Objective. To examine the relationship of handgrip strength with forearm blood flow (BF) and vascular resistance (VR) in rheumatoid arthritis (RA) patients. Methods. Forearm BF at rest (RBF) and after upper arm occlusion (RHBF), and handgrip strength were examined in 78 individuals (RA = 42 and controls (CT) = 36). Subsequently, VR at rest (RVR) and after occlusion (RHVR) were calculated. Results. The patients' RBF (P = 0.02) and RHBF (P = 0.0001) were less, whereas RVR (P = 0.002) and RHVR (P = 0.0001) were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P = 0.0001). Finally, handgrip strength was directly associated with RBF , and RHBF , and inversely related to RVR  and RHVR . Conclusion. The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals. Rheumatoid arthritis (RA) results in synovium inflammation and long-term joint damage, that can lead to symptoms of chronic fatigue and muscle pain and weakness –3. SubsePrevious work has shown a strong link between vascular and muscle functions in a variety of populations –16. For Despite the potential cardiovascular benefits of exercise for RA patients, as outlined recently –19, no sThe study is cross-sectional designed to examine regional vascular and muscular functions in randomly selected RA patients and healthy controls (CTs). The RAs were recruited from the rheumatology out-patient clinic in King Abdullah University Hospital (KAUH), Irbid, Jordan. All patients fulfilled the 1987 American College of Rheumatology Criteria  and wereIndividuals with hypertension, unstable myocardial ischemia, angina, diabetes mellitus, anemia, chronic lung diseases, hypercholesterolemia, renal failure, overly obese, and with major cardiovascular risk factors and smokers were excluded from the study. The patients continue to take prescribed medications. The participants received oral and written information about the study and signed an informed consent forms approved by the Institutional Research Board. Data collection was performed by the same examiner throughout a six-month study period.The participants' handgrip strength was measured using a hydraulic hand dynamometer . The average of 3 consecutive all-out gripping trials was used as the maximum effort. During the measurement, the participant remained upright but slightly bent forward at the waist and the head was in midposition facing straight ahead. The elbow was 90° flexed while the shoulder and wrist were 0° extended. The grip size was adjusted so that the middle finger's midportion  was approximately at a right angle .r2 = 0.8–0.9) with other prominent vascular measures and was recently found highly reliable (ICCC = 0.8–0.9) [Forearm blood flow was obtained in the dominant forearm using mercury in-silastic strain-gauge plethysmography . Measures were obtained at rest and following 5 minutes of arterial occlusion . This no0.8–0.9) , 23.Prior to the experiment, blood pressure cuffs were positioned around the upper arm and wrist, and a mercury-in-silastic strain gauge placed around the forearm approximately 10 cm distal to the olecranon process . Followi−1·min−1). Forearm vascular resistance (VR), at rest (RVR) and after occlusion (RHVR), was then determined as  and expressed as unit (U).Best-fit slopes drawn at the change in plethysmography volume graph at rest and after occlusion were used to calculate blood flow. The RBF was calculated by dividing the product of 60 seconds and full paper rang by the horizontal distance needed for the slope to reach the top of plethysmography chart. Whereas, RHBF calculated from 60 seconds multiplied by paper speed divided by horizontal distance needed for the slope to reach vertical distance of 20 mm. Forearm RBF and RHBF were expressed as mL of blood per 100 mL tissue per min  in the RAs compared to CTs, as depicted in Handgrip strength was significantly lower (P = 0.02) and RHBF (P = 0.0001) were greater in the CTs than in the RAs, whereas RVR (P = 0.002) and RHVR (P = 0.0001) were significantly lower in the CTs.r = 0.43; P = 0.0001) and RHBF . Figures r = −0.3; P = 0.009) and RHVR .Figures The aim of the present study was to examine regional measures of arterial and muscular functions in rheumatoid arthritis patients and healthy controls. The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in RAs and CTs. In addition, this study confirms the presence of vascular and muscular dysfunction in RAs, as evidenced by lower RBF, RHBF, and handgrip strength as compared to CTs.As indicated in The mechanism(s) contributing to muscle weakness are not precisely known, however, systemic inflammation seems to lead to joint impairment, characterized by joint swelling, pain, and tenderness , 28. ConOften due to the nature of the disease, this chronic inflammatory state contributes to a vicious cycle of greater functional impairment and disability. The proposed model indicates that disablement process among those patients begins with pathology/injury or defect resulting in impairment of the tissue, organ, and/or system .The lower blood flow and higher vascular resistance at rest and following a period of occlusion, in the current study are consistent with the stated hypothesis. As shown in Unfortunately the design of the present study does not allow an in depth discussion of the specific maladaptive vascular changes and the underlying causes. However, pro-inflammatory cytokines produced in the synovial fluid, and enter the systemic circulation, can directly alter vascular function by reducing the vascular wall endothelium permeability and increased leukocytes and platelets adhesion , 31. CytThe unique contributions of this study are presented in Figures The mechanisms that may explain these vascular differences between the groups may include reduced endothelium and metabolic vasodilatation, vasoresponsiveness, and capillary-to-tissue ratio, subsequently blunted blood flow to muscle tissue. Certainly the sequence of these changes remains to be revealed. However, since inflammation and regular physical inactivates seem common denominators for muscular and vascular dysfunctions in RA , 30, 32,Either way, this regional specific link is an important consideration for intervention. Adding exercise to the treatment regimen might be a valuable complement to manage the complex and interrelated nature of the disease. It is well known that a regional specific exercise training regimen induces significant and rapid localized vascular and muscular changes –37. GiveThe present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in rheumatoid arthritis patients and healthy controls. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to the controls. The associations between regional measures of vascular and muscle functions suggests a strong possibility that regional-specific training may preserve functionality in patients with rheumatoid arthritis.


Posterior reversible encephalopathy syndrome is a clinical and radiological entity. The most accepted theory of posterior reversible encephalopathy syndrome is a loss of autoregulation in cerebral blood flow with a subsequent increase in vascular permeability and leakage of blood plasma and erythrocytes, producing vasogenic edema. In infection-associated posterior reversible encephalopathy syndrome, a clinical pattern consistent with systemic inflammatory response syndrome develops. Parainfluenza virus has not been reported in the medical literature to be associated with posterior reversible encephalopathy syndrome.We report herein the case of a 54-year-old Caucasian woman with posterior reversible encephalopathy syndrome associated with parainfluenza virus infection who presented with generalized headache, blurring of vision, new-onset seizure and flu-like symptoms.Infection-associated posterior reversible encephalopathy syndrome as well as hypertension-associated posterior reversible encephalopathy syndrome favor the contribution of endothelial dysfunction to the pathophysiology of this clinicoradiological syndrome. In view of the reversible nature of this clinical entity, it is important that all physicians are well aware of posterior reversible encephalopathy syndrome in patients presenting with headache and seizure activity. A detailed clinical assessment leading to the recognition of precipitant factors in posterior reversible encephalopathy syndrome is paramount. The com [et al. . In a castations .Imaging is essential in the differential diagnosis of PRES, which includes hypertensive encephalopathy, uremic encephalopathy, lupus cerebritis, meningitis, encephalitis, stroke and cerebral venous thrombosis. Magnetic resonance imaging (MRI) allows more precise characterization and recognition of PRES than computed tomography does . The mosIn 20% to 30% of patients who develop PRES, blood pressure is essentially normal at the time of presentation, a finding that has been reported in many large series, including those concerning women with eclampsia, as well as in patients with cyclosporine toxicity after allogeneic bone marrow transplant, in broader PRES studies and in many isolated case reports .In adult patients, more than 90% have antibodies to parainfluenza virus. Even in the presence of high levels of serotype-specific antibodies, primary infection and reinfection can occur . ParainfA 54-year-old Caucasian woman presented to the emergency department (ED) of our institution with uncontrolled hypertension and new-onset seizures. Two weeks prior to this admission the patient's hypertensive medication had been switched in a tapered fashion from clonidine to lisinopril because of a reported intolerance in the form of general malaise, sinus headache and non-productive cough. Five days before presentation she had developed generalized headache, blurred vision and nausea, and she decided to visit her closest ED, an outside facility in Northwestern Massachusetts, which found her hypertensive with systolic blood pressure of 260 mmHg. At that time, she was treated with analgesics and parenteral antihypertensive medications, which led to partial improvement of her symptoms and subsequent discharge to her home in rural western Massachusetts. Twenty-four hours before her hospital admission, she again visited the ED of the same outside facility complaining of recurrent, severe headaches accompanied by blurred vision. Her blood pressure recorded at that time was 260/160 mmHg. She was again treated with intravenous narcotics and antihypertensive's; however, while being treated, she developed confusion, and the decision was made to transfer the patient to our hospital. En route to our hospital she had an episode of tonic-clonic seizure activity lasting three to four minutes. In our ED, she received a dose of 1000 mg intravenous fosphenytoin once upon arrival and was subsequently intubated for airway protection because of unresponsiveness. Her admission blood pressure was 194/115 mmHg, and she was given two doses of 10 mg of intravenous labetalol.Her medical history was notable for hypertension, systemic lupus erythematosus (SLE), end-stage renal disease (ESRD) secondary to lupus nephritis on daily ambulatory intermittent peritoneal dialysis, with a history of good dialysis compliance and blood pressure control. Her most recent peritoneal dialysis treatment had been the day preceding admission. She had also had a mechanical aortic valve replacement for a history of aortic stenosis and underwent chronic anticoagulation treatment. She was no longer on any immunosuppressive therapy for lupus. She did not use alcohol, tobacco or recreational drugs. There were no reported sick contacts, recent travel or outdoor exposures.3. No thrombocytopenia or schistocytes were noted on peripheral blood smear. Her liver panel was normal. Her blood urea nitrogen was 68 mg/dl with serum creatinine of 5.6 mg/dl. Her baseline serum creatinine was 5.2 mg/dl. Continuous cycling peritoneal dialysis was initiated in the Intensive-Care Unit (ICU). She underwent computed tomography of the brain, which showed subtle evidence of a possible acute abnormality in the right occipital lobe in addition to an unusual pattern of calcifications in the cerebral hemispheres  and the time to recovery from PRES was two to 10 days  [et al. reported mortality of more than 25% with significant residual neurologic morbidity in survivors as well [There are no specific guidelines for the management of hypertension in PRES; however, the general recommendation is to treat all PRES patients presenting with malignant hypertension with parenteral agents for a goal reduction in diastolic blood pressure to 100 to 105 mmHg within two to six hours while not exceeding a decline in mean arterial pressure by more than 25% to avoid cerebral hypoperfusion and stroke. Those patients who present with lesser degrees of hypertension should be managed with smaller incremental changes in blood pressure decline as per ischemic stroke guidelines . Treatmecurrence . In the  as well .Our patient was treated symptomatically, with particular attention given to aggressive blood pressure control. She recovered fully with no residual neurological deficit and with resolution of the generalized body rash, which was ultimately attributed to an allergic reaction. She was discharged to home nine days after admission to our institution.We postulate that our patient experienced an episode of coexistent hypertensive SLE and infection-associated PRES precipitated by a combination of uncontrolled hypertension and parainfluenza virus type 3 infection. Both associations favor the contribution of endothelial dysfunction in the pathophysiology of this clinicoradiological syndrome.In view of the reversible nature of this clinical entity, it is important that all physicians are well aware of PRES in patients who present with headache and seizure activity. A detailed clinical assessment leading to the recognition of precipitant factors in PRES is paramount, as early diagnosis and management may have significant prognostic implications.Written informed consent was obtained from the patient for publication of this manuscript and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.OO was a major contributor to analyzing and interpreting the data in this case, reviewing the literature and writing the manuscript. JH was a major contributor to the coordination, design and revision of the manuscript critically for important intellectual content. YO was a major contributor to reviewing the literature and developing the images. IO was a major contributor to reviewing the literature. DL was a major contributor to critically reviewing and revising the manuscript for important intellectual content. All authors read and approved the final manuscript.


