In some studies, magnetic resonance imaging parameters of arterial stiffness  were correlated with blood pressure reduction . Conclusions: Assessing arterial stiffness prior to RDN predicted procedural success, since stiffness parameters were strongly correlated with a significant blood pressure response. Our endeavor should be tackled as a step forward in selecting appropriate hypertensive patients scheduled for RDN therapy. Non-invasive measurements could be an alternative to invasive parameters for response prediction.Background: Accurately selecting hypertensive candidates for renal denervation (RDN) therapy is required, as one-third of patients who undergo RDN are non-responders. We aimed to systematically review the literature on RDN response prediction using arterial stiffness assessment, optimizing the selection of patients referred for interventional blood pressure lowering procedures. Methods: A literature search was performed in MEDLINE, Embase, Scopus, and Cochrane databases to retrieve potential eligible studies from the inception to 30 June 2022. Results: Ten studies were finally included in this systematic review. Studies consistently documented that invasive pulse wave velocity (PWV) was correlated with RDN’s significant success. Nevertheless, non-invasive ambulatory arterial stiffness index and PWV derived from ambulatory blood pressure monitoring were independent predictors of blood pressure response ( Arterial hypertension (AHT) exerts a significant burden on public health, as it constitutes one of the most critical risk factors for cardiovascular disease (CVD) and death globally . Almost n = 3,207,911) reported a 10.3% prevalence of true-resistant hypertension, which was even higher in the presence of chronic kidney disease  or older age (12.3%) [According to the latest European and American guidelines, resistant AHT is defined as persistent increased blood pressure despite optimal drug therapy with at least three antihypertensives (including a diuretic) ,4. Altho (12.3%) .p < 0.001). Compared to patients with controlled AHT, those with resistant AHT exerted a 2.5-fold higher risk of adverse cardiovascular events [Clinical trials consistently documented an increased risk of cardiovascular events in patients with resistant AHT. During a follow-up of 3.8 years, these patients expressed an increased risk of death, myocardial infarction, heart failure, stroke, and CKD , with similar safety profiles [p < 0.001) but also daytime SBP (p < 0.001), nighttime SBP (p = 0.006), and office SBP (p < 0.001) [Besides drug therapy, interventional procedures are available for lowering blood pressure. Previous European guidelines on hypertension management recommended renal denervation intervention (RDN) in patients refractory to drug therapy  . Howeverprofiles . Using fprofiles ,12. A reprofiles . RDN red< 0.001) .The matter might not reside exclusively in trying to confirm the superiority of RDN versus standard drug therapy but in identifying the appropriate subgroup of patients that would benefit from the interventional procedure. This argument is also the main reason for our current paper. The  markers of RDN response could prove efficient in selecting patients. Higher baseline blood pressure, larger renal artery diameter, and higher baseline office heart rate were associated with a significant blood pressure reduction following RDN ,15. AddiThe concept of arterial stiffness refers to the arteries’ elasticity, distensibility, and compliance proprieties ,18. The Pulse wave velocity (PWV) is a strong marker of arterial stiffness (though the terms are not synonymous), being related to arterial wall distensibility . MoreoveTherefore, we aimed to systematically review the literature on RDN response prediction using arterial stiffness to optimize the selection of patients referred for interventional blood-pressure-lowering procedures.For standardized reporting, the present systematic review was conducted according to the updated Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines . The stuA comprehensive literature search was performed in MEDLINE (PubMed), Embase, Scopus, and Cochrane databases to retrieve potential eligible studies from the inception to 30 June 2022. No language restrictions or filters were applied in the search process. We also screened references from cited articles, the Google Scholar search engine, and the ClinicalTrials.gov database of clinical trials, as endorsed by the PRISMA checklist. Combinations between the following keywords and MeSH terms (for MEDLINE database) or Emtree terms (for Embase database) were used to build a search strategy: “arterial hypertension”, “resistant hypertension”, “uncontrolled hypertension”, “high blood pressure”, “renal sympathetic denervation”, “renal denervation”, “response”, “responders”, “prediction”, “arterial stiffness”, and “pulse wave velocity”. The search strategy for each database and the retrieved studies were reported in Two independent investigators carried out the eligibility assessment of retrieved studies based on pre-established inclusion and exclusion criteria. Studies were considered for inclusion in the present systematic review if they fulfilled the following inclusion criteria: (1) observational studies or randomized clinical trials; (2) participants aged ≥18 years with AHT who underwent RDN were enrolled; (3) arterial stiffness was appraised invasively or non-invasively prior to RDN procedure; and (4) original data were reported concerning the association between arterial stiffness and response to RDN during follow-up . In addition, critical exclusion criteria were set to guide the eligibility assessment: unpublished data, studies with overlapping populations, editorials, meta-analysis, case reports, and missing data or inability to extract data.p-values whenever available.The following data were extracted from eligible studies that met the inclusion criteria: first author, publication year, population sample size, age of enrolled participants, clinical setting, methods of arterial stiffness measurement, reported outcomes, and follow-up period. Moreover, essential inclusion and exclusion criteria of individual studies that could affect outcome interpretation were extracted and critically analyzed. Data were presented as median or mean values, the area under the curve (AUC), odds ratio (OR), and The quality of included studies was assessed according to their design. The risk of bias in randomized clinical trials was appraised using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) . In the Our search in pre-specified databases and sources retrieved 511 references. Afterward, duplicate records were excluded. The remaining 315 articles were initially screened for eligibility based on title or abstract, and 273 records were excluded. In the next step, 42 records were assessed in full text for inclusion and exclusion criteria. Finally, 10 studies that fulfilled the inclusion criteria were included in the present systematic review .General data from analyzed studies, including population sample size, age of enrolled patients, clinical setting, outcomes, and follow-up duration, are provided in The majority of included studies had an observational design ,27,29,30Definitions of variables and methods used were different across studies. Of the included studies, five measured arterial stiffness exclusively by non-invasive methods: PWV, central pulse pressure, ambulatory arterial stiffness index (AASI), and magnetic resonance-derived parameters ,29,30,31Data on non-invasive PWV measurement were available from three studies ,28,31. Mp < 0.0001) [n = 53) limits the application of the results in all AHT patients [In one of the two studies investigating classic non-invasive PWV, the authors reported that estimated PWV from ambulatory blood pressure monitoring was independently associated with blood pressure response at multivariate analysis . However, PWV measured by magnetic resonance imaging was not correlated with blood pressure drop at univariate analysis (p = 0.07) [The most recent trial investigated response prediction to RDN using invasive PWV compared to non-invasive markers  . Invasiv = 0.07) .p < 0.01) [In terms of cut-off values, invasive PWV < 14.4 m/s was linked to a better blood pressure response than invasive PWV above the established value ( < 0.01) . Notably < 0.01) .p = 0.019). Other parameters failed to prove significant in multivariate analysis [Another study compared non-invasive arterial stiffness measurement using magnetic resonance imaging with invasive PWV . Invasivanalysis . The autanalysis ,25. Moreanalysis .p = 0.012). Pulse pressure measured non-invasively was not associated with blood pressure response (p = 0.16). However, response to RDN was defined as a drop ≥ 20 mmHg in ambulatory daytime average blood pressure, which differed from other analyzed studies. Therefore, the study’s methodology might affect the results and should be considered in case of extrapolation to other patients [Another study investigated the association between invasive PWV or non-invasive pulse pressure with blood pressure drop following RDN . The autpatients .p = 0.038 for SBP and p = 0.014 for DBP). Although 24 h blood pressure drop was slightly bigger in subgroup with low central pulse pressure, it did not reach statistical significance (p = 0.07 for 24 h SBP and p = 0.112 for 24 h DBP) [Unconvincing results regarding pulse pressure and blood pressure response were obtained in another study . Low cen4 h DBP) .p = 0.04). When the AASI cut-off was set at 0.64, it had a 100% sensitivity, 29% specificity, 32% positive predictive value, and 13% negative predictive value for RDN response [AASI derived from 24 h ambulatory blood pressure monitoring was associated with RDN response, as was documented in one study . AASI loThe overall quality of analyzed observational studies was modest to good, as appraised using the NOS scale . There wTo the best of our knowledge, this systematic review is the first to investigate reported data in the literature on the validity of arterial stiffness for blood pressure response prediction following RDN.Our endeavor should be perceived as a step forward in selecting those patients with resistant hypertension who most likely will respond to RDN therapy. Moreover, it certainly is a background for future studies and clinical models to increase the discriminatory capacity between responders and non-responders to RDN. Arterial stiffness could improve cardiovascular risk stratification in AHT patients who are candidates for RDN, as it is associated with adverse cardiovascular events and all-cause mortality . In addiThe guidelines describe and endorse several methods to evaluate arterial stiffness . Non-invNon-invasive PWV is a ‘marker of arterial stiffness’ referred to as the ‘gold standard’ of arterial stiffness measurement . NotablyMagnetic resonance measurement could also acquire non-invasive data regarding blood flow velocity as well as arterial distensibility and compliance, with good technical reproducibility . MoreoveInvasive aortic PWV assessment constitutes an accurate and reproducible tool to evaluate arterial stiffness. Nevertheless, this ‘old-fashioned’ intravascular PWV assessment might not provide additional  information compared to non-invasive assessment. In addition, invasive PWV evaluation has limited applicability in the general population due to its invasiveness and potential complications .Though randomized clinical trials documented a benefit in blood pressure reduction after RDN, almost one-third of patients who underwent RDN were non-responders ,36. In oHowever, none of the investigated predictive parameters could accurately identify all patients who would benefit from RDN . New marOn another note, arterial stiffness could also distinguish that one-third of non-responder patients were unlikely to exhibit a blood-pressure reduction. Most patients with AHT and increased arterial stiffness were non-responders (84%), as highlighted in one study . Consequp < 0.0001) [As arterial stiffness could be evaluated non-invasively, it represents a feasible marker that could be implemented in clinical practice. Ascending aortic distensibility measured non-invasively by magnetic resonance imaging performed slightly better in predicting RDN response than invasively PWV (AUC 0.714 vs. AUC 0.695). Accordingly, ascending aortic distensibility could accurately distinguish between responders and non-responders in 71% of cases, which was improved by integrating non-invasive markers in different prediction models . In addi 0.0001) .In combination with other clinical and paraclinical parameters, arterial stiffness could be included in a multivariate prediction model further to refine the selection of patients . ProposeA potential explanation for the association between arterial stiffness and RDN response relies on AHT and RDN pathophysiology . RDN infNevertheless, non-invasive measurement of arterial stiffness is susceptible to different physiological and methodological confounders, which should be considered when implementing arterial stiffness in clinical practice or research . Mean arNotably, sodium–glucose co-transporter-2 (SGLT2) inhibitors could also alleviate arterial stiffness parameters and the blood pressure reduction effect ,42. TherAnother limitation derives from the RDN techniques performed. RDN could be achieved by applying three distinct ablation types: radiofrequency, ultrasound, and alcohol-mediated ablation. In our systematic review, radiofrequency ablation was used in most clinical studies ,29,30,31Arterial stiffness constitutes a significant part of the solution for selecting appropriate hypertensive patients for renal denervation intervention. Accurately selecting candidates for RDN is required, as almost one-third of patients who undergo RDN are non-responders. The solution provided by assessing arterial stiffness is attractive, as it could be measured non-invasively—a standing alternative to invasive parameters for response prediction. As reported in clinical studies, arterial stiffness parameters were strongly correlated with a greater blood pressure response to RDN. The ability of arterial stiffness to discriminate between responders and non-responders was good in all analyzed studies. Arterial stiffness could be integrated with other  parameters as part of a multivariate prediction model to refine further the selection of patients who would benefit from RDN. Therefore, this systematic review should be tackled as a step forward in selecting appropriate AHT patients scheduled for RDN therapy. More standardized and robust data is required before introducing arterial stiffness as a major predictor of RDN response, due to heterogeneity in the methodology, RDN techniques, and center experience across studies.


