Routine testing of microalbuminuria and retinopathy is not done among patients with high blood pressure in resource-limited settings. We determined the prevalence of microalbuminuria and retinopathy and their risk factors among hypertensive patients at a large hospital in western Uganda. We consecutively recruited nondiabetic patients with hypertension at the outpatients' clinic over a period of 3 months. Spot urine samples were tested for urine albumin. Direct fundoscopy was done to assess retinal vasculature and optic disc for signs of hypertensive retinopathy. Logistic regression was done with retinopathy and microalbuminuria as primary outcomes.We enrolled 334 patients and, of these, 208 (62.3%) were females, with median age of 55 years (range: 25–90). The prevalence of microalbuminuria was 59.3% (95% CI: 50.1–72.2) and that of retinopathy was 66.8% (95% CI: 58.6–76.5). The independent correlates of retinopathy and microalbuminuria were systolic blood pressure (SBP) > 140 mmHg  and treatment with beta-blockers . Use of ACEIs was unrelated to the study outcomes.The prevalence of retinopathy and microalbuminuria is high. Clinicians should aim for better control of blood pressure and routinely perform fundoscopy and urine albumin, especially for patients with poorly controlled blood pressure. Hypertension is the most common cardiovascular disorder in the world, affecting approximately one billion people globally, and accounts for approximately 7.1 million deaths annually –4 with aHypertension is a major modifiable risk factor for end organ failure, although the exact level at which these complications start to develop is not completely understood . The kidMicroalbuminuria is predictive of all-cause and cardiovascular disease (CVD) mortality in men and women independently of other established CVD risk factors, with microalbuminuric individuals having approximately a 50% increased risk of all-cause mortality –18. TherThe occurrence of kidney and retinal complications may be higher than that observed in studies in the western world. Routine monitoring of microalbuminuria and assessment for retinopathy are not done in limited-resource settings because the clinics are very large with limited human resources and laboratory testing capacity. Therefore, the aim of this study was to determine the prevalence of retinopathy and microalbuminuria and their correlates among hypertensive patients attending medical outpatients' clinic of Mbarara Regional Referral Hospital, a large urban public clinic in western Uganda.We conducted a cross-sectional study at the hypertension clinic at the medical outpatients' department of Mbarara Regional Referral Hospital (MRRH), a tertiary facility in the southwestern region of Uganda. The hospital is also a teaching facility for Mbarara University Medical School. The clinic is held once weekly and attends to patients referred from lower health centers including district hospitals and also consultations from within Mbarara Hospital. The clinic is the largest facility providing care for hypertensive patients in the southwestern region and receives approximately 70 patients per clinic day.Patients were eligible to participate if they were 18 years and older, had a previous clinician's diagnosis of hypertension defined as seated systolic/diastolic blood pressure of 140/90 mmHg or above , and/or Patients seeking treatment for hypertension were given information about the study procedures and if they agreed to participate, they were asked to provide written consent. We collected blood to test for random blood glucose (RBS) level and urine samples to test urine for features of UTI using dipsticks. A standardized, pretested questionnaire was administered to all patients who met the inclusion criteria. Data collected included sociodemographic information such as age, gender, address, occupation, and marital status. We also collected medical history data, duration, and treatment for hypertension. Patients were asked which medications they were taking and clinic books and records were checked to ascertain these medications. Patients were then screened for retinopathy by direct fundoscopy. Urine samples were sent to the Clinical and Research Laboratory at Mbarara University for measurement of urinary albumin and creatinine.p(1 − p)∗(Z2α/21−)/d2. In the formula, the estimated prevalence of microalbuminuria is 32% in Nigeria [d is the margin of error at 5% using a 95% confidence interval and adjusting for 10% refusal rate; we calculated a sample size of 330 patients. We used consecutive sampling to enroll the participants until the required number was completed.We used a standard formula  for esti Nigeria  and d isData were entered in Epi Info (version 2007) and exported to STATA 12  for analysis. We summarized sociodemographic and clinical characteristics using descriptive statistics. The categorical or binary variables such as gender and smoking status were summarized using proportions and continuous variables like body mass index (BMI) with means and standard deviations. For nonuniform data, we summarized using medians and interquartile ranges instead of means and standard deviations.p value < 0.25 were chosen for inclusion in the multivariate model as important confounding factors. Odds ratios for the association and 95% confidence intervals were reported. Crude and adjusted odds ratio were reported. Results from statistical tests were considered statistically significant if the p value was less than 0.05.The primary outcomes in the analysis were microalbuminuria and retinopathy. First, we analyzed retinopathy separately and then a combination of the two outcomes, collectively called target organ damage. A participant was considered to have target organ damage (TOD) if they had either one or a combination of both retinopathy and microalbuminuria. Using logistic regression analysis, we explored the association of hypertensive retinopathy and microalbuminuria with predictor variables like gender, smoking status, and duration of hypertension. In the univariate analysis, variables with a All participants provided individual and informed consent. All study procedures were clearly explained to the participants in the language of their choice. Participants who were unable to write offered a thumbprint instead of signature. Patients were assured of their entitlement to standard care even when they chose not to participate or even withdraw from the study after providing consent. Laboratory results and fundoscopy findings were shared with the caregivers to ensure that the participants received adequate management. Data were anonymous and kept in a locked cabinet and were only accessible to study staff. The study received approval from the Research Ethics Committee of Mbarara University of Science and Technology (12/03-13).n = 33), had features of UTI (n = 20), had missing urine albumin results (n = 7), declined to participate (n = 4), or failed to provide urine samples for analysis (n = 2). Data was available for analysis for 334 patients. 208 (62.3%) of the patients were female, the median age was 55 years (range: 55 years), and the majority were from Mbarara district. The details of the sociodemographic characteristics are shown in We screened 400 patients for eligibility and 66 were excluded because they were known diabetics or had RBS > 11.1 mmol/l . The majority of patients with retinopathy were graded as stage 1. Stage 1 hypertensive retinopathy was detected in 90 (40.4%) patients, stage 2 in 81 (36.3%), stage 3 in 50 (22.4%), and stage 4 in only 2 (0.9%) patients.n = 118) of the patients had normoalbuminuria. The prevalence of microalbuminuria (ACR: 30–300 mg/g) was 59.3% (95% CI: 50.1–72.2). The remaining patients (n = 18 or 5.4%) had macroalbuminuria About 35%  .149 (44.6%) of all study participants had both retinopathy and microalbuminuria; 74 (22.2%) had retinopathy but had normal urine albumin. 67 (20.1%) had no retinopathy but had microalbuminuria with proteinuria and 44 (13.1%) had normal urine albumin and no retinopathy. A chi-square test did not show a significant association between retinopathy and microalbuminuria . Patients who used beta-blockers had a 2.1-fold increase in the odds of TOD  compared to those not using beta-blockers.Our study among an African hypertensive and nondiabetic population has shown that prevalence of microalbuminuria and that of retinopathy are very high. Patients with poorly controlled blood pressure were more likely to have target organ damage, and so did patients with long-standing hypertension. These findings are comparable with other studies on the African continent but some differences emerge on and outside the continent.The prevalence of microalbuminuria at 57.5% in our study is higher than that found in similar studies in Uganda . The preIn the Microalbuminuria A Genoa Investigation on Complications (MAGIC) study , which wIn our study, no medications were associated with microalbuminuria. This does not agree with findings from other studies. One such study in an African setting  showed tThe present study found 66.8% prevalence of hypertensive retinopathy in outpatients on treatment for hypertension in MRRH. The findings on retinopathy are fairly homogenous to those found in other African studies. In an Ugandan study, the prevalence of hypertensive retinopathy among patients on treatment for hypertension in Mulago Hospital, a national referral hospital, was 70.2%. This is also comparable to findings in a study done in Nigeria, which found 71% prevalence of hypertensive retinopathy . The resOutside the African continent, comparable results were also found in Turkey, where the prevalence of hypertensive retinopathy was 66.3% . Similarβ-blockers, calcium channel blockers, and diuretics. The correlates of multiple target organ damage  included uncontrolled hypertension and taking beta-blockers. Duration of hypertension was not a significant predictor. Surprisingly, the use of ACEIs was not a protective factor. Controlled blood pressure was protective of target organ damage. This is a very important observation because it makes the case for advocating for tight BP control and use of ACEIs in our patients. It has already been shown in many other studies that ACEIs reduce microalbuminuria [Factors associated with retinopathy were high systolic BP, being hypertensive for more than five years, high BMI, and being on treatment with uminuria . PotentiOur study has some limitations. Firstly, we did not have a fundus camera. This would have enabled recording of retinal photographs and their subsequent interpretation by independent assessors to improve accuracy of diagnosis. Secondly, some of our patients were elderly and, at that age, retinal changes may begin to manifest . Thirdly, we did not measure renal function due to limited funds. Lastly, we were unable to perform urine culture and lipid profiles. These variables may be potential confounders in this study because infections and hyperlipidemia have an effect on hypertensive retinopathy and microalbuminuria.β-blockers and those with systolic BP > 140 mmHg despite taking antihypertensive treatment.In conclusion, the prevalence of hypertensive retinopathy and microalbuminuria in hypertensive patients attending the medical outpatients' clinic of a large urban public hospital in Uganda is high. On the basis of our findings, we recommend rigorous blood pressure control to maintain systolic BP < 140 mmHg. Clinicians should endeavor to conduct fundoscopy and measure urine albumin of all hypertensive patients who are on treatment with


