Chronic kidney disease (CKD) is a common occurrence in patients with diabetes mellitus (DM), occurring in approximately 40% of cases. DM is also an important risk factor for cardiovascular disease (CVD), but CKD is an important mediator of this risk. Multiple CVD outcomes trials have revealed a greater risk for CVD events in patients with diabetes with CKD versus those without. Thus, reducing the risk of CKD in diabetes should result in improved CVD outcomes. To date, of blood pressure (BP) control, glycemic control, and inhibition of the renin-angiotensin system (RASI), glycemic control appears to have the best evidence for preventing CKD development. In established CKD, especially with albuminuria, RASI slows the progression of CKD. More recently, sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1RA) have revolutionized the care of patients with diabetes with and without CKD. SGLT2i and GLP1RA have proven to reduce mortality, heart failure (HF) hospitalizations, and worsening CKD in patients with diabetes with and without existing CKD. The future of limiting CVD in diabetes and CKD is promising, and more evidence is forthcoming regarding combinations of evidence-based therapies to further minimize CVD events. Diabetes mellitus (DM) and chronic kidney disease (CKD) are two of the strongest risk factors for cardiovascular disease (CVD) . This inp < 0.0001), congestive HF , kidney replacement therapy , and death  compared to those without DM. Patients with DM are more than twice as likely to die from cardiovascular disease (CVD) compared to those without DM, and CVD accounts for approximately 60% of the life years lost from diabetes ). In the landmark trial by the Collaborative Study Group, Captopril (an angiotensin converting enzyme inhibitor—ACEI) was shown to have significant effects in slowing the rate of loss of kidney function and reducing the risk of death, or kidney replacement therapy, by half independent of its anti-hypertensive effects. Additionally, ACEI was found to demonstrate significantly less proteinuria . AngioteIn addition, albuminuria has been identified as a risk factor for cardiac and kidney outcomes in patients with type 2 diabetes . RASI haHyperlipidemia is a common finding among patients with diabetes. Current guidelines recommend treatment with statin to achieve target LDL cholesterol of <100 mg/dL, with the goal of <70mg/dL in patients with concomitant DM and CVD. Hyperlipidemia is also associated with CKD, with dyslipidemia worsening as CKD progresses . Statins2. Interestingly, there was no statistically significant reduction in major adverse cardiovascular events (MACE) in patients on SGLT-2 inhibitors with eGFR > 60 mL/min/1.73 m2. However, in patients with eGFR < 60 mL/min/1.73 m2, there was a 15% risk reduction in MACE [Sodium/glucose cotransporter 2 (SGLT2) inhibitors prevent glucose reabsorption in the proximal tubules of the kidney and lower the threshold for glucose excretions, leading to a negative sodium and water balance and an ultimate reduction in blood pressure ,50. Seve in MACE . When co in MACE . Additio in MACE .Glucagon-like peptide-1 receptor agonists (GLP-1RA) are another class of medications that have gained favor in their use in treating patients with concomitant diabetes and kidney dysfunction by preventing the onset of albuminuria and reducing the decline in eGFR. GLP-1RA has effects on traditional risk factors for CKD, including hypertension, by inducing natriuresis and diuresis . The effAldosterone is secreted in response to low sodium intake, a reduction in blood volume, or an increase in serum potassium levels. Aldosterone acts on the mineralocorticoid receptor (MR) in the distal nephron to cause reabsorption of sodium and potassium secretions. MRs are found in the vascular bed, inflammatory cells, and podocytes of the kidneys . OveractPatients with CKD have low-grade systemic inflammation, which has been associated with increased morbidity and mortality. The kidney microcirculation is tightly regulated, and inflammation alters the regulatory pathways and allows toxins like reactive oxygen species (ROS) to cause irreversible damage, nephron injury and failure, and lead to CKD . The inf


The purpose of this study was to investigate the morphological characteristics of the aortic valve and identify factors associated with the progression of aortic valve stenosis (AS) in osteoporosis patients.In this single-center prospective cohort study, we recruited 10 patients  who were taking anti-resorptive medicines at the outpatient clinic of University of Miyazaki Hospital, Japan. Baseline assessments, including transthoracic echocardiogram, blood sampling, and dual energy X-ray absorptiometry, were performed. Follow-up assessments were conducted at 6, 12, 18, and 24 months.th percentile, 9.7 ng/mL; 75th percentile, 23 ng/mL). The baseline levels of AV PFV values were negatively correlated with 25-hydroxyvitamin D levels, determined by univariate linear regression analysis .During the 2-year follow-up, three patients with aortic valve peak flow velocity (AV PFV) ≥2 m/s at baseline developed moderate AS, which is defined as AV PFV ≥3 m/s. However, seven patients with AV PFV <2 m/s did not exhibit any progression of AS. There were significant variations in terms of bone mineral density, T-score values, and biomarkers associated with bone turnover  among the enrolled patients, but none of these factors were found to be associated with the progression of AS. All patients exhibited low vitamin D status, with a median level of 16.1 ng/mL (25Our data suggest that low vitamin D status might be a potential risk factor for the progression of AS in osteoporosis patients undergoing treatment with anti-resorptive medicines.Elderly patients with osteoporosis patients exhibited a subset of aortic valve stenosis. Our data suggest that the baseline aortic valve peak flow velocity predicts the progression of aortic valve stenosis, and there might be an association between the progression and the co-existing low vitamin D status in these patients.The online version contains supplementary material available at 10.1007/s11657-023-01339-2. Degenerative calcified aortic valve stenosis (AS) is the most prevalent form of valvular heart disease . Its preMild-to-moderate and severe AS have been incidentally observed in 26% 142/550)  of patie2/550  ofIn this single-center prospective cohort study conducted at the outpatient clinic of University of Miyazaki Hospital, Japan between November 20, 2017, and March 31, 2020, the inclusion criteria were as follows: i) Japanese osteoporosis patients regardless of etiology, ii) age ≥50 years for both sexes, and iii) patients who were already taking or had recently started anti-resorptive therapy (bisphosphonate or denosumab). The exclusion criteria were: i) scheduled aortic valve replacement within 6 months, and ii) undergoing regular hemodialysis for end-stage renal disease. A total of 10 patients with osteoporosis were recruited by an orthopedist (T.F.), who was unaware of any prior diagnosis of valvular heart disease at the time of enrollment. Clinical history and medication details were obtained from the patients’ medical records. All patients underwent echocardiography, blood sampling, and dual energy X-ray absorptiometry (DXA) at baseline and at 6, 12, 18, and 24 months of follow-up. Hypertension was defined as having a systolic blood pressure of ≥140 mmHg, a diastolic blood pressure of ≥90 mmHg, or taking any antihypertensive medications. Diabetes mellitus was defined as having a fasting plasma glucose level of ≥126 mg/dL, a 2-hour postprandial glucose of ≥200 mg/dL, or taking any medication for diabetes mellitus. Dyslipidemia was defined as having a fasting plasma total cholesterol level of ≥220 mg/dL and/or triglyceride level of ≥150 mg/dL, or taking any medication for dyslipidemia. Blood pressure measurements were taken with the patient in a seated position at the hospital. Primary osteoporosis was diagnosed when no other disease-causing low mineral density, apart from osteoporosis, was observed, and the results of bone assessment met the required criteria . The estimated glomerular filtration rate (eGFR) was calculated using the following formula: eGFR (mL/min/1.73 m2) = 194 × (serum Cr)−1.094 × (age)−0.287  ; and 1,25-dihydroxyvitamin D [1,25(OH)All study echocardiograms were performed by dedicated ultra-sonographers using the following equipment: Aplio 400 , EPIQ7G , and iE33 . A standardized protocol, in accordance with international guidelines , 21, was2, which is crucial for assessing fracture risk. Scans were obtained for the posterior–anterior lumbar spine (L2–L4) and hip, following the standard practice in Japan [DXA is the standard technique employed in clinical practice for measuring bone mineral density (BMD) in units of g/cmin Japan –26 and tin Japan . BMD meain Japan .The primary endpoint of this study was to evaluate the morphological changes of the aortic valve, as assessed by AV PFV, mean pressure gradient, and aortic valve area index at the 24-month follow-up. The progression of AS was defined as a change in AS severity to moderate AS, indicated by a peak velocity greater than 3.0 m/s and a mean gradient higher than 20 mmHg. In cases where a patient did not attend the 24-month visit, either the 12- or 18- month visit was used as the final visit for analysis. The secondary endpoint aimed to explore the parameters associated with the progression of AS.All statistical analyses were performed using SPSS software, version 29 . Data were presented as means ± standard deviations for continuous variables, and as medians with interquartile range (Q1 – Q3). Categorical variables were expressed as the number of patients. Spaghetti graphs were used to visualize the measurements of baseline, 6-, 12-, 18-, and 24-month follow-up for each patient. Furthermore, univariate linear regression analysis was conducted to examine the association between 25(OH)D levels and AV PFV values at baseline. The coefficient (β) and 95% confidence interval (CI) were calculated. A p-value <0.05 was statistically significant.3 analogs  in combination with bisphosphonates (see Online Resource 1). Two patients received native vitamin D and calcium supplement when administered denosumab [The baseline characteristics of the patients are presented in Table enosumab . Daily cFigure 2D (J) over the 24-month follow-up period. There were significant variations in terms of AS progression and biomarkers associated with bone turnover among