To analyze the association between hypertension and urinary uric acid excretion in patients with chronic kidney disease (CKD).2) and Cur2 (Cur ≥ 6.2 ml/min/1.73m2) groups according to the median of FEua or Cur, respectively.We screened 87 patients who had been admitted at the Dept of Nephrology, Huadong hospital between April 2017 to April 2019 who had completed 24-h ambulatory blood pressure monitoring and retained 24-h urine biochemical test specimens, thirty adult patients (age ≤ 65 years) with CKD 1–2 stages were recruited in the study. Pearson’s correlation analysis and multiple linear regression analysis were used to study the correlation of urinary uric acid excretion with ambulatory blood pressure values and the association of morning mean diastolic pressure (mMDP), night mean diastolic pressure (nMDP) and CV of dMSP (coefficient of variation of day mean systolic pressure) with fractional excretion of uric acid (FEua) and uric acid clearance rate (Cur). Independent T test was used to compare the differences of blood pressure values in FEua1 (FEua< 6.0%) and FEua2 (FEua≥6.0%) or Cur1 (Cur < 6.2 ml/min/1.73 mP < 0.05), level of CV of dMSP in Cur2 group were higher than that in Cur1 group (P < 0.01).After adjusting for confounding factors, multiple linear regression analysis showed that FEua was positively associated with the mMDP and nMDP, Cur was positively associated with CV of dMSP. Levels of mMDP and nMDP in FEua1 group was lower than that in FEua2 group (both We demonstrated that there is a positive correlation of FEua with morning and night mean diastolic pressure separately and Cur is positively related to CV of dMSP in CKD population. Monitoring the trend of urinary uric acid, may have a role in the early detection for hypertension or relative risks in the population of CKD. Hypertension (HTN) is quite prevalent in chronic kidney disease (CKD) and is the leading cause of death. The important characteristics of hypertension in CKD are morning blood pressure surge (MBPS) and nocturnal hypertension. Previous studies have shown that MBPS and nocturnal hypertension may increase the risks of cardiovascular event, vascular disease and inflammation and silent cerebrovascular disease , 2. The + and K+ are depended on Na+-K+-ATPase (NKA). In fact, the driving force of urate transporters in renal tubules comes from its basolateral Na+-K+-ATPase too. Furthermore, the NKA/Src complex has been shown to be activated in the kidney to address excess salt, and the tradeoff could be the development of salt-induced hypertension [Hyperuricemia is also common in CKD, with a prevalence as high as 8.4% in China . We havertension .Therefore, we made a reasonable hypothesis that urinary uric acid excretion would lead to the abnormality of HTN in CKD. Hence, we study the association of urinary uric acid excretion with ambulatory blood pressure values. In this study, the urinary uric acid excretion indicators are measured in 24-h urinary uric acid (24-hUua), fractional excretion of uric acid (FEua), excretion of uric acid per volume of glomerular filtration (EurGF) and uric acid clearance rate (Cur).2) /(SUA × Ucr) × 100, expressed as percentage. Cur was calculated as Uur × UV/SUA. EurGF was calculated as (Uur × Scr)/ Ucr. Cur and EurGF were corrected for the body surface area.The values of blood pressure were recorded by ambulatory blood pressure monitoring. Patients are randomly assigned two kinds of models . The blood pressure measurement and measurement accuracy of the two machines are same, but the measurement range of them has slightly difference, with the former ranging from 25 mmHg–270 mmHg and the latter ranging from 0 to 300 mmHg, which has no effect on the results. The monitoring interval is every 20 min during the daytime and 30 min during the night time in the two machines. Ambulatory blood pressure monitoring offers a special way of automated measurements of blood pressure during a 24-h period while patients are engaged in their usual activities, including the sleep. This type of measurement is superior to standard office measurement in getting more time points’ value and more accurate data. We could obtain diverse data, such as average blood pressure, even the blood pressure coefficient of variation (CV) of each time period and all day long. As an indicator for variability in blood pressure, it is defined as CV of BP as standard deviation (s.d.) divided by corresponding average BP. Each day is divided into three periods, morning hours (6 a.m.-8 a.m.), daytime (8 a.m.-10 p.m.) and night time (10 p.m. to next 6 a.m.); average blood pressure in each period was separately abbreviated as mMSP, mMDP, dMSP, dMDP, nMSP and nMDP, for all day substituted for 24-h MSP and 24-h MDP.2) was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula [After fasting for 12 h at night, each patient was taking venous blood for routine biochemical test by nurses. We could get symbols of each patient about the serum levels of uric acid (SUA), creatinine (Scr), urinary nitrogen (BUN), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and fasting blood glucose (FBG). The estimated glomerular filtration rate (eGFR) (milliliters per minute per 1.73 m formula .Height and weight were measured by well-trained nurses in a standard process. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared.Hypertension was defined as the average daytime blood pressure above 135/85 mmHg, nighttime blood pressure above 120/70 mmHg, and 24-h blood pressure above 130/80mmHg ; in clin2; Cur2: Cur ≥ 6.2 ml/min/1.73m2).Study participants were divided into two groups according to the median of FEua  and Cur  are presented in case of nonparametric data. Comparisons between groups were made by Student’s t-test and one-way ANOVA. Least significance difference (LSD) test was used when the variance was homogeneous, or Tamhane’s T2 test was used. Non-normally distributed data was compared using Mann-Whitney U test. Categorical data was compared using the Chi-square test. Correlations were detected by Pearson’s or Spearman’s depending on the distribution of the data. If Pearson’s correlation analysis was statistically significant, multiple linear regression analysis was performed. Multiple linear regression analyses were performed to determine the association of urinary uric acid excretion with 24 h ambulatory blood pressure values. Statistical significance for all analyses was set at 1 adrenergic receptor blockers, and there was no difference in the distribution of these drug between groups. The impression of data is shown in Table P < 0.05, Table This study embraced 30 participants with the age of approximately 53.40 years and with 21 males (70.0%). Causes of renal injury in 30 CKD patients were showed  and 24-h blood pressure values , all combinations are calculated after further permutations as shown below.r = 0.408, P = 0.031; r = 0.415, P = 0.025; r = 0.413, P = 0.023, respectively), and not related to 24-h mean blood pressure values and other relevant time-period values, including 24-h MSP , 24-h MDP , CV of 24-h MSP and MDP , mMSP , CV of mMSP and mMDP , dMSP , dMDP , CV of dMDP , CV of nMSP and nMDP . There was a positive correlation between Cur and CV of dMSP .Pearson correlation analysis showed that FEua was positively associated with mMDP, nMDP and CV of dMSP . Multiple linear regression analysis showed that Cur was still positively associated with CV of dMSP after adjusting confounding factors  ; model 3 plus eGFR, TC and TG)  group were higher than that in the lower Cur1 (Cur < 6.2 ml/min/1.73 m2) group  was lower than that in the higher FEua2 (FEua≥6.0%) group  and hydrogen peroxide (H2 O2) are produced as by-products of the oxidation step [Diastolic blood pressure is more closely related to uric acid levels. As we all know, systolic blood pressure is the pressure on the blood vessels when the heart contracts, while the diastolic blood pressure is generated by the elastic retraction of arteries. Therefore, diastolic blood pressure is more dependent on the elasticity and resistance of the blood vessel wall. In the Maastricht study , it is cion step . These R+ and secretion of K+. As we said before, the change of excretion of sodium and potassium is responsible for the increasing of blood pressure. Moreover, molecular clock in renal function plays a major role, which manifested in the renal excretion of water and major electrolytes [+ and K+. When dietary purine intake was kept constant, monophasic circadian fluctuations of fractional urate excretion (FEua) were observed with peak values in the afternoon, about 50% higher than during the night [Some mechanisms may be responsible for the positive correlation of FEua with morning and night mean diastolic pressure, which had a special time range. Variations in blood pressure show a diurnal change, a surge in the morning and a decrease in sleeping time. The differences in blood pressure over the course of the day are due to circadian changes, and more specifically, behavioral changes in activity and rest , external environment (including ambient temperature and noise levels) and endogenous circadian rhythms in hemodynamic, endocrine, endothelial and neural variables, such as plasma noradrenaline and adrenaline levels (the autonomic nervous system), and renin, angiotensin and aldosterone levels  –24. RNA-trolytes . What wehe night . Due to he night . Experimhe night , 33. Furhe night .Cur, as a parameter to measure the uric acid removed from body, is positively related to CV of dMSP. In this research, the variability of blood pressure is not simply described as the standard deviation (SD) of the 24-h, morning, daytime and nighttime mean values obtained by using ambulatory BP monitoring, it was calculated as standard deviation (s.d.) divided by corresponding average BP called coefficient of variation of blood pressure (CV of BP). As proved in the prior study, SUA levels are independently associated with different BPV (the standard deviation of each time period) components in a population of newly diagnosed patients with essential hypertension [This study had several potential limitations. First of all, the sample size is relatively small and there may be considerable deviations. Second, the values of blood pressure are generally not high, and some patients have accepted the antihypertensive treatment. Other limitations of this study include its cross-sectional design and one-time ABPM. Since the study explored the correlation between urinary uric acid excretion with blood pressure, antihypertensive treatment will affect the results of the observation and detection.In summary, we demonstrated that there is a positive correlation of FEua with morning and night mean diastolic pressure separately and Cur is positively related to CV of dMSP in CKD population. Monitoring the trend of urinary uric acid, may have a role in the early detection for hypertension or relative risks in the population of CKD. More researches are needed to elucidate mechanism underlying higher urinary uric acid excretion leading to hypertension.