In order to develop an equation that integrates multiple clinical factors including signs and symptoms associated with uraemia to assess the initiation of dialysis, we conducted a retrospective cohort study including 25 haemodialysis centres in Mainland China. Patients with ESRD (n = 1281) who commenced haemodialysis from 2008 to 2011 were enrolled in the development cohort, whereas 504 patients who began haemodialysis between 2012 and 2013 were enrolled in the validation cohort comprised. An artificial neural network model was used to select variables, and a fuzzy neural network model was then constructed using factors affecting haemodialysis initiation as input variables and 3-year survival as the output variable. A logistic model was set up using the same variables. The equation’s performance was compared with that of the logistic model and conventional eGFR-based assessment. The area under the bootstrap-corrected receiver-operating characteristic curve of the equation was 0.70, and that of two conventional eGFR-based assessments were 0.57 and 0.54. In conclusion, the new equation based on Fuzzy mathematics, covering laboratory and clinical variables, is more suitable for assessing the timing of dialysis initiation in a Chinese ESRD population than eGFR, and may be a helpful tool to quantitatively evaluate the initiation of haemodialysis. The early initiation of haemodialysis leads to an accelerated decline in residual renal function, poor quality of life, and waste of medical resources. In contrast, the late initiation of haemodialysis increases the incidence of complications, causes higher mortality, and increases treatment costs. Over the past three decades, several studies have attempted to assess the initiation time of dialysis; however, no consensus has been reached.Maintenance haemodialysis is the main renal replacement therapy used for patients with end-stage renal disease (ESRD). However, the optimal time of haemodialysis initiation remains a vital factor to reduce the morbidity of complications and mortality associated with dialysis7. In the USA, the mean estimated GFR (eGFR) at dialysis initiation has gradually increased from 1996 until 2008. In particular, the proportion of patients beginning haemodialysis with an eGFR of >10 mL/min has increased from 20% to 52%, whereas those beginning haemodialysis with an eGFR of ≥15 mL/min has increased from 4% to 17%8. However, subsequent observational studies based on these registries included a large number of patients, but produced controversial results14. In particular, the IDEAL study in 2010 showed that survival did not significantly differ between ESRD patients with early and late dialysis initiation14.From the 1970s to 1990s, studies have shown that a high initial KT/V level  for urea can improve dialysis outcomes15. The equations for GFR estimation do not consider essential clinical factors such as nutrition, diabetes mellitus, and signs and symptoms of uraemia , which may affect dialysis initiation. Therefore the updated 2015 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend that the decision to initiate dialysis should be based on an assessment of multiple factors, such as signs and symptoms of, for example, uraemia, volume overload, and heart failure, and not only the eGFR level16. However, these clinical factors are subjectively assessed by doctors and depend on their individual experience. Hence, the quantitative assessment of these aforementioned clinical factors may enhance the accuracy of the assessment of the timing of haemodialysis initiation, especially for doctors who lack extensive clinical experience.One reason for the conflicting results was that the definitions of “early” and “late” were based on serum creatinine-based GFR estimations, including equations such as the Modification of Diet in Renal Disease (MDRD) study equation17. In the present study, we adopted ‘fuzzy’ methods instead of traditional statistical methods. In past decades, the development of fuzzy mathematics has impacted the fields of modelling because it can describe vague statements18. Artificial neural networks (ANNs), as one of the widely used techniques of fuzzy mathematics, have the advantage of being able to detect complex, non-linear problems19. Generally, ANNs consist of multiple layers; hence the information transfers from the input layer to the output layer of the neuronal network layer by layer. They can be calibrated using almost any type of input data , and the output can be one-dimensional or high dimensional  and can simultaneously consider all possible interactions between those risk factors. Therefore, ANNs have been used to predict technique survival for peritoneal dialysis, and the results showed ANNs have higher accuracy than logistic regression models21. Marshall et al. created an ANN model to predict GFR, which showed better results than algebraic formulas. These studies confirmed that ANNs could deal with dialysis datasets22. In our previous study, we established an improved ANN model termed the kernel logistic neural network-restricted Boltzmann machine (KLNN-RBM) to solve complex variable screening problems efficiently23.However, it is difficult to quantify these ‘fuzzy’ clinical factors, especially the non-linear relationships between these factors and outcomes, using traditional statistical methods24. This technique has been applied in biological and clinical fields for modelling, especially in the processing of time-delay datasets  and has produced satisfactory results26. Therefore, the KLNN-RBM and the T-S type fuzzy neural networks appear to be viable methods to select variables and for modelling for assessing dialysis initiation.Moreover, fuzzy neural networks combine the advantages of fuzzy logic in processing vague and uncertain information, and neural networks in good learning abilities. The Takagi–Sugeno (T-S) type fuzzy neural network is the most widely used modelling method among fuzzy neural networksTo the best of our knowledge, this is the first report of the use fuzzy mathematics to develop a novel equation to assess dialysis initiation, which we termed as the “dialysis initiation based on fuzzy mathematics equation” (DIFE). Furthermore, we compared the DIFE with the conventional eGFR-based assessment and showed that the DIFE is more accurate to evaluate dialysis initiation. Our results suggest that the DIFE offers a novel method to assess the initiation of dialysis, and may have implications for decision-making related to dialysis initiation in clinical practice.This retrospective cohort study encompassed 25 haemodialysis centres covering seven geographical regions of Mainland China. All the study centres serve as quality control centres of blood purification or were recommended by these centres in each province, municipality, or autonomous region.The protocols were approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University; the Chinese PLA General Hospital; the First Affiliated Hospital of Xi’an Jiaotong University; Guangdong General Hospital; Beijing Friendship Hospital; Capital Medical University; West China Hospital of Sichuan University; Zhongshan Hospital; Fudan University; Dalian Municipal Central Hospital; the First Affiliated Hospital; Sun Yat-sen University; the General Hospital of Shenyang Military Area Command; the General Hospital of Ningxia Medical University; Renji Hospital; School of Medicine; Shanghai Jiaotong University; Huashan Hospital; Fudan University; Xijing Hospital; the Fourth Military Medical University; the General Hospital of Benxi Iron and Steel Co., Ltd; Daping Hospital & Surgery Institute; the Third Military Medical University; the Affiliated Zhong Shan Hospital of Dalian University; Lanzhou University Second Hospital; the First Affiliated Hospital of Harbin Medical University; the First Affiliated Hospital of Xinjiang Medical University; Zhejiang Provincial People’s Hospital; An Steel Group Hospital; Henan Provincial People’s Hospital; and The People’s Hospital of Zhengzhou University. We obtained written informed consent from each patient, and personal information was protected during data collection. All the study methods were performed in accordance with relevant guidelines and regulations.2 within 3 months before haemodialysis initiation, and had commenced haemodialysis for a minimum of 3 months. The exclusion criteria were as follows: patients who were diagnosed with acute kidney injury (AKI); those who underwent or were scheduled to undergo peritoneal dialysis or kidney transplantation; those with a malignancy that significantly affected survival ; and those who experienced accidental death caused by unexpected reasons, including traffic accidents and suicide.Patients with ESRD who began maintenance haemodialysis between January 1, 2008, and September 30, 2013, were enrolled. Patients were 18–85 years of age, were diagnosed with chronic kidney disease (CKD), had two successive eGFR measurements of ≤30 mL/min/1.73 mOf the 1802 patients who began haemodialysis between January 1, 2008, and September 30, 2013, 17 patients with missing serum albumin and serum phosphate data were excluded. The enrolled patients were divided into two cohorts according to the start time of haemodialysis. A total of 1281 patients who started haemodialysis between January 1, 2008, and December 31, 2011, were included as the development cohort, whereas 504 patients who started haemodialysis between January 1, 2012, and September 30, 2013, were retained within the validation cohort  independently reviewed the data of a random sample of 100 records. The documentation used for abstraction included inpatient medical records for haemodialysis initiation, first-time haemodialysis records, laboratory data, and surgical records for first access. Baseline demographic data and clinical data included sex, birth date, date of haemodialysis initiation, first access, death date, primary disease, and comorbidity. The clinical signs and symptoms at the time of haemodialysis initiation were grouped as follows: heart failure, vomiting, uremic encephalopathy, and oedema grade 2+ and 3+. Determinations of the clinical signs and symptoms were made based on the clinical guidelines by nephrologists during the outpatient or inpatient consultations2) at the initiation of haemodialysis was computed using the Chinese modified MDRD study equation 7: eGFR = 170 × serum creatinine−0.999 × age−0.176 × blood urea nitrogen−0.170 × serum albumin0.318 . All participating investigators were nephrologists and had received uniform study training.Laboratory data collected within 3 months prior to haemodialysis initiation included haemoglobin, serum albumin, blood urea nitrogen, serum creatinine, serum potassium, serum sodium, free calcium, and serum phosphorus levels. In all the clinical laboratories of the study centres, serum creatinine levels were measured using the sarcosine oxidase method. The eGFR  or 36 months for the surviving patients.16 and our previous study27, 13 candidate variables were considered for inclusion in the DIFE, including age, sex, serum creatinine level, blood urea nitrogen level, serum albumin level, blood haemoglobin level, serum potassium level, serum phosphorus level, heart failure, vomiting, oedema grade 2+ and 3+, uremic encephalopathy, and diabetes mellitus. Sex, diabetes mellitus, heart failure, vomiting, oedema grade 2+ and 3+, and uremic encephalopathy were used as binary variables, and were transformed using dummy variable encoding .Based on the recommendation of the timing of haemodialysis initiation in the 2015 KDOQI guidelinesUsing the KLNN-RBM model, the variables adopted to establish the DIFE equation were detected in the development cohort. We initialized weight and bias parameters with the help of RBM first, and then optimized the parameters using a modified maximum likelihood estimation and stochastic gradient descent method to obtain higher classification accuracy. The structure of the KLNN-RBM model is shown in Fig. W was introduced for numerical indicators to establish a new haemodialysis initiation evaluation equation. After removing the outliers, 10-fold cross-validation was used for network training, and the parameters of the model were adjusted by particle swarm optimization (PSO)28. Based on a survival time of more or less than 36 months, patients in the development cohort were divided into two groups to determine the threshold and to evaluate the performance of the equation. Patients who survived for ≥36 months were assigned to the good survival group, whereas patients who survived for <36 months were assigned to the poor survival group. The sensitivity, specificity, and diagnostic accuracy of the 3-year mortality prediction after haemodialysis initiation were used to evaluate the equation’s performance. The candidate threshold with the best performance was determined as the final threshold. Meanwhile, we developed a logistic model with the same variables as the DIFE using the development cohort.The final variables were used to establish a T-S type fuzzy neural network in the development cohort. The weighting function multiplier 2) were also created. The performance of the DIFE was validated based on the bootstrap-corrected Receiver-operator characteristic (ROC) area of the 3-year mortality prediction after haemodialysis initiation, and by comparing this with the logistic model and the conventional eGFR-based measurements, wherein eGFR was calculated by both the Chinese modified MDRD study (C-MDRD) equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Furthermore, we calculated the sensitivity, specificity, and diagnostic accuracy rate of the C-MDRD equation at various eGFR thresholds  for 3-year mortality in the validation cohort.We divided the patients of the validation cohort into predicted timely and late start groups based on the DIFE threshold and