Hypertension affects over a billion people worldwide and is the leading cause of cardiovascular disease and premature death worldwide, as well as one of the key determinants of chronic kidney disease worldwide. People with chronic kidney disease and hypertension are at very high risk of renal outcomes, including progression to end-stage renal disease, and, even more importantly, cardiovascular outcomes. Hence, blood pressure control is crucial in reducing the human and socio-economic burden of renal and cardiovascular outcomes in those patients. However, current guidelines from hypertension and renal societies have issued different and sometimes conflicting recommendations, which risk confusing clinicians and potentially contributing to a less effective prevention of renal and cardiovascular outcomes. In this review, we critically appraise existing evidence and key international guidelines, and we finally formulate our own opinion that clinicians should aim for a blood pressure target lower than 130/80 in all patients with chronic kidney disease and hypertension, unless they are frail or with multiple comorbidities. We also advocate for an even more ambitious systolic blood pressure target lower than 120 mmHg in younger patients with a lower burden of comorbidities, to minimise their risk of renal and cardiovascular events during their lifetime. Hypertension affects 1.39 billion people worldwide  and is the leading cause of cardiovascular disease, including stroke and myocardial infarction, and premature death [2 or 15–29 mL/min/1.73 m2, respectively), as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [Hypertension is also a leading cause of chronic kidney disease (CKD) through its harmful effects on kidney vasculature; in turn, worsening CKD leads to increased sympathetic tone and salt sensitivity, upregulation of the renin–angiotensin–aldosterone system (RAAS), endothelial dysfunction, and worsening arterial stiffness, eventually driving the further progression of hypertension . This viidelines .Hence, blood pressure control is crucial to slow the progression of CKD and reduce the catastrophic socio-economic burden of CV events in this high-risk population ,10. PossThe current review will critically appraise all existing evidence used to create the different and subtly divergent guidelines for hypertension control in CKD patients and try to formulate a balanced opinion on the role of tight BP control in CKD by specifically focusing on BP targets rather than specific drug classes. However, for the sake of clarity we will also briefly consider the evidence on the specific reno- and cardioprotective role of some antihypertensive agents independently of the degree of BP control.Key guidelines from hypertension and renal societies are summarised in Amongst the hypertension guidelines published over the last decade, the JNC-VIII guideline initially suggested a BP target <140/90 mmHg in CKD patients aged 18–69. In patients aged 70 or above, no specific recommendations were issued, apart from a generic advice that ”treatment should be individualized taking into consideration factors such as frailty, comorbidities, and albuminuria” . The JNC2 (study A) and the second one in 255 patients with a GFR of 13–24 mL/min/1.73 m2 (study B). Although in both trials tight BP control  ≤92 mmHg, i.e., 125/75 mmHg) did not improve the primary composite outcome of ESRD, time of doubling of serum creatinine or GFR reduction compared to standard BP control over 2.2 years of follow-up, a post-hoc analysis indicated a benefit from tight BP control in patients with baseline proteinuria levels >1 g/24 h [The MDRD study  was desi1 g/24 h . However1 g/24 h .2/year in the standard BP control group). During the 4.1 years of follow-up, the achieved BP averaged 128/78 mmHg in the lower BP group and 141/85 mmHg in the standard BP group. Interestingly, ACEis allowed a significant reduction in the risk of the primary outcome compared to CCBs and β-blockers. However, ramipril allowed a 22% and 38% greater reduction in the composite outcome compared to metoprolol and amlodipine, respectively.The AASK trial  enrolledp = 0.99).The REIN-2 trial  enrolledp < 0.001). Additionally, intensive BP control allowed a significant reduction in all-cause mortality . Similar benefits were observed in the subgroup of patients with stage 3 or 4 CKD (approximately 28% of the study population), which was considered as strong evidence in favour of a BP target lower than 130/80, especially because most patients with CKD die due to CV complications [After three years from the publication of the JNC-VIII guidelines, in 2017, the ACC took a very different stance by suggesting a much more ambitious BP target of <130/80 mmHg in all hypertensive adults with CKD, regardless of the levels of proteinuria . In thisp = 0.01), a finding without significant heterogeneity that was consistent across multiple subgroups. However, the committee also noted that achieved systolic BP was 132 mmHg in the “intensive” BP control group, and expressed some concerns on pursuing an even tighter control . They mentioned that a systematic review by Upadhyay et al. failed to show any clinical benefit to the risk of death, CV events, ESRD or change in renal function with a BP target of <130/80 compared to <140/90 in non-diabetic CKD [In 2018, the ESH/ESC issued updated guidance on BP control in CKD patients, which seems to be a compromise between the JNC-VIII and the ACC guidelines. In fact, the ESH/ESC guideline suggests that “in patients with CKD, BP should be lowered to <140/90 mmHg and towards 130/80 mmHg” ,29,30. Tetic CKD ,23,24. Tetic CKD . Howeveretic CKD . This isAll hypertension guidelines concur that either ACEis or ARBs should be first-line drugs in CKD patients regardless of diabetic status, although the ACC states that ACEis should be tried first, whereas ARBs should only be used in patients who are intolerant to ACEis.p = 0.93) or ESRD  compared to standard BP control (achieved BP: 139.2/84.5 mmHg). On the other hand, the recommendation for intensive BP control (<130/80) in patients with abnormal albuminuria or proteinuria mainly relied on observational data from the Multiple Risk Factor Intervention Trial (MRFIT) and the Okinawa mass screening program [The critical appraisal of major renal guidelines published over the last decade allows the immediate identification of a clear turning point, namely the publication of the SPRINT trial in 2015 . In the  program ,36. In M program . Along t program ,23,26 an program . AlthougAfter the publication of the SPRINT trial in 2015 , which iIn August 2021, NICE finally released their updated guidance for CKD patients . HoweverAt each level of achieved BP, ACEis guarantee additional renoprotective benefits compared to other antihypertensive drugs that do not block the RAAS in patients with non-diabetic kidney disease. Those class-specific renoprotective benefits do not simply translate into an additional reduction in urinary protein excretion despite identical BP reduction , but intARBs reduce proteinuria over the short- (1–4 months) and long-term (5 to 12 months) to a similar degree as ACE inhibitors, whereas a dual RAAS blockade with ACE inhibitors and ARBs reduces proteinuria even further compared to either agent alone , althougp < 0.001), but those benefits were not evident in individual outcomes of the composite endpoint [ACEis or ARBs significantly reduced a composite CV outcome of myocardial infarction, coronary revascularisation, unstable angina, stroke and other adverse cardiovascular events compared to the control treatment in patients with non-diabetic kidney disease . Those benefits were even higher in children with higher baseline proteinuria. The findings from the ESCAPE trial have been recently appraised by the NICE committee, which agreed that the therapeutic target in children and young people with CKD and proteinuria is to keep systolic BP below the 50th percentile for their corresponding height [The main evidence on BP targets in children with CKD derives from the Effect of Strict Blood Pressure Control and ACE inhibition on the Progression of CKD in Pediatric Patients (ESCAPE) trial , which rg height . This reg height .In 2021, the NICE committee critically appraised the scant evidence on specific BP targets in the elderly and concluded that none of the available data are useful for formulating a specific recommendation in those patients . The comThe 2021 KDIGO guideline supported the idea that, in most CKD patients and hypertension, the CV benefits of a target systolic BP < 120 mmHg versus <140 mmHg outweigh the risk of harm, even in the frail and elderly . As the 2  in the intensive arm, versus 1.4 g/m2, (IQR: −11.6 to 10.4) in the standard arm, p = 0.43). A non-statistically significant increase in the risk of hospitalisation and vascular access thrombosis was observed in the intensive arm. Unfortunately, no major CV events were assessed in this pilot trial [In patients with ESRD undergoing haemodialysis or peritoneal dialysis, there is a staggering increase in CV morbidity and mortality, which can be 10- to 100-fold higher than in the general population . Unsurprot trial . Althougot trial , the 200ot trial  and the ot trial  consisteot trial . This isot trial ,84,85,86ot trial  or simplot trial . Hence, Despite many years of heated debate in the hypertension and nephrology communities, the jury is still out on the desirable BP target in CKD patients. Undoubtedly, the publication of the SPRINT trial in 2015  has been2 died from CV disease over the extended follow-up period , whereas only 461/5545 developed ESRD [Thus, what kind of BP target should be adopted by clinicians in daily clinical practice for their patients with CKD and hypertension? Our attempt to provide a balanced answer to this clinical dilemma will start from what we consider to be a critical point: in CKD patients, the risk of dying from CV disease widely exceeds the risk of developing ESRD . Shockinped ESRD . In otheped ESRD . Our triped ESRD ,92. Notaped ESRD , which mped ESRD .Based on our recent trial sequential analysis and the meta-analysis from Zhang et al., we feel that clinicians should preferably follow the ACC guideline  and the Although we commend the KDIGO working group for their courageous position on the systolic BP target of <120 mmHg, we are reluctant to endorse their statement that such a target should be routinely pursued “even in the frail and elderly”. In fact, the large majority of patients enrolled in the SPRINT trial were not frail , and we In terms of first-line drugs for CKD patients, current hypertension and renal guidelines consistently recommend the usage of either ACEis or ARBs in both diabetic and non- diabetic kidney disease for their clear reno- and cardiovascular benefits ,107,108,In conclusion, we recommend that clinicians pursue a target BP of <130/80 mmHg in all CKD patients with hypertension, unless they are frail (36-item FI > 0.21) , or very