Objective: Endovascular treatment (EVT) for lower-limb peripheral artery disease patients reduces blood pressure (BP) and improves prognosis. This study retrospectively examined hemodynamics during EVT to clarify the mechanism.Materials and Methods: Systemic vascular resistance (SVR) was measured using a noninvasive continuous cardiac output monitoring system during EVT. Furthermore, ankle brachial index was measured before and after EVT.Results: The study included 88 lesions of 56 patients (hypertension in 98%). SVR significantly decreased from 2409.1±746.8 dynes·s·cm−5 to 2033.7±635.0 dynes·s·cm−5 (p<0.0001). The difference in SVR before and after EVT was significantly greater in the Fontaine IV group than in the Fontaine IIa group . The change in SVR was correlated with a change in mean BP in the upper limb (p=0.0026). When the change in pressure gradient between the upper limb and the diseased lower limb was large, mean BP of the upper limb significantly decreased (p=0.0022).Conclusion: EVT can reduce SVR and BP by canceling the pressure gradient between central BP and diseased lower-limb BP. Cigarette smoking, diabetes mellitus, hypertension, and dyslipidemia are well-known risk factors of PAD. High blood pressure (BP) affects the formation of lower limb and systemic atherosclerosis and, in turn, atherosclerotic arteries can exacerbate hypertension. Patients with PAD frequently report cardiovascular complications and poor prognosis. Significant stenosis due to advanced arteriosclerosis produces a pressure gradient (PG) between the central and peripheral sides of the lower limbs, resulting in high BP at the central side , pressure overload to the heart and other organs, and hypoperfusion of the diseased lower limbs. Successful endovascular treatment (EVT) improves the quality of life and hemodynamic status of patients with lower-limb PAD. We have recently shown that systemic BP improvements after EVT were related to patient prognosis. However, the mechanism of BP reduction by EVT is unknown. Therefore, we examined hemodynamic status, change in BP, and systemic vascular resistance (SVR) using a noninvasive continuous cardiac output monitoring system during EVT for patients with PAD.Peripheral artery disease (PAD) is a worldwide problem, and the number of affected patients is currently increasing.2 or the presence of a kidney abnormality such as proteinuria. Hemoglobin, platelet, albumin, blood urea nitrogen, serum creatinine, uric acid, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, hemoglobin A1c , brain natriuretic peptide, and left ventricular ejection fraction using echocardiography were measured before EVT. The eGFR was calculated using the Modification of Diet in Renal Disease study equation coefficients modified for Japanese patients. The ankle brachial index (ABI) was measured on the day before and within 1 week after EVT in all patients. Cardiac output, stroke volume, and SVR were measured during EVT using the AESCULON mini® noninvasive continuous cardiac output monitoring system. This device can measure stroke volume using electrical velocimetry, a technique of measuring stroke volume that captures a change in conductivity of the orientation change of erythrocytes flowing through the aorta. It requires the attachment of four electrocardiographic electrodes to the body and has been proven comparable to the thermodilution method. SVR and cardiac output were calculated by stroke volume, non-invasive BP measured in the upper limb, right atrial pressure (uniformly 5 mmHg), and heart rate. Mean BP was calculated using the equation: (systolic BP−diastolic BP)/3+diastolic BP.This retrospective study included patients with consecutive lower-limb PAD, who underwent EVT, and measured hemodynamic status using an AESCULON mini® noninvasive continuous cardiac output monitoring system  between June 2014 and February 2017 at the National Hospital Organization, Disaster Medical Center, Tokyo, Japan. Patients with only a below-knee lesion were excluded from this study. All data were retrospectively collected. Lower-limb PAD severity was determined according to Fontaine classification. Study participants were surveyed for lesion area, position, length, Trans-Atlantic Inter-Society Consensus (TASC) II classification, hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, hemodialysis, coronary artery disease, cerebral vascular disease, and smoking habits. Patients were deemed to have hypertension if they had a history or were being treated with antihypertensive drugs. Diabetes mellitus was defined based on the World Health Organization criteria or treatment for the condition. Dyslipidemia was defined as a serum total cholesterol level >220 mg/dL or being treated for the condition. Chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 mThis study complied with the Declaration of Helsinki, and the ethical review board of the National Hospital Organization, Disaster Medical Center approved the study protocol (reference number: 2015-10). Informed consent was obtained from all patients or their family members before enrollment.The interventional strategy and device used were chosen by the operator. In principle, the stent was implanted for aortoiliac lesions. For femoral stenotic lesions, balloon expansion was first used. If major dissection occurred, optional stenting was performed. In cases with femoral chronic total occlusion, primary stenting was used. All patients started dual antiplatelet therapy 1 month in advance and were continuously treated after EVT. In all cases, no additional vasodilator was administered on the day of EVT.All data are represented as mean±standard deviation, mean±standard error, or median (range or 25%–75% interquartile range). The paired t-test and Wilcoxon signed-rank test were used to examine changes from baseline in hemodynamic status and ABI data. Single regression analysis was used to show the correlation between the difference in upper-limb mean BP and the difference in SVR and the correlation between the difference in PG of the upper limb and diseased lower limb before and after EVT. Tukey’s honest significant difference test was used for comparison based on Fontaine classification and TASC II classification. P-values <0.05 were considered statistically significant. Statistical analyses were performed using a standard statistical program package .The baseline patient characteristics are shown in −5 to 2033.7±635.0 dynes·s·cm−5 (p<0.0001) after EVT. Similarly, cardiac output and stroke volume significantly increased after EVT. A positive correlation was confirmed in the single regression analysis of the difference in upper-limb mean BP and the difference in SVR before versus after EVT   becomes hypertensive, that is, PG occurs. Subsequently, increased peripheral vascular resistance and hypertensive status occur. Pharmacological therapy is required for good BP control, and BP control can be resistant to multi-drug antihypertensive therapy in cases of severe organic stenosis.Based on lifestyle-related diseases, the prevalence of lower-limb PAD is increasing worldwide, In studies using a multi-sensor catheter, Murgo et al. found that ascending aorta pressure was affected by forward pressure and backward pressure, and that manual compression of bilateral iliac arteries increased ascending aorta pressure as backward pressure increased. In other words, patients with lower-limb PAD are at a risk of exposure to high aortic pressure and upper-limb BP because the backward pressure is gradually increasing by the chronic progression of peripheral atherosclerotic lesions. Thus, the cancelation of significant arterial stenosis reduces systemic or upper-limb BP. In this study, we have shown that EVT could reduce PG at the stenotic/occlusive lesion, SVR, and systemic BP levels.Studies have demonstrated that EVT for patients with lower-limb PAD reduces upper-limb and central BP. reported that central iliac arteriovenous anastomosis reduces the BP of patients with uncontrolled hypertension. Furthermore, Lobo et al. highlighted that the hypotensive effect due to this device lasted until the chronic phase. In their trial , office-based systolic BP decreased by a mean 25.1 mmHg and diastolic BP by 20.8 mmHg (p<0.0001 for both), whereas the mean 24 h ambulatory BP decreased by 12.6/15.3 mmHg at 12 months after central iliac arteriovenous anastomosis. These results suggest that arteriovenous anastomosis at the femoral vessel level reduced the peripheral vascular resistance and sustained hypotensive effect, even in patients with drug-resistant hypertension. Although the target patients in these studies were different from ours, the data were similar to ours in terms of the treatments that reduced peripheral vascular resistance. In our study, decreasing peripheral vascular resistance via EVT in patients with PAD led to decreased systolic and mean BP and improved lower-limb BP. Additionally, for patients with severe symptoms, the relief of leg pain may attenuate sympathetic activity and lead to a subsequent preferable effect on hemodynamic status. Jujo et al. recently reported that EVT may improve sensory disturbances associated with peripheral ischemic sensory neuropathy in patients with critical ischemia. Lawes demonstrated that systolic BP and mean arterial pressure were associated with both fatal stroke and ischemic heart disease in the Asia–Pacific region. Most importantly, EVT of the target lesions can lower peripheral vascular resistance, decrease BP, and reduce future cardiovascular events.Fudim et al.Our study has some limitations. This was a single-center retrospective study and not a randomized double-blind placebo-controlled trial. Furthermore, this study included a small sample size because the AESCULON mini® was used at the discretion of the attending physician. Also, AESCULON mini® was used instead of a reliable right heart catheter because it is noninvasive. Twenty-four-hour BP monitoring and AESCULON mini® data on days other than that of the EVT were lacking. EVT may be affected by sympathetic tension and sedation. The right atrial pressure used for SVR calculation was set to 5 mmHg, but an error may occur depending on the case. No significant difference was observed in SVR before and after EVT comparing chronic total occlusion and nonchronic total occlusion groups, iliac lesions, and femoral lesions. Furthermore, no significant difference was observed in SVR before and after EVT between TASC II classifications in both iliac and femoral lesions. It could be because the problem of vascular bed due to residual peripheral or contralateral lesions and the difference in the improvement rate of stenosis degree due to EVT were not considered. Finally, long-term outcomes were not evaluated in this study.The mechanism of BP reduction by EVT for patients with lower-limb PAD includes the reduction of SVR and PG between central BP and diseased lower-limb BP.