plotted the Kaplan–Meier curves. Kaplan–Meier curves stratified by different eGFR thresholds . For the comparison of patient baseline data between the two cohort groups, continuous variables were evaluated using the Mann-Whitney U test, and categorical variables were evaluated using the χwww.Rproject.org) was used for validation.Statistical analysis was conducted using SPSS software . All statistical tests were two-sided. Statistical significance was set at p < 0.05. All ANN models were constructed using MATLAB software , whereas R (version 3.4.1) open source software  and the validation cohort (n = 504) are presented in Table 281 and tWithin the first 3 years of haemodialysis, 156 patients died in the development cohort, and 57 patients died in the validation cohort. The 3-year mortality rate in the development cohort was 12.2 deaths per 100 patient-years, whereas the corresponding rate in the validation cohort was 11.3 deaths per 100 patient-years.29 and eight potential clinical factors . Classification accuracies obtained by the combination of different candidate variables are listed in Appendix Table A total of 13 candidate variables were considered as the input variables in the KLNN-RBM model, including five variables  as part of the MDRD study equation 7W in the equation was a function of six numerical variables , and served as a multiplier representing the effects of these variables on the patients’ outcomes.A T-S type fuzzy neural network model was established in the development cohort using the nine selected variables. P = 0.428) (shown in Table The parameters of the equation variables are shown in Appendix Table 2). The best sensitivity, specificity, and diagnostic accuracy rates for the conventional assessment of 3-year mortality in the validation cohort were 19.3%, 77.0%, and 70.6% respectively, when the eGFR was 5 mL/min/1.73 m2; however, the values were all lower compared with those obtained using the DIFE  and 0.53 for the CKD-EPI equation ; the P values were 0.013 and 0.006 after 2000 times bootstrapping  was 0.70  for the DIFE and 0.60  for the logistic model; the 31. Hence, we developed a novel equation, termed the DIFE, based on fuzzy mathematics and ANNs, which integrated multiple affecting factors, to assess dialysis initiation.The GFR is commonly used to assess renal function and was also considered as a critical factor to evaluate the dialysis initiation time. However, eGFR alone is not sufficient to assess the dialysis initiation timeIn this nation-wide prospective cohort, all the participants were enrolled from major haemodialysis centres in Mainland China. Nephrologists at these centres have considerable clinical experience and can make precise subjective judgments regarding dialysis initiation. Therefore, the new equation developed based on data from these centres, would ensure the optimum and precise assessment of dialysis start time in China.40. Moreover, the KDOQI guidelines recommended that the decision to initiate dialysis should be based on an assessment of multiple clinical factors, including demographic factors, renal function, nutritional status, clinical signs and symptoms, and comorbidity16. Hence, we included these factors in the KLNN-RBM model as candidate variables, among which the signs and symptoms variable was the most frequently documented and routinely obtained.Some observational studies and meta-analyses suggested that several clinical factors at dialysis initiation  were associated with the prognosis of patients with ESRD, and some of these variables were already present in certain predictive models for CKD, renal failure, and risk of death45. However, to optimize the initial parameters and promote the classification capability of the logistic model, we combined a kernel logistic neural network with RBM and established the KLNN-RBM model. In our previous study, we validated KLNN-RBM in a single centre prospective cohort of dialysis patients. The results showed that the KLNN-RBM achieved higher accuracy compared with traditional logistic regression27. We also used six University of California Irvine (UCI) Machine Learning Repository datasets to test the performance of KLNN-RBM. The UCI Machine Learning Repository is a widely used primary source of machine learning data sets for the empirical analysis of machine learning algorithms, which has some biological and clinical datasets. The results also showed that the KLNN-RBM could achieve higher accuracy for the binary classification and multi-class classification problems23. These suggested that the KLNN-RBM model is an appropriate method for candidate variable screening.The kernel logistic regression models and restricted Boltzmann machines are both proven techniques to handle feature selection and dimensionality reduction, and to determine the initial value of the model in classification situations. These two techniques have been used in disease diagnosis, gene screening, and other biological/ clinical studies35. Based on these studies, we successfully determined the quantitative combination of these clinical factors for the first time. We initially compared the results of DIFE with a logistic model that had the same variables as the DIFE, and the DIFE demonstrated better model discrimination (the AUC of the DIFE was 0.70 vs. the AUC of the logistic model of 0.60). This result indicated that when integrating multiple variables, especially including some subjective judgments, fuzzy mathematics could be a more appropriate modelling method than traditional statistical methods. We also compared the AUC of the DIFE with those of two conventional eGFR-based assessments, and neither result was better than that of the DIFE (0.55 for the C-MDRD equation and 0.53 for the CKD-EPI equation). Therefore, the DIFE was more accurate to assess dialysis initiation than the conventional eGFR-based assessments. Furthermore, the Kaplan–Meier curves between the predictive timely and late start groups showed a significant difference based on the DIFE equation (P < 0.001); however, the C-MDRD equation and the CKD-EPI equation did not show any difference in the start time of dialysis for any eGFR value (P > 0.05). This result indicated that the DIFE could be a more suitable assessment method for the timing of dialysis initiation compared with the eGFR based conventional assessment.In the present study, the results showed that the combination of sex, age, serum creatinine, blood urea nitrogen, serum albumin, haemoglobin, serum phosphorus, diabetes mellitus, and heart failure as equation variables resulted in the best accuracy. The clinical factors employed within the DIFE equation were consistent with those in the clinical guidelines and other cohort studies2 , could not be included as candidate variables. We are conducting a prospective, multicentre, randomized, controlled trial concerned nutrition status, including SGA and malnutrition symptoms, to verify and improve the equation . Although neural network techniques have been developed in a wide range of applications in recent years, and are proven to be superior to conventional statistical models to assess initiation of dialysis, how to optimize the structure and parameters in neural networks remains a challenge.In the present study, we developed a novel fuzzy neural network model to evaluate the optimal time of haemodialysis initiation in a Chinese ESRD population. The variables in the equation included the clinical indicators of haemodialysis initiation, and the performance of the equation was found to be more precise than conventional eGFR-based assessments. This equation may be a helpful tool to quantitatively evaluating the initiation of haemodialysis.appendix tables and figures


Hypertension is the most prevalent clinical symptom arising from various cardiovascular disorders. Likewise, it is considered a precursor or sequelae to the development of acute coronary artery disease and congestive heath failure (CHF). Hypertension has been considered a cardinal criterion to determine cardiovascular function. According to the World Health Organization (WHO) global observatory data, hypertension causes more than 7.5 million deaths a year, about 12.8% of the total human mortality. Similarly, the Center for Disease Control (CDC) states that 35% of the American adults have been estimated to have a persistently high blood pressure, which makes it about one in every three adults. Hypertension is a modifiable symptom that can be managed through pharmacological and non-pharmacological methods and standard protocols set forth by the American Heart Association (AHA). With new findings from various clinical trials related to the management of hypertension, new developments and recommendations have been made to update the previously established protocols for hypertension. This article aims to discuss and dissect the modern updates of hypertension management as comprehensively elaborated in the 2017 Hypertension Clinical Practice Guidelines. Hypertension (HTN) is part of a clinical syndrome that results from multifaceted etiologies and can contribute to the development of complex cardiovascular disorders. In addition, it is a significant clinical symptom that directly relates to a dysfunctional cardiovascular system. HTN can be of two types: essential or secondary. In essential HTN, the etiology is unknown while in secondary HTN, a known pathological disorder is the cause. Hypertension (HTN) is primarily observed when there are pressure changes in the vascular system secondary to an abnormal cardiovascular fluid regulation and/or loss of vascular/arterial tone. It can also be due to abnormal contractility and/or aberrant electrical conductivity of the heart. Moreover, HTN can also be caused by conditions that are not organ-based and that predispose an individual to have these pressure changes.The new definition of hypertensionHTN is diagnosed through non-invasive means with the application of a sphygmomanometer. It is necessary to ensure that blood pressure (BP) measurements are undertaken accurately. The apparatus determines the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of an individual in millimeters of mercury (mm of Hg). According to the updated guideline  providedWell-elaborated management guidelinesHTN is classically managed with a plethora of interventions, ranging from pharmacological to non-pharmacological measures to decrease or manage increased BP. According to the 2017 Hypertension Clinical Guidelines by AHA, decisions to manage HTN using BP-lowering medications, in addition to non-pharmacological interventions, should be determined by the level of BP and the patient's risk for atherosclerotic cardiovascular disease (ASCVD)  diet, soThiazide diuretics, calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs), or angiotensin-converting enzyme (ACE) inhibitors  have beeHypertension with comorbiditiesIn addition, the guidelines provide varied treatment strategies for individuals diagnosed with HTN and other clinical comorbidities. Many pathologies affect clinical decision-making  in HTN. Heart Failure with Reduced Ejection Fraction (HFrEF)According to these guidelines, the recommended goal for adults with HFrEF and HTN is set at 130/80 mmHg . GuideliChronic Kidney Disease (CKD)HTN is the most prevalent clinical symptom associated with chronic kidney disease CKD . About 6Intracranial HemorrhageElevated BP is highly prevalent in the setting of acute intracranial hemorrhage (ICH) . It is lPeripheral Arterial DiseaseHTN is a common factor for patients with peripheral arterial disease (PAD) -24. ThesAtrial FibrillationPatients with atrial fibrillation (AF) have HTN in 80% of the cases  and it'sDiabetes MellitusThe prevalence of HTN among adults with diabetes mellitus (DM) is approximately 80% , and HTNFollow-upTreatment monitoring and the follow-up routine were also amended in the new guidelines. Substantial changes to various stages of HTN were included. For patients with normal BP, the guidelines suggest a yearly follow-up assessment. For patients with an elevated BP and stage 1 HTN, assessment should be made every three to six months with an assessment and optimized adherence therapy. Follow-up assessment every month is advised for patients with stage 2 HTN.Improving treatment and blood pressure (BP) control in adults with hypertension (HTN) involves a system of techniques and strategies that are individualized according to the needs of the patient. Hypertension Clinical Guidelines 2017 provides us with a well-researched tool that effectively improves current HTN management. It is a systematic algorithm for healthcare professionals who follow evidence-based clinical practice to restrain the complications brought by elevated BP.