It is important to determine those clinical factors that imply a greater risk of rehospitalization in psychotic patientsTo determine the rate and predictors of rehospitalization in psychotic patients after their first hospitalizationWe include all Psychotic patients admitted for first time in their life in our Psychiatric Unit between 2009 and 2019 (N=359) , including all diagnosed according DSM-IV of Schizophrenia or other Psychotic disorders -Multiple clinical, sociodemographic and biological variables of the basal hospitalization were recorded With the SPSS program we compared the variables between patients who needed any hospitalization in the follow-up until 31th December 2019 and those who do not. We use the Chi square  and the Student T ( quantitative variables)109 psychotic inpatients had at least one rehospitalizations . The qualitative variables significantly associated with rehospitalization were : cannabis in urine at admission (P<0.03), and treatment with risperidone (P<0.014). Instead treatment with long acting paliperidone was associated with absence of rehospitalization (P<0.005) .The quantitative variables relationed significantly with multiple rehospitalization were : lower age  lower HDL cholesterol levels (P<0.02) and higher years of follow-up after discharge (P<0.000)1-More of 30% of psychotic patients need rehospitalization after their first hospitalization in a mean of follow up of 5,8 years 2-Lower age, longer follow-up period and treatment with risperidone are significantly associated with rehospitalization , instead treatment with long acting paliperidone are significantly associated with absence of rehospitalizationNo significant relationships.


Cardiovascular diseases (CVD) are the leading cause of death globally. Cardiac rehabilitation (CR) programs’ benefits are overall consensual; however, during exercise, progressive physiological effects have not been studied yet in cardiac patients. Our study aims to analyze physiological parameters of thermography, heart rate variability (HRV), blood pressure, central nervous system (CNS) fatigue, and cortical arousal in heart attack patients (HAP) who belong to CR programs of High-Intensity Interval Training (HIIT) and Moderate-intensity Continuous Training (MICT) compared to healthy participants. In this case control study, two HAP patients  and two healthy people  were randomly assigned in a 1:1:1:1 allocation ratio to one of four groups: cardiac MICT, cardiac HIIT, control MICT, and control HIIT. The HIIT at ≈85–95% of peak heart rate (HR) was followed by a one-minute recovery interval at 40% peakHR, and MICT at ≈70–75% of peakHR. Outcome measurements included thermography, HRV, blood pressure, CNS fatigue, and cortical arousal; The HAP presents more than twice the CNS fatigue in MICT than control participants, but HIIT has almost the same CNS fatigue in HAP and control. In addition, both of the HAP groups presented higher temperatures in the chest. The HIIT protocol showed better physiological responses during exercise, compared to MICT in HAP.  According to World Health Organization (WHO) , cardiovCardiac rehabilitation (CR) is a multidisciplinary process for patients recovering after an acute cardiac event or chronic cardiovascular disease that reduces mortality and morbidity and improves the quality of life . CR is tHypertension, hyperlipidemia, diabetes, and obesity are cardiovascular risk factors that can be reduced with this type of exercise program ,12, and CR programs’ benefits are internationally consensual ,2, but dActually, new evaluation and control methods are applied to different sport areas such as performance, but also health. One of these is the analysis of the HRV as a tool to understand the autonomous nervous system status and response to different stimulus ,18, factThis case control study aims to analyze the physiological parameters of thermography, HRV, blood pressure, and cortical arousal in cardiac patients who belong to CR programs of HIIT and MICT, compared to healthy participants.Two patients were recruited within the cardiology unit of the Hospital of Évora . Two patients who had undergone a heart attack and were referred by their cardiologist to the cardiac rehabilitation (CR) phase III, two months after angioplasty and low-risk medical recommendations, were evaluated for inclusion in this case control study. The inclusion criteria were age 18–80 years, who had left ventricular ejection fraction ≥ 45%, and were New York Heart Association (NYHA) functional Class I, II, or III. In addition, patients were excluded from the study if the following criteria were met: severe exercise intolerance, uncontrolled arrhythmia, uncontrolled angina pectoris, severe kidney or lung diseases, musculoskeletal or neuromuscular conditions preventing exercise testing or training, and signs or symptoms of ischemia. The control group included two healthy participants without cardiovascular diseases. This case control study had four participants, two HAP patients  and two healthy controls  who were randomly assigned in a 1:1:1:1 allocation ratio to one of four groups: cardiac HIIT (n = 1), cardiac MICT (n = 1), control HIIT (n = 1), and control MICT (n = 1) . All groInitially, participants read and signed an informed consent form on the first visit, and the two HAP were submitted to a clinical evaluation performed by a cardiologist. A supervised graded exercise test to record volitional fatigue, risks, or symptoms of ischemia was performed on a treadmill, using the Bruce protocol, before the intervention. The test was done in non-fasting conditions and under medication. Electrocardiography was recorded continuously, and blood pressure was measured with an arm cuff every 3 min. On the second visit, each participant completed a standardized questionnaire including demographic data, medical history, medication use, family history of CVD, and smoking status; then, the peripheral vascular response was collected using a thermography system in two different moments: pre- and post-treadmill protocol. All thermal images were collected in compliance with the European Association of Thermology guidelines . The theTime-Domain Analysis: (a) square root of differences between adjacent RR intervals (RMSSD);Non-linear analyses:©) non-linear metrics: the RR variability from heartbeat to short term Poincaré graph (width) (SD1), the RR variability from heartbeat to long-term Poincaré graph (length) (SD2), short-term fluctuation of the detrended fluctuation analysis , long-term fluctuation of the detrended fluctuation analysis , and the sample entropy (SampEn), which measures the regularity and complexity of a time series.The Heart Rate Variability (HRV) was measured by a H10 chest strap  and recorded using a RS800CX monitor . This wireless device was placed below the participants’ chest muscles, allowing a reliable recording ; then, tThe cortical arousal was measured by the critical flicker fusion threshold (CFFT) by a Lafayette Instrument Flicker Fusion Control Unit model 12,021 , using standards protocols previously used . ParticiFinally, the perception of fatigue was measured by a visual analogue scale (VSA) wherein the subjective fatigue was scaled to a 0–100 scale, 0 being no fatigue and 100 being an extreme fatigue following similar VSA .Regarding assessment procedures, participants had to rest for 15 min prior to baseline HRV collection in a sitting position, as recommended ,39. AfteThe assessments and data acquisition were performed by an external agent who was trained to do so, so that the researchers were totally blinded in the management of the data.Training sessions on the treadmill were initiated with a 5–10 min warm-up at 50–60% peak Heart Rate (peakHR), and ended with 5 min of cool-down at 40% peakHR. The HIIT trial involved a total of 20 min at 85–95% peakHR, followed by a one-minute recovery interval at 40% peakHR, predicted with a supervised graded exercise test on a treadmill, using the Bruce protocol. During the high-intensity exercises, the participants were motivated to gradually increase their exercise intensity toward 15–17 on the Borg scale. The MICT protocol consisted of a continuous bout of moderate-intensity exercise to elicit 70–75% peakHR for 27.5 min, to equate the energy expenditure with the HIIT protocol .As training intensity increased, the patients’ heart rate, rate of perceived exertion , and cardiac symptoms were also taken into consideration. All work was conducted following the Declaration of Helsinki and registered at ClinicalTrials.gov (NCT03538119). Ethics approval was obtained from the University of Evora Ethics Committee (reference number: 17039). All participants signed a written informed consent before participating in this study.Before starting the protocols on the treadmill, the temperature was quite similar between the HAP and healthy participants’ groups. From pre- to post-protocols, there was always a decrease in temperature in all body variables evaluated in the study, except for the temperature of the right hand, where both HIIT groups increased temperature (temperature difference: 0.8 ± 0.5 °C in HAP vs. 1.0 ± 0 °C in control). In contrast, the MICT groups maintained the temperature from pre- to post-protocol. The same was not observed in the temperature of the left hand, which remained the same .The temperature difference in the chest was greater in patients with adverse cardiac events than in patients without events (temperature difference: 2.3 ± 1.2 °C in HIIT vs. 3.0 ± 1.6 °C in MICT). In the groups of healthy participants, the temperature remained practically the same. There was also a greater difference in temperature in the abdomen in the MICT group (temperature difference: 3.7 ± 1.8 °C in the HAP vs. 2.8 ± 0.0 °C in the control group) compared to the HIIT group (temperature difference: 1.5 ± 1.0 °C in the HAP vs. 1.0 ± 0.0 °C in control) .2 vs. control: 346 ± 0.00 ms2) compared to the MICT groups (HAP: 120.5 ± 74.2 ms2 vs. control: 81.7 ± 0.00 ms2). However, no significant interaction or main effects were observed in RMSSD , it is still difficult to find participants to apply high-intensity exercise stimulus; thus, we decided to carry out a case study. Another limitation was the use of indirect measures of cortical arousal; an electroencephalography would more deeply explain all cortical responses in this population group. As perspectives for the future, we believe that this methodology is safe and can be beneficial in the recovery of patients who have suffered a heart attack , and can be a method of education or re-education towards healthier lifestyles. Therefore, we propose that this method be used in a larger sample of patients after a heart attack.Finally, we concluded that both training protocols (HIIT and MICT) produced a similar thermographic response in both heart attack patients and control participants, showing in some body segments  lower temperatures in the heart attack patients. Regarding the autonomic response, heart attack patients presented higher sympathetic modulation in both trainings, showing that HIIT had higher sympathetic modulation than MICT; however, in the post evaluation, the HRV was equal between HIIT and MICT in heart attack patients. The MICT training produced higher subjective fatigue and a greater decrease in cortical arousal in heart attack patients than HIIT, contrary to that in control participants. No differences in systolic and diastolic blood pressure were found between HIIT and MICT training in heart attack patients; however, they presented higher systolic and lower diastolic blood pressure than control participants during both trainings.


