The objective of this study was to identify the epidemiological and clinical characteristics of hypertension in octogenarians and to identify the factors associated with uncontrolled hypertension in this population.th April 2019 and 15th May 2019 as part of the National Tunisian Registry of Hypertension. We included in our study patients aged 80 years or more with hypertension. We described the epidemiological and clinical profile of this population, and we studied the associations between uncontrolled hypertension and socio-demographic, lifestyle, clinical and therapeutic factors using logistic regression models.we used data collected in the outpatient cardiology department of the University Hospital of Sfax between 15we included 346 subjects (45.1% (n=156) male and 54.9% (n=190) female), with a mean age of 84.36 (SD 4.01) years. More than half of them had uncontrolled hypertension. Dyslipidemia was the most common cardiovascular risk factor found in 43.6 % (n=151) of patients followed by diabetes . One-third of patients had a history of coronary artery disease and/or stroke. Renal failure and kalemia disorders were observed, respectively, in 12.1% (n=42) and 25.2% (n=40) of patients. In multivariate analysis, factors associated with uncontrolled hypertension (HTN) were male sex (adjusted odds ratio (aOR): 1.663, 95% confidence interval (CI): 1.045-2.647; p=0.032), diabetes  and poor adherence to blood pressure (BP) medications .our results showed that more than half of octogenarian hypertensive patients did not reach the BP target and that poor adherence to BP medications was the main factor of uncontrolled HTN. In this population, the presence of other comorbidities and poor adherence to BP medications are very common. Systematic research for behaviors suggesting poor medication adherence should be a priority for physicians caring for these patients. Hypertension (HTN) is one of the most common morbidities and the main risk factor for most morbidities of elderly subjects, with a significant impact on their prognosis . Large sStudy design and settings: we used data collected in the outpatient cardiology department of the University Hospital of Sfax between 15th April 2019 and 15th May 2019 as part of the National Tunisian Registry of Hypertension (NATURE HTN). The NATURE HTN registry is a national, observational, cross-sectional and multi-center study planned by the Tunisian Society of Cardiology and Cardiovascular Surgery and validated by an ethics committee. It was designed by a multidisciplinary committee of cardiologists from different hospital structures in Tunisia. The main objectives of this registry were to describe the epidemiological profile of HTN in Tunisia and to assess the level of cardiovascular risk of hypertensive Tunisian patients.Study population: our study through the data we analyzed aimed to describe the epidemiological and clinical profile of octogenarian hypertensive patients and determine factors associated with uncontrolled hypertension in this population. The inclusion criteria were an age greater or equal to 80 with a confirmed essential HTN. Patients with short life expectancy and end-stage kidney failure with chronic hemodialysis were excluded.Blood pressure (BP): systolic BP (SBP) and diastolic (DBP) was measured using a manual or automated electronic sphygmomanometer in accordance with the guidelines of the European Society of Cardiology (ESC) [gy (ESC)  on the rgy (ESC) . From thCovariates: we collected, through a questionnaire, demographic data (age and sex), weight and height with calculation of the body mass index (BMI), lifestyle behavior , history of cardiovascular and cerebrovascular diseases  and therapeutic data (number and classes of anti-hypertensive drugs namely angiotensin converting enzyme (ACE), angiotensin receptor blocker (ARB), calcium channel blocker (CCB), diuretic and beta blocker (BB). The adherence to treatment was assessed using the Girerd score [2 in women and 115g/m2 in men) [2 as non-obese, and ≥ 30 kg/m2 as obese; we divided kalemia into 3 groups using the serum potassium standards of the hospital laboratory, indicated between 3.5 and 4.5 mmol/l.rd score . Patientrd score  and calc in men) . RegardiStatistical analysis: the data collected were analyzed using IBM SPSS Statistics version 23.0 for Windows . We first performed a descriptive analysis comparing the two sexes. We then performed univariate analysis followed by multivariate analysis to investigate the relationship between uncontrolled HTN (BP ≥ 140/90 mmHg) and the different variables using logistic regression models. Furthermore, we have included in the multivariate statistical model all variables with p-value < 0.25 in the univariate analysis. A p-value <0.05 was considered significant.Ethical considerations: the NATURE HTN registry was conducted after obtaining approval from the ethics committee of the Tunis internal security forces hospital. The ethical aspects were respected. Informed patient consent was required for all study participants. Participation in the study was free. Confidentiality and anonymity were guaranteed to patients who participated in the study.Epidemiological, clinical and paraclinical characteristics of the population: we included 346 subjects (45.1% (n=156) male and 54.9% (n=190) female), with a mean age of 84.36 (SD 4.01) years. More than half of the patients  had uncontrolled HTN. Nearly a third of patients  had systolic isolated HTN and 57% of patients had an increase in PP (≥60 mmHg). Dyslipidemia was the most common cardiovascular risk factor found in 43% (n=151) of subjects with a significant male predominance (51.3% (n=80) versus 37.4% (n=71), p <0.009), followed by diabetes present in more than one-third of subjects with equal distribution between the two sexes. One-third of patients had a history of coronary artery disease and/or stroke, and 14.2% of patients had a history of atrial fibrillation. The mean value of creatinine was 96.31(SD 42.70) mmol/l. Renal failure was noted in 12.1% (n=42) of patients. In addition, kalemia disorders were present in 25.2% (n=40) of patients and were, for the most part, a hyperkalemia . The socio-demographic, clinical and paraclinical characteristics of the population are summarized in Factors associated with uncontrolled hypertension: in univariate analysis , but we did not find any significant association between dyslipidemia and uncontrolled HTN. The prevalences of diabetes and dyslipidemia increase with age and are higher in hypertensive patients with uncontrolled HTN . Senior  control . While t control . However control . The pre control . Age-rel control  these ra control  which exThe relationship between uncontrolled HTN and cardiovascular disease has been proven by numerous epidemiological studies in octogenarian patients . These rHowever, unlike to the results observed in many studies studying the effect of weight  and physThe results of our study show that more than half of octogenarian hypertensive patients did not reach the BP target. In this population, the presence of other comorbidities and poor adherence to BP medications are very common. We have shown that poor adherence to antihypertensive therapy is the main factor of uncontrolled HTN in these patients. Systematic research for behaviors suggesting poor medication adherence should be a priority for physicians caring for this population.Hypertension is the main risk factor for most morbidities of elderly subjects, with a significant impact on their prognosis;Africa is not spared by this global health problem, with an annual mortality rate due to hypertension;Hypertension is a complicated disease that requires optimal control and persistent drug-adherence.This is the first Tunisian study to report results focused on hypertensive patients over 80 years of age;More than half of octogenarian patients had uncontrolled hypertension;Poor adherence to anti-hypertensive drugs was very common in this population, and it was the main factor associated with uncontrolled hypertension.


Background: Changing the term/concept of the non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction associated fatty liver disease (MAFLD) may broaden the pathological definition that can include chronic renal involvement, and, possibly, changes chronic kidney disease's (CKD's) epidemiological association with liver disease, because CKD is associated with metabolic disorders and almost all patients with CKD present some form of an atherogenic dyslipidemia. Our study explores the relationship between MAFLD and CKD using Transient Elastography (TE) with a Controlled Attenuated Parameter (CAP).Methods: We evaluated 335 patients with diabetes with MAFLD and with high CKD risk using TE with CAP (FibroScan®). The CKD was defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Logistic regression and stepwise multiple logistic regression were used to evaluate the factors associated with CKD. In addition, a receiver operating characteristic curve (ROC) analysis was used to assess the performance of CAP and TE in predicting CKD and its optimal threshold.Results: The prevalence of CKD in our group was 60.8%. Patients with CKD had higher mean liver stiffness measurements (LSM) and CAP values than those without CKD. We found that hepatic steatosis was a better predictor of CKD than fibrosis. Univariate regression showed that CAP values >353 dB/m were predictive of CKD; while the multivariate regression analysis , low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc), and fasting glucose) showed that CAP values >353 dB/m were more strongly associated with the presence of CKD compared to the LSM (fibrosis) values.Conclusion: In patients with MAFLD, CAP-assessed steatosis appears to be a better predictor of CKD compared to LSM-assessed hepatic fibrosis. Recent data have proven that fatty liver, associated liver inflammation, and fibrosis [NAFLD and non-alcoholic steatohepatitis (NASH)] increase the risk of chronic kidney disease (CKD) . HoweverPatients who were previously diagnosed with MAFLD, by imaging methods (MRI or/and CAP), were prospectively enrolled in the study conducted in the Departments of Nephrology, Gastroenterology and Hepatology, and Diabetes and Metabolic Diseases in Timisoara Emergency County Hospital for a period of 1 year (January 2018 to December 2018). All patients were Caucasians and underwent transient elastography with controlled attenuation parameters. As inclusion criteria, patients were required to be over 18 years of age and with presence of MAFLD.2 if persistent for more than 3 months. The eGFR was estimated using the CKD-Epi formula (Chronic kidney disease (CKD) was defined by an albumin-to-creatinine ratio (A/Cr) >30 mg/g and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m formula .Exclusion criteria were as follows: pregnancy, ascites, outliers , decompensated liver disease, cardiac pacemaker, malignancy, end-stage renal disease, heart failure, unreliable or invalid TE and CAP measurements, and elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which are more than five times the upper limit of normal. Known severe chronic liver disease- patients with liver cirrhosis  were also excluded from the study due to their previously