Patients with chronic kidney disease (CKD) are exposed to both traditional ‘Framingham’ and uremia related cardiovascular risk factors that drive atherosclerotic and arteriosclerotic disease, but these cannot be differentiated using conventional ultrasound. We used ultra-high-frequency ultrasound (UHFUS) to differentiate medial thickness (MT) from intimal thickness (IT) in CKD patients, identify their determinants and monitor their progression.Fifty-four children and adolescents with CKD and 12 healthy controls underwent UHFUS measurements using 55-70MHz transducers in common carotid and dorsal pedal arteries. Annual follow-up imaging was performed in 31 patients.2 64%).CKD patients had higher carotid MT and dorsal pedal IT and MT compared to controls. The carotid MT in CKD correlated with serum phosphate , PTH  and mean arterial pressure . Following multivariable analysis, being on dialysis, serum phosphate levels and mean arterial pressure remained the only independent predictors of carotid MT . At 1-year follow-up, transplanted children had a decrease in carotid MT (p = 0.01), but an increase in dorsal pedal IT (p = 0.04) that independently correlated with annualized change in BMI.Using UHFUS, we have shown that CKD is associated with exclusively medial arterial changes that attenuate when the uremic milieu is ameliorated after transplantation. In contrast, after transplantation intimal disease develops as hypertension and obesity become prevalent, representing rapid vascular remodeling in response to a changing cardiovascular risk factor profile. Cardiovascular disease begins early in the course of chronic kidney disease (CKD),2 and isConventional IMT is unable to differentiate between changes in arterial intima and media. Recently, ultra-high frequency ultrasound (UHFUS) imaging has enabled visualization of the intimal and medial layers of the vessel wall in exquisite detail so that We recruited 54 consecutive children and adolescents with CKD stage 4–5, on dialysis or with functioning renal transplants from clinics at Great Ormond Street Hospital for Children, London. We excluded children <5 years of age  and thoAll patients had vascular imaging by both UHFUS and conventional ultrasound in the carotid and dorsal pedal arteries at the same site at baseline and follow-up.IT and MT were measured using UHFUS  with 55 and 70 MHz peak frequency linear array transducers for carotid and dorsal pedal imaging respectively  patients could be scanned with the 70 MHz transducer, whereas 96% of carotid measurement were possible with the 55 MHz transducer. All the dorsal pedal vessels, which are more superficial, were clearly visualized with the 70 MHz transducer, and measured above the proximal part of the first metatarsal bone in the foot.Conventional IMT measurements were performed in all children as part of the Cardiovascular Comorbidity in Childhood CKD (4C) study, a longitudinal cohort study that includes 700 children across Europe with annual cardiovascular assessments. The intSpacelabs Healthcare) and time–averaged 24-hour mean arterial pressure (MAP) used for further comparisons. All BP readings were normalized to standard deviation scores (SDS) using European reference data[ABPM was performed in all patients at baseline and 12 months using Spacelabs 90207-2Q oscillometric devices , 25(OH)D (isotope-dilution liquid chromatography-tandem mass spectrometry), high-sensitivity CRP , lipid profile , FGF23 , s-klotho . Estimated GFR was calculated using the modified Schwartz formula. Serum calcium, phosphate and PTH levels are described as mean time-averaged levels over one year.Blood tests and vascular measures were performed at the same clinic visit: before a mid-week session of hemodialysis or at clinic review for predialysis CKD, peritoneal dialysis, and transplant recipients. Routine non-fasting blood samples were collected and serum was frozen at -80°C; all analyses were performed in a blinded fashion. We did not have ethical approval to perform blood tests in the healthy controls. The following biochemical analyses were performed in all patients at baseline and 12-month follow-up: renal function tests, measures of mineral dysregulation D and PTH were log-transformed to achieve normality. All analyses were performed with GraphPad Prism  or SPSS , and a two-tailed p<0.05 was considered statistically significant.Data are presented as mean ± SD or median (range) as appropriate. Univariate comparisons of continuous variables between the groups  were performed by one-way ANOVA. Comparisons of continuous variables between baseline and final follow-up were performed using a paired Carotid MT was higher in patients compared with controls  and PTH levels  over the preceding year and the MAP SDS , the mean carotid MT correlated with time-averaged serum phosphate , serum phosphate and MAP SDS were significant and independent predictors of a higher carotid MT, explaining 64% of the variance in carotid MT .2 = 0.16; The dorsal pedal artery MT in CKD and dialysis patients weakly correlated with diastolic BP SDS D, FGF23 or soluble-klotho levels, serum cholesterol or triglycerides, or treatment with phosphate binders or vitamin D analogues.A 1-year follow-up, vascular measurements were examined in two groups: (i) patients who remained in pre-dialysis CKD (n = 16) and (ii) patients who were transplanted (n = 15); Over 12 months, CKD patients had an increase in serum phosphate, FGF23 and MAP SDS . In the transplanted patients, over the same time period of 12 months, there was an increase in BMI SDS, systolic BP SDS and MAP SDS and serum cholesterol level , but no change in uremic risk factors such as serum phosphate or PTH.2 29%). No change in conventional cIMT was seen on annual follow-up in either CKD or transplant groups.Children and adolescents who remained in pre-dialysis CKD did not show changes in any vascular measures at annual follow-up. In contrast, transplanted patients had a decrease in carotid MT . Carotid IMT by conventional ultrasound showed an overestimation of IMT by 0.15 ± 0.04 mm for conventional ultrasound compared to the sum of carotid IT and MT on UHFUS Click here for additional data file.S2 Table(PDF)Click here for additional data file.


