Portopulmonary hypertension (POPH) is characterized by pulmonary vasoconstriction, while hepatopulmonary syndrome (HPS) is characterized by vasodilation. Definite POPH is a risk factor for the survival after orthotopic liver transplantation (OLT), as the congestive pressure affects the grafted liver, while subclinical pulmonary hypertension (PH) has been acknowledged as a non-risk factor for deceased donor OLT. Given that PH measurement requires cardiac catheterization, the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography is used to screen for PH and congestive pressure to the liver. We investigated the impact of a subclinical high TRPG on the survival of small grafted living donor liver transplantation (LDLT).n = 34). The mean pulmonary artery pressure (mPAP) measured after general anesthesia with FIO20.6 (mPAP-FIO20.6) was also assessed. Patients exhibiting pO2 < 80 mmHg and an alveolar-arterial oxygen gradient (AaDO2) ≥ 15 mmHg were categorized as potentially having HPS . The clinical course after LDLT was investigated according to subclinical high TRPG.We retrospectively analyzed 84 LDLT candidates. Patients exhibiting a TRPG ≥25 mmHg on echocardiography were categorized as potentially having liver congestion  and older donor age (p = 0.008) were correlated with a poor 40-month survival. Although a higher mPAP-FIO20.6 was expected to correlate with a worse survival, a high mPAP-FIO20.6 with a low TRPG was associated with high frequency complicating subclinical HPS and a good survival, suggesting a reduction in the PH pressure via pulmonary shunt.A subclinical high TRPG (20.6 may not accurately reflect the congestive pressure to the liver, as the pressure might escape via pulmonary shunt. A subclinical high TRPG is an important marker for predicting a worse survival after LDLT, possibly reflecting congestive pressure to the grafted small liver.In cirrhosis patients, mPAP-FIO The most commonly found pulmonary vascular complication is hepatopulmonary syndrome (HPS), in which the pulmonary arteries dilate, resulting in arterial deoxygenation  . Althougpoxemia) .2 < 50 mmHg), the implications for OLT are understood to apply not only with deceased donor LT (DDLT) but also living donor related LT (LDLT). However, the post-OLT course of POPH-complicated patients is often unsatisfactory, and severe (mPAP > 45 to 50 mmHg) patients are considered absolutely contraindicated for OLT. The International Liver Transplant Society Practice Guidelines indicate that, unlike HPS, there are no data to support the concept that POPH (treated or untreated) should be an indication for OLT [Given that HPS can be resolved after orthotopic liver transplantation (OLT) even when hypoxemia is severe PaO2 < 0 mmHg, t for OLT . FurtherThe objective of the present study was to investigate the impact of cirrhosis-related cardio-pulmonary complications on the LDLT survival. Although patients with confirmed POPH and HPS are rare, those with mild pulmonary hypertension and mild HPS are more common. Given that right heart catheterization is not performed for all patients during the pre-operative investigation, the tricuspid regurgitation pressure gradient (TRPG) measured by transthoracic echocardiography (TTE) was adopted to estimate the PH-related congestive pressure in the transplanted liver. The peak systolic pressure gradient between the right ventricle (RV) and the right atrium (RA) can be estimated using the peak systolic TRPG . The TRPThe risk factors associated with the 3-month, 1-year, and 40-month survival were investigated.The study group consisted of 84 retrospectively analyzed liver cirrhosis patients who received LDLT at our hospital Table . All patInformed consent was obtained from each patient included in the study, and the study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in the approval by the ethics committee at Okayama University Hospital. After obtaining the patients’ written informed consent, a detailed medical questionnaire was completed by the doctors.2 levels (> 15 mmHg) and decreased PaO2 levels (< 80 mmHg) according to the definition by a European Respiratory Society task force [All of the patients underwent an arterial blood gas analysis and TTE before OLT as pre-operative screening. The patients were classified as having subclinical HPS when they exhibited elevated AaDOsk force . If a pask force . There w2 with mechanical ventilation and was likely affected by this condition. We used these advisory mPAP data, namely mPAP-FIO20.6, to identify subclinical high TRPG patients in detail.We performed Swan-Ganz catheterization just before the operation after administering general anesthesia for OLT to determine the mPAP. Although mPAP> 25 mmHg could be diagnosed with definite POPH, the mPAP obtained in the present study was performed under 60% OPost-OLT, the patients were treated with a standard immunosuppressive regimen (tacrolimus or cyclosporine A with steroids and/or mycophenolate mofetil). Patients with hepatitis C recurrence were treated with interferon-containing regimens, except for five recently transplanted patients who received direct anti-viral agents.U-test or chi-squared test was used to compare the parameters between patients with subclinical HPS and subclinical non-HPS or patients with a subclinical high TRPG and subclinical non-high TRPG. A univariate analysis to define the factors affecting the survival was performed by a log-rank test. The factors found to be significant according to a univariate analysis and the widely accepted post-OLT survival-related factor ‘MELD score’ were used in the multivariate Cox regression analysis. The correlations between the TRPG and mPAP were analyzed using Spearman’s rank correlation method. Statistical significance was set at P < 0.05. The four subgroups were compared using the Mann-Whitney U-test or chi-squared test with Bonferroni’s correction.The JMP software program  was used to conduct the statistical analyses. Continuous variables were expressed as the median (interquartile range), and the Mann-Whitney p = 0.033), indicating a more severe condition of cirrhosis. TTE revealed right ventricular dilatation more frequently in subclinical high TRPG patients than in other patients (p = 0.022).The baseline liver diseases were 43 hepatitis C virus (HCV)-related cirrhosis, 7 hepatitis B virus (HBV)-related cirrhosis, 13 non-alcoholic steatohepatitis (NASH), and 21 other etiologies. Twenty-nine patients (34.1%) had hepatocellular carcinoma (HCC)  were most frequently identified, exhibiting the lowest MELD score among the groups examined, as expected. Patients with a high TRPG and high-mPAP-FIO20.6  with clinically definite PH tended to have a high MELD score (p = 0.006 vs Group 4). Patients with a high TRPG and low mPAP-FIO20.6  did not show right heart dilatation. Patients with a low/normal-TRPG and high mPAP-FIO20.6  had the highest rate of positive subclinical HPS (p = 0.003 vs Group 4), suggesting that the high congestive pressure might be decreased via right-to-left pulmonary shunting.The TRPG levels observed by TTE and mPAP-FIOted Fig. . To detep = 0.004). A higher donor age and MELD score and a subclinical high TRPG were significantly correlated with the one-year survival. However, a multivariate analysis revealed a subclinical high TRPG to be the only significant factor (p = 0.003). The standard cardiac function as reflected by the ejection fraction was not correlated with the survival or post-LDLT renal function.The pre- and peri-operative risk factors that correlated with the short-term (three-month and one-year) survival are shown in Table p = 0.008 and 0.012 respectively). The survival rate according to the subclinical high TRPG status is shown in Fig. p = 0.002). The standard cardiac function as reflected by the ejection fraction was not correlated with the survival or post-LDLT renal function, as in the short-term analysis.The pre- and peri-operative risk factors that correlated with the 40-month survival are shown in Table 20.6 was a significant risk factor for the post-LDLT survival, the post-LDLT survival was investigated according to the TRPG and mPAP-FIO20.6 status in Table 20.6, while a high mPAP was not found to be a significant risk factor in the present study, despite it being widely accepted as such (p < 0.001). Group 3 patients with a high mPAP-FIO20.6 and low TRPG showed a good survival, probably because co-existing HPS released the regurgitation pressure.Given that a high TRPG but not a high mPAP-FIOThe causes of death were not significantly different between groups, but the rate of recurrence of HCV was lower in the subclinical high TRPG patients than in the non-subclinical high TRPG patients (2/10 vs. 2/4) (Table 20.6, the co-existence of subclinical HPS might reduce the TRPG, thus resulting in a good prognosis. The TRPG but not mPAP-FIO20.6 was a critical factor that may reflect the pressure directed to the grafted small living-donor liver. Given that this study was retrospective and the sample size was relatively small, larger prospective studies to confirm the present results are needed.In the present study, a high TRPG was a definite survival-defining factor after LDLT that might be able to be controlled before or during operation. Even in patients with a high mPAP-FIOReported factors associated with a worse survival after primary DDLT include a high MELD score, HCV positivity, aged recipient, aged donor , mechaniIn LDLT settings, graft blood flow in the initial few weeks after surgery has been reported to influence the overall outcome of small-for-size liver graft OLT. Poor venous outflow and resulting hepatic congestion have been shown to be strong factors for a poor graft function . Several20.6 and TRPG. Given that O2 administration is an accepted supportive therapy for PH, the present mPAP-FIO20.6 may be lower than the mPAP measured by standard right heart catheterization used as a diagnostic marker for PH. Although the present mPAP-FIO20.6 is different from the mPAP measured by the standard method, all of our patients were in a similar medical condition, and therefore the investigation of the correlation in this population was deemed acceptable. The difference between standard mPAP and mPAP-FIO20.6 cannot be determined. The clinical impact of these values on the post-LDLT survival also differed, as a higher TRPG was significantly correlated with the outcome, while a higher mPAP-FIO20.6 was not. The patients included in our present study exhibited a relatively large left atrium with high AaDO2 compared with the normal range observed in the Japanese population, indicating right-to-left shunt predominance with subclinical HPS. The co-existence of subclinical HPS was particularly predominant in Group 3, indicating that TRPG is not high even when mPAP is high. The pressure against the grafted liver is reflected by the TRPG, not by the mPAP, as the pressure may be reduced due to pulmonary arterial bypass with HPS. Given the small sample size, especially in Group 1 and 3, larger studies are needed to confirm this possibility.TRPG measured by TTE is usually positively correlated with mPAP measured by right heart catheterization . However20.6 values were high. Under these conditions, regurgitation pressure from the pulmonary artery might escape via an intra-pulmonary shunt.HPS is more frequently found than POPH and has been acknowledged as a life-threatening complication; however, this condition can be resolved with OLT . The patThe cardio-pulmonary clinical condition of Group 2, who had a high TRPG and low mPAP, was associated with the worst outcome of the examined groups. This condition is similar to left-to-right shunting or right heart failure although not clinically evident. In addition, the Group 2 patients exhibited a lower frequency of RA dilatation than those in Group 1, showing a high TR pressure without RA dilatation, which indicated a strong pressure directed to the grafted liver. RA dilatation may relieve the direct pressure to the graft.20.6 for predicting the post-OLT survival. A high TRPG, even below the limit of PH, may reflect pressure to the grafted liver that might be critical for relatively small-for-size LDLT. Given that this study was retrospective and the sample size was relatively small, larger prospective studies to confirm the present results are needed. When patients with a high TRPG undergo LDLT, the administration of therapies to reduce the TRPG should be considered.TRPG as assessed by TTE may be more useful than mPAP by pre-operational right heart catheterization under FIO