established diagnostic and well-known etiology to avoid biases. The study protocol was conducted according to Declaration of Helsinki after the approval of “Pius Branzeu” County Emergency Clinical Hospital Ethical Committee (no. 131/25.10.2017). All patients gave their informed consent for the procedures.Age, body mass index (BMI), waist circumference, and medical history were collected. Laboratory data including serum creatinine, AST, ALT, platelets, glycemia, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, urine albumin, and urine creatinine were also assessed in the same session with transient elastography, at 1, 2, and 3 months to identify the true CKD.Transient elastography was performed with a FibroScan® device . At the time of the procedure, patients were in fasting condition for more than 4 h. Patients were placed in a supine position, with their right arm in a maximum abduction, by intercostal approach, in the right liver lobe. In each patient, we aimed for 10 valid liver stiffness measurements (LSMs). The examination was performed using the M probe  or the XL probe (transducer frequency 2.5 MHz). The M and XL probes were used according to the European recommendation on M and XL probe selection .To discriminate between fibrosis and steatosis stages, we used the TE and CAP cut-off values from a published multicentric trial compared with biopsy  , and Mann–Whitney U-test or Kruskal–Wallis tests  to assess the differences between numerical variables. The proportions were analyzed using the chi-square test. Logistic regression and stepwise multiple logistic regression were used for the evaluation of the factors associated with CKD. The ROC analysis was used to assess the CAP and TE performance in predicting CKD and the optimal thresholds.MedCalc software (version 19.3.1) and Microsoft Excel 2019 were used for the statistical analysis. The distribution of numerical variables was tested with Kolmogorov–Smirnov test. In addition, we used From the 402 patients, 355 patients met the inclusion criteria ; of thesp < 0.0001); more likely to be men (p < 0.0001); and had higher values of triglycerides (p = 0.04), fasting glucose, HbA1c , mean LSM values (p = 0.04), mean at CAP (p = 0.03), and similar rates of hypertension, steatosis, and significant fibrosis (p > 0.05)  .No significant differences between the two subgroups were found regarding the waist circumference, BMI, AST, ALT, cholesterol, platelets, LDL, or HDL .p = 0.04; and 320.09 ± 57.12 vs. 306.29 ± 61.21, p = 0.04, respectively).Mean fibrosis LSM and CAP values were significantly higher in patients with CKD than in those without  than in TE , p = 0.001. The best CAP cut-off value was 353 dB/m, with a sensitivity of 75% and a specificity of 45.1% ; The correlation between TE and the presence of CKD was r = 0.52, p = 0.12.The ROC curves were used to determine if the transient elastography with controlled attenuation parameter could predict the presence of chronic kidney disease by assessing liver stiffness measurements or liver steatosis. The area under the receiver's operating characteristic curve of CAP was higher , male gender (p < 0.0001), HbA1c (p = 0.002), fasting glucose (p = 0.04), CAP values (p = 0.03), angiotensin converting enzyme (ACE) inhibitors (p = 0.04), and creatinine (p < 0.001)  .In multiple logistic regression analysis, all variables showed in Klebsiella pneumoniae) may influence the evolution of fatty liver disease , diabetes, or the presence of metabolic dysregulation. To establish metabolic dysfunction, at least two of the following characteristics must be present: waist circumference ≥102/88 cm in white men/women or ≥90/80 cm in Asian men/women, prediabetes, high serum C-reactive protein values, increased BP values or BP under treatment, low HDL-cholesterol, increase in serum triglyceride levels, and a HOMA score of >2.5. Specific individual characteristics such as genetic predisposition, age, sex, ethnicity, diet, metabolic status, and gut microbiota increase the risk of developing MAFLD. More importantly, MAFLD does not exclude other causes of fatty liver , and the more severe NASH characterized by steatosis, inflammation , liver cell injury with the possibility of progression to fibrosis, cirrhosis, and end-stage liver disease. Some consider NAFLD a hepatic manifestation of metabolic syndrome . In the  disease . It seem disease . The incty liver . The chaty liver . Moreovety liver .Concerning the risk of CKD in patients with MAFLD, the data are scarce and contradictory. However, in analyzing the NHANES III 1988–94 database, the authors found that MAFLD can identify the patients with CKD risk better and that the risk of CKD and albuminuria is strongly correlated with the severity of liver fibrosis  . However2, and hypercholesterolemia). Under these conditions, the prevalence of CKD was high (60.8%). Subjects with CKD, who were older than those without, were more likely to be men, and had higher triglyceride values, poorer glycemic control, and higher rates of hypertension (as expected). Concerning the TE findings with CAP, higher mean LSM values and higher mean CAP were recorded in patients with CKD, and similar rates of steatosis and fibrosis were evidenced in patients with patients . In all models, the higher CAP values were independently associated with CKD. Although all patients with CKD tend to develop dyslipidemia (more frequently the very atherogenic type) , the queIn patients with established MAFLD and with multiple metabolic risk factors for CKD, the liver fatty overload evaluated with CAP seems to be a better predictor of CKD than LSM and fibrosis. However, more studies with a higher number of patients are needed to confirm our results. Furthermore, some questions remain to be answered in future research: In the liver–kidney crosstalk, how is CKD influencing the MAFLD outcomes, since CKD is a one-way pathological process? Additionally, does MAFLD influence CKD progression to an end-stage kidney disease.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by County Emergency Hospital “Pius Branzeu” Timisoara Ethical Committee. The patients/participants provided their written informed consent to participate in this study.LM and AS: conceptualization. AM and FB: methodology. RL and BT: software. AS, IS, and RT: validation. IG, FB, and FG: formal analysis. RL, LM, and LC: investigation. AS, RT, and IS: resources. LM, RL, and AM: data curation. LM, RL, and VT: writing—original draft preparation. AS, IG, AM, and FB: writing—review and editing. IG, AM, and NO: visualization. AS: supervision. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Objectives: To analyze the clinical characteristics and renal pathological manifestations of patients with monoclonal gammopathy (MG) and kidney injury.Methods: This was a multicenter retrospective cohort study conducted at four tertiary hospitals in China. The study population comprised patients with MG admitted from January 1 2013 to December 31 2020. Hospitalization records, laboratory data, and kidney biopsy reports of all patients were collected from the electronic hospital information systems. The study outcomes included kidney disease progression and major hemorrhagic complications after kidney biopsy.Results: We identified 1,164 patients with MG, 782 (67.2%) of whom had underlying kidney injury. Of 101 patients who underwent kidney biopsy, 16 had malignant neoplasms. Amyloid nephropathy was the most common finding , followed by membranous nephropathy  and membranoproliferative nephritis . Among 85 patients with non-malignant hematologic conditions who underwent kidney biopsy, 43 had MG of renal significance (MGRS) related lesions and 42 had MG-unrelated lesions. The risk of kidney disease progression was higher in patients with kidney injury than in patients without kidney injury.Conclusion: Among patients with MG and kidney injury, only 12.9% underwent kidney biopsy and more than 40% of these patients had MG-unrelated lesions. A kidney biopsy is safe and essential to maximize the possibility of correct diagnosis for patients with clinically suspected MG of renal significance (MGRS). Monoclonal gammopathy (MG) is defined as the presence of a monoclonal immunoglobulin (MIg) in serum resulting from the clonal proliferation of Ig-producing plasma cells or B-lymphocytes , 2. MonoThe MIg or its fragments (light chains and/or heavy chains) are secreted into the blood and subsequently filtered by the glomerulus before entering the urine. The kidneys are commonly involved in such hematologic conditions and there are various types of renal disease . Kidney Chronic kidney disease (CKD) is a leading public health problem worldwide. The global estimated prevalence of CKD is 13.4% 11.7–15.1%) . During .7–15.1% In this retrospective cohort study, we described the clinical characteristics of MG patients with kidney injury, the spectrum of kidney biopsy findings in these patients, and the clinical outcomes of these patients. We also evaluated the risk of hemorrhagic complications and the potential benefit of kidney biopsy in these patients.This was a retrospective multicenter cohort study conducted at four tertiary hospitals in China . The study cohort comprised patients admitted to a participating hospital from January 1, 2013, to December 31, 2020, who had at least one positive serum immunofixation result during hospitalization. The admission date of the hospitalization during which the patient was first diagnosed with MG was considered the baseline for analysis.The study centers were asked to export the hospitalization records, laboratory data, and kidney biopsy reports of all patients from the electronic hospital information systems. Hospitalization records consisted of patients' age, sex, date of admission, diagnosis code at admission and discharge, and in-hospital death. Laboratory data included the value and time of patients' serum and urinary tests. Kidney biopsy reports included histologic diagnosis and detailed histologic reports based on light microscopy, electron microscopy, and immunofluorescence assays. The specimens were regularly stained with hematoxylin-eosin, periodic acid Schiff, periodic acid-silver methenamine, and Masson's trichrome, and tested for IgA, IgG, IgM, C3, C4, C1q, and κ/λ light chains by immunofluorescence assays.The exported data from all study centers were pooled and cleaned at the National Clinical Research Center for Kidney Disease in Guangzhou. The Medical Ethics Committee of Nanfang Hospital approved the study protocol (NFYY-2015-073).2 (CKD-EPI equation), or daily urinary protein excretion > 0.5 g/24 h.All patients were divided into two groups (with and without kidney injury) based on their kidney function and urinary test results at baseline for more detailed analysis. Patients were considered to have kidney injury at baseline if they met any of the following inclusion criteria: urinary protein ≥ 1+, estimated glomerular filtration rate (eGFR) ≤ 60 ml/min/1.73 mAmong MG patients without hematologic malignancy who underwent kidney biopsy, lesions were considered to be associated with MGRS based on the consensus guideline issued by the IKMG. C3 glomerulopathy and thrombotic microangiopathy are not associated with renal deposition