Background: Several determinants of exercise intolerance in patients with precapillary pulmonary hypertension (PH) due to pulmonary arterial hypertension and/or chronic thromboembolic PH (CTEPH) have been suggested, including diaphragm dysfunction. However, these have rarely been evaluated in a multimodal manner. Methods: Forty-three patients with PH  and 43 age- and gender-matched controls  underwent diaphragm function (excursion and thickening) assessment by ultrasound, standard spirometry, arterial blood gas analysis, echocardiographic assessment of pulmonary artery pressure (PAP), assay of amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac magnetic resonance (CMR) imaging to evaluate right ventricular systolic ejection fraction (RVEF). Exercise capacity was determined using the 6-min walk distance (6MWD). Results: Excursion velocity during a sniff maneuver  and diaphragm thickening ratio  were significantly lower in PH patients versus controls. PH patients with worse exercise tolerance (6MWD <377 vs. ≥377 m) were characterized by worse SniffV, worse DTR, and higher NT-pro-BNP levels as well as by lower arterial carbon dioxide levels and RVEF, which were all univariate predictors of exercise limitation. On multivariate analysis, the only independent predictors of exercise limitation were RVEF  and NT-proBNP . Conclusion: Patients with PH showed diaphragm dysfunction, especially as exercise intolerance progressed. However, diaphragm dysfunction does not independently contribute to exercise intolerance, beyond what can be explained from right heart failure. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) as forms of precapillary pulmonary hypertension (PH) are associated with significant exercise intolerance, but the exact mechanisms leading to exercise limitation are multifactorial and still not well understood .In precapillary PH, and in PAH and CTEPH in particular, increased pressure in the pulmonary arteries overloads the right ventricle (RV), causing hypertrophy and failure . The majRecently, inspiratory muscle strength has emerged as a potential new contributor to exercise intolerance in PH ,9. IndeeTherefore, this prospective study was conducted in patients with precapillary PH and age- and sex-matched controls to evaluate whether diaphragm function, assessed by diaphragm ultrasound,  contribua priori approval by the Institution’s Human Research Committee . All participants gave verbal written informed consent to participate in the study. The project was prospectively registered and continuously updated under the German Clinical Trials Registry (drks.de Identifier: DRKS00014695).The present study was conducted at the University Hospital of Münster (Universitätsklinikum Münster) from June to September 2018. Informed consent was obtained from each subject and the study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in Patients with Nizza class I PAH or Nizza class IV CTEPH were consecutively recruited based on the latest European Society of Cardiology (ESC) criteria . All patA group of healthy volunteers well matched for age, gender and body mass index (BMI) was enrolled as control group and underwent evaluation of diaphragm function. All volunteers were required to have normal electrocardiogram (ECG) findings, pulmonary function natriuretic peptide hormone levels.ECG-gated CMR studies were performed on a 1.5-T scanner  using commercially available cardiac software and cardiac-dedicated surface coils. Cine-imaging was performed using a steady-state-free-precession (SSFP) sequence in four long-axis slices  and a stack of short-axis slices completely covering the ventricles.CMR analysis was performed off-line by two experienced readers. Ventricular volumes and ejection fraction were derived by contouring the endocardial borders at end-diastole and end-systole on the short-axis cine images and including the left ventricular (LV) papillary muscles/RV trabeculations in the ventricular cavity. For optimal segmentation of the RV, the tricuspid valve and apical planes were first defined using the four- and modified two-chamber for RV slices. RV systolic dysfunction was defined according to the latest available published data .A portable ultrasound machine  with a 3.5-MHz convex transducer was used for assessment of diaphragm excursions in the subcostal view, and a 10-MHz linear transducer was used for evaluation of diaphragm thickness in the zone of apposition. Measurements were performed on the right hemidiaphragm in the supine position because posture is known to directly affect diaphragm thickness . All meaFor evaluation of diaphragm excursions, the 3.5 MHz probe was positioned between the mid-clavicular and anterior axillary lines, in the subcostal area with the probe held as medially as possible and directed cranially A. Excurst test or Mann–Whitney U test, as appropriate, while categorical data were compared using the Chi-Square test, with Fisher’s exact test, as appropriate. Pearson product moment correlation was used to explore the relationship between continuous variables: strength of correlation was classified as weak (0.20–0.38), moderate (0.39–0.58), strong (0.58–0.78) or very strong (0.79–1.00). Determinants of exercise intolerance were evaluated using univariate and multivariate regression analyses forcing age and gender into the equation with 6-min walk distance (6MWD) as the dependent variable. Based on pilot data and assuming a two-sided significance level of 5% (α) and 80% power (β), a sample size of 35 patients was calculated to be required to detect a 20% reduction in DTR. To allow for dropouts, the target sample size was 43 patients and the same number of controls. For all analyses, a P-value of <0.05 was considered statistically significant.All analyses were performed using Sigma Plot™ software . Before analysis, data distribution was tested using the Kolmogorov–Smirnov test. Results are expressed as mean and standard deviation or median and interquartile ranges for continuous variables with normal or skewed distribution, respectively, and as percentages for categorical data. Comparison of continuous variables between groups was done using independent 2) and 43 control subjects matched for gender, age, and BMI  were enrolled in the study (n=36) and the others had CTEPH (n=7).Forty-three consecutive patients with precapillary PH .PH patients had moderate to severe PH (systolic PAP 51 ± 7 mmHg) as indicated by the fact that most (58%) were in New York Heart Association (NYHA) functional class III with moderate to severe exercise impairment (based on 6MWD achieved). Patients with PH also had systolic RV dysfunction (63% of cases) and elevated NT-pro-BNP levels. Respiratory data revealed a mild but significant reduction in forced vital capacity (FVC) and the presence of hypocapnia (capillary carbon dioxide) COP<0.01; diaphragm velocity: 1.7 ± 0.9 vs. 1.1 ± 0.4 cm/s, P<0.01). Excursion velocity during a sniff maneuver  and the DTR  were significantly reduced in precapillary PH patients versus controls , higher levels of NT-pro-BNP (1000 [interquartile ratio (IQR): 557–2689] vs. 450 [IQR: 109–1000] ng/l, P<0.01) and lower pCO2 values . They also showed worse SniffV  and worse DTR  (1). Supplemental Videos S1 and S2 summarize diaphragm ultrasound abnormalities found in a patient with preserved RV systolic function and in a patient with impaired RV systolic function.When dichotomized into two groups based on 6MWD above or below the median, precapillary PH patients with more pronounced exercise intolerance (6MWD <377 vs. ≥377 m) had worse right ventricular systolic ejection fraction (RVEF)  . Of noteP=0.03; DTR: r = 0.44, P=0.004) and pCO2 .SniffV and DTR were weakly–moderately correlated with RVEF  and its correlation with exercise intolerance is close to that reported by Kabitz and coworkers  and supp2 (which reflects baseline hyperventilation), and diaphragm strength  and is, on the other hand, also responsible for diaphragmatic impairment through chronic hypoperfusion.In precapillary PH, increased pressure in the pulmonary arteries overloads the RV, eventually causing hypertrophy and failure . Most mestrength ). We hypMost of our pathophysiological understanding of diaphragm involvement stems from numerous studies on this topic in patients with systolic HF . HoweverIn light of the findings presented above see  it may b1 40 ± 15% predicted) with COPD in whom we collected diaphragm ultrasound data and in whom the presence of precapillary class III PH is very likely based upon echocardiographic measures . In these patients diaphragm abnormalities similar to those seen in patients with Nizza classes I and IV were found suggesting that diaphragm dysfunction does also occur there. This was evidenced by significantly lower amplitude during maximal inspiration of 5.4 ± 1.5 cm and a significant reduction in DTR of 2.2 ± 0.3: both P<0.05 against a control group matched for age, gender, and BMI).In the current study, diaphragm ultrasound assessment was related to a volitional maneuver and is therefore subject to bias. However, the use of repeated measurements for each variable (mean over three samples) as well as the fact that the degree of diaphragm dysfunction was comparable with that observed using non-volitional assessment by magnetic phrenic nerve stimulation appear to support the validity of ultrasound in this setting. Plus, as per guideline recommendations, right heart catheterization was used to diagnose PH, but only echocardiography was repeated during follow-up visits, including at study enrollment. Although this may potentially introduce a lack of precision and exclude some relevant hemodynamic data, this topic has been evaluated in previous studies ,15,17 anPatients with progressive precapillary PH are characterized by diaphragm dysfunction which may develop in response to chronic hyperventilation. However, diaphragm dysfunction does not independently predict exercise intolerance beyond what can be explained by RV systolic function. Additional research is needed to further elucidate the underlying pathophysiological mechanisms that lead to diaphragm dysfunction in PH.This prospective study was conducted in patients with precapillary PH and age- and sex-matched controls to evaluate whether diaphragm function, assessed by diaphragm ultrasound, contributes to exercise intolerance, evaluated by the 6-min walking test, over and above impaired right ventricular pump function, as assessed by CMR imaging.The present study confirmed that diaphragm impairment is a very common finding in patients with precapillary PH. Diaphragm dysfunction seems to develop as exercise intolerance progresses. However, the most important new finding of the present study is that inspiratory muscle strength impairment did not independently contribute to exercise intolerance in precapillary PH, beyond RV systolic dysfunction.Patients with progressive precapillary PH are characterized not only be RV systolic dysfunction but also by diaphragm dysfunction which may develop in response to chronic hyperventilation. Additional research is needed to further elucidate the underlying pathophysiological mechanisms that lead to hyperventilation and diaphragm dysfunction in PH, since these alterations are not (yet) part of a targeted therapy in PH.The study funders had no role in study design, data collection and analysis, preparation of the manuscript, or the submission process.


