The nephron number is thought to be associated with the outcome of chronic kidney disease (CKD). If the nephron number can be estimated in the clinical setting, it could become a strong tool to predict renal outcome. This study was designed to estimate the nephron number in CKD patients and to establish a method to predict the outcome by using the estimated nephron number.The hypothesis of this study is that the estimated nephron number can predict the outcome of a CKD patient. This will be a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD patients aged over 14 years who have undergone a kidney biopsy. From January 2011 to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to the National Hospital Organization of Japan. The primary parameter for assessment is the composite of total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year. The nephron number will be estimated by the glomerular density in biopsy specimens and the renal cortex volume. This study includes one sub-cohort study to establish the equation to calculate the renal cortex volume. Enrollment will be performed at the time of the kidney biopsy, and the data will consist of a medical interview, ultrasound for measurement of the kidney size, blood or urine test, and the pathological findings of the kidney biopsy. Patients will continue to have medical consultations and receive examinations and/or treatment as usual. The data from the patients will be collected once a year after the kidney biopsy until March 2016. All data using this study are easily obtained in routine clinical practice.This study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. Furthermore, this is the first prospective study to examine whether the nephron number predicts the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice.UMIN-Clinical Trial Registration, UMIN000004784. Previous studies suggested that chronic kidney disease (CKD) is one of the most important risk factors for cardiovascular disease among known other risk factors, such as diabetes, hypertension, hyperlipidemia, obesity, smoking, and lifestyle ,2. FurthLow birth weight (LBW) is a risk factor for the progression of kidney diseases in compliance with the Barker hypothesis -9. In paThis PRONEP study was designed to establish a method for predicting the renal outcome based on the nephron number estimated in patients with CKD that can be easily used in routine clinical practice. This is the first prospective study to examine whether the nephron number can predict the outcomes of CKD patients. The nephron number will be estimated by the glomerular density in biopsied samples and the volume of the renal cortex, in which glomeruli exclusively exist. In addition, this study includes one sub-cohort study to develop an equation to calculate the renal cortex volume, because there is currently no method to measure it in the typical clinical setting.The nephron number, which is estimated from the glomerular density in kidney biopsy specimens and the volume of the renal cortex, can predict the outcome of a CKD patient Figure .In a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study, approximately 600 patients with CKD who undergo a kidney biopsy for their diagnosis and will be enrolled from January 2011 to March 2013. These CKD patients will be recruited from 10 hospitals belonging to the National Hospital Organization of Japan. The hospitals participating in this study are spread throughout Japan . This protocol was submitted to the UMIN-Clinical Trial Registration on January 1, 2011, and its unique trial number is UMIN000004784.Participants will be eligible for inclusion if they (1) have CKD according to the K/DOQI CKD Guidelines , (2) areIn this study, the estimated glomerular filtration rate (GFR) will be calculated using the following formula, which was developed for Japanese subjects :In this study, all attending CKD patients will undergo a needle biopsy of the kidney for their diagnosis. Therefore, although this protocol determines the exclusion criteria by the patients' CKD stage, most of the attending patients should not be in stage 4 or 5.Enrollment should be performed at the time of the kidney biopsy after informed consent, followed by permission to participate in this study, is obtained. All patients will undergo: 1. a medical interview, 2. an ultrasound to measure the kidney size, 3. blood or urine tests, 4. a kidney biopsy to investigate the pathological findings data at the enrollment is shown in Figure In the medical interview, the question about birth weight may be difficult to answer, especially for elderly patients. If the subjects cannot answer the question about their birth weight, the question will be changed to whether their birth weight was normal  or not, because LBW is defined as a newborn birth weight of less than 2500 g by the World Health Organization.Patients will continue to have medical consultations and will receive examinations and/or treatment as usual. We will not direct physicians to prescribe any preferred drug, examination, or to give any specific medical advice. We will also not ban the physicians from prescribing any particular drugs.The data for patients will be collected once a year after the kidney biopsy, and will be followed until March 2016. We will permit the data collected during the antero-posterior three months of the day of the kidney biopsy to be analyzed as well. The data collection plan is shown in Figure In this study, a cerebro-cardiovascular event was defined as an acute myocardial infarction, angina pectoris, and cerebro-vascular diseases. In addition, in order for a myocardial infarction to be reported in this study, it has to fulfill at least two of the following: (1) chest symptoms, (2) ECG changes, (3) elevated cardiac enzymes. Angina is defined as the presence of ECG abnormalities with chest symptoms and the need for catheter or surgical treatment. Furthermore, a cerebro-vascular event is defined as cases with neuropathy lasting more than 24 hours continuously and with proof of a causative lesion by CT scan or MRI . If no data is tracked during the follow-up, the reason will be recorded .The primary parameter that will be assessed is the composite of the total mortality, renal death , cerebro-cardiovascular events , and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year.http://www.mhlw.go.jp/english/database/db-hw/vs01.html. The rate of LBW may be higher in the CKD patients than in normal subjects. We assumed that the rate of LBW would be 0.095 in the CKD patients in this study. This study is planned with an accrual interval of 2 years, and additional follow-up after the accrual interval of 3 years. The event rates were assumed to be 0.1 in the normal birth weight group and 0.2 in the low birth weight group by several studies [This study aims to predict the outcome of chronic kidney disease using the estimated nephron number. We assumed that the time from entry to event will be independently and exponentially distributed. The planned sample size was based on a two-tailed log-rank test with the significance level set to 0.05, and the power level set at 0.80. The ratio of low birth weight infants per total newborns in Japan was reported to be 0.086 in 1960 and 0.097 in 2007. During this period, the rate has been consistently increasing  studies . The req studies . AssuminWe will record the major and the minor axis of the longitudinal plane, and the diameter of the transverse plane of the kidney by ultrasound examination as shown in Figure As a general rule, sections stained by PAS or PAM-HE will be used for the measurement of the glomerular number and the length of the cortex Figure . At the Based on previous studies, we will first assume that there is 31% volume shrinkage in the paraffin-embedded specimens due to fixation in formalin ,23,24. Tformalin ,17,23,24The total number of glomeruli is estimated as follows:The formula of the spherical volume can be derived using integral calculus, i.e. disk integration to sum the volumes Similarly, the average area of the observed glomeruli on one section in the biopsied specimen is estimated as follows:o(5 μm). We observe only circles parallel to the section of this solid, whose height is defined as 2 h. Considering a 2 h-high cylinder whose volume is equal to this solid, the cylindrical base area is equal to the average cross-sectional area of this solid cut at random parallel to the base of the solid  is calculated as:Ab is the internal diameter of the biopsy needle and La+b is "a + b" in Figure Where dglom/cortex (Volume fraction of glomeruli/cortex) is equal to AFglom/cortex (Area fraction of glomeruli/cortex on the section).VF s is the number of observed glomeruli in a biopsied specimen.Where Ntotal) was calculated as:Finally, the total number of glomeruli . The primary parameter for assessment is the composite of the total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. We will use a Cox proportional hazard model for the analysis. We will check for confounders, interactions and multicollinearity among the independent variables. The final models will be adjusted by all significant variables, as well as confounders and other baseline covariables judged to have clinical importance. The secondary parameter is the rate of eGFR decline per year. A multivariate regression analysis will be used for the analysis. The significance level on both sides in the hypothesis testing will be set at 0.05. The analyses will be performed using the SPSS statistics software program version 19.0. (IBM Corp.)Some of the participating patients will undergo MRI to measure the cortex volume of their kidney, because MRI is the safest procedure and has highest resolution to separate the cortex from the medulla, as reported in other studies ,17. HoweWhile MR imaging sometimes does not provide sufficient contrast for the soft tissues, in many cases, it is possible to distinguish the cortex and the pith of the kidney by tomography. Therefore, we will image the entire kidney with axial MRI, and calculate the renal cortical volume by multiplying the slice thickness and the slice number of the kidney which we measured on each axis tomogram. For this purpose, we found that an MR image that provided the best contrast between the cortex and medulla of the kidney was obtained using the following sequence: 2D Turbo FLASH TR = 1570 ms, TE = 2.74 ms, TI = 1000 ms, Flip Angle = 15°, Fat sat (-). We will manually draw the ROI in the kidney, and the regional choice in the axial image of the kidney will be determined by specialized radiological technologists .The calculations used for the renal cortical and whole kidney volume are as follows:Chronic kidney disease is regarded as public health problem throughout the world . In thisAs mentioned above, although it is likely that estimating the nephron number will be useful to predict the outcomes of CKD patients, it is currently not possible to determine the nephron number in living subjects. It was reported that the glomerular density is correlated with the prognosis of IgA nephropathy . AlthougFor this purpose, 3 obstacles will have to be overcome. First, it is not possible to measure the renal cortex volume in the normal clinical setting. To develop a method for estimating this parameter, a one sub-cohort study is being performed. MRI can differentiate the cortex from the medulla because of its high resolution. Other studies also evaluated the total nephron number of dog kidneys or human donor kidneys by the cortex volume measured by MRI ,17. HoweIn this study, we aim to establish a method to predict the outcome of CKD patients at the time of their kidney biopsy. Therefore, the data collected during the follow-up period will be restricted Figure . BecauseThis study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. In addition, this study is the first prospective study to examine whether the nephron number can predict the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice.This study is being conducted in accordance with the "Ethical Guidelines for Clinical Studies"  and the "Ethical Guidelines for Epidemiological Studies" . All medical professionals involved in this study must comply with these ethical standards. All subjects will provide informed consent to participate in the study at the time of the kidney biopsy.This trial was approved by the Committee on Ethics in Human Research of National Hospital Organization Chiba-East National Hospital in December 2010 (No. 19).The authors declare that they have no competing interests.TI: Principal investigator; the conception, design of the study and the writing of the manuscript draft; TN: statistical expertise; HI, HF, RN: developed the methodology to be used for the imaging analysis by MRI and ultrasound; TI, YA, MY, MN, KY, OS, TY, RK, TY, TK, MN: participated in the design and co-ordination of the study; HK: developed the methodology to be used for the pathological analysis; TK, AS; critical review of the manuscript. All authors read and approved the final manuscriptThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/13/11/prepub


