and the possible association of heart rate derivatives with MPV. A total of 82 patients (aged 30–70 years) were divided into 2 groups according to the presence of either OSA or non-OSA as the control group. The OSA group consisted of 52 patients and the control group consisted of 30 subjects. Neither group was significantly different in terms of MPV values as well as heart rate (HR) derivatives such as minimum HR, maximum HR, the difference between maximum HR and minimum HR, mean HR, and heart rate performance index (HRPI) [(HR max. − HR min.)/HR mean] ( Recently, some studies suggest increased mean platelet volume as a platelet dysfunction in obstructive sleep apnea (OSA) syndrome , 2, whicAlthough both resting heart rate and mean platelet volume (MPV) have been demonstrated as cardiovascular risk factors , 9, littThis research was an observational retrospective and cohort study. The study initially comprised 450 consecutive subjects admitted to our neurology clinics for polysomnographic examination to detect whether or not they had OSA. Patients were excluded for a range of reasons: if they had cardiac rhythm other than normal sinus rhythm; heart failure; history of coronary artery disease (CAD); history of cerebrovascular events; diabetes mellitus; metabolic syndrome; history of smoking; hypertension (>140 and or >90 mmHg); dyslipidemia; those treated with antihypertensive or antihyperlipidemic agents; overt/active hematological disorders; and those suffering from disorders such as renal, hepatobiliary, respiratory, infectious, inflammatory, or thyroid.All the patients were asked for medical histories in terms of history of CAD, previous thromboembolic events, durations of OSA, and current medications. Diabetes was defined as the American Diabetes Association defines it . HT was 2 < 90% were obtained for each subjects. The heart rate parameters of all the participants were obtained by screening the minimum HR, maximum HR, and mean HR in the supine position during PSG examination. Total sleep times were also obtained from the PSG data.Polysomnographic (PSG) findings were obtained using a computerized system . Respiratory parameters were analyzed automatically and then reexamined visually to ensure accuracy of the data. Cessation of airflow for ≥10 seconds was defined as apnea. A reduction in thoracic excursion of ≤50% for ≥10 seconds or oxygen desaturation of ≥3% was defined as hypopnea. AHI was calculated from the number of apnea and hypopnea events per hour of sleep. Percentages of recording time spent (PRTS) at SaOThe difference between maximal HR and minimum HR was calculated and then heart rate performance index (HRPI) was calculated. HRPI was obtained by dividing the mean HR by the difference of maximal HR and minimum HR. [HRPI = (HR max. − HR min.)/HR mean]. Recently, we showed it as a novel index of autonomic nervous system that correlates with left ventricle ejection fraction in heart failure in the context of 24-hour Holter ECG monitoring in our previous study . LogicalThe body mass indexes (BMI) of all participants were calculated as weight in kilograms divided by height in meters squared and routinely recorded in the PSG data. Both the OSA and the control groups baseline characteristics such as age, gender, status of hypertension or diabetes, the circumference of waist, duration of OSA, fasting glucose, creatinine, C-reactive protein, fibrinogen levels, hemoglobin, red blood cell distribution width (RDW), white blood cells count (WBC), neutrophil count, lymphocyte count, platelet count, low-density, lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride concentrations, and mean platelet volume (MPV) were recorded from their medical recordings in our hospital.Fasting antecubital venous blood samples were collected in the morning after overnight fasting using a sterile 21-gage needle syringe without stasis in our biochemistry department; Vacutainer tubes  containing dry dipotassium ethylenediaminetetraacetic acid (EDTA) were used for blood sampling and the blood samples were collected in 2 mL tubes for platelet count and MPV measurement. Common blood counting parameters were measured using Roche Sysmex XT-2000i autoanalyser  and the same commercial kits within 30 minutes of venipuncture. For all measurements, both intra- and interassay coefficients of the variations were <5%. Lipid profile was determined by standard methods. The local ethics committee approved the study.t-test or Mann-Whitney U test was used to compare the continuous variables between the two groups. Categorical variables were denoted as percentages and compared with