ObjectiveThe present study was conducted to delineate the prevalence and clinical features of portopulmonary hypertension in patients with hepatic cirrhosis. Possible associations between echocardiographic variables and portopulmonary hypertension were also explored.MethodsA prospective, observational study was conducted between September 2017 and August 2018. Differences in demographics, clinical presentation, laboratory findings, and echocardiographic findings in cirrhosis patients with and without portopulmonary hypertension were compared.ResultsThe prevalence of portopulmonary hypertension in patients with hepatic cirrhosis was found to be 9.3%. Hemoglobin was significantly lower among patients with portopulmonary hypertension compared to those without portopulmonary hypertension . All patients with portopulmonary hypertension displayed right atrial (major: p=0.0001 and minor: p=0.001) and right ventricular  dilation. Several variables such as right ventricular systolic pressure (p=0.0001), pulmonary artery diameter , pulmonary vascular resistance (p=0.0001), tricuspid regurgitation (p=0.0001), pulmonary regurgitation peak pressure gradient (p=0.0001), pulmonary regurgitation end diastolic gradient (p=0.0001), left atrial dimension (major axis: p=0.002), left atrial volume (p=0.04), left ventricular outflow tract (p=0.001), inferior vena cava diameter (p=0.001), and inferior vena cava collapsibility (p=0.001) were higher in patients with portopulmonary hypertension compared to patients without portopulmonary hypertension.ConclusionsThe present study revealed a 9.3% prevalence of portopulmonary hypertension among patients with hepatic cirrhosis. Patients with portopulmonary hypertension displayed significantly lower haemoglobin levels, right and left ventricular dilation, and higher values of several echocardiographic variables as compared to those without portopulmonary hypertension. Portopulmonary hypertension occurs due to coexistence of pulmonary hypertension and portal hypertension. Despite prevalence in patients with and without hepatic cirrhosis, it is more often observed in the former . EtiologPortopulmonary hypertension remains a vastly unexplored condition, especially in the Indian population. The low incidence of this condition eludes its prevalence as well as clear understanding of its clinical features which are yet to be delineated in their entirety. Moreover, the scarcely available clinical data are inconsistent in terms of study design, sample size, patient population, clinical features, protocol/guideline adherence, and diagnostic techniques. All these inconsistencies provide a rather vague depiction of this condition. Against this background the present study was conducted to (i) determine the prevalence of portopulmonary hypertension in patients with hepatic cirrhosis and (ii) determine the association of portopulmonary hypertension in cirrhotic patients, with respect to clinical features and echocardiographic variables.Study design and patient populationThis prospective, observational study was conducted at a tertiary-care centre in India during the study duration between September 2017 and August 2018. King George's Medical University Institutional Ethics Committee issued approval ECR/262/Inst/UP/2013/RR-16. All patients provided written informed consent for study participation. Patients from the Inpatient Department aged 18 to 65 years with chronic liver disorders  were included in this study.The exclusion criteria included patients with congenital heart disease, valvular heart disease, pulmonary veno-occlusive disease, left ventricular disease, pulmonary capillary hemangiomatosis, lung disease, lung and liver transplantation, liver tumours, spleen resection, connective tissue disorders, thyroid gland disorders, sickle-cell disease and related conditions, sarcoidosis, human immunodeficiency virus infection, bacterial infection, current smokers, clinical history of peripheral venous thrombosis or Budd-Chiari syndrome, and adherence to fenfluramine or its derivatives, amphetamines, dasatinib, or interferon-alpha.Diagnosis of pulmonary hypertension and portal hypertensionPulmonary hypertension was diagnosed as mean pulmonary arterial pressure ≥25 mmHg according to the 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) Guidelines for the diagnosis and treatment of pulmonary hypertension . PulmonaLaboratory testsThe tests performed were arterial blood gas (ABG), complete blood count (CBC), serum bilirubin, serum albumin, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alpha feto protein (AFP), prothrombin time (PT)/ international normalized ratio (INR), serum creatinine, hepatitis B surface antigen (HBsAg), hepatitis C antibody test, and activated partial thromboplastin time (APTT).Data collectionData for patient demographics , clinical presentation, laboratory investigations,  and several echocardiographic variables were collected. Echocardiography was performed in line with recommendations outlined by the American Society of Echocardiography in 2015 ,8. A comStatistical analysisContinuous variables are presented as mean ± standard deviation, while categorical variables are presented as frequency and percentages. Continuous variables were compared using unpaired t-test. Categorical variables were compared using chi-square test. A p value <0.05 was considered statistically significant. The statistical evaluation of data was done using the using Statistical Package for Social Sciences version 20 .Demographic characteristicsPortopulmonary hypertension was prevalent in eight (9.3%) patients among the 86 cirrhotic patients. Portopulmonary hypertension was most prevalent in the 51-60 years age group. There were no gender related differences with regards to prevalence of portopulmonary hypertension. Partial pressure of oxygen , carbon dioxide  and systolic  and diastolic blood pressure  did not differ significantly between patients with and without portopulmonary hypertension. Demographic characteristics of the study population are outlined in Table Laboratory investigations and etiologyHemoglobin was significantly lower among patients with portopulmonary hypertension compared to those without portopulmonary hypertension . Pulmonary hypertension prevalence was observed in two of nine (22.2%) patients with severe ascites which was greater compared to patients with mild or moderate ascites (p=0.20). Hepatitis B was observed in four of eight (50.0%) patients with portopulmonary hypertension and Hepatitic C was observed in four of eight (50.0%) patients with portopulmonary hypertension. No patients with portopulmonary had Class A Child Pugh Turcott severity of cirrhosis, five of eight (62.5%) had Class B Child Pugh Turcott severity of cirrhosis, and three of eight (37.5%) had Class C Child Pugh Turcott severity of cirrhosis. Laboratory investigations are detailed in Table Right atrial and right ventricular dilation and other variablesAll patients with portopulmonary hypertension displayed right atrial (major: p=0.0001 and minor: p=0.001) and right ventricular  dilation which was statistically significant. Several variables such as right ventricular systolic pressure (p=0.0001), pulmonary artery diameter , pulmonary vascular resistance (p=0.0001), tricuspid regurgitation (p=0.0001), pulmonary regurgitation peak pressure gradient (p=0.0001), pulmonary regurgitation end diastolic gradient (p=0.0001), left atrial dimension (major axis) (p=0.002), left atrial volume (p=0.04), left ventricular outflow tract (p=0.001), inferior vena cava diameter (IVC) (p=0.001), and inferior vena cava collapsibility (p=0.001) were significantly higher in patients with portopulmonary hypertension compared to patients without portopulmonary hypertension. Right atrial and right ventricular dilation and other echocardiographic variables are elaborated in Tables 5 [The present study explored the prevalence of portopulmonary hypertension among patients with hepatic cirrhosis. The prevalence was found to be 9.3%. Similarly, Chiva et al.  document5 . Atsukaw5  reportedThe prevalence of portopulmonary hypertension was higher among females than males, although not statistically significant. It is possible our study lacked statistical significance owing to the small sample size. However, this finding was found to be statistically significant in the study by Shao et al. . MoreoveHepatitis B was the most common etiology. This observation is further fortified by other studies ,11. HepaLeft ventricular dilatation can be explained by higher severity of anemia seen in portopulmonary hypertension patients . In lineA numerical increase in Child-Pugh scoring classification was observed in the present study, which was found to be statistically significant. This infers that portopulmonary hypertension was observed in all Child-Pugh classes. Although one study has shown a weak association between portopulmonary hypertension and the severity of liver disease ,17, seveStudy limitationsThe present study is limited by the small sample size. In the time spanning the conduction of this study and its publication, the latest guidelines redefining portopulmonary hypertension have been published. The impact of these guidelines in clinical practice warrant further investigations in a population of greater sample size. Secondly, computed tomography (CT) thorax was not performed to rule out interstitial lung disease or ` which can also independently cause pulmonary hypertension. Lastly, right heart catheterization remains the gold standard for the diagnosis of pulmonary hypertension. It is an invasive as well as resource intensive method. However, cardiac catheterization-derived PVR index (PVRI)/PA mean are more representative. These drawbacks have led to echocardiography as a more preferred method. This imaging modality has further been supported by recent literature .The present study revealed a 9.3% prevalence of portopulmonary hypertension among patients with liver cirrhosis. Hemoglobin was significantly lower among patients with portopulmonary hypertension compared to those without portopulmonary hypertension. All patients with portopulmonary hypertension displayed right atrial and right ventricular dilation. Moreover, several echocardiographic variables were significantly higher in patients with portopulmonary hypertension compared to patients without portopulmonary hypertension.