the enrolled patients. Case 1 experienced overt heart failure accompanied by an elevation in BNP levels during the observation periods. This patient exhibited increased FGF-23 levels, followed by elevations in BAP and TRACP-5b levels after switching to daily teriparatide administration. Meanwhile, the plasma 25(OH)D levels consistently decreased over the 24-month period. Figure Figure 2D levels were found to be insensitive in terms of predicting the progression of AS over the 24-month follow-up period (data not shown). Low vitamin D status contributes to bone loss by stimulating PTH production [2D is tightly regulated by PTH, and it reflects both endogenous production and the effect of activated vitamin D3 analogs in this study [3 analog experienced AS progression along with an increase in serum calcium levels exceeding 10.5 mg/dL [2D levels suggest excessive administration of activated vitamin D3 analog. Further research is needed to determine whether activated vitamin D3 analogs have an additive risk in AS progression. The natural history of AS typically involves a prolonged asymptomatic period, but symptoms develop, initially presenting as exertional dyspnea, and progressing to heart failure [This exploratory study provides the first-time demonstration of the temporal changes in aortic valve morphology and parameters of bone and mineral metabolism in osteoporosis patients receiving anti-resorptive therapy such as bisphosphonates or desunomab. Our data provide support for the notion that the pre-existing aortic valve calcification is a predisposing factor for the progression of AS , 29. Addoduction . 25(OH)Doduction . In thisoduction . It is pis study , 33. Theis study , 35. How.5 mg/dL . The dec failure , 38. Fur failure , 40. The3 analogs [This study has several limitations. Firstly, the sample size was very small, and this may limit the generalizability of the findings. Additionally, there is a possibility of selection bias, which could have influenced the prevalence of AS in the study population. The assessment of AS severity relied on echocardiography, which is subjected to measurement errors, and hemodynamic parameters such as peak velocity, mean pressure gradient, aortic valve area can be influenced by factors like left ventricular function, aortic compliance, and presence of hypertension , 42. Ano analogs , warrantIn conclusion, our findings indicate that low vitamin D status might be a potential risk factor for AS progression.ESM 1(PPTX 46 kb)


Background: Acute kidney injury (AKI) affects increasing numbers of hospitalized patients worldwide. The diagnosis of AKI is made too late in most individuals since it is still based on dynamic changes in serum creatinine. In recent years, new AKI biomarkers have been identified; however, none of these can reliably replace serum creatinine yet. Metabolomic profiling (metabolomics) allows the concomitant detection and quantification of large numbers of metabolites from biological specimens. The current article aims to summarize clinical studies on metabolomics in AKI diagnosis and risk prediction. Methods: The following databases were searched for references: PubMed, Web of Science, Cochrane Library, and Scopus, and the period lasted from 1940 until 2022. The following terms were utilized: ‘AKI’ OR ‘Acute Kidney Injury’ OR ‘Acute Renal Failure’ AND ‘metabolomics’ OR ‘metabolic profiling’ OR ‘omics’ AND ‘risk’ OR ‘death’ OR ‘survival’ OR ‘dialysis’ OR ‘KRT’ OR ‘kidney replacement therapy’ OR ‘RRT’ OR ‘renal replacement therapy’ OR ‘recovery of kidney function’ OR ‘renal recovery’ OR ‘kidney recovery’ OR ‘outcome’. Studies on AKI risk prediction were only selected if metabolomic profiling allowed differentiation between subjects that fulfilled a risk category (death or KRT or recovery of kidney function) and those who did not. Experimental  studies were not included. Results: In total, eight studies were identified. Six studies were related to the diagnosis of AKI; two studies were performed on metabolic analysis in AKI risk (death) prediction. Metabolomics studies in AKI already helped to identify new biomarkers for AKI diagnosis. The data on metabolomics for AKI risk prediction , however, are very limited. Conclusions: Both the heterogenous etiology and the high degree of pathogenetic complexity of AKI most likely require integrated approaches such as metabolomics and/or additional types of ‘-omics’ studies to improve clinical outcomes in AKI. Acute kidney injury (AKI) evolves in increasing numbers of hospitalized patients worldwide. The overall in-hospital incidence has been shown to range from 15 to 30% , and theThe principal aim of the so-called ‘-omics’-concept is to elucidate cellular/tissue response patterns under both physiological and pathological conditions in a more integrated fashion. The term ‘-omics’ represents datasets on the detection, quantification, and characterization of biological molecules. The following types of ‘-omics’ have been proposed as the ‘big four’: genomics, transcriptomics, proteomics, and metabolomics . ParticuThe following databases were searched for references: PubMed, Web of Science, Cochrane Library, and Scopus, and the period lasted from 1940 until 2022. The following terms were utilized: ‘AKI’ OR ‘Acute Kidney Injury’ OR ‘Acute Renal Failure’ AND ‘metabolomics’ OR ‘metabolic profiling’ OR ‘omics’ AND ‘risk’ OR ‘death’ OR ‘survival’ OR ‘dialysis’ OR ‘KRT’ OR ‘kidney replacement therapy’ OR ‘RRT’ OR ‘renal replacement therapy’ OR ‘recovery of kidney function’ OR ‘renal recovery’ OR ‘kidney recovery’ OR ‘outcome’. Studies on AKI risk prediction were only selected if metabolomic profiling allowed differentiation between subjects that fulfilled a risk category (death or KRT or recovery of kidney function) and those who did not. Experimental  studies were not included. Metabolic profiling, also referred to as metabolomics, is the analysis of lower molecular weight (<1.5 kD) metabolites in biological systems/specimens. The latter potentially encompasses individual cells, certain types of tissue, body fluids, or even nutritional components. The term ‘-omics’ represents datasets on the detection, quantification, and characterization of biological molecules . DettmerThe first reference to metabolic profiling in a broader sense was published in 1948. Williams and Kirby  performeIn the following paragraphs, the methods used and the general approach (non-targeted vs. targeted) for metabolic profiling will be mentioned if necessary.2. The last criterion exclusively applies to patients younger than 18 years. Finally, urine output over time may also indicate the stage, independently from dynamic changes in serum creatinine [Acute kidney injury (AKI) must be diagnosed if one of the following criteria is (are) fulfilled: an increase in serum creatinine of at least 0.3 mg/dL or a 1.5-fold increase within seven days or a reduction in urine output to under 0.5 mL/kg/h for 6 h or longer . Three Keatinine . AKI evoeatinine . A compaeatinine . The coieatinine . In the eatinine .® test [Serum creatinine is far from being a so-called optimal biomarker. Kidney excretory function must decline by at least 60% until serum creatinine rises. The marker is by no means specific and offers almost no prognostic value at all. In addition, creatinine does not reflect structural kidney damage that is not associated with diminished excretory function. This particular condition has been defined as ‘subclinical AKI’ . Therefo® test , a comme® test . Thus, t® test . The cli® test ,34,35,36® test . In the ® test ; an upda® test  is, howeThe following paragraphs will summarize all relevant clinical studies on metabolomics regarding AKI diagnosis and risk prediction. The risk categories of interest are KRT, in-hospital death, and recovery of kidney function. Experimental studies will not be discussed since the topic has been addressed in a separate article.A 2016 study published by Elmariah et al.  was perfIn 2018, Zhang et al.  performeA Chinese study from 2021  favored n = 28). Additional groups were (I) patients that received vancomycin for infection control but who did not acquire AKI (n = 23), (II) chronic kidney disease subjects (n = 23), and 23 healthy persons. No individual from any group required KRT. The method used was ‘Triple Quadrupole MS/MS’ [An also more recent study (2021—) investie MS/MS’ . Althouge MS/MS’ . Oxidatie MS/MS’ . MetabolTian et al.  performen = 15), established AKI (n = 22), and controls (n = 30). Patients were recruited from the respective cohorts of two older studies, from which the first compared cystatin C with serum creatinine in critically ill children [Another urine-based study on AKI prediction was published in 2022 . Urine schildren . The secchildren . The iniIn summary, recent studies on metabolic profiling in AKI revealed several new molecules that differ between affected and non-affected individuals, either in serum or urine. Some metabolites, such as the combination of symmetric dimethylarginine (SDMA) and tryptophan  or the 5The data on metabolomics for AKI risk prediction are limited. As mentioned earlier, the risk categories of interest are in-hospital death, the transient or persistent need for KRT, and recovery of kidney function. As summarized by Ostermann et al. , at leasn = 97) and day eight patients (blood was collected on day eight after study inclusion—n = 105). Survival numbers in the two groups were n = 46 on day eight (day one patients) and n = 80 on day 28 (day eight patients). The authors revealed significant differences in metabolite concentrations between survivors and non-survivors, respectively. In the end, several mortality-predictive metabolite combinations were identified. For instance, four distinct markers  were death-predictive regarding day eight (AUC 0.64), whereas a panel of 11 metabolites , LysoPC(16:1), LysoPC(18:2), 1-arachidonoyl-lysoPC, 1-eicosatetraenoyl-IysoPC, tyrosine) was death predictive regarding day 28 (AUC 0.78).Sun and colleagues  performeMetabolomics studies in AKI already helped to identify new biomarkers for AKI diagnosis.One study even revealed AKI-related metabolic patterns that emerged several days before the clinical diagnosis of the syndrome.The data on metabolomics for AKI risk prediction , however, are very limited.Both the heterogenous etiology and the high degree of pathogenetic complexity of AKI most likely require integrated approaches such as metabolomics and/or additional types of omics studies to improve clinical outcomes in AKI.