Background. The incidence of hypertension in the Western countries is continuously increasing in the elderly population and remains the leading cause of cardiovascular and morbidity. Methods. we analysed some significant clinical trials in order to present the relevant findings on those hypertensive population. Results. Several studies  have demonstrated the benefits of treatment  in aged hypertensive patients not only concerning blood pressure values but also the other important risk factors. Conclusion. Hypertension is the most prevalent cardiovascular disorder in the Western countries, and the relevance of receiving pharmacological treatment of hypertension in aged patients is crucial; in addition, the results suggest that combination therapy—nitrendipine plus enalapril—could have more benefits than those observed with the use of nitrendipine alone. Also population aged 80 or older is increasing; the prevalence of hypertension in this group of people is above 60% and continues to grow. It is well known that hypertension is  (45.4%) . It is e (45.4%) , the genSystolic Hypertension in Europe trial (Syst-Eur), where our group has actively participated, clearly proved the benefits of hypertensive treatment versus placebo, in contrast to the nihilistic attitude to leave the disease to itself. The significant results of the Syst-Eur trial are based on the research and the ten-year followup of 4,227 patients from 23 European countries. The protocol of this trial has been described in detail before [However, the results of the l before . In concP = 0.05) compared to the group treated with placebo.Also, it is well-known that life expectancy is rising around the world which is related to an increased risk of developing dementia; this is becoming a major public health problem. The Syst-Eur study showed that randomized patients actively treated presented a lower incidence of dementia up to 50% (from 7.7 to 3.8 cases every 1000 patients/yr) , which was designed to provide a clear, definitive, and scientific answer to the treatment of hypertension in individuals older than 80 years.On the other hand, several observations suggested that calcium antagonists could have a specific neuroprotective effect. It is well known that both in vascular and mixed or degenerative dementias the values of the minimental state examination (MMSE) are less decreased in patients treated with nimodipine than in those treated with placebo. Brain aging is accompanied by alterations of intracellular calcium regulation, which leads to several cellular disorders, resulting in cellular death. Disorders of calcium homeostasis are related to the brain's aging process and the Alzheimer's disease. Antihypertensive treatment and reduction in blood pressure levels decrease the risk of developing dementia in aged patients, which is an important finding for the public healthcare system; calcium antagonists (nitrendipine and nimodipine) can have a specific neuroprotective effect. Important advances have been achieved relating physiopathological, pathogenetic, and therapeutic mechanisms of arterial hypertension. However, few studies have been made until now including the treatment of hypertension in patients aged 80 or older. These significant results led the researchers to investigate whether the benefits of the Syst-Eur trial could be extrapolated to patients aged 80 or older. However, empiric therapy is not adequate to this important pathology. The question was the The adequate control of these patients is greatly important for the general practitioners, internists, geriatrists, and other specialists, since hypertension together with other chronic conditions such as diabetes, hypercholesterolemia, and obesity are the main pathogenetic factors of cardiovascular disease, which is today the first cause of morbidity and mortality in the Western countries. The risks and benefits of treating hypertensive patients were studied in the HYVET trial, in which our group participated actively. The pilot study was carried out in 1,283 patients and was supported by the British Heart Foundation. Three different therapies were designed: (1) no treatment; (2) low-dose diuretic-based regimen (hydrochlorothiazide 12.5–25 mg daily); (3) an angiotensin-converting enzyme inhibitor , following accurate inclusion and follow-up clinical criteria, and quality of results and procedures carried out according to protocol. The cases studied  were recruited from several European countries  , 8. ThisAround 5,000 patients were included in the study. In conclusion, HYVET trial demonstrated the benefits of reducing blood pressure values in patients aged 80 or older and provided clear evidences about the need to treat hypertension in this growing population; this has become very important in the clinical practice and therapeutic guides , 10. For2, 50.4%); dyslipemia, 31.3%; tobacco abuse 22.6%; diabetes, 19.8%, and in a lower incidence others such as known vascular disease, left ventricular hypertrophy, previous myocardial infarction, transient cerebral ischaemia, and so forth. Results showed a similar efficiency in the reduction of the cardiovascular disease with the calcium antagonist agents than with diuretics and beta blockers agents [At the beginning, physicians could choice the treatment with hydrochlorothiazide (HCTZ) or atenolol, and the possibility to add controlled-onset extended-release verapamil, if necessary. The protocol permitted an increase of the doses or the number of drugs until reaching values lower than 140/90 mmHg. A total of 16,602 patients were included in the study selected from 15 countries and 661 centres. The mean age of the patients was 65.6 ± 7.4 years. The main risk factors of the participants were overweight  a difficult access to the healthcare system, (2) the lack of symptoms of hypertension, (3) the side effects of the antihypertensive agents, (4) the presence of other risk factors , (5) the concomitance of other associated noncardiovascular diseases , and (6) the difficulty in adjusting dosage.Despite the therapeutic advances, uncontrolled hypertension is a growing problem in the developed countries and populations having easy access to the healthcare system. Unfortunately, not all the hypertensive patients receive treatment when the values of the diastolic blood pressure are 90–95 mmHg, specially, when only systolic blood pressure values between 140–160 mmHg are considered. Therefore, the aim to reach values ≤130 mmHg is still far away. This is a very important problem, since in hypertensive people brain alterations secondary to vascular diseases lead to intellectual impairment and a worse quality of life of these patients [The ACTION study  was carrHypertension is a very important disorder in aged people and is associated with higher risk of cardiovascular morbidity and mortality. The fact of reducing blood pressure values decreases the risk for cardiac death as well as neurological, metabolic, and musculoskeletal system sequelae in aged people. Therefore, the aim of the antihypertensive treatment must be to reduce cardiovascular risks and to maintain an adequate quality of life and good functional capacity in these patients.


It has been shown that administration of lacidipine markedly reduces systolic blood pressure in elderly patients with hypertension without increasing the incidence of cardiovascular events and total mortality. But in Korea, there were no available data about the effectiveness and safety of lacidipine.The goal of our study was to compare the effect of lacidipine and amlodipine besylate on sitting systolic blood pressure (SBP) and edema regression time as primary parameters, and sitting diastolic blood pressure (DBP) and tolerability as a secondary parameter in patients with hypertension.This was a prospective, randomized, open-label, noninferiority study in which patients received 14 weeks of treatment with either lacidipine or amlodipine besylate. Patients aged 55 to 80 years having uncomplicated, mild-to-moderate essential hypertension (SBP 140 to <180 mm Hg or DBP ≥90 mm Hg) and receiving no antihypertensive medications during the 2 weeks before randomization were randomly assigned to receive lacidipine or amlodipine. The incidence of adverse events was also assessed.P >0.05). Because the 1-sided 95% CI for the difference in mean SBP changes between groups (−4.18 to 0.72) was within the pre-specified lower limit (−5 mm Hg), lacidipine was considered noninferior to amlodipine. There were no differences in mean edema regression time and in mean DBP changes. These results were consistent in the isolated systolic hypertension subgroup analysis. The overall incidence of clinical adverse events was comparable between the 2 groups . The most common adverse events were headache and facial flushing  were included in the intent-to-treat analysis and randomly assigned to receive lacidipine (n = 162) or amlodipine besylate (n = 153); 286 patients were included in the per-protocol analysis  . There were no differences in demographic profiles between the 2 groups. Mean (SD) SBP changes at 14 weeks were −18.9 (12.7) mm Hg in the lacidipine group and −20.6 (12.4) mm Hg in the amlodipine group (Fourteen weeks of lacidipine treatment significantly reduced blood pressure in older Korean patients with mild-to-moderate hypertension. The efficacy of lacidipine was not inferior to that of amlodipine besylate and tolerability was comparable between the 2 treatment groups. ClinicalTrials.gov identifier: NCT00460915. Arterial hypertension is a major public health problem in developed as well as developing countries. It has been shown that adequate control of blood pressure could reduce cardiovascular morbidity and mortality. Changing patterns of blood pressure occur with increasing age. In elderly patients, systolic blood pressure (SBP) increases progressively with age, whereas diastolic blood pressure (DBP) increases until age 55 or 60 years then tends to decrease later in life. Hypertension in elderly patients is characterized principally by increased systolic blood pressure, predominantly isolated systolic hypertension (ISH), in contrast to the patterns in young adults.To date, many studies have been conducted to evaluate the effect of various antihypertensive drugs in elderly patients with hypertension; however, in many of these studies, only limited subgroup analyses of patients with either systolic or diastolic hypertension were performed,Lacidipine is a third-generation CCB in the dihydropyridine group. According to the The Systolic Hypertension in the Elderly: Lacidipine Long-term StudyThis was a Phase IV, 14-week, prospective, randomized, open-label, noninferiority clinical trial conducted at 13 sites in Korea. Patients were enrolled and randomized from February 2007 to August 2009, and the randomized patients were followed until January 2010. The study protocol was approved by both national and regional review boards. This study was conducted in accordance with the Declaration of Helsinki/Good Clinical Practice Guideline and its amendments.This study was conducted in Korean adults aged between 55 and 80 years who had uncomplicated, mild-to-moderate essential hypertension .1c] >8.0%), a history of metabolic acidosis or diabetic ketoacidosis, cancer, known hypersensitivity to CCBs, alcoholism, or other drug addiction.Patients were excluded from this study if they had severe hypertension (SiSBP ≥180 mm Hg), secondary hypertension, a history of myocardial infarction or unstable angina pectoris, congestive heart failure, anemia (hemoglobin <10.0 g/dL), renal disease (serum creatinine concentration >1.4 mg/dL), coagulopathy, peripheral arterial disease, hepatic disease , uncontrolled diabetes  via telephone interview or clinic visit. Patients were randomly assigned, using a method of stratified block randomization by site, to receive either lacidipine or amlodipine besylate for 14 weeks.For the first 2 weeks, patients received either lacidipine 2 mg or amlodipine 2.5 mg in the morning. Patients