Antihypertensive medications complicate studies of blood pressure (BP) natural history; BP if untreated (“underlying BP”) needs to be estimated. Our objectives were to compare validity of five missing data imputation methods to estimate underlying BP and longitudinal associations of underlying BP and age. We simulated BP treatment in untreated hypertensive participants from Atherosclerosis Risk in Communities (ARIC) in visits 1–5 (1987–2013) using matched treated hypertensive participants. The underlying BP was imputed: #1, set as missing; #2, add 10 mmHg for systolic, 5 mmHg for diastolic; #3, add medication class-specific constant; #4, truncated normal regression; and #5, truncated normal regression including prior visit data. Longitudinal associations were estimated using linear mixed models of imputed underlying BP for simulated treated and measured BP for untreated participants. Method 3 was the best-performing for systolic BP; lowest relative bias  and average deviation from expected (0.04 to -1.79). Method 2 performed best for diastolic BP; lowest relative bias  and average deviation (-1.25 to -1.68). Methods 4 and 5 were comparable or slightly inferior. In conclusion, constant addition methods yielded valid and precise underlying BP and longitudinal associations. Hypertension, systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg, is prevalent in the U.S, affecting more than 30% of adults . Along wIncreasing use of antihypertensive medications is certainly important for preventing complications of hypertension but makes studies of blood pressure (BP) natural history difficult to investigate. For instance, setting BP to missing for all subjects receiving antihypertensive treatment can substantially reduce the sample size and power to detect effects of interest. Alternatively, including treated BP measures while investigating BP natural history can bias results towards subset of non-hypertensive subjects. In order to prevent these biases, several methods have been proposed to impute the “underlying BP”, BP that would have been measured if the individual was not taking antihypertensive medications. Adding a constant BP to the measured BP of the treated individual has been most commonly used, especially in genetic epidemiology –10. MoreTherefore, the objective of this study is to comprehensively compare existing methods to impute underlying BP among individuals taking antihypertensive medications in a longitudinal setting using data from a large community-based cohort, the Atherosclerosis Risk in Communities (ARIC) Study, with repeated BP measurements over 26 years of follow-up.The ARIC Study recruited 15,792 individuals aged 45–64 years from four communities in Forsyth County, NC; Jackson, MS; northwest suburbs of Minneapolis, MN; and Washington County, MD. To date, ARIC has completed the baseline in 1987–89 and four follow-up visits in 1990–92, 1993–95, 1996–98 and 2011–13, respectively. Detailed study design and methods have been previously described . All visBP was measured via a random zero sphygmomanometer in visits 1–4 and an automatic sphygmomanometer (OMRON HEM-907 XL) in visit 5 by a certified trained technician in accordance with ARIC manual of procedures ,15. BrieFor this study, participants with measurements of SBP and DBP at 2 or more visits and data on antihypertensive medication use and class of medication were included. Other requisite variables were age, sex, race, and body mass index (BMI). Detailed inclusion criteria for visits 1–5 are presented in 2. Using antihypertensive medication literature to guide us  / βmeasured untreated BP). Controls were matched on diabetes and kidney dysfunction status. Abbreviations: SBP, systolic blood pressure; Var, variance; DBP, diastolic blood pressure.The relative bias (%) was calculated as the average relative difference in regression coefficient from each simulation (100 x [β(DOCX)Click here for additional data file.


An increasing number of end-stage heart failure patients are now implanted with continuous-flow left ventricular assist devices (CF-LVADs). Although this therapeutic approach is associated with improved clinical outcomes, continuous flow physiology reduces arterial pulse pressure and pulsatility to an extent that is unique to this population. Recent data suggest that high blood pressure (BP) contributes to life-threatening complications such as pump thrombosis and stroke of CF-LVAD patients. However, limited understanding of the distinct hemodynamics of these pumps makes measurement and, consequently, medical management of BP quite challenging. Here, we review the evolution of LVAD design, the impact of CF-LVAD flow, and “artificial pulse” technology on hemodynamics and BP measurement, as well as suggest new approaches for the assessment and interpretation of the unique physiology of modern LVADs. More than five million Americans are currently suffering from heart failure (HF) , a chronOver the past decade, close to 20,000 patients have been supported by LVADs either as a temporary substitute or definitive alternative to heart transplantation, with comparable short-term survival . HoweverThe field of MCS has rapidly evolved over the past two decades. First-generation LVADs  were pulsatile devices that attempted to mimic the native pumping of the normal heart, providing enhanced arterial pulsatility. However, limited durability and reliability of the pump led to marginal improvements in patients’ survival. Contemporary second-generation LVADs are all continuous flow (CF-LVADs), and although they differ in the way they move blood within the pump , mechanistically, they are quite similar. A CF-LVAD consists of the inflow cannula that sits in the left ventricular (LV) cavity, the pump impeller that rotates at a constant pre-set speed, and the outflow graft that continuously delivers blood into the aorta, augmenting the circulation throughout the entire cardiac cycle with low to no arterial pulsatility. Although longevity of the pump and patients’ survival have substantially improved in CF-LVADs compared to HeartMate XVE , they arCurrently, FDA-approved CF-LVADs are the HeartMate II , as bridge to transplant (BTT) and destination therapy (DT), and the HVAD  for BTT indication only. The primary difference between the two devices is in the impeller design as it relates to the angle between the impeller outflow and its axis of rotation . HeartMaAccurate BP measurement and control has a critical importance in identification and management of CF-LVAD patients. Elevated BP has been associated with CF-LVAD-related complications, including stroke and pump thrombosis , 20. Sug.Several mechanisms may account for the association between hypertension and adverse events in CF-LVADs . ElevateThe increased afterload secondary to the elevated BP may cause reduced frequency of aortic valve opening, commissural fusion, and ultimately aortic insufficiency . In bothThough BP is associated with stroke and pump thrombosis, it is still unclear whether high BP pre-LVAD represents a marker of hypertension to stroke while on CF-LVAD support or rather the marker of a poor BP control in the outpatient in the outpatient setting. The recent PREVENtion of HeartMateII Pump Thrombosis Through Clinical Management (PREVENT) trial protocol demonstrated a low rate of pump thrombosis (2.9% at 3 months and 4.8% at 6 months) when applying standardized implant and perioperative management techniques including MAP maintenance below 90 mmHg. However, BP levels were similar in patients with and without pump thrombosis in this study . More reAccurate measurement of BP in patients implanted with CF-LVADs is traditionally considered a challenge due to the continuous flow outputs associated with these devices. Several interlinking endogenous and device-related factors determine the degree of flow and pressure oscillation observed in the individual patient. For a specified pump speed, LVAD flow varies inversely to the head pressure gradient resulting in more flow during systole and less during diastole. In end-stage HF, the reduced contractility of the failing LV translates into a diminished oscillatory flow during the cardiac cycle. As a result, systolic BP (SBP) is usually lower than that observed in the general population. However, the continuous addition of blood volume to the circulation causes a reduction in pressure decay during diastole. Thus, patients’ pulse pressure (PP [PP = SBP − DBP]) is reduced to the extent that a pulse may not be palpable via traditional means.Unlike the hemodynamics of healthy individuals Fig. a, in CF-Indwelling arterial catheters (A-line) are considered the most accurate method to measure BP in CF-LVAD patients, but its use is limited to hospitalized patients during their stay in the intensive care unit. Common automated BP monitors often fail to measure BP due to the lack of detectable flow oscillations in CF-LVAD patients. In fact, Doppler ultrasound is often used as an alternative to automated BP monitors in patients without an A-line . UnfortuTo better understand why common automated BP monitors are often unable to read BP in CF-LVAD patients, it is worth to review how BP cuff systems work. A typical oscillometric BP monitor is composed of an inflatable BP cuff connected to a pressure transducer. When activated, the cuff initially inflates to a pressure above the SBP and then gradually deflates until the transducer senses an increase in oscillations (this point corresponds to SBP); the system continues to deflate until the transducer senses the maximum oscillation amplitude (this point corresponds to MAP). Using SBP and the MAP values, the system can estimate DBP. In CF-LVAD patients, the narrow PP critically reduces the difference between the first increase in oscillation  and the point of maximum oscillation . Background noise from the continuous flow pump further impairs the ability of oscillometric BP monitors to obtain a BP reading in this unique population. However, the Terumo Elemano BP Monitor  could overcome this limitation thanks to a slow and more sensitive cuff deflation process . Unfortu+AP), the HeartMate 3, provides intermittent swings in flow that result in the creation of an artificial pulse. Every 2 s, this pump alternatively powers down the rotor speed by 2000 rpm for 0.15 s, then increases by 4000 rpm for 0.20 s, before returning to the set speed [The new generation CF-LVAD with an artificial pulse  may not recognize and/or accurately interpret pump-specific patterns of oscillations during cuff deflation. For example, accurate calculation of MAP may require assessment over extended periods of time that include several cardiac cycles. In addition, BP monitors will not be able to recognize separately heart and LVAD systolic and diastolic BP values. This might represent an important limitation since it is conceivable that measurement of individual BP components could be relevant for the prediction of adverse events in this patient population.In 1966, Shepard and colleagues developed a concept of energy equivalent pressure (EEP) , where B+AP  is expected to markedly increase over the next number of decades. It is therefore critical to meet patients’ needs by identifying valid methods to measure and manage their BP as a way to reduce morbidity and mortality. Currently, automated BP monitors (and/or Doppler) can be effectively used in the majority of patients who are implanted with an FDA-approved CF-LVADs such as the HeartMate II and HVAD. However, the HeartMate 3 offers a new challenge since it incorporates artificial pulse technology. This fixed pulse is asynchronous to the native heartbeat, and because of that, it generates an erratic BP profile that includes cardiac and LVAD-generated systolic and diastolic components. Nevertheless, accurate assessment and interpretation of the (patho)physiological consequences of this unique hemodynamic profile may play an important role in optimizing safety and efficacy of this novel CF-LVAD technology.