Peripheral arterial stiffness (PAS) as measured using the brachial-ankle pulse wave velocity (baPWV) is considered a valuable predictor of cardiovascular event risk in the general population. The study investigated the correlation between serum PCS levels and PAS (baPWV > 18.0 m/s) in 160 patients with stage 3–5 CKD. Liquid chromatography–mass spectrometry was used to assay serum PCS levels. PAS was detected in 54 patients (33.8%), and it was linked to older age, a higher prevalence of hypertension, higher systolic and diastolic blood pressure, higher serum calcium–phosphorus product and PCS levels, and lower height and body weight. Multivariable logistic regression analysis for independent factors associated with PAS illustrated that, in addition to age and diastolic blood pressure, serum PCS levels exhibited an odds ratio (OR) of 1.098 . These findings demonstrated that serum PCS levels were associated with PAS among patients with stage 3–5 CKD. Cardiovascular disease (CVD) is more frequent in patients with chronic kidney disease (CKD) than in the general population . There aArterial stiffness had been recognized as a strong predictor of CVD and mortality independent of traditional risk factors ,4. Pulsep-Cresyl sulfate (PCS), generated by protein fermentation mainly in the large intestine, is a protein-bound uremic toxin, which contributes to many biological and biochemical (toxic) effects in patients with CKD [with CKD ,6. In thwith CKD . High sewith CKD ,9.It is known that increased serum PCS levels are associated with an elevated CVD risk among patients with CKD. In response to the lack of significant data of the association between serum PCS levels and PAS, we investigated the correlation between serum PCS content and PAS as measured via baPWV in patients with clinically significant stage 3–5 CKD.n = 106) and PAS (n = 54 (33.8%)) groups. Compared with the control group, the proportion of non-dialysis stage 3–5 CKD patients with hypertension was significantly higher in the PAS group (p = 0.026). In addition, compared with the control group, the PAS group was typified by older age (p < 0.001), shorter height (p = 0.033), lower body weight (p = 0.012), and higher systolic blood pressure , diastolic blood pressure , serum calcium–phosphorus product levels (p = 0.030), and PCS levels (p = 0.038). By contrast, there were no significant differences in sex, the prevalence of comorbid conditions, including chronic glomerulonephritis and diabetes mellitus, or the CKD stage between the groups.p for trend < 0.001).Serum concentrations of PCS across CKD stages 3–5 were depicted in p = 0.005), age , and DBP  were the independent predictors of PAS in patients with stage 3–5 CKD , SBP, DBP, eGFR, calcium–phosphorus product, and PCS) in multivariable logistic regression analysis revealed that serum PCS levels (odds ratio (OR) = 1.098, 95% confidence interval (CI) = 1.029–1.171,  3–5 CKD .p = 0.0096, Receiver operating characteristic (ROC) curve analysis indicated that the area under the curve (AUC) for predicting PAS was 0.628 . In multivariate stepwise linear regression analysis, age  = 0.165, p < 0.001), body weight , DBP , and higher log-PCS  were significantly correlated with left baPWV, whereas age , body weight , DBP , and higher log-PCS  were significantly correlated with right baPWV.The correlation and linear regression of brachial-ankle pulse wave velocity and clinical variables are shown in In our CKD participants, who were divided into PAS and control groups, 33.8% of them were classified as having PAS. The major findings of the present study were that old age, elevated DBP, and high serum PCS levels are independent predictors of PAS among non-dialysis patients with stage 3–5 CKD. Furthermore, age, DBP, and log-PCS were positively associated with baPWV, whereas body weight was negatively associated with baPWV.Age and blood pressure (SBP and DBP) are considered the two most important factors in the pathophysiology of arterial stiffness ,11. Over2) or obese (BMI ≥ 28 kg/m2) subjects (49.8%), illustrated that PAS, as measured via baPWV, increased with BMI in the overweight/obese group, whereas BMI was negatively associated with baPWV in the whole cohort [Overweight and obesity are strongly associated with advanced arterial stiffness and pronounced risks of CVD and mortality ,18. The e cohort . Therefoe cohort . In our Elevated serum calcium–phosphorus product levels are associated with vascular calcification, and they contribute to arterial stiffness with increased pulse pressure ,23. In pAlthough our previous study noted a positive association between serum PCS levels and central arterial stiffness in patients on hemodialysis , the exaThe main limitations of the study were its cross-sectional and single-center design and small sample size. The result might not be applicable to the general conditions in the CKD population, which exhibits considerable heterogeneity. In addition, patients with non-CKD and early-stage CKD (stage 1–2) were not included, and gut microbiota was not assessed in this study. Meanwhile, the exact mechanism by which PCS could influence the development of PAS remains unclear, and some biomarkers potentially mediating the link between PCS and arterial stiffness, such as matrix Gla protein and osteopontin, were not available. Therefore, additional longitudinal studies with large samples and diverse designs are needed to clarify these findings.In addition to older age and elevated DBP as the traditional risk factors, increased serum PCS levels were independently predictive of PAS in patients with non-dialysis stage 3–5 CKD. The baPWV values also positively associated with serum PCS levels in this study. These findings suggested that PCS may influence the development of PAS among patients with stage 3–5 CKD, but the mechanism remains to be elucidated.2 were considered indicative of CKD, and the patients were classified according to the Kidney Disease Outcomes Quality Initiative criteria as follows: stage 3 CKD, eGFR = 30–59 mL/min/1.73 m2; stage 4 CKD, eGFR = 15–29 mL/min/1.73 m2; and stage 5 CKD, eGFR < 15 mL/min/1.73 m2 [Non-dialysis CKD patients older than 18 years with regular follow-up at the nephrology outpatient department of a medical center in Hualien, Taiwan, were invited to participate in the study between January 2016 and December 2016. CKD was defined by two measurements of the estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration equation, in which the measurements were separated by an interval of >3 months . eGFRs o/1.73 m2 . All patThe information regarding smoking status, comorbid diseases , and drugs used  was collected from the electronic medical record.2) [After an overnight fast, the anthropometric variables were measured in the morning. Height and body weight were recorded to the nearest 0.5 cm and 0.5 kg, respectively. BMI was calculated as weight (kg) divided by height-squared (m2) .Serum levels of fasting glucose, blood urea nitrogen, creatinine, albumin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine, total calcium, and phosphorus were determined by an autoanalyzer  immediately after the blood samples were obtained from participants after a fast for 10 h ,33.® 3.0 software .We used a Waters e2695 high-performance liquid chromatography system containing a mass spectrometer  to determine the serum total PCS levels according to our previous study [Patients were placed in the supine position and rested for 10 min after blood sampling. Then, four pneumatic cuffs connected to both plethysmographic and oscillometric sensors were wrapped around both upper arms and ankles to assess baPWV using a volume plethysmography apparatus  as described previously . baPWV >Assuming that PAS is present in one-third of participants, with a mean PCS level of 16 ± 9 mg/L and an odds ratio of 1.07 per 1 mg/L increase in PCS, a total of at least 136 patients should be enrolled to achieve a power of 90% (α-level 0.05) [t-test or the Mann–Whitney U-test, as appropriate. Categorical variables were expressed as numbers with percentages and compared using the χ2 test. Multivariable logistic regression analysis (“Enter” model) was applied to the significant variables between control group (baPWV ≤ 18.0 m/s) or PAS group (baPWV > 18.0 m/s) . The ROC curve was used to calculate the AUC and determine serum PCS levels predictive of PAS in patients with stage 3–5 CKD. The correlation analysis was performed using Pearson’s correlation (for continuous variables) or Spearman’s rank correlation coefficient . Non-normally distributed continuous variables were logarithmically transformed when applied to the Pearson correlation. Multivariate stepwise linear regression analyses were used to analyze the variables predicting left or right baPWV in patients with stage 3–5 CKD. SPSS software for Windows  was used for all statistical analyses. p < 0.05 indicated statistical significance.The normality of continuous variables was evaluated by Kolmogorov–Smirnov test. Continuous data were expressed as the mean ± standard deviation for those with normal distribution and as the median with interquartile range for those with non-normal distribution. Between-group comparisons were performed using Student’s independent


To investigate the correlation between prognosis and intracranial carotid artery calcification (ICAC) in patients with acute ischemic stroke (AIS) who receive intravenous thrombolysis (IVT).A total of 156 AIS patients who received IVT from March 2019 to March 2020 were enrolled. The modified Woodcock visual score was used to evaluate ICAC in nonenhanced head CT scans. Patients were divided into high calcification burden  and low calcification burden  groups. Demographic, laboratory, imaging and clinical data were compared between the two groups, and whether HCB was a prognostic factor was evaluated.P < 0.001) and coronary heart disease  and higher serum homocysteine  and hemoglobin A1c  levels. Binary logistic regression analysis showed that atrial fibrillation  and HbA1c  were independent risk factors for ICAC. After adjusting for other risk factors, symptomatic-side and bilateral ICACs were independent risk factors for poor prognosis ,  and mortality ,  in patients with AIS who received IVT.Compared with the LCB group, the HCB group had a higher incidence of atrial fibrillation (49.2 vs.22.1%, ICAC is closely related to the prognosis of acute ischemic stroke after intravenous thrombolysis. Thrombolysis is known to improve outcomes following acute ischemic stroke. Intravenous thrombolysis using recombinant tissue-type plasminogen activator (rt-PA) is still considered the first line of treatment . HoweverIntracranial carotid artery calcification (ICAC) was first observed with radiographic pathology in the early 1960s . Later sIn this context, we examined the relationship of the burden of ICAC with poor outcome, complications and mortality in patients treated with IVT for AIS. Studying the effect of ICAC on the prognosis of IVT in AIS may not only help to understand the