achieving the target blood pressure level (SBP <140 mm Hg and DBP <90 mm Hg) at Week 2 were maintained at the initial dose. Patients who did not achieve the target blood pressure level were titrated to lacidipine 4 mg or amlodipine 5 mg. At Week 6 of drug treatment, patients who failed to reach the target blood pressure level were titrated to lacidipine 6 mg or amlodipine 10 mg, and those who still failed to reach the target blood pressure level at Week 10 were given thiazide diuretics  in addition. Concomitant use of statins or thiazolidinediones was permitted during a 14-week treatment period; however, dose increase or reduction was not allowed. Other medications or substances that may interact with the study drug were prohibited during the study period. These include other types of antihypertensive medications, psychotropic agents, oral steroids, daily nonsteroidal anti-inflammatory drugs, estrogen, and antioxidant vitamin supplements.1c, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, high-sensitivity C-reactive protein [hs-CRP], and chest radiography. Laboratory analysis was verified according to prespecified normal ranges accepted by the institutional review board at the study center and a central coordinating committee.At the initial screening visit, patients underwent a complete physical examination, medical history, laboratory assessment, baseline electrocardiography test, and chest x-ray. Laboratory analysis of collected blood samples was done at sites certified by the Korean Association of Quality Assurance for Clinical Laboratories and have regular follow-up of quality-care performance. Laboratory parameters included complete blood cell count, blood chemistry . Three consecutive recordings were taken, each separated by at least 5 minutes. The mean of the 2 higher blood pressure values was calculated and recorded. Patients were excluded from the analysis if they had a discrepancy of >5 mm Hg between any 2 mean blood pressure measurements or a discrepancy of >20 mm Hg between the blood pressure measurements in both arms.Edema regression time (ERT) was measured at the pretibial area twice during the study, at baseline (first visit) and 14 weeks after treatment.The primary efficacy end points were the mean change in SiSBP from baseline to Week 14 and the mean change in ERT from baseline to Week 14. The secondary efficacy end points were the incidence of adverse events in each treatment group and the mean change in SiDBP from baseline to post-treatment Week 14.At each study visit, tolerability was assessed by evaluating medical history and laboratory measurements. Investigators collected information about laboratory measurements and clinical adverse events (AEs) by asking each patient a standardized question. All AEs occurring after treatment until the follow-up visit or the last visit were recorded in case report forms and reported appropriately. Furthermore, all AEs were evaluated by the investigator for relationship to the study drug  and for strength of event . A clinical AE that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in significant permanent disability, or congenital anomaly was defined as a serious AE. If a laboratory or clinical AE was considered to be associated with the study drug and was serious enough to merit possible discontinuation of treatment, the clinical investigators determined if treatment with the study drug should be discontinued.To determine the compliance rate, the investigator counted all unused medications returned by patients at each visit. Compliance rate was calculated as follows:Compliance rate (%) = number of drugs actually taken / duration of prescription × 100.Information about compliance to study treatment was recorded in the case report forms, including a reason for missed dose, if applicable. Patients who had compliance rate <70% at more than 2 visits were withdrawn from the study.This is a noninferiority study. To demonstrate that the efficacy of lacidipine was not inferior to that of amlodipine, the lower bound of the 2-sided 90% (1-sided 95%) CI for the difference in SBP between the 2 groups after 14 weeks of treatment was calculated, and evaluated in comparison with the prespecified noninferiority margin of -5 mm Hg. If the lower bound of the 1-sided 95% CI is above -5 mm Hg, lacidipine would be assumed to be noninferior to amlodipine. The analyses of all other efficacy end points were performed at 2-sided significance level <5%.The efficacy analysis population for this study was the intent-to-treat (ITT) population and per-protocol (PP) population. The ITT population consisted of all randomized patients. Of the ITT population, those who did not complete the 14 weeks of treatment had a compliance rate of <70% for 2 times or more, or had used a prohibited medication during the study were excluded from the PP population.The efficacy analyses were performed on both ITT and PP populations; and the primary efficacy analysis was performed using the PP population analysis. For imputation of missing data for Week 14 SiSBP, ERT, or SiDBP, the last-observation-carried-forward method was used. The safety analysis was performed on the ITT population.t test, and categorical variables were analyzed and compared between 2 groups using χP ≤ 0.05.Baseline characteristics were compared between the 2 treatment groups. Continuous variables were analyzed using the Student A total of 322 patients were enrolled in this study, and 317 of them provided written consent.Excluding 2 patients who failed the screening, 315 patients were included in the ITT population  and were randomly assigned to receive lacidipine (n = 162) or amlodipine besylate (n = 153) .1C.There was no significant difference in mean (SD) age between the lacidipine group (68.1 [6.1] years [range 56–83 years] and amlodipine group (67.1 [5.7] years [range 56–82 years]). There was also no significant difference between the 2 groups in sex . Baseline SiSBP and SiDBP were comparable between the treatment groups, with 152.1 (10.3) mm Hg and 90.6 (8.9) mm Hg in the lacidipine group and 151.9 (10.9) mm Hg and 90.7 (9.5) mm Hg in the amlodipine group, respectively . With reThere was no significant difference in the dropout rate between the 2 groups. Of 315 patients randomized, 29 (9.2%) were early discontinued from the study: 12 patients from the lacidipine group and 17 patients from the amlodipine group. There were 3 patients (1.9%)  in the lacidipine group and 3 patients  in the amlodipine group, who discontinued the study due to AEs. A total of 6 patients (1.9%) were discontinued due to noncompliance, and 11 patients (3.5%) were discontinued due to consent withdrawal. Thus PP population who completed the study according to the protocol contained 286 patients  .In older Korean patients with mild-to-moderate hypertension, both PP and ITT analyses were performed to assess the primary end point and to compare the therapeutic effect of lacidipine and amlodipine.The difference in change in mean SiSBP between the lacidipine and amlodipine groups was 1.7 mm Hg (95% CI -3.4 to 1.3). Because the 95% CI for the difference between groups was within the lower limit of -5 mm Hg, lacidipine was considered noninferior to amlodipine .P < 0.001) (P = 0.25)  . The dif = 0.25) .P < 0.001) (P = 0.95)  . The dif = 0.95) .P < 0.001) (P = 0.47)  SiSBP decreased significantly from baseline after 14 Weeks of treatment in the 2 groups  . The dif = 0.47) .P < 0.001) (P = 0.74) (Mean (SD) SiDBP decreased significantly after 14 weeks of treatment in the 2 groups  . The dif = 0.74) .The difference between the 2 groups in SiSBP response rate did not reach statistical significance, with 73.5% of patients (119 out of 162) in the lacidipine group and 78.4% (120 out of 153) of those in the amlodipine group achieving this end point. The difference between the 2 groups in SiDBP response rate also was not significant, with 81.5% of patients (132 out of 162) in the lacidipine group and 83.7% of patients (128 out of 153) in the amlodipine group achieving this end point .P < 0.001 vs baseline)  .P > 0.05).The changes in ERT from baseline to Week 14 are presented in the P = 0.36), SiSBP , SiDBP , ERT , and hs-CRP .The number of patients who had ISH (SiSBP ≥ 140 mm Hg and SiDBP <90 mm Hg) was 60 in the lacidipine group and 58 in the amlodipine group . No significant difference between the 2 groups was observed in baseline clinical and laboratory characteristics. There was no significant difference between the 2 groups in mean (SD) age , SiDBP , and ERT .There was no significant difference between the 2 groups in the blood pressure-lowering effect from baseline to Week 14 . There wP > 0.05).There was no significant difference between the 2 groups in the rate of clinical and laboratory AEs . The ratThe most common drug-related AEs were headache (n = 3), facial flushing (n = 2), and dizziness (n = 2) in the lacidipine group, and headache (n = 6), facial flushing (n = 5) in the amlodipine group. In addition, 1 patient in the lacidipine group and 5 patients in the amlodipine group reported low extremity edema. Cardiovascular system, general, and skin AEs were comparable between the 2 groups, and no significant difference between the 2 groups in the rate of other AEs was observed.Laboratory analysis, including blood cell count and blood chemistry, showed no abnormal finding in either group, as verified by prespecified normal ranges accepted by the institutional review board at each study center and the central coordinating committee. The number of patients who required treatment discontinuation due to drug-related clinical AEs determined by investigators was 3 in the lacidipine group  and 3 in the amlodipine group .lacidipine and amlodipine besylate, this was the first prospective, randomized, head-to-head comparison of lacidipine and amlodipine in the older patients with hypertension. In patients with hypertension aged 55 years or older, the effectiveness and AEs of 2 CCBs, lacidipine and amlodipine, were compared. Overall, in this 14-week, multicenter, prospective, randomized, open-label, noninferiority clinical trial, lacidipine was found to be noninferior to amlodipine besylate in the reduction of SiSBP and SiDBP, SiSBP reduction rate, clinical and laboratory AE rate, and overall tolerability profiles in older Korean population with mild-to-moderate hypertension both in the PP and ITT analysis.According to a MEDLINE search using the terms SBP is an independent risk factor for stroke, coronary artery disease, heart failure, and renal failure.P<0.001).P = 0.03); however, the study failed to demonstrate that the use of amlodipine might prevent progression of atherosclerosis, compared with placebo.Antihypertensive medications that are effective in elderly persons include CCBs and diuretics. Amlodipine is widely used for the treatment of hypertension and angina pectoris and has a relatively fast onset of activity. The effectiveness of amlodipine has been demonstrated in many studies. The Valsartan Antihypertensive Long-Term Use Evaluation studyIn contrast, lacidipine, a third-generation lipophilic dihydropyridine CCB, has intrinsically slow onset of activity, which results in less reflex tachycardiaAccording to the subgroup analysis in patients with ISH, the reduction in SBP in the subgroup was consistent with that in the total population, but the reduction in DBP in the subgroup was relatively lower. Thus, it was concluded that in patients with ISH who have normal DBP, lacidipine is as effective and safe as amlodipine.There was also no significant difference between the lacidipine group and amlodipine group in ERT, indicating that the rate of edema, a most common AE associated with CCBs, in the lacidipine group was comparable to that in the amlodipine group.The rates of AEs, including those of the autonomic nervous system and cardiovascular system, dermatologic, and laboratory, were not significantly different between the 2 groups. In previous studies,Limitations of this study include a relatively small sample size, short duration of follow-up, and use of clinical blood pressure instead of 24-hour blood pressure monitoring.In this prospective study, we found that lacidipine was noninferior to amlodipine besylate in the reduction of blood pressure in older Korean patients with uncomplicated, mild-to-moderate essential hypertension or ISH. The safety and tolerability of lacidipine were consistent with those of amlodipine besylate.The authors have indicated that they have no conflicts of interest regarding the content of this article.