Introduction: Adequate treatment of hypertension is infrequent in older patients. Determiningthe prevalence of hypertension in older patients, identifying the pattern of the treatment in thisage group and evaluating their awareness of the disease may help healthcare systems to deviseappropriate programs for controlling the disease.Methods: This descriptive cross sectional study included a sample from population of Tabriz, alarge city in North-West of Iran, who were 60 years or older. Data collection and blood pressuremeasurements were conducted in the households of the participants from 1st June 2015 through1st August 2015. Hypertension was defined as systolic and/or diastolic blood pressure (DBP)≥150/90 mm Hg or receiving anti-hypertensive medications. Prevalence and determinantsof hypertension, awareness of patients about their diagnosis and prevalence of treatment andadequately controlled blood pressure were determined.Results: The prevalence of hypertension was 68.0%. Among hypertensive patients 81.8% wereaware of their diagnosis, 78.0% were receiving antihypertensive medications. Among treatedpatients, 46.2% were adequately controlled. In univariate analysis, prevalence of hypertension wassignificantly higher in women . Women were more likely to be awareof diagnosis and to receive antihypertensive medications; however, the prevalence of adequatelycontrolled blood pressure was similar in treated men and women. Among included variables inlogistic regression analysis, older age, lower number of family members in household, cardiacdiseases, being on low salt low fat diet, higher Body mass index (BMI) and not being educatedwere independently associated with having hypertension.Conclusion: Hypertension is highly prevalent among older population of Tabriz. Despite highrate of treatment, the rates of control are relatively low, indicating a demand for prevention andbetter management of hypertension in older individuals. Along with that, hypertension imposes substantial financial burden on health care systems.5 While the prevalence of hypertension is declining in higher income countries, lower income countries are encountering an increasing number of patients with hypertension.6 Since demographic and social changes in these societies contribute to this issue, improving lifestyle and increasing the awareness of patients about the disease can help healthcare systems overcome the problem.5 On the other hand, developing countries encounter a growing number of aging populations. Even though prevalence of hypertension increases with age,8 adequate treatment is infrequent in older patients.2 Consequently, identifying the pattern of disease prevalence and risk factors is essential for devising a targeted screening program and promoting the awareness of people about the modifiable risk factors of hypertension.Although the global prevalence of hypertension is estimated to be about 22% in adult population of 18 years or higher, the prevalence differs between countries and among age groups.Regarding these facts, we devised a cross-sectional study focused only on older population to determine the prevalence of hypertension in Tabriz, the largest city in northwest of a middle-income country, Iran. The awareness of patients about their disease and prevalence of appropriate control of blood pressure and its determinant were also investigated in our study.This descriptive cross sectional study included a sample from Tabriz population, who were 60 years or older. Tabriz is the largest city in North-West of Iran, a middle-income country located in Middle East. Data collection and BP measurements were conducted in the households of the participants from first June 2015 through first August 2015.2*p*q/d2) with 95% CI, P = Q and d=0.03, the sample size was calculated to be 1067 cases. Participants were selected by probability sampling and classified using multistage clustering and probability proportional to size (PPS) technique. The study comprises representative household surveys in Tabriz.In accordance with the Cochran’s sample size formula .To obtain demographic and health related information, trained health workers for interviewing older people, visited the participants in their homes. Interviewers filled out the prepared questionnaires. Demographic information included questions regarding age, city of born, marital status, number of children, number of household members, educational level and employment status. The participants were asked to provide subjective information about cardiovascular comorbidities including diabetes mellitus, smoking status, hyperlipidemia, history of coronary artery disease, and family history of hypertension. The information regarding the amount of physical activity and dietary habits, awareness about hypertension diagnosis and annual physician visits were also gathered. Medical history was gathered by asking from patients along with reviewing their prescriptions.After volunteers rested for five minutes, trained interviewers measured their blood pressure from right and left arm, using sphygmomanometer and auscultatory method of measurement. While the arm of the patient was supported on the heart level, the bladder of appropriately sized blood pressure cuff was placed on midline over the brachial artery pulsation.Hypertension was defined as systolic blood pressure of 150 mm Hg or more and/or diastolic blood pressure of 90 mm Hg or more in right and/or left arm. Using anti-hypertensive medications for treatment of raised blood pressure was also considered as having hypertension regardless of the level of blood pressure measured at the time of the study. Isolated systolic hypertension (ISH) was defined as systolic blood pressure (SBP) of 150 mm Hg or more and diastolic BP of less than 90 mmHg.Participants who were on anti-hypertensive medications and their measured blood pressure was <150/90 mm Hg, were considered as the group with controlled blood pressure.A person with hypertension was considered “aware” if he/she gave a positive response to the question, “Have you ever been told by a doctor or other health professional that you had hypertension, also called high blood pressure?” A person with hypertension was classiﬁed as “treated” if he/ she reported taking antihypertensive medication at the time of the survey. A treated person was considered “controlled” if his/her average SBP was <150 mm Hg and average diastolic blood pressure (DBP) was <90 mm Hg.Diabetes mellitus was defined by a positive response to any of the questions, “Have you ever been told by a doctor that you have diabetes?”, “Are you now taking insulin?”; “Are you now taking diabetes pills to lower your blood sugar?”Height was measured using a stadiometer and weight was measured using a weighing scale that was periodically calibrated. Body mass index (BMI) was calculated by dividing body weight in kilograms to square of height in meters.The prevalence of hypertension was determined in study sample. Patients with and those without hypertension were compared and independent predictors of hypertension were determined by multivariate logistic regression analysis. Further, patients under treatment with anti-hypertensive medications were allocated into two groups and compared regarding appropriate control of blood pressure. The independent predictors of having controlled blood pressure were determined. To evaluate sex related differences, demographic and clinical data were compared between men and women with hypertension.t test. To evaluate the independent predictors presence of hypertension in study population multivariate logistic regression analysis was performed. The inclusion of variables in the final regression model was based on likelihood ratio test. A probability value of less than 0.05 was considered as statistically significant.Data were analyzed using the statistical software SPSS-16 . Categorical variables were expressed as frequencies and percentages and compared with chi-square test between groups. Continuous variables were described as mean ± standard deviation (SD) and compared between two groups using independent The mean age of patients was 70.1± 8.2 years and 514 (48.0%) of 1071 patients were male. The place of born was a rural area in 526 (49.1%) and an urban area in 514 (48.0%) patients. The mean number of family members living in one household was 3.1 ± 1.6 persons. The majority of individuals were married  and 278 (26%), 15 (1.4%), 7 (0.7%), 7 (0.7%) were widowed, divorced, single, in other relationship status, respectively.Among 1071 individuals included in our survey, 724 (67.6%) had hypertension. The measured systolic blood pressure was 150 mm Hg or more in 241 patients (22.5%). Diastolic blood pressure of 90 mm Hg or more was present in 235 (32.5%) of 724 patients. In 172 (23.8%) of 724 patients both SBP and DBP was above 150/90 mm Hg threshold.Among 724 hypertensive patients, 585 (80.8%) were aware of their diagnosis and 565 (78%) were receiving antihypertensive medications but in just 261 patients (46.2%) out of 565 treated patients blood pressure was adequately controlled. The most common medication used by patients was beta-blockers, which was used by 306 (54.2%) of 565 patients, followed by angiotensin receptor blockers (ARBs) used by 281 patients (49.7%). Among patients under treatment with antihypertensive medications, 278 patients (49.2%) were using a single medication while 287 (50.8%) were using two antihypertensive medications or more.P < 0.001). Hypertensive individuals were more likely to be illiterate, to have sedentary lifestyle and to be overweight. Diabetes mellitus and cardiac diseases were more prevalent in hypertensive group. Patients in hypertensive group were more aware of their blood pressure level and they were more likely to have annual ophthalmological and cardiovascular examinations and consume low-sodium low-fat diet. Waist circumference and waist to hip ratio were both higher in hypertensive group. Patients in non-hypertensive group were more likely to be active smoker and to have diagnosed cancer. The prevalence of asthma, hyperlipidemia, anxiety disorders and depression was similar in two groups  with higher level of education. Males were more likely to be married and to live in a nuclear family. Compared to men, women were significantly more aware of their diagnosis . Females were more likely to be under treatment with antihypertensive medications. . The prevalence of adequately controlled blood pressure in treated individuals was similar in males and females . Females had higher BMI level and lower physical activity level in comparison to males. The prevalence of diabetes mellitus was higher in females than in males. Females were more likely to receive monotherapy for treatment of hypertension 42.2% vs. 33.3%, P < 0.001). Waist to hip ratio was higher in females but waist circumference was similar in two groups. The rate of having health insurance was similar in males and females  but males were more likely to have supplemental health insurance plans 44.5% of females vs. 57.6% of males, P = 0.001).14 In a report from North-East of Iran, hypertension defined as blood pressure ≥140/90 mm Hg was present in 62% of individuals older than 60 years.9 In comparison, the prevalence of hypertension in elderly differs among low to middle income countries.15 Sought Africa is reported to have a very high prevalence of 78 %, while the prevalence of hypertension in older population is 59% in China and 32% in India. However, it should be noted that in all these studies, unlike our survey the threshold for defining high SBP is set to be 140 mm Hg.6As shown in this study, the prevalence of hypertension, as a major cardiovascular risk factor is 67.6% in our elderly population and as expected the prevalence increases with age. Unlike our study, most studies in Iran have included different age groups with no special focus on elderly.16 In our survey, 78% of hypertensive patients were aware of their hypertension but only 52.8% were under treatment with anti-hypertensive medications. The awareness of diagnosis in our region is higher than previous reports from Iran. In a study from Northeast of Iran, only 42.6% of patients older than 60 years were aware of their diagnosis and 17.6% were under treatment with hypertensive medications.9 In a recent survey from south of Iran, only 22.1% of patients of 60-69 years and 11.6% of patients older than 70 years were aware of their diagnosis.10 In comparison to developed countries, the reported prevalence of awareness is generally lower in low to middle income countries. However, the Federation of Russia had a prevalence of 72%.6 The prevalence of awareness is higher in developed countries and is reported to be about 80% in United States.18 The increasing level of awareness in the United States as a result of national health programs and advocates for decreasing cardiovascular diseases17 underscores the importance and efficacy of such health policies to detect and treat the affected individuals.Although the rise of blood pressure as a result of aging is inevitable, due to greater risk of cardiovascular diseases in older adults, proper treatment of hypertension as a major cardiovascular risk factor is mandatory.11 In another report from southern parts of Iran including