Autonomic neural system (ANS) regulates the circulation to provide optimal perfusion of every organ in accordance with its metabolic needs, and the quantitative assessment of autonomic regulation is crucial for personalized medicine in cardiovascular diseases. In this paper, we propose the Dystatis to quantitatively evaluate autonomic regulation of the human cardiac system, based on homeostatis and probabilistic graphic model, where homeostatis explains ANS regulation while the probability graphic model systematically defines the regulation process for quantitative assessment. The indices and measurement methods for three well-designed scenarios are also illustrated to evaluate the proposed Dystatis: (1) heart rate variability (HRV), blood pressure variability (BPV), and respiration synchronization (Synch) in resting situation; (2) chronotropic competence indices (CCI) in graded exercise testing; and (3) baroreflex sensitivity (BRS), sympathetic nerve activity (SNA), and parasympathetic nerve activity (PNA) in orthostatic testing. The previous clinical results have shown that the proposed method and indices for autonomic cardiac system regulation have great potential in prediction, diagnosis, and rehabilitation of cardiovascular diseases, hypertension, and diabetes. Autonomic neural system (ANS) regulates the circulation to provide optimal perfusion of every organ in accordance with its metabolic needs. Together with the endocrine and immunological systems, it adjusts the internal environment of the organism to respond the changes in the external environment . TherefoIn clinical settings, autonomic dysfunction has been linked to direct detrimental effects towards heart failure and chronic kidney disease ; thus, qSince the quantitative assessment of the autonomic regulation is tremendously important for clinical and healthcare applications, there is urgent need to quantitatively evaluate the ANS regulation status. Unfortunately, there are only two invasive methods to measure certain aspects of the ANS thus far: (1) microneurography to assess muscle sympathetic nerve activity and (2) the norepinephrine isotope dilution to determine noradrenalin in the blood to evaluate spillover of the sympathetic nervous system . AlthougWe propose the Dystatis to quantitatively evaluate autonomic regulation of the human cardiac system, based on homeostatis and the probabilistic graphic model, where homeostatis explains ANS regulation while the probability graphic model systematically defines the regulation process for quantitative assessment.HRV, BRV, and Synch in resting situation: Dystatis provides theoretical model and guidelines for the test design and data processing and interpretations, in order to solve existing inconsistence problems.CCI in graded exercise testing: Dystatis metabolic requirement is enlarged by graded exercise so that CCI can be obtained without considering effects from other internal and external interactions. These are minor compared to graded exercises.BRS, SNA, and PNA in orthostatic testing: based on Dystatis, orthostatic testing creates a large blood pressure drop and then a large BRS output to sympathetic and parasympathetic nerves. As such, the mathematical model for solution of BRS, SNA, and PNA can be greatly simplified by neglecting other internal and external interactions in the ANS regulation.The Dystatis is elaborated in three well-designed scenarios, where indices and measurement methods for each scenario are also proposed and illustrated by clinical applications:In summary, ANS regulation of the cardiac system plays a central role in both research and clinical practices, and we will focus on the quantitative assessment of autonomic regulation of the cardiac system in this paper. The main contributions are as follows:Human body is a complex biological system, of which homeostasis is a crucial property in maintaining the life. It is the self-regulating process by which biological systems maintain stability in order to adjust to conditions that are optimal for survival. The stability attained is a dynamic equilibrium, in which continuous change occurs yet relatively uniform conditions prevail.Dystasis is built up on homeostasis and defined as follows: ANS regulation of the cardiac system is a part of body's complex biological system. Through ANS self-regulating process, the cardiac system tends to reach and maintain a dynamic equilibrium state, in order to supply cells and organs with their metabolic needs, e.g., oxygen, nutrients, and removal of waste, survive in various internal and external environments, and support various physical and mental activities. The characteristics of Dystasis are (1) equilibrium: the ANS self-regulating process of the cardiac system reaches and maintains an “equilibrium” state in a relative steady internal and external environment, with no or minor changes in terms of physical and mental activities. The property and its numerical measures of the state of this equilibrium of the individual's ANS self-regulating process shall provide quantitative performance evaluation of how well one's ANS regulation system works; (2) dynamic: the ANS self-regulating process of cardiac system should be “dynamic” enough, being able to work in dynamic environment, support various physical and mental activities of the body, and defend virus invasions. In other words, it should be able to reach new equilibrium state as soon as possible when there is a change of internal/external environment or physical/mental activities. For instance, ANS regulation interacts with the immune system to control inflammation  and ANS In order to quantitatively evaluate the state and capability of ANS regulation of the cardiac system, one feasible approach is the probabilistic graphic model-based approach , as showA is the state of ANS to be estimated through observations connected with ANS in the graph of Variability of the heart rate and blood pressure (HRV and BPV) while the subject is in resting or other steady state: the ideal measurement scenario is zero or known steady physical activity, minimal mental activity, and minimal viscera disturbance. The variability indices are used to characterize the state of equilibrium of individual's ANS self-regulating process, which directly reflects states of immune system, linking with inflammation biomarkers.CCI in graded exercise testing: the effect of physical activity on ANS is maximized so that the influences from the rest sources can be neglected. CCI provide numerical measures to characterize the capability of ANS regulation to accommodate changes of exercise intensity.BRS, SNA, and PNA are obtained by model-based analysis of blood pressure (BP) and heart rate (HR) pairs acquired in orthostatic testing: Via orthostatic test, large blood pressure drops around 30 mmh is obtained. The input from baroreflex to SNA and PNA becomes the major effect, and the rest can be neglected. As such, the mathematical model for the solution can be simplified as a subgraph of the graphic model in For the estimation purpose and from The indices of HRV and BPV consist of time-domain second-order statistics, for example, standard deviation of ECG normal-to-normal intervals (SDNN) and standard deviation of differences of neighboring normal-to-normal intervals (SDSD). Frequency-domain indices are calculated at very low frequency band , low frequency band , and high frequency band (0.15–0.4 Hz). The problem is then to quantitatively evaluate the state of ANS and infer the physiological and psychological implications, given measured variabilities of the heart rate, blood pressure, respiration, and assessment scenario that the physical activity is zero or constant. Based on Dystasis framework, according to equation . The wisdom of the body to maintain the homeostasis is achieved by synchronizing heartbeats with breathing and consequently to maximize the efficiency of the cardiopulmonary system in metabolic and circulation process. This equilibrium state is the result of resonance of the cardiopulmonary system. There are indices proposed to evaluate the degree of the resonance of the cardiopulmonary system. The most common used one is coherence measure (Coh), the cross power spectral density of the heart rate and respiration signals .th week) without pregnancy-induced hypertension and diabetes were randomly assigned to the HRVB group and the control group. Participants in the HRVB group practiced HRVB for 30 minutes per day, while participants in the control group did not. Following checks are conducted for all participants every two weeks: blood pressure (BP), fasting blood glucose (FBG), HRV of pregnant women (PHRV) and their fetuses (FRHV), and subjective assessment on pressure using Pregnancy Pressure Scale (PPS), depression using Edinburgh Postnatal Depression Scale (EPDS), and sleep quality using Pittsburgh Sleep Quality Index (PSQI). The clinical trial continued for subjects until they are in hospital for delivery. In the trial, the HRVB group has shown significant improvement over the control group with respect to blood pressure stability (p > 0.05), depression reduction (p=0.013), and sleep quality improvement, while fetuses in the HRVB group has shown significant improvement with respect to HRV SDNN (p < 0.01) and LF spectrum power (p < 0.01).The resonance of the cardiopulmonary system represents the equilibrium of ANS regulation, where one reaches both physiological and psychological healthy state. Therefore, Coh can be used to compose numerical measures to visually represent one's health state, especially psychological health state, and then, variability-biofeedback training is used to help one to gain resonance state. A clinic trial was conducted in the University of Chinese Academy of Sciences (UCAS) Hospital to test the effectiveness of HRV biofeedback (HRVB) for pregnant women in managing anxiety and depression . 20 pregHRV and BPV can be used as a noninvasive assessment tool for autonomic nervous system function, and reduced and/or abnormal HRV and BPV are associated with increased risk of mortality in cardiac patients. For both adults and children, increased blood pressure variability (BPV) appears to be directly related to sympathetic overactivity with increased risk of end-organ damage and cardiovascular events. Decreased HRV has been observed in adults and children with chronic kidney disease and is an independent predictor of mortality .Autonomic dysfunctions are the most common nonmotor symptoms of Parkinson's disease (PD) and often precede the motor symptoms of the disease. Clinical study has shown that HRV and BPV can be used as markers to indicate the treatment progress and stages of the disease .A review of research literature  tells thGraded exercise tests, such as cardiopulmonary exercise test (CPX), have been used in clinical practice to test the exercise capability in terms of maximum oxygen metabolism . In DystChronotropic incompetence (CI) is a terminology describing the status of attenuated heart rate response to exercises. CI has been studied for the last 50 years . Typical(1)Resting heart rate (HRrest) and resting blood pressure (BPrest): The resting heart rate and resting blood pressure are defined as the heart rate and blood pressure when a person is awake, in a neutrally temperate environment, and has not been subject to any recent exertion or stimulation, such as stress or surprise.(2)HR and CRBP): chronotropic rate represents the rate at which the heart rate and blood pressure increase as exercise intensity increases. It is measured as the amount of heart rate or blood pressure increase in response to every unit of metabolic equivalent (MET) exercise intensity increase. In practice, it can be measured and calculated asChronotropic rate (CRHR is similar with the “Exercise HR” in EACPR/AHA Joint Scientific Statement [CRtatement . It diretatement .(3)max is the maximal heart rate one achieves during the exercise test and HRPredM is the predicted maximal heart rate, usually calculated as 220 − age. The maximal heart rate is usually obtained when reaching peak exercise, which can be identified during CPX testing. In this case, the normal value of CL is 0.8–1.3. However, when CPX testing or peak exercise is not achievable, then CL normal values are different for types of exercises. For example, in a 6-minute walking test, CL = 0.4 for a 60-year-old person should be considered normal. With a resting heart rate of 75 bpm, CR would be 10 beats per MET and the maximal heart rate would be 109 bpm with an exercise intensity of 4.4 MET.Chronotropic limit (CL): chronotropic limit represents the maximal heart rate an individual can achieve without severe problems through exercise stress, as well as the blood pressure measured at the same time. It is measured as heart rate reserve and calculated as(4)Chronotropic acceleration (CA): ANS requires certain time to adjust the heart rate and blood pressure to reach a new stable state or equilibrium when the exercise intensity increases to a new level in the graded exercise test. CA is defined as the time taken to reach new equilibrium after exercise intensity increases. CA is measured in seconds and represents the ability of the ANS regulation of the cardiac system in fulfilling metabolic needs.