of MIg. Other MGRS-related lesions are caused by deposition of MIgs, fragments thereof, or various aggregation products. Patients with thrombotic microangiopathy were considered to have an MGRS-related lesion if no other obvious cause of thrombotic microangiopathy  was identified.2 or the need for maintenance renal replacement therapy) or a permanent 30% reduction in the eGFR relative to the initial level at biopsy. The secondary outcome was major hemorrhagic complications, which were defined as hemorrhagic complications requiring blood transfusion or other invasive procedures after kidney biopsy.The primary outcome was kidney disease progression, which was defined as progression to end-stage renal disease  were diagnosed with malignant neoplasms (15 MM and 1 smoldering MM). Among 85 patients with non-malignant hematologic conditions, 43 had MGRS-related lesions and 42 had MG-unrelated lesions . There wAs shown in P < 0.0001). However, the risk of kidney disease progression significantly differ between MG patients who underwent kidney biopsy and those who did not (P = 0.03)  were followed up for more than 3 months and included in the primary outcome analysis. Over a median of 13 months  of follow-up, kidney disease progression (the primary outcome) occurred in 58  patients. Among 85 non-maligancy MG patients who have received kidney biopsy, kidney disease progression occurred in 1 of 43 (2.3%) patients with MGRS-related lesions and 3 of 42 (7.1%) patients with MG-unrelated lesions. Kaplan-Meier curves in  = 0.03) . Of two In this multicenter retrospective cohort of 1,164 patients with MG, 782  had underlying kidney injury. Among them, only 101  underwent kidney biopsy and 2  suffered from major hemorrhagic complications. Kidney lesions were not related to MG in more than 40%  of these patients. Kidney biopsy was a safe and simple procedure for pathological diagnosis and prognosis. In our cohort, amyloid nephropathy was found to be the most common MGRS-related lesion, while membranous nephropathy was the most common MG-unrelated lesion. Given that the therapeutic regimens of MGRS and other types of kidney disease are different, our findings suggest that kidney biopsy is essential and can provide clinicians with useful information to guide subsequent treatment.Over the last decades, the prevalence of CKD and MG has increased dramatically in China. CKD is prevalent in hospitalized patients with MG. Therefore, patients can simultaneously have CKD and MG without a direct causal relationship between the two disorders. The kidney biopsy is the gold standard for diagnosis of most kidney diseases however the procedure was underperformed in our country. There was only 12.9% (101/782) of our study population with kidney biopsy. Except for patients with absolute contraindications , the main reasons why most patients with MG and kidney disease did not undergo kidney biopsy may be that (1) patients with MG and kidney injury were diagnosed with MGRS by default and kidney biopsy was arbitrarily considered unnecessary, and (2) patients refused to undergo kidney biopsy because it is invasive and the risk of hemorrhagic complications might be higher in patients with hematologic disease. Our study showed that kidney biopsy is safe and the risk of massive hemorrhage in MG patients is similar to that reported in general patients , 17. MorIn the IKMG consensus, MGUS does not require treatment, while specific management usually employing chemotherapy toward the pathologic clone and type of kidney injury is recommended for MGRS due to the nephrotoxicity of monoclonal immunoglobulin. MGRS is complex and heterogeneous concerning clinical, pathogenetic, pathologic, and prognostic findings, therefore, a close collaboration between several specialties is required for optimal patient treatment and management. Treatment of MGRS intends to eliminate the underlying clonal plasma cell or B-cell population, and thereby decrease or abolish production of the offending MIg . This isConsistent with the results of previous studies, amyloid nephropathy was the most common type of MGRS-related lesions in our study, followed by membranoproliferative glomerulonephritis . Due to Furthermore, among patients who underwent kidney biopsy, 18 and 3 were diagnosed with membranous nephropathy and IgA nephropathy, respectively. This is unsurprising because these two disorders are the most common type of biopsy-identified glomerulonephritis in general patients . Among tBesides, a higher frequency of light chain only subtype (IgA&IgG&IgM(−)) was observed in MG patients with kidney injury and kidney biopsy group. Light chain excretion, following by deposition and crystallization in kidney, could results in tubular nephropathy. The finding made by Klomjit and coworkers demonstrated a higher concentration of free serum light chain in MG patients with kidney biopsy who tended to have more severe CKD. However, whether the concentration differs among MG subclasses and to what extent it affects the kidney function needs further evacuation.The investigation conducted in Mayo Clinic depicted that proteinuria ≥1.5 g/d, hematuria and elevated free light chain ratio are potential predictor for MGRS. However, in our cohort, with free light chain ratio inaccessiblem, the clinical measurements, including ratio of κ and λ, proteinuria, hematuria and total light chain showed no differences between patients with MGRS-related lesions and with MG-unrelated lesions. We tend to accounted it to the selection bias in the subcohort since kidney biopsy is more likely to be applied in patients with more severe CKD.in situ hybridization were unavailable for most patients. Thus, the correlations between these clinical indicators and MRGS could not be analyzed.Our study with a large cohort has comprehensively described the clinical characteristics and spectrum of kidney biopsy findings in patients with MG and renal injury. Most previous studies focused on a specific type of MGRS, such as amyloidosis or light chain deposition disease, but without kidney biopsy findings. Furthermore, our cohort is unique because patients with hematologic conditions (MM and WM) were analyzed separately, suggested that we could more accurately describe the characteristics of MGRS and MG-unrelated kidney disease. Finally, this was a multicenter study and the sample size was relatively large. There are some limitations to our study. First, underlying inherent selection bias could not be addressed due to the retrospective nature of this study. Second, important clinical indicators such as free light chain analysis, morphologic assessment, peripheral blood flow cytometry, and myeloma fluorescent Only 12.9% of MG patients with kidney injury underwent kidney biopsy and more than 40% of these patients had MG-unrelated lesions, among which amyloid nephropathy accounting for the most. Combined the fact that renal insufficiency sigficantly worson the kidney survival in MG patients and the relative low rate of complication after kidney biopsy, we conclude that kidney biopsy is a safe and essential procedure to maximize the possibility of correct diagnosis, and should be encouraged for patients with suspected MGRS.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Medical Ethics Committee of Nanfang Hospital (NFYY-2015-073). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.GW and SN contributed to the study design and result interpretation. GW and DC took the lead in drafting the manuscript and received major funding for the study. SN, MW, and QW obtained and analyzed the data. SN, MW, YK, JO, and NJ prepared and cleaned the data. XZ, FL, YC, XL, and RC contributed to the data collection. MZ and DC contributed to revising the manuscript. All authors contributed to the interpretation of data, provided critical revisions to the manuscript, and approved the final draft.LW and XL were employed by the company Kingmed Diagnostic Laboratory Ltd, Guangzhou, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.


Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder that leads to end stage renal disease (ESRD). Cyst expansion in ADPKD is strongly associated with the decline in renal function. However, the correlation between total kidney volume (TKV) and glomerular filtration rate (GFR) at an early stage has not been well demonstrated. There is growing evidence that utilization of estimated GFR (eGFR) may induce misleading information in a population with near normal renal function. Therefore, a more accurate method is essential.A prospective cohort of ADPKD patients was conducted with clinical data and laboratory collection. Measured GFR (mGFR) was assessed by iohexol plasma clearance method using ultra performance liquid chromatography. eGFR was calculated using the CKD-EPI equation. Kidney volumes were evaluated using MRI imaging protocol.2. The mean change in mGFR per year was –2.99 mL/min/1.73m2/year. The mean initial height-adjusted TKV (htTKV) was 681.0 mL/m. The mean percentage change in htTKV per year (%ΔhtTKV/y) was 4.77 %/year. mGFR had a better association with clinical parameters than eGFR. Initial mGFR was significantly and inversely correlated with initial htTKV and age. The percentage change in mGFR per year was significantly and inversely correlated with the %ΔhtTKV/y and 24-hr urine albumin. The %ΔhtTKV/y was significantly correlated with initial htTKV.Thirty two patients completed the study. The mean age was 56 years old. The mean initial mGFR was 83.8 mL/min/1.73mOur studies demonstrated that mGFR using iohexol is a more reliable and accurate method than eGFR for evaluating GFR changes in the early stages of ADPKD patients. There is a strong inverse correlation between kidney volume and mGFR in an Asian ADPKD population. The initial htTKV is a good predictor of kidney volume progression. The %ΔhtTKV/y is a good early surrogate marker for the decline in renal function. 24-hr urine albumin is also a good indicator for renal progression. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder that leads to end stage renal disease (ESRD) , 2. ClinImaging methods that reliably and accurately measure total kidney volume (TKV) in ADPKD patients have been developed utilizing magnetic resonance imaging (MRI) and computerized tomography –16. The In this study, we compared the efficacy between eGFR using CKD-EPI and mGFR using iohexol plasma clearance for evaluating GFR changes in the early stages of patients with ADPKD and investigated the relationship between clinical parameters, total kidney volume and renal function and identified the risk factors associated with the progression in kidney structure and function decline in the Thai ADPKD population.2 by CKD-EPI and willing to join the study. The exclusion criteria included undergoing transplantation, contraindication for MRI, pregnancy, and a high mortality disease such as cancers. At each visit, the medical history, adverse events, medical changes, and hospitalizations were recorded. Other clinical data were prospectively collected including: age of enrollment, weigh, height, body mass index (BMI), mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), serum creatinine (sCr), serum uric, fasting blood sugar, and LDL-cholesterol. 