individuals of age 20-74 years, the prevalence of controlled blood pressure among treated patients of all age groups was 34%.14 In comparison, the rate of adequately controlled blood pressure in treated patients was 72.7% in a recent report from united states in which the blood pressure goal of <150/90 mm Hg was applied for defining at-goal blood pressure.19 Different underlying factors may contribute to successful treatment of hypertension in older patients. In our study, the higher level of education and annual visits for ophthalmologic and cardiovascular examinations were associated with better control of blood pressure. This may originate from better adherence and optimal prescription of medications in annual visits. Also, patients who were receiving a single antihypertensive medication was more likely to have uncontrolled blood pressure. Even though older patients are prone to experience adverse effects of anti-hypertensive medications, effective treatment of blood pressure in older ages is generally achieved with multi-pharmacy.21 However, physicians may tend to underuse anti-hypertensive medications to avoid side effects of medications and decrease the risk of hypoperfusion in older patients.22 Despite the fact that we used a threshold of 150/90 mm Hg for defining controlled blood pressure, the prevalence of uncontrolled blood pressure in treated patients is still high. Increasing the quality of care with optimum use of anti-hypertensive medications and promoting life-style changes in patients may help in lowering the prevalence of uncontrolled blood pressure in our region. In a systematic review including data from Iranian population, it is reported that many patients consider hypertension as a consequence of daily stresses and quit using medications after relief from common symptoms such as headache and dizziness.23 Increasing the awareness of patients about the benefits of lowering blood pressure may also promote the rate of controlled blood pressure in our population.Among patients who were receiving anti-hypertensive medications, blood pressure was adequately controlled in only 46% of patients. This number is consistent with the results of a report from central regions of Iran, Isfahan, in which the prevalence of uncontrolled blood pressure was about 60% in patients older than 65 years.2 One of the important modifiable gender-related differences in our study population is lower level of physical activity in women compared to men. Along with increasing physical activity levels, reducing the sitting time with similar activity levels can also help in lowering the risk of cardiovascular diseases.24 In addition, hypertensive women in our region are more likely to be overweight. Since higher BMI level is associated with increased risk of cardiovascular diseases,2 increasing physical activity along with improving diet may also help patients to lose body weight and achieve lower BMI level. On the other hand, in comparison to women, men in our region are more likely to be unaware of their diagnosis. They are also less likely to receive anti-hypertensive medications. However, among treated patients, there is no significant difference in prevalence of controlled blood pressure. Our results regarding the sex-differences in prevalence of awareness and treatment with anti-hypertensive medications are in agreement with the results of the surveys took place in other regions of Iran10 as well as other low-middle income countries6 and United States.25 Promoting the awareness about the diagnosis of hypertension and potential benefits of treatment is essential, particularly among men.Another important finding of our study is the gender-related differences in prevalence of hypertension and associated comorbidities in affected individuals. According to our results, women are more likely to suffer from hypertension in older age groups. In comparison to men with hypertension, women are more likely to have concurrent diabetes mellitus, which further increases the risk of cardiovascular diseases.Prevalence of hypertension in older population is high in our region. Despite the fact that, awareness of the patients about their diagnosis is high, the prevalence of adequately controlled blood pressure in treated patients is low.This study was reviewed and approved by deputy of research ethics committee of Tabriz University of Medical Science. Informed consent was obtained from all participants.Authors declare no conflict of interest in this study.


However the treatment arm reported a drop of 2.4 mmHg of BP drop during the 8-week trial period. Analysis suggests that there was a significant difference in blood pressure readings at the end of 8 weeks among patients treated with losartan (P < 0.001). However, no such statistical association was observed in the standard arm (P 0.75). A slow, steady significant decline in post-dialysis BP was observed among euvolemic hypertensive patients that were treated with losartan 50 mg.To assess the effectiveness of losartan 50 mg on post dialysis euvolemic hypertensive patients against standard antihypertensive pharmacotherapy. A multicentre, prospective, randomized, single-blind trial was conducted to assess the effect of losartan 50 mg every other day (EOD), once a morning (OM) among post-dialysis euvolemic hypertensive patients. Covariate-adaptive randomization was used to allocate participants to a standard or treatment arm, and they were followed up for eight weeks. Pre-, intra- and post-dialysis session blood pressure (BP) measurements were recorded along with any adverse events. A total of 88 patients were randomized into standard (n = 44) and treatment arms (n = 44) and were followed for a period of 8 weeks. In the standard group, the mean post-dialysis blood pressure dropped by 0.3 mmHg by the end of the 8 With annual mortality rates of 23%, hypertension is one of the most prevalent conditions reported among haemodialysis patients1Hypertension in haemodialysis is multi-factorial and is not completely elucidated with volume overload. Renin angiotensin aldosterone system (RAAS) activation has been identified as one of the major contributors. Although patients may have a normal range of plasma rennin activity, its relation to exchangeable sodium has long been identified as associated with hypertension. Interestingly, the renin angiotensin system is activated in haemodialysis patients by the fact that renin is increased with haemodialysis ultra-filtration leading to hypertension4Fluid balance is an integral part of the management of haemodialysis patients, to prevent under- or over-hydration, which are associated with cardiovascular and other complicationsThe current study is a multicentre, prospective, randomised, parallel design, single-blind trial. The Hospital Universiti Sains Malaysia (HUSM), Kelantan, is the main research site. Patients from three private dialysis centres were also included in the current trial. The study protocols were approved by the ethical and research committee of Universiti Sains Malaysia (USM/JEPeM/15050173), and the trial was registered under Australian New Zealand Clinical Trials Registry (ACTRN12615001322527). The trial was registered on 2/12/2015, the first patient was enrolled on 10/12/2015, and the trial formally began on 8/02/2016. The study purpose was explained and informed consent was obtained before enrolling study participants. The study protocols met consolidated standard of reporting trials (CONSORT) guidelines. All study procedures were in accordance with national kidney foundation kidney disease outcome quality initiative (NKF KDOQI) practice guidelines for haemodialysisPost-dialysis euvolemic patients with systolic blood pressure >140 mmHg post dialysis, patients aged 30–80, patients undergoing dialysis for of at least 12 months, and patients willing to participate were included in the trial. Patients with amputations, pre-existing heart disease, neoplasm and cystic kidneys, patients treated with ARBs and patients with symptomatic, predialytic hypotension (SBP less than 110 mm Hg) or high blood pressure >200/100 mmHg were excluded from the study. Consent was taken from all the study participants. An appropriate time was given to patients for their consent to join the study. No patient was recruited for the study unless he/she had agreed to join the study without any external or internal pressure. Only the study participants were blinded during the course of study. All study participants underwent dialysis thrice a week. Hence all patients were regularly monitored for their blood pressure, adherence to medication and other study related parameters.A body composition monitor device (BCM) by Fresenius (BCM 4BJA3641) was used for assessing the volume status of patients at the end of a dialysis session and was also used for estimating patients’ dry weight13In randomized controlled clinical trials, a balanced allocation of covariates is an essential component in ensuring valid treatment comparisons. Covariate-adaptive randomization has an advantage over other randomization techniques, in that it is able to achieve a balance over a large number of covariates when the sample size is small to mediumBoth standard and treatment arms were randomized with equal number of patients. The standard arm patients received antihypertensive therapy (except RAAS inhibitors) including calcium channel blocker, diuretic, alpha and beta blockers, whereas the treatment arm patients were prescribed ARB (losartan) alone or in combination with standard antihypertensive pharmacotherapy. In both study arms, patients were allowed multiple antihypertensive pharmacotherapies to control blood pressure, upon discussion with a panel of experts, but only where entirely necessary to avoid any deterioration in a patient’s health. Finally, study intervention (losartan) and antihypertensive medication were given to the patients on a weekly basis by the principle investigator. A member of family was consented to monitor patient adherence at home whereas a pill check was performed once a week.A medication dose of losartan 50 mg/day for three weeks as a test dose was initiated to note any incidence of hypotension. Upon satisfaction, patients were continued with 50 mg/day every day apart from dialysis days. A persistent >180 mmHg post-dialysis blood pressure despite adding three hypertensive agents resulted in dose titration. The dose titration was initiated with losartan 50 mg to 100 mg followed by non-RAAS antihypertensive agents for treatment group. For the standard group, the choice of dose titration was left to expert opinion19The sample size for the current study was based on a statistical superiority trial (continuous data) design of a randomized control trialwhere, N = size per group; p = the response rate of standard treatment group; p 0 = the response rate of new drug treatment group; z = the standard normal deviate for a one or two sided x; d = the real difference between two treatment effect; a clinically acceptable margin; S = Polled standard deviation of both comparison groups. The sample size calculated from statistical superiority for randomized control trials is 35 for each arm, so altogether 70 euvolumic hypertensive euvolemic patients. Moreover a 25% dropout was also included, making total of 88 patients (44 in each arm).P less than 0.05. All statistical calculations were performed using SPSS version 20.Results were expressed as mean or percentage. Comparisons between treatment groups were made by using Wilcoxon tests after adjustment for the dynamic stratification variables . Cohen’s d test was applied to note the effect size. In addition, linear regression was applied to note any influence of patient characteristics on treatment outcome. This data is presented as hazard ratios and 95% confidence intervals. Statistical significance was set at All 88 patients [standard (n = 44) and treatment arm (n = 44)] completed the entire study and were followed for a period of 8 weeks. About 97% of the patients were ethnically Malay. Altogether, 45 male and 43 female patients were enrolled: 21 male and 24 female patients were randomized to the standard arm compared to 23 male and 20 female patients in the treatment arm. The mean age  & median age  age of both the arms were similar. 