(5)recovery1 and BPrecovery1): it is defined as the reduction in the heart rate and blood pressure 1 minute after stopping exercise. The measurement of HRrecovery1 and BPrecovery1 requires the testee to try his best in the exercise, but not necessarily to reach one's maximum capacity. EACPR/AHA Joint Scientific Statement [recovery1 provides insight into speed of parasympathetic reactivation and that the normal value of HRrecovery1 should be > 12 beats. There have been a number of clinical studies on prognosis value of HRrecovery1. For example, Dhoble et al. [recovery1 < 12 beats were found independently associated with mortality (P < 0.001).Chronotropic recovery at 1 minute after exercise . Consistently, after 3 months of rehab training, the rehab group is significantly better over the control group with respect to all three 3CT objective measures: 6-minute walking distance, chronotropic rate, and 1-minute heart rate recovery .Comparison between control and rehab groups after 3 months of rehab training using the Estimation of BRS, SNA, and PNA is carried out in orthostatic testing scenario where the subject is requested to suddenly stand up from a sitting position. As a result, blood pools in the vessels of the legs for a longer period and less is returned to the heart, thereby leading to a reduced cardiac output and fall in blood pressure. In order to counteract these changes, the frequency of afferent impulses in the aortic and carotid sinus nerves is reduced, which leads to parasympathetic withdrawal and sympathetic activation. Here, the nerve activity will be referred to as the baroreflex firing rate or simply the firing rate. Sympathetic activation leads to a growing release of norepinephrine which contributes to restoration of BP by increasing HR, cardiac contractility, and vasoconstrictor tone. In addition, parasympathetic withdrawal leads to decreased release of acetylcholine which also causes the increase of HR. This whole ANS regulation process can be described by a mathematical model , 38.The subject wears the device and sits on a chair, with the upper body straight up until reaching a stable state of heart rateThe subject stands up and keeps standing for 40 secondsThe above process is repeated for three timesIn the measurement, the subject wears a device which measures ECG, radial artery pulse wave and branchial artery pulse wave, and acceleration data to locate phases of the orthostatic posture. The orthostatic testing protocol is as follows:The device records all the data and sends the data to the computer wirelessly. The heart rate is calculated from ECG signal. The average blood pressure is estimated via pulse transmission time from radial artery pulse wave and branchial artery pulse wave with assumption that the physical properties of the blood vessel and the blood do not change within the measurement time. BP is used to calculate the baroreflex firing rateWith baroreflex firing rate, sympathetic and parasympathetic outflows are predictedConcentrations of noradrenaline and acetylcholine are computed as functions of the sympathetic and parasympathetic outflowsHeart rate is computed as a function of these two chemical concentrationsComputed HR is compared with the measured HRFor each BP and HR pair, the following is performed:th hypertension person. Other parameters, such as baroreflex sensitivity, can be derived from those curves and BP and HR data.For all BP and HR pairs, optimization for the minimizing error is performed between computed HR and measured HR to get curves of baroreflex firing rate and sympathetic and parasympathetic outflows. The blood pressure change in the orthostatic test is maximized, and the mathematical model defining the ANS regulation of heart rate due to blood pressure changes can then be simplified as a small subgraph of the probability graphic model in Noninvasive measurement of BRS, SNA, and PNA provides useful meanings to discover mechanisms that act to keep cerebral blood flow (CBF) constant, to understand immune system, for better management of metabolic syndrome and hypertension. The quantitative estimation of baroreflex sensitivity has been regarded as a synthetic index of neural regulation at the sinus atrial node, which has been shown to provide clinical and prognostic information in a variety of cardiovascular diseases, including myocardial infarction and heart failure . ChronicWe have described a systematic method for the quantitative assessment of autonomic cardiac system regulation, named Dystatis. The fundamental part of Dystatis is a quantitative assessment methodology based on homeostatis and the probabilistic graphic model, where homeostatis explains ANS regulation while the probability graphic model formally defines the regulation process and provides quantitative assessment basis. As instances of Dystatis, indices and measurement methods for three well-designed scenarios are also described together with clinical applications: (1) HRV, BPV, and Synch in resting situation, (2) CCI in graded exercise testing, and (3) BRS, SNA, and PNA in orthostatic testing.Numerous clinical research results have shown that the proposed method and indices for autonomic cardiac system regulation have great application potential in the prediction, prognosis, and rehabilitation of cardiovascular diseases, hypertension, diabetes, and other autonomic nerves-related areas. Further researches are being carried out to work with various research institutions and hospitals to conduct multicenter clinical research to investigate potential applications of the proposed methods in the prediction, prognosis, and rehabilitation of cardiovascular diseases, hypertension, diabetes, and other autonomic nerves-related problems.


Hypertension is a leading cause of cardiovascular disease, stroke, and death. It affects a substantial proportion of the population worldwide, and remains underdiagnosed and undertreated.Long-standing high blood pressure leads to left ventricular hypertrophy and diastolic dysfunction that cause an increase in myocardial rigidity, which renders the myocardium less compliant to changes in the preload, afterload, and sympathetic tone. Adequate blood pressure control must be achieved in patients with hypertension to prevent progression to overt heart failure. Controlling blood pressure is also important in patients with established heart failure, especially among those with preserved ejection fractions. However, aggressive blood pressure lowering can cause adverse outcomes, because a reverse J-curve association may exist between the blood pressure and the outcomes of patients with heart failure. Little robust evidence exists regarding the optimal blood pressure target for patients with heart failure, but a value near 130/80 mmHg seems to be adequate according to the current guidelines.Prospective studies are required to further investigate the optimal blood pressure target for patients with heart failure. A meta-analysis of 23 BP-lowering trials showed that 28.9% of the patients developed HF, which amounted to 8.5 events per 1000 patients [Chronic HTN causes structural and functional changes in the heart that ultimately lead to HF, which further increases mortality and morbidity. Although treating high BP intensively prevents and reverses myocardial changes in patients at risk of HF, defining the optimal BP target for patients with established HF is challenging, because the evidence is inconsistent and scarce. In this brief review, we aim to provide an insight into the pathophysiology of hypertensive heart disease and to summarize the current evidence relating to BP control in the prevention and treatment of HF.High BP increases the left ventricular (LV) afterload and peripheral vascular resistance, and prolonged exposure to an increased load leads to pressure- and volume-mediated LV structural remodeling , 10. VenDiastolic dysfunction is one of the first changes observed in a heart that has been exposed to an increased load. In response to LV end-diastolic pressure elevations, the left ventricle becomes hypertrophied and more rigid, and additional changes are induced by neurohormonal pathways activated by the BP increase . VentricHypertensive HF primarily manifests as diastolic dysfunction, followed by concentric or eccentric LV hypertrophy. Diastolic dysfunction increases the LV filling pressure and left atrial (LA) volume, which, in turn, increase the pulmonary artery pressure .The pathway from LV hypertrophy to overt HF is complex and unclear. Most patients with concentric hypertrophy develop HFpEF, but despite the absence of a history of myocardial infarction, some can progress to HFrEF. The development of HFpEF seems to be associated with changes in the extracellular matrix that cause progressive fibrosis of the myocardium and, subsequently, an increase in LV stiffness . It is aCardiac structural changes are mostly caused by a chronic rise in the BP, and they are markers of preclinical or asymptomatic CV disease . The prePatients with long-standing HTN are more sensitive to changes in pressure, volume, and sympathetic tone . AlthougHypertensive acute HF occurs when adverse conditions result in a volume redistribution and a shift from the splanchnic and peripheral vasculature to the pulmonary circulation. This ventricular-vascular uncoupling manifests as a rapid onset of pulmonary edema in patients with LV hypertrophy and diastolic dysfunction. Although intravenous diuretics are the first choice in treating acute HF with volume overload (Class I), reducing the preload and afterload using vasodilators  should be also considered, as the volume overload might not be involved in the clinical congestion in some patients . ResiduaThe prevalence of HTN as an HF etiology varies geographically and temporally Table . The finIn contrast, the presence of HTN as a comorbid condition in patients with HF has become more pronounced over time. The findings from studies of the KorHF and KorAHF registries showed that the prevalence of HTN increased from 47 to 59% over 10 years , 37. TheWhether HTN is a cause or a contributor to the development of HF is not clear. Although a BP elevation alone may not be sufficient to trigger HF, it increases the risk of CV diseases progressing to HF. For example, the activation of neurohormonal pathways induced by a persistent BP elevation in addition to LV hypertrophy could lead to adverse modifications of postinfarct ventricular remodeling, rendering the heart vulnerable to the development of HF after a myocardial infarction . FactorsTwo issues arise regarding HF when treating HTN. The first is strictly controlling high BP to prevent structural remodeling and the development of HF. The presence of a J-curve association between BP and CV outcomes have been long debated, but evidence has been controversial , 52. TheIdentifying patients at an increased risk of developing hypertensive HF is important to enable attentive monitoring and begin timely treatment. LA enlargement in the absence of mitral valve disease could be a marker of diastolic dysfunction; this has been demonstrated by the correlation between the LA volume and the natriuretic peptide levels in asymptomatic patients with preserved systolic function . BiomarkHTN treatment relies on many classes of drugs, including angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs), and diuretics. A meta-analysis of randomized clinical trials that analyzed HF as an outcome showed significant reductions in the new-onset HF rates in association with all of these classes of drug, except for ARBs, which may have been a consequence of the small number trials reviewed. The findings from head-to-head comparisons of the different drug classes have shown that CCBs seem to be inferior at preventing HF compared with ACE inhibitors/ARBs, beta-blockers, and diuretics; however, the inferiority of the CCBs was largely attributable to differences in the use of concomitant drugs . ThiazidThe other issue regarding HF and HTN is managing high BP in established HF patients. Treating high BP is more complicated in patients with established HF, but it remains important with respect to HF progression and patients’ prognoses. As all medications that have favorable effects on HF outcomes lower BP to some extent, we can assume that a close relationship exists between BP and HF outcomes. However, data describing the optimal BP in patients with HF are limited and contradictory. The findings from the OPTIMIZE-HF  trial suggested that BP elevations in patients with HF were associated with lower in-hospital mortality rates , 62. A mThe relationship between BP and the HF prognosis is not necessarily always linear. A J-curve that is similar to that which describes the relationship between the BP and CV outcomes, has been indicated repeatedly in patients with HTN –70. The The trade-off between prescribing adequate doses of guideline-directed medical treatments and maintaining a lower BP threshold is an issue that many physicians encounter in daily practice. The benefits of treatment in relation to the outcomes must be weighed against the adverse effects induced by lower BPs. Although medications with survival benefits remain effective within lower BP thresholds, no definitive evidence is available that supports intensive BP treatment. The current evidence suggests that all patients with HF should receive triple therapy comprising ACE inhibitors or ARBs, beta-blockers, and diuretics, with the doses adjusted to maintain an adequate BP, and if a patient remains hypertensive, thiazide-like diuretics can be added . Based oAmong patients with chronic HTN, structural and functional changes in the heart can lead to the development of HF. BP management not only prevents asymptomatic HTN-mediated organ damage that can cause HF but can also prevent further disease progression. The intensive control of BP is recommended for patients with HTN who are at risk of HF; however, the optimal range within which BP should be controlled and the benefits of intensive BP control in patients with established HF remain unclear. Future randomized clinical trials are warranted to understand the complex association between BP and patients’ prognoses in the context of HF management.