Hypertension prevalence is high in China, while patients’ levels of hypertension awareness, treatment and control are low. General practitioners’ knowledge and training relating to hypertension prevention may be an important related factor. We aimed to investigate general practitioners’ knowledge of hypertension prevention and potential training needs.A questionnaire survey was conducted among all general practitioners at five community health service centers selected by convenience sampling. A total of 160 questionnaires were distributed and 147 were returned (response rate 91.9%) The questionnaire included general information; 12 subjective questions on health promotion, education and training needs; and 19 objective questions in 5 domains  measuring knowledge of hypertension prevention and treatment.P = 0.003), and type of center . Most physicians (87.8%) reported being willing to attend training courses regularly and the preferred frequency was once every 2 ~ 3 months (53.5%). The preferred course was medical treatment of hypertension (82.3%) and the most favored training approach was expert lectures (80.3%).The major difficulties in health education practice for general practitioners were poor patient compliance (77.6%) and lack of medical consultation time (49.0%). The average accuracy rate of hypertension prevention knowledge was 49.2%, ranging from 10.5% to 94.7%. The factors associated with accuracy rate were physician’s education level (medical university vs. professional school, β = 13.3, The knowledge level of hypertension prevention is low among general practitioners in urban settings. Physicians working in community clinics where they participate in a series of teaching, assessing and evaluating systems for hypertension prevention perform better than those in general healthcare centers who lack specific training. Continuing hypertension education is urgently needed to ensure that physicians in general practice are aware of and adhere to the national hypertension prevention guidelines. Hypertension is a common chronic disease worldwide and a major risk factor for cardiovascular disease. National survey data suggest that the prevalence of hypertension in the Chinese adult population has quadrupled from 5% in 1959 to nearly 19% in 2002 . A crossLow awareness of hypertension prevention among Chinese physicians may be an important factor relating to increasing prevalence of hypertension. In China, general practitioners provide comprehensive healthcare for people of all ages with all diseases. They function in the same way as family physicians (FPs), primary care physicians or general practitioners (GPs) in other countries. However, primary care is provided by general practitioners with different levels of education; they can either be graduates of a medical college with no postgraduate training, or they can be doctors with postgraduate training and specialization . AlthougThe first edition of the “Chinese Hypertension Prevention Guide” was officially released in December 2009 . It was The Chinese Hypertension Prevention Guide is directed to the general population  and is designed to serve as the standard teaching guide for training primary care physicians. However, goals to increase general practitioners’ awareness of the Guide, to carry out hypertension education, prevention and control in the communities and to improve hypertension awareness, treatment and control rates in hypertensive patients remain difficult tasks to accomplish nationwide. As a preliminary approach, this study aimed to investigate general practitioners’ knowledge of hypertension, understanding and use of the national hypertension prevention and control guidelines, and potential training needs. Results may provide a basis for developing a hypertension training program targeted at community physicians.Five community health service centers in Xuhui District, Shanghai, were selected by convenience sampling based on their accessible urban setting; geographic location of the centers were considered and included one suburban area, two urban areas (not downtown) and two downtown areas to represent the general metropolitan area, which has a similar health network to other regions of China. All general practitioners in the centers were invited to participate in this study. A questionnaire survey was conducted among general practitioners at those centers from March 2011 to June 2011. A total of 160 questionnaires were distributed and 147 were returned (response rate 91.9%).General practitioners in China are similar to family physicians (FPs) or general practitioners (GPs) in other countries and provide comprehensive healthcare for people of all ages, sexes, diseases and parts of the body.In China, physicians include junior, attending, and senior physicians, corresponding to resident, attending physician and chief physician or deputy chief physician in other countries. Physicians’ medical education levels vary from: (a) graduates of a 5-year regular medical university (“bachelors”) equal to having a Bachelor of Medicine degree without clinical internship or research work; (b) graduate students with Master of Medicine or Doctor of Medicine degrees who study and perform clinical and research work for 3 to 6 years; and (c) graduates of professional school  and medical college (3-year training in medicine after high school), a category that is being reduced.The network includes small community clinics set up as work stations by community health service centers providing public health services and patient education in residential communities. The clinics’ main function is to facilitate management and follow-up of residents’ chronic diseases , including measuring blood pressure, monitoring blood glucose, dispensing medicine and performing injections or intravenous infusion. Each site has 4 to 5 health service personnel  as well as out-patient clinics and wards. Community health service centers also conduct community workshop to provide academic exchange between community general practitioners and health education for community residents and patients with chronic diseases.Full medical service: Suburban community healthcare centers have fewer surrounding secondary and tertiary hospitals/medical center to share medical services and therefore provide full medical service with a greater workload, including more patients and more types of diagnosis and treatment. (2) Basic healthcare: Downtown community healthcare centers provide basic medical services with a smaller workload, including fewer patients, fewer types of diagnosis and treatment. Urban community healthcare centers provide medical services between basic and full service.The five community health centers included in this study had similar functional characteristics but affiliated medical facilities in the suburbs and urban/downtown areas had differences in the scope of clinical diagnosis and treatment, as follows: (1) A questionnaire survey was conducted to investigate the hypertension knowledge and training needs of community general practitioners. The questionnaire comprised three sections (refer to Appendix A for full questionnaire): (A) General information, which included physicians’ baseline characteristics; health promotion, education and training needs; and knowledge of hypertension prevention and treatment; (B) Health Education and Training Needs, which included hypertension promotion, education of community general practitioners and physicians’ hypertension-related training needs. It originally included 12 subjective questions presented as true/false and multiple choice questions but two items were deleted due to the low in CVI; and (C) Knowledge of hypertension prevention and control, which included 5 domains with 19 items derived from the China Hypertension Prevention Guide . DomainsThe questionnaires were distributed and interpreted by survey administrators. Participants were asked to complete the self-reported questionnaire without discussing with others. The completed questionnaires were collected personally by survey administrators along with signed informed consent to participate. The survey administratos were faculty of community health service centers who had received a short training course about the study purpose, questionnaire content and how to answer the questionnaire. Researchers standardized the procedure to distribute and recover the questionnaire. The authenticity and validity of the returned questionnaires were verified by researchers in research team  before performing data processing and statistical analyses.P < 0.05 were discarded, but age of physicians was always forced into the model for adjustment. All statistical analyses were performed with SAS software version 9.2 . A two-tailed P < 0.05 indicated statistical significance.Continuous variables were summarized by mean ± SD and categorical variables were expressed by frequencies and percentages. Differences in the distribution of physicians’ demographic characteristics among the five participating community healthcare centers were detected by Chi-square test or Fisher’s exact test, as appropriate. The accuracy rate of hypertension-related knowledge was calculated as number of correctly answered items divided by total number of items for each physician. For example, if a physician correctly answered 12 items among a total of 19 items, his accuracy rate of hypertension-related knowledge would be 12/19 = 63.2%. To investigate factors associated with the accuracy rate of hypertension-related knowledge, the generalized estimating equation (GEE) model was applied to accommodate the correlated data of physicians clustered within the same healthcare center. The accuracy rate served as a continuous dependent variable, and demographic characteristics of physicians as well as characteristics of community healthcare centers served as independent variables. Univariate and multivariate GEE models with identity links were used to calculate unadjusted and adjusted mean differences and standard errors (SE) of the accuracy rate, compared to the appropriate reference group. The multivariate GEE model was constructed using backward selection procedure, wherein variables that did not improve model fit at P = 0.018), title (P = 0.003), working position (P < 0.0001) and number of years worked (P = 0.001).The baseline characteristics of general practitioners are summarized in Table Almost all physicians (99.3%) believed that changing unhealthy lifestyles will help control blood pressure, and all general practitioners (100%) intended to practice health education for hypertensive patients during their clinic work Table . PhysiciA majority of physicians 92.5%) had previously attended training courses on knowledge of hypertension prevention, and most physicians (87.8%) reported being willing to attend training courses regularly  answered correctly. Regarding diagnosis, 44.2% (65/147) of general physicians mistakenly chose the item “For patients without the use of any antihypertensive drugs, hypertension can be diagnosed if two measurements on different days show systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg.” For blood pressure measuring procedure, 45.6% (67/147) general physicians mistakenly chose the item “The time interval between two blood pressure measurements is 1 to 2 minutes.” Only 49.7% (73/147) of general physicians correctly chose the item “The blood pressure of elderly patients (age ≥ 