Cardiac autonomic function was assessed during the response to standing (tilt) and deep breathing tests (expiration/inspiration ratio-E/I). Results: HR and BP responses to the tilt test were similar in both groups. MG patients, as compared to controls, were characterized by altered SBPV at rest, significantly reduced HR response to the deep breathing test (p < 0.001), increased sympathovagal balance after tilt , and lower values of BRS (p = 0.007) and hemodynamic parameters, i.e., cardiac index, index contractility, left ventricular work index, at rest and during tilt. There was no association between disease duration and autonomic parameters. Disease severity, as determined by MGFA (Myasthenia Gravis Foundation of America) corrected for age and sex, was an independent predictor of diminished vagal tone (E/I ratio) and increased sympathetic response to tilt (delta LF/HF-RRI) as measured with HRV. Lower BRS was associated with greater disease severity and older age. Hemodynamic parameters were predominantly predicted by age and sex. Conclusion: Our results confirm cardiac autonomic dysfunction among MG patients with predominant parasympathetic impairment. Clinicians should consider evaluation of autonomic balance in MG patients with, or at risk for, cardiovascular disease.Introduction: The aim of the study was to assess cardiac and autonomic function in patients with myasthenia gravis (MG) and to explore its relationship with disease outcomes. Methods: Thirty-eight patients with an MG were enrolled . Cardiovascular parameters, baroreflex sensitivity (BRS), spectral indices of short-term heart rate (HRV), and systolic blood pressure variability (SBPV) were compared with age- and gender-matched controls ( Myasthenia gravis (MG) is a rare, autoimmune, and T helper cells-mediated neurological disease characterized by fluctuating fatigability and weakness of extraocular, bulbar, respiratory and limb muscles . ClinicaLocalized or general muscle weakness are the cardinal symptoms of MG, however, some patients may experience various non-motor symptoms such as sleep abnormalities , cognitiThe most life-threatening ADs are related to the cardiovascular system and include decreased heart rate variability (HRV), cardiac arrhythmias, and even atrial fibrillation ,12,13. CFew studies in different MG subgroups using cardiovascular reflex tests, as well as HRV measures, have revealed mainly parasympathetic than sympathetic cardiac impairment ,26, wherImpedance cardiography (ICG) is a simple, non-invasive method of hemodynamic parameters, left ventricular function, myocardial contractility, and thoracic fluid content. Most studies have demonstrated a good correlation between ICG, echocardiography, and invasive diagnostic techniques . Only a The primary aim of this study was to compare cardiac and autonomic function between patients with MG and healthy controls (HCs). An additional purpose was to assess whether cardiac and autonomic measures are associated with clinical outcomes in individuals with MG.It was a cross-sectional and case-control study conducted between January 2017 and March 2022. All subjects gave their written informed consent for this study, which was approved by the Bioethical Committee of Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun (KB 747/2017). The study included 38 patients with MG aged 19–69 years  and 30 age-matched healthy control subjects (HCs) . All patients underwent a detailed clinical and neurological examination in the outpatient clinic  by the same neurologist (Ł.R.). All HCs were normal in the neurological examination. Inclusion criteria for the MG patients were: age above 18 years old, diagnosis of MG, and no disease exacerbation within 90 days preceding the study. The inclusion criteria for controls included the following: no history of autoimmune disorders or neurological diseases. The exclusion criteria for MG patients and controls included: past history of cardiac disease; arrhythmia, including atrial fibrillation; the presence of major concurrent illness (respiratory involvement or in state of MG crisis); diabetes, hypertension, hyperthyroidism, hypothyroidism, or any other disease that might affect the autonomic nervous system; treatment with beta-blockers, antihypertensive drugs. In all patients, the cardiac autonomic function was assessed while receiving treatment for MG. Demographic and clinical data were obtained from medical records . HCs werThe diagnosis of MG was established by characteristic clinical presentation (fluctuating weakness of ocular and/or extraocular muscles) and at least one of the following criteria: positive AChR autoantibodies (AChR-Abs), or MuSK antibodies (Musk-Abs), electrophysiological findings (repetitive stimulation and/or single-fiber electromyography), and clinical response to cholinesterase inhibitors. All of the patients had a stable course of disease for a minimum three months period.Patients were categorized into subgroups according to age at onset , the clinical disease type , antibody status , current MG therapy, thymic pathology and history of thymectomy . Serum lThe Myasthenia Gravis Foundation of America (MGFA) classification was developed as a tool for assessing disease severity. The MGFA classes are pure ocular weakness (class I), mild-generalized weakness (class II), moderate generalized weakness (class III), severe generalized weakness (class IV), and intubation/myasthenic crisis (class V). Within generalized MG (II-IV), patients are classified as class A  or class B  ,29.The cardiac and autonomic functioning of participants was recorded using the TFM software version 2.3.20.20 . In the present study, recordings were performed in a supine position for a minimum of 10 min and during the head-up tilt test (HUTT), using a 70° angle of tilt for 5 min. All the functions of TFM have been validated and successfully used in recent clinical studies ,31,32.max; left ventricular work index, LVWI = constant × (mean blood pressure − pulmonary artery occlusion pressure) × CI]. Thoracic fluid content (TFC = 1/kOhm]) was measured as an indicator of the volume of thoracic intravascular and extravascular fluid in the chest cavity. The afterload was calculated as the total peripheral resistance index (TPRI = mean BP/cardiac index) and preload as the end-diastolic index (EDI).TFM integrates ECG signal (electrocardiography), oscillometric, continuous plethysmographic blood pressure registration, and ICG (impedance cardiography), allowing analysis of the power spectral analysis of HRV and SBPV. Heart rate (HR) was obtained from the ECG. Continuous arterial systolic (sBP), diastolic (dBP), and mean (mBP) blood pressure were measured noninvasively beat-to-beat by finger plethysmography on the right hand. The finger blood pressure values were automatically calibrated (every 3 min) against oscillometric upper left arm measurements of arterial blood pressure . In geneSympathetic reactivity was assessed with the HUTT, while parasympathetic reactivity was evaluated by testing HR response to deep breathing (DBT).During DBT, subjects were instructed to breathe slowly at 6 breaths/min (5 s inspiration and 5 s expiration). The E/I-ratio was calculated as the mean value of the longest R-R interval during expiration divided by the mean value of the shortest R-R interval during inspiration, averaged over 6 cycles. E/I was abnormal if it was ≤1.11 .The ANS function was evaluated by baroreceptor sensitivity (BRS) using the sequence method and the power spectral analysis of the short-term heart rate (HRV) and systolic blood pressure variability (SBPV) applying an autoregressive (AAR) methodology as described by Bianchi et al. .TFM automatically calculates a set of variables accounting for the variability of the heart rate  and blood pressure: low frequency , high frequency , total power spectral density (PSD), representing total variability. For analysis, results were expressed in absolute and normalized values . To assess sympathovagal balance, the ratios between LF and HF bands for heart rate and blood pressure variability was also calculated  .As previously described, the LF band reflects contributions from both the parasympathetic and sympathetic modulation of the sinoatrial node (LF-RRI) and sympathetic modulation of the vascular tone (LF SBPV), while the HF band reflects parasympathetic modulation of cardiovascular activity influenced by respiration .Baroreceptor sensitivity (BRS) was calculated using the sequence method as the slope of the linear regression between beat-to-beat sBP values (mmHg) during 10 min of supine rest .All measurements were performed at the same time of the day, between 8–12 a.m., in a quiet, darkened room with a standard temperature (22 ± 1 °C) and air humidity, by the same investigator [M.Z.K.]. All participants were instructed to refrain from alcohol and caffeine consumption, smoking, and intensive exercise for at least 12 h before testing .In our study, HRV and BPV data were exported from the TFM software into Microsoft Excel for further analysis and then transferred Statistica.  The AAR model may produce outliers when analyzing RR intervals, thus, all HR beat-to-beat data were filtered using Grubbs’s test for outliers’ elimination. This method of filtering is well-described and has a strong mathematical background .p < 0.05.All data are presented as median (lower quartile–upper quartile). The data distribution of the study variables was verified with the Shapiro–Wilk test. Differences in the distribution of qualitative variables were determined with the Chi-square test, while the differences in quantitative variables were determined with the use of the nonparametric Mann–Whitney test. The strength and significance of the correlation between selected variables were calculated using the nonparametric Spearman’s test. The multiple regression model, based on three predictors , was also used in order to determine significant predictors for cardiac, BRS, HRV, and SBPV variables. The level of significance for all tests was set at p > 0.05. Early disease onset before the age of 50 occurred in 35 patients (92.1%), while 3 cases (7.9%) were late disease onset. With respect to AChR-Ab status, 23 (60.5%) patients were seropositive, whereas 15 (39.5%) were seronegative. MGFA class at the moment of testing was available for all patients. Eight (21.1%) patients presented ocular weakness (Class I); 19 (50.0%) mild symptoms (Class II); and 11 patients (28.9%) with moderate muscle weakness (Class III) was documented. Thymic pathology was detected in 22 (59.5%) MG patients and fourteen of them underwent thymectomy. Histopathological evaluation revealed thymoma in one case. Most patients classified and had a generalized form (81.6%) of the disease. At the time of the study, all MG patients were on pyridostigmine (240 mg/day), 23 of them used corticosteroids .The demographic and clinical characteristics of the study population are presented in p = 0.015), IC (p = 0.029), LVWI (p = 0.006), EDI (p = 0.032), thoracic fluid content (p < 0.001) and significantly higher values of TPRI (0.045). In contrast, no significant differences were observed between the groups in HRV parameters, p > 0.05. MG patients had significantly lower BRS and LF/HF-sBP, and higher HF-sBP compared to the HCs , CI, LVWI, as well as lower TFC, HF-RRI, and LF-RRI (p > 0.05. In response to the deep breathing test (DBT), MG patients had a significantly lower E/I-ratio compared to HCs (p < 0.001). An abnormal HR response to deep breathing (E/I ratio) was found in 12 (31.6%) of patients and only 1 (3.3%) of the HCs , HRV parameters, both at rest , during HUTT  as well as in response to HUTT , respectively  as well as during HUTT . Lower HRV parameters were significantly associated with higher disease severity . Overall, there was no association between disease duration and autonomic hemodynamic measures, except for delta index of contractility .MGFA negatively correlated with thoracic fluid content, both at rest . There was no significant correlation between AChR-Ab status and the autonomic parameters, p > 0.05.There was a significant negative association between AChR-ab-positive MG patients and LVWI  as well as E/I ratio  explaining 18% and 15% of the variance, respectively (see p = 0.005), and age  were found to predict lower BRS explaining 33% of the variance  . Our finUsing ICG, we have demonstrated that MG patients’ demographics were associated