24-h urine protein and 24-h urine albumin were collected after being enrolled in the study for 4 weeks. Kidney volume and GFR were measured annually. All methods were performed in accordance with the relevant guidelines and regulations of the institute. Written informed consent was obtained from all patients. The study was approved by the Institutional Ethics Committee on Human Rights Related to Research Involving Human Subjects of the Ramathibodi Hospital, Mahidol University.A prospective cohort study was conducted, with test subjects being patients under the care of the nephrology division, Department of Medicine, Ramathibodi Hospital, during 2015–2019. The inclusion criteria are as follows: diagnosis of ADPKD  of plasma concentration curve. Since the Cl1 did not include the whole area of plasma concentration curve, the mathematical correction for the first fast exponential curve is needed. Herein, we used the correction equation proposed by Brochner-Mortensen (BM) to calculate the measured GFR [Cl1) − (0.001218× Cl12). All mGFR results were adjusted for body surface area.mGFR was determined by the plasma clearance of iohexol. Briefly, iohexol was administered as Omnipaque® 300 mg I/mL . Venous blood samples were collected at four time points  after a single 5-ml intravenous injection of iohexol. Plasma concentration of iohexol was determined by ultra performance liquid chromatography (UPLC). The UPLC analytical system was performed with Agilent technologies . The system was connected to the autosampler UV detector. The manager software was ChemStation. The intra-assay and inter-assay variant of UPLC were 0.94 and 2.44 %, respectively. A curve was obtained expressing iohexol elimination. We calculated measured GFR by using the one-compartment model, often referring as the slope-intercept technique. The one-compartment clearance, ured GFR . GFR froThe morning of each iohexol clearance study, serum creatinine concentration was measured with enzymatic method using an automatic device . eGFR was calculated using the CKD-EPI equation .All renal MRI imaging were performed on a 3.0-T MRI scanner . The MRI protocol included sshT2W, IDEAL, non-contrast enhanced T1W, and dynamic contrast enhanced MRI sequences. Following this acquisition of pre-gadolinium images, 0.1 mmol/kg gadobutrol  was injected at 1mL/s. The post-gadolinium dynamic imaging was acquired in three initial phase , and then after a delay of 3, 5, and 10 min, with a bolus tracking technique and fat saturation. Kidney volumes were measured by manually tracing the kidney contours using volume analysis solfware implemented on an Advantage Windows Workstation  as previously prescribed in the study protocol . The sshp values of < 0.05 were considered to indicate a statistically significant difference.The study was designed as a prospective cohort study. Statistics were analyzed with SPSS V 18.0. Numerical data were shown with mean ± SD or median (range). Pearson’s correlation coefficients were used to examine the association among eGFR or mGFR, the percentage change in eGFR or mGFR per year (%ΔeGFR/y or %ΔmGFR/y), the percentage change in height-adjusted total kidney volume per year (%ΔhtTKV/y), and selected clinical variables. Univariate and multivariate regression analyses were used to determine independent predictors of baseline eGFR or mGFR, %ΔeGFR/y or %ΔmGFR/y, and %ΔhtTKV/y. Two-tail Initially, there were 41 ADPKD patients included in the study. One patient was excluded from the study due to nephrotic syndrome and eight were dropped off due to incomplete follow up. Thirty two  patients completed the study. The mean duration of follow-up time was 1.79 ± 0.58 years. Table 2.The mean initial mGFR was 83.8 ± 26.1 mL/min/1.73m2. The mean change in eGFR and mGFR per year (ΔeGFR/y & ΔmGFR/y) was –2.91 ± 2.75 and –2.99 ± 2.86 mL/min/1.73m2/year, respectively. The mean percentage change in eGFR and mGFR per year (%ΔeGFR/y & %ΔmGFR/y) was –4.14 ± 4.87 and –4.21 ± 4.45 %/year, respectively  baseline serum creatinine was 0.94 ± 0.39 mg/dL. The mean initial eGFR by CKD-EPI was 80.3 ± 24.9 mL/min/1.73mr = 0.718, p < 0.001). The equation was as follows: y = 0.933x + 0.11 . Table p initial mGFR vs. p initial eGFR: 0.006 vs. 0.030).Renal function evaluated by eGFR had a strong association with mGFR , initial htTKV , 24-hr urine protein , and 24-hr urine albumin  as shown in Table Using Pearson’s correlation coefficients, the study demonstrated that initial mGFR was significantly inversely correlated with 4 clinical parameters, including age (p < 0.001) and age (p = 0.016), Table Further investigation by using multivariate regression analysis revealed that initial mGFR was significantly, independently, and inversely correlated only with initial htTKV  and inversely correlated with other 3 clinical parameters, including 24-hr urine protein , 24-hr urine albumin  and %ΔhtTKV/y  as shown in Table The %ΔmGFR/y was significantly correlated with initial mGFR (p = 0.032) and 24-hr urine albumin (p = 0.034), Table Further multivariate analysis showed that the %ΔmGFR/y was significantly, independently, and inversely correlated only with the %ΔhtTKV/y p = 0.02 and 24-y = –0.572x – 1.486, r = –0.501, p = 0.004.Figure p = 0.003.For purpose of clinical application, univariate regression analysis was utilized to study the relationship between the %ΔmGFR/y and the %ΔhtTKV/y. It was found that there was an association between a 5 % change in %ΔhtTKV/y and a 5 % change in %ΔmGFR/y. In this study, no patients who had a %ΔhtTKV/y of less than 5 % developed a %ΔmGFR/y of more than 5 %. By contrast, patients who had a %ΔhtTKV/y of more than or equal to 5 % had a high prevalence (61.5 %) to develop a %ΔmGFR/y of more than 5 %, 2 were less likely (13.0 %) to develop a %ΔmGFR/y of more than 5 %. On the other hand, patients who had a 24-hr urine albumin more than or equal to 30 mg/day/1.73 m2 had a higher chance (55.6 %) to develop a %ΔmGFR/y of more than 5 %, p = 0.023.In the case of albuminuria, the ROC curve was used to find the cutting point of 24-hr urine albumin to predict the change in %ΔmGFR/y of 5 %. We found that 24-hr urine albumin at 30 mg/day had a sensitivity of 62.5 % and specificity of 79.2 % to predict this change. In this study, patients who had a 24-hr urine albumin of less than 30 mg/day/1.73 mr = 0.420, p = 0.017) and 24-hr urine albumin  as shown in Table p = 0.017), Table y = 0.003x + 0.429, r = 0.420, p = 0.017.The %ΔhtTKV/y was significantly correlated with initial htTKV . Likewise, the mean 24-hr urine protein also had a tendency to be lower in patients using ARBs/ACE inhibitors group , although this did not reach a statistically significant p-value. In addition, the mean 24-hr urine sodium tended to be higher in patients using ARBs/ACE inhibitors group , but also not statistically significant. The %ΔhtTKV/y was not significantly different between the two groups , and neither was the %ΔmGFR/y .In this study, there were 19 patients using at least one ARB or ACE inhibitor for treatment of hypertension. The other 13  patients did not use ARBs or ACE inhibitors. Clinical parameters of ADPKD patients using ARBs/ACE inhibitors versus without ARBs/ACE inhibitors were shown in Table Evaluation of renal function is a crucial part in assessing kidney disease, especially in ADPKD patients whose kidney functions remain stable for years, followed by a sharp decline in GFR once a critical renal size is reached , 7. Asse2/year, which was comparable to GFR change measured by iothalamate clearance –2.79 mL/min/1.73m2/year in the US population [2) and initial TKV (this study 1083 VS US 1193 mL) being comparable between our and the US population. When compared with the Japanese ADPKD population, the estimated GFR change per year in Japanese ADPKD was –2.8 mL/min/1.73m2/year by using the MDRD Japanese equation [2 and initial TKV of 1595 mL in Japanese studies were quite different to our population. This discrepancy in results may be explained by the difference in method used to evaluate GFR between the Japanese and our population (estimated GFR by Japanese MDRD equation and measured GFR by iohexol).The mGFR change in ADPKD patients in our studies was –2.99 mL/min/1.73mpulation . This isequation . The GFRThe calculated annual kidney growth rate in our study was 4.8 % (baseline TKV of 1083 mL) which was in agreement with the previous reported of 4 % with baseline TKV of 1194 mL , and 5.2The relationship between the total kidney volume and renal function was well demonstrated in our studies Table . Our stu2 had a good prediction for a 5 % change in GFR per year. Patients who had 24-hr urine albumin of less than 30 mg/day/1.73 m2 were less likely to develop GFR change of more than 5 % per year. On the other hand, patients who had a 24-hr urine albumin more than or equal to 30 mg/day/1.73 m2 had a higher prevalence of developing GFR change of more than 5 % per year.Albuminuria is well known to be strongly associated with progression in glomerular diseases. A number of studies have shown that in patients with ADPKD, which was classified as a non-glomerular disease, renal progression is also associated with albuminuria , 33, 34.In this study, the mean 24-hr urine albumin in patients using ARBs/ACE inhibitors was lower than that of patients without ARBs/ACE inhibitors. However, there was no statistically significant difference in the %ΔhtTKV/y and %ΔmGFR/y between the two groups. The benefits of slowing kidney volume progression did not occur in patients using ARBs/ACE inhibitors in this study. This could be explained by a considerable number of non-hypertensive patients (8/13) in the non ARBs/ACE inhibitors group who may have a better prognosis in the changes of TKV or GFR than hypertensive patients. In addition, the study period may be too short to claim the beneficial effects of these drugs.Some potential limitations in our study should be acknowledged. Due to the small number of participants, our trial may have had inadequate power to demonstrate the statistical significance of some clinical correlations. Another limitation is the technique used to quantify TKV which we manually measured on the MRI. This gives rise to more variation and inconsistency when compared to other automatic techniques. However, this method was preferred over other techniques such as the fully automated segmentation technique as enlarged ADPKD cysts tend to distort the surrounding anatomical structures of the kidneys, causing differentiation of the anatomical boundaries by automated segmentation almost unfeasible. Hopefully, in the future, a more accurate automated technique will be developed to assess TKV in ADPKD kidneys, allowing for a more consistent measurement.Our studies demonstrated that mGFR by iohexol plasma clearance is a more reliable and accurate method than eGFR for evaluating GFR changes in the early stages of patients with ADPKD. There is a strong inverse correlation between kidney volume and renal function assessed by mGFR in an Asian ADPKD population. The initial htTKV is a good predictor for kidney volume progression. The %ΔhtTKV/y is a good early surrogate marker for following up the decline in renal function. 24-hr urine albumin is also a good indicator for renal progression.