65 years) with hypertension should be reduced to below 150/90 mmHg.” For drug-related questions, 27.9% (41/147) of general physicians mistakenly thought the indications of dihydropyridine calcium antagonists was left ventricular dysfunction, and 23.1% (34/147) mistakenly thought the taboo against the use of diuretics was diabetic nephropathy. For management grade of hypertensive patients, 36.7% (54/147) of general physicians mistakenly chose the item “For patients with target organ damage who are managed by grade, the management grade can be adjusted based on the actual situation after 1 year of management.” For ambulatory blood pressure monitoring, 23.1% (34/147) of general physicians mistakenly thought that normal ambulatory blood pressure values in China are: 24-h average < 130/80 mmHg, daytime average < 140/90 mmHg, night time average < 120/70 mmHg.P = 0.003) and type of training center  were still significant factors associated with accuracy rate.The factors associated with accuracy rate of hypertension prevention knowledge were investigated using univariate and multivariate GEE models Table . In univThis study investigated general practitioners’ needs for continuing education and knowledge of hypertension prevention, which are closely associated with their understanding and use of the national hypertension prevention and control guidelines. For the questions regarding hypertension prevention knowledge, the average accuracy rate of all 19 items was 49.2%, ranging from 10.5% to 94.7%, suggesting that the knowledge level of general practitioners in Xuhui District, Shanghai was low. Physicians with better understanding of hypertension  were more likely to be younger, with at least an undergraduate education level , fewer years of working experience (indicating more recent education and training) and working in a training-base. Regarding training needs, most general practitioners reported being willing to attend training courses regularly. Their preferred frequency of training courses was once every 2 ~ 3 months, and the most preferred course was “medical treatment of hypertension” followed by “education for hypertensive patients (including non-pharmacologic lifestyle treatment). The most favored training approaches were expert lectures and case study. These findings indicate that physicians are eager to receive more training on addressing hypertension prevention in their communities. The increasing prevalence of hypertension and the related high risk for cardiovascular disease is a growing public health problem. Based on the quantity and structure of the Chinese population in 2010, about 200 million patients are projected to have hypertension in China, or about 2 hypertensive patients in every 10 adults . The pubBarriers to adherence to national guidelines in China were suggested by results of this study. General practitioners reported four main obstacles in their practice: poor patient compliance, not enough time for medical consultation, lack of their own knowledge related to hypertension and lack of technique in behavioral medicine. Although most physicians thought that health education could influence lifestyle changes in hypertensive patients to some extent, 7 in 10 physicians reported spending only one third to one quarter of their practice time in medication consultation to educate patients about lifestyle changes that may help to reduce blood pressure and benefit their health status. Similar barriers to adherence to national and international hypertension guidelines are reported by general practitioners in other countries. The main obstacles to guideline use in Ireland as support for ambulatory blood pressure monitoring is physicians’ time and the costs related to monitoring, as well as a lack of remuneration . In SwedIn summary, responses from general practitioners in this study implied that they did not conduct hypertension consultations effectively due to lack of consultation time, which was compounded by patients’ poor compliance with physicians’ instructions. Although the healthcare network in China includes community health service centers that provide public health services and patient education in residential communities, with management and follow-up of residents’ chronic diseases  performed by smaller clinics, there is clearly a need for a well-organized program for hypertension monitoring and consultation so that all hypertensive patients can receive necessary attention and education by trained physicians. The need to promote the national guidelines is obvious. The question of how to promote them remains, especially given the structure of the community health centers and the mixed educational backgrounds of general practitioners working in these centers. China has tried to standardize care throughout the national healthcare network and improve care delivered by the community health centers. Our study results do show that physicians working in the training base with a series of teaching, assessing and evaluating systems and settings for hypertension prevention perform better than those that are in general healthcare centers. This makes a strong case for continuing education for general practitioners.The new, updated Chinese Hypertension Prevention Guide  sets theThe present study is limited because it only surveyed general practitioners in one district of one city in China. Results may not represent the state of general practice throughout the country or in different types of institutions in the national healthcare network. Also, although we evaluated general practitioners’ interest in receiving certain types of education and training to address hypertension in their communities, specific areas of weakness in their knowledge of hypertension were not evaluated in depth. In addition, our survey instrument was self-reported and general practitioners’ hypertension-related skills and knowledge should ideally be measured quantitatively with an instrument designed and validated for that purpose.In conclusion, the knowledge level of community general practitioners in Xuhui District, Shanghai, on understanding, preventing and managing hypertension in their communities is limited and their awareness of practice guidelines for hypertension is low. Physicians working in training bases, where they participate in a series of teaching, assessing and evaluating systems for hypertension prevention, had higher accuracy rate in hypettension knowledge than those in general community clinics where they lack specific training. Continuing education is urgently needed to ensure that physicians in general practice are aware of and adhere to hypertension prevention and treatment strategies presented in the Chinese Hypertension Prevention Guide. Increasing general practitioners’ awareness and understanding of hypertension prevention and treatment is necessary to reduce the prevalence of hypertension in China. Further study is needed with a larger sample representing broader geographic distribution. Investigation of existing hypertension awareness programs, monitoring system and their level of success in terms of outcomes and control of hypertension also may be of value.A. General Information1. Name:2. Gender: □Male □Female3. Age: □□4. Position title: □Junior physician □Attending physician □Senior physician5. Workplace: □Outpatient clinic □Ward □Community health station6. Education: □Professional school □Medical college □Medical university □Graduate school7. Work Experience: □Less than 10 years □10 ~ 20 years □20 ~ 30 years □More than 30 yearsB. Health Education and Training Needs1. Do you think that changing unhealthy lifestyles helps to control blood pressure? □ Yes □ No2. Do you consciously conduct health education for patients with hypertension in your daily work? □Yes □NoYou can choose more than one answer.)3. What is the difficulty in providing health education during clinical practice to patients with hypertension? ((A) Lack of relevant educational knowledge(B) Poor compliance of patients(C) Lack of behavioral medicine techniques(D) Patients’ visits do not allow long enough time(E) Other4. Do you think that health education will change the lifestyle of patients with hypertension?(A) Yes, definitely (B) Yes, to some extent (C) No5. How much medical consultation time did you spend on providing health education to patients with hypertension?(A) 3/4 or more (B) 1/2 (C) 1/3 (D) 1/4 (E) Lesser or 0\6. Have you received any training courses on hypertension prevention and control knowledge? □ Yes □ No7. Would you like to attend training courses on hypertension prevention regularly?□ Yes □ No8. What is the most appropriate frequency of related training course?(A) Weekly (B) Bi-weekly (C) Monthly (D) Once every 2 ~ 3 months (E) Don’t need training courseYou can choose more than one answer.)9. What topics should be covered in the related training course? ((A) Diagnosis and evaluation of hypertension(B) Medical treatment of hypertension(C) Education for hypertensive patients (including non-medication treatment)(D) Management of hypertensive patients in community(E) Two-way referral of hypertensive patients(F) Treatment for patients with complications/comorbidity(G) OtherYou can choose more than one answer.)10. What kind of format(s) should be used in the related training course? ((A) Expert lectures (B) On-site guidance (C) Case Study (D) Community workshop (E) OtherC. Knowledge of hypertension prevention and control1. The epidemiological data show that the current prevalence of hypertension in China is?(A) 50 million (B) 100 million (C) 160 million (D) 200 million (E) 250 million2. Which of the following is correct about the diagnosis of hypertension?(A). For patients without the use of any antihypertensive drugs, hypertension can be diagnosed if two measurements on different days show systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg.(B). Systolic blood pressure > 140 mmHg and diastolic blood pressure ≤ 90 mmHg is isolated systolic hypertension.(C). Systolic blood pressure <140 mmHg and diastolic blood pressure > 90 mmHg is isolated diastolic hypertension.(D). When grading hypertension, if the patient’s systolic and diastolic blood pressure belongs to different grades, a lower grade should be selected.(E). At the same time as diagnosing hypertension, the risk should be stratified according to patient’s blood pressure levels, existing risk factors, target organ damage, and combined clinical disorders.(You can choose more than one answer.)3. Which of the following is correct about detecting patients with hypertension in communities? (A.) At all levels of medical institutions, blood pressure should be measured at the first visit of patients over age 35 years.(B.) For populations susceptible to hypertension , it is recommended that blood pressure should be measured every six months.(C.) A variety of public places should be used to measure blood pressure, including elderly activity stations, clinics at institutions and blood pressure measuring stations.(D.) Make plans to measure the blood pressure of all adults in the community, and blood pressure of adults with normal blood pressure should be measured at least once every 2 years.