relationship between ICAC and stroke, but also modify the acute management strategy, because ICAC information is usually available before treatment decision-making .Medical records of the patients registered in China Cerebrovascular Disease Registration Platform with discharged diagnosis of “AIS” between March 2019 to March 2020 in the stroke center of our hospital were reviewed.Inclusion criteria included the following: (1) 18 years of age or older; (2) diagnosis of AIS based on the diagnostic criteria of acute cerebral infarction formulated by the Compilation Committee of Chinese Cerebrovascular Disease Prevention Guidelines ; (3) hosIn order to increase the safety, feasibility and rationality of the study and increase the homogeneity of the study object to a certain extent, the following cases are excluded: (1) posterior circulation infarction; (2) pre-stroke Modified Rankin Scale (mRS) score > 2; (3) standard contraindications for intravenous rt-PA therapy; (4) Patients receiving endovascular treatment; and (5) patients with malignant tumors, severe liver and kidney dysfunction or drug/alcohol abuse.The study was approved by the ethics committee of our hospital.All AIS patients were treated with rt-PA at a dose of 0.9 mg/kg according to internationally recognized guidelines. Routine monitoring of neurological function scores and blood pressure was conducted. Cranial CT was repeated 24 h after thrombolysis to determine whether there was intracranial hemorrhage. If there was no intracranial hemorrhage, antithrombotic therapy and statin therapy were administered.The following information was collected from all patients: sex, age, and medical history, including hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, coronary heart disease, and history of smoking or alcohol intake. Definition of hypertension: systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥90 mmHg (measured at least three times at different times and in the same way at rest), or normal blood pressure when taking antihypertensive drugs; Definition of diabetes: dry mouth, polyuria, emaciation and other diabetes symptoms and random blood glucose ≥11.1 mmol/L, or fasting blood glucose ≥7.0 mmol/L, or oral glucose tolerance test (OGTT) 2 h blood glucose ≥11.1 mmol/L, (at least two times); Definition of dyslipidemia ; Atrial fibrillation and coronary heart disease were determined according to previous medical history and ECG, or was being treated for it. Smoking history: smokers who smoke more than 1 cigarette a day for more than 1 year; those who quit smoking for more than 15 years are equivalent to non-smoking; Definition of drinking: The conversion method of alcohol consumption and the standard of excessive drinking refer to the research of Kehui Liu et al. (P < 0.001). If the result was inconsistent, it should be decided by both parties through consultation. The calcification score of siphon segment represents the severity of internal carotid artery calcification. Absence or near absence of calcifications was recorded as one point; thin and discontinuous calcification was scored as two points; thin and continuous, or thick and discontinuous calcification was scored as three points; and thick and continuous calcification was recorded as four points  at admission, all images were reconstructed at 0.625 mm axial sections. The ICAC scores were evaluated by a radiology specialist and a neurologist who were blinded to the clinical information, using the modified version of the Woodcock visual scoring . They har points . The calr points , 18.Patient neurological function was evaluated at 3 months after discharge using the mRS score by trained neurologists blinded to other clinical data. The patients who were unable to show up for the follow-up visits were subjected to the mRS score questionnaire via multiple phone calls.The mRS score was dichotomized into favorable  or unfavorable [mRS score 3–6 ].t-tests, and the Mann-Whitney U-test was used for continuous non-normally distributed variables. Logistic regression was used for the multivariate analysis of baseline characteristics as risk factors for ICAC. The factors with statistical significance (P < 0.1) in univariate analysis were taken as independent variables and entered into logistic regression equation for statistical analysis. An enter method was used to design the final model. To further evaluate the interactive effect of atrial fibrillation and HbA1c, a new term  was calculated and included in the relevant regression models as an additional variable. Multivariate logistic regression analyses were used to analyze whether ICAC was an independent risk factor for intracranial hemorrhage, poor prognosis at 3 months, and mortality after thrombolysis adjusted for potential influencing factors selected based on univariate analyses, P < 0.05 was taken as the cut-off for inclusion. P < 0.05 and 95% CIs of ORs (logistic regression) were considered statistically significant.SPSS for Windows, version 22.0  was used for statistical analysis. Continuous variables were presented as the mean ± SD or median (interquartile range), and categorical variables were presented as percentages. The chi-square test was used for categorical data. The normally distributed variables were compared with independent P < 0.001) and coronary heart disease , and higher HbA1c  and higher serum homocysteine levels . Stroke etiology, admission clinical parameters and clinical outcomes of HCB patients and LCB groups were compared. The NIHSS score while admitted to the HCB group was significantly higher than that of the LCB group . The NIHSS score on the 7th day was significantly higher in the HCB group than the LCB group , and the proportion of deterioration (deterioration in NIHSS ≥4) in the HCB group was higher than that in the LCB group . The mRS score of the HCB group was higher than that of the LCB group at 3 months  (P = 0.009) and HbA1c  were independent risk factors for ICAC. The interaction term model showed that the interaction between atrial fibrillation and HbA1c was not significant . Clinical characteristics associated with poor outcome, sICH, mortality were shown in P < 0.001], , sICH ,  and mortality ,   and death , but not with sICH , as shown in A total of 156 patients were included in the study. A total of 61 patients (39.1%) had a high calcification burden (HCB). A comparison of the baseline characteristics of HCB patients and LCB patients was summarized in < 0.001] . The pot< 0.001] . In the The retrospective patient cohort study including 156 acute ischemic stroke patients who received intravenous thrombolysis analyses risk factors for ICAC and the prognostic value of high ICAC for functional decline, intracranial hemorrhage and all-cause mortality during 3 months follow-up. The main findings of the study were that atrial fibrillation and HbA1c were independent risk factors for ICAC and that total ICAC score and ICAC score of the symptomatic side predicted the outcomes of functional decline, intracranial hemorrhage and all-cause mortality.Although our study found that ICAC was closely related to atrial fibrillation, whether there was a causal relationship between ICAC and atrial fibrillation was uncertain. Atrial fibrillation may be a downstream reaction of ICAC. It is generally believed that most patients with ICAC have coronary artery calcification, which is a risk factor for atrial fibrillation –21.Previous studies have found that diabetes mellitus or random blood glucose are independent risk factors for ICAC , 22, 23.ICAC is a manifestation of vascular aging and a risk factor for acute cerebrovascular disease. However, there are few studies on the effect of thrombolysis and the prognosis of acute ischemic stroke. Vascular calcification can be divided into two different forms in morphology, depending on the location, namely, in the intima or media . The effThe effect of ICAC on intravenous thrombolysis is still unclear. Xin et al.  found thConsidering that calcification is a sign of more severe atherosclerosis, we can reasonably expect that increased arterial calcification would impair autoregulation and make blood vessels more likely to rupture. However, whether ICAC is a risk factor for intracerebral hemorrhage after thrombolysis is still controversial. Lin et al.  assertedThe cycle of repeated rupture and healing of the plaque, accompanied by inflammation of the core and fibrous cap, leads to the presence of heterogeneity and calcified carotid plaque . In animLee et al.  found thAn important strength is that only few studies have investigated the relationship between ICAC and the prognosis of patients with acute ischemic stroke who receive intravenous thrombolysis. Yet, our study has several limitations. First, we investigated the prognosis of patients at only 3 months after discharge; longer-term follow-up studies are needed in the future. Second, this was a single-center study, and there was inevitably selection bias. And the sample size is relatively small, especially the sample of sICH and mortality, which leads to the imbalance of sample size. This could have affected the meaningfulness of results obtained. All of these limitations will be addressed in future studies by using a larger sample size. Third, patients who underwent revascularization treatment or received conventional conservative treatment within 4.5 h of onset were not included in the study. We would consider including such patients in the next study. Fourth, undoubtly, the un-calcified plaques were also identified as risk factor to their prognosis. However, in the original design of the project, only calcified plaques were studied, and the number and size of un-calcified plaques were not counted. The interaction between those morphologic characteristics of plaques will be added in future studies. And the types of calcification were not distinguished in our study.Our study showed that atrial fibrillation and glycosylated hemoglobin were independently associated with the prevalence of ICAC. ICAC was an independent risk factor for poor prognosis and mortality of cerebral infarction after intravenous thrombolysis. CT scans coupled with modeling algorithms will provide an objective marker for the prognosis of intravenous thrombolysis in acute cerebral infarction. Intervention of atrial fibrillation or control of high glycosylated hemoglobin may improve the prognosis of acute cerebral infarction after thrombolysis from another perspective.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the Yancheng Third People's Hospital. The patients/participants provided their written informed consent to participate in this study.YS and ZD drafted the manuscript. YS, PP, and ZC participated in the literature collection. YS and GX analyzed the MRI features. HS and JZ reviewed and revised the manuscript. All authors read and approved the final manuscript.This work was supported by the Research Project Fund of Clinical College of Jiangsu Medical Vocational College (20209127).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.