Endothelial dysfunction can be studied measuring myocardial perfusion reserve (MPR). MPR is the ratio of stress and rest myocardial perfusion (MP) and reflects the capacity of vascular bed to increase perfusion and microvascular responsiveness. In this pilot study, our aim was to assess MPR of 19 patients with kidney transplant (CKD stages 2–3) and of ten healthy controls with quantitative [p = 0.0015]. After correction of basal MP by cardiac workload [MPcorr = basal MP/individual rate pressure product (RPP) × average RPP of the healthy controls], the difference between the groups disappeared . There was no difference in stress MP between the kidney transplant patients and the healthy subjects . Although MPR was reduced, MPRcorr  did not differ between the kidney transplant patients and the healthy controls .Basal MP was statistically significantly higher at rest in the kidney transplant patients than in the healthy controls [1.3 (0.4) ml/min/g and 1.0 (0.2) ml/min/g, respectively, MP during stress is preserved in kidney transplant patients with CKD stage 2–3. The reduced MPR appears to be explained by increased resting MP. This is likely linked with increased cardiac workload due to sympathetic overactivation in kidney transplant patients. The cardiovascular mortality risk is 10–20 times higher in dialysis patients compared to the general population .Endothelial dysfunction and oxidative stress are associated with rapidly developing atherosclerosis in advanced kidney disease . The amoMyocardial perfusion reserve (MPR), the ratio of hyperemic and basal blood perfusion, integrates the hemodynamic effects of epicardial stenosis, diffuse atherosclerosis, smooth muscle relaxation, and endothelial function . CV mortThere are only a few Doppler echo-based studies of MPR in patients with kidney transplant , 18. Stu15O]H2O PET and evaluate the technique for our future prospective study.In this pilot study, our aim was to assess MPR of kidney transplant patients without manifest atherosclerosis by means of H2O PET. Laboratory samples were taken at the time of myocardial imaging. Pretransplantation AAC score was assessed from lateral lumbar radiography. Echocardiography was made as pretransplantation examination while the patients were in predialysis follow-up or in dialysis.Basal and stress MP and MPR were measured with H2O and adenosine. The subjects were positioned supine in the camera . A low-dose helical CT scan with automatic dose modulation  was acquired during normal breathing before the resting PET scan to correct for photon scatter and attenuation. Electrocardiogram (ECG), heart rate (HR), and blood pressure were monitored continuously during the studies.Venous catheter was placed in an antecubital vein for injection of oxygen-15-labeled water [15O]H20 PET was performed as described earlier [15O]H2O radioactivity, an identical [15O]H2O PET (470 MBq) sequence was performed during hyperemia. Adenosine was initiated 2 min before the stress scan for maximal vasodilatation. The mean radiation dose was 1 mSv for the perfusion study.Rest and stress MP imaging with . All patients had normal EF [mean EF 66 (5)%].p < 0.0001). P-ProBNP and P-Tnt were significantly higher in the kidney transplant group than in the controls .There was a statistically significant difference in eGFR and plasma creatinine between controls and transplant patients . Systolic blood pressure and MAP at stress were higher in the kidney transplant patients than in the healthy controls .Hemodynamic measurements are shown in Table p = 0.0044 and p = 0.0015, respectively). The difference of basal MP between the groups disappeared after correction of basal MP by RPP (p = 0.31). There was no difference of statistical significance in stress MP or stress MPR between the groups . There were no differences in regional stress MP between the main coronary arteries. MPR in kidney transplant patients was lower than in controls, and the difference was statistically significant (p = 0.0029). However, after correction by RPP, the difference between the groups disappeared (p = 0.8).MP values are presented in Table p = 0.74; stress MP, p = 0.19; MPR, p = 0.31) or between women and men . The previous dialysis type did not have any statistically significant effect on MP . There was no statistically significant correlation between Hb, subject’s age, age of the transplant, dialysis vintage, BMI or EF and basal or stress MP or MPR . There was a statistically significant correlation between LVMI and stress MP and MPRcorr .There was no statistically significant difference in MP values between diabetics and non-diabetics . However, the correlation disappeared after correction by cardiac workload . There was no correlation of statistical significance between the change of eGFR after transplantation (difference between eGFR at 1 year after transplantation and at the time of PET imaging) and MP values .Basal MP correlated with eGFR when 29 subjects of both groups were combined  ml/min/g in the kidney transplant patients compared to the value 1.0 (0.2) ml/min/g of the healthy controls. Because the resting MP is related to myocardial work and metabolic demand, HR, and systolic blood pressure must be considered when comparing MP basal values within a study . After RElevated RPP in patients with kidney transplant can be explained by sympathetic overactivation. Sympathetic overactivation has been established already in early stages of CKD . StudiesStress MP did not differ between the groups. It is very likely, that there was no obstructive CAD either in the patients or in the healthy controls, because there were no regional differences in stress MP between main coronary arteries. Furthermore, we used pretransplantation AAC score to estimate CV risk. Increasing AAC score, especially score values greater than 8–15, has been associated with severely increased risk for CV events in dialysis patients –31. AAC 13N] ammonia PET between patients with stages 1–3 CKD and the healthy controls [15O]H2O PET comparable stress MP between patients with stages 3–5 CKD and the control subjects [82Rb] PET study in patients with CKD stage 3 H2O PET in measuring MP of patients with kidney transplant. The difference in MPR between the healthy controls and the patients with kidney transplant can be explained by increased cardiac workload in transplant patients, which is probably associated with increased sympathetic activity. We are continuing our cardiac studies with prospective cohort of dialysis patients on kidney transplant waiting list.In conclusion, this study showed the capability of [


Vascular injury is a landmark of hypertension and enhanced external counterpulsation (EECP) has been identified as a noninvasive treatment to restore the capacity of endothelial cells. However, the effect of EECP on blood pressure lowering in hypertension and the potential mechanism remain unknown.n = 20) or control group (n = 20). We also evaluated in vitro function of endothelial progenitor cells (EPCs). Furthermore, multivariate analysis was performed to determine the actual correlation between EPC function and FMD.We measured the ambulatory blood pressure (AMBP) and flow-mediated endothelial dilation (FMD) in the essential hypertensive patients who were randomly assigned to the EECP group (P < 0.05] and diastolic  blood pressure and increased FMD value . In addition, the migration  and adhesion  functions of EPCs in the EECP group were improved significantly, whereas no change was observed in the control. Both migration  and adhesion  of EPCs correlated with FMD. After multivariate analysis, the migration  and adhesion  functions still independently correlated to FMD.Compared with the control, EECP group exhibited decreased systolic [(133.2 ± 4.9) mmHg vs. (139.3 ± 6.4) mmHg, The present study demonstrates for the first time that EECP decreases both systolic and diastolic blood pressure and increases FMD value in hypertension. The fall in endogenous EPCs repair capacity might be an important mechanism of hypertensive vascular injury and could be restored by EECP. Hypertension affects 30% of Chinese adult population and remains the most important risk factor for cardiovascular disease . VasculaAccelerated re-endothelialization is an important approach for injured artery repair. Our previous study demonstrated that circulating endothelial progenitor cell (EPC) number and activities declined in hypertension . AccumulThis study proposed to investigate the effect of EECP on BP and flow-mediated endothelial dilation (FMD). Furthermore, the correlation of EPCs capacities and FMD were examined to explore the underlying mechanism of EECP effect.n = 20) or control group (n = 20). Patients with essential grade 2 or 3 secondary hypertension, coronary artery disease (CAD), aortic valve disease, or medication history were excluded.This study was a prospective, randomized controlled study approved by the Medical Ethics Committee of Eighth Affiliated Hospital of Sun Yat-sen University. Forty outpatients aged 20–45 years with essential grade 1 hypertension without any medication treatment were included and randomized into the EECP group (AM to 8:59 PM and every 60 min during 9:00 PM to 8:59 AM the next day.Ambulatory blood pressure monitering (ABPM) measurement was in accordance with the method recommended by the clinical guidelines . DiagnosFMD reflects artery endothelial dilation and is a marker of endothelial function . All subComplete EECP protocol was performed on all subjects in the EECP group with 35 times, 5 times a week , and 60 min for each time.2. Effective hemodynamic changes of EECP were demonstrated by achieving a diastolic-to-systolic ratio of 1.2 with the use of the plethysmographic technique  consisted of a treatment bed attached to an air compressor unit that was attached to a computerized control console. The therapy used a series of three cuffs placed on the calves, lower thighs, and upper thighs/buttocks. The cuffs received sequential distal-to-proximal pneumatic inflation upon onset of diastole and simultaneous release of pressure at end-diastole. Sequential cuff inflation during EECP treatment produced two opposite blood flow patterns: antegrade flow in the brachial artery and retrograde flow in the femoral artery. Sequential cuff deflation also produced systolic hyperemia. The pressure applied to the cuffs was set at 0.035–0.040 mPa/cmechnique .EPCs were cultured and characterized as detailed previously . Briefly3 cells/well. After incubation for 24 and 48 h, the cell proliferation was determined by Cell Counting Kit-8 (CCK-8) (Dojindo) according to the manufacturer’s protocol. The absorbance was measured at 450 nm using Elx800 Reader . EPC migration was determined using a modified Boyden chamber. Briefly, 2 × 104 EPCs, resuspended in 250 μL EBM-2, were pipetted in the upper chamber of a modified Boyden chamber . The chamber was placed in a 24-well culture dish containing 500 μL EBM-2 supplemented with either phosphate-buffered saline (PBS) or 100 ng/mL SDF-1 . After 24-h incubation at 37°C, transmigrated cells were counted by independent investigators blinded to grouping.The EPCs were incubated in a 96-well culture plate at 5 × 105 CM-DiI –labeled EPCs were added to each well and incubated for 3 h at 37°C. Nonattached cells were gently removed with PBS, and adherent EPCs were fixed with 4% paraformaldehyde and counted by independent investigators blinded to grouping.A monolayer of HUVECs was prepared 48 h before the assay by plating 2 × 105 cells in each well of a four-well plate. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without 1 ng/mL tumor necrosis factor-α (Peprotech) for 12 h. Then 1 × 104) were resuspended with EBM-2 and loaded on the top of the Matrigel. Each conditional group contained three wells. Following incubation at 37°C for 2 h, each well was imaged directly under a microscope, and an average of tubules was counted from three to five random fields.EPC tube formation experiment was conducted as follows: a growth factor–reduced Matrigel (Corning) was warmed up at 4°C overnight. After having been completely thawed, 60 μL of Matrigel was plated to 96-well plates at the same level to distribute evenly, and incubated for 1 h at 37°C. Late EPCs  software (version 22.0) .All the results are expressed as mean ± standard deviation. The Student We recruited 40 grade 1 hypertensive outpatients and randomized them into EECP  or control  group. The basic clinical characteristics of both groups are presented in P < 0.05] and diastolic BP  of EECP group decreased greatly, whereas there was no obvious difference in the control  was observed in the control group (ABPM and office BP are the standard methods for the diagnosis of hypertension. Both systolic [SBP: (133.2 ± 4.9) mmHg vs. (139.3 ± 6.4) mmHg,  control . FMD refol group .We grew early EPCs by culturing PBMCs in specific media for 7 days. Fluorescent staining showed that the vast majority of adherent cells expressed endothelial marker proteins  and a monocytic marker CD14 at comparable levels . All theP < 0.05), migration (P < 0.05), adhesion (P < 0.05), and tube formation (P < 0.05) capacities of EPCs. However, no similar pattern was found in the control  and adhesion  function of EPCs correlated with FMD  and adhesion  activities were still associated with FMD, which indicated that the migration and adhesion functions were independent predictors for FMD decline  = 0.47, 95% confidence interval (CI) = 0.27–0.64, with FMD . After m decline .The present study revealed that (1) EECP reduced both SBP and DBP in hypertension; (2) EECP increased endothelium-dependent, flow-mediated vasodilation; (3) declined EPC capacity in patients with hypertension could be restored by EECP and independently correlated with FMD. Our findings for the first time provide novel evidence that EECP regulates EPC capacity to repair hypertensive vascular endothelial injury, and EECP may become a noninvasive approach for hypertension management besides medication.The impact of hypertension for the increased risk of cardiovascular disease is initiated by altering endothelial function of the arterial vessels. Endothelium plays a critical role in regulating arterial compliance and resistance. Endothelial cells release numerous vasodilator and vasoconstrictor substances that help regulate blood flow and vascular tone during rest and exercise . FMD of EECP is a noninvasive therapy for the treatment of patients with CAD. Growing evidence suggests that improvement in endothelial function represents an important mechanism for the clinical benefits of EECP . Acute iImbalance between endothelial injury and repair requires a more effective approach to maintain endothelial homeostasis. Thus, regeneration of the vascular endothelium is of great importance . The endIn the present study, we found both EPC migration and adhesion activities positively correlated with FMD. After multivariate analysis, the correlation still existed. Therefore, EPC function can be considered as the independent predictor of endothelial-dependent vasodilation. Our results validated that endothelial-mediated vasodilation independently correlated to EPC function, which could be restored by EECP in hypertension. Collectively, EECP can improve endothelial-dependent vasodilation and lower BP in hypertension via regulating EPC function.It should be pointed out that this study has some limitations. First, this is a small sample size study; a larger-population study should be performed to strengthen these results. Second, the exact molecular mechanisms underlying the impairment of EPC functions related to vascular injury should be further elucidated in the future. Third, the efficacy of EECP on BP in different grades and stage of hypertension should be quantitatively analyzed by further prospective randomized clinical trials.In summary, we demonstrate for the first time that EECP modulates EPC function to improve endothelial-related vascular dilation. Taken the effect of EECP on BP lowering together, our data provide an impetus for future evaluation of EECP in hypertension therapeutic efficacy and prognosis.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Medical Ethics Committee of Eighth Affiliated Hospital of Sun Yat-sen University. The patients/participants provided their written informed consent to participate in this study.GW designed the project and are responsible for the overall content, contributed to revise the manuscript. JL, JS, and WW carried out all the experiments. JL and JS prepared the manuscript. All authors have seen and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In contrast to severe gestational hypertension, it is questioned whether antihypertensive medication for mild to moderate gestational hypertension prevents adverse maternal and offspring outcomes. Hypertensive drugs halve the risk of severe hypertension, but do not seem to prevent progression to preeclampsia or reduce the risk of complications in offspring. In fact, beta-blockers, a first line therapy option, are suspected to impair foetal growth. Disappointing effects of antihypertensive medication can be anticipated when the pharmacological mode of action does not match the underlying haemodynamic imbalance. Hypertension may result from 1) high cardiac output, low vascular resistance state, in which beta blockade is expected to be most effective, or 2) low cardiac output, high vascular resistance state where dihydropyridine calcium channel blockers or central-acting alpha agonists might be the best corrective medication. In the latter, beta-blockade might be maternally ineffective and even contribute to impaired foetal growth by keeping cardiac output low. We propose a randomized controlled trial to determine whether correcting the haemodynamic imbalance in women with mild to moderate hypertension reduces the development of severe hypertension and/or preeclampsia more than non-pharmacological treatment does, without alleged negative effects on foetal growth.Women diagnosed with mild to moderate hypertension without proteinuria or signs of other organ damage before 37 weeks of pregnancy are invited to participate in this randomized controlled trial. Women randomized to the intervention group will be prescribed tailored antihypertensive medication, using a simple diagnostic and treatment algorithm based on the mean arterial pressure/heart rate ratio, which serves as an easy-to-determine proxy for maternal circulatory state. Women randomized to the control group will receive non-pharmacological standard care according to national and international guidelines. In total, 208 women will be randomized in a 1:1 ratio. The primary outcome is progression to severe hypertension and preeclampsia and the secondary outcomes are adverse maternal and neonatal outcomes.This trial will provide evidence of whether tailoring treatment of mild to moderate gestational hypertension to the individual haemodynamic profile prevents maternal disease progression.NCT02531490, registered on 24 August 2015. Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality in the western world . In mostA drawback in studies investigating treatment of mild to moderate gestational hypertension is that they do not consider the maternal circulatory state or the circulatory response to the blood pressure lowering drug. Instead, most reported treatments involve stepwise use of compound drug classes, based on the physician’s experience; in this treatment approach, chosen medications are only changed if severe side effects are observed or if increasing dosages do not achieve the target blood pressure. This trial-and-error approach may not only delay the time interval to effective circulatory control, but may also negatively affect foetal wellbeing that may prelude to preterm birth.Antihypertensive drugs lower blood pressure via different mechanisms. Blood pressure is regulated within narrow boundaries by beat-to-beat baroreceptor-mediated alteration of cardiac output and vascular resistance. Blood pressure only changes when these two determinants are unable to compensate deteriorations; therefore, elevated blood pressure can be lowered by reducing cardiac output or vascular resistance, or both. Beta-blockers, central-acting alpha agonists, and calcium antagonists are commonly used to lower blood pressure during pregnancy. Selective beta-blockers lower elevated blood pressure predominantly by lowering the heart rate (HR) and reducing contractility, resulting in reduced cardiac output. Beta-blockers with additional ɑ-adrenergic receptor blockade activity, like labetalol, concurrently reduce peripheral resistance , 10. CenThe haemodynamic profile of gestational hypertension differs between individuals. On the one hand, gestational hypertension can originate from hyperdynamic circulation characterized by high cardiac output and low vascular resistance; this profile is often accompanied by late onset preeclampsia and normal foetal growth Fig. . On the In non-pregnant individuals with uncontrolled hypertension, haemodynamically tailored antihypertensive treatment almost doubled the chance of reaching the target blood pressure within 3 months of initiating or adjusting the therapy compared with conventional standard treatment based on the specialist’s preference , 24. DurThe aim of this study is to determine whether haemodynamically tailored antihypertensive therapy in pregnant women with mild to moderate hypertension reduces the incidence of severe hypertension and preeclampsia and improves offspring outcome compared with standard care.Our primary objective is to determine whether haemodynamically tailored treatment of mild to moderate hypertension reduces disease progression to severe hypertension and preeclampsia compared with standard care. Our secondary objectives are to assess the effects of this treatment approach on maternal and offspring outcomes, including concomitant HELLP syndrome and eclampsia, gestational age at delivery, and neonatal birth weight and centile.The Early Vascular Adjustments (EVA) trial is a randomized controlled open-label superiority trial, with two parallel groups (intervention and control). Progression to severe hypertension or preeclampsia is the primary endpoint. A schematic overview of patient enrolment and follow-up, and the SPIRIT timetable for the study are presented in Figs. Participants will be recruited from the outpatient clinic and department of obstetrics in Maastricht University Medical Centre, which is both a secondary and tertiary referring hospital. During every routine pregnancy check-up, blood pressure is measured. Women with mild to moderate hypertension (defined as systolic blood pressure measures ≥140 and < 160 mmHg and/or diastolic blood pressure ≥ 90 and < 110 mmHg) without symptoms or signs of preeclampsia will be given the study patient information form, and follow-up on blood pressure is planned at least 4 h later and within a few days. Eligible women who give consent will be randomized to the intervention or control group, after which they will continue regular pregnancy check-ups with blood pressure measurements; additional laboratory analysis will be performed as indicated. After 37 weeks’ gestation, induction of labour will be recommended to all participants, as this is associated with improved maternal outcome . Study eWomen must provide written informed consent before any study procedure occurs.Age ≥ 18 years;Living foetus before 37 weeks’ gestation;Diagnosed with mild gestational hypertension .Patients eligible for the trial must meet the following criteria at randomization:Severe hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mmHg);Diagnosed with preeclampsia, HELLP syndrome, or eclampsia;Taking antihypertensive drugs;Intending to terminate the pregnancy;Foetus has a major anomaly or chromosomal abnormality;Not able to comprehend the study outline;Contraindication for one of the possible prescribed antihypertensive medications.5 during the second and third trimester [5, the upper limit of healthy dilated total peripheral vascular resistance is 1300 dyne.s/cm5. Women can be considered vasoconstricted when gestational vascular resistance exceeds 1300 dyne.s/cm5 and vasodilated when vascular resistance is below 1300 dyne.s/cm5. To avoid the need for an additional tool to assess cardiac output (stroke volume × HR), the MAP/HR ratio is used as a proxy for the haemodynamic profile. The MAP/HR ratio differs from total peripheral vascular resistance assessment in that it does not account for stroke volume. During healthy pregnancy, the mean ± SD stroke volume is 75 ± 10 ml. In the estimation of which proportion of women can be assumed to be vasoconstricted or vasodilated using the MAP/HR ratio, we can estimate the range in which total peripheral vascular resistance must be by taking the mean ± 2 SD stroke volume. When the MAP/HR ratio exceeds 1.4, more than 95% of all women must be considered vasoconstrictive. Contrary, when the MAP/HR ratio is 1.1 or less, more than 50% of women are likely to have a vasodilated circulation  or standard care (control group). The antihypertensive medications we plan to administer to participants in the intervention group can be safely prescribed to pregnant women . Total primester , 29. ConA 34-year-old woman, eligible for participation is randomized for the intervention group. Her blood pressure is 145/80 (102) mmHg, with a HR of 60 bpm (MAP/HR ratio 1.7) and therefore she is prescribed slow release nifedipine 30 mg once a day, and at follow-up her blood pressure is 135/74 (94) mmHg, HR of 72 bpm (MAP/HR ratio 1.3). Therefore, methyldopa 250 mg 3 times daily is added. One week later her blood pressure is 118/74 (89) mmHg, HR of 74 bpm (MAP/HR ratio 1.2), which is below  treatment threshold, and adequate blood pressure control is reached. Check-ups are continued every 2 weeks.A 23-year-old woman eligible for participation is randomized for the intervention group. Her blood pressure is 155/91 (112) mmHg, and her HR is 94 bpm (MAP/HR ratio 1.2). She is prescribed methyldopa 250 mg three times daily. At the follow-up visit, her blood pressure measures 141/85 (104) mmHg, HR is 101 bpm (MAP/HR ratio 1.0). As she did not achieve target blood pressure, labetalol 100 mg 3 times daily is added. One week later, blood pressure is 125/75 (92) mmHg, 92 bpm (MAP/HR ratio 1.0) and adequate blood pressure control is reached. Check-up are continued every 2 weeks.Severe hypertension, defined as a systolic blood pressure ≥ 160 mmHg and/or a diastolic blood pressure ≥ 110 mmHg .Proteinuria (spot urine protein/creatinine ≥30 g/mol or ≥ 300 mg/24 h);Renal insufficiency (creatinine levels ≥90 μmol/L);Liver involvement ;Neurological complications ;9/L, disseminated intravascular coagulation, haemolysis) [Haematological complications (thrombocytopenia defined as platelet count below 150*10molysis) .Preeclampsia defined as hypertension and one or more of the following new-onset conditions:Maternal outcomes: side effects of medication, required level of care, serious maternal complications , birth-related variables, and placental abruption.Neonatal outcomes: miscarriage, gestational age at delivery, birth weight and centile, Apgar score at 1 and 5 min after birth, use of antenatal corticosteroids and surfactant, adverse perinatal outcomes , required level of care, and duration of care.Data will be recorded in predesigned case record forms. Data on pregnancy and neonatal outcomes will be collected from the hospital maternity records. Additional neonatal outcomes will be collected from the discharge summary when neonates are admitted to the neonatal care department.Severe hypertension and preeclampsia develop respectively in 20% and 15–25% of women initially diagnosed with mild to moderate gestational hypertension , 32. As 2 test, or Fisher’s exact test in groups with less than five cases, to compare the incidence of severe hypertension and preeclampsia in the intervention group and the control group. We planned to conduct a per protocol sub-analysis in with women with at least 80% of their medication intake assessed by self-report at each pregnancy check-up. Secondary outcomes will be assessed by using X,2 Fisher’s exact test, Mann-Whitney U or T test as appropriate. For both primary and secondary outcomes, crude and adjusted odds ratio’s will be calculated (control group will be considerate as reference) and adjustments will be made for gestational age at recruitment. Separate analyses will be conducted to evaluate whether or not optimal blood pressure control was reached, if the type of medication and dosage affected the outcomes, which haemodynamic profiles were most prevalent, and if the initial haemodynamic profile affected the outcome, and to explore the effect of BMI, parity and age on the haemodynamic profile and response to medication.The effectiveness of haemodynamically tailored treatment of mild to moderate gestational hypertension will be evaluated based on the intention-to-treat principle. Descriptive statistics will be used to compare baseline characteristics between study groups. The primary analysis will be an XMild to moderate hypertension is a common complication during pregnancy, leading to increased maternal and foetal mortality and morbidity when it progresses to severe hypertension, preeclampsia and associated sequela. Previous studies show paradoxical maternal and foetal outcomes when a general, stepwise antihypertensive medication strategy is used. Previous studies on treating gestational hypertension have not considered the maternal circulatory profile and pharmaceutical mode of action of the prescribed medication, and the contemplated response to the medication class, while hypertensive pregnant women exhibit distinct circulatory profiles. This trial will investigate whether haemodynamically tailored treatment of mild to moderate gestational hypertension prevents progression to severe hypertension and preeclampsia without paradoxical maternal and offspring outcomes as observed in traditional non-tailored stepwise treatment approaches. We will tailor antihypertensive treatment to participants’ individual haemodynamic profiles using a simple diagnostic and treatment algorithm that includes the MAP and HR values. Directly measuring cardiac function might determine the underlying haemodynamic profile more precisely, but these methods (such as echocardiography) are labour-intensive and require expertise. Our designed algorithm represents a pragmatic approach to choosing appropriate antihypertensive drugs and can be easily implemented since both parameters are readily available in daily clinical practice.