To what extent are clinicians adhering to the 2017 Clinical Practice Guideline and using a clinical decision support tool to calculate blood pressure percentiles for pediatric hypertension diagnosis, management, and follow-up?In this cross-sectional study of 23 334 children and adolescents (aged 3-17 years) with elevated blood pressure, less than half had a corresponding diagnosis in their medical record or attended the recommended follow-up visit. Using the clinical decision support tool was associated with higher rates of diagnosis, but the tool was underused.These findings suggest that pediatric hypertension and elevated blood pressure remain underdiagnosed and undertreated among children and adolescents, which may have negative health consequences in adulthood. This cross-sectional study examines the rates of adherence to the 2017 Clinical Practice Guideline for the diagnosis, management, and follow-up of hypertension and use of a clinical decision support tool to calculate blood pressure percentiles in children and adolescents. The 2017 Clinical Practice Guideline (CPG) for the diagnosis and management of pediatric hypertension (PHTN) categorizes a greater proportion of children with elevated blood pressure and PHTN, yet several barriers to CPG adherence have been noted.To assess adherence to the 2017 CPG for the diagnosis and management of PHTN and use of a clinical decision support (CDS) tool to calculate blood pressure percentiles.This cross-sectional study used electronic health record–extracted data from January 1, 2018, to December 31, 2019, among patients visiting 1 of 74 federally qualified health centers in AllianceChicago, a national Health Center Controlled Network. Children and adolescents  who attended at least 1 visit and had at least 1 blood pressure reading at or above the 90th percentile or diagnosis of elevated blood pressure or PHTN were eligible for data to be included in the analysis. Data were analyzed from September 1, 2020, to February 21, 2023.Blood pressure at or above the 90th or 95th percentile.International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10], code I10) or elevated blood pressure (ICD-10 code R03.0) and CDS tool use; blood pressure management ; and follow-up visit attendance. Descriptive statistics described the sample and rates of guideline adherence. Logistic regression analyses identified patient- and clinic-level associations with guideline adherence.Diagnosis of PHTN . Guideline-adherent diagnosis was observed in 8810 children (37.8%) with blood pressure at or above the 90th percentile and 146 of 2542 (5.7%) with blood pressure at or above the 95th percentile at 3 or more visits. The CDS tool was used to calculate blood pressure percentiles in 10 524 cases (45.1%) and was associated with significantly greater odds of PHTN diagnosis . Among 15 422 children with blood pressure at or above the 95th percentile, antihypertensive medication was prescribed to 831 (5.4%), lifestyle counseling was provided to 14 841 (96.2%), and blood pressure–related referrals were given to 848 (5.5%). Guideline-adherent follow-up was observed in 8651 of 19 049 children (45.4%) with blood pressure at or above the 90th percentile and 2598 of 15 164 (17.1%) with blood pressure at or above the 95th percentile. Differences in guideline adherence by patient- and clinic-level factors were observed.In this study, fewer than 50% of children with elevated blood pressure had a guideline-adherent diagnosis code or attended guideline-adherent follow-up. Using a CDS tool was associated with guideline-adherent diagnosis, but the tool was underused. Further work is needed to understand how to best support implementation of tools promoting PHTN diagnosis, management, and follow-up. Another EHR study10 found that although blood pressure was nearly always measured at well-child visits, less than half of children with elevated blood pressure received appropriate, guideline-adherent management. Accurate diagnosis is critical for appropriate treatment planning to reduce the risk of future health consequences, as elevated blood pressure in children is associated with impairments in cardiac  and vascular  structures,14 as well as neurocognitive and psychological effects.15 Consequently, children with PHTN are at greater risk of developing hypertension, metabolic syndrome, and left ventricular hypertrophy in adulthood.17Research shows that children with elevated blood pressure and PHTN frequently go undiagnosed.19 In medicine broadly, heuristic decision-making and implicit bias among clinicians can affect treatment recommendations, particularly among patients who are members of historical minority groups.21 Clinical decision support (CDS) tools in the EHR have been shown to save time and decrease clinician decision-making burden, leading to improved recognition of PHTN.23Numerous barriers to PHTN diagnosis and management have been identified, including high patient volumes and short visit times in primary care; low confidence in blood pressure readings due to poor measurement technique or inadequate equipment; and lack of patient follow-up.To date, most studies examining PHTN guideline adherence, as well as use of CDS tools, have been conducted using the Fourth Report. Our primary aim was to examine the rates of adherence to the 2017 CPG for PHTN diagnosis, management , and follow-up. Our secondary aim was to assess associations with guideline adherence, including patient and clinic characteristics and the use of a CDS tool in the EHR designed to facilitate guideline adherence and patient and clinic characteristics.STROBE) reporting guideline for observational studies. All procedures were approved by Northwestern University’s Institutional Review Board, which waived the need for informed consent owing to the use of retrospective data.This report follows the Strengthening the Reporting of Observational Studies in Epidemiology  or PHTN . Patients were excluded if they were pregnant or diagnosed with heart disease.This study included 23 334 children and adolescents  who attended at least 1 health care visit in the AllianceChicago network during the study period and had at least 1 systolic or diastolic blood pressure reading at or above the 90th percentile (aged <13 years) or systolic blood pressure of at least 120 mm Hg and diastolic blood pressure of at least 80 mm Hg (aged ≥13 years) during the study period, and/or had an Participants in the AllianceChicago network use a centrally hosted, common EHR system (AthenaPractice). All visit information, patient characteristics, vital signs, and orders are recorded in the EHR.The following patient characteristics were extracted as coded in the EHR: sex (boys or girls), age , race , ethnicity , and weight status per body mass index (BMI) percentile . Clinic characteristics included the setting .The CDS tool, available starting January 1, 2018, was designed to automate calculation of blood pressure percentiles, classify blood pressure values, identify abnormal values, provide guidance on obtaining manual blood pressure values, and calculate mean values per the 2017 CPG ; orThe child had at least 1 systolic or diastolic blood pressure value at or above the 90th percentile if younger than 13 years, systolic blood pressure at least 120 mm Hg or diastolic blood pressure at least 80 mm Hg if 13 years or older (hereafter referred to as blood pressure ≥90th percentile), and an elevated blood pressure diagnosis (ICD-10 code I10).The child had at least 3 systolic or diastolic blood pressure values at or above the 95th percentile if younger than 13 years, systolic blood pressure at least 130 mm Hg or diastolic blood pressure at least 80 mm Hg if 13 years or older (hereafter referred to as blood pressure ≥95th percentile), and a PHTN diagnosis . We extracted data concerning receipt of a hypertension-relevant referral .The management options for elevated blood pressure included (1) antihypertensive medications, (2) lifestyle counseling, and (3) referrals to specialists. We extracted data concerning antihypertensive medication prescription  (a complete list is provided in the eMethods in 25).The 2017 CPG recommends that patients with blood pressure at or above the 90th or 95th percentile attend a follow-up visit within 6 months or within 2 weeks, respectively. Thus, patients with blood pressure at or above the 90th and 95th percentiles were included if they attended a first visit between January 1, 2018, and June 30, 2019, and were coded as attending guideline-adherent follow-up if they had a second visit within 6 months of the first. Patients with blood pressure at or above the 95th percentile were included if they attended a first visit between January 1, 2018, and November 30, 2019, and were coded as attending guideline-adherent follow-up if they had a second visit within 1 month of the first  elevated blood pressure diagnosis among children with at least 1 blood pressure measurement at or above the 90th percentile and (2) PHTN diagnosis among children with at least 3 blood pressure measurements at or above the 95th percentile. Outcomes for guideline-adherent management included (1) antihypertensive medications, (2) lifestyle counseling, and (3) referrals for children with blood pressure measures at or above the 90th percentile as well as children with blood pressure measures at or above the 95th percentile. Outcomes for guideline-adherent follow-up included 6-month follow-up attendance among children with blood pressure measures at or above the 90th percentile and 1-month follow-up attendance among children with blood pressure measures at or above the 95th percentile. For the secondary aim, multivariable logistic regressions were used to identify associations with guideline-adherent diagnosis, management, and follow-up. Covariates included in all models were patient sex (boys or girls), age (in years), race , ethnicity , BMI status , clinic setting , and CDS tool use . All analyses were conducted using Stata, version 17 (StataCorp LLC).The sample, consisting of 23 334 children with blood pressure at or above the 90th percentile on at least 1 visit, included 12 811 boys (54.9%) and 10 523 girls (45.1%) with a median age of 8  years, and of diverse racial  and ethnic (11 978 [51.3%] Hispanic or Latino and 10 687 [45.8%] non-Hispanic or non-Latino) backgrounds . Of thosICD-10 diagnostic code (R03.0). Compared with children without the diagnosis code, those with the diagnosis code were more likely to be older (4534 of 5839 children [77.7%] aged ≥12 years vs 1893 of 8139 children [23.3%] aged ≤6 years); Black (2479 of 6084 [40.7%]) vs White (5314 of 13 663 [38.9%]) race and White vs Hispanic or Latino (442 of 1417 [31.2%]), other (53 of 284 [18.7%]), or unknown (243 of 855 [28.4%]) race; Hispanic or Latino (5054 of 11 978 [42.2%]) or unknown (239 of 669 [35.7%]) vs non-Hispanic or non-Latino (3517 