Hypertension is the leading cause of death in human being, which shows high prevalence and associated complications that increase the mortality and morbidity. Controlling blood pressure (BP) is very important because it is well known that lowering high BP effectively improves patients’ prognosis. This review aims to provide a focused update of the 2018 Korean Hypertension Society Guidelines for the management of hypertension. The importance of ambulatory BP and home BP monitoring was further emphasized not only for the diagnosis but also for treatment target. By adopting corresponding BPs, the updated guideline recommended out-of-office BP targets for both standard and intensive treatment. Based on the consensus on corresponding BPs and Systolic Blood Pressure Intervention Trial (SPRINT) revisit, the updated guidelines recommended target BP in high-risk patients below 130/80 mmHg and it applies to hypertensive patients with three or more additional cardiovascular risk factors, one or more risk factors with diabetes, or hypertensive patients with subclinical organ damages, coronary or vascular diseases, heart failure, chronic kidney disease with proteinuria, and cerebral lacunar infarction. Cerebral infarction and chronic kidney disease are also high-risk factors for cardiovascular disease. However, due to lack of evidence, the target BP was generally determined at < 140/90 mmHg in patients with those conditions as well as in the elderly. Updated contents regarding the management of hypertension in special situations are also discussed. Table Accurate measurement of blood pressure (BP) is essential for the diagnosis, management, and risk stratification of hypertension. Measured BP varies according to the measurement environment, behavior of individuals, measurement protocol, device used for the measurement, and technical skill of observers. Therefore, the diagnosis of hypertension should be confirmed by repeat office BP (OBP) measurements with standardized methods at repeat office visits Table  1, 2]. , 2. 1, 2http://www.dableducational.org)  but not elevated out-of-office BP [≤135/85 mmHg in awake BP and home BP or ≤ 130/80 mmHg in 24-hour mean BP]) , 42, (3)Although different among studies, the prevalence of WCH is approximately 15 to 30% in the general population , 42, 44 MH occurs approximately 9 to 30% in individuals with normal OBP , 53 and Unattended automated OBP (AOBP) is measured three times at 1-minute intervals after 5-minute rest in a quiet environment without any medical staff using an automated device . HoweverSeveral novel cuffless wearable mobile devices, such as smartwatches or smartphones, are used for BP measurement , 63. TheApproximately 80% of brachial arterial pressure may be attributed to central arterial pressure. In addition, central BP has been reported to more closely correlate with target organ damage or prognosis . AlthougBecause it is well known that the higher the BP, the higher the risk of CVD and death , 67, regHowever, many observational studies have shown that the earlier the hypertension is detected and treated, the lower the risk of CVD , 70, whiIt is recommended to apply the same corresponding BP to the diagnosis and treatment of hypertension Table . It is v2) indicates a decrease in kidney function [Laboratory examinations are performed to identify additional CV risk factors, secondary causes of hypertension, subclinical organ damage, and concomitant diseases. Routine laboratory tests are mandatory before antihypertensive treatment. Other recommended and extended tests can be performed if necessary Table . In the function . When eGfunction –82. An ifunction , 84. It The CV risk and treatment strategy for hypertension is shown in Table In general, the target SBP is < 140 mmHg and target DBP is < 90 mmHg unless in clinical conditions shown in Table It is clear that antiplatelet therapy can be used for secondary prevention after the onset of CVD in hypertensive patients . HoweverLipid-lowering drug therapy is effective in preventing CVD in high-risk hypertensive patients. In hypertensive patients without CVD, statin was used to lower the LDL-cholesterol level by > 50%, when LDL-cholesterol was ≥130 mg/dL, and its CVD prevention effect is evident . It is rThe goal of glycemic control in diabetic patients is less than 6.5% of glycated hemoglobin. The glycated hemoglobin target may be lowered either if disease duration of diabetes is shorter or if there are no accompanying complications and low risk of hypoglycemia. However, glycemic control goals can be individualized in patients with severe hypoglycemia, short life expectancy, advanced microvascular and macrovascular complications, and the risk of developing hypoglycemia in the elderly aged 75 years or older . Since sWhen starting a new antihypertensive drug or adjusting its dosage or dosing time, it is recommended to follow-up at least monthly until the target BP is reached to check the adherence to the drug and whether the BP is controlled , 106. StReducing the number of dosing increases patient’s adherence, so once-daily antihypertensive dosing is recommended unless there is a special reason . In patiEvidence for the drug treatment of prehypertension in diabetic patients is still limited. In diabetic patients, lowering BP below 130/80 mmHg did not prove a preventive effect on CVD. Rather, lowering BP to < 130/80 mmHg worsened renal function in diabetic patients. Therefore, a general target BP of less than 140/90 mmHg is recommended for hypertensive patients with DM , 115–118Among oral antidiabetic drugs, SGLT-2 inhibitors have an antihypertensive effect . Thus, iAlthough results of SPRINT  and the Orthostatic BP should be periodically measured to check for orthostatic hypotension. Since intensive BP control rather reduces the risk of orthostatic hypotension, there is no need to reduce the drug if orthostatic hypotension is suspected . TreatmeConsidering the “J curve” phenomenon in hypertensive patients with CAD, an excessive decrease in SBP increases CV risk, which is more pronounced in patients with left ventricular hypertrophy. Therefore, hypertensive patients with CAD should be carefully managed so as not to lower SBP to less than 110 mmHg and DBP to less than 70 mmHg .As antihypertensive medication, β-blockers should be considered first for 1 day to 1 month after acute myocardial infarction . ACE inhIf hypertensive patients have atrial fibrillation, the risk of thromboembolism is high, so anticoagulation is considered unless contraindicated , 137.Coarctation of aorta is usually corrected with surgical treatment in childhood. However, even after surgical correction, hypertension can be developed in childhood, requiring long-term follow-up. In some patients, coarctation of aorta is not found until adulthood, which progresses to severe hypertension, resulting in cardiac hypertrophy, left ventricular hypertrophy, and target organ damage accompanied by extensive collateral circulation down the coarctation site. However, there is still randomized study on an appropriate BP treatment strategy in patients with coarctation of aorta .Bicuspid aortic valve is common in men and related to coarctation of aorta. Also, patients with bicuspid aortic valve are more likely to develop aortic disease than the general population. If BP is not controlled, it can progress to aortic aneurysm, leading to dangerous consequences such as aortic rupture , 140. Th2), proteinuria > 1 g/day, and polycystic kidney disease [The main aim of controlling BP in patients with CKD is to slow the deterioration of renal function and reduce the morbidity and mortality of CVD. The SPRINT study has shown benefits in all-cause mortality and cardiovascular morbidity with a target SBP of < 120 mmHg in the hypertensive CKD subgroup without diabetes , 150. Ho disease . The upd disease .In randomized controlled trials and a large network meta-analysis, combination therapy was compared to monotherapy. Despite lowering proteinuria in the short term, combination therapy did not reduce all-cause mortality or cardiovascular morbidity. Also, it did not slow the progression of CKD to end-stage renal disease; however, combination therapy increased the incidence of acute renal injury and hyperkalemia compared to monotherapy –148. TheThe relationship of hypertension and antihypertensive drugs with sexual dysfunction in women is not so clear as in men . AccordiIn order to increase adherence to antihypertensive medications, all hypertensive patients should be regularly checked for sexual dysfunction during the follow-up period as well as at the early stage of diagnosis. In particular, for men complaining of sexual dysfunction, it is recommended to avoid prescription of β-blockers or diuretics, which are relatively related to sexual dysfunction, or to substitute other drugs for them.Hydralazine, methyldopa, labetalol, and nifedipine are useful oral antihypertensive drugs during pregnancy . HoweverAlthough previous studies have not shown a statistically significant preventive effect due to problems such as lack of power and short follow-up duration, it has been found that active BP-lowering treatment tends to reduce the incidence of dementia –186.


Aim: To assess changes in blood pressure (BP) and arterial stiffness among 84 rotating shift and 25 dayworkers (control subjects) at two industrial plants during a 4-year follow-up, and to assess changes in outcome variables among shift workers at the two plants after a reduction in the number of night shifts during the last year of follow-up in one of the plants. Methods: We collected demographic data using a questionnaire, examined systolic and diastolic blood pressure , central systolic and diastolic aorta pressure , augmentation pressure (AP), central pulse pressure (cPP), and pulse wave velocity (PWV). We registered sleep quality. The last 4–14 months of follow-up one plant implemented a 12-week shift plan reducing the total number of night shifts and consecutive night shifts from 16.8 to 14 and from 7.2 to 4. To assess differences in change of outcomes between study groups we applied linear mixed models. Results: The dayworkers were older, more hypertensive, reported less sleep disturbance, and smoked/snuffed less than the shift workers did. The adjusted annual increase in PWV was 0.34 m/s  among shift workers and 0.09 m/s  in dayworkers, yielding a significant difference of change of 0.25 m/s . No significant differences were found between the two groups of shift workers in any cardiovascular disease (CVD) outcome during the last year of follow-up. Conclusions: Shift work in industry is associated with arterial stiffness, reflecting an increased risk of future CVD. No significant changes in arterial stiffness were identified as a consequence of a small reduction in the number of night shifts and consecutive night shifts. Shift work including night shifts and long working days are widespread and increasing. Between 10–30% of the workforce in the Western world is engaged in such work [Shift work includes work beyond conventional work hours. Night shift work is defined as work of three hours or more between 23:00–06:00 o’clock, or which comprises more than seven consecutive hours including midnight and five o’clock in the morning [Shift work increases the risk of accidents, and has been associated with endocrine disorders such as overweight, metabolic syndrome and diabetes 2, increased blood pressure (BP), sleep disturbances, and also some cancers . Recent However, it is established that the circadian system involves a central clock (the suprachiasmatic nucleus) and peripheral clocks, in blood cells, in adipose fat tissue, and even brain tissue. The circadian clock in mammals has adapted to the 24-h day and night cycle on earth. This sheds light on the impact of night shift work as the circadian clock regulates neuronal, metabolic, and hormonal functions. Thus, disturbances