with impaired cardiac function, including subtle reductions in LV myocardial function and decreases in thoracic fluid content pronounced at rest and during HUTT. In addition, the presence of AChR-abs was associated with lower LVWI, which may suggest an underlying autoimmune mechanism of reduced cardiac inotropy parameters in MG.Changes in left ventricular work index paralleled changes in cardiac index, thus, reduction in cardiac output or blood pressure or a combination of both could be compensated by sympathetic α-adrenergic vasoconstriction expressed as an increase in TPR.Similar to our study, Perez et al. found a similar pattern of hemodynamic changes with a decrease in cardiac index accompanied by an increase in TPRI in half of patients with MG and thymoma. They also postulated increased incidence of atrial fibrillation, ventricular and supra ventricular extra systoles and prolonged corrected QT interval .Using variables derived from ECG and echocardiography, Kato et al., found that a small number of patients without ECG abnormality demonstrated cardiac damage, which comprised only diastolic impairment (E/e ratio) and did not include systolic impairment . In the Our study has several clinical implications. Firstly, CAD symptoms should be considered when evaluating MG patients, especially those with an advanced disease stage. Secondly, we have shown that diminished cardiovagal tone and sympathetic hyperresponsiveness are present in MG patients despite the enhancement of vagal tone by the use of acetylcholine esterase inhibitors. Thus, the parasympathetic deficit is underestimated in MG patients and is more extensive than the disturbances of cholinergic transmission at the neuromuscular junction. Furthermore, as the severity of the disease increases, the lower parasympathetic activity is observed, which confirms the strong association between CAD and the immune response. It is noteworthy that by contributing to the reduction of MG severity, we also reduce their risk of cardiovascular events. On the other hand, clinicians should be aware that MG patients with severe disease are more at risk of cardiovascular complications than those with minimal manifestation. Moreover, it can be assumed that autonomic imbalance and LV myocardial function abnormalities may contribute to the lower exercise capacity of MG patients, which is a common feature of this condition.A few limitations of this study should be addressed. First, we did not include patients who were in stage IIIb-V at MGFA classification, which significantly limited the analysis of the overall disease impact on cardiovascular risk. Second, our study did not assess as a subgroup of MG, MUSK-Ab-positive, since they are present in a small proportion of patients. Third, our study is cross-sectional and no longitudinal data are available. Furthermore, we did not take into account the impact of treatment with pyridostygmine, steroids, and azathioprine on cardiac and autonomic parameters. Our study includes pre-diabetic conditions, however, prediabetes is found to be also associated with dysfunction of cardiac autonomic activity and includes decreased HRV, and reduced parasympathetic modulation of the heart . We evalFinally, future research should consider assessing both linear and non-linear measures of HRV and BPV, which can be a promising field for exploring autonomic cardiac loops of circulation in MG patients. Several studies have shown that such methods were useful tools for clinical practice, in particular, in patients with cardiovascular events  ,52,53,54In conclusion, cardiac autonomic dysfunction is associated with predominant parasympathetic impairment in patients with myasthenia gravis. Alterations of cardiac autonomic responses were related to the severity of the disease but not to its duration. Moreover, MG patients were characterized by altered SBPV and lower subclinical LV myocardial function. Clinicians should consider the evaluation of CAD in MG patients with, or at risk for, cardiovascular disease, especially in advanced stages of the disease. Non-invasive monitoring of beat-to-beat BPV and HRV may be helpful in providing insight into the early deteriorating mechanisms of cardiovascular autonomic control.


Chronic kidney disease (CKD) patients are more likely to die from cardiovascular disease (CVD) than develop renal failure. This study aimed to develop a new nomogram for predicting the risk of cardiovascular death in CKD patients.This study enrolled 1656 CKD patients from NHANES 2003 to 2006 survey. Data sets from 2005 to 2006 survey population were used to build a nomogram for predicting the risk of cardiovascular death, and the nomogram was validated using data from 2003 to 2004 survey population. To identify the main determinants of cardiovascular death, we performed univariate analysis and backward-stepwise regression to select the key factors. The probability of cardiovascular death for each patient in 5, 7, and 9 years was calculated using a nomogram based on the predictors. To assess the nomogram’s performance, the area under receiver operating characteristic curve (AUC) and the calibration curve with 1,000 bootstraps resamples were utilized. The prediction model’s discrimination was examined using cumulative incidence function (CIF).Age, homocysteine, potassium levels, CKD stage, and anemia were included in the nomogram after screening risk factors using univariate analysis and backward-stepwise regression. Internal validation revealed that this nomogram possesses high discrimination and calibration . External validation confirmed the same findings . According to CIF, the established nomogram effectively differentiates patients at a high risk of cardiovascular death from those at low risk.This work develops a novel nomogram that integrates age, homocysteine, potassium levels, CKD stage, and anemia and can be used to more easily predict cardiovascular death in CKD patients, highlighting its potential value in clinical application. Chronic kidney disease (CKD) has developed into a global health crisis, lowering patients’ quality of life declining and resulting in disability . At presAlthough adverse cardiovascular outcomes are common in CKD patients, there is currently no reliable tool to predict them . Constru2 or urinary albumin-to-creatinine ratio (UACR) >30 mg/g]; (2) patients with 18–75 years old. Patients with incomplete clinical data or lost contact during the follow-up period were excluded. Based on our clinical experience and literature review, we selected some risk factors that might affect cardiovascular prognosis, including diabetes, hypertension, gender, age, glycosylated hemoglobin (HbA1c), blood urea nitrogen (BUN), serum phosphorus (P), serum potassium, serum uric acid (UA), UACR, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total cholesterol (TC), serum total triglycerides (TG), calcium (Ca), Body Mass index (BMI), albumin (Alb), C-reactive protein (CRP), homocysteine, CKD stage (eGFR < 60 mL/min per 1.73 m2 or eGFR ≥ 60 mL/min per 1.73 m2), and anemia (defined as hemoglobin <13 g/dL for men and <12 g/dL for women). The information of questionnaire was used to determine the presence of complications.In this study, the data of enrolled patients were obtained from the 2003 to 2006 National Health and Nutrition Examination Survey (NHANES). The population from 2005 to 2006 was used to construct the model, whereas the population in 2003–2004 served as an external validation cohort. The inclusion criteria include the following: (1) patients with CKD [defined as estimated glomerular filtration rate  <60 mL/min per 1.73 mCardiovascular death was the main prespecified outcome. Since the occurrence of cardiovascular events in CKD patients may be a long-term process, we measured the probability of cardiovascular deaths at three different time points . The situation of cardiovascular death and the follow-up time were extracted from the public-use linked mortality file from the National Center for Health Statistics (NCHS) and matched with patients’ ID from NHANES database. The follow-up time is defined as the interval between the interview date and the death date.t-test and are presented as mean ± standard deviation (SD). Mann-Whitney U-test was used to determine the non-normally distributed variables, and they were presented as median (1st–3rd quartile). Chi-square tests were performed to compare categorical variables. If the theoretical frequency was less than 10, Fisher’s exact test was preferred. Given the possibility of competitive risk, relying solely on one endpoint-analysis approach can lead to an inaccurate assessment of the probability of adverse events. Compared with Cox proportional hazards model, the competitive risk model can provide a more accurate estimate of the cumulative incidence of multiple outcomes  was considered statistically significant.The three-knot cubic spline  was employed to account for potential non-linear effects of continuous data. Shapiro-Wilk method was utilized to examine the normal distribution of continuous data. The continuous variables conformed to normal distribution were compared using independent samples outcomes . Therefogression . To evalgression  were depgression . Decisiogression . For extgression  to explo1 R software was used to implement the three-knot cubic spline (survminer package), competing risk model , nomogram , CIF (cmprsk Package), ROC curve (timeROC), AUC, and calibration plot.All statistical analyses were performed using R software version 4.05.P < 0.05). According to our prespecified inclusion and exclusion criteria, this study enrolled 1656 CKD patients. Among them, 10.5 and 15.4% died from CVD in training and validation cohorts, accounting for 33 and 35% of the total deaths, respectively. The median ages in training and validation cohorts were 66 and 70 years, respectively. The median follow-up times were 121 and 142 months in training and validation cohorts, respectively. In the training cohort, 53.3% of participants were males, 22.41% had diabetes, and 56.23% had hypertension. In the validation cohort, 53.71% were males, 25.42% had diabetes, and 59.18% had hypertension. Patients with stage 3–5 CKD account for 38.74% in training cohort and 37.82% in validation cohort. According to the observation of clinical characteristics, age, potassium, AST, homocysteine, and sodium levels were significantly different between the two cohorts (P < 0.2) were entered into multivariate competing risk model . DCA curves indicated that the model provided a net benefit across approximately 60, 70, and 75% of the risk threshold range in 5–, 7–, and 9-years, respectively  and three times higher in stage 4 (15–29 mL/min per 1.73 m2) than in individuals with normal kidney function  have a considerably higher risk of cardiovascular mortality than patients with kidney failure . These ffunction , 26. Homfunction . TogetheIt is undeniable that our prediction model has some limitations. First, all data of our enrolled patients were obtained from NHANES database, although we validated using data from many time points. Additionally, multicenter clinical validation is required to assess the nomogram’s external applicability. Second, due to limited data of NHANES database, some crucial indicators of cardiovascular prognoses, such as brain natriuretic peptide or cardiac troponin, were not investigated. Third, our study included a substantial number of non-dialysis patients. The prediction efficacy of the developed nomogram for dialysis patients should be further validated.Through a competing risk model, we established a novel nomogram incorporating age, homocysteine, CKD stage, anemia, and potassium levels. The internal and external validations revealed the good predictive performance of this nomogram. Additional data on CKD patients should be used in the future to confirm the nomogram’s prediction ability.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. Written informed consent was not obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.NL and LZ contributed to the concept and design of this study. NL, YX, JZ, GZ, and YZ were responsible for statistical analysis and writing of the report. WH assisted in statistical analysis. MY, LX, EZ, and WS reviewed the article and provided critical feedback to improve and structure the report. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.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.