Documentation of femoral head blood flow before, during and after head preserving surgery is important for safeguarding vascularity to the femoral head and for documentation in patients in whom the blood flow is compromised. Laser Doppler flowmetry and microsensor intracranial pressure (ICP) transducers have been used to satisfactorily depict such changes. However, these devices are expensive and not universally available in orthopedic operating rooms. We describe a new technique for the assessment of intra-operative blood flow to the femoral head. This is a technical description of a simple system utilized in eight patients to assess the femoral head vascularity using equipment available with the anesthetist.A standard epidural catheter attached to an arterial pressure transducer is introduced into the femoral head from the margin of the articular surface via a small hole drilled with a K wire. The pressure wave within the epiphysis is detected on the anesthesia monitor. Pressure within the femoral head is used as a surrogate for blood flow. The pressure and the wave form are correlated with the electrocardiogram (ECG) wave on the anesthetic machine. The technique was used in eight children with hip pathology requiring hip dislocation for documenting the hip vascularity status.There was good correlation between the pressure wave and the ECG for a patient with presumed normal femoral head vascularity, whereas the pressure measurements were greatly reduced and the wave form was absent in a femoral head wih radiographic or bone scan evidence of avascular necrosis.This new technique is a cheap and readily accessible alternative to Laser Doppler flowmetery and ICPs monitoring probes for the assessment of blood flow to the femoral head. Hip surgeries where preservation of the femoral head is required are becoming common.et al. described laser Doppler flowmetry (LDF) to monitor the circulation in the femoral head during various positions and manoeuvers.Notzli We describe the use of an arterial transducer, commonly available with the anesthetist, for documenting the pressures in the femoral head during surgeries on the femoral head. The device can be easily assembled and is a relatively inexpensive tool to monitor blood flow. We report our observation on eight patients.Between January 2010 and July 2010, eight patients who underwent surgical dislocation of the femoral head for various indications, such as Perthes disease (n=2), acute (n=2) and healed (n=2) slipped capital femoral epiphysis (SCFE), osteoid osteoma (n=1) and osteochondroma of the femoral neck (n=1), had an intra-operative femoral head vascularity assessment. The intra-operative assessment was validated by a post-operative technetium bone scan in those with acute SCFE because of the high risk of avascualrity due to the primary pathology. The patients were followed-up at 2 weeks, 2 months, 3 months, 6 months and longer periods with radiographs depending on the underlying pathology.The intra-operative technique was standardized per-operatively and then carried out in a similar manner in all the patients. This consisted of four steps: (1) exposure of the femoral head and dislocation preserving the blood supply usually by the safe surgical dislocation technique of Ganz, (2) assembling of the device by connecting the epidural catheter to the arterial transducer that is connected to the monitor as explained below , (3) a hThe assembly requires a 16 gauge epidural catheter (B.Braun Melsungen AG), a Luer lock connector, a pressure transducer kit  and an anesthesia monitor . The 16 gauge epidural catheter is connected to a pressure transducer kit via a Luer lock connector. The bacterial filter provided with the kit is excluded as it would dampen the pressure trace. The pressure transducer has a sterile flushing system using normal saline without heparin. The entire kit is primed with saline so that it is free of air bubbles .A hole with a 1.8 mm K wire is drilled at the anterolateral edge of the articular surface deep into the proximal femoral epiphysis. In a vascular head, the blood flows out from this after the drilling. The catheter is inserted in this pre-drilled hole . One shoIn children undergoing the capital realignment technique or surgical dislocation for any surgical procedure, the technique allowed intra-operative monitoring of the head blood flow. In those with suspected avascular necrosis and no flow, such as in acute SCFE, it documented the lack of blood flow to the head, protecting the surgeon medicolegally and allowing recording of any improvement after successful realignment.n = 4), Perthes disease (n = 2), osteoid osteoma (n = 1) and osteochondroma of the neck of the femur (n = 1) [The index procedure was carried out on eight patients . The average age was 12.8 years (6-18 years). The mean follow-up was 5.25 months (2-11 months). The diagnoses were SCFE ( (n = 1) . The chiThe amplitude of pressure recorded varied between the patients; however, all five vascular heads showed a wave form corresponding to the ECG trace. In two patients with acute SCFE, no pressure was recordable initially; however, after capital realignment, the vascularity was restored in one after repositioning of the head and observed introperatively. In both the children with acute SCFE, a bone scan was performed post-operatively, which showed an intact vascularity in one and avascularity of the femoral head in the other. In the two children with healed SCFE, there was a good wave form and pressure. These children underwent osteoplasty for femoro-acetabular impingement. In the child with residual Perthes disease, the pressure recorded was 2 mm Hg and, his preoperative and postoperative radiographs had evidence of avascularity. In one child with modified Elizabeth Town Stage 2 A Perthes disease, the wave form was absent and the pressure was 0. He underwent fusion of the growth plate, osteoplasty, curetting of the avascular anterolateral segment and bone grafting, the latter two surgical steps being performed to improve vascularity. His radiographs also showed avascular changes as expected. The details are described in The technique applied in a 14-year-old undergoing a safe surgical dislocation procedure for osteoplasty in a slipped capital femoral epiphysis showed a mean pressure of 44 mm Hg and a wave form that corresponded to the ECG trace. The trace shown on the monitor represented the femoral head pressure . We alsoIn the remaining two children with osteoid osteoma and osteochondroma, respectively, the monitoring of the head pressure and wave form was done while excising the posterior neck lesions, and the vascualrity stayed intact during the procedure. Their radiographs on follow-up so far have shown no avascular necrosis.The costing of the device when using an epidural catheter is approximately 2000 rupees, excluding the anesthesia monitor. It is possible to further reduce the cost by using an IV canula instead of the epidural catheter for a single attempt at measurement.The measurement of intraosseous pressure of the femoral head for functional studies of the femoral head vascularity has been described by Ficat and Arlet.7Our measurements of the pressure using an arterial transducer in the anesthetized patient undergoing an osteoplasty using safe surgical dislocation by the Ganz approach showed wave forms corresponding to the QRS complex on ECG tracing and to the arterial pulsation. We also found that the wave form disappeared when the vascular pedicle was compressed at the base of the neck posteriorly , only toThe absolute pressures may not be of much significance in the determination of bone blood flow in surgical situations. However, the wave form and its relationship to ECG and arterial flow (pulse oxymeter reading on the anesthesia monitor) is important for determining the arterial supply to the part of the head being assessed.This simple and effective technique is an easily accessible tool for an orthopedic surgeon to assess the hip vascularity, with a wide range of applications in the field of trauma and hip reconstructive surgery. This will also have use in replacement surgery, such as surface replacement arthroplasty, where an on-table assessment of suitability of the posterior head neck area is essential to prevent a future failure due to collapse of an avascular segment.The assessment of the blood flow of the femoral head is an established technique with many indications. The present technique describes an easy cheap alternative using equipment available in most operating rooms with the anesthetist. The system is extremely simple to assemble and use.