of 10 687 [32.9%]) ethnicity; classified with obesity (4337 of 9321 [46.5%]) vs normal (2948 of 9727 [30.3%]) BMI; and have attended a clinic in an urban (7208 of 16 863 [42.7%]) vs suburban (1177 of 3794 [31.0%]) or rural (425 of 2677 [15.9%]) setting. There was no significant difference in diagnosis by sex.Guideline-adherent diagnosis results are presented in ICD-10 code (I10). Children who met criteria had greater odds of having a PHTN diagnosis code if they were older (119 of 1041 [11.4%] aged ≥12 years vs 7 of 493 [1.4%] aged ≤6 years); multiracial (4 of 37 [10.8%]) vs White (79 of 1563 [5.1%]) race; and have attended a clinic in rural (22 of 346 [6.4%]) vs urban (95 of 1714 [5.5%]) setting. There were no significant differences in diagnosis by sex, ethnicity, or BMI status.Of 11 675 children who attended at least 3 visits during the study period, 2542 (21.8%) had blood pressure measurements at or above the 95th percentile at 3 visits or more and thus met criteria for PHTN. Of those children, only 146 (5.7%) had a corresponding ICD-10 code R03.0: 4733 of 8436 [56.1%] vs 4077 of 14 892 [27.4%]) and blood pressure at or above the 95th percentile at 3 visits or more (ICD-10 code I10: 118 of 1089 [10.8%] vs 28 of 1451 [1.9%]) .The CDS tool was used to calculate systolic blood pressure percentile for 10 524 children (45.1%). Associations with CDS tool use are presented in the eResults and eTable 1 in Guideline-adherent management results were similar between blood pressure at or above the 90th and 95th percentiles; thus, results for blood pressure at or above the 95th percentile are presented in Antihypertensive medication was prescribed to 831 children (5.4%). Children prescribed antihypertensive medication were more likely to be older (307 of 4151 [7.4%] aged ≥12 years vs 92 of 5271 [1.7%] aged ≤6 years); boys (572 of 8563 [6.7%]) vs girls (259 of 6859 [3.8%]); White (495 of 9039 [5.5%]) vs Asian (10 of 489 [2.0%]), Black (246 of 3970 [6.2%]), Hispanic or Latino (18 of 924 [1.9%]), and other (5 of 197 [2.5%]) race; non-Hispanic or non-Latino (570 of 7176 [7.9%] vs Hispanic or Latino (236 of 7836 [3.0%]) ethnicity; and have attended a clinic in a rural (221 of 1871 [11.8%]) rather than an urban (490 of 10 915 [4.5%]) setting. There was no significant difference in prescriptions by BMI status.Lifestyle counseling rates were high (14 841 [96.2%]). Children who received lifestyle counseling were more likely to be younger (5195 of 5271 [98.6%] aged ≤6 years vs 4019 of 4151 [96.8%] aged ≥12 years); girls (6680 of 6859 [97.4%]) vs boys (8161 of 8563 [95.3%]); Asian (484 of 489 [99.0%]) or Black (3776 of 3970 [95.1%]) vs White (8718 of 9039 [96.4%]) race; Hispanic or Latino (6816 of 7176 [95.0%]) vs non-Hispanic or non-Latino (7638 of 7836 [97.5%]) ethnicity; and classified with overweight (2346 of 2427 [96.7%]) or obesity (6467 of 6669 [97.0%]) vs normal (5731 of 6010 [95.4%]) BMI. There was no significant difference in counseling by clinic setting.Referrals for specialty services related to elevated blood pressure were provided to 848 children (5.5%). Children who received a referral were more likely to be younger (418 of 5271 [7.9%] aged ≤6 years vs 185 of 4151 [4.5%] aged ≥12 years); White (550 of 9039 [6.1%]) vs Asian (18 of 489 [3.7%]), other (2 of 197 [1.0%]), or unknown (23 of 587 [3.9%]) race; Hispanic or Latino (535 of 7836 [6.8%]) vs non-Hispanic or non-Latino (229 of 7176 [3.2%]) ethnicity; classified with normal (535 of 7836 [6.8%]) vs overweight (134 of 2427 [5.5%]) or obesity (168 of 6660 [2.5%]) BMI; and have attended a clinic in an urban (732 of 10 915 [6.7%]) vs suburban (114 of 2636 [4.3%]) or rural (2 of 1871 [0.1%]) setting. There was no significant difference in referrals by sex.Guideline-adherent follow-up results are presented in Of 15 164 children with blood pressure at or above the 95th percentile who were eligible for the follow-up visit analyses, 2598 (17.1%) attended a follow-up visit within 1 month. Children who attended a guideline-adherent follow-up visit were more likely to be older (1101 of 4118 [26.7%] aged ≥12 years vs 544 of 5128 [10.6%] aged ≤6 years); boys (1529 of 8428 [18.1%]) vs girls (1069 of 6736 [15.9%]); and White (1639 of 8900 [18.4%]) vs Black (611 of 3896 [15.7%]) or Hispanic or Latino (125 of 911 [13.7%]) race. There were no significant differences by ethnicity, BMI status, or clinic setting.7 To our knowledge, this is the first analysis to examine the rates of guideline-adherent PHTN diagnosis and management documented in the EHR using the 2017 CPG. Compared with a prior study in this population using the Fourth Report,12 guideline-adherent diagnosis rates for PHTN using the 2017 CPG were considerably lower (5.7% vs 42%) while the rates of children diagnosed with prehypertension or elevated blood pressure without a diagnosis of hypertension were higher (37.8% vs 17%). Consistent with prior studies, children who were boys, older (aged ≥13 years), and classified with overweight or obesity were more likely to be diagnosed with PHTN or elevated blood pressure.27 Additionally, children seen in urban-based clinics were more likely to have a guideline-adherent diagnosis code for elevated blood pressure, but not PHTN.With the publication of the 2017 CPG for the diagnosis and management of PHTN, the rate of children who meet diagnostic criteria for PHTN has increased.4 Accordingly, 96.2% of patients in this sample received some form of lifestyle counseling, suggesting that recording a guideline-adherent diagnosis had a minimal effect on delivery of guideline-adherent counseling. Children classified with overweight and obesity had 33% and 56% greater odds, respectively, of receiving lifestyle counseling. Among children meeting criteria for elevated blood pressure or PHTN, 5.4% were prescribed antihypertensive medication and 5.5% received a referral for potential blood pressure–related specialty care. Interestingly, antihypertensive medications were more likely to be prescribed to children attending a clinic in a suburban or rural setting, while referrals were more likely to be given to those in in an urban setting. A recent survey of pediatric clinicians in the AllianceChicago network28 found that 71% of clinicians agreed that selecting and prescribing antihypertensive medications was a barrier to PHTN management, and 74% preferred to refer children with PHTN to a specialist for treatment. These findings highlight the need to ensure that pediatric clinicians, particularly those in rural settings where specialty services may not be as readily available, have adequate comfort and familiarity with antihypertensive medications to manage PHTN per the 2017 CPG. Furthermore, reducing barriers to accessing specialty care  is critical for blood pressure management in children.Behavioral change is the first-line intervention recommended for treating elevated blood pressure among children.4 children with blood pressure at or above the 90th and 95th percentiles should attend a follow-up visit within and 6 months and 2 weeks, respectively, for a follow-up blood pressure reading. In the present sample, 54.1% of children with blood pressure at or above the 90th percentile attended a 6-month follow-up visit but only 17.1% of children with blood pressure at or above the 95th percentile attended a follow-up visit within 1 month, similar to a prior study (21%).25 Lack of patient follow-up inherently limits the ability of clinicians to confirm 3 occurrences of blood pressure at or above the 95th percentile and confidently diagnose and treat PHTN. Specific strategies targeting patient attendance, using home or ambulatory blood pressure monitoring,29 and reducing barriers to accessing specialty care might improve follow-up and increase rates of guideline-adherent PHTN diagnosis and subsequent management.Per the 2017 CPG,21 Using EHR-based tools, such as the CDS tool, can be used to mitigate the harmful effects of implicit racial and sex bias and increase equitable identification and management of PHTN.30We observed several differences in guideline adherence by patient-level characteristics. For example, while guideline-adherent elevated blood pressure diagnosis was highest among Black children, rates of antihypertensive medication prescription, referral, and follow-up were higher among White children. Similarly, a higher proportion of boys than girls was prescribed antihypertensive medication and attended follow-up visits. These substantial racial and sex differences in PHTN management may be suggestive of implicit bias.11 Clinical decision support tools are often implemented to support clinicians and improve clinical care, such as increasing adherence to clinical guidelines. Unfortunately, the PHTN CDS tool implemented in AllianceChicago clinics was used on fewer than half the patients with elevated blood pressure readings (≥90th percentile), and uptake was significantly lower in rural compared with urban clinics. These findings are consistent with prior studies in PHTN and more broadly, indicating that these tools are effective but have low adoption rates.31 Thus, comprehensive implementation strategies are needed to increase uptake of effective CDS tools to promote guideline-adherent PHTN diagnosis and management. For example, a stakeholder advisory panel consisting of AllianceChicago pediatricians and academic partners identified 18 discrete implementation strategies needed to improve CPG adherence, including education and training, workflow changes, and leadership support.19The findings from this study underscore the evidence-to-practice gap in guideline implementation.ICD-10 codes. Finally, the true prevalence of PHTN is unknown, as the diagnosis requires 3 instances of elevated blood pressure at or above the 95th percentile, and the rates of follow-up visit attendance were low.This study has some limitations. First, the focus on high-risk children with at least 1 blood pressure reading at or above the 90th percentile limits the generalizability of these findings. Second, data extracted from the EHR limits the information we have, including whether the management options  were specific to elevated blood pressure ; the method of blood pressure measurement  is unknown; follow-up blood pressure measures may have been normal but not entered in the EHR; or diagnoses entered as text in notes may not be included as 32 However, in this cross-sectional study, elevated blood pressure and PHTN were underdiagnosed and undertreated among children seen in safety-net clinics, and a CDS tool to facilitate diagnosis was underused. Comprehensive implementation strategies are needed to address this evidence-to-practice gap, including strategies to support the implementation of health information technology tools.Adhering to the 2017 CPG is critical for reducing PHTN-related morbidity and mortality among children, adolescents, and adults.