The mechanisms underlying the association between orthostatic hypotension (OH) and cardiovascular disease are unclear. We investigated whether OH is associated with circulating cardiovascular risk markers. This was a cross‐sectional analysis of 3857 older, community‐dwelling men. “Consensus OH” was defined as a sitting‐to‐standing decrease in systolic blood pressure ≥20 mm Hg and/or diastolic blood pressure ≥10 mm Hg that occurred within three minutes of standing. Multiple generalized linear regression and logistic models were used to examine the association between cardiovascular risk markers and OH. Consensus OH was present in 20.2%, consisting of isolated systolic OH in 12.6%, isolated diastolic OH in 4.6%, and combined systolic and diastolic OH in 3.0%. Concentration of von Willebrand factor, a marker of endothelial dysfunction, was positively associated with isolated systolic OH  and combined systolic and diastolic OH ; high circulating phosphate concentration, which may reflect vascular calcification, was associated with isolated diastolic OH  and combined systolic and diastolic OH , high‐sensitivity troponin T, a marker of myocardial injury, was positively associated with isolated diastolic OH  and N‐terminal pro‐brain natriuretic peptide, a marker of cardiac stress, was positively associated with combined systolic and diastolic OH . In conclusion, OH is associated with some cardiovascular risk markers implicated in endothelial dysfunction, vascular calcification, myocardial injury, and cardiac stress. Clinicians should consider assessing cardiovascular risk in patients with OH. A small, cross‐sectional analysis has shown OH to be associated with the inflammatory biomarkers midkine, immunoglobulin‐like transcript 3, and regenerating islet‐derived protein 4.However, there are specific limitations to these studies. Firstly, the study showing an association between inflammatory biomarkers and OH was in a cohort of less than 300 people, while the study showing an association between VWF and OH was in less than 200 people. Secondly, the study showing an association between OH and hs‐troponin T and NT‐proBNP was done in middle‐aged adults, in whom OH is approximately five to six times less prevalent than in older adults.22.1Study participants were from The British Regional Heart Study, which is an ongoing prospective cohort study that initially recruited 7735 men aged 40‐59 from one general practice in each of 24 British towns between 1978 and 1980. The sample was socioeconomically representative of the population. Participants were predominantly (>99%) of white European ethnicity. Sampling methods have been described previously.For the 20th year of follow‐up, all surviving men were invited for re‐examination, which took place between 1998 and 2000. The re‐examination involved a self‐completed questionnaire, about lifestyle and medical history, undergoing physical examination and venepuncture. There were 4252 men who completed the questionnaire and underwent physical examination (77% response rate). Anthropometric and physiological measurements included height, weight, waist and hip circumference, sitting and standing blood pressure, heart rate, forced expiratory volume in one second, and forced vital capacity. Specific methods used for data collection have been described previously.Of the 4252 men, 4045 had measurements of biochemistry. From this sample, 117 men with prevalent heart failure were excluded because heart failure is associated with hypertension,2.2Sitting and standing blood pressure measurements were taken on the right arm using an automatic Dinamap 1846SX. The Dinamap blood pressure monitor overestimated systolic blood pressure by ~8 mm Hg compared with the standard mercury sphygmomanometer which was the standard reference instrument for blood pressure measurement at the time.The Dinamap was set to take repeated measurements at one minute intervals. Four consecutive blood pressure measurements were taken: two sitting followed by two standing. Participants had not been seated nor supine for a prescribed duration prior to the first measurement. The participant was asked to stand after the second sitting measurement was completed. The first standing blood pressure measurement began within one minute of the participant standing, while the second standing blood pressure measurement began after one minute of standing. The interval between the start of the first sitting measurement and the completion of the second standing measurement was 3.5 minutes.2.3“Consensus OH” was defined as a decrease in either systolic blood pressure ≥20 mm Hg or diastolic blood pressure ≥10 mm Hg, or both, that occurred between either the first or second standing blood pressure measurements and the mean of the two sitting blood pressure measurements. These specific decreases in blood pressure on standing to define OH are endorsed by the American Autonomic Society, the European Federation of Autonomic Societies, the Autonomic Research Group of the World Federation of Neurology, and the Autonomic Disorders section of the American Academy of Neurology and described in their consensus statement.2.4At the physical examination, a fasting blood sample was taken for laboratory measurements of hematology and biochemistry, including total cholesterol, low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), triglycerides, glucose, urate, phosphate, fibrinogen, von Willebrand Factor (VWF), D‐dimer, c‐reactive protein (CRP), interleukin‐6 (IL‐6), high‐sensitivity troponin T (hs‐troponin T), and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). We chose to examine these markers in this study because they are implicated in cardiometabolic risk, hemostatis and endothelial dysfunction, vascular calcification, myocardial injury, and cardiac stress, mechanisms that may, in part, explain the association between OH and cardiovascular outcomes.2.5P < .05/14 tested markers), arose from this analysis, these biomarkers were selected for further analyses in both multiple generalized linear and logistic models. For the logistic analyses, the biomarkers (independent variable) were grouped into tertiles to examine whether elevated levels (top tertile vs bottom tertile) were associated with increased odds of OH (dependent variable).Statistical analyses were performed using SAS 9.4. Continuous variables that were skewed were log‐transformed to approximate normality for parametric tests. Skewed variables were CRP, IL‐6, D‐dimer, fibrinogen, glucose, triglycerides, NT‐proBNP, and hs‐troponin T. Hypothesis testing was first applied to mean unadjusted biomarker values in univariate generalized linear regression analyses. Where statistically significant associations, as per Bonferroni adjustment , alcohol use (0‐15 units per week and >16 units per week), physical activity (inactive or not inactive), social class  and the presence of prevalent stroke, myocardial infarction, atrial fibrillation, diabetes, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and current antihypertensive medication use. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 mCase definitions were obtained from primary care record reviews and have been reported previously.A sensitivity analysis was done by excluding participants with prevalent stroke and myocardial infarction (n = 352).33.1Of the 3857 participants , 778 men (20.2%) had consensus OH. Among these, 485 (12.6%) had isolated systolic OH, 177 (4.6%) had isolated diastolic OH, and 116 (3.0%) had both systolic and diastolic OH. Only 10.3% of participants with consensus OH were breathless or felt faint within three minutes of standing.Consensus OH was positively associated with age, sitting systolic blood pressure, sitting diastolic blood pressure, heart rate, and resting pulse ≥90 beats per minute. It was not associated with smoking status or alcohol consumption. There were differences in the distribution of baseline characteristics across the components of OH: Heart rate was associated with isolated diastolic OH, but not isolated systolic OH, while BMI was associated with isolated systolic OH, but not isolated diastolic OH, for example Table .3.2Consensus OH was associated with increased odds of prevalent CKD, COPD, antihypertensive medication use, and hypertension Table . The co‐3.3In univariate linear regression analyses, consensus OH was associated with higher levels of phosphate, IL‐6, VWF, D‐dimer, NT‐proBNP, and hs‐troponin T. Total cholesterol, LDL, HDL, triglycerides, glucose, urate, fibrinogen, and CRP were not statistically significantly associated with consensus OH Table . The marIn multiple logistic regression analyses, we calculated the odds of consensus OH, and its components, with elevated levels of phosphate, IL‐6, VWF, D‐dimer, hs‐troponin T, and NT‐proBNP (levels of biomarkers were categories into tertiles and “elevated” was defined as top tertile vs bottom)  associated the diastolic component of OH, but not the systolic component, with increased risk of myocardial infarctionIn the Atherosclerosis Risk in Communities Study, detectable hs‐troponin T was associated with systolic OH, but not diastolic OH, while isolated systolic OH and isolated diastolic OH were both associated with elevated NT‐proBNP.4.3Strengths of our study include the wide range of biomarkers studied and that we examined the components of OH. However, our cohort consisted exclusively of men who were almost entirely of white European ethnicity, limiting the external validity of our findings. Although we examined the components of OH, the sample in each group was relatively small, raising the possibility of type II errors; the confidence intervals in Table We did not have supine and standing measurements of blood pressure and instead used sitting and standing measurements to define OH as per thresholds that are usually applied to supine and standing measurements. Although supine‐to‐standing measurements are more frequently employed in research settings, sitting‐to‐standing measurements are often used in clinical practice for convenience. The decrease in blood pressure that occurs when changing position from supine to standing can be expected to be greater than that which occurs when changing position from sitting to standing because the shift in fluid is greater in the first scenario. It is unknown whether lower thresholds should be used to diagnose OH based on sitting‐to‐standing blood pressure measurements, compared to supine‐to‐standing measurements. If this were the case, then it is likely that our measures of risk are underestimates, as our study would have misclassified people who truly had OH as not having it. The lack of supine blood pressure measurements means we are unable to exclude supine hypertension as a confounding factor. Furthermore, we did not have blood pressure measurements beyond three minutes of standing and would have misclassified men who developed OH after a prolonged period of standing. It has previously been suggested that specific orthostatic changes in heart rate, if they accompany OH, can provide insight into whether the cause of OH is neurogenic or non‐neurogenic.Finally, this analysis was cross‐sectional. We are unable to comment on temporal relationships: While OH appears to be associated with some markers of cardiovascular risk, we are unable to conclude definitively whether OH is simply a biomarker of vascular risk and cardiac dysfunction or if OH induces endothelial dysfunction, vascular calcification, myocardial injury, and/or cardiac stress.5In older men, OH is associated with some cardiovascular risk markers implicated in endothelial dysfunction, vascular calcification, myocardial injury, and cardiac stress. The markers are differentially distributed among the components of OH, suggesting the components may have different etiologies. Our findings support to the hypothesis that OH is associated with increased cardiovascular risk. They may help explain findings from observational studies that have shown OH to be associated with increased risk of cardiovascular disease, including stroke, myocardial infarction, and heart failure. They support the notion that patients with OH should have their cardiovascular risk assessed. Further, prospective work should continue to examine the components of OH and control for markers of cardiovascular risk when attempting to delineate a temporal relationship between OH and cardiovascular morbidity.None declared.AG involved in conceptualization, methodology, formal analysis, investigation, writing‐original draft, and visualization. SR and SPJ involved in writing‐review and editing. OP involved in formal analysis, data curation, and data validation. LL involved in data curation, project administration, and resources. PW involved in data curation, methodology, investigation, resources, writing‐review and editing. GW involved in conceptualization, methodology, formal analysis, investigation, resources, writing‐review and editing, and visualization.