Background. A paradoxical increase in cardiovascular events has been reported with intensively lowering diastolic blood pressure (DBP). This J-curve phenomenon has challenged the aggressive lowering of blood pressure, especially in patients with coronary artery disease. Objective. Our objective was to study the effects of low DBP on mortality and determine a threshold for which DBP should not be lowered beyond. Methods. We evaluated a two-year cross-section of primary care veteran patients, from 45 to 85 years of age. Receiver operating characteristics (ROC) were employed to establish an optimal cut-off point for DBP. Propensity-score matching and multivariate logistic regression were used to control for confounders. All-cause mortality was the primary outcome. Results. 14,270 patients were studied. An ROC curve found a threshold value of DBP 70 mmHg had the greatest association with mortality (P < 0.001). 49% of patients had a DBP of 70 mmHg or less. Using a propensity-matched multivariate logistic regression, odds ratio for all-cause mortality in subjects with a DBP less than 70 mmHg was 1.5 (95% CI 1.3–1.8). Conclusions. Reduction of DBP below 70 mmHg is associated with increased all-cause mortality. Hypertension guidelines should include a minimum blood pressure target. Hypertension affects 29% of male and 25% of female adults worldwide . Its impThe incidence in cardiovascular events, including mortality, increases with extremes in blood pressure. The paradoxical increase in events at lower blood pressures has been represented by a J-shaped or U-shaped curve. The J-curve phenomenon has been researched since 1979  and has This study evaluates the concept of the J-curve in DBP across a large primary care population with a high prevalence of CAD, diabetes, and hypertension. We sought to determine a threshold for which DBP should not be lowered beyond. We also evaluated low DBP as an independent risk factor for all-cause mortality.A cross-sectional study of predominantly male patients at the VA Central California Healthcare System aged from 45 to 85 years was conducted over a 2-year period. Data were collected from the electronic medical record and provided demographic information, vital signs, comorbid diagnoses, and medications. The study was approved by the VA Northern California Health Care System Institutional Review Board.All patients at least 45 years of age or older with a minimum of one outpatient encounter with recorded blood pressure were included in the study.The primary outcome, death from any cause, was used as the dependent variable. Blood pressure (BP) was collected at the time of an ambulatory encounter. Pulse pressure was calculated as systolic BP minus diastolic BP. Covariates were included that were thought to contribute to the overall risk of mortality as well as variables that might alter a patient's blood pressure goals. These included age, body mass index, and the presence of comorbidities including CAD, hypertension, diabetes, cerebrovascular disease, and chronic kidney disease. The investigators felt that these conditions were the most likely to contribute to the cardiovascular causes of death and were important potential confounding variables in this study. CAD was defined by ICD9 code, by a history of myocardial infarction with abnormal electrocardiogram or troponin elevation, coronary artery bypass graft surgery, percutaneous coronary intervention, or coronary stent placement. Data were also gathered on the classes of blood pressure medications used to treat the patients.t-test. Interval likelihood ratios were calculated for each interval for DBP against all-cause mortality along with 95% confidence interval (CI). Multivariate logistic regression (LR) assessed for independence of low DBP as a risk for all-cause mortality.Grouping was based on a cut-off point for DBP. Receiver operating characteristic curve was used to determine the optimal cut-off point for DBP as a continuous scale against death. Baseline characteristics were compared between the two groups with the use of the chi-square test and the independent samples Propensity score matching was conducted using DBP grouping as above mentioned for the dependent variable. Each study subject received a propensity score based on the presence of selected covariates. Covariates included age, comorbidities including CAD, hypertension, diabetes, chronic kidney disease, cerebrovascular disease, total number of antihypertensive medications, and individual medication classes. Finally, subjects were matched based on their scores, looking for the closest match.Statistical analyses were carried out with SPSS Statistics Software for Windows, Version 20.0 . Propensity score matching was carried out using R Project for Statistical Computing, Version 2.12.0  along with the SPSS R Essentials plug-in.A total of 14,270 patients were included in the study. The mean age of study population was 67 years with 96% male patients. The prevalence of comorbid conditions was as follows: hypertension 66.7%, diabetes 29.5%, CAD 19.5%, stroke 9.3%, and chronic kidney disease 6.9%.Interval likelihood ratios of all-cause mortality as a function of DBP were calculated and are shown graphically . The lowP < 0.001). Patients were grouped according to DBP less than 70 mmHg and those at or above 70. Baseline characteristics of these two groups were significantly different with respect to age, comorbidities, and use of antihypertensive medications  and CAD , with more patients having diabetes and CAD in the group with lower DBP. Medication use by class was similar in both groups except for a trend in increased use of loop diuretics in the low DBP group . There was no difference in the total number of antihypertensive medications in the two groups  as an individual risk factor for mortality, after adjusting for pulse pressure, CAD, chronic kidney disease, or cerebrovascular disease. Pulse pressure was included as a potential cofounder due to its association with cardiovascular disease and its unique relationship to DBP: decreases in diastolic blood pressure result in increased pulse pressure. Increased pulse pressure has been reported to increase the risk of developing diabetes , lead toLow DBP was not independent of hypertension or diabetes, which suggests that a low DBP may only be harmful as a consequence of antihypertensive therapy or in patients with diabetes. Current literature on aggressive treatment of hypertension among diabetics has failed to show any benefit on mortality . It was Owing to the debatable nature of the clinical significance of the J-curve –17, majoThe growing body of evidence for J-shaped relationships between blood pressure and cardiovascular outcomes has led to the revision of guidelines from the European Society of Hypertension . This reAs with all retrospective studies we were limited by unidentified or incompletely documented potential confounders. The trend towards increased CAD in the group with DBP <70 mmHg, even after matching, poses a particular confounder in the relationship between low DBP and all-cause mortality, though this was accounted for using a multivariate logistical regression model. This bias remains a concern for nearly all trials of BP treatment, that the group which requires the most vigilant treatment could also be the group that possesses the greatest pretreatment cardiovascular risk profile . Hence, Another limitation is that while this was a large population, it was also a specific population. The Veterans Administration medical record does not routinely record ethnicity as part of patient demographics. While younger veteran groups are more ethnically diverse, World War II and Korean War veterans are more than 88% Caucasian.Finally, our dataset lacks intervals and averages on the recording of BP, and we are limited to the final reading at the time of data collection. It is not possible to consider trends in BP over time with this limitation. While treatment of hypertension reduces mortality due to cardiovascular events, reduction of DBP below 70 mmHg is associated with increased all-cause mortality in this male predominant study population with significant comorbidities. The relationship between DBP and mortality follows a J-shaped curve. Avoidance of DBP less than 70 mmHg may be advisable in the management of hypertension, although prospective studies are warranted in more representative patient populations. Our findings suggest the need of a shift in paradigm with the guidelines including a minimum as well as a maximum BP target. BP therapeutic goals should also be individualized to the patient's comorbid conditions.


Asthma is the most common serious chronic lung disease that affects people of all ages with evidence for a growing prevalence in industrialized as well as in developing countries. Allergic asthma is considered to be a Th2-dominant chronic inflammatory disease of the lungs. Th2 cells secret a panel of cytokines with several overlapping functions including IL-4, IL-5, IL-13, and GM-CSF. Increased Th2-cytokine and IgE levels and accumulation activation of Th2 cells, eosinophils and mast cells are observed in asthmatic lungs. However, recent studies focused on cell-based mechanisms for the pathogenesis of allergic asthma.In this study we compare the anti-IgE treatment modality in the dynamics of immune system cytokine levels of IL-8, IL-17, TGF-beta and GSCF in asthma patients who had no other any allergic disease, newly diagnosed allergic asthma patients and healthy volunteers.The study population consisted of 14 patients suffering of SPA, 14 newly diagnosed allergic asthma patients and 14 healthy volunteers included as controls. Plasma levels of cytokines were measured. Total and specific IgE levels of anti-IgE monoclonal antibody treated patients, serum high-sensitivity C-reactive protein levels, FEV1/FVC rates and asthma control test (ACT) were measured for the clinical follow-up.We observed that patients who had SPA whom were treated with anti-IgE monoclonal antibody presented increasing levels of IL-8, TGF-β and GCSF during the treatment period of sampling times at 4 months and 18 months. However this increase was not correlated neither with serum hsCRP levels nor FEV1/FVC rates. We also noted that the levels of these cytokines did not differ between newly diagnosed allergic asthma patients, non-treated asthma patients and control.