31 (70.5%) diabetic patients were randomized to the standard arm whereas 28 (63.6%) diabetic patients were randomized to the treatment arm .Since the treatment arm involved giving losartan to all 44 subjects, no ARB or ACE inhibitor was prescribed to the standard arm. A calcium channel blocker  was the most common antihypertensive medication prescribed to the standard group followed by a diuretic . Other medication included statins that was prescribed to 33 (75%) patients in the standard group and 32 (71.1%) patients in treatment group .The baseline blood pressure reading between both the groups were almost comparable. The mean baseline post-dialysis blood pressure of the standard arm was 157.5 (±14.3) mmHg compared to the treatment arm 156.3 (±13.4) mmHg. In the standard group, the mean post- dialysis blood pressure dropped by 0.3 mmHg by the end of 8 weeks, whereas in the treatment arm, the mean post-dialysis blood pressure reduced by 2.4 mmHg by the end of 8 weeks. Four (11.4%) patients in the first four weeks and 8 (22.8%) patients in the next four week in the treatment arm were able to achieve post-dialysis blood pressure of <140 mmHg but were not able to maintain it more than 3HD sessions. All study participants were maintained on losartan 50 mg only though out the coarse of study. There were no cases of mortality .Simple linear regression was performed to indicate patient-related factors that affected the study treatment outcome. Male (p 0.01) and diabetes , patients on dialysis >5 years (p 0.01) and ex smokers (p 0.04) had a significant association with blood pressure control among study participants .A mean drop in systolic blood pressure is observed in both the study groups. However, the treatment group indicates a greater decline in mean systolic blood pressure compared to the standard group. Further analysis suggests that blood pressure readings of the treatment group were significantly different at the end of the 8-week period (p < 0.001), whereas the standard arm had a non-significant blood pressure (p 0.75) difference at the end of 8 weeks from the baseline blood pressure reading .During the course of study, there were no cases of drop-out due to non-adherence to medication, adverse events or any other clinical scenario. Headaches were the most common ADR reported in the standard and treatment arms during HD session. Twelve (27.7%) patients reported ≤2 instants of headaches during the HD session in the standard group whereas 10 (22.7%) patients in the treatment group reported ≤2 and 2 (4.5%) reported 3–5 instants of headaches during HD sessions. There were no reported cases of hyperkalemia in either group .In the past, the emphasis has been on an overall BP reduction in haemodialysis patients. However, a “one-size-fits-all” approach for BP management may not be appropriate for all the patients on haemodialysis23et al., <20% of study participants reached the study goal of <140/90 mmHg during 3.5 years of patient follow-upThe current study reports that the losartan (ARB) 50 mg together with other antihypertensive drugs lowered BP by 2.4 mmHg  amongst euvolemic patients that were hypertensive (>140 mmHg) at the end of HD sessions. Our analysis also indicates that there was a statistically significant difference in systolic blood pressure from baseline and at the end of the 8-week study period among the treatment group. In a study by Iseki et al. reported an initial significant decline in blood pressure followed by non-significant difference in blood pressure reading among both groups. The authors attribute these findings to a relatively small sample size and duration, and most importantly vast variability in blood pressureIn a trial demonstrating the effects of telmisartan on haemodialysis patients, Huber et al. report higher incidence of intradialytic hypotension in patients achieving post-dialysis BP targets2931National kidney foundation guidelines recommend a pre-dialysis blood pressure of <140/90 mmHg and a post-dialysis blood pressure of <130/80 mmHg as targeted BPs for haemodialysis patients. However, there are some concerns regarding the targeted blood pressures, since most of the data is largely manipulated from observational studies from non-ESRD patients. Hence, targeted blood pressures among haemodialysis patients remain unclearThe current study also reports a drop in pre-dialysis blood pressure by 3.2/1 mmHg in the standard arm and 9/2.5 mmHg in the treatment arm during the 8-week study period. Studies have reported that lower (<120 mmHg) and higher pre-dialysis (>160 mmHg) systolic blood pressure is associated with high mortality ratesARBs are usually well tolerated, though hyperkalemia is frequently encountered among Haemodialysis patients on RAAS inhibitors irrespective of medication used. Hence blood profiles of all study participants were performed to keep a track of potassium levels and other blood parameters. No cases of hyperkalemia were reported in the current study. Twelve of the patients in the standard arm and 10 patients in the treatment arm suffered headaches ≤2 times during their HD sessions. None of the patients suffered from post-dialysis hypotension. However, 13 treatment-arm patients and 11 standard-arm patients complained of leg cramps ≤2 times after dialysis sessions. Considering their post-dialysis blood pressure readings, leg cramps were more associated with dialysis procedure rather than the effect of antihypertensive medication.A small sample size is one of the main limitations of this study; future studies should consider addressing a similar study question with a bigger population. In addition, there will be some concerns about generalizing the results of this study. The majority of the patients participated in this trial were Malays. Therefore the results of this study cannot be generalized for the whole population of Malaysia. Keeping in mind the principle of genetic influence, it might be possible that other ethnic groups, i.e. Chinese or Indians, might have different outcomes in comparison to Malays. Accurate BP measurement is fundamental to clinical practice and research, yet there is no consensus on which BP measurements to use and define hypertension in haemodialysis patients. Studies indicate that routine pre-dialysis or post-dialysis BP readings may overestimate BPThe management of euvolemic hypertension among ESRD patients has rarely been investigated. The current study demonstrates the beneficial effects of losartan (ARB) in lowering the blood pressure of euvolemic hypertensive patients. The importance of accurate assessment and achieving clinical dry weight cannot be neglected in achieving a euvolemic state at the end of the dialysis session. Treating euvolemic hypertension as a separate entity would not only have benefits in lowering post-dialysis blood pressure, but has also proven to improve pre-dialysis blood pressure subjected to non-pharmacological treatment. Reduction in overall blood pressure would not only lead to an increase in overall survival rates but also improve the quality of life among ESRD patients.How to cite this article: Aftab, R. A. et al. Efficacy of Losartan in the management of Post-Dialysis Euvolemic Hypertension : A Single-Blind Randomized Control Trial. Sci. Rep.6, 36592; doi: 10.1038/srep36592 (2016).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Hyperkalemia is a common electrolyte problem in patients with chronic kidney disease. It is typically caused by medications in patients with poor kidney function. Patients with comorbodities such as heart failure and diabetes are predisposed to electrolyte problems. Salt substitutes and dietary supplements are uncommon causes of hyperkalemia, but we propose that they are under-recognized and underdiagnosed causes in patients with chronic kidney disease. Our case report and literature review illustrates that a careful dietary history is essential in patients presenting with electrolyte disorders, especially hyperkalemia. Hyperkalemia is a serious medical condition requiring early recognition and treatment. Symptoms of hyperkalemia are non-specific, including muscle weakness, malaise, and palpitations. If untreated, it can lead to life-threatening arrhythmias and cardiac arrest. Age, diabetes, chronic kidney disease, heart failure, and medications such as nonsteroidal anti-inflammatory agents, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and mineralocorticoid receptor antagonists are strongly associated with hyperkalemia. Normally, humans require 2000 to 3500 mg per day (50–90 mEq) of potassium if the kidney function is normal. Salt substitutes and dietary supplements pose a real danger in patients with chronic kidney disease since they can cause severe hyperkalemia.A 68-year-old male from Nepal, with recent diagnosis of nonischemic cardiomyopathy, chronic kidney disease Stage II, insulin-dependent diabetes mellitus, and hypertension was admitted to the hospital for recurrent hyperkalemia .During the first admission, his serum potassium was noted to be 6.7 mmol/l with serum creatinine of 1.1 mg/dl. This was attributed to his cardiac medications , which were stopped, and he was advised a low salt diet with restricted fluid intake. On routine laboratory workup at his primary care physician about a week later, he was found to have recurrent hyperkalemia . Since he had electrocardiogram (ECG) changes, he was treated with calcium gluconate, along with medical treatment consisting of sodium polystyrene suspension and insulin/dextrose.On his third admission, his potassium was noted to be 6.9 mmol/l with serum creatinine of 1.1 mg/dl. A detailed medical history revealed that his medications included aspirin, beta blocker, loop diuretic, insulin, statin, and metformin. He denied any recent use of nonsteroidal anti-inflammatory agents and admitted to a low sodium and potassium diet. His cardiomyopathy was well compensated, and he did not any have dyspnea, paroxysmal nocturnal dyspnea or leg edema. After stabilizing and normalizing his potassium (similar treatment as noted above), he was admitted for further laboratory investigation.The laboratory investigation was notable for serum creatinine of 1.1 mg/dl, with a blood urea nitrogen of 35 mg/dl, serum sodium of 133 meq/l, serum osmolality of 286 mOsm/kg, magnesium of 1.6 mg/dl, calcium of 9.4 mg/dl, hemoglobin of 10.4 g/dl, white blood cell count of 5 k/mm3, platelets of 220 k/mm3, urinary pH of six, urinary sodium of 102 meq/l, urinary potassium of 39.1 meq/l, and urinary creatinine of 76 mg/dl. Transtubular potassium gradient (TTKG) was estimated to be above seven. The serum creatinine phosphokinase, renin, aldosterone, cortisol, uric acid, and phosphorous levels were within normal limits. Hemoglobin A1c was 8.1%, with 2+ proteinuria noted. Using the Modification of Diet in Renal Disease (MDRD) equation, the glomerular filtration rate was calculated around 70 ml/min/1.73 m2. ECG showed QTc interval of 421 ms and prolonged PR interval of 244 ms on his third admission.On further questioning the patient during the course of the hospitalization, the patient admitted to using salt substitute for the past few weeks. The salt substitute he was consuming had 610 mg of potassium in ¼ teaspoon (1.2 g). In this particular patient, who had pre-existing cardiomyopathy, chronic kidney disease Stage II, and concomitant beta blocker use, the salt substitute led him to severe hyperkalemia and multiple admissions. A careful dietary history including use of supplements, dietary substitutes, herbal medications, and over-the-counter products is essential in patients presenting with electrolyte problems. Informed consent was obtained from the patient for this study.Severe hyperkalemia, defined as plasma potassium greater than 6.0 mM, can lead to life threatening arrhythmias. Impaired kidney excretion is typically the cause of hyperkalemia. Drugs  can also cause hyperkalemia in the appropriate setting. Patients with diabetes, chronic kidney disease, and heart failure are particularly susceptible to hyperkalemia. Dietary supplements such as salt substitutes are rare causes of hyperkalemia, though they can be potentially life threatening. Even cardiac arrest has been noted from exogenous potassium supplements .A literature review shows that salt substitutes and muscle-building supplements both can cause severe hyperkalemia . PatientHyperkalemia is often discovered on routine laboratory monitoring or classic ECG changes . The ECGThere have been reported cases of hyperkalemia from the use of salt substitutes in patients who have been on ACE inhibitors. Interestingly, the serum potassium returned back to baseline after stopping the salt substitutes. The treatment suggested in these cases is to stop the salt substitute and not erroneously withdraw the ACE inhibitors in the long term, given the cardio-renal protection of ACE inhibitors . Salt suTreatment of hyperkalemia from overdose due to ingestion of potassium salt substitutes includes calcium chloride for cardiac membrane stabilization if ECG changes are noted, dextrose and insulin in water, and correction of acidosis with sodium bicarbonate solution. The modalities help in controlling acute arrhythmias. Excess potassium is removed either via ion-exchange resins or mechanically via hemodialysis .Though it is rare, fatal hyperkalemia has occurred from the use of salt substitutes. In the majority of cases in the literature where hyperkalemia has occurred, it is due to massive ingestion of potassium supplement in suicidal patients with normal kidney function. Patients who have impaired renal function or heart failure are at even greater risk for life-threatening hyperkalemia. A case report highlights that one tablespoon of Nu-Salt was enough to produce fatal hyperkalemia in a suicidal patient with normal renal function .A careful history is essential to elucidate the cause of hyperkalemia. Though historically thought to be a rare cause of hyperkalemia, we propose that salt substitutes are an under-recognized and underdiagnosed etiology contributing to hyperkalemia in patients with chronic kidney disease. Some cardiac and blood pressure medications further compound the hyperkalemia, causing the “perfect storm”; and hence, dietary history is essential in patients presenting with electrolyte problems.