Outside of a clinical setting, oscillometric devices make remote monitoring of blood pressure and virtual care more convenient and feasible. HeartBeat Technologies Ltd developed a novel approach to measuring blood pressure remotely after an initial blood pressure reading by a nurse using the conventional measurement method. Using a finger pulse oximeter, a photoplethysmogram wave is transmitted by Bluetooth to a smartphone or tablet. A smartphone app (MediBeat) transmits the photoplethysmogram to a server for analysis by a proprietary algorithm—the person’s current blood pressure is sent back to the smartphone and to the individual’s health care provider.This study sought to determine whether the HeartBeat algorithm calculates blood pressure as accurately as required by the European Society of Hypertension International Protocol revision 2010 (ESH-IP2) for validation of blood pressure measuring devices.ESH-IP2 requirements, modified to conform to a more recent international consensus statement, were followed. The ESH-IP2 establishes strict guidelines for the conduct and reporting of any validation of any device to measure blood pressure, including using the standard manual blood pressure instrument as a comparator and specific required accuracy levels for low, medium, and high ranges of blood pressure readings. The consensus statement requires a greater number of study participants for each of the blood pressure ranges. The validation of the accuracy of the algorithm was conducted with a Contec CMS50EW pulse oximeter and a Samsung Galaxy XCover 4 smartphone.The differences between the HeartBeat-calculated and the manually measured blood pressures of 62 study participants did not meet the ESH-IP2 standards for accuracy for either systolic or diastolic blood pressure measurements. There was no discernible pattern in the inaccuracies of the HeartBeat-calculated measurements.The October 4, 2019 version of the HeartBeat algorithm, implemented in combination with the MediBeat app, a pulse oximeter, and an Android smartphone, was not sufficiently accurate for use in a general adult population.ClinicalTrials.gov NCT04082819; http://clinicaltrials.gov/ct2/show/NCT04082819 Accurately assessing blood pressure is necessary for the proper diagnosis of hypertension, implementing treatments and monitoring whether those treatments are working ,2. To meA novel approach to measuring blood pressure remotely has been developed . The measurement is taken after an initial blood pressure reading using the conventional measurement method, supplemented by specific characteristics of a person  to establish a baseline for the person. Unlike other devices -9, this The purpose of this study was to test whether the accuracy of the HeartBeat algorithm, available as of October 4, 2019 and for a general adult population (ages 25 years and older), was sufficient to seek regulatory approval when compared with a standard aneroid sphygmomanometer with stethoscope for measuring blood pressure.The European Society of Hypertension International Protocol revision (ESH-IP2) for the validation of blood pressure measuring devices in adults  was follAn international consensus statement group  reviewedThe pulse oximeter  used toPotential participants were recruited by mass email and offline posters at a single-site multistory office building in Markham, Ontario, Canada, where they worked; participants provided informed consent  and wereThree registered nurses who had training and expertise in blood pressure measurement carried out the measurements required for this study between October 4, 2019 to November 22, 2019. One nurse was the supervisor, and two nurses were the observers throughout the duration of the study. The nurses were trained as per ESH-IP2 directives and were instructed on how to follow the protocol guidelines for data collection. Blood pressure measurements were recorded to the nearest 2 mmHg.Two new sphygmomanometers , whose The observers were instructed that, in the event that an abnormal blood pressure reading was detected , they were to remeasure the blood pressure using conventional means to determine if the abnormal reading was accurate. If the abnormal blood pressure measurement was accurate, the nurse supervisor was to act according professional standards. The abnormal blood pressure measurement should also be recorded on ESH-IP2 Form 2.2 (oxygen saturation) values. (4) Once the values were displayed, the supervisor initiated a new session on the smartphone to connect the phone to the Contec device via Bluetooth. This connection started the 1-minute calibration process, at which point each participant was asked to remain still until the calibration had been completed successfully.Participants’ blood pressure measurements were taken in a room that was a comfortable temperature, without any noises or other influences that would have caused disturbances, such as telephones. The temperature in the room was the same as that throughout the building—20 °C to 24 °C. All participants participated in the study between the working hours of 9 AM and 4:30 PM. The pulse oximeter and the supervisor’s smartphone were charged and tested each day prior to interactions with participants. The MediBeat app was calibrated for each participant as follows: (1) Reference data for the individual  were entered. (2) The participant rested for 10 minutes while seated comfortably with their legs uncrossed, back supported, and arm resting on the table at heart level. (3) The supervisor attached the finger pulse oximeter to the participant’s index finger  and waited for a few seconds until a stable signal was received and the device displayed both the participant’s pulse and SpOpass (an acceptable level of accuracy) if it meets 4 pass criteria.Overseen by an independent supervisor, measurements were recorded by the two observers who were blinded from both the other observer’s readings and from the reading calculated by the HeartBeat algorithm. Each participant’s blood pressure was measured as illustrated in The study was reviewed and approved by the Southlake Regional Health Centre Research Ethics Board, Newmarket, Ontario, Canada (007-1920).A total of 105 individuals volunteered and were screened for the study, of whom 62 participants met the ESH-IP2 criteria, and 43 were excluded . As requy-axis) and the average of the 2 measurements (x-axis). r=0.04, P=.53; diastolic blood pressure: r=.04, P=.54). This indicates that the HeartBeat-calculated blood pressure measurements are not sufficiently accurate. There was no discernible pattern in the inaccuracies in the HeartBeat-calculated measures; therefore, the source of the inaccuracies is not known.The Bland-Altman plots show that the October 4, 2019 version of the HeartBeat algorithm, used in conjunction with a Contec CMS50EW pulse oximeter, MediBeat app, and a Samsung Galaxy XCover 4 smartphone, was not sufficiently accurate to meet ESH-IP2 standards for measuring the blood pressure of adults in the general population; therefore, as per the protocol, it is not recommended for personal or clinical use in this configuration.