The number of adults with diabetes mellitus is increasing worldwide, particularly in Asia and Africa. In sub-Saharan Africa, renal complications of diabetes may go unrecognized due to limited diagnostic resources. The prevalence of chronic kidney disease (CKD) among adult diabetics in sub-Saharan Africa has not been well described.This study was conducted at the diabetes mellitus clinic of Bugando Medical Centre in Mwanza, Tanzania. A total 369 consecutive adult diabetic patients were enrolled and interviewed. Each patient provided a urine sample for microalbuminuria and proteinuria and a blood sample for serum creatinine level. Estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault equation. CKD was staged according to the Kidney Disease Improving Global Outcomes system.A total of 309 (83.7%) study participants had CKD; 295 (80.0%) had significant albuminuria and 91 (24.7%) had eGFR < 60 ml/min. None of these patients were aware of their renal disease, and only 5 (1.3%) had a diagnosis of diabetic nephropathy recorded in their file. Older age was significantly associated with CKD in this population .Chronic kidney disease is highly prevalent among adult diabetic outpatients attending our clinic in Tanzania, but is usually undiagnosed. Nearly ¼ of patients had an eGFR low enough to require dose adjustment of diabetic medications. More diagnostic resources are needed for CKD screening among adults in Tanzania in order to slow progression and prevent complications. Diabetes mellitus is a steadily growing global epidemic. The World Health Organization (WHO) predicted that the number of people living with this disease would reach 221 million by 2010 and will further increase to 300 million by 2025 with the majority of new cases occurring in Asia and Africa ,5.Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus. Screening for CKD is not routinely performed in many diabetic clinics in sub-Saharan Africa due to limited diagnostic resources. In particular, microalbumin testing is available in very few centers .Few studies have described the burden of CKD among adults with diabetes in sub-Saharan Africa. Therefore, in this study we aimed to determine the prevalence, awareness and factors associated with CKD among diabetic adult outpatients attending our clinic in Tanzania for routine care using both serum creatinine and urine microalbumin testing.This was a cross-sectional study conducted at the outpatient diabetes clinic of Bugando Medical Centre (BMC) in Mwanza, Tanzania. BMC is the zonal hospital for the Lake Victoria region in northwest Tanzania, and it serves a population of approximately 13 million people. Our outpatient diabetes clinic follows approximately 1000 children and adults from the Mwanza region for primary diabetes care. In Tanzania, the large majority of diabetic patient care is provided at referral and regional hospital clinics as these are the only facilities that have a reliable supply of the necessary equipment and drugs for diagnosis and management of diabetes mellitus. Referral hospitals like BMC provide primary diabetes patient care in the Lake Zone region.We consecutively enrolled patients between October 2011 and March 2012. All adults (≥18 years) with known diabetes mellitus who attended the BMC clinic during this time period were eligible for this study. Those who gave informed consent and agreed to provide samples of urine and blood were enrolled. In order to determine the prevalence of CKD within a confidence interval of +/- 5%, a required sample size of 368 was calculated using the Kish-Leslie formula.At the time of enrollment, all study participants were asked to complete a pre-validated, standardized questionnaire that included sociodemographic and clinical characteristics related to diabetes mellitus. The sociodemographic and clinical information collected in the questionnaire were as follows: age, gender, occupation, level of education, body mass index (BMI), duration of diabetes, hypoglycemic agent/s used, presence and treatment of hypertension, smoking/alcohol intake, HIV serostatus, family history of kidney disease, and urinary symptoms. In order to ascertain awareness of renal disease within the study population at the time of enrollment, we asked the following question, “Have you been previously informed about a decrease in your kidney function or about a kidney problem by your doctor or nurse?”Chart review was used to determine whether patients had prior diagnoses of hypertension or renal disease. Patients were labeled hypertensive if their charts documented a diagnosis and/or treatment of hypertension. For those attending the clinic for the first time on the day of study enrollment, the diagnosis of hypertension was made if systolic blood pressure was >140 mmHg and/or diastolic blood pressure was >90 mmHg.2 or evidence of kidney damage .Random blood glucose measurement was performed . A fresh urine sample was tested for microalbumin using a dipstick . Patients were considered to have microalbuminuria if the urine albumin concentration was above 20 mg/L, as per instructions provided by the manufacturer and according to prior research ,7. A secThe primary outcomes were prevalence and severity of CKD within the study population according to the KDIGO classification. Data was entered into Microsoft Excel and analyzed using STATA version 10 . Categorical variables were described as proportions (%), and continuous variables were described as medians [interquartile range]. In the univariate analysis, Fisher’s exact and chi-squared tests were used for categorical and binary variables respectively and the Wilcoxon rank-sum test was used for continuous variables. Predictors with a p < 0.10 were included in the multivariate model using logistic regression.Ethical clearance for the study was obtained both from the Research and Publications Committee BMC and the Institutional Review Board of Weill Cornell Medical College.Between October 2011 and March 2012, 960 diabetic patients attended the BMC clinic. Out of these, 591/960 were ineligible because they were <18 years old. All of the remaining 369 adult diabetic patients consented, were enrolled, and provided urine and blood samples.2 [22.6 – 29.6 kg/m2], the median duration of diabetes was 6 years [3 – 11 years], and 347/369 (93.8%) had type 2 diabetes mellitus. Among these diabetic adults, 212/369 (57.5%) had co morbid hypertension but only 35/212 (16.5%) had achieved target blood pressure control (<130/80 mmHg). Among our diabetic patients, 199/369 (53.9%) were on an Angiotensin Converting Enzyme inhibitor (ACE-I) or an Angiotensin II Receptor Blocker (ARB). See Table Of the 369 study participants, 197 (53.4%) were female, and 258/369 (70.3%) were from Mwanza City. The median age was 54 years [45-62 years]. The median BMI was 25.6 kg/mOf all study participants, 309/369 (83.7%) had CKD and 91/367 24.7%) had eGFR < 60 mL/min. A total of 295/369 (80.0%) had moderately to severely increased albuminuria , gender (p = 0.09), use of only oral hypoglycemic agents (p = 0.03), presence of hypertension (p = 0.07), and duration of hypertension (p = 0.03). The above variables were then subjected to multivariate analysis and only one variable, older age, was found to be significantly associated with CKD .2. This highlights the importance of implementing routine screening for CKD among adult diabetics in sub-Saharan Africa [CKD was almost ubiquitous among the Tanzanian adults with diabetes mellitus attending our clinic. More than 80% of patients had CKD and nearly 25% had an eGFR <60 ml/min/1.73 mn Africa , a region Africa ,7,10. Ean Africa ,12.TheseThe prevalence of moderately to severely increased albuminuria was particularly high in our study population. The rate of overt proteinuria in this study (34.1%) was even higher than other studies in the sub-Saharan Africa, with the highest rate in comparative studies being 20% . The pre2[2 represents loss of half or more of adult kidney function and is an ominous finding in a setting where few options exist for advanced kidney disease. Such a low eGFR also has implications for drug therapy for diabetes mellitus and, if undetected, could lead to complications such as lactic acidosis from metformin or hypoglycemia from sulfonylureas or insulin. In our clinical experience, drug toxicities due to lack of adjustment of drug therapy in the setting of renal dysfunction are a common cause of admission among Tanzanians with diabetes.In addition to a high prevalence of albuminuria, nearly 25% of our adult Tanzanian diabetic patients had an eGFR <60 ml/min/1.73 m2. An eGFROlder age was significantly associated with CKD in our study population. This is consistent with other studies . HoweverThe high prevalence of advanced nephropathy among our Tanzanian adult diabetic patient may be related to several factors. First, patients in our setting may be diagnosed with diabetes at a later stage of their disease . The medOne weakness of this study is the possibility of referral bias since this study was conducted at a referral hospital. On the other hand, most diabetes mellitus care in Tanzania occurs at referral hospitals and almost all of the patients in our study were receiving primary care  services at our hospital. Another limitation of this study was the use of the Cockroft-Gault equation to calculate eGFR. Other equations, such as the MDRD equation, may be superior in estimating the GFR but the best eGFR equation for East African adults has not yet been determined. Lastly, as mentioned above, the presence of NDRDs could not be excluded.2. These results highlight the urgent need for regular nephropathy screening among African diabetic adults in order to prevent progression to chronic renal disease [In conclusion, our study identified an alarmingly high prevalence of CKD among the Tanzanian adult diabetics attending our clinic. More than 80% of our diabetic outpatients had CKD and nearly 25% had an eGFR <60 mL/min/1.73 m disease . This isACE-I: Angiotensin converting enzyme inhibitor; ARB: Angiotensin II receptor blocker; BMC: Bugando Medical Centre; BMI: Body mass index; CKD: Chronic kidney disease; eGFR: Estimated glomerular filtration rate; KDIGO: Kidney disease improving global outcomes; NDRD: Non-diabetic renal disease; OHGA: Oral hypoglycemic agent; OR: Odds ratio; UKPDS: United Kingdom prospective diabetes study; WHO: World Health Organization.The authors declare that they have no competing interests.MNJ conceived of the idea, designed the study, collected and analyzed the data, and drafted the manuscript. SEK participated in the design of the study. AM assisted with the design of the study. RK assisted with the design of the study. LRS edited the manuscript. JAD assisted with data analysis and edited the manuscript. RNP assisted in design and coordination of the study, data analysis, and editing of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/14/183/prepub