(E.) Place semi-automatic or automatic electronic blood pressure monitors at a variety of public places to facilitate the public’s self-measurement of blood pressure.4. For a patient with hypertension whose blood pressure is 165/95 mmHg, the correct risk stratification should be  if he/she has three prognostic risk factors: smoking, obesity, and dyslipidemia(A) Low risk(B) Moderate risk(C) High risk(D) Very high risk(E) Cannot be determinedYou can choose more than one answer.)5. For the blood pressure measuring procedure, which of the following descriptions is incorrect?((A) A mercury sphygmomanometer or an upper arm electronic blood pressure monitor that complies with international standards should be used.(B) The subject rests for at least 2 minutes before the measurement, and the subject is in a sitting position during measurement while keeping quiet and relaxed.(C) The cuff wraps the upper arm evenly, the lower edge is 2 to 3 cm above the cubital fossa and at the same level as the heart.(D) During auscultation, systolic blood pressure is when the first korotkoff sound is heard and the diastolic blood pressure is when the fourth korotkoff sound is heard.(E) The time interval between two blood pressure measurements is 1 to 2 minutes.6. The main goal of hypertension treatment is to reduce the blood pressure to certain standards. Which of the following blood pressure control standards is correct?(A) The blood pressure of the average patient with hypertension should be reduced to below 130/80mmHg.(B) The blood pressure of elderly patients (age ≥65 years) with hypertension should be reduced to below 150/90mmHg.(C) The blood pressure of patients with diabetes, cerebrovascular disease, and chronic kidney disease should be reduced to below 140/90mmHg.(D) Blood pressure of patients with all grades of hypertension should reach the control standard within 1 to 2 weeks, and long-term blood pressure control should be achieved.(E) Patients with coronary heart disease or elderly patients (age >65 years) require attention when the diastolic blood pressure is lower than 50mmHgYou can choose more than one answer.)7. Non-drug treatment for hypertensive patient includes.(2(A) Weight loss; body mass index (BMI) should be controlled to <24 kg/m(B) Regular exercise, which is generally low or moderate intensity exercise, 3 to 5 times a week, 30 minutes per time.(C) Reduce sodium intake; the daily sodium intake should not exceed 6 grams.(D) Smoking cessation and limiting alcohol consumption; daily alcohol consumption should not exceed the amount equal to 50 grams of ethanol.(E) Reduce fat intake; the energy provided by dietary fat should be less than 40% of the total calories consumed.8. Among the following principles of hypertension drug treatment, which is correct?(A) Start the treatment from a smaller effective dose, gradually increase the dose or add combined drugs; the goal is to lower the blood pressure to the standard within 1 to 2 weeks.(B) Intermediate- or short-acting drugs are recommended to lower the blood pressure as soon as possible to prevent target organ damage.(C) Try to apply only one drug to avoid the adverse effects of antihypertensive drugs.(D) Following the principle of individualized treatment, choose appropriate antihypertensive drugs according to the specific circumstances of each patient.(E) Diuretics are preferred in elderly hypertensive patientsYou can choose more than one answer.)9. Contraindications of angiotensin II receptor blocker (ARB) include:((A) Congestive heart failure(B) Tachyarrhythmias(C) Pregnancy(D) Hyperkalemia(E) Bilateral renal artery stenosisYou can choose more than one answer.)10. Indications of the dihydropyridine calcium antagonists for the treatment of hypertension are.((A) Elderly patients (age >65 years) with hypertension(B) Supraventricular tachycardia(C) Isolated systolic hypertension(D) Cardiac angina(E) Left ventricular dysfunction11. Which of the following is the taboo against the use of diuretics ?(A) Elderly patients (age >65 years) with hypertension(B) Congestive heart failure(C) Post-myocardial infarction(D) Diabetic nephropathy(E) Renal failure12. Which of the following is correct regarding β-blockers?(A) There are three types of β-blockers: selective (β1), non-selective (β1 and β2) and those with combined α receptor blockage.(B) They have better efficacy for elderly patients (age >65 years) with hypertension.(C) They can only lower the blood pressure in the resting state.(D) Non-selective β-blockers are preferred in the treatment of hypertension in clinical practice.(E) The main adverse effect is orthostatic hypotension.13. Which of the following combination regimens of antihypertensive drugs is inappropriate?(A) Calcium antagonists and angiotensin-converting enzyme inhibitors (ACEI) or ARB(B) Small dose of diuretic and ACEI or ARB(C) ACEI and ARB(D) Dihydropyridine calcium antagonists and small doses of beta blockers(E) Calcium antagonists and small doses of diuretics14. Which of the following hypertension-related treatments is correct?(A) With continuously elevated blood pressure and serum total cholesterol (TC) levels and TC ≥ 5.2 mmol / L, lipid-lowering therapy using statins should be considered, and the target TC is <4.1mmol / L.(B) For patients with hypertension and coronary heart disease, diabetes, ischemic stroke, peripheral vascular disease and serum total cholesterol (TC) ≥ 4.1mmol / L, blood lipid-lowering therapy using statins should be considered, and the target TC is <3.1mmol / L.(C) For patients with hypertension and ischemic heart and cerebrovascular diseases , or diabetes, daily aspirin at a dose of 75 ~ 100mg is recommended.(D) For patients with hypertension and type 2 diabetes, the target blood pressure is <140/90mmHg.(E) For patients with hypertension and type 2 diabetes, the target blood glucose is: fasting blood glucose ≤ 10 mmol / L, glycosylated hemoglobin (HbA 1c) ≤ 6.0%You can choose more than one answer.)15. Populations susceptible to hypertension are?((A) High blood pressure values (systolic blood pressure 130 ~ 139mmHg and / or diastolic blood pressure 85 ~ 89mmHg)(B) Overweight (BMI 24 ~ 27.9kg/m2) or obese (BMI ≥ 28 kg/m2), and / or abdominal obesity: waist circumference, men ≥ 90cm (2.7 feet), women ≥ 85cm (2.5 feet)(C) Family history of hypertension(first and second degree relatives)(D) Long-term excessive alcohol consumption(daily consumption ≥ 200ml / 40 grams)(E) Age ≥ 50 years16. Which is correct regarding the management grade of hypertensive patients by general practitioners in the community?(A) Low-risk patients receive first-grade management and drug therapy is started immediately. They are followed once every 6 months after the blood pressure reaches the standard and is stable.(B) Patients with moderate risk receive second-grade management and drug therapy is started immediately. They are followed once per month and the blood pressure is monitored if it did not reach the standard or is unstable.(A) (C) Patients with high risk receive third-grade management and drug therapy is started immediately. Renal function, blood glucose, and lipid profile are measured and urinalysis and electrocardiogram are done once every two years.(C) Patients with hypertension and comorbidities such as heart, brain and kidney diseases and diabetes are classified as high risk, therefore the management grade will remain unchanged long term.(D) For patients with target organ damage who are managed by grade, the management grade can be adjusted based on the actual situation after 1 year of management.You can choose more than one answer.)17. The referral criteria for the newly diagnosed hypertensive patients in the community include:((A) Young hypertensive patients(B) Elderly (age >65 years) hypertensive patients(C) Pregnant and breast-feeding women(D) Patients with severe combined clinical conditions or target organ damage(E) Patients with suspected secondary or white coat hypertension18. Which one is correct among the following referral criteria for patients with hypertension who are followed up at community health stations?(A) The treatment regimen was followed for 2-3 weeks, but the blood pressure did not reach the goal.(B) Patients with stable blood pressure control who experience an increase in blood pressure(C) Patients who experience adverse reactions after administration of antihypertensive drugs(D) Patient requires referral to higher level hospitals(E) Patients with great blood pressure fluctuations or combined multiple risk factors whose clinical treatment is difficult19. Which one is correct regarding ambulatory blood pressure monitoring?(A) Ambulatory blood pressure monitoring can be used for diagnosis of white-coat hypertension, masked hypertension, refractory hypertension, paroxysmal hypertension or hypotension.(B) Normal ambulatory blood pressure values in China are: 24-h average <130/80mmHg, daytime average <140/90mmHg, night time average <120/70mmHg.(C) Under normal circumstances, the average nighttime blood pressure is 15% to 20% less than the average daytime blood pressure.(D) Ambulatory blood pressure monitoring is mainly used for the assessment of prognosis, the efficacy of new drugs or treatment regimens, and it gradually replaces the blood pressure measurement at clinics.(E) The time interval for blood pressure measurement is generally set at once every 60 minutes during the day and once every 120 minutes at night.The authors declare that they have no competing interests.We declare that all the listed authors have participated actively in the study and all meet the requirements of the authorship. Dr.  designed the study and wrote the protocol, Dr.  performed research/study, Dr.  managed the literature searches and analyses, Dr.  undertook the statistical analysis, Dr.  wrote the first draft of the manuscript. All authors read and approved the final manuscript.Qian Chen and Xiangjie Zhang are co-first authors in this study.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/14/16/prepubTable S1. Responses for knowledge of hypertension.Click here for file


Septic shock patients are submitted to many therapeutic strategies, including sedation. It is unknown if different sedative drugs influence microcirculation.We performed a prospective observational study, using sidestream dark-field imaging (SDF), to evaluate sublingual mucosa of septic shock patients admitted to our ICU. SDF was applied in two settings: continuous sedation with propofol and with midazolan. We repeated each examination after an interval of 30 minutes. Eight fields (videos) were analyzed during propofol and midazolan infusion. Two videos were obtained from each side of the tongue. The Bispectral index was monitored along with the Richmond Agitation Sedation Scale: the dose of both sedatives was titered to maintain light sedation. All demographic and severity of illness data were collected. Vasopressor agents were maintained to a mean arterial pressure of 70 mmHg and the cardiac index was kept stable through the protocol study.P = 0.005), although RASS was the same for both groups. Large-vessel perfusion was similar for both groups. The small perfusion vessel proportion was significantly reduced with propofol . The microvascular flow index was also lower during propofol infusion . We observed a higher heterogeneity index when patients were sedated with propofol .We included 15 patients; APACHE II score was (median) 17.5 points and SOFA score 9 points. The Bispectral index was lower in the midazolan group (43 vs. 48.5 points, Propofol reduces small-vessel perfusion and increases the heterogeneity of circulation in the sublingual mucosa, when compared with the use of midazolan in septic shock patients.