Optimal blood pressure management of patients with basilar artery occlusion (BAO) remains uncertain. This study aimed to investigate the relationship between admission blood pressure and clinical outcomes following acute BAO.We analyzed data from a prospective, nationwide cohort study of 829 patients with acute BAO and posterior circulation stroke. Baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded on admission. The primary outcome was neurological functional disability based on the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included successful reperfusion, mortality within 90 days, and National Institutes of Health Stroke Scale (NIHSS) score change. Multivariable logistic regression was used to assess the associations of SBP and DBP with outcomes.We include 829 patients with posterior circulation stroke and BAO between January 2014 and May 2019. Multivariate logistic regression showed high SBP and DBP correlated with unfavorable outcomes. The favorable prognosis (mRS ≤ 3) rates of the low-to-normal and the hypertension groups were 34.8 and 23.9%, respectively. After adjusting for covariates, multivariate regression analysis demonstrated that an SBP > 140 mm Hg was associated with a poor functional outcome  and mortality at 90 days , and predicted a lower probability of successful reperfusion . The risk of symptomatic intracranial hemorrhage and the NIHSS score at 24 h were not significantly different between the high SBP group and the low-to-normal blood pressure group. And the results for DBP were similar.Trail Registration: [http://www.chictr.org.cn], [ChiCTR1800014759].Among patients with acute BAO, higher systolic or DBP at admission was associated with poor stroke outcomes and had a lower probability of successful reperfusion, with an increased risk of mortality.  According to admission blood pressure levels, 29.5% of patients have low-to-normal systolic blood pressure (SBP < 140 mm Hg), while 70.5% have hypertension (SBP ≥ 140 mm Hg). With EVT, approximately one-quarter of patients attain independent outcomes, indicated by a modified Rankin Scale (mRS) of 0–2. However, about 77% of the patients in the Basilar Registry, a nationwide registry of patients with BAO in China, remained functionally dependent or died . We knowJ- and U-shaped curves between SBP and clinical outcomes ; both low and high SBP have been associated with poor outcomes , pre-stroke mRS score, and imaging findings. Hypertension: SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg . FastingThe admission blood pressure was the first recorded non-invasive SBP and DBP obtained using an automated sphygmomanometer in the emergency department or other areas. Mean arterial pressure (MAP) readings were estimated using the following formula: (2 × DBP + SBP)/3. The severity of stroke was assessed using the NIHSS score which uses a graded scale to comprehensively assess the full range of neurological dimensions such as consciousness, eyes movement, visual fields, limb movement and sensation, limb ataxia, language, cognition, and attention. Assessment of collateral status was done using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology Collateral grading system . IntraceThe primary outcome was the mRS score at 90 days, as assessed by telephone or during clinical visits by trained local neurologists who were blinded to the patient’s clinical details and the course of treatment. The mRS is divided into seven levels, ranging from 0 (no symptoms) to 6 (death), which are used to evaluate the recovery state of neurological function in stroke patients , with hi2 tests were used for categorical variables, and non-parametric tests (Mann–Whitney U test) were used for continuous variables.Stroke was differentiated from intracerebral hemorrhage using head computed tomography or magnetic resonance imaging. Baseline characteristics and clinical outcomes of this study population were compared between the two admission blood pressure groups. The characteristics of all patients are shown as medians [interquartile range] or numbers with percentages. Associations between admission blood pressure and clinical parameters were tested using univariate analysis. The Fisher’s exact test or χTaking the clinical hypertension value as a reference point, multivariable ordinal logistic regression or binary logistic regression analysis was performed on the two groups to determine the adjusted OR (aOR) and corresponding 95% CIs to estimate the differential effects of low and high groups of blood pressure on functional outcomes. Parameters affecting clinical outcomes were included in a multivariable logistic regression model to evaluate the predictive value of blood pressure values. We conducted a univariate analysis of the two populations based on baseline characteristics, with factors that differed in a statistically significant way between the two populations being used as adjusted covariates. We adjusted for serum glucose level, history of hypertension, hyperlipidemia, atrial fibrillation, and the stroke causative mechanism. A multivariable ordinal logistic regression model was used to calculate the adjusted common OR for a shift in the direction of an adverse outcome on the mRS score.p-values < 0.05 were considered significant, and all tests of hypotheses were 2-sided. Statistical analysis was performed using SPSS 26.0 (IBM) and Stata 16.0. Figures were drawn using the Word software 2019 (Microsoft). The forest plot was drawn using GraphPad Prism 8 and 3D mesh generated by SigmaPlot 14.0.Missing data for baseline characteristics and outcomes were excluded from our analysis. For all statistical methods, A total of 826 patients with BAO were included in the current analysis. Admission blood pressure and mRS scores at 90 days were available for all patients. Of these, 644 were treated with standard medication plus EVT, and 182 received only standard medication. The median age was 65 years, and 611 patients were male. The mean admission SBP and DBP were 151 mm Hg and 85 mm Hg, respectively.P < 0.001) and hyperlipidemia , higher serum glucose , but a lower prevalence of atrial fibrillation ; furthermore, there was a significant difference in the causative mechanism of stroke  between groups. Other baseline characteristics did not differ statistically between the two groups.Patients’ baseline characteristics according to their admission SBP are presented in The outcomes according to admission SBP are shown in P < 0.01). Patients with an admission SBP ≥ 140 mm Hg had a higher median mRS score than those with an SBP < 140 mm Hg  at 90 days was significantly lower in the higher SBP group (≥140 mm Hg) than in the low-to-normal SBP group  and a lower rate of successful reperfusion , with an adjusted odds ratio of 1.447  and 0.550 . Specific adjusted variables are annotated in the figure notes  and hypertension group (SBP ≥ 140 mm Hg), including those based on age, sex, baseline NIHSS, baseline pc-ASPECTS, occluded segment, EVT and IVT. Overall, the hypertension group is more likely to have a worse functional outcome than the low-to-normal group . What’s more, it’s more likely for hypertension group to have worse functional outcomes than the low-to-normal group in these subgroups: age < 65, female, baseline NIHSS score 0–27, baseline pc-ASPECTS score 8–10, occluded segment in BA-middle, no EVT and no IVT. Interaction tests showed that the effect of hypertension on clinical outcomes in BAO patients was not significantly affected by age, sex, baseline NIHSS, baseline pc-ASPECTS, occluded segment, EVT, and IVT, after adjusting for confounders  or DBP (≥90 mm Hg) negatively impacts clinical outcomes, including higher mortality and lower probability of reperfusion. These distinctions suggest that the different anatomy and characteristics of the anterior and posterior circulation may indicate different admission blood pressure management. It may be related to the difference in vessel diameter in the anterior and posterior circulation and the sympathetic distribution in the anterior and posterior circulation. On the one hand, chronic hypertension is mainly related to extensive cerebral small artery sclerosis. Due to the difference in vessel diameter in the anterior and posterior circulation, atherosclerosis causes a greater impact on the posterior circulation than on the anterior circulation . On the New secondary stroke prevention guidelines support a target blood pressure of <140/90 mm Hg and suggest individual tailoring of blood pressure therapy combined with lifestyle modifications . HoweverAnother possible explanation is that the higher admission SBP or DBP may indicate that these patients are inherently unhealthy or that the acutely elevated blood pressure results from physical stress. However, at present, we are unable to provide evidence to support this hypothesis.Our study had several strengths and limitations. This is the first nationwide, prospective study using detailed and near-complete data to systematically elaborate on the relationship between admission blood pressure and clinical outcomes. However, although blood pressure was measured at the time of admission, there were no subsequent blood pressure measurements; the documentation of a single SBP and DBP increased the risk of measurement error, and it is difficult to interpret whether the changes in blood pressure occurred before or after stroke. Furthermore, individuals with a clinically significant pre-existing disability were excluded from our study, which could have introduced inclusion bias; thus, the sample does not represent all patients with ischemic stroke.In summary, we found an association between higher admission SBP and DBP with poor clinical outcomes and a lower probability of successful reperfusion in stroke patients with BAO. Further studies are needed to examine the role of blood pressure during the entire treatment period and blood pressure levels and trends as they relate to outcomes in ischemic stroke patients with BAO.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by Medical Ethics Committee of Second Affiliated Hospital of Third Military Medical University, PLA. The patients/participants provided their written informed consent to participate in this study.YC and RL performed experiments and participated in data analysis and manuscript writing. SJ, JG, XL, JM, JCL, BZ, JD, YZ, and SY participated in the study. WZ and QY analyzed the results. LW was responsible for reviewing and revising the first draft of the article. JL and GJ supervised the design of the research. All authors 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.