Symptomatic intracranial hemorrhage (sICH) and malignant brain edema (MBE) are well-known deleterious endovascular treatment (EVT) complications that some studies found to be associated with postprocedural blood pressure (BP) variability. We aimed to evaluate their association with periprocedural BP changes, including its intraprocedural decrease.We retrospectively analyzed the data of 132 consecutive patients that underwent EVT between 1 December 2018 and 31 December 2019, for anterior circulation ischemic stroke. Analyzed predictors of sICH and MBE included non-invasively obtained BP before and 5-min after treatment, intraprocedural relative decreases of BP from baseline, and its post-treatment increases. SICH was defined in accordance with the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria and MBE as brain edema with midline shift on the follow-up imaging. We used binary logistic regression analysis to investigate the association of BP parameters and the incidence of sICH and MBE.Among the included patients, 11 (8.3%) developed sICH and 31 (23.5%) MBE. The intraprocedural decrease of mean arterial blood pressure (MAP) was independently associated with MBE occurrence . Over 40% MAP drop was associated with a higher risk of sICH in the entire cohort , but not in the subgroup with successful reperfusion . Post-treatment systolic blood pressure (SBP) and MAP elevation above their minimal values during MT are significantly associated with the development of sICH .In the anterior circulation ischemic stroke patients relative MAP decrease during EVT is associated with a higher risk of MBE occurrence, and over 40% MAP drop with a higher incidence of both MBE and sICH. Post-treatment elevation of SBP and MAP increased the risk of sICH. Significant oscillations of periprocedural blood pressure (BP) in patients with acute ischemic stroke (AIS) treated with mechanical thrombectomy (MT) are now considered to be a common finding . AccumulIt is hypothesized that blood pressure decreases in the setting of large vessel occlusion (LVO) compromises collateral flow and promotes the progression of penumbra to the ischemic core, as well as exacerbates endothelial ischemic injury. After reperfusion treatment with complete or only partial LVO recanalization, BP elevation may result in hemorrhagic transformation (HT) of AIS or reperfusion-induced cerebral edema (CED) . FindingSICH and MBE are known to have serious deleterious consequences on MT-treated patients with AIS and efforts should be made to find their modifiable risk factors. In this study, we examined the effects of periprocedural BP changes on those early EVT complications.We conducted a retrospective observational study of consecutive patients with AIS and LVO undergoing EVT. The study was conducted at the academic comprehensive stroke center: Department of Neurology, Clinical Regional Hospital No. 2, Rzeszow, Poland. It was confirmed by the Bioethics Committee of the University of Rzeszow. Written consent was waived due to its observational status.We retrospectively analyzed the prospective database comprising adult (age ≥ 18 years) patients with AIS due to occlusion of the intracranial internal carotid artery (ICA) and/or middle cerebral artery (MCA) in its first (M1) or second (M2) segment. All patients were treated with EVT using modern stent retrievers and/or direct aspiration technique over a period of 13 months (1 December 2018 and 31 December 2019). Patient demographic data, medical history, baseline characteristics, and imaging data were obtained from electronic medical records.All treatment decisions were made by the endovascular treatment team (experienced vascular neurologist and neuroradiologist) in accordance with the Polish Neurological Society stroke treatment guidelines . The choPeriprocedural variables included age, sex, comorbidities, admission NIHSS, onset-to-groin puncture time (minutes), onset-to-reperfusion time (minutes), procedure duration (minutes), localization of LVO, type of anesthesia, administration of bridging intravenous thrombolysis (IVT), and additional procedures performed during hospitalization: intra-/extracranial stenting and/or decompressive hemicraniectomy.Post-MT reperfusion was graded by the Thrombolysis in Cerebral Infarction (TICI) scale: grades 2b (perfusion >50% of the vascular distribution of the occluded artery) and 3  were considered successful reperfusion .Functional status and mortality at 3-months  were evaluated either in person or by telephone in accordance with our standard procedure.Blood pressure data were obtained from the patient's anesthesia report following the intervention. These data included systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MAP) measured non-invasively before EVT procedure, every 5 min during MT, and 5 min after procedure termination .Baseline BP was defined as the value of the measurement directly preceding induction of anesthesia. The lowest intraprocedural BP measured before successful reperfusion or termination of the procedure in case of unsuccessful reperfusion was considered as the intraprocedural minimal BP value and the difference between baseline and minimal BP as the maximal BP drop.All patients underwent non-contrast CT or magnetic resonance imaging as part of their routine clinical work-up at 24–36 h post-EVT or earlier/later if significant clinical deterioration occurred. One patient was excluded from the study due to death before having an imaging study performed. The imaging characteristics were assessed by two experienced neurologists. If discrepancies occurred, the final result was determined by consensus opinion.SICH was defined in accordance with Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria as parenchymal hematoma (PH) type 2 (hematoma occupying >30% of the infarcted area with significant space-occupying effect) with the National Institutes of Health Stroke Scale (NIHSS) score increment ≥4 points . CED subt-test or Mann-Whitney U-test for continuous variables, as appropriate. Associations of hemodynamic variables with outcome parameters were determined using ordinal logistic regression models adjusted for predefined factors selected according to prior studies and theoretical considerations. Analyses of sICH associations were adjusted for recanalization status, bridging thrombolysis, NIHSS score at admission, onset-to-reperfusion time, and MBE for recanalization status, NIHSS score at admission, onset-to-reperfusion time, presence of intracranial hemorrhage on post-treatment brain imaging. Subgroup analysis of patients with successful recanalization was further performed . All statistics were computed using PQStat Software 1.8 . Statistical significance was set at P < 0.05 (two-tailed).Analyzed variables were presented as mean ± standard deviation (SD) or median (interquartile range) depending on the normality of the distribution. Categorical variables were presented as numbers (percentage). Univariate analyses were performed using chi-square or Fisher's exact test for dichotomous variables and 2-tailed One hundred thirty-two patients were included with a mean age of 70 ± 11 years, 67 (50.8%) females, and 15.4 ± 5.6 NIHSS score at admission. SICH was found in 11 (8.3%) and MBE in 31 (23.5%) cases. Six patients had an extracranial portion of ICA stenting and in 3 subjects decompressive hemicraniectomy was performed. Almost all of the reviewed patients (97%) experienced MAP decrease during EVT. Baseline characteristics and periprocedural hemodynamic measures were divided into subgroups according to the outcome measures (ICH and MBE) and presented in Among patients with sICH the higher rate of ICA occlusion , >40% drop of MAP compared to baseline , and higher increase of postprocedural MAP  and SBP  over their minimal intraprocedural values were observed . More thIn our cohort, the occurrence of MBE was significantly associated with the history of hypertension (P = 0.047), baseline NIHSS (P = 0.004), and intracranial ICA occlusion (P < 0.001). Periprocedural hemodynamic parameters associated with MBE were: higher baseline SBP (P = 0.036) and MAP (P = 0.033), intraprocedural maximal MAP decrease compared to baseline value calculated as the absolute value (P = 0.014), and a fraction of baseline MAP (P = 0.020), over 20% (P.049), >40% (P = 0.001) intraprocedural MAP decrease, and postprocedural SBP elevation (P = 0.037). After adjusting for potential confounders, the independent MBE predictors were: intraprocedural MAP decrease  and postprocedural SBP elevation .In the subgroup analysis of patients with successful recanalization, >40% intraprocedural MAP drop was the only hemodynamic variable found to be independently associated with the risk of MBE . Interestingly, intraprocedural MAP decrease from its baseline value measured as absolute and percentage drop from its baseline value remained an independent risk factor of MBE occurrence in the cohort with complete reperfusion , but not in subgroups of only partial (TICI 2a and 2b) or unsuccessful reperfusion.In the cohort of final TICI ≥ 2b, postprocedural SBP and MAP elevation were independent risk factors of sICH .Both sICH and MBE were associated with poor long-term functional outcomes and higher mortality .Selected hemodynamic variables according to primary outcome parameters (sICH and MBE) were presented graphically in We found that BP variations during MT treatment are associated with serious hemorrhagic and edematous early treatment complications. The intraprocedural MAP drop compared to its baseline value was an independent predictor of MBE and its over 40% decrement of both MBE and sICH occurrence. Postprocedural MAP elevation was associated with higher rates of sICH, and a rise in SBP with sICH and MBE incidence. The association of higher post-EVT BP values with those treatment complications stays in line with data from previous studies , 11.Hemorrhagic transformation after EVT most probably results from the blood flow restoration in the settings of blood-brain-barrier (BBB) disruption and increased tissue permeability due to previous ischemic endothelial injury , 12. It We found that large (>40%) MAP decreases during MT treatment are associated with higher rates of sICH in our entire cohort, but not in the subgroup with successful reperfusion. This may be explained by the observation that post-treatment TICI 2b-3 score significantly reduces the risk of sICH and it could potentially mitigate the hypoperfusion effect . DiffereCED is a natural sequela of brain ischemia that primarily results from tissue necrosis (cytotoxic edema), but can also be the EVT complication secondary to the reperfusion syndrome or HT . Larger The weakness of our analysis is that we did not assess FIV. It is, therefore, impossible to differentiate between MBE being a result of larger infarct size or its other pathophysiological causes: reperfusion injury and HT. The finding of postprocedural SPB elevation being independently associated with MBE occurrence might suggest the role of reperfusion syndrome in its formation. However, this association did not reach statistical significance in the subgroup of patients with successful recanalization. The importance of reperfusion syndrome may be further underlined by the observation of several parameters of intraprocedural hypotension impact on MBE occurrence in the cohort of complete reperfusion, but not in the subgroups with only partial (TICI 2a and 2b) or unsuccessful reperfusion. This may suggest that patients with blood pressure decreases during MT treatment who achieved the treatment goal (full recovery of blood supply) may be at the greatest risk of MBE formation. Due to the limited number of included patients, our study probably does not have enough statistical power to fully evaluate those effects.According to the literature, other factors that were found to be the post-EVT MBE predictors were unsuccessful recanalization, intracranial ICA occlusion, poor collateral status, and higher values of post-treatment BP , 18. BP Limitations of our study include the retrospective design and small sample size, with a potential for selection bias. Second, there was no protocol for periprocedural blood pressure maintenance that resulted in larger BP drops than those reported in other studies with a similar design . This miIn conclusion, MAP decrease during EVT compared to pre-treatment value is associated with MBE occurrence in the anterior circulation LVO cohort. Patients with large, over 40% MAP drop are at higher risk of sICH, but this effect is probably mitigated by the successful recanalization. Post-treatment elevation of SBP and MAP is the independent risk factor for sICH. Further evaluation of these effects is much needed to establish the optimal blood pressure targets in order to avoid serious treatment complications and improve outcomes.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 Bioethics Committee of the University of Rzeszow. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.MW designed the study, performed the analytic calculations, and wrote the manuscript. MS, KW, and HB-P collected data, discussed the results, and contributed to the final manuscript. All authors contributed to the article and approved the submitted version.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.