Age , hypercholesterolemia , history of CVD , and creatinine clearance  all demonstrated a correlation with RAS. Although AASI is higher in patients with RAS, AASI does not independently predict the presence of RAS in hypertensive subjects.The ambulatory arterial stiffness index (AASI) is a marker of arterial stiffness and is derived from ambulatory 24-h blood pressure registration. We studied whether the AASI could be used as a predictive factor for the presence of renal artery stenosis (RAS) in patients with a suspicion of secondary hypertension and as such as a diagnostic tool for RAS. We included 169 patients with difficult-to-treat hypertension. They all underwent 24-h ambulatory blood pressure monitoring registration, imaging of the renal arteries, and cardiovascular risk measurement, including smoking, history, biometrics, blood pressure, renal function, lipids, and glucose metabolism. Performing univariate and multivariate analyses, we investigated if AASI and the other cardiovascular risk factors were related to the presence of RAS. Of the 169 patients (49% women), 31% had RAS. The mean AASI was 0.44 (0.16). The presence of RAS showed no significant correlation with AASI ( Increased arterial stiffness results from reduced elasticity of the arterial wall and is an independent predictor for cardiovascular risk. The ambulatory arterial stiffness index (AASI) is an indirect arterial stiffness index, which can be simply calculated from 24-h ambulatory blood pressure monitoring (ABPM) and has proven to be associated with cardiovascular adverse events and vascular damage, over and beyond 24-h pulse pressure and mean arterial pressure –3.Hypertension is one of the major causes in the development of atherosclerotic vascular and organ damage and decline in renal function. Increasing arterial stiffness is a forerunner and early sign of atherosclerotic disease and is associated with and a consequence of hypertension . AtherosTherefore, it can be hypothesized that arterial stiffness might be higher in the case of concomitant hypertension and RAS than in the case of hypertension without RAS. If this proves to be so, it could be used to distinguish patients with RAS from those without it. The arterial stiffness index could possibly aid in the detection and diagnosis of RAS. In treating hypertensive patients, it can have implications to know whether or not a renal arterial obstruction is present, and it might be valuable to look for this condition, therefore, particularly in cases of hypertension that are difficult to treat. In such cases, it is advisable to choose the least invasive screening option. As the AASI is derived from an ABPM that can be obtained without too much inconvenience to patients, it could be a real step forward if the AASI could be used in this respect.Therefore, we studied whether the AASI is associated with the presence of RAS in patients with hypertension and the clinical suspicion of secondary hypertension, more in particular of the presence of atherosclerotic RAS. RAS caused by fibromuscular dysplasia (FMD) is much less common, has a distinct pathophysiology, and is not a subject of this study.We included 169 consecutive patients with a clinical suspicion of secondary hypertension mainly based on difficult-to-treat hypertension indicated by a persistent blood pressure over 140/90 mmHg, who were referred to our tertiary hypertension unit. The study was retrospective in nature, and we used a pre-specified protocol. All included patients underwent imaging of the renal arteries and 24-h ABPM. Patients were excluded if they were diagnosed with a parenchymal renal disease other than that caused by atherosclerotic or hypertensive changes. Subjects with diabetic nephropathy with proteinuria >1.0 g/day were also excluded.This study was retrospective in nature and had no effect on the treatment of patients who enrolled. No experimental investigations were done, and all data were obtained in the course of usual patient care management. The data were completely de-identified. According to the guidelines of the institutional ethics board, it was not necessary, therefore, to obtain written informed consent of all patients. All conditions of the latest version of the Declaration of Helsinki of the World Medical Association were met.State-of-the-art transcatheter angiographies [intra-arterial (i.a.) TCA], CT angiographies (CTA), or magnetic resonance angiographies (MRA) of the renal arteries were made in all patients. The state-of-the-art MRA and CTA result in reliable estimates of renal artery obstruction in comparison to i.a. TCA . If therEach renal artery was analyzed for the presence of stenosis, which was graded on the basis of the most severe reduction of arterial diameter compared with an uninvolved renal artery segment proximal or distal to the stenosis. A renal artery was graded as normal if no luminal obstruction was present. A stenosis was considered high-grade if it was over 50% of luminal surface and low-grade if it was under 50% of luminal surface.According to the radiological reports, which were conducted by radiologists experienced in this field, subjects were classified into three groups as (1) having no RAS, (2) having low-grade RAS (<50%), and (3) having at least one high-grade RAS (>50%). Baseline and follow-up clinical and biochemical data were gathered through a pre-specified protocol. The angiographies and the ABPM measurements were done during the initial work-up of the patients after referral to our institution.Hypertension was defined according to European guidelines as conventional systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg. Experienced clinicians measured conventional blood pressure by computing the mean of three blood pressure recordings after resting 10 min in the semi-supine position, with the cuff placed at the level of the heart and patients’ legs uncrossed. ABPM recordings were programed at 15–30-min intervals during daytime and at 30–60-min intervals during nighttime. ABPM quality criteria included an interval range of 15 min, with at least five readings between midnight and 0600 hours and at least 15 daytime readings . If thes2) as a measure of goodness of fit of the AASI regression line , duration of hypertension, and the number of antihypertensive drugs. Hypertensive patients received antihypertensive drugs with a diastolic target BP ≤90 mmHg and systolic <140 mmHg or lower according to comorbid conditions .2. End-stage renal failure was defined as a glomerular filtration rate of less than 15 mL/min/1.73 m2.Renal function was measured by estimating creatinine clearance, using the Cockroft–Gault formula . Renal fWe measured serum cholesterol and blood glucose by automated enzymatic methods. Hypercholesterolemia was defined as a serum total cholesterol level of ≥5.2 mmol/L or the intake of lipid-lowering drugs. Diabetes mellitus type was a self-reported diagnosis, or a fasting or random blood glucose level of at least 7.0 mmol/L (126 mg/dL) or 11.1 mmol/L (200 mg/dL), respectively, or the use of anti-diabetic drugs. Presence of cardiovascular disease (CVD) was defined as a medical history with coronary artery disease (defined as ischemic changes on exercise tolerance testing or by significant obstruction on coronary angiography), myocardial infarction, transient ischemic attack, ischemic stroke or death from any cardiovascular cause, peripheral arterial disease, or vascular surgery.2 statistic, respectively, and evaluated unadjusted associations with Pearson’s correlation coefficient. To evaluate the association between AASI and RAS, we calculated unadjusted, age- and sex-adjusted and multivariable-adjusted odds ratios (ORs) plus 95% confidence intervals (CIs), with the study subgroup without RAS set as the reference group. In regression analysis, we adjusted for selected baseline characteristics that are known to increase risk of RAS, including sex, age, BMI, current smoking, diabetes mellitus, hypercholesterolemia, previous CVD, and family history of CVD.For statistical analysis and database management, we used SPSS v.22 for Windows . We compared means and proportions by ANOVA and the χThe 169 participants included 83 females (49.1%). Blood-pressure-lowering drugs at the time of referral were used by 154 (91.1%) of the patients. This medication had been stopped in a few patients because of insufficient effect before referral. The number of different antihypertensive medications per patient was 2.3 ± 1.3. Mean (±SD) age was 48.0 ± 13.5 years.At enrollment, 66 participants (39.1%) were current smokers; 61 (36.1%) reported intake of alcohol; 89 (52.7%) reported a history of CVD; 54 (32.0%) showed hypercholesterolemia or were treated for it; 25 (14.8%) had diabetes mellitus; and 14 (8.3%) had renal insufficiency, 1 of whom had end-stage renal failure.In the whole study population, the mean (±SD) 24-h blood pressure averaged 152.4 ± 20.0 mmHg SBP and 94.3 ± 13.8 mmHg DBP. The 24-h mean (±SD) arterial pressure averaged 114.8 ± 15.0 mmHg. The mean heart rate was 73.1 ± 13.6 bpm. The mean (±SD) AASI was 0.44 ± 0.16.An i.a. TCA of the renal arteries was obtained in 129, a CTA in 21, and an MRA in 29 patients. RAS was diagnosed in 52 participants (30.8%), 32 (18.9%) of whom had severe RAS with a luminal obstruction over 50%, and 7 (4.1%) of the entire group with a stenosis had bilateral RAS over 50%. Table P = 0.01), had a marginally lower BMI , and more often had hypercholesterolemia , a history of CVD  or renal failure  with an average creatinine clearance of 84.9 versus 108.7 mL/min (P < 0.001). The AASI in patients with RAS versus without RAS was 0.48 ± 0.15 (CI ±0.03 range 0.40–0.46) versus 0.43 ± 0.17 (CI 0.05 range 0.43–0.53) (P = 0.06)  (Table P = 0.06).In all 52 subjects, RAS was independently associated with creatinine clearance with an OR of 20.49 (In this study population, the AASI was not independently associated with the presence of RAS in patients with a suspicion of secondary hypertension. In the univariate analysis, higher age, lower creatinine clearance, hypercholesterolemia, and history of CVD were associated with RAS, whereas only lower creatinine clearance was independently associated with RAS.Renal artery stenosis carries a high risk for cardiovascular complications and is associated with increasing mortality. Even low-grade RAS, defined as RAS <50% of the arterial lumen, is associated with future cardiovascular events . TherefoThere are at present several specific clinical and biochemical clues that can suggest various forms of secondary hypertension . If presThe presence of atherosclerotic vascular lesions is in itself also a very strong indicator of cardiovascular morbidity and mortality . The preOne expression of vascular damage is increased arterial stiffness, which as such is an important marker and predictor of CVD complications , 16. ThiTaking these corroborations together, it seemed likely that hypertensive patients with RAS would show greater arterial stiffness when compared to those without RAS and that the difference might be such that it might be possible