The background is that intravenous adrenaline administration is recommended for advanced cardiovascular life support in adults and endotracheal administration is given low priority. The reason is that the optimal dose of adrenaline in endotracheal administration is unknown, and it is ethically difficult to design studies of endotracheal adrenaline administration with non-cardiopulmonary arrest. We otolaryngologists think so because we administered adrenaline to the vocal folds for hemostasis after intracordal injection under local anesthesia, but have had few cases of vital changes. We hypothesized that examining vital signs before and after adrenaline administration for hemostasis would help determine the optimal dose of endotracheal adrenaline.We retrospectively examined the medical records of 79 patients who visited our hospital from January 2018 to December 2020 and received adrenaline in the vocal folds and trachea for hemostasis by intracordal injection under local anesthesia to investigate changes in heart rate and systolic blood pressure before and after the injection.P-values of 0.136, and 0.450, respectively, indicating no significant differences.The mean heart rates before and after injection were 83.96 ± 18.51 (standard deviation) beats per minute (bpm) and 81.50 ± 15.38 (standard deviation) bpm, respectively. The mean systolic blood pressure before and after the injection were 138.13 ± 25.33 (standard deviation) mmHg and 135.72 ± 22.19 (standard deviation) mmHg, respectively. Heart rate and systolic blood pressure had Although this study was an observational, changes in vital signs were investigated assuming endotracheal adrenaline administration. The current recommended dose of adrenaline in endotracheal administration with cardiopulmonary arrest may not be effective. In some cases of cardiopulmonary arrest, intravenous and intraosseous routes of adrenaline administration may be difficult and the opportunity for resuscitation may be missed. Therefore, it is desirable to have many options for adrenaline administration. Therefore, if the optimal dose and efficacy of endotracheal adrenaline administration can be clarified, early adrenaline administration will be possible, which will improve return of spontaneous circulation (ROSC) and survival discharge rates. Adrenaline, which is indicated in cases of cardiopulmonary arrest, can be administered endotracheally. However, the evidence presented by the Japan Resuscitation Council Resuscitation Guidelines 2020  includes® 0.1% solution; Daiichi Sankyo Co. Ltd., Tokyo, Japan) is administered directly to the vocal folds, the dose being 0.67 mg of adrenaline. By contrast, the adrenaline kit  1 ampule, which is administered intravenously to patients with cardiopulmonary arrest, contains 1 mg of adrenaline in 1 mL which is at most 1.5 times higher than the dose of adrenaline used for hemostasis after our intracordal injection. In our experience, however, endotracheal adrenaline administration for hemostasis after the injection rarely results in a sudden immediate increase in heart rate or systolic blood pressure.In the field of otorhinolaryngology head and neck surgery, adrenaline may be administered to the vocal folds for hemostasis after intracordal injection under local anesthesia. In our hospital, after intracordal injection, adrenaline  it is ethically difficult to design a prospective clinical study with a high level of evidence for endotracheal adrenaline administration in humans under non-cardiopulmonary arrest, and (2) in our experience, we have never experienced a sudden change in vital signs when adrenaline is administered around the vocal folds, so the dosage of adrenaline is small, i.e., the optimal endotracheal adrenaline dose is unknown.Therefore, we hypothesized that the administration of adrenaline for hemostasis in intracordal injection is similar to the endotracheal adrenaline administration in non-cardiopulmonary arrest. We investigated medical records to retrospectively analyze the changes in heart rate and systolic blood pressure before and after the administration of adrenaline for hemostasis in intracordal injection under local anesthesia in our institution. Thus, we investigated the extent to which endotracheal adrenaline administration to vocal folds affected the heart rate and systolic blood pressure in human with non-cardiopulmonary arrest, and to test the appropriateness of the endotracheal adrenaline dose in cardiopulmonary arrest.Retrospectively study using medical records. This study was carried out in accordance with ‘WMA Declaration of Helsinki 2013–Ethical Principles for Medical Research Involving Human Subjects’ and our national research guideline ‘Ethical Guidelines for Medical and Health Research Involving Human Subjects’.All 351 patients had blood samples, electrocardiograms, and chest radiographs taken prior to injection to ensure that they were in a general condition to tolerate the injection procedure. And they were performed intracordal injection after confirming that they had no history of hepatic disorders, cardiovascular or respiratory diseases, other serious systemic diseases, other laryngeal diseases, laryngeal cancer, or drug allergies. Of the 351 patients, 79 had bleeding from the vocal cords after injection and adrenaline was administered to the vocal cords for hemostatic purposes -soaked gauze into both nostrils for 30 min to anesthetize the nose. Afterward, the patient was moved to the operating room, where laryngeal anesthesia was performed by dropping 4% lidocaine hydrochloride hydrate into the larynx using a laryngeal endoscope while in a sitting position. The sites of laryngeal anesthesia included the epiglottis at the base of the tongue, epiglottis at the laryngeal side, vocal folds, and arytenoid portion. A 23-gauge esophageal variceal indwelling needle  was used to inject two drugs into the right and left vocal folds: triamcinolone acetonide , and trafermin . After injection, when bleeding was observed in the vocal folds, a dose of 3000-fold diluted adrenaline  was dropped directly onto the vocal folds with vocalization for hemostasis. The composition of the adrenaline was 100 mL of adrenaline diluted with 200 mL of saline solution to make a total volume of 300 mL, of which 2 mL was used only once for hemostasis.The intracordal injection under local anesthesia is shown in Figs. Trafermin is basic fibroblast growth factor (bFGF) preparation. Trafermin is used as a dermatological spray to treat bedsores and skin ulcers and in emergency medicine to treat burns. In the field of voice medicine, trafermin injection into the vocal folds has been reported to improve voice disorders in diseases such as vocal fold atrophy, scarring, paralysis, and sulcus. Several institutes have reported the usefulness of intracordal trafermin injection in improving voice –9. In thThe methods of measuring heart rate and systolic blood pressure are shown in Fig. P < 0.05 was set as statistically significant.The Wilcoxon signed rank test was used because changes in inspection results before and after surgery were for the same subject in the comparative test, thus the data did not follow a normal distribution. The Table In systolic blood pressure, 7 patients had a decrease of 20 or more after injection compared to pre-injection, 12 patients had a decrease between 10 and 19, 22 patients had a decrease between 1 and 9, 21 patients had an increase between 0 and 9, 14 patients had an increase between 10 and 19, and 3 patients had an increase of 20 or more.P-values for the differences in heart rate and systolic blood pressure were 0.136 and 0.450, respectively, indicating no significant differences.The mean changes in heart rate and systolic blood pressure before and after the injection in the 79 adrenaline-treated patients are shown in Fig. In this study, we used medical records to retrospectively investigate the changes in heart rate and systolic blood pressure in 79 patients who underwent intracordal injection under local anesthesia and received adrenaline for hemostasis at our hospital. The results showed no significant difference between before and after adrenaline administration.Currently, the intravenous administration of adrenaline is the most recommended method of administration in cases of cardiopulmonary arrest. The efficacy of endotracheal adrenaline administration in cardiopulmonary arrest is inferior to that of intravenous. In the endotracheal adrenaline administration, Redding et al.  in 1967 In the field of otorhinolaryngology head and neck surgery, endoscopic examinations and injections are commonly performed. In the field of voice medicine, drugs are injected directly into the vocal folds for the purpose of improving voice. For example, triamcinolone acetonide injection has been reported to improve voice in cases of chorditis, nodules, bamboo nodes, and polypoids . Triamci® topical solution 0.1%, which is commonly used for the treatment of local bleeding, mucosal hyperemia, and swelling in otorhinolaryngology head and neck surgery. The dosage is not specified in the package insert, which states that the solution should be used as is or diluted five- to tenfold and applied directly or nasally, sprayed, or used as a tampon. The dose of adrenaline used for hemostasis in this study corresponds to 0.67 mg. On the other hand, an ampule of adrenaline kit  administered intravenously to a patient in cardiopulmonary arrest contains 1 mg of adrenaline, which is at most 1.5 times the dose of adrenaline we use to stop bleeding for hemostasis after injection. However, we have had few cases of rapid vital changes after the injection, which led to the design of this study.As a complication of intracordal injection under local anesthesia, edema of the vocal folds may cause airway emergencies. We have been performing more than 200 intracordal injections per year and have never experienced a case of tracheotomy or dyspnea after the injection. However, other complications may be encountered, such as cases of bleeding from the vocal folds when the drugs were injected into the vocal folds using an esophageal variceal needle. Continued bleeding from the vocal folds may cause blood to drip from the bronchial tubes into the lungs, causing swallowing and aspiration pneumonia. To prevent this, we dropped adrenaline onto the vocal folds directly after intracordal injection to stop bleeding. The adrenaline we used to stop the bleeding was BosminThe AHA  suggestsThe limitations of this study are listed as follows. This was an observational study, which may have been susceptible to selection bias, information bias, and confounding factors. In addition, we did not report continuous heart rate and systolic blood pressure measurements because we used medical records to study heart rate and systolic blood pressure. Systolic blood pressure after adrenaline injection was measured approximately 1–3 min after the injection, but the blood pressure measurements may have been performed before or after the onset of adrenaline action. It might have been better to measure vital signs more often, with the sole purpose of ascertaining the patient's condition. In this study, triamcinolone acetonide and trafermin were injected, but the effects of these drugs on heart rate and systolic blood pressure have not been discussed. We used 4% Xylocaine as a local anesthetic, but its effects on heart rate and systolic blood pressure are also unknown. Adrenaline was administered directly to the vocal folds while the patient was vocalizing, but the actual proportion of the endotracheally administered 2 mL of adrenaline that was available to cause biological effects by actually reaching the alveoli may vary from case to case. Only 2 ml of adrenaline was administered, and other doses and concentrations could not be studied. Because the patients were not intubated in this study, the impact of positive pressure ventilation on drug dispersion and absorption after intubation was not discussed.In this study, no statistically significant changes were observed in the heart rate and systolic blood pressure in 79 patients who underwent intracordal injection under local anesthesia and received adrenaline endotracheally for hemostasis. We believe that the dose of adrenaline currently recommended by the AHA for endotracheal administration is too low to be used in patients with cardiopulmonary arrest. For medical ethical reasons, it is difficult to construct a study design in which adrenaline is administered endotracheally to human with non-cardiopulmonary arrest. Therefore, we believe that this study will provide useful information regarding the dosage of endotracheal adrenaline administration.We, too, do not question the usefulness of intravenous and intraosseous adrenaline administration. In some cases of cardiopulmonary arrest, however, it is difficult to secure the peripheral venous pathway owing to a significant drop in blood pressure or inadequate peripheral circulation, and resuscitation opportunities may be missed. In addition, intraosseous routes of adrenaline administration requires a specialized needle and experience with the procedure. In some cases, such as limb disarticulation due to multiple traumatic injuries, intravenous and intraosseous administration may be difficult. In these cases, it is advisable to have many options for adrenaline administration. Therefore, if the optimal dose and efficacy of the endotracheal adrenaline administration are clarified, early adrenaline administration can be performed, which may improve the ROSC and survival discharge rates as well as intravenous and intraosseous administration. We will continue to investigate and analyze more cases, and hope that the findings of this study will be of value to clinicians in this regard.