Cardiovascular diseases (CVDs) are the leading causes of mortality worldwide, accounting for nearly 18 million deaths per year. Among other considerations, treating CVDs requires better understanding their risk factors. Sleep-disordered breathing, especially obstructive sleep apnea (OSA), is a likely contributor to several CVDs. We review key epidemiological data that addresses the link between OSA and cardiovascular outcomes such as hypertension, atrial fibrillation (AF), stroke, atherosclerosis, and heart failure (HF), and proposed pathophysiological mechanisms underlying this association. There are several biological pathways linking OSA and an increased propensity to cardiovascular diseases, and we discuss the evidence on the benefits of treatments of OSA on the prevalence of cardiovascular complications. This phenomenon reduces or prevents airflow and causes frequent arousals, and has several metabolic and physiological consequences3. The diagnosis of OSA is ideally made using overnight polysomnography (PSG) with 12 recording channels and specialized professional observation and data analysis, although there are lower cost alternatives, such as portable monitoring devices, that are also validated diagnostic methods4. The severity of OSA is determined by the number of apneas and hypopneas per hour of sleep and is quantitated using the apnea-hypopnea index (AHI) (see Obstructive sleep apnea (OSA) is the most common type of sleep-disordered breathing, and is characterized by repetitive partial or complete collapse of the upper airways during sleepAHI) see .5. Although the comorbidities and risk factors for these conditions are numerous and diverse, OSA frequently occurs in patients with CVDs, in part, due to the global epidemic of obesity8. The metabolic syndrome (MS) is one of the most important risk factors for the development of OSA (OR=2.87/95%CI=2.41 3.42)8. The MS is an umbrella term describing a constellation of conditions, such as obesity, hypertension, insulin resistance, and hyperlipidemia that not only increases the risk of OSA but also of CVDs9.Cardiovascular diseases (CVDs) are the leading causes of mortality worldwide, accounting for nearly 18 million deaths per year. Common CVDs include functional abnormalities in the cardiac and vascular system that can result in heart failure, strokes, arrhythmias, atherosclerosis, hypertension, and cardiac ischemiaEven though OSA and cardiovascular outcomes often present in partnership, their association can reflect either a cause/effect relationship or as different endpoints having similar risk factors. The coexistence of these conditions does not prove causality, and potential confounding variables should be considered. In addition, treating OSA can also effect the prevalence of CVDs. This review summarizes our current understanding of the relationship between sleep apnea and CVDs based on current evidence.10. Intrathoracic pressure becomes very negative during apneas, and increases right heart volume due to a greater venous return11. The substantial changes in ventricular transmural pressure increases cardiac wall stress (afterload) and atrial enlargement, leading to cardiac remodeling and arrhythmias16.OSA is associated with a multitude of cardiovascular pathological mechanisms see . Sleep a20. This phenomenon generates shear stress and, combined with hypoxia, leads to dysfunction of the vascular endothelium10. The combination of hypoxia and enhanced sympathetic nerve activity increases myocardial oxygen demand, cardiac ischemia and atrial fibrillation22.OSA is also associated with increases in oxidative stress, which contributes to atrial remodeling and arrhythmic pathologies. Sleep apnea promotes the production of systemic inflammatory proteins and the activation of the sympathetic nervous system by cyclical arousals, leading to swings in blood pressure (BP) and heart rate in patients with OSA24. However, activation of the sympathetic nervous system and increases in blood pressure in patients with OSA are not restricted to the sleep state, but can also occur during wakefulness, and can trigger left ventricular systolic dysfunction27. These OSA induced stressors generate long-t erm electrical and mechanical remodeling of both atria and ventricles, and eventually can lead to heart failure31, although the onset of heart failure can also increase vulnerability to OSA31. Patients with heart failure accumulate fluid in the lower limbs during the day while in an upright position; this increases venous return when they lay down to sleep, resulting in rostral fluid redistribution and neck edema that exacerbates OSA10.The augmented sympathetic nerve discharge increases BP in individuals with OSA during sleep, which is in contrast to nocturnal decreases that usually occur in those without OSA32. Consequently, OSA also predisposes cerebrovascular accidents, as many of the risk factors for stroke  are increased in OSA patients33.Atherosclerosis is an important cause of myocardial infarction that can also lead to heart failure. OSA can contribute to atherosclerosis via multiple mechanisms such as increased oxidative stress, systemic inflammation, vascular smooth cell/lymphocyte activation, augmented adhesion molecule expression, enhanced lipid accumulation by macrophages, and endothelial dysfunction35. The overactivation of the sympathetic system leads to reduced secretion of insulin and hyperglycemia as well, especially due to a reduction of pancreatic P-cell metabolism35.An added factor is that intermittent hypoxia increases insulin resistance due to decreases in the phosphorylation of tyrosine kinases and the effectiveness and sensitivity of insulin receptors36.Importantly, the irregular and incomplete sleep patterns of OSA patients causes drowsiness during the day, weight gain, deposition of adipose tissue and ectopic fat, besides decreased activity and energy expenditure. These alterations exacerbate obesity, so aggravating dyslipidemia, insulin resistance and hyperglycemia, increasing the risk of developing cardiovascular diseases38. In patients with drug-resistant hypertension this number increases to 70%, with OSA being by far the most common secondary associated condition38. A longitudinal study that analyzed data from the Wisconsin sleep cohort study concluded that sleep-disordered breathing increased the risk of developing hypertension by ~3fold, even when confounding factors such as age, gender, body habitus, smoking, alcohol use, education, and physical activity were accounted for. Having higher AHI values strengthens the association between OSA and hypertension39. A recent systematic review and meta-analysis reported a significant association of essential hypertension with mild , moderate  and severe OSA 40. For studies comparing OSA and non-OSA participants, the pooled OR was 1.80 39. Finally, there is a pooled OR of 2.84  in six studies that explored the association between OSA and resistant hypertension40.The association between OSA and systemic arterial hypertension is a subject of intense investigation. OSA and hypertension often coexist, with the prevalence of OSA in hypertensive patients varying between 30-50%41. Two alternative hypotheses could be the different phenotypic expression of sleep apnea related to the proportion of mixed and central apneas, which can impact the underlying pathophysiology, and the co-existence of other medical conditions affecting the interaction between OSA and systemic hypertension in the elderly42.It is important to note that no significant association was reported between hypertension and OSA in patients aged 60 years, although the reasons for this are unclear. It could be related to a selection bias and the cross-sectional nature of the studies44, as both conditions share several risk factors such hypertension, congestive heart failure, and coronary artery disease, hampering the determination causal relationships44. Multivariate analysis reports a strong independent association between the odds of having OSA and developing AF (OR=2.2)45. A multicenter cohort study reports that the chances of developing cardiac arrhythmias are three times greater in patients with OSA compared to patients with no sleep-disordered breathing 46. The strength of the proposed causal link is strengthened by a meta-analysis indicating that AF is prevalent in OSA patients 47.Atrial fibrillation (AF) occurs frequently in patients with OSA48. Reversal of AF reversal is associated with an increased risk of recurrence of AF after one year  in those untreated for OSA49.Higher AHI scores increase the susceptibility to AF, with an odds ratio of 2.91 in men with an established OSA diagnosis43. A recent prospective cohort study of patients with AF reported an OSA prevalence of 85%, which is significantly higher than the prevalence of 18.2 % reported in other studies51. One reason for these differences in prevalence of AF may be that OSA may be under-recognized in some arrhythmic patient groups, as patients with cardiac arrhythmias are not routinely screened for OSA51.The higher prevalence of OSA in patients with AF also suggests that sleep apnea could initiate and perpetuate arrhythmias55. A meta-analysis of 12 prospective cohort studies  suggests an increased risk (2.15 greater) of incident fatal and non-fatal strokes in patients with severe OSA56. Another meta- -analysis also supports this assertion, even after adjustment for confounding factors such as age, sex, BMI, diabetes, hypertension, coronary artery disease, previous coronary artery intervention, heart failure, smoking, alcohol use and dyslipidemia 55.Recent studies propose OSA as an independent risk factor for cerebrovascular diseases, and