Aim. The association of pressure load with elasticity in vascular system has not been studied fully. We proposed a hypothesis whether gender could modify the association of blood pressure variability (BPV) and arterial stiffness assessed by carotid-femoral pulse wave velocity (CF-PWV) in prehypertensive patients. Methods. 24h ambulatory blood pressure monitoring (24h-ABPM) and CF-PWV were measured in 723 participants with prehypertension. Univariate and multivariate regression analyses of these clinical and biological parameters were performed in total population, male and female. Results. A total of 723 participants  were enrolled into the study. Compared with female, body mass index (BMI), fasting plasma glucose (FPG), uric acid (UA), and homocysteine (HCY) were significantly higher . Arterial stiffness  and BPVs  were higher in male. Multivariable linear regression analysis showed that 24 h BPV were linearly and positively related to CF-PWV in total population  and female  independent of traditional risk factors and medications. Conclusion. BPV was independently associated with arterial stiffness in total population and the relation was modified by gender. 24 h BPVs in prehypertensive patients were useful to identify the early arterial stiffness. Clinical Trials Registration. This trial was registered with Clinical Trials.gov Identifier: NCT02569268. Prehypertension was defined as SBP of 120–139 mmHg and/or a DBP of 80–89 mmHg, and the prevalence of prehypertension was increased in the decades –6. PreviArterial stiffness was assessed by noninvasive measurement of carotid-femoral pulse wave velocity (CF-PWV), which had been recommended to assess the risk of future vascular events , 16. TheNCT02569268). BEST study was a post hoc analysis which recruited subjects aged 45-75 years through clinic or hospital from the western of Beijing, China. Our study recruited 723 subjects with prehypertension who completed 24-hour ambulatory blood pressure monitoring (24h-ABPM) and assessed arterial stiffness. Prehypertension was defined as SBP of 120–139 mmHg and/or a DBP of 80–89 mmHg [The participants of our study were selected from the part of Beijing Vascular Disease Patients Evaluation Study  on a typical working day with appropriate exercise. The 24 h ABPM was programmed to automatically obtain BP recordings. Day and night were defined based on the waking and sleep time. The BP cuff was located on the participant's nondominant arm and the cuff size was determined by the upper arm circumference. 24 h ABPM parameters included 24-hour systolic blood pressure (24h SBP), 24-hour diastolic blood pressure (24h DBP), 24-hour pulse pressure (24h PP), 24-hour systolic blood pressure standard deviation (24h SBP SD), 24-hour diastolic blood pressure standard deviation (24h DBP SD), daytime systolic pressure (D SBP), daytime diastolic pressure (D DBP), daytime pulse pressure (D PP), nighttime systolic pressure (N SBP), nighttime diastolic pressure (N DBP), and night pulse pressure (D PP). We used standard deviation (SD) as the indicator of BPV.CF-PWV was simultaneously and automatically measured by the device Complior SP . After subjects rested in the supine position for 5-10 minutes, we preformed the measurement to obtain CF-PWV values. CF-PWV was primarily obtained by measuring the distance of two cuffs  and the conduction time of pulse wave. We used a correction factor of 0.8 to explain the difference between the measured distance between both cuffs and the reference distance . The meaIn the cross-sectional study, all continuous variables were expressed as mean (SD) or quartile ranges by gender. We used independent-samples Student's test to analyze the clinical features, 24 h ABPM recordings, and CF-PWV, and the results were presented by gender. P < 0.05 was considered to be of statistical significance. Multivariable linear regression was used to assess the relationship between CF-PWV and 24 h ABPM recordings in the total population, male, and female separately after adjusted for age (continuous), body mass index , heart rate (HR), smoking, family history, fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), high-sensitivity C-reactive protein (hs-CRP), diabetes, coronary artery disease (CAD), peripheral arterial disease (PAD), agents of hyperlipidemia, and agents of hypoglycemic. CF-PWV was used as the dependent variable, 24 h ABPM parameters; age and heart rate (HR) were independent variables. Statistical analysis was performed by SPSS 24.0 statistical software.2. Compared with female, age, BMI, FPG, UA, and HCY levels were significantly higher in male . Conversely, TC, HDL-c, and LDL-c were significantly higher in female.The clinical features of the study population by gender were shown in The summary statistics of 24 h ABPM recordings were shown in 2=0.368, P=0.003; 24 h DBP SD, B=0.035, R2=0.364, P =0.06, 2=0.379, P=0.008) and 24 h DBP SD. But the relationship did not occur in male . We analyzed the difference of regression coefficients in male and female  were independent factors and linearly correlated with CF-PWV, but not in male. Women showed a steeper relationship between CF-PWV and age, PP.Many studies consistently believed that BPV was associated with cardiovascular disease and cerebrovascular diseases. However, the BP level in patients with hypertension as a confounding factor may affect the relationship between BPV and cardiovascular disease. Previous study had showed that hypertension could increase the arterial stiffness and damage the baroreflex sensitivity, which in turn influenced BPV . TherefoIn addition, we found a gender difference in the relationship between BPV and arterial stiffness. We performed the analysis of the interaction between gender, BP, and BPV; it showed that gender difference may affect the relationship between 24 h SBP SD, 24 h DBP SD, and CF-PWV. After adjusting for traditional risk factors and medications, BPV and CF-PWV showed an independent and positive correlation in female, and the linear regression coefficient was significantly higher. There were only a few studies focused on gender in the reports of BPV and CF-PWV, and the conclusions were also inconsistent. A study showed that BPV was an independent predictor of cardiovascular events in women . And a UAge contributed to the development of arterial stiffness . It provIn the present study, further intense clinical research was needed to clarify the potential gender difference in hypertension and antihypertensive therapy, not only in the general population but also in specific subgroups, such as patients with diabetes, cardiovascular disease, and chronic kidney disease. Multicenter and large-scale sample are further needed to validate the results. Moreover, further basic research was of paramount importance to uncover the biological plausibility and the mechanisms which mediated the potential gender difference in hypertension and cardiovascular disease.It is the first time to present an interesting clinical phenomenon that arterial stiffness was closely related to BPVs in the female population and independent of traditional risk factors. Our clinical phenomenon provided the basis that gender difference may affect vascular function and further promote the multicenter research about the relationship between BP, BPV, and vascular function. In addition, subjects were both from clinics and hospital to reduce sample selection bias. Also, some limitations existed. First of all, when assessing the variability of noninvasive ambulatory blood pressure monitoring techniques, the time frequency of blood pressure measurements was important and the results of the study should be confirmed by shorter interval dynamic blood pressure measurements. Second, we did not use weighted 24 h BP SD and the assessment of 24 h BPVs was difficult to replicate. Finally, our cross-sectional study did not adequately explain the causal relationship between 24-hour ABPM and arteriosclerosis and the relationship between BPV, CF-PWV, and vascular-related diseases.All 24 h ABPM parameters were higher in male, except for PP. Blood pressure variability (BPV), age, pulse pressure, and heart rate were linearly positively correlated with CF-PWV, especially in female. The results indicated that stable blood pressure control may delay the development of atherosclerosis.