Supplemental Digital Content is available in the text Available evidence shows conflicting results with regard to a potential detrimental effect of hypertension on clinical outcomes in patients who undergo mechanical thrombectomy (MT). We performed a meta-analysis to evaluate the impact of hypertension on the prognosis of patients with acute ischaemic stroke (AIS) treated by MT.We systematically reviewed previous studies in the PubMed, EMBASE, and Cochrane library databases that reported MT outcomes in AIS patients and their relationships with hypertension or blood pressure. We used a poor outcome (modified Rankin score >2 at 3 months) as the primary end point. Mortality and symptomatic intracranial hemorrhage were the secondary end points. We incorporated a random effect for trials in all models.I2 = 43%) and higher mortality . Symptomatic intracranial hemorrhage did not differ by patient hypertension status.Data from 6650 patients in 31 articles that evaluated the effect of hypertension or blood pressure on outcomes after MT were included. Compared with patients without hypertension, patients with hypertension had significantly higher odds of a poor outcome (odds ratio 0.70; 95% confidence interval 0.57–0.85; The present study confirms that hypertension and high blood pressure are associated with a poor outcome at 3 months after MT in AIS patients. However, the causal relationship between hypertension and a poor outcome remains undetermined, and further investigations are required to ascertain whether AIS patients receiving MT could benefit from intensive blood pressure control. Ischaemic stroke contributes to 70% to 80% of all stroke cases. Several randomized clinical trials have demonstrated the safety and efficiency of mechanical thrombectomy (MT) in the management of acute ischaemic stroke (AIS) caused by larger vessel occlusion. Although significant improvements have been demonstrated by recent randomized clinical trials, many patients do not have good functional outcomes even though timely and successful revascularization is achieved.Stroke is the second-leading cause of death in the world and is a major cause of serious disability for adults.,5 It is speculated that hypertension may also be associated with the treatment efficiency of MT, and several post hoc trials have indicated that in patients treated with MT, hypertension was independently associated with poor outcomes at 3 months.,7 In contrast, other studies showed that there was no significant difference in 90-day independent functional outcomes and complications between the hypertension group and the nonhypertension group. Available evidence shows conflicting results with regard to a potential detrimental effect of hypertension on clinical outcomes. Therefore, we aimed to conduct a meta-analysis of published studies to determine whether hypertension or admission blood pressure was associated with a poor outcome in patients treated with MT for AIS.Previous studies have shown that hypertension is related to poor functional outcomes, mortality and haemorrhagic transformation after intravenous or intra-arterial thrombolysis.2 The common evidence-based medicine framework Patient/Population, Intervention/Exposure, Control, Outcome was used to specify our research question: Did patients with AIS caused by emergent large vessel occlusion who received MT (patient population) accompanied with hypertension (exposure) have a poor functional outcome, higher rates of mortality and symptomatic intracerebral hemorrhage (sICH) (outcomes) than did patients without hypertension (control)?The systematic review and meta-analysis were performed according to the preferred reporting items for systematic reviews and meta-analyses statement.2.1The meta-analysis data was from published research studies. Hence, ethical review is not applicable.2.2We searched studies without language restrictions from the MEDLINE, EMBASE, and Cochrane library databases from January 2010 to November 2018 to identify potentially relevant studies reporting the influence of hypertension or blood pressure on efficacy or safety outcomes in AIS patients treated with MT. Search terms were set with the subject headings and keywords “Stroke or Brain Infarction or Cerebral Infarction or Cerebrovascular Disorders,” “Thrombectomy or Mechanical Thrombolysis or Endovascular Treatment or Endovascular Therapy,” and “Hypertension or Blood Pressure.”2.3Two qualified investigators (Zhengzhou Yuan and Ning Chen) independently screened titles and abstracts of references identified by the searches. In cases of disagreement, consensus was achieved through referral to a third reviewer (Muke Zhou). After primary selection, the full text of closely related studies was obtained and re-evaluated for eligibility, which determined the final inclusion of the study in the meta-analysis Fig. . Studies(1)the age of included AIS patients was ≥18 years old, and the sample size was ≥30;(2)all included patients were treated with MT; and(3)a statistical analysis of the association of outcomes (efficacy or safety) with a history of hypertension or blood pressure was reported. criteria: use of antihypertensive medicines, systolic blood pressure (SBP) ≥140 mm Hg, or diastolic blood pressure (DBP) ≥90 mm Hg. Only those that were published as full-length articles were considered. We excluded case reports, nonhuman studies, meta-analyses, guidelines, technical notes, or studies with treatment time >24 hours after stroke onset. A study pertaining to posterior circulation AIS was excluded. For studies with overlapping published data from the same institution, the most updated or most inclusive data were chosen for the analysis.Hypertension was identified from self-reports or doctors’ measurements at baseline and follow-up measures or questionnaires meeting at least 1 of 3 JNC82.4Data extraction from eligible studies was also performed by 2 investigators (Jian Guo and Yanan Zhang) with a standardized data extraction form that included the first author, publication year, country included, study period, study design, number of participants, participants’ age and sex, occlusion sites, National Institutes of Health Stroke Scale [NIHSS] score at admission, MT devices used , definition and incidence of outcomes , and associations with hypertension or blood pressure (maximum systolic blood pressure or diastolic pressure during the first 24 hours following MT) on functional outcomes. The quality of the articles was assessed using the Newcastle–Ottawa quality assessment scale. All the articles fulfilling the inclusion criteria were included in the meta-analysis independently of the quality score.2.5The primary end point of the present study was a poor outcome, defined as a modified Rankin scale score (mRS) of 3 to 6 at 90 days after MT treatment. The second outcome included sICH  and mortality at 90-day follow-up.I2 statistic . We performed random-effects meta-analyses to pool the estimates for each comparison. We performed subgroup analysis to investigate the primary end point. We also performed a sensitivity analysis examining the comparative outcomes only including multi-center studies. Funnel plots were used to assess publication bias. Meta-analysis and meta-regression were conducted using Review Manager 5.3. A probability value of <0.05 was considered significant. Except for heterogeneity testing, the significance was accepted at a probability value of 0.10.Using patients without a history of hypertension as the reference group, the effect size for hypertension according to the odds ratio (ORs) and associated 95% confidence interval (CIs) was calculated by the Mantel–Haenszel method. The effect sizes for maximum SBP and DBP during the first 24 hours following MT were reported as the mean difference based on the inverse variance method between patients with and without poor outcomes. Heterogeneity between studies was quantified with the 33.1,7,10–38 that included a total of 6650 patients (4174 hypertension and 2476 nonhypertension) were included in the meta-analysis. The preferred reporting items for systematic reviews and meta-analyses flow diagram is provided in Figure A total of 15,659 articles were found in the initial literature search, and 5402 records were duplicated. After the records were reviewed at the title or abstract level, 9905 records were eliminated: 6513 studies not related to our study; 2732 reviews, errata, comments, case reports, or study protocols; and 313 studies in which the number of patients was <30. Of the 347 remaining articles, the full text was reviewed. In total, 31 articlesThe proportion of hypertension patients was 62.8% 4174/6650). All studies reported the occlusion location, 18 studies included anterior circulation strokes only, and the remaining 13 studies included both anterior circulation strokes and posterior circulation strokes. Of the 23 studies that reported the correlation between hypertension and the 3-month follow-up mRS score, 11 studies were conducted in Europe, 6 in the United States, and 6 in Asia. Details of the individual trials used for analysis for each group, including methodological and baseline characteristics of the included studies, are listed in Table 74/6650. 3.2I2 = 43%)   . Compared with those without hypertension, patients with hypertension were associated with significantly lower odds of functional independence at the 90-day follow-up  Fig. .I2 = 33%)  , and less than 17 points  were both associated with significantly lower odds of functional independence. The results of the multi-center studies that were included were also highly consistent .Hypertension was also associated with higher mortality after 90-day follow-up  Fig.  between 3.3The funnel plot did not suggest publication bias for hypertension to poor outcomes and mortality after 3 months of follow-up Fig. .4 Most strokes in the United States are ischemic. Ischemic stroke is due to occlusion of a cerebral blood vessel and causes cerebral infarction. Awakening with or experiencing the abrupt onset of focal neurologic deficits is the hallmark of the diagnosis of ischemic stroke. The most common presenting symptoms of ischemic stroke are unilateral weakness and speech disturbance. Atherosclerotic thrombotic disease of the cerebral or extracerebral vessels, and cerebral embolism are 2 main causes of ischemic stroke. Epidemiologic studies have established many ischemic stroke risk factors, such as age, family history, chronic kidney disease, and sleep apnea, but the most importance of these are hypertension, diabetes mellitus, atrial fibrillation, and hyperlipidemia. There is a well-established relationship between blood pressure and the risk for developing of ischemic stroke, the relationship is consistent, continuous, and independent of other risk factors.Among all the neurologic diseases in adults, stroke ranks first in importance and frequency. Since 2015, there has been clear evidence that addition of MT can further improve the outcome in patients with severe neurologic deficits from a proximal intracranial vessel occlusion. The addition of MT with second-generation devices to alteplase within 6 hours of ischaemic stroke doubles the rate of reperfusion at 24 hours and functional independence, and increases the likelihood of improving by 1 point or more on the mRS by 2.5 times. Candidates for MT are patients with severe neurologic symptoms (NIHSS score ≥6), no major ischemic changes on the baseline CT scan (Alberta Stroke Program Early CT Score score ≥6), good pre-stroke functional status (mRS ≤2), early presentation (Time from symptom onset to groin puncture <24 hours) and Presence of proximal intracranial artery occlusion.Over the past 2 decades, the