it is estimated that 3070% of people who have suffered a stroke also have OSA57. Taken together, these results indicate an enhanced risk of stroke in patients with OSA that occurs independently of other risk factors and which is related to OSA severity. The absence of effective OSA treatments can have a detrimental effect on stroke risk57.The relationship between OSA and stroke was also highlighted by a meta-analysis of 10 prospective studies showing that OSA was associated with a ~2.1-fold higher risk for fatal or non-fatal stroke, increasing to a ~6.4-fold higher risk in untreated patients (AHI>10 events/hour) over a median of 6.8 years of follow-upp=0.01) greater risk of non-calcified/mixed plaques independent of other risk factors, so increasing their vulnerability to acute coronary syndrome58.Coronary computed tomography angiography images indicate that the severity of OSA increases both non-calcified/ mixed coronary plaques and total arterial stenosis scores. Patients with severe OSA have 3.8- times , similar risk factors (obesity and comorbid conditions), AHI cutoff, and severity of HF62.Patients with heart failure (HF) frequently report sleepdisordered breathing, and pathophysiological links between these conditions lead to decompensation of heart failure in OSA patients61. This association is reinforced by two different studies of patients with OSA confirmed by polysomnography63. These studies report that 21% of individuals with HF and preserved ejection fraction (HFpEF) have OSA, 11% of individuals with HF and reduced ejection fraction (HFrEF) have OSA, and 7.7% of all OSA patients have left ventricular ejection fraction <50%63. Despite the positive findings proposing a strong association between OSA and HF, large RCTs with longer follow-up periods have not been reported.A cross-sectional analysis of 6,424 adults from the Sleep Heart Health Study indicates that OSA is associated with a 2.38 increase in the relative odds of presenting with HFThe current gold-standard treatment for OSA is the continuous positive airway pressure (CPAP) device, which consists in a mask that is attached to a pump that forces air into the upper airways through the nasal passages. The continuous pressure during both inspiration and expiration must be sufficient to overcome the structural obstruction in the upper airways. The majority of studies of OSA treatment is based on interventions with CPAP see , althoug79. There are many advantages of CPAP treatment in preventing atherosclerosis, although RCT studies and metaanalysis are needed to investigate changes in blood pressure and inflammatory markers by CPAP.There is much evidence that CPAP reduces blood pressure and AF progression/recurrence in patients with OSA, but the benefits of CPAP in stroke (risk and/or progression) is unclear91. The reported amelioration of HF in RCTs should thus be evaluated with caution. The improvements noticed with CPAP therapy were assessed by measuring fatigue, drowsiness and humor, with no analysis of exercise capacity or shortness of breath (dyspnea). Improvements in the latter markers would better characterize improvements in cardiac insufficiency resulting from HF in OSA.Most studies on the impact of CPAP on LVEF and other cardiac markers in HF are 1-3m onths in duration70.Despite some positive results, additional studies are still needed to access the benefits of CPAP on preventing CVD development and progression. Results may vary in their findings of CPAP benefits, likely due to differences in sample sizes, study designs, confounding variables, gender, OSA diagnostic methods, and variability in the duration and compliance of the CPAP treatments78. These results suggest that CPAP therapy should not be used as a primary treatment for protection against CV events or reducing mortality78, and also supported by a more recent systematic review of the poor efficacy of CPAP therapy in reducing cardiovascular risk92. Nevertheless, it is important to note that there are other benefits of CPAP therapy, such as improvements in sleep quality and daytime function, in patients with cardiovascular diseases93. In addition, it must be recognized that the patients in the SAVE study were in general not sleepy and CPAP adherence was low; these may have also contributed to the null results95.The sleep apnea cardiovascular endpoints (SAVE) study, an international, multicenter, randomized trial evaluated the long-term benefits of CPAP on cardiovascular events in 2,717 OSA patients. CPAP and control groups were matched for age, gender and BMI. The SAVE study reported that CPAP treatment failed to improve cardiovascular outcomes and did not prevent progression to more chronic conditions such as heart failureThe literature describing the effects of lifestyle changes on cardiovascular outcomes and OSA is scarce and inconclusive. Despite overall favorable improvements in measures of sleep apnea, possible benefits of CVD in OSA are unclear except for reductions in blood pressure in such patients. Studies of the comparative, additive or independent benefits of weight loss and lifestyle modifications in obese OSA patients with cardiovascular comorbidities are unavailable. It is likely that improvements were likely related to the direct effects of lifestyle modifications on CVD outcomes rather than on reducing the impact of OSA on cardiovascular pathologies. Nevertheless, the clinical benefits of reductions of blood pressure and OSA parameters  due to lifestyle modifications have not been reported in RCTs with long follow-up periods.113. Potential reasons for this may be that some studies failed to adjust for the use of antihypertensive medications, had differences in outcomes such as UPPP success rates and frequency of blood pressure measurement . Importantly, the majority of studies were case reports or cohort studies with limited sample sizes.Studies on the effects of uvulopalatopharyngoplasty (UPPP) on blood pressure report mixed results115. Renal sympathetic denervation (RSD) shows promising effects on reducing AF115, possibly due to reductions of arrhythmogenic atrial autonomic, structural and electrical remodeling; RSD is as efficient as combined therapy with beta-blockers and angiotensin receptor blockers116. These findings are mostly from isolated pre-clinical animal studies; clinical studies in OSA populations are needed to establish RSD as an alternative approach.Several recent publications report some benefits of surgical procedures on AF116, although a cohort study reports that oral appliances are as effective as CPAP in reducing cardiovascular death (HR=1.08)108, although this is inconsistent with other findings that show that CPAP does not alter cardiovascular mortality92.The positive outcomes of oral appliance therapy (OAT) in the treatment of OSA are mostly inconclusive. Comparative studies on cardiovascular outcomes using different therapies for OSA are relatively scarce119, as they were based on the findings using relatively short follow-up periods (1-3 months) with small patient sample sizes109.Although small reductions in blood pressure are important (every 5mmHg reduction in the mean systolic BP reduces cardiovascular risk by 17%), the minor reductions observed in many studies using alternate therapies for OSA (ranging from-0.07 to-0.77mmHg) may have limited clinical impact107. Only few studies evaluated the effects of OAT circulating cardiovascular biomarkers of OSA119; these studies were generally underpowered and evaluated a variety of outcomes, such as oxidative stress parameters  and inflammatory markers . More extensive studies are needed to elucidate the effects of OAT on circulating cardiovascular biomarkers of OSA and their clinical relevance to atherosclerosis and cerebrovascular disease. The evidence describing the therapeutic potential of OAT on CVD outcomes in OSA is still at its infancy. Additional studies directly comparing cardiovascular event rates are important, but will probably require RCTs with large patient groups and also long-term follow-up studies.Two studies reported improvements in arterial stiffness and endothelium function with OATOur understanding of OSA and its association with CVDs continues to evolve. This brief survey of the literature indicates that OSA both predisposes to and aggravates hypertension, atrial fibrillation, and cerebrovascular disease. The relationship between OSA and atherosclerosis and HF, while being plausible, needs more extensive investigation. It is difficult to establish a causal effect of OSA on CVDs, as these are related in a multidirectional manner. Future studies should focus on risk stratification of OSA patients related to adverse cardiovascular outcomes. Studies to identify new OSA-specific biomarkers of cardiovascular risk are needed.Additionally, there is a need for large-scale, randomized, well-controlled studies on the effects of CPAP on cardiovascular diseases such as hypertension, atrial fibrillation, stroke, atherosclerosis, and heart failure that are unhindered by issues of poor compliance.There are only a few studies on the modest benefits of alternative therapies for OSA on reducing CVDs in OSA. The clinical benefits of surgical treatment of OSA on CVD in OSA are unclear. Lifestyle changes can improve sleep-apnea parameters and hypertension. However, the degree of their influence (additive or independent) and whether these changes are clinically relevant is unclear. Oral appliances likely reduce blood pressure, atherosclerosis and stroke in OSA, but more rigorous large scale RCTS are needed. Long-term populational studies that directly compare cardiovascular event rates with different management protocols of OSA would be informative.