The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI.Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments.  Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as deep vein thrombosis and long–term risk for coronary heart disease and systemic atherosclerosis are also described.  Proper prophylaxis, including non–pharmacologic and pharmacological strategies, diminishes the occurrence of the vascular dysfunction following SCI. Each vascular disturbance requires a specific treatment.  Spinal cord injury (SCI) is one of most important health problems worldwide, and one of the most devastating of all traumatic events, with an annual incidence of 15 to 52.5 cases per million of population. About 80% are young males, aged between 15 and 35 years, and 5% are children. NeurologThe aim of this article is to evaluate the vascular dysfunctions following SCI. Vascular dysfunctions are common consequences of SCI, and are issues of interest worldwide. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI.–9Impairment in control of the autonomic nervous system, mostly in patients with cervical and high thoracic SCI, causes arterial hypotension, bradycardia, and autonomic dysreflexia. Besides, additional vascular complications, such as deep vein thrombosis and long–term risk for coronary heart disease and systemic atherosclerosis, may occur. SCI causes important cardiovascular disturbances, with short and long term consequences.  An adeqAll the patients with motor complete cervical SCI (ASIA A and B) develop bradycardia, 68% develop arterial hypotension, 35% of the patients require vasopressors, and cardiac arrest occurs in 16% of them. From patThe prevalence of autonomic dysreflexia is 48–90% of SCI above T6.[Deep vein thrombosis occurs in 47–90% cases. ProximalCoronary heart disease and systemic atherosclerosis are common findings in patients with chronic SCI, due to the lack of physical activity, obesity, hiperlipidemia, insulin resistance and diabetes, which are more frequently encountered in this group than in the general population. Insula, medial prefrontal cortex, hypothalamus, and cuneiform nucleus project into cardiovascular nuclei within medulla oblongata.–16 ParasThe preganglionic sympathetic neurons are located within the lateral horn into the intermediolateral nuclei of T1–L2 cord segments. They exit the spinal cord via the ventral root, and synapse with postganglionic neurons from paravertebral sympathetic chain. Postganglionic sympathetic fibers outflow through peripheral nerves vessels and heart. Besides the well–known motor and sensitive deficits, autonomic disturbances are frequently encountered. Autonomic nervous system pays a highly important role in the cardiovascular control. Blood pressure and heart rate are controlled by impulses from the autonomic nervous system: sympathetic and parasympathetic. They act antagonistically, according to various needs. The parasympathetic decreases the heart rate. The sympathetic increases the heart rate, myocardic contractibility, raises peripheral vascular resistance and the arterial blood pressure, by inducing vasoconstriction. The arterial blood pressure control depends on the activity of the supraspinal centers, which send activator impulses, through descendent pathways, to sympathetic spinal preganglionar neurons. Secondary to SCI, descendent pathways are interrupted and spinal circuits become incapable to generate sympathetic activity. Disruption of descendent pathways results in sympathetic hypoactivity and unopposed parasympathetic outflow through the intact vagal nerve. Sympathetic hypoactivity results in low resting blood pressure, loss of regular adaptability of blood pressure, and disturbed reflex control. The spinal shock with the neurogenic shock represent a vascular dysfunction that occurs during the acute phase of SCI. Autonomic dysreflexia, coronary heart disease and systemic atherosclerosis are encountered during the chronic phase of SCI. Arterial hypotension and deep vein thrombosis are found in both acute and chronic periods of time. The initial response to SCI is a massive sympathetic stimulation and reflex parasympathetic activity that usually lasts for 3 to 4 minutes and it is mediated by alpha–adrenergic receptors. The hemodynamic effects are severe hypertension and reflex bradycardia or tachyarrhythmia. The massive sympathetic stimulation is due to norepinephrine release from the suprarenal glands. There is also a pressor response caused by the disruption of the cervical and high thoracic vasoactive neurons.Following this first phase, a massive decrease of sympathetic activity occurs, due to the disruption of descendent sympathetic tracts. The result is physiologically similar to spinal anesthesia and leads to cutaneous vasodilatation, venodilation and reduced venous return, low blood pressure, low cardiac output, bradycardia, bradyarrhythmias and atrioventricular nodal block, due to the lack of vasoconstrictor and inotrope sympathetic activity. The patient is prone to hypothermia, arterial hypotension and bradycardia, by the absence of sympathetic tone and unopposed vagal tone. Following this brief hypertensive peak, spinal shock occurs. The spinal shock is a physiological disruption of the spinal cord functioning that accompanies SCI. It is a transitory suspension of function and reflexes below the level of the injury. Inputs from autonomic central centers modulate the activity of sympathetic spinal neurons. Sudden disruption of communication between these centers and the sympathetic neurons in the intermediolateral thoracic and lumbar spinal cord leads to spinal shock.Spinal shock was described for the first time by Whytt in 1750, and the term ‘spinal shock’ was later introduced in the literature by Hall in 1841. Spinal sNeurogenic shock consists of severe arterial hypotension, bradycardia and hypotermia.–23  It iThe spinal shock usually lasts for days–weeks, the average being of 4–12 weeks.,27,27–30Neurogenic shock should not be mistaken with hypovolemic shock. In neurogenic shock, hypotension is associated with bradycardia, while in hypovolemic shock tachycardia occurs. In neurogenic shock, the skin is usually warm and dry, except for patients exposed to a cold environment. Neurogenic and hypovolemic shock may coexist, and when this happens, neurogenic shock exacerbates the effects of hypovolemic shock by disabling the vasoconstrictive reflexes that ordinarily preserve blood flow to vital organs. The abolished compensatory vasoconstriction, secondary to changes in sympathetic activity, especially into large vascular beds, like skeletal muscle and splanchnic region vessels, in association with reduced venous blood return, contribute to low blood pressure. Arterial hypotension, especially orthostatic hypotension, improves within days–weeks, thanks to the appearance of compensatory mechanisms involving the vascular bed, skeletal muscles activity, spasticity, increase in the muscular tone, reappearance of spinal sympathetic reflexes, and rennin–angiotensin–aldosterone system. ArterialOrthostatic hypotension is very difficult to control, and severely impairs the quality of life. OrthostaThe Consensus Committee of the American Autonomic Society and the American Academy of Neurology Orthostatic established in 1996 that hypotension is a decrease in the systolic blood pressure of 20 mmHg or more, or a decrease in the diastolic blood pressure of 10 mmHg or more; this being based upon the assumption of an upright posture from a supine position, regardless of whether symptoms occur.From clinical point of view, the orthostatic hypotension can be symptomatic, the patients experiencing dizziness, light–headedness, headache, fatigability, nausea, faint, pallor, sweating and loss of consciousness or it can lack any symptoms. The disruption of efferent pathways from vasomotor center, located within the medulla oblongata, to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 segments involved in vasoconstriction, causes failure of blood pressure regulatory mechanisms and venous pooling.,21,33,36The pathological mechanisms responsible for the orthostatic hypotension of SCI patients, still remain unclear. There are a few predisposal factors of occurrence of hypotension in SCI. The etiology of orthostatic hypotension is multifactorial.Sympathetic nervous system dysfunctionLow plasma catecholamine levelsRennin–angiotensin–aldosterone activityPeripheral alpha–adrenoceptor hyperresponsiveness Impaired function of baroreceptorsHyponatremia and low plasmatic volumeCardiovascular deconditioningMorphologic changes in sympathetic neuronsPlasticity within spinal circuitsMotor deficit leading to loss of skeletal muscle pumping activitySympathetic system dysfunction: The sympathetic nervous system plays an important role in cardiovascular control. Sympathetic system dysfunction consists of the disruption of efferent pathways, with supraspinal control loss of spinal centers, both excitatory and inhibitory control with absent or decreased sympathetic tone below the injury level.The parasympathetic outflow is preserved, but the synergy between the parasympathetic and the sympathetic control is lost in patients with cervical or high thoracic SCI. SCI above T6 disrupt the supraspinal control and the sympathetic tone to the splanchnic vascular bed, predisposing the patient to orthostatic hypotension. In order to maintain the systemic blood pressure and the cerebral perfusion in orthostatism, systemic vasoconstriction is induced via an increase in the tonic sympathetic activity and the baroreceptor–mediated mechanisms. The disruption of efferent pathways from the brainstem cardiovascular center to the spinal sympathetic centers causes failure of short–term blood pressure regulation., 21, 23It depends on injury level. It is more severe in cervical or high thoracic, complete SCI. The dynamic test performed on SCI patients and normal individuals stresses the importance of the sympathetic nervous system dysfunction.Both the resting systolic and diastolic arterial pressures are lower in SCI patients than in normal individuals. Following the assumption of an upright seated position the SCI subject has a marked, progressive decrease in systolic and diastolic arterial pressure in the upright posture, the characteristic of the orthostatic hypotension, in contrast with normal individuals who have an increase in the systolic and diastolic arterial pressures.The sympaLow catecholamine levels: Plasmatic catecholamine levels, both adrenaline and noradrenaline, are low in SCI patients, comparative to normal individuals. Plasma catecholamines, noradrenaline and adrenaline levels,  are abnormally low in the supine position in both the recent and chronic SCI.,32,43–46The elevation in plasma noradrenaline in chronic SCI is caused by a reflex sympathetic discharge from