The most effective and accurate treatment of hypertensive patients reduces cardiovascular events and improves the quality of life.This study compared the efficacy and safety of combined (combination therapy) with an angiotensin-receptor blocker (ARB) a calcium-channel blocker (CCB) (Losartan / Amloidipine 50/10mg) vs maximal combination doses of ARB with hydrochlorothiazide (Losartan /HCTZ 100/25 mg) and maximal combination doses of CCB with HCTZ (Amlodipine /HCTZ 10/25 mg) in the management of stage 2 hypertension.This randomized clinical trial (RTC) comprised 478 hypertensive patients with mean age 50.5±5.21 years, and took place between January 2010 and December 2011 in Vasei Hospital clinic in Sabzevar. Antihypertensive drugs were washed out after 5 days of discontinuation of drugs and the patients with mean blood pressure in sitting position ≥ 160 and <200 mmHg in systole and ≥ 100 and <110 mmHg in diastole were randomized into three groups: Losartan / Amlodipine 50/10 mg (n =164) , Losartan / HCTZ 100/25 mg (n =155) and Amlodipine / HCTZ 10/25 mg (n =159). The end point was reaching the blood pressure below 140/90 within 56 days of treatment in each group.There was a significant difference in systolic blood pressure reductions between treatment groups (P<0.001) and also there was a significant difference between groups in reducing diastolic blood pressure (P<0.01). The highest systolic and diastolic blood pressure reduction respectively was found in Amlodipine/losartane and losartane/HTCZ group. The ANCOVA analysis revealed that only treatment regimen had a significant effect (P=0.01) and other factor including Age, Gender, Diabetes Mellitus, Smoking and High serum cholesterol didn’t have significant effect on blood pressure reduction.ARB/CCB combination therapy reduced blood pressure more effectively than the maximal doses of ARB or CCB with HCTZ in stage 2 hypertensive patients within this period of study. Hypertension is one of the most common worldwide diseases afflicting humans and requires meticulous control to produce the maximum reduction in clinical cardiovascular end points. Approximately 26.4% of the adult population worldwide had hypertension in 2000, and this is expected to increase to 29.2% by 2025 . The preThis study was a randomized clinical trial on treatment of stage 2 systolic hypertension conducted at Vasei hospital clinic of Sabzevar city in IR Iran between January 2010 and December 2011. The diagnosis and staging of arterial hypertension was based on the mean value of two consecutive office BP measurements that were taken between 17:00 and 20:00 . The study design is summarized in The Statistical Package for the Social Sciences (SPSS) program version 19.0 was used to perform the statistical analyses. Descriptive statistics were used to show the frequencies and percentages. Systolic and diastolic blood pressure measurements and percentage of systolic and diastolic blood pressure reduction were shown as Mean±SD. Pared student t-test was performed to compare baseline blood pressure readings with the readings after intervention and also one-way ANOVA was performed to compare study parameters between each treatment groups. Chi-square was used to compare gender, history of smoking and high serum cholesterol between treatment groups. The analysis of covariance (ANCOVA) for repeated measures was performed to identify the interaction between study categories and systolic and diastolic blood pressure changes. Confidence interval was considered as 0.95 and p values lesser than 0.05 were considered as significant.Among 478 hypertensive cases, the mean age was 50.27±5.17 years (Median age was 50 years and IQR was 9 years). Among the study population, baseline systolic and diastolic blood pressures were slightly higher in men than women but this difference was not significant as shown by (P=0.79) for systolic blood pressure and (P=0.92) for diastolic blood pressure. No significant difference was observed between age of men and women in this study (P=0.18).Independent t-test revealed no significant difference in age between diabetic and non-diabetic patients (P=0.93). Also no significant difference was found in mean systolic and diastolic blood pressures between diabetic and non diabetic cases; (P=0.81) for systolic blood pressure and (P=0.52) for diastolic blood pressure. Among the 99 diabetic patients there was no difference between the number of men and women (P=0.84). Diabetic patients used to smoke significantly more than the non-diabetics (38.4% of diabetics and 16.6% of non- diabetics were smokers) (P<0.01). Chi-square test was used to identify the relationship between diabetes and high serum cholesterol levels. High serum cholesterol levels were detected in 94(96%) of diabetics which was significantly higher than 6(1.6%) of non-diabetics (P<0.01). Metabolic syndrome was found in 92 (25.5%) of non-diabetics while none of the diabetics exhibited metabolic syndrome, which was found to be significantly higher (P<0.01). In respect of response to treatment there was no relationship among diabetics (P =0.57).There was no relationship between response to treatment and gender, smoking, serum cholesterol level, metabolic syndrome and history of diabetes .There was a significant difference in systolic blood pressure reductions between the three treatment groups (P<0.001). There was also a significant difference between groups in reducing diastolic blood pressure (P<0.01). The highest systolic blood pressure reduction was found in treatment with Amlodipine/losartane followed by amlodipine/HCTZ and losartane alone . The ANCRepeated measure test revealed significant difference in reduction rate of both systolic and diastolic pressure (P<0.001). Repeated measure test also showed that there is a significant relation in interaction between the before and after blood pressures (P<0.001).Combination therapy is proved to have better effects on blood pressure control in patients with stage 2 hypertension -12. It wAmlodipine/losartane combination therapy resulted in the highest systolic blood pressure reduction (20.5%) in this study. In a study by Kim et al.  systolicIn this study combination therapy with Losartan/HCTZ resulted in the highest (33.3%) reduction in diastolic BP. In the study by Bonner et al. , combinaOne of the limitations of this study was that there was no control on patients’ lifestyle including usual physical activity and food or drink intakes. It is recommended that further controlled trials be performed by selecting matched cases with similar lifestyle and BP.


Soluble epoxide hydrolase inhibitors (sEHIs) are demonstrating promise as potential pharmaceutical agents for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease. The present study determined the ability of a first-in-class sEHI, AR9281, to decrease blood pressure, improve vascular function, and decrease renal inflammation and injury in angiotensin hypertension. Rats were infused with angiotensin and AR9281 was given orally during the 14-day infusion period. Systolic blood pressure averaged 180 ± 5 mmHg in vehicle treated and AR9281 treatment significantly lowered blood pressure to 142 ± 7 mmHg in angiotensin hypertension. Histological analysis demonstrated decreased injury to the juxtamedullary glomeruli. Renal expression of inflammatory genes was increased in angiotensin hypertension and two weeks of AR9281 treatment decreased this index of renal inflammation. Vascular function in angiotensin hypertension was also improved by AR9281 treatment. Decreased afferent arteriolar and mesenteric resistance endothelial dependent dilator responses were ameliorated by AR9281 treatment of angiotensin hypertensive rats. These data demonstrate that the first-in-class sEHI, AR9281, lowers blood pressure, improves vascular function and reduces renal damage in angiotensin hypertension.  Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites generated by cytochrome P450 epoxygenase enzymes. Soluble epoxide hydrolase (sEH) can further metabolize EETs to form dihydroxyeicosatrienoic acids (DHETs). Metabolism of EETs to DHETs is the primary mechanism whereby the biological actions of EETs are decreased or eliminated ,2,3,4. EThe effect of the sEHI, AR9281 on blood pressure in angiotensin hypertension is shown in Even though the ability for sEHIs to lower blood pressure have been variable, the ability of sEHIs to protect from end organ damage in hypertension has been much more consistent. Experimental findings have demonstrated that the glomeruli in the juxtamedullary region of the kidney cortex are the first to be injured in hypertension . Others Comparing mRNA expression of inflammatory genes between groups assessed renal inflammation. Real-time PCR arrays were used to profile mRNA expression of 84 inflammatory cytokines and receptors in the kidney cortex. Data presented in Afferent arteriolar dilator responses to acetylcholine in the animal groups are presented in Flow-mediated dilation in mesenteric resistance arteries was also assessed. An increase from zero flow to 50 μL/min (low flow) or zero to 300 μL/min (high flow) in mesenteric resistance arteries resulted in a 20 ± 4% and 49 ± 4% (n = 4) relaxation, respectively in control rats. This vasodilatory response was blunted in angiotensin hypertensive rats and averaged 14 ± 1% to low flow and 20 ± 1% (n = 3) to high flow. AR9281 treatment restored the mesenteric resistance arteries responses to low flow (21 ± 9%) and high flow  in angiotensin dependent hypertensive rats. The findings of impaired endothelial mediated responses in renal and mesenteric arterioles is in agreement with numerous studies that have demonstrated endothelial dysfunction in animal models of hypertension and human hypertension ,31,32,33in vitro and in vivo and known pharmacokinetic profile in rats. Angiotensin was infused at a continuous rate via a mini-pump (65 ng/min). Systolic blood pressure was measured using tail-cuff plethysmography.The Medical College of Wisconsin Institutional Review Committee according to National Institutes of Health Guidelines approved all animal studies for the Care and Use of Laboratory Animals. Male Sprague-Dawley rats were divided into three experimental groups; the first group was subjected to sham surgery, the second group received angiotensin and vehicle treatment (5% (2-hydroxypropyl)-β-cyclodextrin), and the third group received angiotensin and AR9281 , a SEH transition state inhibitor of the 1,3-disubstituted urea, carbamate and amide class. The dose of AR9281 was based on its demonstrated ability to inhibit sEH At the end of the two week AR9281 treatment period, kidneys were immediately fixed in 10% buffered formalin solution and embedded in paraffin for light microscopic evaluation. Sections were cut at a thickness of 2 to 3 μm and stained with hematoxylin-eosin, periodic acid-Schiff reagent and periodic acid-methenamine-silver. For semiquantitative evaluation, two individuals evaluated histological sections for renal injury in a blind fashion. Approximately 30 subcapsular and 30 juxtamedullary glomeruli from each specimen were analyzed for glomerular injury: Grade 1, normal glomerulus by light microscopy; Grade 2, involvement of up to one-third of the glomerular area; Grade 3, involvement of one to two thirds of the glomerulus; and Grade 4, two-thirds to global sclerosis. Histological sections were evaluated from four animals in each group and an average score for each category determined. ® Plus Mini kit  according to the manufacturer’s protocol. RNA concentrations were determined using absorbance at 260nm. Reverse-transcription was performed on 2μg of RNA from each sample using the RT2 PCR Array First Strand Kit . Each cDNA synthesis reaction was diluted before being added to an RT2 Real-Time SYBR Green PCR Mastermix (SupoerArray) which was aliquoted onto a 96-well PCR Array plate, one sample per plate; each well contained a primer pair for a different gene or control. Thermal cycling and real-time detection were done with a Bio-Rad iCycler : step 1) 95 °C for 10 minutes, step 2) 95 °C for 15 seconds followed by 60 °C for 60 seconds (repeated 40 times). Melt-curve analysis was completed after each PCR reaction. Analysis was conducted using templates provided by SuperArray Biosciences.Threshold cycle (Ct) values were normalized to a set of housekeeping genes Rplp1, Hprt1, Rpl13a, Ldha, and Actb as recommended by SuperArray Biosciences to get a ΔCt value and fold-changes were calculated using the equation: (2-ΔCt test)·(2-ΔCt control)-1. Total RNA was extracted from 20 mg kidney cortex using the RNeasyRats were anesthetized with pentobarbital (40 mg/kg body weight i.p.). The right kidney was isolated and after a midline laparotomy, the right renal artery was cannulated through the superior mesenteric artery. The kidney was immediately perfused with a Tyrode’s solution containing 6% albumin and a mixture of L-amino acids. After the microdissection procedures were completed, the renal artery perfusion pressure was set to 100 mm Hg. The tissue surface was continuously superfused with a Tyrode’s solution containing 1% albumin. After a 20-minute equilibration period, an afferent arteriole was chosen for study, and baseline diameter was measured. After the control period, the afferent arteriole was constricted with phenylephrine and the endothelium-dependent relaxation was assessed using increasing concentrations of acetylcholine (0.01–10 μm). The afferent arteriole diameter changes to acetylcholine were monitored for 3 minutes at each concentration. Steady-state diameter to acetylcholine was attained by the end of the second minute, and the average diameter at the third minute was used for statistical analysis. 