Recent guidelines recommended a systolic blood pressure (SBP) target of < 130 mmHg for patients with or without diabetes but without providing a lower bound. Our study aimed to explore whether additional clinical benefits remain at achieved blood pressure (BP) levels below the recommended target.We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) among the non-diabetic population and the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial among diabetic subjects. We used the propensity score method to match patients from the intensive BP group to those from the standard group in each trial. Individuals with different achieved BP levels from the intensive BP group were used as “reference.” For each stratum, the trial-specific primary outcome , acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure (HF), or cardiovascular death for SPRINT; non-fatal MI, non-fatal stroke, or cardiovascular death for ACCORD-BP) was compared by Cox regression.A non-linear association was observed between the mean achieved BP and incidence of composite cardiovascular events, regardless of treatment allocation. The significant treatment benefit for primary outcome remained at SBP 110–120 mmHg  and SBP 120–130 mmHg for SPRINT  but not for ACCORD-BP . The results were similar for the secondary outcomes including all-cause mortality, cardiovascular mortality, MI, stroke, and HF. Intensive BP treatment benefits existed among patients maintaining a diastolic BP of 60–70 mmHg but were less distinct.The treatment benefit persists at as low as SBP 110–120 mmHg irrespective of diabetes status. Achieved very low BP levels appeared to increase cardiovascular events and all-cause mortality.The online version contains supplementary material available at 10.1186/s12916-022-02407-z. Numerous studies have shown that lowering blood pressure (BP) in patients with hypertension reduces the risk of BP-related adverse outcomes , 2. HoweThe results from the analyses of achieved BP in clinical trials and in observational studies have been commonly used to set the BP treatment targets among patients with or without diabetes mellitus –12 or coPartially overlapping achieved BP levels from SPRINT and ACCORD-BP trials provided a unique opportunity to investigate the treatment effects among patients with similar but low achieved BP levels . Therefore, in the current study, we employed the propensity score method to match patients with different achieved BP levels from the intensive BP group (“reference”) to those from the control group in two randomized clinical trials. On the basis of these comparable data across the groups, our study aimed to explore the optimal achieved BP range to reduce major cardiovascular events in hypertensive patients with or without diabetes.The current study is a post hoc analysis of limited-access SPRINT  and ACCOIn general, both studies are similar in terms of their study design  and treatment algorithms. However, the most notable difference is in the patient populations, with the absence of patients with diabetes in SPRINT and the inclusion of patients with diabetes in ACCORD-BP. Details of the inclusion and exclusion criteria are shown in Additional file BP was measured while the participant was seated with the same oscillometric device  in both trials. However, an observer remained present during the BP measurements in the ACCORD-BP trial, unlike in the SPRINT trial. BP measurements were taken monthly in the first 3 months and every 3 months thereafter in the SPRINT trial. In the ACCORD-BP trial, patients allocated to the intensive treatment group were seen every month for 4 months and every 2 months thereafter. In the standard treatment group, visits were scheduled at 1 and 4 months and then every 4 months thereafter.Achieved BP was calculated by averaging the BP values measured from the 6-month visit until the visit before an event or their last visit. We chose the 6-month visit because of the stability of BP values after this visit. Patients were categorized into 4 prespecified strata of achieved BP: < 110 mmHg, 110 to 120 mmHg, 120 to 130 mmHg, and ≥ 130 mmHg for SBP and < 60 mmHg, 60 to 70 mmHg, 70 to 80 mmHg, and ≥ 80 mmHg for diastolic BP (DBP).The original primary outcomes for the SPRINT and ACCORD-BP trials were adopted in our analysis. For the SPRINT trial, this was a composite outcome of myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure (HF), or cardiovascular death. For the ACCORD-BP trial, the primary outcome was non-fatal MI, non-fatal stroke, or cardiovascular death. The secondary outcomes in our analysis included cardiovascular death, MI, stroke, HF, and all-cause mortality. A committee blinded to the treatment assignment adjudicated the clinical outcomes in each trial.We used the propensity score method with replacement to match each patient in the intensive treatment group with a patient in the standard treatment group with similar baseline characteristics. This is to account for potential confounding attributable to the differences in baseline characteristics for each achieved BP stratum in the intensive treatment group with their counterpart in the standard treatment group. A multivariable logistic regression model with the baseline variables shown in Table We used the Cox model to calculate the treatment effect according to each achieved BP stratum, with a robust variance estimator to account for the clustering within matched sets. The incidence rate of each clinical outcome for each trial (events per 100 patient-years) after 6 months is summarized. To further explore the relationship between achieved BP and primary outcome in both trials, we employed spline analysis within the Cox regression model among the intensive BP control group, which included SBP and DBP as natural cubic splines to account for a continuous non-linear functional dependence. We specified 140 mmHg and 90 mmHg as the reference value for SBP and DBP, respectively. Spline knots were placed at the 10th, 30th, 70th, and 90th centiles of the overall distribution of SBP and DBP.We also performed a series of sensitivity analyses including repeated analysis for the secondary outcome and the unmatched analysis  to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of treatment effect within each achieved BP stratum. All analyses were performed using STATA version 15.0 (Stata Corporation).Tables A non-linear relationship between achieved BP and incidence rate of primary outcome was found in both trials with a higher incidence rate at higher and lower BP values, particularly among the intensive treatment group Fig. . For theThe results from individual cardiovascular events and mortality as well as the unmatching analysis  generally confirmed the findings for the primary outcome, especially for the achieved BP at 110–130 mmHg for SBP and 60–80 mmHg for DBP  events, which was supported by a spline analysis in the intensive treatment group. A similar pattern was observed for achieved DBP at 60–70 mmHg in both SPRINT and ACCORD trials, although achieved DBP values had diverse benefits for different outcomes. There was no apparent excess risk of adverse events in patients who achieved SBP at 110–130 mmHg and DBP at 60–80 mmHg from available SPRINT trial safety data.Analysis based on the achieved BP, in comparison with the randomized BP target as per the intention-to-treat principle, is attractive and has commonly been used to set BP treatment targets , 16, 17.Although researchers argued that inadequate perfusion of organs from very low BP would result in a higher rate of adverse outcomes, treatment might offer additional protection at some level of low BP. In our current analysis, we demonstrated that the benefit of the intensive SBP lowering could exist at achieved SBP (110–130 mmHg) or DBP (60–80 mmHg) but might be associated with a higher risk of CVD outcome or mortality for very low achieved BPs (< 110 mmHg or < 60 mmHg). These findings persisted in our sensitivity analyses without matching and for our secondary outcomes . Our results were generally in line with a recent large-scale analysis of 48 randomized trials showing that drugs to lower BP are similarly effective for primary and secondary prevention of major cardiovascular disease over the whole BP range, even if BP is in an apparently healthy range (< 120 mmHg) , regardlAlthough our study confirmed the prior findings of the non-linear association  between achieved BP and incidence of the combined CVD events, there are several strengths in our study including the assessment of the treatment benefit from achieved BPs  with their matched comparators rather than solely relied on the BP-CVD risk association. This study also has some limitations. First, the sample size and the number of events in the subgroups with the lowest achieved SBP (< 110 mmHg) were small, which prevent us to reveal a conclusive association between the groups among this stratum. Second, this is a post hoc analysis of two clinical trials data; thus, the results from our analyses based on post-randomized data (such as achieved level of BP) may still be subject to residual confounding and reverse causality. Third, selection bias may occur due to matching but our unmatching analysis provided consistent results with those from propensity score matching analysis. Finally, different methods were used to measure BP in SPRINT and ACCORD-BP. Studies have shown automated BP measurements performed in the absence of an observer could yield significantly lower SBP and DBP values compared with conventional BP measurements , 29. HowOur analysis revealed that the treatment benefit persists at as low as SBP 110–120 mmHg irrespective of diabetes status. Achieved very low BP levels appeared to increase cardiovascular events and all-cause mortality.Additional file 1: Table S1. Inclusion and exclusion criteria of SPRINT and ACCORD trial. Table S2. Characteristics of patients in the intensive blood pressure control group and propensity score-matched patients from the standard blood pressure control group across the achieved diastolic blood pressure strata in the SPRINT trial. Table S3. Baseline characteristics of patients in the intensive blood pressure control group and propensity score-matched patients from the standard blood pressure control group across the achieved diastolic blood pressure strata in the ACCORD trial. Table S4. Mean standardized difference for all of the covariates used in the propensity score-matched method. Table S5. Incidence (per 100 person-years) of serious adverse events in the intensive and standard blood pressure control groups across achieved SBP and DBP strata . Fig. S1. Data exclusion in the present analysis. Fig. S2. The standard difference in the means of each covariate used in the propensity score-matched method in the SPRINT trial. Fig. S3. The standard difference in the means of each covariate used in the propensity score-matched method in the ACCORD trial. Fig. S4. Incidence rate and HRs in the intensive and standard blood pressure control groups across Achieved SBP and DBP strata for the major coronary events and all-cause death.