of the circadian system as a result of night shift work may affect metabolic and cardiovascular health ,9.Arterial stiffness is regarded as one of the earliest manifestations of vascular damage ,11, and It is possible to measure PWV several ways, but in the present study, we use the carotid to femoral PWV (cfPWV) approach. cfPWV is considered the gold standard method for assessing large arterial stiffness with a high degree of reproducibility ,14.2max), but also assessing glycosylated hemoglobin, lipids, inflammatory and adhesion markers [In a systematic review of shift work and early arterial stiffness Gusmao et al. selected 11 articles in which PWV indicated arterial stiffness. Most of the studies are cross-sectional or prospective studies of short duration. Three of these papers were sub-studies within the present cohort ,16,17. T markers . In our  markers . We also markers .The main aim of this study was to assess changes in BP and arterial stiffness and to determine if (i) PWV continues to increase among shift workers compared to dayworkers during the 4-year follow-up and (ii) if PWV differs between shift workers who had implemented fewer night shifts in their schedule as compared to those who maintained the old shift plan schedule during the last year of the follow-up.The present study, initially planned to last for 3 years , is a 6-We collected background data , work history and smoking, snuff use or “snus” habits and history) at the 4-year follow-up using questionnaire. We measured weight in kg using a Seca 22089 balance . The participants provided height in cm and reported aerobic PA with a high degree of intensity in minutes per week, in an administered questionnaire developed at the Institute . We calcInitially the shift workers at both plants followed a 5-week schedule. For this schedule, day, evening, and night shifts rotate in a clockwise direction. The ordinary shift plan comprises seven days shifts and seven nights shifts . At plan® . Following a five-minute rest, we performed measurements on the left arm three times in intervals of one minute while the participant was sitting. We applied the mean of three measurements of the systolic (sBP) and the diastolic pressure (dBP), and the mean of the final three measurements of resting heart rates (RHR) in the statistical analysis. The measurements were performed right after summer vacation mostly between 8 o’clock in the morning and 4 o’clock in the afternoon. We also performed measurements before evening and night shifts to exclude effects on outcome variables due to night shifts.We measured blood pressure (BP) and resting heart rate (RHR) by the means of BpTRU® . PWV is the speed in m/s of arterial pressure waves moving along the aorta and large arteries from the carotid to the femoral artery, cfPWV. The instrument is calibrated annually, and we carried out the measurements according to the recommendations from the manufacturer .We assessed augmentation pressure (AP), central pulse pressure (cPP), central systolic aorta pressure (cSP), central diastolic aorta pressure (cDP), and pulse wave velocity (PWV) by the means of SphygmoCor XCELWe used the Bergen Insomnia Scale (BIS)  to identWe expressed data as mean (±SD). Visual inspection of residuals Q-Q plots confirmed that all outcome variables were approximately normally distributed (plots not shown). Unadjusted differences between the shift workers and dayworkers were calculated using the independent samples t test. Linear correlations were determined using Pearson’s correlation coefficient (ρ). Linear mixed models were applied to determine whether the group of shift workers differed over the four years of follow-up from the dayworkers (control subjects) in terms of annual change in health outcomes. For this purpose, we added the two covariates total number of years since baseline and number of years of shift work since baseline as fixed effects. This approach enabled us to take into account that shift work status had changed for four participants during the last year of follow-up. Total years and years of shift work were considered continuous variables and we assumed a linear change in health outcome with year. In order to investigate the possible health effects of a reduction in number of night shifts, we also did a linear mixed analysis comparing workers with different shift-schedules at the two plants during the 4-years follow-up. This included an extra continuous variable, total number of years with new reduced shift schedule, that enabled us to estimate the difference between shift schedules in terms of annual change of health outcome. To further investigate the possible health effects of a reduction in number of night shifts, we also did a linear mixed analysis comparing shift workers at the two plants during the final year of the follow-up (at the 3-year and the 4-year follow-up). This included an interaction term between plant and time to estimate the difference between plants in the change of health outcome. All mixed model analyses were adjusted for pack-years, being a daily smoker, age, sex, and physical activity (number of minutes per week of high intensity activity) . In addiThe dayworkers, compared to the shift workers, were somewhat older, more hypertensive and to a higher degree on antihypertensive medication, but smoked and used “snus” less than the shift workers. The shift workers reported more sleep problems as compared to dayworkers, The annual increase in measurement of the arterial stiffness measures PWV was 0.34 m/s  among shift workers as compared to that of the dayworkers of 0.09 m/s . This yielded a significant difference in change of 0.25 m/s  in favour of the shift workers. No other differences between shift vs. dayworkers for the other outcome variables were registered, Over the last year of follow-up, there were no significant differences in changes of outcomes comparing shift workers at plant B (new 12-week shift schedule) with those at plant A (old 5-week shift schedule). The difference in change between plant B and A in PWV was 0.06 m/s . The results for the other variables are shown in the p = 0.027. PWV correlated positively with the total number of years of shiftwork as well as with age, BMI, pack-years, BP and RHR (results not shown).At the 4-year follow-up, all blood pressure measurements were highly correlated with each other and with arterial stiffness variables, as well as with BMI, age, and pack-years (results not shown). Sleep score correlated positively with number of years of “snus” use, ρ = 0.216, In this 4-year follow-up study of shift workers and dayworkers in industry, we found an increase in PWV indicating a possible augmentation of arterial stiffness among the shift workers. There were no differences in increase in PWV during the last year of follow-up when comparing the shift workers with a reduced number of total night shifts and consecutive night shifts with those who remained in the original 5-shift schedule.Higher blood pressure affects shift workers . In the The most significant finding following the four years of follow-up was the obvious increase in PWV among shift workers. At baseline registration the shift workers were on average 40 years old with a mean PWV of 7.6 m/s  which isThe results of the 11 papers presented in the review of shift work and arterial stiffness were conflicting when it comes to identify increase in PWV, two in favour and two not being able to detect any association . Our resThe changes in the shift schedule at one of the plants did not affect the PWV results. One explanation being that the reduction of number of night shifts/consecutive night shifts was limited. The new shift schedule yields ≥ 3 consecutive night shifts ≥16 times annually which slightly exceeds the corresponding figure of >15 times resulting in an excess risk for cerebral vascular disease in Bigert’s study . As for Studies suggest, on a general basis, that arterial stiffness could be mitigated by sodium restriction, exercise-based intervention, weight reduction, smoking cessation, and BP and statin treatment ,11,13. AShift work is associated with a high use of tobacco products . The useA strength of the present study is its prospective design with the assessment of BP and arterial stiffness. On all occasions of data collection during follow-up, we perform the measurements of BP and arterial stiffness shortly after summer vacation and the same technician performed the arterial stiffness measurements. A limitation of the study is the inclusion of new workers. In 2019 and 2020 we recruited 20 more shift workers and in 2022 additionally 29 but also three dayworkers wanted to take part in the study. This makes the present study a mix of a cross sectional and a follow-up study. However, the novel participants will take part in the study the last years, and this will strengthen the quality of the data at the final follow-up. Another limitation to be considered is that the workers are different when it comes to their “circadian time” relative to our measurements since shift workers are involved in night shift work. This could have an impact of the mean results of PWV and BP measurements. However, Drager et al.  found noSelf-selection of fit, highly motivated shift workers who were interested in taking part in the study could pose a problem as more shift workers from plant A than plant B participated at baseline registrations. At the 3-year and 4-year follow-up, however, the participation rate is similar in the two plants. Another study limitation is sleep registration as sleep was reported by questionnaire only at follow-up and no objective registrations of sleep quality are available.Arterial stiffness, by the means of PWV, more than doubles as expected during a 4-year follow-up of industrial shift workers. This may increase the risk for future CVD. A small reduction in number of night shifts and consecutive night shifts does not significantly mitigate arterial stiffness.


Furthermore, they had a 38.2% lower relative increase of FMD (FMD%) and a 23.1% thicker IMT compared to the controls . On echocardiography, the CRAO group was characterized by increased dimensions of the left atrium and thicker left ventricular walls, together with impaired left ventricular diastolic function. CRAO is related to vascular endothelial damage, atherosclerosis, and left ventricular diastolic cardiac dysfunction. Thus, non-invasive ultrasound assessments, such as FMD%, IMT, and echocardiography, may be helpful in screening patients with increased CRAO risk, particularly those with other comorbidities.Central retinal artery occlusion (CRAO) is an emergency state characterized by sudden, painless vision impairment. Patients with CRAO have an increased risk of cardiovascular events, including stroke, likely related to vascular endothelial damage. Therefore, we investigated flow-mediated dilatation (FMD) of the brachial artery as a marker of endothelial dysfunction, intima-media complex thickness (IMT) of the common carotid artery, pointing to the arterial wall atherosclerotic alteration, and transthoracic echocardiographic parameters in 126 consecutive CRAO patients  and 107 control participants . Most CRAO patients ( A central retinal artery occlusion (CRAO) is an ophthalmic emergency typified by a sudden, non-traumatic, and painless vision loss. The visual prognosis, although usually poor, varies depending on the etiology and duration of retinal ischemia . AtherosInterestingly, CRAO is widely considered to be an ocular form of acute ischemic stroke, as follows: both have similar etiology, and in both, the pathogenesis is strongly associated with cardiovascular risk factors. Therefore, patients with CRAO should be assessed immediately in a stroke center to minimize the risk of further ophthalmic complications, such as blindness and irreversible retinal damage ,5. AdditAlthough the pathogenesis of CRAO is