There was evidence of a nonlinear association between diastolic blood pressure and atrial fibrillation with a steeper increase in risk at lower levels of diastolic blood pressure, but for systolic blood pressure the association appeared to be linear. For both systolic and diastolic blood pressure, the risk increased even within the normal range of blood pressure and persons at the high end of systolic and diastolic blood pressure around 180/110 mmHg had a 1.8–2.3 fold higher risk of atrial fibrillation compared to those with a blood pressure of 90/60 mmHg. These results suggest that elevated blood pressure and hypertension increases the risk of atrial fibrillation and there is some increase in risk even within the normal range of systolic and diastolic blood pressure.Elevated blood pressure and hypertension have been associated with increased risk of atrial fibrillation in a number of epidemiological studies, however, the strength of the association has differed between studies. We conducted a systematic review and meta-analysis of the association between blood pressure and hypertension and atrial fibrillation. PubMed and Embase databases were searched for studies of hypertension and blood pressure and atrial fibrillation up to June 6th 2022. Cohort studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of atrial fibrillation associated with hypertension or blood pressure were included. A random effects model was used to estimate summary RRs. Sixty eight cohort studies were included in the meta-analysis. The summary RR was 1.50 (95% CI: 1.42–1.58, IThe online version contains supplementary material available at 10.1007/s10654-022-00914-0. Atrial fibrillation presents a considerable public health burden and is the most common type of arrhythmia affecting around 1–2% of the general population, increasing to around 10% of persons by 80 years of age . In the Elevated blood pressure is the leading cause of death and disability-adjusted life-years (DALYs) globally with 10.4 million deaths and 218 million DALYs attributable to elevated systolic blood pressure in 2017 according to the Global Burden of Disease Study . AlthougEstablishing whether hypertension and elevated blood pressure increases the risk of atrial fibrillation would be important from a preventive point of view as it is a risk factor that could be modified by diet, physical activity, weight control and pharmaceutical drugs . In addiWe searched Pubmed, and Embase databases up to June 9th 2022 for eligible studies. The search strategy is provided in the Supplementary Text. We followed standard criteria for conducting and reporting meta-analyses . In addiWe included published retrospective and prospective cohort studies and nested case–control studies within cohorts that investigated the association between blood pressure or hypertension and the risk of atrial fibrillation (any type). Retrospective case–control studies were excluded because of their potential for recall bias and selection bias and cross-sectional studies were excluded because of difficulties in establishing cause and effect relationships. Estimates of the relative risk adjusted for at least one confounding factor had to be available with the 95% confidence intervals (CIs) in the publication. Conference abstracts, grey literature and non-English publications were not included. When multiple publications were available from the same study, the study with the largest number of cases was used in general. However, overlapping publications were used in specific subgroup analyses by sex or ethnicity, when the article used for the main analysis did not report such stratified analyses. Overlapping publications that reported risk estimates in three categories or more were also used for the nonlinear dose–response analyses  if the article included in the main analysis only reported risk estimates on a continuous scale. A list of the excluded studies can be found in Supplementary Table 1. DA, YMS, EK and TF did the study selection in duplicate and any disagreements were resolved by discussion.The following data were extracted from each study: The first author’s last name, publication year, country where the study was conducted, study period, sample size, number of cases and participants, exposure , subgroup , relative risks (RRs) and 95% CIs for hypertension versus no hypertension or for increments in systolic or diastolic blood pressure and variables adjusted for in the analysis. DA did the data extraction and it was checked for accuracy by YMS.We calculated summary RRs (95% CIs) of atrial fibrillation for participants with hypertension compared with participants without hypertension and for systolic and diastolic blood pressure using the random-effects model by DerSimonian and Laird  which ta2 statistics [2 is an estimate of how much of the heterogeneity that is due to between study variation rather than chance. I2-values of 25%, 50% and 75% indicates low, moderate and high heterogeneity respectively. We conducted main analyses  and stratified by study characteristics such as sample size, number of cases, whether prevalent cases were excluded or not, geographic location, study quality and by adjustment for confounding factors to investigate potential sources of heterogeneity and we used meta-regression analyses to test for differences in summary estimates between subgroups. Study quality was assessed using the Newcastle Ottawa scale which rates studies according to selection, comparability and outcome assessment with a score range from 0 to 9 [Heterogeneity between studies was evaluated using Q and Iatistics . I2 is am 0 to 9 .Publication bias was assessed using Egger’s test  and by iFrom a total of 32,876 records that were identified by the search we included a total of 69 publications –82 with 2 = 98.1%, pheterogeneity < 0.0001)  or by inspection of the funnel plot . The summary RR ranged from 1.47 (95% CI: 1.42–1.52) when excluding the study by Zoller et al. [Fifty six cohort studies  –9, 17–65r et al.  to 1.51 r et al.   per 20 mmHg increment , but some indication of asymmetry in the funnel plot . When using the trim and fill method, eight studies were added, but the results were similar, summary RR = 1.17 (95% CI: 1.14–1.19) . The summary RR ranged from 1.18 (95% CI: 1.16–1.20) when the Atherosclerosis Risk in Communities Study [nonlinearity < 0.0001, the association was approximately linear, and there was a dose-dependent increase in risk with increasing systolic blood pressure from a systolic blood pressure level of 90 mmHg and above  , 77–80  per 10 mmHg increment  or by inspection of the funnel plot . The summary RR ranged from 1.05 (95% CI: 1.00–1.10) when excluding the UK GPRD study [nonlinearity < 0.0001) with a slightly steeper increase in risk at lower levels of diastolic blood pressure than at higher levels, however, there was an increased risk from a diastolic blood pressure level of around 60 mmHg  , 81, 82 ent Fig. c. There RD study  to 1.07 RD study  , and a weaker association among studies with adjustment for smoking (p = 0.03) when compared to those without such adjustment. Further subgroup analyses by ethnicity showed summary RRs of 1.53  for Caucasians [2 = 7.5%, n = 6) for African Americans [p = 0.77) .There were positive associations between hypertension and risk of atrial fibrillation across all subgroup analyses defined by sex, duration of follow-up, geographic location, number of cases, whether prevalent cases were excluded or not, study quality and adjustment for confounding  factors , although the number of studies was small in some subgroups Table . With meucasians , 59 and mericans , 46, 59 p = 0.03) and physical activity (p = 0.04) with stronger associations among studies with compared to without such adjustments, however, relatively few studies made such adjustments. For diastolic blood pressure there was heterogeneity in analyses stratified by sex (p = 0.009) and by adjustment for BMI or obesity (p = 0.04), coronary heart disease (p = 0.01), and heart failure (p = 0.009). However, the association was weaker in studies of both sexes combined than in studies among either men or women, and there was no heterogeneity when comparing men with women (and excluding studies in both sexes combined)  study quality scores were 7.7 (8.0) for the analysis of hypertension, 7.8 (8.0) for systolic blood pressure, and 7.8 (8.0) for diastolic blood pressure.This meta-analysis of cohort studies suggests that persons with hypertension have a 50% increase in the relative risk of developing atrial fibrillation compared to persons without hypertension. There was a 19% increase in the relative risk of atrial fibrillation per 20 mmHg increase in systolic blood pressure and 6% increase in relative risk per 10 mmHg of diastolic blood pressure. Although the test for nonlinearity was significant both for systolic and diastolic blood pressure in relation to atrial fibrillation, the association with systolic blood pressure appeared to be approximately linear, while the association for diastolic blood pressure was nonlinear with a slightly steeper increase in risk at lower levels than at higher levels of diastolic blood pressure. However, there was an increased risk even within what is considered the normal blood pressure range and the lowest risk was observed at a systolic and diastolic blood pressure of 90/60 mmHg, respectively, while there was a 1.8–2.3 fold increase in risk at the high end of systolic and diastolic blood pressure around 180/110 mmHg. Positive associations were observed both in men and women, and among European, American, Asian and Australian studies, however, data from other regions are lacking. In the few studies that reported results stratified by ethnicity, there was a positive association between hypertension and atrial fibrillation among both Caucasians and African Americans. Our findings of an increased risk of atrial fibrillation with higher systolic and diastolic blood pressure are partly consistent with several recent Mendelian Randomization (MR) studies –97, as wSeveral