treatment of acute ischemic stroke has been deeply transformed. Began 20 years ago, administered Intravenous alteplase thrombolysis within 4.5 hours, increases the odds of no significant disability (mRS 0–1) by about a third. Second, Asians have a higher proportion of intracranial atherosclerosis, and higher blood pressure can provide more cerebral perfusion; Third, the heterogeneity among the American studies included is greater (I2 = 63%). Finally, the sample size of the United States (n = 864) and Asia (n = 828) is smaller than that of the European studies (n = 2738).Evidence from currently available data suggests that hypertension and maximum SBP and systolic blood pressure (SDP) during the first 24 hours following MT are associated with lower rates of good functional outcomes at 3 months after MT in AIS patients; moreover, hypertension is associated with higher rates of mortality. In contrast, no difference in sICH was found between patients with and without hypertension. The subgroup analysis showed that Europeans with hypertension were significantly associated with poor functional outcomes but that Asians and Americans  were not. This finding may be attributable to the following explanations. First, there are differences in the genetic form and type of hypertension among Europeans, Americans, and Asians. Numerous studies have confirmed that hypertension and high blood pressure are associated with sICH and poor functional outcome in acute ischaemic stroke,,47 and higher maximum SBP was also associated with poor functional outcomes after MT. The post hoc data analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands reported that BP did not affect the benefit or safety of MT in patients with AIS, but it also confirmed a strong correlation between systolic blood pressure and functional outcomes in ischaemic stroke, and the association was U-shaped. Both low and high baseline mean SBP measurements were associated with poor functional outcomes. They also found that higher mean SBP was associated with increased sICH risk. In our meta-analysis, hypertension was associated with poor outcomes but did not increase sICH risk. The proportion of patients with high systolic hypertension in this study was small, and these studies started later, when the technology was more mature.It has been estimated that 26% of the world's adult population had hypertension in the year 2000, and the proportion will increase to 29% by 2025. The proportion of hypertension patients was 62.8% in our study. However, the optimal guided blood pressure treatment data during and after MT are very limited. The ESCAPE studies suggest that SDP ≥150 mm Hg may help to promote and maintain adequate collateral blood flow when the artery is still occluded, and once reperfusion is achieved, it is a wise choice to control the patient's blood pressure within a normal range. The DAWN study recommended that SDP is maintained at a level <140 mm Hg in the first 24 hours after arterial recanalization in MT patients. A network meta-analysis also indicates that treating patients with a reduction in SBP below 140 mm Hg may significantly reduce the risk of vascular disease and all-cause mortality. These findings support more intensive SBP control among adults with hypertension. It is reasonable to assume that the effect of intensive SBP and SDP control would become visible in AIS patients. Although our results show that maximum SBP and SDP during the first 24 hours following MT are related to unfavorable functional outcomes, the precise association between maximum SBP and SDP with functional outcomes in AIS patients needs to be further studied.The 2019 update of the American Heart Association/American Stroke Association early stroke management guidelines recommend the treatment of BP if it is higher than 180/105 mm Hg both during the procedure and for 24 hours afterward for patients with AIS who undergo MT; the guidelines also recommend the maintenance of BP at a level of <180/105 mm Hg if patients achieve successful reperfusion.Our meta-analysis has some limitations. First, all the studies included in our analysis were observational, and most of them cannot control for baseline characteristics. It is reported that patients with hypertension are often older and have more frequent histories of diabetes, dyslipidemia, heart failure and carotid stenosis, which indicates that the pooled unadjusted results of this study may be influenced by baseline data. However, similar results were obtained in studies in which the average NIHSS score at admission was greater than or less than 17, and the same results were also achieved in multi-center studies, which partly enhanced the reliability of our results. Second, subgroup analysis by region showed that Europeans with hypertension had poor functional outcomes, but the relationship between hypertension and poor outcomes is not statistically significant in Asia, which affects the applicability of this result to a certain extent. Third, the definition of sICH was obtained from the original study, rather than from a standardized definition, which may affect the reliability of the pooled results at this end point. Finally, because the direct comparison of blood pressure and prognosis of MT is too limited, we included some articles indirectly comparing blood pressure and prognosis, and we did not evaluate the quality of the included studies. We tried to overcome this problem through sensitivity analysis, which included an analysis of studies with high NIHSS scores at admission and subgroup analysis of studies conducted at multiple centers. Intravenous medication, even intravenous combination therapy, will be an important part of this solution. The application of non-pharmacological methods, such as weight loss and dietary sodium restriction, may be helpful for hypertension but may be insufficient for most patients with AIS who are treated with MT. Randomized trials of these patients with different blood pressure control strategies are clearly warranted, as these strategies concern a strong prognostic factor related to the poor prognosis of MT, and they also represent a few controllable risk factors for cerebrovascular disease.Several research questions have arisen from this work, the most important of which is how to achieve and maintain the optimal range of blood pressure control after MT, because these experiments have found that lower maximum blood pressure is related to good function outcomes; however, there is no optimal range of blood pressure control.In conclusion, our study revealed that hypertension, high maximum SBP and SDP are associated with poor functional outcomes at 3 months after MT in AIS patients. However, the causal relationship between hypertension and poor outcomes remains uncertain. Further larger and multi-institutional randomized controlled studies may provide important novel information for the management of AIS patients with hypertension who received MT and determine the ideal blood pressure management strategy.Conceptualization: Zhengzhou Yuan.Data curation: Zhengzhou Yuan, Jian Guo, Yanbo Li, Li He.Formal analysis: Zhengzhou Yuan, Jian Guo.Funding acquisition: Jian Guo, Li He.Investigation: Zhengzhou Yuan, Muke Zhou, Jian Guo, Yanbo Li, Li He.Methodology: Zhengzhou Yuan, Muke Zhou, Jian Guo, Yanan Zhang, Yanbo Li, Li He.Project administration: Muke Zhou.Resources: Muke Zhou, Yanan Zhang, Li He.Software: Ning Chen, Yanan Zhang, Yanbo Li.Supervision: Yanan Zhang.Validation: Ning Chen.Visualization: Ning Chen.Writing – original draft: Zhengzhou Yuan.Writing – review and editing: Ning Chen, Jian Guo, Li He.


Previous epidemiological evidence has identified many risk factors for coronary artery disease (CAD). Pulse pressure (PP) was reported to be associated with CAD. However, more attention was paid to aortic PP than to brachial PP. This cross-sectional study aimed to investigate the direct relationship between brachial PP and the presence and extent of CAD in stable angina patients.We recruited a total of 1118 consecutive patients with stable chest pain suspected of CAD. After screening with exclusion criteria, 654 patients were finally included in our study. Every patient underwent both blood pressure measurement and selective coronary angiography. Univariate and multivariate analysis were performed to analyze the association between PP and the presence and extent of CAD.P < 0.0001). Binary logistic regression analysis further confirmed this association. The risk of multivessel CAD increased significantly in patients with brachial PP ≥ 60 mmHg  and as per 1 mmHg increased in brachial PP , independent of age, gender, body mass index (BMI), smoking, diabetes, hypercholesterolemia and creatinine (Cr). This association was still of statistical significance in subgroup analysis of hypertension and diabetes.This study revealed that brachial PP was an independent correlate of multivessel CAD. In multivariate generalized linear regression model, increasing brachial PP (per 1 mmHg) were associated with the increased number of diseased vessels (β = 0.01, SE = 0.00, Increasing brachial PP was significantly and independently associated with increased risk of multivessel coronary disease in stable angina patients. The association of brachial PP with CAD was more pronounced in hypertension group than in non-hypertension one. Coronary artery disease (CAD) is the leading cause of death worldwide , 2. GiveFrom December 2012 to February 2014, we consecutively recruited 1108 patients with stable chest pain suspected of CAD undergoing selective CAG. We excluded those with unstable angina, non-ST segment elevation myocardial infarction, ST-segment elevation myocardial infarction, previously coronary angiographically confirmed CAD or a history of revascularization (241). Patients with any of the following conditions were also excluded: treated with medications affecting blood pressure (BP) within 12 months  (94); a history of heart failure with a left ventricular ejection fraction (LVEF) less than 50% (68); renal failure (36), thyroid diseases (12), or incorrect BP measurements or reports (3). A total of 654 patients were finally included in our study . Smoking status depended on self-report. Diabetes was defined as fasting blood glucose≥7.1 mmol/L and/or random blood glucose≥11.1 mmol/L and/or receiving hypoglycemic treatment. Hypercholesterolemia was defined as total cholesterol≥5.72 mmol/L and/or low-density lipoprotein cholesterol≥3.64 mmol/L and/or receiving lipid-lowering treatment. Serum creatinine (Cr) was determined by the biochemical analyzer and expressed in μmol/L. Hypertension was defined on the basis of previous diagnoses and also the two BP measurements taken during the study (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg).To obtain the required information, every individual received standardized interviews and basic checks prior to the CAG. Body mass index (BMI) was calculated by dividing weight (kg) by height . Measurements were repeated 1 to 2 min apart and the average of two readings was recorded. If two readings of SBP or DBP differed by more than 5 mmHg, the BP then was remeasured and the average of the three readings was recorded.Continuous data were expressed as mean and standard deviation (SD), while discrete data as numbers and percentages. Continuous data were compared by the variance analysis or the Kruskal-Wallis test, while discrete data by the chi-square test  or FisheP values< 0.1. Multivariate logistic regression analyses were applied to investigate the relationship between brachial PP and the multivessel CAD. Subgroup analyses were performed to further explore the relationship between brachial PP and CAD.Univariate