The TOPVAS study provides information on current kidney graft and patient survival, eGFR trajectories, and rejection rates, as well as infectious and surgical complication rates under different immunosuppressive drug regimens. More importantly, it provides an extensive and well-characterized biobank for the future discovery and validation of prognostic methods.Kidney transplantation is the preferred method for selected patients with kidney failure. Despite major improvements over the last decades, a significant proportion of organs are still lost every year. Causes of graft loss and impaired graft function are incompletely understood and prognostic tools are lacking. Here, we describe baseline characteristics and outcomes of the non-interventional Transplant Outcome Prediction Validation Study (TOPVAS). A total of 241 patients receiving a non-living kidney transplant were recruited in three Austrian transplantation centres and treated according to local practices. Clinical information as well as blood and urine samples were obtained at baseline and consecutive follow-ups up to 24 months. Out of the overall 16 graft losses, 11 occurred in the first year. The patient survival rate was 96.7% (95% CI: 94.3–99.1%) in the first year and 94.3% (95% CI: 91.1–97.7%) in the second year. Estimated glomerular filtration rate (eGFR) improved from 37.1 ± 14.0 mL/min/1.73 m The incidence and prevalence of kidney disease is increasing globally . Kidney Today, different immunosuppressive drug regimens have been established to prevent acute and chronic rejection and are adjusted to the expected immunological rejection risk. Patients with a low-risk for rejection have few to no HLA-mismatches and are non-sensitized prior to organ or tissue transplantations . GlucocoAllograft loss and rejection can be further reduced using a T-cell depleting and modulating induction therapy ,15,16. WTOPVAS is a two-part non-interventional national multicenter study in patients undergoing a first or second deceased donor kidney transplant. In the observation part of the study, a prognostic panel of molecular biomarkers was derived from a set of transcriptomic profiles from zero-hour transplant kidney biopsies of 72 transplant recipients and correlated with clinical follow-up data to predict graft survival . In the Patients over the age of 18, awaiting their first or second kidney transplant and with a panel reactive antibody frequency below 10% were informed about the study, and written informed consent was obtained. Patients were included in the study when none of the following exclusion criteria were met: Immunosuppressive regimen not containing either Tacrolimus or MMF at three months after transplantation, multi-organ, and living donor transplantation. Due to the non-interventional design, patients were eligible to participate in other prospective randomized trials.The primary endpoint for the non-interventional prospective cohort study within TOPVAS is kidney transplant outcome  as well as validating the prognostic potential of candidate biomarkers, utilizing models of kidney transplant outcome derived from the first part of the study. Secondary outcomes are the incidence of clinically suspected and treated and/or biopsy proven acute and/or chronic rejection, delayed graft function, infections , post-transplant diabetes mellitus (PTDM), and surgical complications potentially affecting allograft function. A Major Adverse Cardiovascular Event (MACE) was defined as non-fatal myocardial infarction, heart failure, non-fatal stroke, peripheral amputation, or death due to cardiovascular disease. A non-functioning kidney graft was defined as dialysis dependence or creatinine clearance ≤ 20 mL/min at 3 months post-transplantation.In order to report all data accurately, completely and transparently, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiatives recommendations were followed . The basThe study was conducted in accordance with the World Medical Association Declaration of Helsinki. Written informed consent was obtained from each study participant prior to study, inclusion using a standardized patient information and consensus form according to Good Clinical Practice (GCP) guidelines, and the study protocol was approved by the ethics committees of the Innsbruck Medical University (Study ID AN2015-0101 348/4.25 357/5.15 (3745a)), Vienna Medical University (Study ID 1619/2015), and Upper Austria (Study ID E-38-15), prior to study initiation. All patient associated information was managed entirely coded. Data collection was conducted using an electronic evaluation form (case report form) according to GCP recommendations. All patient samples as well as clinical data are subject to privacy protection, according to the current European General Data Protection Regulation, the Health Insurance Portability and Accountability Act (HIPAA), and Research Ethics Board guidelines and recommendations.The baseline characteristics of patients at time of transplantation are shown in In this study, glomerulonephritis was the leading cause for renal replacement therapy , followed by type 2 diabetic kidney disease , hypertensive kidney disease , and hereditary kidney disease , details are provided in Donor characteristics are summarized in In total, no mismatches were present in 16 (6.64%) patients, one in 14 (5.81%) patients, two in 37 (15.35%) patients, three in 86 (35.68%) patients, four in 57 (23.65%) patients, five in 18 (7.47%) patients, and six in 12 (4.98%) patients. Details on the immunosuppressive regimen are shown in n = 18), followed by lymphoceles (n = 10), as well as ureter necrosis and leakage .Details on relevant clinical outcomes are given in Infections with cytomegalovirus and BK-Viruses occurred mainly during the first year after transplantation. Among 94 CMV infections that were first documented after transplantation, 71 (75.5%) occurred in CMV seropositive recipients (164 patients), while 23 (24.5%) occurred in previously CMV seronegative recipients (77 patients). Thus, 46% of seropositive recipients and 29.87% of previously seronegative recipients developed a CMV infection during the follow-up period. Out of 23, 21 (91.3%) CMV seronegative recipients developing a CMV infection post transplantation received an allograft from a seropositive donor. The majority of post-transplant CMV infections were purely serology-confirmed, only three patients had clinically active CMV disease. Fortunately, no kidney grafts were lost due to CMV- or BK Virus-related infection. The death-censored CMV infection-free survival probability was 65.1% (95% CI: 58.8–71.9%) in the first year and 55.5% (95% CI: 49.0–63.0%) in the second year after transplantation . The deaPTDM was diagnosed mostly in the first year after transplantation. In total, 13 patients suffered a non-lethal MACE in the follow-up period: Five patients had a heart failure episode and five patients experienced myocardial infarction, three patients were not further specified.There is a trend towards an increase in newly diagnosed malignant diseases over the course of the study.Post-transplant dialysis was required in 90 (37.34%) patients and 9 (3.73%) patients remained with a non-functioning kidney graft, see Selected laboratory and clinical data are depicted in Patients receiving their first or second kidney transplant in one of three Austrian transplant centres  were recruited and followed for two years in the prospective observational, non-interventional, national, multicenter TOPVAS study. Here, we present the baseline characteristics and clinical outcomes of 241 kidney allograft recipients that were primarily treated with a Tacrolimus and MMF containing immunosuppressive regimen.Data on patient and graft survival as well as other clinical outcomes  are provided for the first two years after transplantation. Based on the recruitment method and study design these data are highly representative for daily clinical practice. Today, kidney transplant recipients in industrialized countries are included in large clinical registries like the Austrian Dialysis and Transplantation registry or the United States Renal Data System (USRDS). However, clinical data included in these databases are often limited due to administrative demand. Therefore, the present study provides additional clinical information for patients in the first two years after kidney transplantation receiving an immunosuppressive drug regimen primarily based on Tacrolimus and/or MMF. Due to the non-interventional study design, immunosuppression was adjusted according to the clinical requirements and circumstances . Several studies have been investigating different immunosuppressive drug regimens and dosages to improve kidney graft and patient survival. Foremost, the Efficacy Limiting Toxicity Elimination (ELITE)-Symphony Trial offered important clinical insights into different immunosuppressive drug regimens including Tacrolimus/MMF after one and three years ,32. ImmuCompared to unadjusted USRDS and European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Registry data, death-censored graft survival probability in the first year after deceased donor kidney transplantation is higher in our study population  . HoweverWhile 75.5% of post-transplant CMV infections occurred in previously CMV seropositive recipients, 24.5% of CMV infections were found in previously CMV seronegative recipients, predominantly resulting from seropositive donor allografts (21 of 23 cases). This is in line with data reported in the literature . CMV proPTDM is a serious complication as it may fuel kidney function decline by the development of diabetic kidney disease, and poses as an additional risk factor for metabolic disorders and infections . FurtherCardiovascular disease is one of the major causes of death in the kidney transplant recipient population ,54. The Compared to data regarding the primary disease leading to dialysis in the Austrian Dialysis and Transplantation registry, patients with glomerulonephritis are overrepresented and patients with vascular or diabetic kidney disease are underrepresented in this study . In the The previously described disparity of men and women in the access to deceased donor kidney transplantation might also account for the present study population, as significantly more men received a kidney transplant ,58.The initial minimal recruitment count was met; however, more patients dropped out and were lost to follow-up than expected, being a limitation of the current study. The phenomenon of many patients choosing to perform follow-up visits at the outpatient nephrology clinic of their local hospital, instead of the transplant centre, may serve as a potential explanation. The data of these respective follow-up visits was not available for further work-up and inclusion in the study. To account for this attrition bias, we provided the number of all active patients at the time of visit.This study was carried out before the SARS-CoV-2 pandemic. Current outcome data of transplant recipients infected with SARS-CoV-2 is conflicting: The majority of studies show a high mortality rate in transplant recipients hospitalized due to COVID-19, especially in the first months after transplantation, and in the elderly ,60. HoweBesides therapeutic drug monitoring, different strategies to tailor the immunosuppressive therapy are currently under investigation. Several biomarker driven approaches for immunological and rejection monitoring already show promising results ,63,64,65Therefore, combining sophisticated bioinformatic models with clinical (outcome) data and multiomics approaches, based on biobanked human samples, all of which are available for the TOPVAS study population, might stimulate further research and enable us to enter the age of precision transplantation medicine by individualizing (immunosuppressive) transplant recipient management.