biological pathways could explain an increased risk of atrial fibrillation in patients with hypertension. Elevated blood pressure increases the risk of coronary heart disease and heart failure , conditiThe present systematic review and meta-analysis has some limitations that need to be discussed. Persons with hypertension often have less healthy lifestyles than persons without hypertension, including higher BMI, less physical activity and they may be more likely to smoke. Several of the included studies adjusted for the most important confounding factors and the results persisted across most subgroup analyses, and we found little evidence of heterogeneity between these subgroups. However, we cannot exclude the possibility that residual confounding could partly explain the results. There was very high heterogeneity in the analyses of hypertension and diastolic blood pressure and moderately high heterogeneity in the analysis of systolic blood pressure and this persisted in many of the subgroup analyses, but there was lower heterogeneity in studies with a longer duration of follow-up. The heterogeneity observed appeared to be more driven by differences in the effect sizes rather than differences in the direction of the association, as all except one study found positive associations between hypertension or systolic blood pressure and atrial fibrillation. Since the studies only had one baseline assessment of hypertension status or blood pressure, regression dilution bias could have attenuated the association between hypertension or blood pressure and risk of atrial fibrillation. Some participants with high blood pressure at baseline may have undergone subsequent treatment for high blood pressure with pharmaceutical medications or lifestyle changes, which would have lowered their blood pressure, but any such effects would most likely have led to conservative estimates of the associations between hypertension and blood pressure and risk of atrial fibrillation. Some of the included studies may also have over-adjusted by including hypertension status and blood pressure in the same models, adjusting rather than stratifying for blood pressure treatment, and/or by adjusting for potentially intermediary conditions such as coronary heart disease, heart failure, valvular heart disease, and left ventricular hypertrophy in the multivariable models. Any further studies might want to adjust for potential confounders and mediators separately to evaluate the impact of both on the observed associations.Strengths of the present meta-analysis include (1) the cohort design of the included studies , (2) the detailed subgroup and sensitivity analyses, (3) the very large sample size with 14.3–30.5 million participants and 333,000 to 1,080,000 cases providing a more robust estimate of the association between blood pressure and hypertension and risk of atrial fibrillation than most individual studies, and (4) the detailed dose–response analyses. Our findings have important clinical and public health implications as the number of people with hypertension worldwide increased from 594 million in 1975 to 1.13 billion in 2015, mainly due to population growth and ageing, but also due to lifestyle factors . This inIn conclusion, this meta-analysis suggests that people with hypertension have a 50% increase in the relative risk of developing atrial fibrillation compared to those without hypertension. Increasing systolic and diastolic blood pressure even within the normal range was associated with increased risk and at the high end was associated with a twofold increase in risk. These results strongly support a role of elevated blood pressure in the development of atrial fibrillation.Supplementary file1 (PDF 559 kb)Below is the link to the electronic supplementary material.


Perioperative stroke occurred in 12 cases (5.9%). The results of the univariate analysis showed that older age, history of hypertension, preoperative cerebral infarction as the main symptom, lesions involving the posterior circulation, and high perioperative blood pressure are the risk factors of perioperative stroke. The results of multivariate logistic regression analysis showed that preoperative cerebral infarction as the main symptom (p = 0.015) is an independent risk factor for perioperative stroke. The occurrence of perioperative complications was not related to the improvement of follow-up mRS  score and long-term cerebral rehemorrhage. Conclusions: Clinically, patients with MMD have multiple episodes of preoperative symptoms, lesions involving the posterior circulation, and preoperative cerebral infarction and should be attached when undergoing revascularization.Objective: To analyze the risk factors of transient neurological deficits (TND) and perioperative stroke in patients with MMD after extracranial–intracranial revascularization. Methods: A retrospective analysis of the clinical data of 183 patients with MMD undergoing 203 EC–IC bypass operation procedures from January 2018 to August 2020. According to whether TND and stroke occurred within 14 days after operation, univariate analysis and multivariate logistic regression were used. Results: TND occurred in 26 cases (12.8%) of revascularization. The results of the univariate analysis showed that history of diabetes, multiple episodes of preoperative symptoms, lesions involving the posterior circulation, and high postoperative blood pressure are the risk factors of TND. Further multivariate logistic regression analysis showed that multiple episodes of preoperative symptoms ( Moyamoya disease is a chronic progressive cerebral vascular occlusive disease of unknown causes . With thA total of 183 patients and 203 cases of MMD revascularization were included. Inclusion criteria: ① Patients with MMD admitted to our hospital from January 2018 to August 2020. ② Patients with MMD who meet the diagnostic criteria released by the Research Committee on the Pathology and Treatment of Spontaneous Occlusion of the Circle of Willis from the Ministry of Health and Welfare of Japan in 2012 . ③ Patie2, perioperative blood pressure , 24 h cranial drainage volume after operation, perioperative complications after operation, follow-up mRS score, and long-term cerebral rehemorrhage : New symptoms of local neurological dysfunction during the perioperative period after operation, including aphasia, limb weakness, sensory abnormality, epilepsy, vomiting, vertigo, facial paralysis, blurred vision, drinking water cough, and disturbance of consciousness. There was no new responsible focus of stroke in an imaging examination, and the symptoms recovered within 14 days or 1 month at the latest. Perioperative stroke: New ischemic and hemorrhagic stroke events within 14 days after operation must have new responsible lesions defined upon imaging examination. There is no intersection between perioperative stroke and TND. Patients with TND first and then stroke were recorded as within the perioperative stroke group because it was impossible to distinguish TND from the precursor of stroke.Long-term cerebral hemorrhage: New hemorrhagic stroke incident one month after surgery, which must have imaging (CT) evidence and excludes cerebral hemorrhages caused by trauma, ruptured aneurysm, and other causes that are not related to MMD.Main clinical symptom of patients: Refers to the most obvious symptom caused by MMD. Patients with both a preoperative history of cerebral infarction and cerebral hemorrhage were included in the cerebral hemorrhage group because cerebral hemorrhage is often more serious. The interval between the last attack and operation: Patients in the acute operation group underwent operation within 1 month after the onset of cerebral infarction or within 3 months after the onset of a cerebral hemorrhage. Patients in the stable operation group were operated on within 1 to 6 months after the onset of cerebral infarction, or within 3 to 6 months after the symptoms of a cerebral hemorrhage. Patients who underwent operation more than 6 months after the onset of stroke symptoms were regarded as members of the long-term operation group.MMD stage: Refers to the staging on the side of the operation. Suzuki stage 1–2 or MRA score 0–1 is in the early stage, Suzuki stage 3–4 or MRA score 2–7 is in the middle stage, and Suzuki stage 5–6 or MRA score 8–10 is in the late stage [Preoperative blood pressure: Patients previously diagnosed with hypertension did not regularly use antihypertensive drugs, and patients newly diagnosed with hypertension  were recorded as preoperative hypertension.Intraoperative blood pressure: Intraoperative high blood pressure was recorded when arterial systolic blood pressure ≥150 mmHg or arterial diastolic blood pressure ≥100 mmHg and the duration was more than 5 min.2 during operation: PCO2 < 35 mmHg measured at one-third of the time or recorded twice randomly during the operation was regarded as low PCO2 during the operation. PCO2 > 45 mmHg measured at one-third of the time or recorded twice randomly during the operation was regarded as high PCO2 during the operation.Postoperative blood pressure: Systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg measured 3 times, not in the same day, during the perioperative period after operation was regarded as postoperative high blood pressure. PCOCerebrovascular occlusion times: During direct bypass surgery, the time from arterial clamp clamping to completion of anastomosis, removal of arterial clamp, and recanalization of recipient vessels. They were divided into three groups: ≤20 min, 20 min~40 min, and >40 min. Simple indirect bypass surgery was placed into the ≤20 min group because the recipient vessels were not clipped.The surgical methods include combined revascularization and indirect revascularization. Indirect revascularization mainly refers to encepho-duro-myo-synangiosis (EDMS), Combined revascularization refers to the simultaneous implementation of extracranial–intracranial bypass surgery + EDMS. Extracranial–intracranial bypass surgery, that is, direct bypass surgery, used