To explore the relationship between plasma leucine-rich α-2-glycoprotein 1 (LRG1) level and the degree of urinary albumin excretion in patients with type 2 diabetes.We evaluated 332 patients with type 2 diabetes in a cross-sectional study.p for trend = 0.003) under adjustment with other covariates. A positive correlation was found between plasma LRG1 level and urinary albumin excretion . According to a multivariate model, the association between LRG1 and urinary albumin excretion remained significant, under adjustment for confounding factors .The plasma LRG1 level differed significantly according to the quartiles of urinary albumin excretion (Q1 [<7.7 mg/g], 17.1 μg/mL; Q2 [7.7–15.0 mg/g], 17.5 μg/mL; Q3 [15.1–61.4 mg/g], 18.6 μg/mL; Q4 [≥61.5 mg/g], 22.3 μg/mL; Plasma LRG1 level was independently associated with urinary albumin excretion in patients with type 2 diabetes. This study suggests that LRG1 may be associated with increased excretion of urinary albumin in the early stages of diabetic nephropathy. Leucine-rich α-2-glycoprotein 1 (LRG1), a member of the leucine-rich repeat family, is a secreted glycoprotein . PreviouDiabetic nephropathy is a leading cause of end-stage renal disease , with onThis study aimed to investigate the relationships between LRG1 level and degree of urinary albumin excretion in patients with T2DM, while also evaluating the relationships with other clinical indices of patients with T2DM.Measurements.A total of 332 individuals with T2DM, enrolled consecutively from our hospital’s diabetes clinic, were evaluated in the cross-sectional study. T2DM was diagnosed in line with the expert committee’s report on the diagnosis and classification of diabetes mellitus . Subject1c) were determined using ion-exchange liquid chromatography , while creatinine levels were measured using the Jaffe method. Plasma LRG1 level was measured by a sandwich enzyme-linked immunosorbent assay kit  following the manufacturer’s instructions. The reported intra- and interassay coefficients of variation were 3.0%–4.9% and 4.2%–5.1%, respectively. Urinary albumin excretion was measured using the urinary albumin-to-creatinine ratio. The mean values for urinary albumin excretion were determined from two spot urine collections acquired on two consecutive mornings. Albuminuria was defined as urinary albumin excretion ≥30 mg/g, while normoalbuminuria was <30 mg/g. The glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation (Venous blood samples were collected after overnight fasting. Glycated hemoglobin levels (HbAequation .i); Model 3 was adjusted for the variables in Model 2 plus the duration of diabetes, HbA1c, and use of OHAs and insulin. The variance inflation factor was used to evaluate multicollinearity. A variance inflation factor > 5 was excluded from the model. All statistical analyses were performed using SPSS version 23.0 . A p-value of <0.05 denoted statistical significance.Data are expressed as the mean ± standard deviation (SD), median (interquartile range), or frequency (percentage) unless otherwise indicated. The test for linear trend across increasing categories of plasma LRG1 level treated categories as continuous variables in the model. A linear-by-linear association test was conducted for qualitative parameters and Spearman’s rank correlation analysis was used to evaluate the association between plasma LRG1 level and other clinical variables. An analysis of covariance (ANCOVA) was conducted to compare the average LRG1 level according to the quartiles of urinary albumin excretion. Plasma LRG1 was analyzed after logarithmic transformation because of a skewed distribution. We evaluated the association between LRG1 level and urinary albumin excretion using a multiple linear regression model. Model 1 was adjusted for age and sex; Model 2 was adjusted for age, sex, smoking, body mass index, systolic blood pressure (BP), hyperlipidemia, high-sensitivity C-reactive protein (hs-CRP), and use of angiotensin II receptor blocker (ARB)/angiotensin-converting enzyme inhibitor , DM duration , HbA1c level , and hs-CRP , and correlated negatively with total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol , and estimated glomerular filtration rate . In the subgroups of diabetic patients categorized by albuminuria, a significant correlation of LRG1 with DM duration, total cholesterol, and hs-CRP was only found in subgroups of T2DM patients who did not have albuminuria. A significant correlation of LRG1 with estimated glomerular filtration rate and hs-CRP was only found in the subgroup of T2DM patients with albuminuria. For all T2DM patients, a significantly positive correlation was found between LRG1 and urinary albumin excretion . The same significant correlation was also found in the T2DM patient subgroups with normoalbuminuria and albuminuria.Selected significant results of the Spearman correlation analysis for LRG1 and other clinical indices in T2DM patients are shown in p for trend = 0.003), after being adjusted for age, sex, smoking, body mass index, systolic BP, hyperlipidemia, hs-CRP, duration of diabetes, HbA1c, use of ARB/ACEi, OHAs and insulin.1c, use of ARB/ACEi, OHAs and insulin (β = 0.285, p < 0.001; i use were excluded, LRG1 level was still associated with urinary albumin excretion (We carried out multiple linear regression analysis to investigate independent associations Table 4,In this study, we determined that plasma LRG1 level correlated positively with the degree of urinary albumin excretion and correlated negatively with the estimated glomerular filtration rate. In the individual groups, plasma LRG1 level was positively correlated with urinary albumin excretion in patients with albuminuria and normoalbuminuria. In addition, the multiple regression analysis identified that plasma LRG1 level was independently associated with urinary albumin excretion after adjustments for the conventional confounders.LRG1 is a secretory glycoprotein with multifunctional properties in a context-dependent manner , 3. LRG1Recent studies have also suggested close associations between LRG1 and renal injury . Several1c level and diabetes duration, which are important contributors to diabetic kidney injury (in vitro study showed that LRG1 expression increased in response to hyperglycemic conditions (In the present study, we found that LRG1 was associated with glycemic status reflected by HbAy injury . An in vnditions . Previounditions , 17. In nditions , 23. Thunditions . HoweverPotential mechanisms could link LRG1 to diabetic nephropathy. First, increased angiogenesis is a trait of diabetic glomerulopathy  and occuCRP has been considered a marker of systemic inflammation . AlthougThis study has some limitations. First, because this study was performed in a single center and the participants were limited to one ethnic group, our results might not be generalized to other population with diabetes throughout the world. In addition, our results might not be applicable to other types of nephropathy. Second, information about the duration of drug use was not obtained in this study. Third, the causality of the associations between plasma LRG1 level and urinary albumin excretion could not be determined, because this was a cross-sectional study. Finally, even if several potential confounding variables were considered in the regression model, the relationship between LRG1 and urinary albumin excretion could be influenced by confounders that have not yet been measured . DespiteIn conclusion, this study showed that plasma LRG1 level was independently associated with urinary albumin excretion in T2DM patients. Our results suggest that LRG1 level may be an early indicator of diabetic nephropathy in patients with T2DM. However, further large-scale longitudinal studies are necessary to elucidate the precise role of LRG1 in early-stage diabetic nephropathy.The original contributions presented in the study are included in the article/The studies involving humans were approved by an ethics committee of Chonnam National University Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.JC designed the study, analyzed data, drafted the manuscript, and approved its final version. S-YP and MC contributed to the statistical analyses and interpretation of data. JC, D-HC, DC acquired data. All authors reviewed and approved the final manuscript.