Existing obesity- and lipid-related indices are inconsistent with metabolic syndrome (MetS) in chronic kidney disease (CKD) patients. We compared seven indicators, including waist circumference (WC), body mass index (BMI), visceral fat area (VFA), subcutaneous fat area (SFA), visceral adiposity index (VAI), Chinese VAI and lipid accumulation product (LAP), to evaluate their ability to predict MetS in CKD patients with and without Type 2 diabetes mellitus (T2DM) under various criteria. Multivariate logistic regression analysis was used to investigate the independent associations between the indices and metabolic syndrome among 547 non-dialysis CKD patients, aged ≥18 years. The predictive power of these indices was assessed using receiver operating characteristic (ROC) curve analysis. After adjusting for potential confounders, the correlation between VAI and MetS was strongest based on the optimal cut-off value of 1.51  and 2.35 , with OR values of 40.585 (8.683–189.695) and 5.076 (1.247–20.657) for males and females with CKD and T2DM. In CKD patients without T2DM, based on the optimal cut-off values of 1.806  and 3.11 , the OR values were 7.514 (3.757–15.027) and 3.008 (1.789–5.056) for males and females, respectively. The area under ROC curve (AUC) and Youden index of VAI were the highest among the seven indexes, indicating its superiority in predicting MetS in both male and female CKD patients, especially those with T2DM. Metabolic syndrome (MetS) is a group of syndromes characterized by cardiometabolic risks, including central obesity, elevated blood pressure, dysglycemia, elevated triglyceride levels and low high-density lipoprotein cholesterol (HDL-C) levels . As of 2Chronic kidney disease (CKD) is a global public health problem due to its high morbidity and mortality ,6. The gA number of studies have found that various obesity- and lipid-related parameters are highly correlated with MetS, which can be used to predict MetS. Body Mass Index (BMI) is traditionally the most widely used measure of obesity, but it fails in differentiating lean and fat masses . Waist CWe hypothesized that a simple, clinically measurable alternative could be used to identify MetS in people with CKD, especially those with type 2 diabetes. Therefore, our aim was to compare the predictive power of these 7 “optimal” obesity- and lipid-related parameters to identify MetS in Chinese male and female CKD patients with and without T2DM, based on different criteria.This cross-sectional study included 570 patients with CKD who were hospitalized in the Department of Nephrology of the First Medical Center of the Chinese People’s Liberation Army General Hospital between March and November 2021. Participants aged ≥18 years, diagnosed with CKD, and those with no missing biochemical measurements were included. Pregnant women, patients who are on dialysis , patients who are unable to perform visceral fat area testing due to multiple serous effusions and patients who omitted WC measurements were excluded. Finally, 547 non-dialysis CKD patients with anthropometric and clinical examination information were included in the analysis . This stVAI = WC (cm)/[39.68 + 1.88 × BMI (Kg/m2)] × [TG (mmol/L)/1.03] × [1.31/HDL (mmol/L)]Male: The information collected in this study included sociodemographic characteristics, medical history, family history, laboratory tests and visceral fat area. All practicing physicians who have been trained by Good Clinical Practice (GCP) and have passed the consistency evaluation assessment, collect and encode the clinical trial electronic data capture system (EDC) platform, and retrieve it after review and inspection by professionals. Anthropometric measurements, including weight, height, waist circumference, blood pressure and visceral fat area, were measured by professional researchers following standard protocols. The patients were asked to wear light clothing, and were barefoot when the weight and height were measured. Waist circumference was measured using a flexible plastic tape measure around the navel level after the patient exhaled. Visceral fat area and subcutaneous fat area were measured using an Omron Visceral Fat Detection Device . Blood pressure in the patient’s non-dominant arm was measured using automated electronic equipment, and after a 5-min rest, blood pressure was measured three times with a one-minute interval. The mean systolic and diastolic blood pressures of the three readings were recorded using a questionnaire. BMI was calculated as weight divided by height squared. The calculation of VAI , CVAI 1 and LAP CVAI = −267.93 + age (y) + 0.03 × BMI (Kg/m2) + 4.00 × WC (cm) + 22.00 × Lg TG (mmol/L) − 16.32 × HDL (mmol/L)LAP = [WC (cm) − 65] × TG (mmol/L)2.VAI = WC (cm)/[36.58 + 1.89 × BMI (Kg/m2)] × [TG (mmol/L)/0.81] × [1.52/HDL (mmol/L)]Female: CVAI = −187.32 + age (y) + 4.32 × BMI (Kg/m2) + 1.12 × WC (cm) + 39.76 × Lg TG (mmol/L) − 11.66 × HDL (mmol/L)LAP = [WC (cm) − 58] × TG (mmol/L)Venous blood was collected on the morning of the second day of hospitalization after the patient had fasted for 8–10 h, in order to determine fasting blood glucose (FBG), uric acid (UA), creatinine (Cr), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and other biochemical indicators. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation .2 (2) markers of kidney damage (1 or more); and urinary sediment abnormality, abnormalities on histology and history of kidney transplantation.According to international guidelines , CKD is T2DM was defined as previously diagnosed diabetes mellitus, use of insulin or hypoglycemic drugs, or fasting blood glucose ≥ 7.0 mmol/L.MetS was identified by the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020 Edition) , the revt-test, chi-square test or Mann-Whitney U test. Binary logistic regression analysis was used to determine the relationship between obesity- and lipid-related indices and the incidence of MetS. Data were summarized as odds ratios (ORs) and regression coefficients (95% CIs). Adjusted variables were diagnosed by collinearity, and the diagnosis was based on the following criteria: variance inflation factor (VIF) > 10 or tolerance around 0.1; condition index > 30; and variance ratio > 50%. Select variables are not collinear. Considering possible complete separation or quasi-complete separation , Firth’s bias-reducing penalized likelihood method was used for analysis.Data were tested for normality and homogeneity of variance before performing statistical analysis. Normally distributed measurement data were expressed as mean ± standard deviation (SD), while non-normally distributed data were expressed as the median of the interquartile range (IQR) . Comparisons between groups were performed using Student’s p values (two-sided) of <0.05.When performing binary logistic regression, adjustments were made for patients’ age, systolic blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol and eGFR. Receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic performance of obesity- and lipid-related indices for MetS. All statistical analyses were performed using IBM SPSS statistical software, version 25 . Differences were considered statistically significant at A total of 537 CKD patients participated in the basic analysis, including 372 male patients with an average age of 49.64 ± 13.78 years and 165 female patients with an average age of 51.96 ± 12.46 years. The prevalence of T2DM was 57.5% in males and 42.4% in females; while the prevalence of MetS in CKD patients with T2DM was 80.4% in males and 84.3% in females; and the prevalence of MetS in patients with CKD without T2DM was 50% in males and 27.4% in females.p < 0.05). In addition, only female patients with MetS had significantly higher SBP than those without MetS (p < 0.05), while there were no significant differences in other indicators between men and women (p > 0.05). Obesity and lipid-related parameters , clinical indicators  in MetS men and women in CKD patients without T2DM were higher than those without MetS , and only male patients with MetS had significantly higher DBP and FBG levels than those without MetS (p < 0.05), while there was no significant difference in other indicators between men and women (p > 0.05).According to the optimal cutoff value, BMI, WC, VFA, SFA, VAI, CVAI and LAP were significantly associated with MetS in all criteria. After adjusting for age, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and eGFR, using the criteria of the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020 Edition), the OR value of VAI was the largest among male and female CKD patients with T2DM, being 40.585 (95% CI 8.683–189.695) and 5.076 (95% CI 1.247–20.657), respectively. The OR value of VAI was also the largest among male and female CKD patients without T2DM, being 7.514 (95% CI 3.757–15.027) and 3.008 (95% CI 1.789–5.056), respectively . After ap < 0.05). Among them, the areas under the ROC curve of VAI in men and women CKD patients with T2DM were the largest, at 0.920 (p < 0.001) and 0.902 (p < 0.001), respectively. The maximum cut-off value of Youden’s index for men was 1.51, with a sensitivity of 86.84% and a specificity of 91.18%; the maximum cut-off value of Youden’s index for women was 1.806, with a sensitivity of 98.11% and a specificity of 72.73%. Among CKD patients without T2DM, the area under the ROC curve of LAP was the largest in male patients, but there was no significant difference with VAI, at 0.921 vs. 0.910 (p < 0.001), and the area under the ROC curve of VAI was the largest in female patients.p < 0.001). In the diagnostic criteria for IDF MetS, except for male patients without T2DM, the area under the ROC curve of CVAI was the largest at 0.980 (p < 0.001) and the area under the ROC curve of the other subgroups of WC was the largest, being 0.998, 1, 0.923 (p < 0.001), respectively.This study investigated the value of commonly used obesity- and lipid-related parameters, including BMI, WC, VFA, SFA, VAI, CVAI and LAP in identifying different criteria for MetS in the CKD population. Our results show that these parameters have reliable predictive accuracy for the diagnosis of MetS, according to the criteria of China (2020) and ATP III. Based on our findings, the VAI may outperform other parameters in predicting MetS. Among the IDF criteria, BMI had the best performance in diagnosing MetS. This is the first report to analyze and compare the use of different criteria to predict obesity- and lipid-related parameters of MetS in Chinese patients with CKD based on the presence and absence of T2DM.MetS has become a global problem with the influence of Western lifestyles, including fast food consumption and reduced physical activity due to a sedentary work culture ,26, and The MetS definition of the International Diabetes Federation (IDF) and the ATPIII standard updated by the American Heart Association/American Heart, Lung and Blood Association (AHA/NHLBI) in 2005 are the most recognized and widely used standards in the world, and are often used in China, particularly in clinical trials and research. Our China Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020 Edition) diagnostic criteria for MetS, which cut-off points for WC, HDL-C and hyperglycemia differed from IDF and NECP-ATPIII, may be more suitable for the Chinese population. In addition, an update to this guideline is already being published in 2022. According to this latest guideline , the eld2) and 485 Chinese people. It has been reported in the literature [Obesity, especially central obesity and T2DM, is an important part of the diagnosis of MetS. The occurrence of MetS in people with central obesity may be closely related to an increase in visceral adipose tissue, a decrease in subcutaneous tissue expansion and the related metabolic changes caused by ectopic storage of triglycerides in different organs . Obesityterature  that CVAterature  on ruralterature , whereinterature . It is eThis study has certain limitations. First, our study had a cross-sectional design and we could not identify causality, and thus, we will follow up with the patients further. Second, the surveyed population was Chinese and aged ≥18 years, and caution should be exercised when generalizing the results to other ethnicities. Third, details about long-term medication use, education and health status were not recorded in this study, which may have influenced the results. Finally, the lack of fasting insulin in this study makes it difficult to analyze information on insulin resistance.Our study indicated that VAI is an important risk factor for T2DM in Chinese patients with CKD. In CKD patients, especially those with T2DM – superior to that of BMI, WC, VFA, SFA, CVAI and LAP–VAI demonstrated the best predictive power for MetS based on the Youden index in both sexes.