3, 4.6 KCl, 1.2 KH2PO4, 1.2 MgSO4, 1.8 CaCl2, 11.0 glucose, Sigma) at pH 7.4 and 37 ºC. Under no flow conditions, over a span of 18 min, the pressure within the vessel was increased at 10 mmHg increments from 20 to 65 mmHg. The vessel was then equilibrated at 65 mmHg for 30 min and remained at that pressure for the duration of the experiment. Lumen diameter measurements were acquired and logged using the MyoView 1.2P user interface. The control lumen diameter was calculated as the mean diameter during the last 15 min of the 30 min equilibration. Diameter of the constricted vessel was calculated as the mean during the last 2 min of 15 min following the addition of U46619. Following U46619 treatment, the mesenteric artery diameter responses to low (50 μL/min) or high flow (300 μL/min) were determined.Mesenteric artery segments were obtained from the rats and mounted between two cannulae in a pressure myograph system (Danish Myo Technology model 111P). The interior and exterior of the vessel were in oxygenated (95% O2/5% CO2) Krebs physiological salt solution  for repeated measures followed by a Duncan’s multiple range post hoc tests. An unpaired t-test was applied to compare the histological grading. A The findings of the present study demonstrate the anti-hypertensive effect of AR9281 in an angiotensin dependent model of hypertension. In addition to decreasing blood pressure, AR9281 decreased glomerular injury and renal inflammation. Endothelial dilator responses of the afferent arterioles and mesenteric resistance arteries were also improved in angiotensin hypertensive rats receiving AR9281. More importantly, these results provide strong evidence that besides lowering blood pressure the first-in-class sEHI, AR9821 has added renal and cardiovascular beneficial effects in angiotensin dependent hypertension. The additional anti-inflammatory actions, vascular endothelial and end organ protection provided by AR9281 makes this a promising pharmaceutical agent for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease.


Then, CAVI might reflect the proper change of arterial wall by antihypertensive agents. Arterial stiffness has been known to be a surrogate marker of arteriosclerosis, and also of vascular function. Pulse wave velocity (PWV) had been the most popular index and was known to be a predictor of cardiovascular events. But, it depends on blood pressure at measuring time. To overcome this problem, cardio-ankle vascular index (CAVI) is developed. CAVI is derived from stiffness parameter 1 blocker, doxazosin for 2-4 hours, Those results suggested that CAVI reflected the arterial stiffness composed of organic components and of smooth muscle cell contracture. Angiotensin II receptor blocker, olmesartan decreased CAVI much more than that of calcium channel antagonist, amlodipine, even though the rates of decreased blood pressure were almost same. CAVI might differentiate the blood pressure-lowering agents from the point of the effects on proper arterial stiffness. CAVI shows high value with aging and in many arteriosclerotic diseases and is also high in persons with main coronary risk factors. Furthermore, CAVI is decreased by an administration of αThis paper reviewed the principle and rationale of CAVI, and the possibilities of clinical applications, especially in the studies of hypertension.  The significance of arterial stiffness for the prognosis of cardiovascular diseases is nearly established -4. Arteret al. [et al. [1) [1 [In1980, Hayashi et al.  proposed al. [1) . The rat. [1) [1 -26.1-aderenoceptor blocker and α1-aderenoceptor blocker indicated that CAVI was independent of blood pressure at measuring time, and reflected not only organic stiffness, but also the functional stiffness composed of smooth muscle contracture [Especially, the studies using βtracture . This review described the principle of CAVI and reviewed the recent reports about CAVI, focusing on the roles of CAVI in hypertension research. 1.1)1, from ref.et al. [The CAVI reflects the stiffness of the whole arterial segment comprising the aorta, femoral artery and tibial artery  x ln(Ps/Pd) PWVwhere, Ps is systolic blood pressure, Pd is diastolic blood pressure, PWV is pulse wave velocity from the origin of the aorta to tibial artery at the ankle through the femoral artery, ∆P is Ps - Pd, ρ is blood density, and a and b are constants. Theoretically, blood pressure applied must be obtained at each every point from the origin of the aorta to tibial artery at the ankle. The problem is that the blood pressure is increasing from the origin of the aorta to the femoral artery, and is decreasing from the femoral artery to peripheral artery. Conveniently, mean blood pressure of the whole artery could be applied. In place of a mean blood pressure of the whole artery, blood pressure at the brachial artery was applied in CAVI. Thus, CAVI is originated from the stiffness parameter β = ln(Ps/Pd) . (D/∆D). D/∆D is calculated from PWV of some length of the artery and ∆P, in place of diameter change (D/∆D) . 2)et al. [There still remain several questions for CAVI. One is whether it is valid to apply Bramwell–Hill’s equation to the equation of the stiffness parameter β, which is essentially applied to some segment of the artery. Takaki et al.  providedNext question is that, the most conspicuous feature of CAVI is theoretical independence of the blood pressure at the time of measurement. However, this has to be proven, experimentally. Several reports -24 showe1 receptor blocker, metoprolol as shown in Fig. (2A) [We tried to solve this question using a selective βig. (2A) . When meThen, CAVI could be used to evaluate the effect of blood pressure control on the proper stiffness of arterial wall. 3)1)CAVI of healthy people in Japan without cardiovascular risk factors increases with aging from 20 to 70 years . CAVI ofet al. [As for coronary artery disease, CAVI increases as the number of coronary vessels with stenosis (>75%), increases . The cutet al.  also repet al. -31. et al. [Sairaku et al.  reported2)As for intima-media thickness (IMT) of carotid artery, several workers showed strong correlation between CAVI and IMT, but, plaque score showed much more stronger correlation with CAVI -30. The combination of CAVI and IMT might be a much significant predictor of cerebral thrombosis in highly atherosclerotic patients.3)As for chronic kidney disease, there were several reports that CAVI correlated with estimated glomerular filtration rate , 33. CAV4)CAVI was high in metabolic syndrome. And, body weight reduction improved CAVI in obese patients on metabolic syndrome as well as reduction of risk factors .5)CAVI was related with cerebrovascular accidents .6)CAVI is reported to be high in patients with diabetes mellitus , 38, 39.et al. [CAVI is not so closely related with hypercholesterolemia as with diabetes mellitus , 39, 54.et al.  reportedet al. , ezetimiet al.  and triget al.  were rep7)Weight reduction through diet and exercise therapy over a 3-month period decreased CAVI values, significantly . CAVI waCAVI was high in smoking group, and decreased by stopping smoking , 47 CAVI1,2). Above results might suggest that the CAVI could be a good maker of arterial stiffness, and also is a marker of controlling the coronary risk factors  [The factors regulating CAVI were composed not only of organic stiffness such as collagen or elastin, but also of smooth muscle cell contracture. Those were shown by the studies using αg.  . CAVI waCAVI was reportedly decreased by anesthesia, although not significantly . It is i2(PGI2) analogue with vasodilatory, antiplatelet and cytoprotective effects. Recently, Takahashi reported that beraprost sodium, PGI2 analogue, decreased CAVI without blood pressure lowering effect as shown in Fig. (3). [Beraprost sodium (beraprost) is active prostaglandin Iig. (3). .CAVI was correlated with flow-mediated dilatation of the artery . Those r2), and NO synthesis in endothelial cells, in addition to organic stiffness. Above these results support the idea that CAVI reflects the contracture of arterial smooth muscle cells controlled by cathecholamines, prostacyclin (PGI3.1)CAVI is not affected by blood pressure at the time of measurement , 24, 57.There were many papers reporting that CAVI showed high values in patients with hypertension , 54-56 TInterestingly, when sunitinib maleate, which is interferes with the growth of cancer cells and raises blood pressure as a side effect, was administered to a patient, the increase of CAVI was observed before blood pressure increased . This fi2)3). The decreasing rates of blood pressure by those agents are not necessarily be correlated with improvement rate of CAVI.Several papers reported the effect of antihypertensive agents on CAVI (Table (1)et al. reported that amlodipine decreased CAVI  [et al. reported that the decrease by amlodipine was a little, and not significant [Calcium channel blocker (CCB) is one of the most useful antihypertensive agents. However, it is known that some of CCB have the activating action of the renin-angiotensin system (RAS) or catecholamine system as an unfavorable characteristic. And, there are several types such as L-channel blocker type. T-channel blocker type and N-channel blocker type. Amlodipine is known to be a L-channel blocker type. Kurata 24 week) . Miyashinificant . et al. [4). But, CAVI was significantly reduced by efonidipine, but not by amlodipine. So, it is suggested that various types of Ca channel blockers had their own properties on arterial wall stiffness. Sasaki et al.  comparedIt is very interesting point whether CAVI can differentiate the effects of different types of calcium channel blockers or not.(2)et al. [Renin angiotensin aldosterone system is very important regulator of blood pressure. As for angiotensin II receptor antagonists (ARB), there were several reports. Telmisartan were reported to decrease CAVI . Uehara et al. . The bloAs for prognosis of the treatments for hypertension, angiotensin 2 receptor antagonists or angiotensinogen converting enzyme inhibitor is reported to have better effect on the prognosis of cardiovascular diseases than calcium channel blockers . The coi(3)Diuretics are known to decrease blood pressure, but may exacerbate insulin resistance. Real effects of diuretics on arterial wall stiffness have not been done. There were no reports available to obtain the conclusion.But, the combination of olmesartan and azelnidipine has advantages over the combination of olmesartan and thiazide with respect to CAVI in patients with moderate hypertension . It mighA tablet combining losartan and hydrochlorothiazide has been found to decrease CAVI . Both ag(4)Now, there were no reports available concerning the effects of α blocker, β blocker, and spironolactone on CAVI for long term. But, above data might suggest that CAVI might discriminate the effects of those antihypertensive agents on arterial stiffness in addition to blood pressure itself. It is almost established that CAVI is reflecting the arteriosclerotic change, and also smooth muscle cell contracture. Blood pressure control system were involving many factors such as cardiac output, arterial compliance and circulating blood volume. Among them, CAVI might be reflecting compliance. The analysis of the pathogenesis of hypertension and also the prognosis of the hypertension control might be more adequately evaluated with monitoring CAVI. CAVI may become useful index to evaluate the real effects of blood pressure control on the arteries.