Asthma is a diverse disease with various etiologic bases. Severe asthma can be associated with increased mortality, hospitalization, and decreased quality of life for asthma patients. High blood eosinophil counts were associated with severe asthma, but recent studies have failed to confirm this as a marker of severe asthma among adult asthma patients. As a result, the purpose of this study was to determine the association between the severity of asthma and high blood eosinophil count.A simple random sampling technique was used to select 291 asthmatic patients for an institution-based cross-sectional study. Socio-demographic, behavioral, and clinical characteristics were collected by using a pre-tested structured questionnaire. Four milliliters of venous blood were collected from asthmatic patients for complete blood count and peripheral morphology assessment. The eosinophil count was analyzed by the Unicel DxH 800  analyzer. A statistical package for social science version 20 (SPSS) software was used to analyze the data. The non-parametric (Mann-Whitney U) test was used to compare the eosinophil count with different background variables. A binary logistic regression analysis was used to assess the factors associated with eosinophilia. A p-value less than 0.05 in multivariable logistic regression analysis was considered statistically significant.In this study, the overall magnitude of eosinophilia was 19.6% (95% CI = 14.8–24.1). Being admitted to the emergency department  and being female  were shown to have a statistically significant association with eosinophilia. Moreover, the absolute eosinophil count was significantly higher among asthmatic patients infected with intestinal parasitic infection (p < 0.045).Being female and admission to the emergency department were negatively associated with eosinophilia. Lack of eosinophilia can be related to the low-T2 asthma phenotype. The absolute eosinophil counts were higher among intestinal parasite-infected patients. Therefore, different biomarkers will be considered for the proper diagnosis and management of adult asthma patients. Asthma is a diverse disease characterized by chronic airway inflammation . It is dAsthma is a heterogenous disease with various etiologic bases , 7. AsthThe European Respiratory Society (ERS)/American Thoracic Society (ATS) task force defines severe asthma as “asthma that needs treatment with high-dose inhaled corticosteroids (ICS) plus additional controller and/or systemic corticosteroids to keep it from being “uncontrolled” or it remains “uncontrolled” despite maximally optimized Global Initiative for Asthma (GINA) step 4 or 5 therapy and treatment of contributing factors, or it worsens when optimized therapy is reduced”. It is estimated that about 3 to 10% of asthma patients have severe asthma .Severe asthma is associated with higher mortality, hospitalization, and a decreased quality of life. Also, it results in physical, mental, emotional, social, and occupational costs for individuals as well as a financial impact on health care systems , 13.Eosinophils are responsible for inflammatory effects when triggered by allergens. Persistent eosinophilic airway inflammation and airway remodeling lead to persistent airflow obstruction . A high Eosinophils are important predictors of disease severity and progression . As a reThe ERS/ATS task force considered sputum and blood eosinophilia as markers for severe asthma . HoweverMany studies have revealed that eosinophil levels rise in cases of severe asthma. However, asthma is a diverse disease with different etiologies and phenotypes. Therefore, the main aim of this study was to determine the magnitude of the elevated peripheral eosinophil count and its association with the severity of asthma among adult asthmatic patients.An institutional cross-sectional study was conducted from June to August 2021 in Northwest Ethiopia, at the University of Gondar Comprehensive Specialized Hospital (UGCSH) and Tibebe-Ghion Specialized Hospital (TGSH). UGCSH is located in Northwest Ethiopia, Amhara Regional State, in Gondar Town. The hospital can provide service for over 7 million people in the catchment area. There are over 400 regular follow-ups of asthmatic patients in the chronic outpatient department of the hospital. On the other hand, TGSH is located in Northwest Ethiopia, in Bahirdar City. The hospital provides health services for eight nearby zones in the Amhara regional state.This study included all adult asthmatic patients (≥ 18 years old) attending UGCSH and TGSH during the study period. On the other hand, patients with known chronic diseases such as HIV/AIDS, hematological malignancies, chronic kidney disease, and tuberculosis were excluded from this study by reviewing their medical records.2 (0.5 × 0.5)/(0.05)2 = 384.The sample size was determined by using the single population proportion formula by considering a proportion of 50%, 5% margin error, powe of 80%, and a 95% confidence interval. By using a formula, Since the total number of asthmatic patients in two hospitals per year was less than 10,000 . Thus, a reduction formula was used. So, The study participants were proportionally allocated from each hospital Fig. . The lotAsthma: any person who has been diagnosed with asthma by a physician working as a pulmonary medicine specialist under GINA guidelines. The diagnosis was made based on the following criteria: asthma medication use, history of various respiratory symptoms, and confirmed variable expiratory airflow limitation [mitation .Admission to the emergency department: asthmatic patients who were admitted to the emergency department for health care utilization due to asthma [o asthma .The severity of asthma was classified based on the GINA 2019 guideline [uideline .Stages of asthma were classified as intermittent, mild persistent, moderate persistent, and severe persistent based on the GINA 2019 guideline [uideline .A physical exercise habit: a study subject who has experience doing the physical exercise once per day for at least 20–30 min as a continuous activity [activity .Elevated blood eosinophil count: is defined as an absolute eosinophil count greater than 0.04 × 103/µl [× 103/µl .The socio-demographic and behavioral characteristics of study participants were collected by using a structured pre-tested questionnaire via face-to-face interview. The clinical data of study participants, such as asthma duration, family history of asthma, history of asthma medication, asthma drug type, chronic disease, severity and stages of asthma, symptoms of asthma, and history of drug intake other than asthma before 3 months, were collected from the patient’s medical record (chart review) by using a checklist. Study participants were sent to the laboratory room, where the blood specimen was drawn and analyzed after trained clinical nurses completed data via face-to-face interview and chart review.A venous blood specimen (4 milliliters) was collected from asthmatic patients with a syringe method by the trained laboratory technician. Then it is dispensed into the tube containing ethylene-diamine tetra-acetic acid anticoagulant for complete blood count (CBC) and peripheral morphology assessment. Complete blood counts of the study participants were analyzed by using five differential Unicel DxH 800 Coulter cellular analysis systems  automated hematological analyzers through Coulter counting, spectrophotometry, and VCS technology.A peripheral blood morphology examination was performed to confirm flags generated by the automated hematology analyzer and to check whether the automated hematology analyzer provides a consistent result. A thin blood smear was prepared from leftover blood from CBC. Wright stain was used to stain the dried smear. The smear was carefully examined with a 100X oil immersion objective by laboratory technologists. All laboratory tests, such as CBC and peripheral morphology, were performed in the UGCSH and TGSH laboratories. The results of every study participant were recorded in a format designed for laboratory result registration.The questionnaire was prepared in the English version, translated into the local language (Amharic), and retranslated back to the English version to check the accuracy and consistency. It has been pretested on 5% of asthmatic patients at Felege Hiwot Comprehensive Specialized Hospital. Then a questionnaire was modified based on the result of the pretest. Before the data collection began, training was given for data collectors to reduce technical and observer bias.Pre-analytical, analytical, and post-analytical phases of quality assurance were maintained in the overall laboratory process to assure the quality of data. Quality control for working equipment and reagents was ensured by using standard controls. Standard operating procedures and manufacturers’ instructions were strictly followed during sample collection and laboratory procedures. The questionnaire was checked for consistency, clarity, and completeness by the principal investigator. The results of every test were properly recorded, reviewed, and transcribed.The data was entered into Epi-data software (Version: 3.0.4), cleaned, and exported into Statistical Package for Social Science version 20 software  for analysis. To summarize the data, descriptive statistics such as frequencies and percentages were used. The Shapiro-Wilk test and histogram were used to check the normal distribution of continuous variables. The data was presented using tables.Non-parametric (Mann-Whitney test) was used to compare median values of absolute eosinophil count with different background variables. Binary logistic regression, such as bivariable and multivariable logistic regression analysis, was performed. The strength of association between predictors and outcome was determined using the crude odds ratio (COR) and adjusted odds ratio (AOR) with a 95% confidence interval (CI). In the bivariable logistic regression analysis, variables having a p-value of less than 0.25 were fitted into the multivariable logistic regression analysis. Hosmer and Lemeshow’s goodness of fit statistics were used to test the model’s fitness. In all cases, a p-value of less than 0.05 was considered statistically significant.Ethical clearance was obtained from the ethical review committee of the School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, on March 3, 2021, with letter reference number SBMLS-2748. The Department of Hematology and Immunohematology provided a support letter, which was forwarded to the directors of UGCSH and TGSH. In addition, a permission letter to conduct research was obtained from the UGCSH and TGSH directors.Informed written consent was obtained from each study participant after the objective of the study was explained. For illiterate patients, informed consent was obtained after objective of study and detailed information was read by data collectors. Then fingerprint signature was taken from each study illiterate participant. Study participants were identified by using codes rather than individual identifiers. The results and information of the study participants were kept confidential. Study participants who had elevated eosinophil counts were linked to the UGCSH and TGSH chronic outpatient departments for proper management. All methods were performed per the relevant guidelines and regulations (Declaration of Helsinki).In this study, we included a total of 291 study participants. Of those, about 164 (56.4%) were females. The age ranges from 18 to 65 years, with the median and interquartile range (IQR) of 50 (38 to 60) years. About 188 (64.6%) of the study participants were over 40 years old. Regarding the residence of study participants, 186 (63.9%) participants were urban residents. The majority of study participants were unable to read and write in their educational status, 126 (43.3%)  of the study participants were overweight.Of the study participants, 5 (1.7%) were current cigarette smokers; 52 (17.9%) had a habit of doing physical exercise; and 75 (23.4%) had a habit of drinking alcohol. About 64 (22%) had an alcohol-drinking habit. The mean ± standard deviation value of BMI is 2.26 ± 2.97 kg/mThe majority of the study participants had been living with asthma for less than five years, 121 (41.6%). Regarding severity and stages of asthma, about 176 (60.5%) and 186 (63.9%) had moderate severity and moderately persistent stages of asthma, respectively. Among study participants, about 241 (82.8%) had taken asthmatic drugs in the previous three months. In addition, about 86 (29.6%) were admitted to the emergency department  with a median and IQR of 0.2 (0.07–0.4). The non-parametric Mann-Whitney U test was used to compare median differences in absolute eosinophil counts between groups because the data were not normally distributed. Based on this analysis, only asthma medication, asthma-related ED admission, and intestinal parasitic infection showed a statistically significant median difference Table .A binary logistic regression analysis was performed to check for factors associated with eosinophilia. In bivariable logistic regression analysis, variables like gender, alcohol drinking habit, and asthma-related emergency department admission were shown to have an association with eosinophilia. In addition, the factors with a p-value less than 0.25 were fitted into multivariable logistic regression analysis. Being admitted to the emergency department  and being female  were showed a statistically significant association with eosinophilia in a multivariable logistic regression model  of asthmatic patients. This finding was consistent with the study conducted in the USA (18.5%) , the UniThe comparison of absolute eosinophil count with different background variables was done in the present study. Based on the findings of this study, the absolute eosinophil count was higher among patients who were infected with intestinal parasitic infections than among patients who were not infected with intestinal parasitic infections. This finding was supported by different studies , 48. TheIn this study, we used binary logistic regression analysis to observe the association between the severity of asthma and eosinophilia. However, severe asthma did not show a statistically significant association with eosinophilia in the present study. This might be due to the fact that the majority of study participants were older (> 40 years old) and females, which are characteristics of adult-onset asthma. This finding was supported by the West Sweden Asthma study (WSAS) and Obstructive Lung Disease in Northern Sweden (OLIN) studies. A 15-year follow-up WSAS study showed that the severity of asthma was associated with blood neutrophilia rather than blood eosinophilia , 52. AmeOn the contrary, various studies have found that an elevated eosinophil count is associated with severe asthma , 54, 55.Females were less likely to develop eosinophilia than males . This might be because women had a higher incidence of adult-onset asthma when compared to males –59. It iStudy participants who were admitted to the ED  were less likely to develop eosinophilia than patients who were not admitted to the ED. The possible explanation might be that the patients attending the ED might be treated with a high dose of inhaled corticosteroids to reduce exacerbation according to GINA guidelines , 11, 62.This study was limited to showing cause and effect relationships due to the cross-sectional nature of the study. We did not assess the association between the time of oral corticosteroid use and the drug dose with eosinophil level. Another limitation was that the asthma control status of patients was not studied.In conclusion, the elevated blood eosinophil count was not associated with the severity of asthma among adult asthmatic patients. Lack of eosinophilia can be related to the low-T2 asthma phenotype. Elevated blood eosinophil counts were negatively associated with female sex and ED visits. However, the eosinophil values were higher in asthmatic patients infected with intestinal parasitic infection when compared to their counterparts. Therefore, different biomarkers will be considered in addition to eosinophil count for appropriate diagnosis and therapeutics among adult asthma patients.