to distinguish between these groups based on arterial stiffness. We chose the AASI as the measure of arterial stiffness because this information is readily available from 24-h ABPM, which is regarded as the golden standard of blood pressure measurement. Several studies confirmed the clinical usefulness of the AASI as a measure of arterial stiffness as well as its prognostic significance for the appearance of cardiovascular complications in patients with hypertension , 19, 20.In the present study, AASI did show an independent relation with RAS but only to bilateral RAS and not to unilateral stenosis. However, the number of patients with bilateral RAS is too small to permit definitive conclusions. Could the number of patients overall in this study be too small to detect a significant difference? Given the CI of the means and the differences between the two groups, it is doubtful whether such a difference is in fact present. From the number of patients in this study and the outcomes, a power of 0.5 could be calculated. To get a power of 0.8, the number of patients in each group would have to be 163.On the basis of these results of this study, it seems reasonable to conclude that there is no clinically important difference in AASI between these two groups. Almost all patients were on hypertensive medication when the ABPM values were obtained. A recent study showed convincingly that antihypertensive treatment has only a marginal effect on the AASI over time . So, theSo, the hypertensive patients in this study showed the confirmed parameters of advanced vascular disease, but the AASI was not one of them, only among those with bilateral stenosis, a group known for its high risk of imminent CVD complications . The AASThere are some possible explanations for this. First, the average AASI in the group without RAS was 0.43; the average AASI in the group with RAS was 0.48; and in the group with bilateral RAS it was 0.56. These values are in the highest quintiles, as was shown in a study of hypertensive patients . Those wThis study was not aimed at directly evaluating whether AASI correlates with arterial stiffness, as we performed no direct measure of arterial stiffness such as pulse wave velocity. We merely studied the relation of an indirect measure of arterial stiffness with the presence of a serious atherosclerotic complication in hypertensive patients. Another matter could be the generalizability of the outcome. The patients in this study had difficult-to-treat hypertension and other clinical or biochemical indicators suggesting secondary hypertension. Since there were no other selection criteria for this specific group, they can be considered representative for this group of hypertensive patients in general .Though we did indeed reveal that hypertensive patients with RAS have a mean higher AASI than those without, this difference was not large enough to be useful as a distinctive feature. So, in this study, we could not find a value of the AASI that indicates the presence of RAS. Therefore, we could not advise introducing the AASI in the clinical decision-making in hypertensive patients suspected of secondary hypertension.All authors listed, have made substantial, direct, and intellectual contribution to the work, and approved it for publication.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.


The slope of the CCA displacement/pressure curve showed a progressive reduction with increasing age and EH disease occurrence . Our method provides an explicit reference value and relationship for the manner in which the CCA wall responds to changes in BP. Short-term and continuous BP were significantly correlated with CCA displacement and exhibited a close inverse relationship with each subject’s BP and EH, age, and systolic blood pressure.The physiological relationship between local arterial displacement and blood pressure (BP) plays an integral role in assess- ment of the mechanical properties of arteries. In this study, we used more advanced methods to obtain reliable continuous BP and the displacement of the common carotid artery (CCA) simultaneously. We propose a novel evaluation method for arterial stiffness that relies on determining the physiological relationship between the axial and radial displacements of the CCA wall and beat-to-beat BP. Patients  were divided into groups according to the following three criteria: essential hyper- tension (EH) and normotension, male and female, elderly and younger. The Pearson correlation test and canonical correlation analysis showed that the CCA indices were significantly correlated with BP indices ( Atherosclerosis has been considered the main cause of morbidity and mortality in relation to cardiovascular diseases. As a result, the evaluation of arterial stiffness has become a popular research field, receiving wide attention235610The displacement of the arterial wall has been under study for many decades. As a physical phenomenon, the radial displacement of the artery is easy to explain based on the combined action of variations in the BP gradient, the elastic properties of the arterial wall, and the periphery of the pressure wave reflection1516172324The aim of this study was to determine the relationship between two-dimensional  motions of the CCA wall and beat-to-beat BP to explore the mechanism of arterial stiffness in longitudinal ultrasound images. We aimed to solve the limitations of current methods for assessing carotid artery motion properties in which continuous BP is estimated by complex mathematical assumptions and arterial expansion evaluations are not accurate enough. Our method may have several advantages: (1) an index of arterial dispensability that includes the integrated characteristics and interactive influence of axial and radial displacements are provided, which ensures the influence of each individual indicator; (2) BP is used as a new, continuous physiological parameter and the issue of how 2-D arterial function varies on a beat-to-beat BP basis has never been addressed previously; (3) A more accurate 2-D displacement of the CCA has been obtained by a novel and reliable motion-tracking algorithm; and (4) it simultaneously obtains a reliable short-term BP measurement and measurement of 2-D displacement of the CCA wall at same time.The study protocol was designed according to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the Second People’s Hospital of Shenzhen in China. The study objectives and design have not been previously published. All participants provided written informed consent. The study population consisted of 138 Chinese participants aged 29 to 81 years (59.6 ± 11.4 years). Among the participants, 85 participants were suffering from essential hypertension and 19 participants were diagnosed with diabetes. Risk factors such as smoking, alcohol, and body mass index were recorded.In the experiment, both the beat-to-beat BPs and CCA displacements were gathered as continuous data, Hence to complete our analysis, we needed to measure the values at the same time. Beat-to-beat recordings of the systolic BP (mmHg) and diastolic BP (mmHg) were measured using a Finometer system Model-2 (Midi). A cuff was attached to the left upper arm close to the elbow for continuous beat-by-beat measurement of BP. For both the entire group and each of the individuals in this study, one ultrasound physician with more than 10 years of experience measured and evaluated the axial and radial displacements of the left and right carotid artery walls using a high-resolution ultrasound system  and 7.5 MHz linear array transducer. During collection, all of the measurements were made with patients in a supine position. Scanning was performed on both CCAs in the lateral plane, 2–5 cm proximal to the carotid bifurcation, so that the CCA segment was displayed as a rectilinear structure . Video c∞-based block matching method (HBM). The HBM uses the state-space equation to describe the motion of the target tissue on the carotid artery wall as below28The 2D displacement of the carotid artery wall in the ultrasound sequence was tracked using the HXn is the estimated location of the target tissue, Yn is the observed location of the target tissue acquired by the block matching method, Wn and Vn are noise terms, and n is the time or frame index. Then, the H∞ filter was used to compute the optimal estimate of the target tissue location using a min-max approach. Given the worst possible disturbances from the data, our HBM method can still ensure optimal estimation of carotid artery wall motionwhere According to the separate axial and radial displacements of the left and right carotid artery walls and BP signals, 4-type displacement/pressure curves were obtained via software, which was developed with MATLAB. From the recording time, an initial alignment of pressure and 2-D displacement waveforms was obtained. Then, a correction factor of 30–60 milliseconds was applied to the CCA displacement to correct the delay due to the propagation of the carotid artery pressure wave. It was also applied for removal of nonlinear waveforms and dealing with semiautomatic irregular waveforms. Once aligned, the beginning and end of the segments to be analyzed within each waveform were visually identified on a complete cardiac cycle between two late diastole phases . When CCThe motion of the CCA wall includes axial motion in the left CCA wall (LAM), radial motion in the left CCA wall (LRM), axial motion in the right CCA wall (RAM), and radial motion in the right CCA wall (RRM). The systolic blood pressure variability (SBPV) and diastolic blood pressure variability (DBPV) were examined using the systolic blood pressure (SBP) and diastolic blood pressure (DBP). The measurements from the beat-to-beat BP and motion of the CCA wall were assessed by the mean level and variability indices in the time and frequency domains. The BP indices in the time domain included the mean value (MEAN), standard deviation (SD), coefficient of variation (CV), successive variation (SV), average real variability (ARV), and residual standard deviation (RSD)243031X =  and Y =  of random variables, and there are correlations among the variables, canonical correlation analysis will identify linear combinations of Xi and Yi that are maximally correlated with each otherCanonical correlation analysis is an approach for making sense of cross-covariance matrices. When there are two vectors U and V are the first pair of canonical variables. The vectors a and b such that the random variables a′X and b′X maximize the correlation ρ = corr. Canonical correlation analysis is the general procedure for investigating the relationships between two sets of variableswhere Canonic correlation analysis is used to investigate the relationships between two sets of variables and it is preceded by a hypothesis test. In this case, we used Lilliefors test to validate our data satisfying the normal distribution . The Pearson’s linear correlation coefficient was used to detect multiple co-linear relationships among the variables. The results showed that there was a correlation between