still not fully elucidated, several explanations have been suggested, related mainly to thromboembolic blockage of the central retinal artery or, less frequently, to vasospasm . HoweverSince typical risk factors of cardiovascular diseases, including classical, genetic, and metabolic ones, are involved in the pathogenesis of CRAO , they maConsidering the possible association between CRAO and vascular endothelial damage, we decided to measure the brachial artery flow-mediated dilatation (FMD) in those patients. We also analyzed intima-media complex thickness (IMT) in the common carotid artery, which can be a helpful tool in assessing the advancement of atherosclerosis, especially at the beginning of the process, as a CVD risk factor . FurtherThe study had a case-control, single-center format and the Bioethics Committee of the Jagiellonian University Medical College approval was obtained (permit No: KBET/79/B/2013). All procedures were carried out under the ethical guidelines of the Declaration of Helsinki. Patients were instructed about the purpose, methodology, and safety protocol of this study. Informed consent was obtained from all participants in this study.We investigated 126 adult patients suffering from CRAO, 66 [52.4%] men, median age as follows: 55, range 18–80 years. We enrolled patients in the period from 2013 to 2019 at the Outpatient Clinic of the Department of Allergy and Clinical Immunology, University Hospital, Krakow, Poland, who were referred from the Department of Ophthalmology, Clinic of Ophthalmology and Ocular Oncology of the Jagiellonian University Medical College in Krakow, Poland, after an episode of CRAO. The diagnosis of CRAO was determined by an ophthalmologist based on the following typical symptoms: a history of sudden, painless visual loss in the involved eye, profound relative afferent pupillary defect, and the presence of characteristic findings on fundoscopy including ischemic retinal edema, a “cherry-red spot” sign in the macula, retinal arteriolar attenuation, segmentation of blood flow in retinal arterioles, and normal appearance of the optic disc . The sevThe control group comprised 107 healthy sex, age, and body mass index (BMI)-matched individuals, 56 men [52.3%], median age as follows: 53, range 34–78 years. Controls were recruited voluntarily from the hospital personnel and their relatives and had no history of thromboembolic diseases.2. Patients with arterial hypertension, hypercholesterolemia, or diabetes mellitus were included in the study. Arterial hypertension was determined by a history of higher blood pressure (BP) than 140/90 mmHg or current antihypertensive treatment. Hypercholesterolemia was stated as serum total cholesterol more than 5.2 mmol/L or current antihypercholesterolemic therapy. Diabetes mellitus was defined as fasting serum glucose above 7.0 mmol/L or present use of insulin or hypoglycemic agents. Smoking habit was defined as the use of at least one cigarette daily. Family history of CVD was considered positive in patients with confirmed CVD in a first-degree relative.In both groups, exclusion criteria included the following: any acute illness during the last few months, history of myocardial infarction or stroke, ongoing cancer treatment, congestive heart failure, liver dysfunction, or renal insufficiency. Liver dysfunction was defined as an elevation of serum alanine aminotransferase more than twice above the upper limit of the reference range. Renal failure was described as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 mv/v, 9:1) centrifuged at 2000× g for 10 min at room temperature within two hours of collection. The values of CRP < 5 mg/L and homocysteine < 16 μmol/L were considered normal.Fasting blood samples were drawn in the morning from the ulnar vein with minimal tourniquet use after sufficient rest. Complete blood cell count, glucose, creatinine, and lipid profile were measured with routine laboratory techniques. The measurement of C-reactive protein (CRP) was performed with the Johnson & Johnson VITROS 250. The homocysteine level was evaluated with a chemiluminescent microparticle immunoassay. The blood samples were kept in tubes with 0.109 mol/l sodium citrate . Two ultrasound experts conducted these examinations independently of each other. The final result for each parameter was the mean of these measurements.We measured FMD of the brachial artery using Celemajer’s method, as described previously . BrieflyMeasurements of intima-media thickness (IMT) of the common carotid artery were performed on both sides of the longitudinal projection immediately proximal to its bifurcation, using a 10 MHz linear transducer. The mean value of the right and left IMT was used for further analysis.Additionally, a transthoracic echocardiogram (TTE) was performed for every participant with measurements of left ventricular (LV) ejection fraction (LVEF) and systolic pulmonary artery pressure (SPAP) using standard methods by two echocardiographers . Other e2 test. The Shapiro–Wilk test evaluated data distribution. The continuous variables were provided as medians with interquartile range or mean with 95% confidence interval (CI) and compared using the Mann-Whitney U test, Kruskal–Wallis, or unpaired t-tests appropriate. A one-way analysis of covariance (ANCOVA) was performed to adjust for potential confounders, including age, sex, BMI, smoking habit, family history of CVD, and comorbidities, such as hypertension, diabetes mellitus, and hypercholesterolemia. A Pearson correlation coefficient was used to analyze the associations between continuous variables. According to the severity of degenerative aortic/mitral valve changes, Kruskal–Wallis and multiple comparison tests with Hochberg correction were used in the subgroup analysis. Multiple linear regression models, built by a forward stepwise selection procedure , were established to find independent determinants of FMD% and IMT. The R2 was checked to measure the variance. Receiver Operating Characteristic (ROC) curves were established to determine optimal cut-off values of FMD% and IMT and calculate odds ratio (OR) with a 95% CI. The statistical significance was set at a p-value lower than 0.05.Statistical analyses were obtained using STATISTICA Tibco 13.3 software . Categorical variables were presented as numbers (percentages), and differences between patient and control groups were compared using the ChiThe demographic, clinical, and laboratory characteristics, including cardiovascular risk factors and basic laboratory tests in CRAO patients and controls, have been presented in n = 111) of the CRAO group had at least one out of five previously mentioned cardiovascular risk factors. Additionally, systolic and diastolic blood pressure were significantly higher in the CRAO patients . As expected, CRAO subjects also frequently received internal medicine medications, such as angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, used by 60 (48%) patients, diuretics by 35 (28%), beta-blockers by 29 (23%), and calcium channel blockers by 25 (20%) of them. Moreover, 25 (20%) patients were treated regularly with statins, and 45 (36%) received aspirin.Altogether, 88.1%  ranged from 2 h to 5 days. At the presentation, the best-corrected visual acuity (BCVA) was between light perception and hand motions, and intraocular pressure ranged from 12 to 22 mmHg (mean: 17.4 mmHg). The relative afferent pupillary defect was profound in all patients. In all cases, the fundoscopy revealed a pale fundus with the “cherry-red spot” appearance of the macula and the attenuation of the retinal arterioles with the segmentation of blood flow. The optic disc was normal.As shown in The detailed results of FMD% and IMT in the CRAO group and controls are provided in p < 0.001, also after adjustment for potential confounders) (The CRAO patients were characterized by a 38.2% decrease in FMD% compared with the control group (ounders) . In addip < 0.001 and r = −0.25, p = 0.01, for CRAO and control, respectively) and in controls to BMI . In patients, it was also lower in men .Interestingly, in both groups, FMD% was inversely related to age , whereas in controls, only with hemoglobin .Among laboratory parameters, in CRAO we documented a negative association of FMD% with blood levels of creatinine and CRP  and calcium channel blockers .Surprisingly, internal comorbidities, smoking status, and a positive history of CVD in the family did not influence FMD% in the CRAO group. However, FMD% values in patients were lower in those who were receiving angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists   . The patp < 0.001) and BMI . On the contrary, in the CRAO group, it remained in positive correlation with systolic and diastolic blood pressure , but also with glucose  and total cholesterol levels . As expected, according to CRAO patients, IMT was higher in smokers , and in those with diabetes .Interestingly, in controls but not in patients, IMT was positively associated with age .Finally, as expected, FMD% and IMT remained in an inverse relationship in both CRAO patients and controls . Additionally, the thickness of the posterior LV walls was associated with left atrium indices, including diameter , area  and volume . In the patient group, CRP level was positively correlated with the thickness of the interventricular septum and the posterior LV wall .The results of TTE parameters are provided in p < 0.001, all). Of note, in the CRAO group, the severity of degenerative valve changes was associated with selected ultrasound parameters, including FMD%, IMT, interventricular septum and left ventricle posterior wall thickness, and a left atrium diameter. For more details, see Interestingly, in patients with CRAO, degenerative and atherosclerotic changes of the aortic/mitral valves were found significantly more often than in controls. Proper structures were documented in 45 (35.7%)/85 (79.4%) subjects, mild lesions in 55 (43.7%)/19 (17.8%), and severe lesions in 26 (20.6%)/3 (2.8%) individuals, in the CRAO group/controls, respectively (p < 0.001), posterior wall thickness , right ventricular mid diameter , and left atrium diameter , area , and volume . Furthermore, there was a positive relationship between the IMT and interventricular septum thickness , posterior wall thickness , and the left atrium diameter  and volume .In the CRAO group, unfavorable decreased FMD% and thicker IMT remained in association with echocardiographic parameters describing increased heart chambers and their remodeled thicker walls. For example, FMD% values correlated inversely with the interventricular septum thickness . Thus, we believe that the comorbidities did not affect the final results. Secondly, FMD% and IMT are, to some extent, subjective. Therefore, they were measured by two independent and experienced sonographers, blinded according to the case and control, and the final results were presented as an arithmetic mean to reduce the error. Furthermore, some of the presented associations may be incidental and not represent a cause-and-effect relationship. Eventually, largely observational and prospective studies are needed to verify our findings; however, it is worth emphasizing that in this study, the CRAO group of patients is the largest one that has been analyzed till now.Our study showed that CRAO patients demonstrated vascular endothelial injury, thicker IMT, and diastolic LV cardiac dysfunction, likely related to the increased risk of cardiovascular events. Performed measurements are non-invasive and straightforward; thus, we recommend them as a valuable diagnostic tool in identifying asymptomatic subjects with an increased risk of CRAO development. As CRAO may herald the onset of severe and even life-threatening cardiovascular events, these patients require an immediate systemic approach and initiate the necessary systemic treatment to minimize the risk of future vascular complications.