and multivariate generalized linear regression analyses were used to determine the relationship between brachial PP and the number of diseased vessels. Confounders were selected on the basis of their relevance to the outcome or the presence of more than 10% mutations in effect estimate or For missing of covariates , we used multiple multivariate imputations. Our purpose was to maximize statistical power and minimize bias caused by excluding covariates of missing data in data analysis. In addition, we used sensitivity analysis to identify whether created complete data had significant difference from pre-imputation data. Our findings demonstrated that created complete data showed no significant difference from raw data.P value < 0.05 as of statistical significance. EmpowerStats version 2.17.8 (http://www.empowerstats.com/cn/) and R software (http://www.R-project.org) were used for statistical analysis in our study.We regarded a Patient demographics are presented in Table P < 0.0001), after adjusted for age, gender, BMI, smoking, diabetes, hypercholesterolemia and Cr. This association was also observed when patients divided into non-hypertension and hypertension  were associated with the increased number of diseased vessels  and as per 1 mmHg increased in brachial PP , independent of age, gender, BMI, smoking, diabetes, hypercholesterolemia and Cr (Table P = 0.0135) and hypertension group , while a trend for patients with brachial PP ≥ 60 mmHg, among non-hypertension group  and hypertension group   had multivessel CAD . Among the included patients, the risk of multivessel CAD increased significantly in patients with brachial PP ≥ 60 mmHg (OR = 1.69, 95% CI = 1.14–2.48, In this cross-sectional study, we explored the association between brachial PP and CAD in patients with stable angina. What we found was that increasing brachial PP was significantly and independently associated with increased risk of multivessel coronary disease. This association was more pronounced in hypertension group than in non-hypertension one.Many studies have so far investigated the association between PP and CAD. Lee et al.  were theStudies on the relationship between aortic PP and CAD are numerous, but few are directly examining brachial PP and CAD. Brachial PP, calculated by subtracting DBP from SBP, can be easily acquired without invasive equipment. As an easily available and non-invasive indicator, it can be better applied in clinical practice. Gatzka et al.  found thPP, either measured in aortic or brachial artery, has shown a significant association with CAD. However, the jury is still out on the underlying mechanisms of the association between PP and CAD. In terms of hemodynamics, PP is largely determined by arterial stiffness, stroke volume and wave reflections . Among tAlthough brachial PP has been reported to be associated with the risk of CAD, studies have also shown that brachial PP gives less indications on the severity of coronary atherosclerosis than aortic PP. However, as a non-invasive indicator, brachial PP can be easily acquired without invasive equipment, thus, can be more acceptable to patients and better applied in daily clinical practice. Brachial PP can not only help to identify high-risk CAD patients for early intervention, but also be applied to develop effective therapeutic strategies for these patients.The limitations of our study are worth noting. First and foremost, the design of the study was cross-sectional. However, whether there is a real causal relationship between brachial PP and CAD has not been confirmed. Secondly, the patients enrolled in our study were from a single center. The study subjects might not represent the whole population, affecting the generalization of the conclusion. What’s more, the bias in data collection should not be ignored. The treatment of antihypertensive medications within 12 months was self-reported. And the definition of hypertension was depended on previous diagnoses and the two BP measurements taken during the study. Also, the bias regarding blood pressure measurements should not be ignored.A positive relationship between brachial PP and the number of diseased coronary vessels was found in our study. Increasing brachial PP was significantly and independently associated with increased risk of multivessel coronary disease in the stable angina patients. The association was more pronounced in hypertension group than in non-hypertension one.


To compare the plasma N-terminal pro-C-type natriuretic peptide concentrations of normotensive pregnant women, patients with mild preeclampsia, and patients with severe preeclampsia. U tests.  We collected venous blood samples from 25 normotensive pregnant women, 15 patients with mild preeclampsia, and 15 patients with severe preeclampsia. The women were at 30th to 40th weeks of gestation and in an age range of 20 to 35. The N-terminal pro-C-type natriuretic peptide levels were measured by ELISA. Statistical comparisons were made by one-way analysis of variance, Kruskal–Wallis, and Mann–Whitney P < 0.001), whereas there was no significant difference between those with mild preeclampsia and the normotensive groups (P > 0.05).  The median (interquartile range-IQR) values of the N-terminal pro-C-type natriuretic peptide were 6.48 (3.33) pmol/L in the normotensive women group, 7.37 (3.43) pmol/L in patients with mild preeclampsia, and 11.52 (6.13) pmol/L in patients with severe preeclampsia. The N-terminal pro-C-type natriuretic peptide was significantly elevated in the severe preeclampsia study group ( Our data indicate that the plasma concentration of the N-terminal pro-C-type natriuretic peptide is significantly increased in patients with severe preeclampsia, but not in patients with mild preeclampsia. The severity of preeclampsia may be related to the circulating levels of the N-terminal pro-C-type natriuretic peptide concentrations. The natriuretic peptide family is composed of three principal peptides sharing the same 17 amino acid ring structure: A-type  natriuretic peptide, B-type (brain) natriuretic peptide, and C-type natriuretic peptide . The A-tThe C-type natriuretic peptide was the third member of this family to be identified. The C-type natriuretic peptide is a locally acting peptide in an autocrine/paracrine fashion. It is present at very low concentrations in the plasma, as a consequence of its rapid clearance from the circulation . It has Preeclampsia and eclampsia are two of the hypertensive disorders of pregnancy. The pathophysiological mechanisms in the development of these disorders are not clear yet although it is well known that endothelial dysfunction has a fundamental role . As far   Systolic blood pressure of 160 mm Hg or higher or diastolic blood pressure of 110 mm Hg or higher on two occasions at least 4 hours apart while the patient is on bed rest (unless antihypertensive therapy is initiated before this time)  Thrombocytopenia   Impaired liver function as indicated by abnormally elevated blood concentrations of liver enzymes , severe persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnoses, or both  Progressive renal insufficiency   Pulmonary edema  New-onset cerebral or visual disturbancesA total of 55 pregnant women followed in the Department of Obstetrics and Gynecology, Zeynep Kâmil Women and Children Diseases Education and Research Hospital, Turkey, were enrolled in this study. 15 patients with severe preeclampsia and 15 patients with mild preeclampsia were selected for the preeclamptic group. A written informed consent was obtained from all women. All women selected were between the ages of 20 and 35 and had singleton pregnancies. Those with diabetes, cardiac or renal disease, and chronic hypertension were excluded from the study. Also, women diagnosed with HELLP syndrome were excluded from the study. All women were also in their third trimester of gestation. None of the women was in labor. Arterial blood pressures were recorded for at least two different times 4 hours apart when the patient is on bed rest from the right arm using a standard sphygmomanometer with an appropriate cuff size by the same clinician. Korotkoff sound K5  was used to determine diastolic blood pressure. Preeclampsia is defined by the minimum criteria of blood pressure ≥140/90 mm Hg after 20 weeks of gestation and proteinuria 300 mg/24 hours or 1+ dipstick, according to the report by the Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy . Twenty 2EDTA). The blood samples of patients with preeclampsia were collected before they received any medication. Immediately after sampling, plasma samples were separated by centrifugation at 2000 × g for 15 min at 4°C and frozen at −80°C until assayed. The N-terminal pro-C-type natriuretic peptide levels in these plasma samples were measured with the ELISA method using the N-terminal pro-C-type natriuretic peptide EIA Kit . The lower detection limit was 0.55 pmol/L. The intraassay variations were 5-6% for a concentration range of 5.1–20 pmol/L, and the interassay variations were 1% for a concentration range of 5–20 pmol/L as stated by the manufacturer. All of the samples were run in a duplicate manner in the same assay. The laboratory staff were blinded to the clinical condition of the women in the study groups.One venous blood sample (10 mL) was collected from the patients with preeclampsia and the healthy controls into tubes containing ethylenediaminetetraacetic acid . Repeated measures of one-way analysis of variance (ANOVA), Kruskal–Wallis, and Mann–Whitney Our study protocol was approved by the institutional review board.P < 0.05) (As shown in  < 0.05) . The disP < 0.001) and mild preeclampsia (P < 0.01) study groups, whereas there was no significant difference among the mild preeclampsia and normotensive study groups (P > 0.05). The median (IQR) values of the N-terminal pro-C-type natriuretic peptide were 6.48 (3.33) in the normotensive women group, 7.37 (3.43) in patients with mild preeclampsia, and 11.52 (6.13) in patients with severe preeclampsia. The spread of data among the study groups and the control group is displayed in With regard to the biochemical findings presented in Nppc) is associated with hypertension in a Japanese study [The C-type natriuretic peptide was the third member of the natriuretic peptide family to be discovered. The natriuretic peptide family has important effects on the control of blood pressure, volume, and the management of the renal function . The C-tse study . Allelicse study . Furtherse study . The C-tse study  and adrese study , aldostese study , and vasse study . Preeclase study . The secse study .In our study, we compared the plasma N-terminal pro-C-type natriuretic peptide concentrations of 55 subjects, composed of 25 normotensive healthy pregnant women and 30 pregnant women with preeclampsia, all of which were in their 30–40 weeks of gestational ages. The preeclamptic study group was further divided into severe and mild preeclamptic groups, each composed of 15 patients, discriminated according to the criteria defined in the report by the Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy . We founOur data indicate that the severity of preeclampsia could be related to the circulating levels of the N-terminal pro-C-type natriuretic peptide. Espiner et al. indicated that preeclampsia and GHT with SGA were associated with raised maternal plasma NTproCNP . Since tSince we know that C-type natriuretic peptide infusion drops blood pressure, it may also find a therapeutic use in treatment of hypertension in pregnant women. It is evident that further studies are needed to clarify the prognostic and therapeutic role of the C-type natriuretic peptide in preeclamptic patient population.