a single bypass  as the donor vessel, and the M4 segment of the middle cerebral artery as the recipient vessel for revascularization.Three months after surgery, the patients were followed up. All-inclusive patients were followed up for ≥3 months . The follow-up content includes Modified Rankin Scale (mRS) score and whether there is a long-term cerebral hemorrhage incident.K-S test for normal testing, and the measurement data that do not meet the normal distribution use the P-P grammar to determine whether they approximately obey the normal distribution or not. The measurement data which conformed to or approximately conformed to the normal distribution were expressed by mean ± standard deviation , and the differences between groups were compared by a rank-sum test. The counting data were expressed by the number of cases and the rate. The chi-square test or Fisher’s exact test was used to compare the differences between groups, and the Bonferroni correction was used for pairwise comparison within the group. A Rank sum test was used for ordinal variable data. Multivariate analysis was conducted using binary logistic regression analysis. p-values < 0.05 were considered statistically significant.Statistical analysis of data was performed using IBM SPSS Statistics version 25.0 . The measurement data use the TND occurred in 26 cases (12.8%) after cerebrovascular revascularization, of which aphasia (26.9%) was the most common symptom. The median time of occurrence of TND was 3 days, and the median duration of TND was 6 days. There were 12 cases of perioperative stroke (5.9%) and 8 cases of long-term cerebral hemorrhage (3.9%) .p < 0.05). Meanwhile, older age, history of hypertension, the main clinical symptom of patients, lesions involving the posterior circulation, and high perioperative blood pressure are the risk factors of the perioperative stroke (p < 0.05). Further multivariate logistic regression analysis showed that multiple episodes of preoperative symptoms  and lesions involving the posterior circulation  are independent risk factors for TND. Meanwhile, the main clinical symptom of patients was an independent risk factor for perioperative stroke , and the pairwise comparison within the main clinical symptom group showed that the incidence of perioperative stroke in the preoperative cerebral infarction group was higher than that in the preoperative cerebral hemorrhage group (p < 0.0125)  .p = 0.094). None of the eight patients with long-term cerebral hemorrhage had perioperative complications, so perioperative complications had nothing to do with long-term cerebral hemorrhage (p = 0.37)  .MMD is a rare cerebrovascular disease characterized by chronic progressive stenosis or occlusion of bilateral internal carotid arteries and secondary to the formation of an abnormal vascular network in the skull base . Its incAt present, reports on the mechanism and influencing factors of TND are still not comprehensive. It was previously reported that the incidence of TND after cerebral revascularization was about 9.4–38.2% ,15,16,17It was previously reported that the incidence of perioperative cerebral infarction events was 3~10.3% ,26,27,28In the past, the incidence of perioperative cerebral hemorrhage was reported as 0.13–3.6% ,31,32,33In this study, we explored the effects of 19 factors on perioperative complications after revascularization of MMD and the relationship between perioperative complications and long-term prognosis. These factors were divided into four types: baseline data of patients, information of MMD, operation and anesthesia management, and perioperative management data.p < 0.05), which may be due to the loss of self-regulating function of cerebral blood flow, or they are more sensitive to cerebral ischemia [Age: Our study found that older patients had a higher incidence of postoperative stroke events  in patients with a history of hypertension, coupled with the impact and cutting effect of high-pressure blood flow on the blood vessel wall, make endothelial cells damaged and prone to form microthrombi, which make hypertensive patients more likely to have postoperative stroke events .p < 0.05). Excessive blood glucose interferes with the endogenous cardiovascular nitric oxide system, resulting in a decrease in nitric oxide-dependent endothelial dilation function and a decrease in brain CVR. In addition, hyperglycemia reduces the oxygen delivery capacity of hemoglobin, aggravates brain ischemia, and leads to lactate accumulation and intracellular acidosis, which in turn aggravates cerebral ischemia [History of diabetes: We found that history of diabetes is related to TND , and 10 cases of postoperative cerebral infarction occurred in patients whose preoperative main clinical symptom was cerebral infarction. However, one of the two patients with postoperative cerebral hemorrhage had cerebral infarction as the main symptom before operation, which indicated that patients with ischemic stroke before operation were more likely to have cerebral infarction after operation. This is consistent with the research of Park et al. [Main clinical symptom: Previous studies have shown that postoperative CHS is independently associated with preoperative ischemic manifestations . Howeverk et al. . Preoperative attack times: Multiple episodes of preoperative symptoms is a relatively clear risk factor, which has been reported by several studies ,28,39. MStage classification of MMD: Zhao et al.  believe Lesions involving the posterior circulation: In this study, the lesions involving the posterior circulation were considered to be related not only to TND but also to postoperative stroke. Posterior circulation is one of the most important intracranial compensatory vessels in patients with MMD. Typical MMD first involves the internal carotid artery system; the posterior communicating artery will open, and the vertebrobasilar artery can supply blood to the anterior circulation through the cerebral arterial circle. According to the Suzuki staging system, at stage 4, the cerebral arterial circle or even the posterior cerebral artery are occluded, and the vertebrobasilar artery system can only play a compensatory role through the new collateral circulation. At stage 6, the blood supply of the brain completely depends on the collateral circulation formed by the external carotid artery and the vertebrobasilar artery system ,40. HoweOperation method: In theory, the direct bypass has a faster impact on intracranial blood flow, so its perioperative complications should be higher in number than that of indirect bypass, but a meta-analysis shows that there is no significant difference in direct and indirect bypass complications . The cen2: Under physiological conditions, intracranial vessels dilate in hypercapnia and contract in hypocapnia, but for patients with MMD, the intracranial diseased vessels have already dilated to the maximum extent, so an increase in PCO2 will only dilate the vessels without lesions, resulting in the phenomenon of blood theft [PCOod theft . This efod theft . Other factors, such as intraoperative blood loss, urine volume, and hemoglobin concentration, represent the effective circulating blood volume, which is mainly involved in the occurrence of ischemic stroke. In addition, Hwang et al.  also fouBlood pressure: Our study found that preoperative, intraoperative, and postoperative high blood pressure were associated with the occurrence of postoperative stroke, and postoperative high blood pressure was also associated with TND. An increase in blood pressure during and after operation will increase the perfusion pressure of donor and recipient blood vessels, and make the contradiction between the two kinds of blood flow more intense, which will not only aggravate hyperperfusion injuries, but also shift the watershed, and even trigger cerebral infarction in the contralateral hemisphere . Fujimurp = 0.016) and lesions involving the posterior circulation (p = 0.014) are the independent risk factors for TND, and preoperative cerebral infarction as the main clinical symptom of MMD (p = 0.015) is an independent risk factor for perioperative stroke in patients with MMD. When this kind of high-risk patient is encountered clinically, indocyanine green video angiography can be used to select appropriate recipient vessels during operation to reduce the occurrence of postoperative hyperperfusion syndrome [The multivariate logistic regression analysis showed that multiple episodes of preoperative symptoms  For a portion of the postoperative stroke events, we cannot clearly judge the time relationship between blood pressure changes and stroke. There may be a situation that reactive blood pressure rises after stroke. We did not collect blood pressure information after complications, as far as possible, to avoid the occurrence of this kind of error. Finally, this study has some limitations: (1) All 183 patients included in this study were from a single center with geographical restrictions. (2) The blood pressure and PCOOur study found that multiple episodes of preoperative symptoms and lesions involving the posterior circulation were independent risk factors for postoperative TND, and preoperative cerebral infarction as the main clinical symptom of MMD was an independent risk factor for postoperative stroke. This suggests that more attention should be paid to patients with multiple episodes of preoperative symptoms, cerebral infarction as the main clinical symptom, and DSA angiography showing stenosis or occlusion of the posterior circulation because they are at high risk of postoperative TND and stroke. It is suggested that SPECT (single-photon emission computed tomography), CTP (computed tomography perfusion), and PWI (perfusion-weighted imaging) should be used to predict and evaluate the imbalance of cerebral perfusion in advance. During the follow-up, it was found that there was no correlation between the occurrence of postoperative complications and the improvement of long-term prognosis and long-term cerebral rehemorrhage.