Sublingual varices (SV) are benign vascular lesions that have questionable associations with aging, smoking, and hypertension. This study purposed to evaluate whether SV frequency differs between hypertensive patients and healthy persons.p < 0.05 level of significance by the SPSS22 statistical package using chi-square test.This cross-sectional study was conducted on 120 dental patients referred to Yazd Oral Medicine Department. At first sublingual surface of the tongue were examined before the routine oral survey, and blood pressure (BP) was measured in a sitting position. SV were classified into Grade 1 (no/mild), Grade 2 (medium to severe), and Grade 3 . Blood pressure was measured in all participants. Participants based on the obtained BP, divided into normal, prehypertension, stage 1, and 2 groups. Frequency of SV was compared in regarding age, gender, and stage of hypertension. All of the analyses were conducted at a p < 0.001). Data analysis showed there was a significant difference between the age groups. There was no significant difference based on SV between two genders. There was no significant difference in the frequency of sublingual varices between males and females. Aging could impact the frequency of SV.Out of 120 patients, 84 (70%) had SV. The frequency of SV in patients with hypertension (HT) (86.8%) was significantly higher than in others (48.1%); (This study revealed that patients with hypertension had more SV. A simple valuable method for dental clinicians to be active in preventive health care is evaluating sublingual surface of tongue. Varicosities are acquired vascular abnormalities which determined as locally increasing the size of the vein’s lumen. Varicosities may be seen in the oral cavity, uncommonly. The most common locations in oral cavities are sublingual, buccal mucosa, retro commissural mucosa. The sublingual area is important in the success of the implant due to its proximity to the alveolar ridge . They apSublingual varicosity (SV), at first, was described by DaCosta in 1930 and later was described with named caviar tongue. Some etiologic factors such as connective tissue and venous structure disorders have been suggested , 7. The The role of high blood pressure in the development of sublingual varicose veins has been studied for a long time. The dentist can play a significant role in the early diagnosis of high blood pressure by carefully examining the tissues of the tongue and under the tongue, and acquaintance with common oral lesions in the elderly can be very helpful for dentists and can prevent further unreasonable treatments .This study purposed to evaluate whether SV frequency differs between hypertensive patients and healthy persons.This cross-sectional study was performed at the Yazd oral medicine department.The sample size was calculated according to one proportion estimation formula. Sampling by census method among those who refer to the Department of Oral Medicine considering the confidence level of 95% power 80%, and 50% prevalence of high blood pressure based on a pilot conducted among the clients of the Department of Oral Medicine in people without varicose veins and people with varicose veins. The minimum required sample size was estimated to be 60 cases. In order to increase reliability, 120 people were included in the study.Patients above the age of 18 years were requested to take part in the study in connection with their regular visits. Those who accepted to participate provided written consent. Exclusion criteria were pregnancy, atrial fibrillation, renal disease, and smoking [Information about age, gender, medical and dental history, and social habits of participants were recorded on the related checklist. At first sublingual surface of the tongue was examined before the routine oral survey. Patients rested for at least 5 min in a quiet room. Blood pressure was measured in a sitting position. The blood pressure of all participants was measured by a Mercury -pressure gauge  at two standard intervals of at least 20 min .In this study blood pressure of all participants was taken by an oral medicine specialist. Considering the nature of dentistry, it is enough to know the stage of hypertension of patients instead of exact quality. All patients placed in one of four groups according to the JNC7 classification . An averThe variables from the checklist were coded. All statistical analyses were performed using IBM SPSS 22 using Chi-square test. strength of the association between hypertension and sublingual varices was assessed. All tests were two-sided and the significance cut-off was set at 0.05.A total number of 120 patients participated in the study. The age range of the participants was between 18 to 79 years (mean age 45.2 ± 15.1). The gender distribution was 55 males and 65 females of the subjects, 52 (43.3%) patients had normal BP and 68 (56.7%) had high BP. According to Table In Table These findings showed that the frequency of sublingual varices in hypertensive individuals was approximately twice as high as in those with normal blood pressure. SV as an indicator of risk for hypertension should be evaluated.Dentists are among the first healthcare groups that may confront the first sign and symptom of systemic disease and play an important role in timely diagnosis and better management of it.SV is a common benign clinical finding that could be related to high blood pressure, it is useful to screen people for identifying the condition of hypertension and timely treatment. It may help in the early diagnosis of patients with hypertension after the detection of sublingual varices. This study is designed to assess the possibility of this relationship.It is worth mentioning that a case–control study should be done based on a minute estimate of past epidemiological studies on similar populations, therefor due to the loss of such studies on our society, our study was designed as an observational clinical study.Our study was similar to other studies that selected their target group from patients who attended the dental center , 18, 19.The present study showed that the frequency of SV was 70%. This percentage is higher than the range of past studies which reported 2.7 to 41.1%0.7 , 20–22. In confirmation of these cases, Rabiei et al. Reported the prevalence of sublingual varicosity in the elderly of Rasht by 22.7% . While MAccording to our findings, there is no significant difference between two genders in the occurrence of sublingual varices. It is in accordance with Nevalainen et al. who reported similar results about sublingual varices . But CorIn some literature, diagnosis of hypertension was not verified by blood pressure measurement, based on what was self-reported , but in According to the discrepancy between the results of various studies, it is necessary to evaluate the relationship between sublingual varices and gender in studies with larger sample sizes. The present study showed that the mean age of patients with sublingual varices was significantly higher than others and with increasing age, the incidence of oral varicosity increased Table . These rThis positive relation could be explained by the degeneration of vascular tissue elasticity with aging. Sublingual varices lesions may be considered as a physiological change associated with aging .Based on the results of this study, the frequency of SV in patients with hypertension was significantly higher than in healthy persons. In addition, in hypertensive individuals, the frequency of SV increased with hypertension staging. This subject wasn’t discussed before. This finding confirms the results of Hedström study found a significant correlation between the incidence of sublingual varices and hypertension . Al-ShayHedström et al. Also found that the mean SBP and DBP in patients with grade 1 varices were higher than those with grade 0 varices .The relationship between hypertension and SV could be explained based on tissue characteristics of the thin lining of the ventral surface tongue. Connective tissue network has an unstable structure in this area, therefor various factors such as hypertension may lead to dilatation and vascular varicosity changes in this area. An exact examination of the oral cavity by the oral clinician to detect sublingual varices with no harm to the patient could be a valuable method to early diagnosis of hypertension.We are aware that our research suffers a number of limitations. The most important limitation lies in cooperating in examination for elderly patients was difficult to some extent. It is vital to be aware of the predictive limitations of cross-sectional studies, and a causal relationship can be clarified by carrying out additional prospective research. There is clearly much room for further research in this respect.The findings of this study showed that the frequency of sublingual varices in hypertensive individuals was approximately twice as high as in those with normal blood pressure. Aging could impact the frequency of SV. Examining the sublingual area as a simple valuable method of timely diagnosis and referral of probable disease would be suggested.