The present review aims to summarize the existing evidence on NIRS and its potential clinical utility in different scenarios of critically ill patients.According to current critical care management guidelines, the overall hemodynamic optimization process seeks to restore macrocirculatory oxygenation, pressure, and flow variables. However, there is increasing evidence demonstrating that, despite normalization of these global parameters, microcirculatory and regional perfusion alterations might occur, and persistence of these alterations has been associated with worse prognosis. Such observations have led to great interest in testing new technologies capable of evaluating the microcirculation. Near-infrared spectroscopy (NIRS) measures tissue oxygen saturation (StO Tissue hypoxia, as results of oxygen supply-demand imbalance at the cellular level, defines circulatory insufficiency or shock. Maintained over time, this situation might lead to cellular and organ dysfunction, organ damage, and the ultimate death of the individual. In our daily clinical practice, hemodynamic resuscitation of shock states aims to restore global tissue oxygenation markers, such as venous saturations  or lactate. Including these endpoint variables in the management of shock has led to remarkable improvements in the survival of critically ill patients . HoweverEvaluating the microcirculation in the critically ill patients has been associated with more than a few technical problems, which have delayed their use at the bedside. In addition to the technical limitations, a clinically relevant issue has been finding the right place to monitor. Since any used technology can only assess the microvascular bed of a given sampled tissue, it is necessary to choose accessible territories and yet sufficiently representative of the whole body wellness. Currently, there are several technologies available for the evaluation of the microcirculation , which cin vivo tissue oxygen provision and utilization. Since then, many studies in humans, along with the development of portable, noninvasive NIRS systems, account for the growing interest in this technology . On the other hand, ReO2 reflects the Hb resaturation, and this will directly depend on blood inflow and capillary recruitment after the hypoxic stimulus. ReO2 has been named as a reflection of endothelial function; however, several observations have also correlated ReO2 to perfusion pressure [2 seems to be derived from the interaction of perfusion pressure and endothelial integrity. In its recovery, absolute StO2 may temporarily raise the above previous baseline values, indicating postischemic vasodilation and capillary recruitment, also known as reactive hyperemia . The lack of standardization of the VOT has led to great difficulties when trying to compare results from different studies. This fundamental issue represents an important limitation of the test, along with the variety of sampled depths and sites used to measure the StO2 response to ischemia [2 value is achieved seems to minimize inter-individual variations, thus homogenizing ReO2 values for their comparison. Future consensus should also be applied to the location and depth of measurement of StO2 [Different VOT methodologies have been described, some of them aimed at maintaining a fixed time of ischemia (3–5 minutes), and some of them sought for an ischemic threshold  the activation of the sympathetic nervous system causes blood flow redistribution from the periphery to the central compartment, through vasoconstriction in certain territories, in order to maintain an optimal perfusion of vital organs . This coovolemia .2 to global variables of flow and oxygen delivery [2 was a better discriminator for survivors to hemorrhage than mixed venous oxygen saturation (SvO2), blood lactate, and base deficit. In human models of central hypovolemia in healthy subjects, StO2 and the tissue hemoglobin index (THI) fall have been shown to detect decreases in blood volume equivalent to 400–500 cc, even before the onset of tachycardia or hypotension [2 has also been tested for its utility in guiding intravascular volume optimization. On that behalf, Cohn et al., in a prospective randomized pilot study in patients undergoing elective colorectal surgery, analyzed the impact of a standard versus restrictive fluid approach on tissue oxygenation and development of complications [2 values, suggesting that StO2 would be a useful parameter for guiding fluid administration during surgery, ensuring tissue wellness, and avoiding unnecessary fluid overload, which has repeatedly been associated to higher morbidity derived from surgery [This hypothesis was initially tested in experimental conditions, in animal models of hemorrhagic shock. First observations correlated StOdelivery –30, suggdelivery , in a protension –34. In aications . The aut surgery , 37.2 correlation to parameters of flow and oxygen delivery has been also verified [2 has repeatedly demonstrated its prognostic value in this patient population. Low StO2 values during the initial approach to these patients have been associated with larger transfusion requirements [2 values, dynamic variables derived from the VOT have also shown their prognosis in trauma patients [2 were independently associated with the need for early interventions . In this observational study, DeO2 was superior to absolute StO2 for predictive purposes. Once again, this association was independent and more sensitive than other physiological variables, such as heart rate or blood pressure. Despite the cumulative evidence on the prognostic value of StO2 in trauma, with its potential use for early identification of at-risk patients, to this day, there is a lack of prospective studies exploring the usefulness of StO2 in trauma resuscitation algorithms, either as a trigger for interventions or as a target in the hemodynamic resuscitation process.In trauma patients, StOverified . Furtherirements –41, incrirements , multiorirements , 43, andirements . Importairements , 41. In patients , 46. In patients  demonstr2 has been also widely explored in patients with severe sepsis and septic shock. While absolute StO2 values have shown robust prognostic implications in trauma patients, in septic conditions this association appears to be more complex [2 values than healthy subjects, there is a huge overlap between these populations [2. Nevertheless, dynamic StO2 VOT-derived variables have yielded much more promising results than the absolute StO2 in terms of prognosis.The value of StO complex , 47, 48.ulations . These oulations . The low2 response to the VOT in sepsis, and the magnitude of such alteration has been directly correlated with the development of organ failure, ICU length of stay, or even mortality [2, represented by lower deoxygenation rates, have been associated with poor prognosis. Since DeO2 reflects local oxygen consumption, it seems reasonable to hypothesize that patients with limited oxygen extraction will develop higher degrees of organ failure [2. Regarding the ReO2 slope, it is also diminished in septic patients when compared to healthy subjects [2 decreased slope has also been correlated to the severity of the episode, and some studies have even demonstrated association with mortality [2 value but the persistence of alterations in ReO2 during resuscitation has been associated with worse prognosis [Several authors have reported alterations in the StOortality , 23, 49  failure , 23. Thi failure . Regrettsubjects , 23, 48.ortality , 22, 48.rognosis .2 has consistently demonstrated its prognostic value in critically ill patients, there is still so much to explore in terms of its clinical applicability at the bedside. One of the major issues that needs to be faced is where to incorporate StO2 in hemodynamic resuscitation algorithms and, of course, testing whether StO2 incorporation is associated with improvement in outcomes.Although, as we have exposed, StO2 was initially explored in its ability to early detect hypoperfusion, and previously to monitor parameters that require invasive procedures or laboratory analysis. Some authors explored the correlation of StO2 with parameters of global oxygenation, such as central venous oxygen saturation (ScvO2) [2 values  specifically predict extremely low ScvO2 values [2 variables to detect these situations of global hypoperfusion is considerably low, and therefore the absolute StO2 value has been proposed as an initial tool to rapidly and noninvasively detect hypoperfusion states, but only while other more sensitive variables are not available [Due to its condition of noninvasive continuous measurement of regional oxygenation status, StO (ScvO2) –55, demo2 values , 51, 52.vailable , 51, 52.vailable , 51.in vivo videomicroscopy studies, Lima et al. recently found, in a population of septic patients, that alterations in StO2 values at the end of the Early Goal-Directed Therapy (EGDT) were associated with higher degrees of organ failure and mortality [2 parameters and prognosis despite macrohemodynamic normalization [2 to the resuscitation algorithm. The fact that whether StO2 might be used instead of or complementary to current global tissue oxygenation endpoints, such as ScvO2 and lactate, deserves further investigation. In a small pilot study, Nardi et al. [2 measured at three different locations as an endpoint parameter for resuscitation in septic patients. In their protocol, once ScvO2 values were normalized according to the Surviving Sepsis Campaign guidelines, StO2 goals were pursued in the treatment group. The authors found no benefit in the inclusion of StO2 in the resuscitation algorithm. However, the small sample size, the use of the absolute value of StO2 instead of dynamic parameters (DeO2 or ReO2), and the fact that a large percentage of patients in the treatment group did not even normalize the endpoint ScvO2 values might account for the lack of differences observed in the evolution of the patients.Cumulative evidence on the association between microcirculatory alterations persistence, despite normalization of macrohemodynamic variables, and poor prognosis  has led ortality . Some otlization , 23. Unfi et al.  attempte2 to our current macrohemodynamic approach to resuscitation. This major limitation would be applied, to date, to every single regional or microcirculatory monitoring system. One might conclude that prospective studies are needed to evaluate the usefulness of adding StO2 may have utility in other clinical scenarios in critical care. Continuous StO2 monitoring has shown encouraging results in cardiovascular performance challenges, as in weaning from mechanical ventilation [2 within a 30-minute spontaneous breathing trial discriminated patients who would succeed in from those who would fail the disconnection from mechanical ventilation process [2 as a monitoring system for detecting limited cardiovascular reserve.In addition to its potential application in shock states, the StOtilation . In a re process , support2 values and/or interpretation [Several limiting factors deserve mention, as they might interfere in StOretation , 59: (a)retation . We alreretation . Finally2 and its dynamic variables derived from the VOT have demonstrated their prognostic value in several critical scenarios. The lack of randomized controlled trials analyzing their inclusion in the resuscitation process is the main constraint to the use of this technology at the present time. In addition to its potential value in resuscitation, StO2 variables might be useful in other clinical settings, where cardiovascular performance needs to be challenged, such as weaning from mechanical ventilation.In conclusion, StO