Sepsis-related acute kidney injury (S-AKI) is a frequent complication of hospitalized patients and is linked to increased morbidity and mortality. Early prediction and detection remain conducive to optimizing treatment strategies and limiting further insults. This study was aimed at evaluating the potential predictive value of the combined prognostic nutrition index (PNI) and neutrophil-to-lymphocyte ratio (NLR) to predict the risk of AKI in septic patients. n = 731) and the S-AKI group (n = 507). Univariate and multivariate logistic regression analyses were performed to screen the independent predictive factors of S-AKI. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of PNI and NLR.  In this retrospective study, 1238 adult patients with sepsis who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to June 2021 were enrolled. Patients were divided into two groups: the non-AKI group (P < 0.001).  Multivariate logistic regression analysis indicated that age, chronic liver disease, cardiovascular disease, respiratory rate (RR), white blood cells (WBC), blood urea nitrogen (BUN), creatinine (CRE), international normalized ratio (INR), neutrophil-to-lymphocyte ratio (NLR), and prognostic nutrition index (PNI) were independent prognostic factors of S-AKI. In the three models, the adjusted OR of PNI for S-AKI was 0.802 (0.776-0.829), 0.801 (0.775-0.829), and 0.717 (0.666-0.772), while that of NLR was 1.094 (1.078-1.111), 1.097 (1.080-1.114), and 1.044 (1.016-1.072), respectively. In addition, the area under the ROC curve of the PNI plus NLR group was significantly greater than that of the CRE plus BUN group (0.801, 95% CI: 0.775-0.827 vs. 0.750, 95% CI: 0.722-0.778, respectively;  PNI and NLR have been identified as readily available and independent predictors in septic patients with S-AKI. PNI, in combination with NLR, is of vital significance for early warning and efficient intervention of S-AKI and is superior to combined BUN and CRE. Sepsis is characterized by life-threatening organ dysfunction induced by a dysregulated host response to infection, with a high rate of morbidity and mortality worldwide . The kidThe pathological processes underlying mechanisms of S-AKI are complex and multifaceted. Recent research on S-AKI has indicated that inflammation, immunologic dysregulation, and malnutrition together contribute to disease progression , 6, 7. ITraditionally, serum creatinine and urine output have been employed to diagnose AKI; nonetheless, these indicators are highly susceptible to extrarenal factors and have a significant lag in the detection of renal impairment . In receFrom January 2015 to June 2021, data on 1238 patients diagnosed with sepsis were retrospectively collected from the First Affiliated Hospital of Xi'an Jiaotong University. The inclusion criteria were as follows: (1) sepsis, defined by the Third International Consensus Definitions as a sequential organ failure assessment score ≥ 2 points and suspected infection  as an in9/L) [All patient data were collected from the First Affiliated Hospital of Xi'an Jiaotong University's electronic medical record system. The following data were extracted: (1) demographic parameters, including age and gender; (2) vital signs, including body temperature (T), respiratory rate (RR), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP); (3) comorbidities such as diabetes, hypertension, cardiovascular disease, chronic liver disease, and malignancy; and (4) within 24 hours of admission, laboratory measurement results such as white blood cell (WBC) count, neutrophil count, lymphocyte count, platelet count, monocyte count, red cell distribution width (RDW), albumin (ALB), glucose (GLU), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), creatinine (CRE), blood urea nitrogen (BUN), and uric acid (UA) were collected. As reported in previous studies, NLR was defined as the ratio of the absolute neutrophil count to the absolute lymphocyte count ; PNI was9/L) . PLR was9/L) .t-test and the Wilcoxon Mann–Whitney test were used to compare continuous variables between the non-AKI and S-AKI groups. Categorical variables were represented as frequencies with percentages and compared using the chi-square test or Fisher's exact test. Multivariate logistic regression analysis was performed to identify variables associated with incident S-AKI and adjusted for confounding factors to determine the predictive value of the combination of PNI and NLR on the occurrence of S-AKI. Receiver operator characteristic (ROC) curve analysis was used to further analyze the accuracy of various indicators for S-AKI. The Z test was used to compare the area under the ROC curve (AUC). All statistical analyses were carried out by SPSS 24.0, and P values < 0.05 were considered statistically significant.All patients' baseline characteristics and laboratory data were stratified based on whether or not they developed AKI. Variables were classified as either continuous or categorical variables. Shapiro-Wilk tests were used to evaluate variable distributions. Continuous variables following the normal distribution were expressed as mean ± standard deviation, whereas variables not following the normal distribution were represented as median and interquartile ranges. In univariate analyses, Student's P < 0.001). Moreover, there were significant differences between patients in the non-AKI group and S-AKI group in RR , DBP , MAP , and comorbidities such as diabetes , hypertension , cardiovascular disease , and chronic liver disease . Meanwhile, no statistically significant differences in HR, temperature, SBP, and malignancy were noted between the two groups (P > 0.05).The patient enrollment flow diagram is illustrated in P < 0.001), neutrophil count , lymphocyte count , platelet count , ALB , AST , ALT , TBIL , CRE , BUN , UA , INR , NLR , PNI , and PLR . However, these differences were not significant for monocyte count, RDW, and GLU.Clinical and laboratory results during and 24 h following admission are listed in Multivariable binary logistic regression analysis was used to identify potential predictors of S-AKI in septic patients. Variables included age, sex, diabetes, RR, MAP, WBC count, platelet count, AST, ALT, TBIL, BUN, CRE, INR, UA, PNI, PLR, and NLR, as well as diabetes, hypertension, cardiovascular disease, chronic liver disease, and malignancy. As outlined in P < 0.001) and NLR , as depicted in P = 0.003).According to ROC curve analysis, the most influential indicators for patients with S-AKI were PNI , the combination of PNI and NLR was able to greatly enhance the accuracy in predicting the occurrence of S-AKI (AUC = 0.801). Among them, the sensitivity of PNI+NLR was significantly higher than that of BUN+CRE . It is worthwhile pointing out that in investigating the course of renal injury in diverse septic patients more comprehensively, patients with cirrhosis, malignancy, and other underlying adverse conditions were also included. That might also be one of the reasons underlying the lower specificity of PNI+NLR compared to BUN+CRE .Nevertheless, our study has several limitations, which are summarized as follows: (1) This was a single-center retrospective study with a small sample size. As a result, prospective follow-up studies with a large sample size are necessitated to validate our findings and confirm the predictive efficiency of combined PNI and NLR. (2) Although we investigated the risk factors for AKI in hospitalized septic patients, it is conceivable that not all of them were considered. (3) We only included serological indicators within the first 24 hours of admission and did not dynamically analyze alterations in patient indicators during hospitalization. (4) Due to a lack of corresponding follow-up data, we were unable to confirm the impact of risk factors on subsequent patient survival status. (5) Owing to missing data, other inflammatory biomarkers like C-reactive protein and lactate were not assessed. (6) The retrospective study had a lengthy data collection period, and advances in septic treatment technologies during this time period may have influenced clinical outcomes.The assessment of prognostic risk in patients with sepsis has always been challenging in clinics. Our study indicated that RR, WBC, BUN, CRE, INR, NLR, PNI, and chronic liver and cardiovascular diseases were independent predictors of S-AKI in septic patients. Furthermore, the combination of the inflammatory marker NLR and the immune-nutritional marker PNI has a higher diagnostic value than the traditional markers CRE and BUN, signaling that they may have complementary advantages and improve the accuracy of early prediction of S-AKI.


The interindividual heterogeneity in response to the antihypertensive effect of irbesartan has received considerable attention because of gene polymorphism. In this study, we investigated the new combinational influences of AGTR1 and ABCB1 gene polymorphism on the therapeutic effect of irbesartan among Chinese hypertensive patients. A total of 353 samples including 168 normal people and 185 hypertensive patients were adopted, and genotypes comprise ABCB1  and AGTR1 (AA and AC) in this study. The results of multiple linear regression models showed that no statistically significant differences were observed in blood pressure change following irbesartan administration in each genotype from either ABCB1  or AGTR1 (AA and AC). However, spline smoothing analysis demonstrated that the blood pressure therapeutic responses of irbesartan presented a noticeable difference among different ABCB1 genotypes when irbesartan doses reached over 300 ng/mL. Eventually, we assumed that the different drug responses of irbesartan among various AGTR1 genotypes were due to the diversity of the irbesartan-conjugated protein, which is responsible for crossing-coupled intracellular G-protein-coupled receptors (GPCRs). Essential hypertension  is defined as a rise in blood pressure  of undetermined cause . It is eIn regard to hypertension treatment, there is not any therapy of elimination and eradication for hypertension. Therefore, for the earlier stages of hypertension, doctors adopt preventive strategies  to reduce the incidence of hypertension complications ; for established hypertension, the combination strategy of pharmacotherapy and abovementioned lifestyle modification will be emphasized . Irrespe1), which is deemed to regulate most of the physiological activities of AII [β-receptor blockers, calcium channel blockers (CCBs), and diuretics [As one of the first-line antihypertensive drugs, irbesartan is orally administered alone or with other antihypertensive drugs, in a dose of 150–300 mg/day, for the treatment of mild to moderate hypertension in clinics , 7. The s of AII . Angioteiuretics , 10. Theiuretics , 11. Actiuretics , which iiuretics –15.Moreover, the study of breeds using molecular techniques is very important and useful for identifying their characteristics –18. The 2. Each subject underwent a detailed history and physical examination by an experienced internist. This study was approved by the Ethics Committee of Jiamusi Medical University. The purpose and procedures of the study were carefully explained to all participants, and written informed consent was obtained from all participants.Patients with mild-to-moderate hypertension were enrolled from The First Affiliated Hospital of Jiamusi Medical University, Jiamusi, China, from June 2015 to July 2016 (Ethics number: IRB-AF/25–1.0). In total, 194 males and 159 females, which include 168 healthy controls and 185 patients, were recruited to participate in the study . In brieSBP and DBP were measured by well-trained nurses using a mercury-gravity manometer with appropriately sized cuffs after the patients rested in a seated position for at least half an hour without smoking or having tea or coffee. A questionnaire survey was conducted to obtain relevant baseline characteristics, including occupation, education background, alcohol intake/smoking history, age, gender, weight, height, and other demographic factors. Additionally, for the patients with diabetes mellitus, fasting plasma glucose levels at baseline and corresponding treatment were collected.nd, 4th, and 8th weeks; i.e., patients were asked to come to the study center every 7 days for the follow-up medication for next 7 days. During the follow-up, patients were requested to record the time they took medication and any side effects in a standardized diary. Patients were excluded from the study if they were unable to tolerate drug therapy or took any other medications during the follow-up. Blood were collected at the time point from predose on the first day and the specific time point before drug administration. Blood plasma was obtained from blood samples after centrifuging  at 48°C and stored in a −80°C freezer before analysis.All patients were instructed to take a 150 mg tablet of irbesartan  once daily in the morning, on an empty stomach, for 2, 4, and 8 consecutive weeks. Irbesartan doses were administered at our study center for the first and the 2Plasma irbesartan concentration was determined using HPLC with fluorescence detection as described in a previous study . To ensuVenous blood samples were collected from all participants. Genomic DNA was extracted using the QIAamp Blood Kit  by