To investigate the potential role of renal arterial resistance index (RI) in the differential diagnosis between diabetic kidney disease (DKD) and non-diabetic kidney disease (NDKD) and establish a better-quantified differential diagnostic model.We consecutively reviewed 469 type 2 diabetes patients who underwent renal biopsy in our center. According to the renal biopsy results, eligible patients were classified into the DKD group and the NDKD group. The diagnostic significance of RI was evaluated by receiver operating characteristic (ROC) curve analysis. Logistic regression analysis was used to search for independent risk factors associated with DKD. Then a novel diagnostic model was established using multivariate logistic regression analysis.p< 0.001). The optimum cutoff value of RI for predicting DKD was 0.66 with sensitivity (69.2%) and specificity (80.9%). Diabetic retinopathy, diabetes duration ≥ 60 months, HbA1c ≥ 7.0(%), RI ≥ 0.66, and body mass index showed statistical significance in the multivariate logistic regression analysis. Then, we constructed a new diagnostic model based on these results. And the validation tests indicated that the new model had good sensitivity (81.5%) and specificity (78.6%).A total of 332 DKD and 137 NDKD patients were enrolled for analysis. RI was significantly higher in the DKD group compared with those in the NDKD group (0.70 vs. 0.63, RI has a potential role in discriminating DKD from NDKD. The RI-based predicting model can be helpful for differential diagnosis of DKD and NDKD. Diabetes mellitus (DM) is a global public health challenge affecting over 463 million adults, according to the report of the International Diabetes Federation in 2019 . HoweverCurrently, the renal pathological diagnosis is the gold standard to discriminate DKD from NDKD. However, the kidney biopsy is an invasive procedure that is impracticable in patients with contraindications, such as pyknotic kidney, bleeding tendency, solitary kidney, uncontrolled hypertension, or severe anemia. Moreover, a renal biopsy could not be routinely performed in some primary hospitals. Thus, the diagnosis and appropriate treatment were usually based on clinical indicators, such as diabetes duration, hematuria, diabetic retinopathy (DR), glycated hemoglobin (HbA1c), and other indices –22. HoweThe Renal atrial resistance index (RI), measured by doppler ultrasound, is a low-cost and non-invasive tool in detecting kidney diseases; it has been extensively used to evaluate renal blood flow as a semi-quantitative parameter. Previous studies suggested that RI is correlated with severe interstitial fibrosis and the progression of chronic kidney disease (CKD) –27. In aA total of 469 T2DM patients with renal impairment from the department of nephrology at Xinqiao Hospital, Army Medical University, from January 2014 to September 2020 were retrospectively analyzed Figure 1The kidney biopsies were performed by an experienced renal pathologist, and every kidney biopsy tissue was investigated by electron microscopy, light microscopy, and immunofluorescence. The kidney biopsy indications were in accordance with the KDOQI Guideline . The patThe following data were collected at the time of kidney biopsy: age, sex, body mass index (BMI), systolic blood pressure, diastolic blood pressure, presence of hypertension and DR, medical history of DM, fasting blood glucose, HbA1c, hemoglobin, platelet, serum albumin, total cholesterol, triglyceride, serum creatinine, uric acid, blood urea nitrogen, 24-hour urine protein, hematuria, and RI value. Blood pressure was measured three times according to a standard protocol, and the average value was calculated. DR was confirmed by fundus photography. Ultrasonography was performed by a Philips IU22 Cart G Ultrasound System with C5-1(Made in United Kingdom). The estimated glomerular filtration rate (eGFR) was obtained using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation .PDKD = exp (α + β1x1+ β2x2+ β3x3+…+βnxn)/[1 + exp(α + β1x1+ β2x2+ β3x3+…+ βnxn)]. PDKD is the probability of DKD diagnosis, α is a constant, β is the estimator, and x is the clinical predictor. If PDKD ≥ 0.5, the patient should be considered as DKD, while the diagnosis should be NDKD if PDKD < 0.5. The Delong test and the calculation of the net reclassification improvement and the integrated discrimination improvement were performed by R language to analyze two models. Then, a better model was selected. Finally, a back-substitution and a validation test  were conducted to evaluate the new model. Correlations between RI and clinical indices were analyzed by the Pearson test. Statistical analyses were performed by SPSS (IBM SPSS Statistics 23.0) and R language. P < 0.05 was considered statistically significant. The number of patients required for the validation cohort is computed using software PASS 15.0.5.Continuous variables were shown as average ± standard deviation or the median and interquartile depending on the data distribution, whereas enumeration data were described as percentages (%). The t-test was applied for normally distributed data, and the Mann-Whitney U test was applied for non-normally distributed data. The chi-squared test was applied for enumeration data. Receiver operating characteristic (ROC) curve analysis was used to explore the optimal cutoff point of the RI to predict DKD. Univariate and multivariate logistic regression analyses (stepwise forward) were performed to search the independent risk factors relating to the DKD diagnosis, with results shown as the odds ratio (OR) and 95% confidence interval (CI). The final significant risk factors were included in two differential diagnostic models (with or without RI). The equation is as follows: A total of 469 patients were divided into two groups based on kidney biopsy results, with 332 patients in the DKD group and 137 patients in the NDKD group. The general clinical information of the two groups was shown in vs. 0.63, p<0.001, p<0.001), duration of diabetes , systolic blood pressure ; serum creatinine ; blood urea nitrogen  and total urinary protein, g/24 h , whereas it was inversely correlated with BMI , hemoglobin , triglyceride , and serum albumin  in diabetic patients with renal impairment  to explore the RI value for the clinical differentiation between DKD and NDKD Table 4.For T2DM patients with renal impairment, it is of great significance to differentiate between DKD and NDKD to guide clinical diagnosis and treatment. Kidney biopsy is the ultimate method of differential diagnosis, but its clinical application is restricted by many contraindications , 36. TheDoppler ultrasound as a non-invasive, low-cost method has been extensively used in the detection of reno-vascular diseases. RI is calculated by the ratio of the difference between peak systolic velocity (PSV) and end-diastolic velocity (EDV) divided by peak systolic velocity (PSV), obtained by the Doppler spectrum analysis from segmental or interlobar arteries. PSV mainly reflects the degree of renal vascular filling and blood supply, while the EDV reflects renal blood perfusion, and RI mainly reflects vascular bed resistance . There iGlomerular hemodynamic changes (including hyperfiltration and hypoperfusion) are key pathological processes in the development of DKD, which could explain why RI value as an indicator of renal hemodynamics has a potential value in the differential diagnosis of DKD . The cauOur research also found that DR and diabetic duration are powerful predictors of DKD, which is consistent with previous studies , 18. GenThere are several limitations in the present research. First of all, this research was a retrospective study performed in a single center with limited data. Secondly, all validation cohort patients came from the department of nephrology of Xinqiao Hospital, lacking external validation. Thirdly, we only measure RI value at the time of kidney biopsy, not continuous testing; certain errors are unavoidable.In conclusion, the RI value might serve as a novel potential indicator in the differential diagnosis of DKD. The RI-based differential diagnostic model has improved the accuracy and could be commonly used in clinical practice.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by The ethical committee of Xinqiao Hospital. The patients/participants provided their written informed consent to participate in this study.HL and YS carried out the studies, participated in data collection, statistical analysis, and the writing of the manuscript. ZY and YH contributed to the data analysis. TH, TX, and YL contributed to the data collection. JZ and JX reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version.This study was supported by research grants from Personal Training Program for Clinical Medicine Research of Army Medical University (No. 2018XLC1007), Frontier specific projects of Xinqiao Hospital (No. 2018YQYLY004), Scientific Renovation Project of Army Medical University (No. 2019XLC3038), and Clinical Medical Research Talents Project of Army Military Medical University (No. 2019XLC3028).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


ARD/BSA ≥2.1 cm/m2 in men or ≥2.2 cm/m2 in women was defined as indicating aortic root dilatation. The patients with DM had lower ARD/BSA, higher left atrial dimension (LAD), lower left ventricular ejection fraction, lower ratio of peak early transmitral filling wave velocity to peak late transmitral filling wave velocity, and higher left ventricular relative wall thickness, than those without DM. After multivariable analysis, DM  was significantly associated with low ARD/BSA. Significantly fewer patients with DM had aortic root dilatation compared to those without DM . In the patients with DM, there were significant associations between a high left ventricular mass index (LVMI)  and high LAD  with a low eGFR slope. However, other parameters, including ARD/BSA, were not associated with eGFR slope. Furthermore, there were no associations between eGFR slope and any of the echocardiographic parameters in the patients without DM. Aortic root dilatation was attenuated in the patients with DM, but it was not associated with a decline in renal function. However, high LAD and LVMI were associated with rapid renal function decline in the CKD patients with DM.Patients with chronic kidney disease (CKD) often have cardiac functional and structural abnormalities which can lead to adverse cardiovascular outcomes. In this study, we investigated associations between diabetes mellitus (DM) and cardiac functional and structural parameters in patients with CKD focusing on aortic root diameter (ARD). We also investigated associations of renal outcomes with DM and cardiac functional and structural characteristics. We enrolled 419 patients with CKD stage 3–5 were enrolled. ARD was normalized to body surface area (BSA) (ARD/BSA), and the rate of decline in renal function was assessed by the estimated glomerular filtration rate (eGFR) slope (mL/min/1.73 m Patients with chronic kidney disease (CKD) are at high risk of cardiovascular (CV) morbidity and mortality due to many factors . TraditiIncreased aortic root diameter (ARD) has been reported to be a predictor of thoracic aortic aneurysm rupture , and aorIn this study, we investigated relationships between DM and cardiac functional and structural parameters, with a focus on ARD, in patients with CKD. We also investigated associations of renal outcomes, assessed using eGFR slope, with DM and cardiac functional and structural characteristics.2): stage 3, eGFR 30–59; stage 4, eGFR 15–29; and stage 5, eGFR < 15. To ensure sufficient data to be able to analyze renal function changes, patients with fewer than three follow-up eGFR measurements (n = 64), and those with less than six months of data (n = 22) during the follow-up period were excluded. In total, we included 419 patients , all of whom provided written informed consent before enrollment. This study was conducted at Kaohsiung Medical University Hospital (KMUH), Taiwan, from May 2006 to January 2010. The Institutional Review Board of KMUH approved this study, which followed the appropriate guidelines. We enrolled 505 patients with CKD stage 3–5. None of the enrolled patients had initiated dialysis. CKD was defined as the presence of kidney disease for three months or longer. The stages of CKD were defined in accordance with the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines  as follo2 in men or ≥2.2 cm/m2 in women [3 − LVIDd3] − 13.6 g [The echocardiographic examinations were conducted by two experienced cardiologists who were unaware of the patients’ data using an ultrasound machine . Two-dimensional and M-mode echocardiographic measurements were performed with the patients in a left decubitus position. ARD was normalized to body surface area (BSA) (ARD/BSA). Aortic root dilatation was defined as ARD/BSA ≥2.1 cm/min women . LVEF wa− 13.6 g . LVMI waData on age, sex, smoking status, baseline information on hypertension, cerebrovascular disease, DM and coronary artery disease were collected by chart review. Patients with a history of cerebral bleeding and infarction were defined as having cerebrovascular disease, and those with a history of ischemic electrocardiogram change, old myocardial infarction, angina, angioplasty