the Chi-square test. Pearson's or Spearman's correlation coefficient tests were used to determine correlations between MPV, HRPI, and other parametric variables or nonparametric variables, respectively. Univariate and multivariate linear regression analysis were performed to determine the independent correlations of MPV. The effects of different variables on MPV were calculated using a univariate analysis for each. The variables for which the unadjusted P value was <0.100 in univariate analysis were adjusted into full model. A two-sided P value < 0.05 was considered significant and confidence interval (CI) was 95%.Data were analyzed using the Predictive Analysis Software Statistics 18 . Continuous variables were tested for normal distribution using the Shapiro-Wilk normality test. Continuous data were reported as a mean and standard deviation or median. Student's 2. There were 39 males (75%) and 13 females (25%) in the OSA group. The control group included 30 subjects aged 44 ± 11 with a BMI of 28.5 (20–49) kg/m2. There were 21 males (70%) and 9 females (30%) in the control group. In the OSA group, the percentage of severe OSA patients and the percentage of mild-moderate OSA patients were similar . Age, gender, and BMI of the two groups were not significantly different (P > 0.05). The two groups were not significantly different in terms of fasting glucose, TG, HDL-C, LDL-C, creatinine, fibrinogen, or CRP levels . No significant difference in WBC, RDW, platelet count, neutrophil, lymphocyte, and neutrophil/lymphocyte ratios was noted between the groups. MPV was similar between the two groups .The OSA group included 52 patients aged 48 ± 11 years with a BMI of 32 (25–47) kg/mr = 0.343, P = 0.013)  and with PRTS at SaO2 <90%  in the OSA group. Else, MPV was negatively correlated with minimum HR  in the control group. There was no correlation between HRPI and MPV in the control group     and with= 0.204) . In addi = 0.01) .r = −0.252, P = 0.022) and HRPI  and negatively correlated with minimum HR  .When we performed correlation analysis on the data of both groups in terms of MPV and heart rate derivatives, MPV was positively correlated with the difference between maximum HR and minimum HR (= 0.048) . In addi2 < 90% were entered as univariate variables into regression analysis to determine the predictors of MPV. In multivariate analysis, the platelet count  and PRTS at SaO2 < 90%  were significant variables associated with MPV  has been shown as a new independent cardiovascular risk factor. MPV is an indicator of platelet activation and plays a key role in the pathophysiology of thrombotic events . In prevPV value , 16, 27.Fibrinogen levels were similar between OSA patients and non-OSA patients in the study and were no correlated with AHI in the OSA group. Although Wessendorf et al.  demonstrNo detailed study of MPV levels have been seen in patients without substantial cardiovascular risk factors until the present study, which showed normal levels in the OSA group, possibly as a result of the absence of concomitant cardiovascular risk factors. Future studies are needed that use OSA patients without substantial cardiovascular risk factors so that their results can determine if intermittent hypoxia may contribute to increased MPV values.Our study has some potential drawbacks. First, we had only a small number of patients with OSA. However, we identified these patients from 450 subjects who had been examined by PSG. We particularly recruited OSA patients who had no substantial cardiovascular risk factors. If we had enrolled patients with OSA who had hypertension, diabetes, and CAD, the relationship between OSA and MPV values would not have been well documented. Second, it was a retrospective study. Third, we used only MPV as a platelet function marker; if the study had used multiple markers of platelet function, such as glycoprotein IIb/IIIa, thromboglobulin, or platelet factor 4, these markers could have validated findings further. We could not use them due to specialized technique and equipment requirements.In conclusion, OSA patients who have no substantial cardiovascular risk factors have not increased MPV and fibrinogen levels. In addition, OSA patients' simpler heart rate derivatives obtained during PGS are not useful for the evaluation overt sympathetic and parasympathetic activity. However, the presence of a positively correlation between MPV and HRPI in the OSA group predominantly suggests that there is a casual relation between MPV and autonomic activation. Hence, further prospective randomized studies are warranted to confirm a causal relation.