standard techniques and stored at −20°C until genotyping. SNP in AGT1R and ABCB1 genes was genotyped using the TaqMan allelic discrimination method . We selected SNPs with minor allele frequency (MAF) more than 0.1 in the population of China, and genotyped SNPs were evenly distributed across the AGT1R gene with an average distance of 15 kb SNPs.t-test between two groups or one-way ANOVA among three groups for continuous variables and the χ2 test for categorical variables. A LOWESS smoothing curve was produced to illustrate a correlation between the BP baseline and the BMI. Blood pressure (BP) response was defined as the BP before treatment minus BP on 28th day. The effect of the SNP on BP response to irbesartan was estimated by multiple linear regression models with adjustment for potential confounding variables. Genotypes, that is, AGTR1 (AA and AC) and ABCB1 , were included in a regression model as 0/1 dummy variables. We also examined the additive interaction effect between SNP and plasma irbesartan concentration on BP responses. A spline smoothing curve of BP therapeutic response in relation to plasma concentration of irbesartan was established through being stratified by ABCB1 genotypes.The SAS statistical program  was used for data analysis. Descriptive statistical analyses were presented as percentages for categorical variables and means (SD) for continuous variables. The between-group data were compared using Student's For hypertensive patients, no responders were taking other antihypertensive drugs except for irbesartan during the study. For demographic information, there is a similar population of males and females, and they were both similarly aged at an average of roughly 48–50 years. Numerous biochemical and physiological indexes in human peripheral blood serum and urine were measured in both groups , and theFurthermore, among the objects in this study, we did not observe any relevance between the BMI of the objects and SBP (systolic blood pressure) and DBP (diastolic blood pressure) .Genotype frequency distributions were determined among several groups of people employed in this study and showed that there were not statistically significant differences in several subtypes of either AGTR1 or ABCB1 .Similarly, no statistically significant differences in subtype distributions in AGTR1 or ABCB1 were witnessed among age, gender, BMI, and baseline SBP/DBP .First, we did not find statistically significant differences in the hypertensive effects of irbesartan of certain concentrations among the genotypes of either ABCB1  or AGTR1 (AA and AC) .However, the hypertensive effects of higher concentrations of irbesartan became statistically different in the diverse genotypes of ABCB1 , which could be observed on the spline smooth plots of blood pressure responses to irbesartan .In order to investigate the underlying mechanism of the aforementioned blood pressure responses to irbesartan, we converted the measurement data into categorical variables and then compared them with the analysis of variance. The result showed that there were statistically significant differences in the genotypes of AGTR1 despite not showing any significant differences in the ABCB1 genotype. Interestingly, we found that the maximum component in the binding site of irbesartan and GPCRs was the family A subtype G-protein-coupled receptor .http://www.swisstargetprediction.ch/).The pie chart shows the proportion of binding proteins of irbesartan, predicted by SwissTargetPrediction (Firstly, we could eliminate the possibility that the blood pressure lowing effects of irbesartan are not derived from the patients' demographic characteristics, such as gene genotype distribution, and the baselines of SBP/DBP and BMI-SBP. It is because we found statistically significant differences in BMI and ALT between control and patients  in the dDrug response is dependent on the combined effect of a variety of factors, such as patients' age, body state, concomitant therapy, and drug interactions. Among numerous factors, the sequence variants in patients' genes encoding drug-metabolizing enzymes or drug-targets are obviously not to be sniffed at and of great value to clinical medication. This is because the observed therapeutic effect is actually a mirror of biochemical and physiological adaptations between the drug and its target. Compared to other influencing factors, the genetic factor of drug response is generally stable throughout patients' lifetime . So, in This further facilitates the mechanism investigation of aforementioned phenotype. During the pursuit process, we pleasantly found that the largest component in the binding site of irbesartan and GPCRs was the family A subtype G-protein-coupled receptor . As we kThe limitation of this prospective study mainly included the following two parts. First, the enrollment numbers of both hypertension patients and healthy controls were restricted because of objective condition. Second, we only chose to study the most important SNPs among AGT1R/ABCB1 genes rather than completely investigate many other SNPs, which might function in the anti-hypertension effect of irbesartan as well.To sum up, our data demonstrated a significant interaction between plasma irbesartan concentration and AGTR1/ABCB1 in SBP/DBP responses, although their manifestations were different. This is to say that various hypotensive effects occur in the patients with different subtypes of AGTR1. Meanwhile, the patients with diverse subtypes of ABCB1 do not show significant difference in response to same plasma concentration of irbesartan. However, in the context of adjusting serum irbesartan concentration, we found that the patients with different ABCB1 subtypes illustrated a different trend of antihypertension, suggesting a role for AGTR1/ABCB1 gene variants in modulating individual responses to irbesartan antihypertensive therapy. There is no doubt that more precise and larger cohort studies are required to confirm our findings.


The current study aimed to investigate the time course of changes in choroidal circulation hemodynamics and their relationship to systemic circulation dynamics during the normal menstrual cycle in young, healthy women using laser speckle flowgraphy (LSFG).This prospective study included 26 eyes from 13 young, healthy women (21.3 ± 4.0 years) with a normal menstrual cycle and 24 eyes from 12 young, healthy men (21.8 ± 4.4 years) as a control group. The macular mean blur rate (MBR), a quantitative index of relative blood flow velocity in the choroid, was measured using LSFG. MBR, intraocular pressure (IOP), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and ocular perfusion pressure (OPP) were evaluated in the late follicular phase and mid-luteal phase in women and at baseline and 10 days after baseline in men, respectively.P = 0.035, P < 0.001, P = 0.041, P = 0.001, P = 0.014, respectively). The average macular MBR values in the late follicular phase and mid-luteal phase were 12.7 ± 5.3 and 13.7 ± 6.6 (+7.7 ± 19.4%), representing a significant increase in the mid-luteal phase (P = 0.041). The rate of change in MBR exhibited a significant positive correlation with changes in DBP and MBP . However, there were no significant changes in any of the factors in the male group during the study period.In the female group, IOP, SBP, DBP, MBP, and OPP values were significantly higher in the mid-luteal phase than those observed in the late follicular phase (Our results suggest that in young, healthy women with a normal menstrual cycle, choroidal blood flow velocity decreases during the late follicular phase and increases during the mid-luteal phase, depending on systemic circulatory dynamics. Normal menstruation comprises a cycle of four phases , with the entire cycle lasting approximately 28 days from the start of menstruation. In the follicular phase, estradiol is produced in the granulosa cells of the follicle, which is involved in the development of the endometrium , 2. EndoBlood pressure (BP) increases during the luteal phase , a phenoLaser speckle flowgraphy (LSFG) is primarily used to evaluate the velocity of ocular blood flow –20. In pIn central serous chorioretinopathy (CSC), the pathogenesis of which involves sympathetic hyperactivity, the MBR is increased in the acute stage , 19. SimThe current study aimed to investigate the time course of changes in choroidal circulation hemodynamics and their relationship to systemic circulation dynamics during the normal menstrual cycle in young, healthy women, using LSFG.This study was approved by the ethics committee of Fukuoka International University of Health and Welfare  and adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants after the nature and possible consequences of the study had been explained.This prospective study included 26 eyes from 13 young, healthy women with a normal menstrual cycle and 24 eyes from 12 young, healthy men as a control group. The number of participants in this study was based on previous reports describing the circulatory dynamics and sympathetic activity associated with the normal menstrual cycle , 14, 15.Each participant underwent thorough examinations including BCVA, slit-lamp microscopy, and color fundus photography; additionally, intraocular pressure (IOP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and LSFG were measured.LSFG-NAVI  targets moving red blood cells in the eye using an 830 nm diode laser to illuminate the ocular fundus. The laser speckle method has the advantage of allowing for non-invasive, quantitative, repeated examinations and reproducible results , 23, 24.For all participants, IOP and BP were measured at each evaluation point. Within a certain range, the relationship between choroidal blood flow and ocular perfusion pressure (OPP) is linear . OPP wasP values less than 0.05 were considered statistically significant. Cohen’s d measure was used as a post hoc analysis, to estimate the study’s statistical power based on our sample size.All results are expressed as the mean ± standard deviation (SD). The Wilcoxon signed-rank test was used to examine changes in IOP, SBP, DBP, MBP, OPP, and MBR values. Spearman’s rank correlation test was used to determine the relationships between the rate of change in MBR and other factors including IOP, SBP, DBP, MBP, and OPP. For all tests, P = 0.421).The demographic characteristics of all participants are shown in Tables P = 0.035, P < 0.001, P = 0.041, P = 0.001, and P = 0.014)  (Changes in IOP and systemic factors are shown in = 0.014) . Convers= 0.166) .P = 0.041), but there was no significant difference at 10 days after baseline in male participants (P = 0.931) (Changes in MBR are shown in Tables = 0.931) .R = 0.456, P = 0.019 and R = 0.474, P = 0.014, respectively). However, no statistically significant correlation was observed between MBR and other factors including IOP, SBP, and OPP .The factors significantly correlated with the rate of change in MBR between the follicular phase and mid-luteal phase are shown in To the best of our knowledge, the present study is the first to investigate the course of quantitative changes in choroidal blood flow velocity during the normal menstrual cycle in young, healthy women. Significant increases in MBR values at the macula were associated with increases in systemic circulation factors including SBP, DBP, MBP, and OPP. Furthermore, the rate of change in the macular MBR was positively correlated with the changes in DBP and MBP. In the normal menstrual cycle, sympathetic hyperactivity during the luteal phase suggests that choroidal blood flow velocity increases along with increases in systemic circulatory dynamics. In contrast, no significant changes in any factors were observed between baseline and 10 days later in the male control group.Autonomic nervous system activity is known to vary during the menstrual cycle. In young women, sympathetic activity increases during the luteal phase, while parasympathetic activity decreases –10. In tPrevious studies have reported that, in non-inflammatory diseases with an etiology characterized by sympathetic hyperactivity, such as CSC, choroidal blood flow velocity increases in the acute phase and decreases in the regression phase , 19. TheThe primary limitations of this study were: first, the relatively small sample size and the resultant statistical power being minimally below the desired threshold (78.2% vs 80.0%); second, the absence of other choroidal examinations. To further investigate choroidal changes in healthy participants, the relationship between choroidal function and morphology should be assessed in large samples using both LSFG and optical coherence tomography angiography.Our results suggest that in young, healthy women with a normal menstrual cycle, choroidal blood flow velocity decreases during the late follicular phase and increases during the mid-luteal phase, depending on systemic circulatory dynamics. Thus, LSFG may be a useful method for non-invasively and quickly performing quantitative assessments of choroidal and systemic involvement during the normal menstrual cycle. In addition, the MBR was 7.7% higher in the mid-luteal phase than that in the late follicular phase, indicating that it may be necessary to consider the menstrual cycle in the interpretation of LSFG results in the future.