the variables, but not a strong correlation . Meanwhile, multivariate statistics and F approximations demonstrated that our data satisfied the linear correlation between the variables group and canonical correlation coefficients significantly .Pearson’s linear correlation coefficient test was employed to measure the correlation between the BP and CCA indices. The Benjamini & Hochberg method was used to construct multiple comparison corrected confidence intervals that corresponded to the FDR-adjusted p-valuesParticipants were a mean (standard deviation) of 59.6 (11.4) years old, and 76 (55.1%) were male. The participants included two diseases: 19 (13.8%) had diabetes, and 76 (55.1%) had essential hypertension. The smoking, alcohol and coffee rates were 23.2%(32), 14.1%(20) and 2.8%(4), respectively. The mean SBP was 140.2 (23.3) mmHg, and the average DBP was 74.5 (13.4) mmHg. The mean LAM was −0.8 (28.6) pixels, and the mean LRM was 3.7 (9.9) pixels. The mean RAM was −3.8 (25.7) pixels, and the mean RRM was 3.6 (9.3) pixels.r = −0.323–0.462, p < 0.05). In particular, the residual standard deviation of axial displacement in the left CCA wall (LAM_SV) was the strongest positive that was significantly correlated with the coefficient of variation of the systolic blood pressure (SBPV_SD) , and LRM_RSD was the strongest positive that was significantly correlated with the SBPV_RSD . LRM_SV was the strongest negative that was significantly correlated with the DBPV_MEAN , and LAM_ARV was the strongest negative that was significantly correlated with the DBPV_MEAN .r = 0.787, p < 0.05). Furthermore, the SBPV_SD, DBPV_SD, DBPV_CV DBPV_SV, LRM_SD, and LRM_ARV were the major positive factor relative contributions to the relationship. Similarly, the SBPV_CV, SBPV_RSD, DBPV_RSD, LRM_RSD, and RRM_ARV were the major negative factor relative contributions to the relationship. Canonical correlation analysis was used to test the integration relativity between the CCA indices and BPV indices. It was also used to study the positive and negative factors in the correlation.There was a strong canonical correlation between the CCA and BP indices (EH:0.496vs.NEH:0.822). Canonical correlation analysis was also used to measure the relativity between the CCA indices and BP indices in both groups, revealing major differences in the contributing factors. There were significant correlations between the CCA and BP indices for both groups . The major positive influencing factors in the EH group were SBPV_CV, SBPV_SV, DBPV_SD, LRM_SD, and LRM_ARV, and the major negative influencing factors were SBP_SD, SBP_ARV, and LRM_RSD. The major positive influencing factors in the NEH group were SBPV_SD, DBPV_CV, LRM_SD, and LRM_ARV. The major negative influencing factors are SBPV_CV, SBPV_RSD, DBPV_RSD, and LRM_RSD. These findings are summarized in According to whether participants had essential hypertension (EH), all of the subject were subdivided into the EH and NEH groups. As shown in vs.0.808), and there were significant correlations between CCA and BP indices for both groups . However, the SBPV_CV, SBPV_SV, DBPV_ARV, and DBPV_RSD mostly had positive coefficients and the SBPV_SD, SBPV_ARV, SBPV_RSD, DBPV_SV, and LAM_ARV had significantly negative coefficients for the correlation in the male group. Similar results were recorded in the female group.age > 60) had lower slopes compared to the younger group (age <= 60), as shown in vs.0.783; without EH: 0.572vs.0.667, respectively). Similar to the results described above, r = 0.870 and 0.926; without EH: r = 0.890 and 0.882, respectively; p < 0.05). DBPV_SD, DBPV_CV, DBPV_CV, DBPV_SV, and RAM_SD were significantly positively correlated in the elderly group. SBPV_CV, SBPV_RSD, DBPV_ARV, DBPV_RSD, and LRM_RSD had a significant positive effect on the correlation. In contrast, SBPV_CV, SBPV_RSD, DBPV_RSD, LAM_SD, LAM_SD, and RRM_SD were major positive correlation factors, and SBPV_SD, SBPV_ARV, DBPV_SD, DBPV_CV, DBPV_SV, LRM_SD, LRM_ARV, and RRM_RSD were major negative correlation factors in the younger group.Participants in the elderly group age > 0 had low∞ filter based standard block matching method (BM) method to estimate the motion of the carotid artery wall from the ultrasound image sequencesIn this study, we estimated the 2-D displacement of the carotid artery wall and beat-to-beat BP as well as the influence of age, sex, and essential hypertension on the estimations. Our goal was to conduct preliminary trials that validated the interrelation and interaction between the CCA and BP indices as well as to assess the mechanical properties of the artery. In previous studies, a series of effective methods for studying the axial and radial movements of the arterial wall was presented363738The CCA wall invariably undergoes displacement with blood pressure changes because the essence of BP is the pressure exerted by circulating blood on the blood vessel walls. In our experiments, the most important finding was a strong canonical correlation between the beat-to-beat BP and carotid artery wall displacement, indicating that the two-dimensional motion of the carotid artery wall has a strong influence on the beat-to-beat BPV. This result is consistent with the findings presented in a previous publication, namely, that a basic physiological feature, the variability in the BP level, is a significant marker of the risk related to cardiovascular complications3240et al. observed that the buffer effect of blood vessels can be enhanced by systemic structural changes in the arteries with age, which leads to increase SBP and, potentially, increased pulse pressure45Age, sex, and disease status, and possibly other independent risk factors, were also strongly and inversely associated with carotid displacement or BPV. Svedlund and Gan suggested that differences in age might have confounded the results of prior studies that showed impaired carotid longitudinal displacement in older adults with coronary artery disease and type- 2 diabetesARV is a more appropriate parameter to measure variability, which provides a computationally simple way to estimate variation in a trend. As for ARV, RSD tends to be larger in absolute value and is influenced, to a greater extent, by large discrepancies between successive measurements. In our Pearson’s linear correlation analysis, the ARV and RSD of carotid artery wall displacement were more significantly correlated with BP indices. We also found the ARV and RSD of carotid artery wall movement had the same tendency of changes with the same BP indices in standardized canonical correlation coefficients. It suggested that ARV and RSD are the most appropriate predictors when expressing the relationship between CCA wall displacement and BP.LRM_SD and LRM_ARV are related to the SBPV_SD, DBPV_SD, DBPV_CV, and DBPV_SV. The data for the left carotid artery were more representative of the influence of the BP on the CCA wall than the data for the right carotid artery. Additionally, we also found the CCA radial displacements were more related to the BP indices than axial displacements, indicating that the changes in BP had more influence on CCA radial than axial displacements. BP plays a crucial role in vascular biology, and may affect IMT through blood vessel remodeling or wall hypertrophy in response to altered circumferential stressThe common carotid artery is present on the left and right sides of the body. The left common carotid artery can be considered to have two parts, the thoracic (chest) and cervical (neck) regions. The right common carotid originates in or close to the neck, containing only a small thoracic portionSBPV_CV means a smaller LRM_RSD based on overall canonical correlation analysis. This enhanced the study in regard to traumatic effects of intravascular pressure excursions on the vessel wall, thereby favoring atherosclerosis formation mechanism research. Similarly, our 2-D artery and BP curves have also verified the slopes of the 2-D displacement-pressure relationship can be obtained from the carotid arteries during most of the ascending and descending portion of the pulse pressure wave, which may allow study of the mechanisms of this CCA variability and their possible alterations with disease. Additionally, the study of EH can be used to understand more about changing BP and stress levels and short-term changes in endothelial function and how they lead to some degree of variation in the reproducibility results.Fully elucidating the mutual roles of CCA wall displacement and the changes in BP based on our limited research is a difficult task as these elements appear to act in a complex system, impacting each other. However, some practical significance results can be obtained by our canonical correlation coefficients. For example, we found that a smaller There are certain limitations in our study. First, we chose a certain set of characteristics for evaluation and we grouped the participants without considering other known and confounding factors  in the study population. Similarly, cultural factors, ethnic differences, and factors such as socioeconomic disadvantages and psychosocial stress may have contributed to the observed differences between the groups. Second, we focused on determining the relationship between the axial and radial displacements of the CCA wall and BP based on longitudinal ultrasound images. Therefore, more research should consider the influence of the circumferential displacement of the CCA wall to our results in the next stage, which also plays an important role in arterial wall mechanics and measurements based on short-axis ultrasound images. Similarly, simultaneous measurement avoids the error that occurs when measurements are made asynchronously. However, we must acknowledge the limitations that our key parameters were measured in different arteries; the blood pressure was measured in the brachial artery and arteria wall displacement was measured in the carotid artery. This limitation should also be investigated further. Finally, further research is needed on the relative contributions of both positive and negative factors for the CCA and beat-to-beat BP indices to improve our understanding of the relationships.The two-dimensional motion of the carotid artery wall had a significant correlation with beat-to-beat BP indices, and positive or negative factors that contributed to the relationship were clearly identified. Additionally, we observed that the variation in the carotid artery wall displacement and BPV features could be influenced by multiple risk factors, including the age, sex, and essential hypertension status. Moreover, this new method allows for a precise, in-depth assessment of the carotid artery mechanical properties at rest. However, more research is required to validate these correlations under physiological stress.How to cite this article: Xu, C. et al. Beat-to-Beat blood pressure and Two-dimensional  motion of the Carotid Artery Wall: physiological evaluation of arterial stiffness. Sci. Rep.7, 42254; doi: 10.1038/srep42254 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.