Methods. We evaluated a population of elderly individuals >60 years of age undergoing CPB to find correlation of MAP during CPB with development of AKI after the surgery. Patients who experienced sustained low MAP during the CPB defined as that of <65 mmHg were compared with those that had sustained high MAP of >65 mmHg for their outcome with regard to AKI. The KDIGO criteria were used to define presence of acute kidney injury. Results. Of the total 92 patients, 50 were in the low-pressure group and 42 were in the high-pressure group. The MAP was 61.14 ± 5.54 mmHg in the low-pressure group and 68.97 ± 3.65 mmHg in the high-pressure group (p < 0.001). 13 (26%) in the low-pressure group and 17 (40.48%) in the high-pressure group developed AKI (p = 0.140). Male sex was associated with an increased incidence of cardiac surgery-associated AKI (p = 0.034). Conclusions. A higher MAP in the range of 65–75 mmHg during the cardiopulmonary bypass does not significantly prevent acute kidney injury in elderly patients undergoing cardiac valve surgery.We aimed to evaluate the role of higher mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) in preventing development of acute kidney injury (AKI).  It is the strongest risk factor of end-stage renal disease and mortality in patients undergoing cardiac surgery , 2. Alth2) , 8 are t2) –11. Furt2) . The art2) . It is g2) . We hypoPatients who underwent cardiac valve surgery at our quaternary academic medical center from May 1, 2019, to December 31, 2020, were evaluated through their medical records for eligibility for inclusion in this retrospective study. The study followed the international regulations in accordance with the Declaration of Helsinki. The study protocol was approved by the Medical Ethics Committee of Zhejiang Provincial People's Hospital (no. 2018KY034). Written informed consent was obtained from all eligible patients prior to their enrollment in the study. All operations were performed by the identical surgery team.μmol/L or estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, previous heart surgery, endocarditis, liver dysfunction, dialysis, AKI, total phenylephrine intravenous doses >2.0 mg and/or continuous intravenous infusion of norepinephrine (NE) > 0.1 μg/kg/min in the operation, organ transplantation, or any case of an acute cardiac surgery after myocardial infarction, defined as a coronary angiography in <24 h of surgery. Patients who had sustained MAP in the range of 50 mmHg to 65 mmHg were categorized as the low-pressure group (LPG), and those who had sustained MAP in the range of 65 mmHg to 80 mmHg during the CPB were defined to belong to the high-pressure group (HPG). Patients reported to have had fluctuation in MAP ranging between both groups were excluded from the evaluation.All patients who were of age >60 years and had cardiac valve surgery with a CPB between May 1, 2019, and December 31, 2020, were evaluated by retrospective chart review. Inclusion criteria were duration of CPB at least of 90 minutes and MAP during the CPB sustained either below or above 65 mmHg without crossing the 65 mmHg pressure threshold for a prolonged time. Exclusion criteria were presurgical evaluation of serum creatinine (sCr) > 200  μg/kg), propofol (1–2 mg/kg), and cisatracurium (0.2 mg/kg). Maintenance of anesthesia was achieved using continuous infusion of remifentanil (10–20 μg/kg/hour) and propofol (3–8 mg/kg/hour).All patients were premedicated with midazolam 0.1 mg/kg orally the night prior to surgery. Anesthesia was induced with fentanyl (102) at the time of CPB. The priming volume of the extracorporeal circuit was about 1500 ml, which was adjusted according to the patients' body weight, and constituted ringer's solution 1200 ml, 20% albumin 100 ml, 20% mannitol 150 ml, and 5% sodium bicarbonate 50 ml. After CPB was established, cooling was initiated, and the patient's temperature was allowed to drift to 34°C. After clamping of the ascending aorta, cardiac arrest was achieved with cold cardioplegic solution. Cardioplegia was prepared by our perfusionist, which is mixed with blood in a ratio of one part crystalloid Del Nido cardioplegia to four part fully oxygenated patient's whole blood [2 level above the identified critical value of 272 mL/min/m2 [2 and carbon dioxide production (VCO2), the blood gas analysis was performed every half hour, and DO2 was calculated using the following equation: DO2(mL/min/m2) = 10  × pump flow (L/min/m2) ×  arterial O2 content (mL/100 mL), where arterial O2 content was calculated as follows: arterial O2 content (mL/100 mL) = hemoglobin (mg/dL) × 1.34 ×  hemoglobin saturation (%) + 0.003 × O2 tension (mmHg) [CPB was performed after systemic heparinization 300 U/kg and maintaining an activated clotting time (ACT) longer than 480s, and temperature-adjusted flow rates were 2.4 L/ for further monitoring and recovery, where they were monitored to maintain adequate cerebral, cardiovascular, pulmonary, and renal function under the meticulous observation of one intensive and critical care resident and fellow each per shift. Patients were discharged from ICU once they were conscious and hemodynamically stable with spontaneous ventilation, without any active bleeding or life-threatening arrhythmias.Trained staff collected detailed data from recruited patients from the electronic medical records at our medical center. Patients' clinical characteristics collected for each patient included age, sex, height, weight, body mass index , diabetes mellitus, hypertension, chronic obstructive pulmonary disease (COPD), preoperative hemoglobin, hematocrit, preoperative serum creatinine (sCr), left ventricular ejection fraction (LVEF), and EuroSCORE II. Intraoperative data included operative time, CPB time, aortic cross-clamp time, amount of intraoperative fluid, plasma and red blood cell infusion, and the type of surgery , aortic valve replacement (AVR), or tricuspid valvuloplasty (TVP)). Intraoperative hemodynamic parameters included mean arterial pressure (MAP) and the dosage of NE and phenylephrine infusion; postoperative data included hemoglobin, hematocrit, LVEF, extubation time, length of ICU, and postoperative hospital stay.The sCr measurement in the preanesthetic checkup was used as the baseline preoperative value. Preoperative estimated glomerular filtration rate was calculated based on sCr using the Modification of Diet in Renal Disease (MDRD) formula. The intraoperative data including the type of surgery, operative notes, range of sustained MAP, CPB duration, cross-clamp time, blood product transfusion, and fluid requirement, along with the postoperative serum creatinine concentrations measured each morning until the discharge of the patient from the hospital were obtained by reviewing the patient medical records. Other outcome measures collected were the in-hospital mortality, renal replacement therapy, duration of ventilation, and length of stay in the ICU and hospital.AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria as follows: an absolute increase of sCr 0.3 mg/dL within 48 hours or relative change higher than 1.5-fold from baseline within 7 days or urine output less than 0.5 mL/kg/h for at least 6 hours .t-test was used to compare the means of normally distributed continuous variables, and the Mann–Whitney U test was used for continuous variables that were not normally distributed. Differences among categorical variables were analyzed using Pearson's chi-squared test. A p value of <0.05 was considered statistically significant.The statistical analyses were performed using the SPSS statistical package, version 16.0  for Windows. Data are presented as mean ± standard deviation, and frequencies and percentages were used for categorical variables. Student's A total of 92 eligible patients undergoing valve surgery with CPB who had sustained low or high MAP during the CPB were analyzed which included 42 in the high-pressure group (HPG) and 50 in the low-pressure group (LPG).No differences in preoperative data were found between the groups .p < 0.001)  , and thep = 0.140). sCr concentrations expectedly peaked on the first day after surgery and then gradually declined in most patients. Among the patients with AKI, most of the sCr (27/30) elevations were in KDIGO AKI stage 1, and only two patients in HPG and one patient in LPG had developed creatinine more than 2 times the preoperative level (Since intravenous bolus of furosemide (20 mg) was given just before off pump, the AKI diagnostic basis of urine volume is not credible, so the diagnosis of AKI was determined based on changes in creatinine; 30 (32.61%) of the patients developed AKI according to the KDIGO criteria. No significant differences were found in the incidence of AKI between the groups which was 17 (40.48%) and 13 (26%) in the HPG and LPG, respectively (ve level .p = 0.034)  with patients who did not develop AKI (NO-AKI) looking at specific risk factors are presented in = 0.034) . A partiThis is the first study to investigate the relationship between an intended higher pressure during CPB and development of AKI after elective valve surgery in elderly patients. In previous studies, the presence of older age, hypertension, chronic obstructive pulmonary disease, and diabetes was found to be an independent predictor for development of AKI after cardiac surgery –21. We pμg/kg/min during CPB to avoid the adverse effects of NE.The mechanisms of CPB-induced AKI include renal hypoperfusion from low-flow, low-pressure, non-pulsatile perfusion with hemodilution and hypothermia, as well as inflammatory response that may induce afferent arteriolar constriction . Lee et 2 is beneficial for the kidneys. The increased flow rates used were 2.7 L/min/m2 and 3.0 L/min/m2 which improved the renal oxygen supply/demand relationship by 14 and 30%, respectively [2) could be maintained at low-dose metaraminol, an α1-adrenoceptor agonist, because low-dose metaraminol increased the perfusion pressure without affecting renal vascular resistance [A recent study with a more direct approach of measuring renal function by renal vein catheterization suggests that a higher flow than 2.4 L/min/mectively . In thissistance .In a study by Skytte et al. involving patients undergoing liver transplantation, data on renal blood flow (RBF) and glomerular filtration rate (GFR) were obtained by the renal vein thermodilution technique and renal extraction of chromium ethylenediaminetetraacetic acid (51Cr-EDTA), and it was found that RBF and GFR are pressure-dependent at mean arterial pressure (MAP) levels below 75 mm Hg . At a taWe found that males were more likely to develop AKI than females. Our data are similar to those previously reported from the United States where Hsu et al. utilized the National Inpatient Sample to identify patients with dialysis-requiring AKI among 24 million hospitalizations, constituting a nationally representative sample of all hospitalizations in the United States between the years 2007 and 2009, and men were 1.9 times more likely to develop AKI than women .CPB time did not influence the development of postoperative AKI. The AKI group did not have significantly longer duration of CPB than NO-AKI group; this result was not consistent with findings by Xu et al. , and theOur study had several limitations. First, this study used an MAP threshold of 65 mmHg in subdividing the groups with the hypothesis that the patients in the high-pressure group have increased renal perfusion; however, because renal autoregulation is likely inoperative during CPB, as evidenced by an unchanging renal vascular resistance with increasing cardiac output and blood pressure, a higher MAP may not be truly corresponding to a sufficient increase in renal perfusion to influence the development of AKI. Second, the KDIGO criteria used to define AKI are based on sCr, which vary depending on age, gender, muscle mass, and race; the sCr in the postoperative period can also vary considerably depending on the degree of hemodilution, making the values less reliable. Third, due to retrospective nature of the study, there were no data to indicate the measure of tissue perfusion and oxygenation. Specific techniques such as renal artery flow probe, fiberoptic probes, and the probe in the bladder catheter equipped to measure urinary oxygenation could have indicated the contribution of increased AP in improving renal perfusion during CPB and its role thereof in preventing AKI. Further investigations are needed to evaluate the role of other hypothesized contributors of AKI in elderly patients undergoing cardiac surgery.In summary, a higher mean arterial pressure of >65 mmHg during cardiopulmonary bypass did not decrease the incidence of acute kidney injury after cardiac surgery. Male sex is associated with an increased incidence of cardiac surgery-associated AKI.