or coronary bypass surgery were defined as having coronary artery disease. Blood pressure (both systolic and diastolic) measurements were recorded. Fasting blood samples were collected from each patient within 1 month of enrollment, and levels of triglycerides, glucose, total cholesterol, hemoglobin and calcium-phosphorous product were measured at out laboratory. Serum creatinine levels were determined using the kinetic Jaffé method with isotope-dilution mass spectrometry . The CKD2/year. The slope was calculated as the regression coefficient between time and a minimum of three eGFR measurements recorded after enrollment.The eGFR slope was used to assess the rate of decline in renal function measured in mL/min/1.73 mp value of less than 0.05 was considered to indicate a significant difference. SPSS version 26.0 for Windows was used for all statistical analyses .Data are presented as percentages, means ± standard deviations, and medians (25th–75th percentiles), and means ± standard errors of the mean for eGFR slope. One-way analysis of variance (ANOVA) was used for multi-group comparisons followed by post hoc adjustments with Bonferroni correction. The independent t-test was used to examine differences between groups for continuous variables, and the chi-square test was used for categorical variables. linear regression analysis was performed to examine associations between the echocardiographic parameters with ARD/BSA and eGFR slope. A The clinical characteristics were compared between ARD/BSA tertiles . The patThe echocardiographic parameters were compared between the patients with and without DM . The patp < 0.001), male , low triglycerides , and low baseline eGFR  were significantly associated with a large ARD/BSA. In addition, DM  was negatively significantly associated with ARD/BSA.p = 0.022). p < 0.001) and high LVMI  were significantly associated with low eGFR slope. However, other parameters, including ARD/BSA, were not associated with eGFR slope. Furthermore, in the patients without DM, none of the echocardiographic parameters were associated with eGFR slope.Associations between eGFR slope and the echocardiographic parameters after multiple adjustments for age, sex, smoking history, cerebrovascular disease, log triglycerides, total cholesterol, systolic blood pressure > 140 mmHg, hemoglobin, hypertension, coronary artery disease, fasting glucose, eGFR, calcium-phosphorous product, proteinuria and the use of ACEIs and/or ARBs are shown in p = 0.010) was statistically significant. However, interactions of the other parameters and DM did not achieve significance.Analysis of the effects of interactions between echocardiographic parameters and DM on eGFR slope is also shown in In this study, we examined associations among echocardiographic parameters and DM, and further evaluated the associations with renal outcomes in patients with CKD. Our results showed a significant association between DM and low ARD/BSA. In addition, in the patients with DM, high LAD and high LVMI were significantly associated with a low eGFR slope, however ARD/BSA was not associated with eGFR slope. Furthermore, in the patients without DM, none of the echocardiographic parameters were associated with eGFR slope.The first important findings of this study are that compared to the patients without DM, those with DM had lower ARD/BSA, and that significantly fewer of the patients with DM had aortic root dilatation. A previous meta-analysis of 8 studies reported that the prevalence of aortic root dilatation in patients with hypertension was around 10%, and that is was even higher in male and elderly patients , which iWe also found an association between low eGFR and high ARD/BSA, but that high ARD/BSA was not associated with rapid renal function decline. Only a few studies have investigated the association between renal function and ARD, and the relationship between the rate in the decline of eGFR and ARD is unclear. A previous study on hypertension reported an inverse association between eGFR and ARD , and thaAnother important finding of the present study is that high LAD and LVMI were associated with a rapid decline in renal function in the patients with DM. The interactions among cardiac dysfunction, DM and CKD are complex, and hemodynamic changes, hypoperfusion, oxidative stress, endothelial dysfunction, cytokines and neurohormonal abnormalities all play roles in organ damage associated with cardiac dysfunction and CKD progression . In our There were several limitations to this study. First, the number of serum creatinine measurements and the intervals between them differed from patient to patient, and thus the eGFR slope also differed. However, only patients who were followed for at least 3 months and had at least three eGFR measurements were included in this study, which may have increased the reliability of the eGFR slope findings. Second, this study was conducted at a single center, and this the result may not be generalizable to all patients with CKD. Third, albuminuria is an early marker of diabetic nephropathy and an important factor influencing DM outcomes, however we did not quantify albuminuria in this study. In addition, the effect of volume overload could not be evaluated as we did not assess volume status. Finally, we lacked data on lipid-lowering agent history, and these medications undoubtedly influence the values of lipid profiles. Therefore, we could not exclude the impact of such medications on our results.In conclusion, aortic root dilation was attenuated in the CKD patients with DM in this study, but it was not associated with renal outcomes. In addition, high LAD and LVMI were associated with rapid decline in renal function in the patients with DM.


The purpose of this retrospective study is to evaluate the effectiveness of early cardiac rehabilitation on patients with heart failure following acute myocardial infarction.Two hundred and thirty-two patients who developed heart failure following acute myocardial infarction were enrolled in this study. Patients were divided into heart failure with reduced ejection fraction group (n = 54) and heart failure with mid-range ejection fraction group (n = 178). Seventy-eight patients who accepted a two-week cardiac rehabilitation were further divided into two subgroups based on major adverse cardiovascular events. Key cardio-pulmonary exercise testing indicators that may affect the prognosis were identified among the cardiac rehabilitation patients.ETCO2 in the cardiac rehabilitation group who developed re-hospitalization. Low PETCO2 at anaerobic threshold (≤ 33.5 mmHg) was an independent risk factor for re-hospitalization.Early cardiac rehabilitation significantly reduced cardiac death and re-hospitalization in patients. There was more incidence of diabetes, hyperkalemia and low PETCO2 at anaerobic threshold is an independent risk factor for re-hospitalization, and could be used as a evaluating hallmark for early cardiac rehabilitation.Early cardiac rehabilitation reduced major cardiac events in patients with heart failure following acute myocardial infarction. The lower P Congestive heart failure (CHF) is a major cause of mortality and morbidity and the end pathophysiological condition of many cardiovascular diseases . One of 2 and VE/VCO2 slope compared to continuous exercise in HF patients [Exercise intolerance, represented as decreased capacity to perform physical activities with symptoms of severe fatigue and/or dyspnea, is a characteristic of CHF and associated with increased mortality and reduced quality of life (QoL) . The patpatients . Furtherpatients . Howeverpatients . UnfortuFrom June 2016 to May 2017, AMI patients with CHF following PCI were identified in the Department of Cardiology at the First Hospital of Jilin University. The retrospective study protocol was approved by Medical ethics committee of the first hospital of Jilin University.AMI patients’ ultrasound cardiogram were performed after hemodynamic stabilization 24 h after PCI. The inclusion criteria was in accordance with the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure . The exc2), carbon dioxide production (VCO2), minute ventilation (VE), partial pressure of end-tidal carbon dioxide (PETCO2), respiratory exchange ratio (RER) and other key CPX variables were measured with submaximal graded exercise test using cardio-respiratory instrumentation Medisoft  after 2-week CR. The exercise load was determined by a cycle ergometer  work rate. The progressive load was 10 watts per minute during the graded exercise test, and the pedaling cadence kept at 55–65 revolutions per minute (RPM) throughout the test. The exercise test was terminated if the patient developed any of the following subjective or objective conditions: abnormal hemodynamic or ECG exercise response, or other causes such as dyspnea, angina or lower extremity muscle fatigue.CPX, a widely accepted evaluation tool in both the United States (US) and Europe, was used for the assessment of CRF , 19. TheAll patients had informed consent and registered their personal contact telephone number. Follow-up data was acquired through hospital records and telephone interviews which were conducted every 3 months from discharge until cardiac death or December 2020, whichever came first. MACE including cardiac death and re-hospitalization were documented. Patients with cardiac death who lost telephone interviews were identified from the population registry bureau. The average duration of follow-up was 4 years.P < 0.05 was considered as statistical significance.Continuous variables were presented as means ± standard deviation, and non-normally distributed variables were presented as medians (interquartile range). Categorical variables were expressed as numbers and percentages. Variable parameters between the groups were compared with means of one-way analysis of variance, or Mann–Whitney U test for continuous variables and chi-square test for dichotomous variables, as appropriate. In all analyses, a two-tailed P value < 0.05 in the univariate analysis were included, and were used to distinguish independent risk factors for MACE. A receiver operating characteristic (ROC) curve was used to predict the prognosis for MACE. All statistical analysis data were performed using the SPSS 19 software .Corrections were made to account for the multiple comparisons by cox multivariate regression analysis, in which test indices and variables showing a A total of 274 AMI patients with CHF following PCI were identified, 21 patients who were lost to follow-up and 21 patients who were not able to participate cardiopulmonary exercise testing (CPX) were excluded Table.Fig. 1ThP = 0.005) due to higher incidence of cardiac death  compared to CR patients (Table P < 0.001) due to higher incidence of heart failure (HF) re-hospitalization  compared to CR patients , had higher serum potassium , and lower PETCO2 at VT   and the non-MACE group (n = 72) Table . CompareETCO2 at VT was an independent risk factor for re-hospitalization , but not serum potassium  and history of diabetes  , P = 0.03)  should be achieved during the test [2 at VT holds broad applicability in the context of assessing the capacity [2 at VT < 10.5 ml/kg/min is an independent risk factor for cardiovascular disease prognosis and could be used as an evaluating hallmark for Phase I cardiac rehabilitation in patients with acute ST segment elevation myocardial infarction (STEMI) after PCI [ETCO2 both at rest and during exercise have been found to be positively correlated with the prognosis of systolic heart failure [ETCO2 in patients with HCM have been thought to enhance pulmonary pressures [Of note, in order to achieve the prediction accuracy of peak VOthe test . Howeverthe test . It corrthe test . The 201capacity . Furtherfter PCI . The PET failure . Abnormaressures .ETCO2 at VT is a marker for prediction of re-hospitalization after adjusted to sex, age, history of diabetes, blood potassium and ejection fraction for patients with CHF after AMI. Lower PETCO2 is an indicator of less CO2 production in the body and/or pulmonary arterial perfusion, or the cardiac output [2 is less, hence, PETCO2 decreases [ETCO2 at VT. Therefore, PETCO2 at VT is an independent risk factor for re-hospitalization but not high serum potassium and history of diabetes.In the present study, we found that Pc output . The senecreases . The re-The limitations of this study include: (1) the participants in the non-CR group were not assessed for CRF using CPX before discharge so it is not clear which parameters of cardiopulmonary fitness  were improved by early rehabilitation in two weeks. (2) Lack of home exercise data in CR group and non-CR group, so further research is needed to explore the influence of early CR on home-based healthy lifestyle development and the influence of home exercise amount on long-term prognosis. (3) Lack of field test application in CR group and non-CR group, future study will be conducted using six-minute walk test.ETCO2 at VT is an independent risk factor for re-hospitalization, and can be used as a key evaluating hallmark for early CR in patients with CHF after AMI.In conclusion, early CR decreases the incidence of cardiovascular events in patients with CHF after AMI following PCI. The P