Obesity is a complex and multifactorial disease, has an inflammatory pattern and is associated with higher cardiometabolic risk. There are recent reports associating an elevated C-Reactive Protein (CRP) with a microscopic endothelial dysfunction. The objective is to evaluate if there is an association between serum levels of CRP and endothelial function in women with overweight/obesity, as well as the correlation between CRP and anthropometric variables.This is a cross-sectional study that analyzed secondary data from patients treated in an institution of tertiary education, as part of the weight excess and cardiometabolic disease survey. The study included patients with overweight/obesity who had CRP and endothelial function tests already made and inserted into the survey database. The endothelial function was evaluated by: reactive hyperemia test (endothelium-dependent vasodilation). All tests were recorded and later analyzed by the same echocardiographer who performed the examination. Statistical analyses were realized in the Statistical Package for the Social Sciences (SPSS) version 14. It was considered statistically significant a P value < 0.05.2, median of CRP of 2.59 mg/L and flow-mediated dilation (FMD) of 8.75% ± 5.22%. There was no correlation between CRP and endothelial dysfunction in this population . No correlation was observed between CRP and BMI. There were no differences of endothelial dysfunction variables and CRP in groups in use or not of medications .This study included 47, nonsmoker women. with a BMI of 32.37 ± 5.06 kg/mThere was no association between CRP and FMD and this can suggest that it is possible that the level of eNOS dysfunction associated with increased CRP is not enough to lead to macroscopic changes and harm vasodilation. Obesity inflammatory state has been a subject of great interest due its importance in the development of various associated pathological conditions, such as endothelial dysfunction .This parainflammation and the oxidative stress produced by an excess of adipose tissue can lead to endothelial dysfunction by different ways , 10-14. This study tested whether plasma C-reactive protein levels are associated with impaired endothelial function, measured by brachial artery flow-mediated dilation (FMD). Secondarily, we tested whether CRP levels are associated with anthropometric variables.This cross-sectional study included women with overweight or obesity treated in an ambulatory of obesity by a multidisciplinary team. These patients had CRP levels measured and endothelial function evaluated already made and entered into the database of a “clinical and epidemiological aspects of obesity” survey, in progress. Patients with CRP ≥ 10 mg/L, in use of anti-inflammatory drugs, or with clinical evidence of acute inflammation were excluded of this study.After signing the informed consent form, patients were evaluated by interview and physical examination that included measures of body mass index (BMI), waist circumference (WC) and blood pressure (BP).CRP dosage was performed preceding endothelial function test, through Nephelometry method in a clinical laboratory with technique quality certification established.Endothelial function assessment was performed by an echocardiographist physician by high-resolution ultrasound. After 30 minutes rest, the subjects had been lying in supine position for 10 min in a stable-temperature room and then was performed a baseline measurement of brachial artery diameter in a longitudinal section (2 - 15 cm above the elbow). Reactive hyperemia was induced by occluding arterial blood by using a sphygmomanometer insufflated to 50 mmHg above the systolic pressure. After 5 min, the cuff was released. The arterial flow velocity was measured by a pulsed Doppler signal at a 60-degree angle to the vessel during the resting scan and for 15 s after the cuff deflated. The artery was scanned for 30 s before and 120 s after cuff release , 17.Every patient had at least 4 hours of fasting before the exam. The mean and median of fasting time was 5.05 ± 1.4 and 4.5 hours, respectively.All the exams was recorded and analyzed by the same ultrasonographer who performed the exam and who did not know the CRP levels of the patients.The brachial artery diameter was measured from the anterior to posterior wall, with reference to the line between media and adventitia layers (“M line”). The mean diameter was calculated from measurements of three cardiac cycles coincident with the R wave on the electrocardiogram. Diameter changes were derived as percentage changes relative to the first scan. The blood flow was obtained multiplying the Doppler-pulsed blood velocity measurements by heart rate in the different stages of exam .It was considered predictive variables of endothelial function: Flow-mediated dilation (FMD); mean flow velocity during reactive hiperemia (FMV); and absolute change in flow-mediated dilation (ΔFMD).Statistical analysis was performed in the SPSS software version 14. Quantitative variables were expressed by mean ± standard deviation and by median and interquartile interval if the variables had a skewed distribution. Comparisons of two means or medians were performed by t-student test for independent samples and Wilcoxon-Mann-Whitney, depending of variable distribution profile. Correlations were performed by Pearson test for parametric variables and Spearman test for nonparametric variables. The statistical significance was defined by two-tailed test and P value < 0.05.2 and waist circumference of 104.8 ± 10.64. CRP median was 2.59 mg/L (interquartile range = 4.26 mg/L) and FMD mean of 8.75% ± 5.22% and FMV mean of 55.92 ± 24.84 cm/s.Among, 70 patients included in the survey, 47 women met the requirement of having CRP levels and endothelial function test in the database. Nine of them were excluded due CRP ≥ 10 mg/L. sr = 0.08, P = 0.64). There was a trend for positive association between CRP and BMI  and between CRP and WC .There was no correlation between CRP and FMD (Dichotomizing groups by CRP median (2.59 mg/L), there was no statistically significant differences on FMD (P = 0.6), FMV (P = 0.2) and ΔFMD (P = 0.4), as seen in Serum CRP levels, FMD, FMV and ΔFMD were not different among users or non-users of antihypertensives, lipid-lowering and hypoglycemic agents  and 4.C-Reactive Protein is an important cardiovascular risk marker and several studies have attempted to demonstrate that this is an active molecule and relevance in the process of Endothelial Dysfunction.The population of our study was exclusively female, nonsmoker, mostly obese with abdominal adiposity and on medications used to treat conditions of high cardiovascular risk . The CRP median was 2.59 mg/L, corresponding to a band of moderate cardiovascular risk. Considering the risk profile of this study population, one would expect higher levels of CRP, as happened in a study by Visser et al that included 8,678 women and demonstrated that obese subjects had CRP 6.21 times higher than those of normal weight . In the This study also demonstrated that there was no correlation between CRP and endothelial dysfunction in overweight and obese women. It is somewhat surprising and disagrees with what has been suggested by recent literature. Hein et al demonstrated in animal model that CRP leads to uncoupling of endothelial nitric oxide sintase (eNOS) and promotes oxidative stress . Two othr = 0.85, P = 0.004) [Other endothelial function variables were tested in this study, such as mean speed flow-mediated (FMV) and none of them were associated with CRP. However, a study in nine men, with similar clinical characteristics of our study population, demonstrated a strong positive correlation between CRP and the decline of brachial blood flow during infusion of a inhibitor of eNOS (= 0.004) , suggestThere was no difference of CRP between users or nonusers of lipid-lowering agents. The current literature suggests that statin use leads to a reduction in serum levels of CRP . PRINCE This study also has not observed show differences of endothelial function variables between users or nonusers of antihypertensive, hypoglycemiant and lipid-lowering agents. It is an attractive field of research, and recent studies indicate that use of statins improves endothelial function by increasing the expression of eNOS and thereby increasing nitric oxide bioavailability . RECIFE Therefore, the present study showed no association between CRP levels and endothelial dysfunction assessed by flow-mediated dilation and a trend of association between CRP and BMI and WC. The lack of association between CRP and endothelial function in overweight and obese women brings new questions and hypotheses: 1), it is possible that the level of eNOS dysfunction associated with increased CRP is not enough to lead to macroscopic changes and compromise vasodilatation; 2), considering that the increase in CRP was moderate and that endothelial function was considered within normal limits, maybe they were really a population of obese with no impaired vascular function enough to change an imaging method of assessing subclinical atherosclerosis. Thus, this study open new perspective for studies evaluating similar population and that reproduce the same methodology analysis of endothelial function.