the isolated spinal cord. This response is free of inhibitory impulses from supraspinal center and baroreceptor reflexes, either of which might restrain the increase in blood pressure.Rennin–angiotensin–aldosteron system: The patients with tetraplegia rely on the renin–angiotensin system for orthostatic blood pressure control.In patients with SCI, the plasmatic rennin activity is higher than normal. Plus, rennin levels rise rapidly and much higher in orthostatic posture or head–up tilt, than in normal individuals.,46 RenniPeripheral alpha–adrenoceptor hyperresponsiveness: As a compensatory mechanism for the decreased levels of cathecolamines, a peripheral alpha–adrenoceptor hyperresponsiveness below the injury site appears. The hypeImpaired function of baroreceptors:Baroreceptors located in the aortic arch, carotid sinus and coronary arteries are involved in the maintenance of blood pressure homeostasis. Baroreceptors detect changes in the arterial pressure and reflex modulate sympathetic and parasympathetic outflow. The impairment in baroreceptor reflex control is encountered particularly in patients with high–level, cervical and high thoracic, injuries, and causes low resting supine blood pressure in SCI individuals.In additiHyponatremia and low plasmatic volume: The plasma volume is directly dependent on the orthostatic tolerance and postural blood pressure homeostasis.In both Cardiovascular deconditioning appears as a consequence of prolonged bed rest and it is a loss of orthostatic tolerance thought to be related to diminished blood volume, decreased muscle or tissue pressure in the extremities or to functional alterations in the sympathetic nervous system. The cardMorphologic changes into sympathetic neurons:Following SCI, atrophy of sympathetic preganglionic neurons occurs, possibly due to partial deafferentation from the loss of descending medullary input and subsequently axonal sprouting. Plasticity within spinal circuits: Atrophy of sympathetic preganglionic neurons, axonal sprouting and synaptic reorganization may result in possible formation of new and often inappropriate synaptic connections.Spinal rMotor deficit leading to loss of skeletal muscle pumping activity: A possible mechanism producing orthostatic hypotension in SCI is the failure of skeletal muscle pumps in paralyzed limbs during postural challenge. The abseThe risk of developing deep vein thrombosis is highest in 7 to 10 days after the injury and during the early phases of recovery and rehabilitation. The risk diminishes in 8–12 weeks. Blood flux diminishes with 50–67% in inferior limbs following SCI, due to the loss of the autonomic nervous system control and to the reduction of the local blood flow.[Factors contributing to deep venous thrombosis occurrence are venous stasis in inferior limbs, secondary to muscle paralysis and lack of muscle pump activity, venodilation, pressure on the calves and hypercoagulability secondary to the reduction of fibrinolitic activity and rising activity of factor 8. Changes in the normal neurologic control of the blood vessels can result in stasis or sludging of the blood.Signs and symptoms of deep vein thrombosis are leg swelling, vein dilation, increased skin temperature, pain, tenderness, and, rarely, a bluish discoloration of the lower leg. Deep vein thrombosis can be present without any signs or symptoms. Thigh deep vein thromboses are a great concern, because the thrombi can dislodge and pass through the vascular tree to the lungs, causing pulmonary embolism, a potentially severe complication of SCI. The major pulmonary embolism has a high mortality rate. There are also no characteristic signs or symptoms of lung clots, signs and symptoms are nonspecific, such as fever, chest pain, cough, or changes in heart rate.The resolution of the acute phase merges with the appearance of hyperactive spinal reflexes, and spastic motor paralysis below the level of injury. The chroAutonomic dysreflexia, first observed by Anthony Bowlby in 1890, and described by Guttmann and Whitteridge in 1947, is the  Autonomic dysreflexia is frequently encountered in cervical injuries. The prevalence of this phenomenon varies between 48 and 90% of SCI above T6.11–13 Some incidence has been reported in SCI as low as T10.,61,62 After the spinal shock resolution, the deafferented spinal cord, in SCI above T6, may generate aberrant impulses to noxious stimuli, leading to autonomic dysreflexia, a life–threatening complication of SCI. Autonomic dysreflexia is a syndrome of reflex sympathetic discharge from the preganglionic neurons in the thoracolumbar spinal cord, occurring in patients with SCI located above the splanchnic sympathetic outflow T5–T6, often triggered by the distension of pelvic viscera. Autonomic dysreflexia is a consequence of supraspinal control loss of sympathetic spinal cord neurons and altered glutamatergic neurotransmission within the spinal cord. The viscThe development of autonomic dysreflexia is correlated with aberrant sprouting of peptidergic afferent fibers into the spinal cord below the injury. Sprouting of nerve growth factor–responsive afferent fibers has been shown to have a major influence on dysreflexia, perhaps by amplifying the activation of the disinhibited sympathetic neurons.Peripheral alpha–adrenoreceptor hyperresponsiveness following SCI may play a significant role in the development of autonomic dysreflexia.There is a constellation of signs and symptoms in SCI above T5–T6 in response to noxious or nonnoxious stimuli below the injury level, including severe arterial hypertension, headache and visual impairment due to cerebral vasodilatation, cutaneous pallor below the injury site, piloerection, secondary to sympathetic activity, reflex bradycardia, profuse sweating and cutaneous vasodilatation above the level of lesion, secondary to parasympathetic activity. Arterial blood pressure can reach up to 300 mmHg, leading to retinal, intracerebral, or subarachnoid hemorrhage, pulmonary edema, myocardial infarction, seizures, confusion and death. According to the increased blood pressure, there are three severity grades: mild/partial: blood pressure increases < 40 mmHgmoderate: blood pressure increases > 40 mmHg, but systolic blood pressure is < 180 mmHgsevere: systolic blood pressure increases > 180 mmHgCoronary heart disease and systemic atherosclerosis: Abnormal lipid profile, with an increase in total cholesterol and low–density lipoprotein (LDL–cholesterol) levels and diminishing of the high–density lipoprotein (HDL–cholesterol) level occur in chronic SCI and lead to a high risk of developing coronary heart disease and systemic atherosclerosis. The reason for diminishing the HDL–cholesterol is still on debate. It is assumed that it is due to an inappropriate diet, adrenergic dysfunction and lack of physical activity. The rati2O. If the hemodynamic instability persists, a Swan Ganz catheter is assembled. It provides accurate information on cardiac output, heart preload and systemic vascular resistance. In cases of profound hemodynamic instability with low central venous pressure, large doses of vasopressors, like norepinephrine, dobutamine and dopamine are required. Intractable hypotension should raise suspicion of a concealed internal hemorrhage. Tissue perfusion must be maintained. Hypotension, consequence of neurogenic and/or hypovolemic shock causes spinal cord ischemia, cord damage and extent of neurological deficit. In tetraplegic patients blood pressure must be maintained ranging from 80/40 mmHg to 100/60 mmHg. Attention should be paid to fluid overload that can cause cord edema, which will further reduce the tissue perfusion. The treatment of neurogenic shock implies the correction of the arterial hypotension and bradycardia. Treatment of neurogenic shock is individualized for each patient, depending on the severity of the blood pressure and heart rate dysfunctions.  The first two venous lines should be established for the administration of resuscitation fluids and medications.Arterial hypotension, associated with a normal heart rate requires volume loading, with crystalloids and colloids in the first 24–48 hours following SCI. In the absence of concomitant hypovolemic shock, Hartmann's solution implies the administration of 50–100 ml per hour, in order to maintain a systolic blood pressure of > 80 mmHg. Neurogenic shock associated with hypovolemic shock is treated with normal saline or Hartmann's solution in order to increase the intravascular volume and blood pressure. Patients having arterial hypotension with arterial systolic blood pressure < 90 mmHg, and bradycardia with heart rate < 60/minute, require 0.5 mg atropine for low heart rate and sympathomimetics for hypotension. Ephedrine is a sympathomimetic drug used for the treatment of hypotension, and it can be given intravenously 5 mg or subcutaneously 25–50 mg, every 4–6 hours. The heart rate of < 50/minute, nodal or ventricular ‘escape’ dysarhythmias require higher doses of atropine administered as often as necessary up to 2 mg per hour. In severe neurogenic shock, the monitorization of the central venous pressure is mandatory in order to ensure the fluid load up to a central venous pressure of 7–10 mmHNonpharmacological management of orthostatic hypotension: Nonpharmacologic measures should be the first line of therapy. PatientsTreatment of deep vein thrombosis:Prophylaxis of deep vein thrombosis is mandatory. Nonpharmacologic prophylactic strategies include the mobilization of the patient, thigh high compression stockings, pneumatic calf compression boots and physical therapy. Pharmacologic prophylactic treatment consists of anticoagulant therapy, such as heparin, low molecular weight heparin or oral anticoagulants.Heparin administered subcutaneously is useful in reducing blood viscosity and improving flow. Low molecular weight heparin has been demonstrated to be superior to standard heparin preparations and the former also significantly reduces the incidence of bleeding. Because of the high risk of developing deep vein thrombosis, in patients with SCI, regular measurement of bilateral calf and thigh circumferences is mandatory. Doppler ultrasound or venograms are frequently performed to establish baselines.    If deep vein thrombosis occurs, intravenous heparin is administrated for 7 to 10 days. Once adequate anticoagulation is provided, the patient is switched to an oral anticoagulant therapy for 3 months.    In patients in whom thromboembolism occurs under anticoagulation therapy or for patients with high risk to anticoagulant therapy, an inferior vena cava filter can be placed.Treatment of autonomic dysreflexia: The avoidance of trigger factors prevents the appearance of this phenomenon. Sympatholitic drugs administration , vasodilator drugs and local anesthetics can prevent the onset of this phenomenon.,73,74 Or