Compared to baseline, at 12 months (follow-up visit 2) decline in cigarette consumption was associated with significant reductions in median  systolic BP  to 130  mmHg; p < 0.001) and diastolic BP  to 80  mmHg; p = 0.006). No significant changes were observed in the control group. As expected, decline in cigarette consumption in the ECs users was also associated with improved BP control. The study concludes that regular ECs use may aid smokers with arterial hypertension reduce or abstain from cigarette smoking, with only trivial post-cessation weight gain. This resulted in improvements in systolic and diastolic BP as well as better BP control.Electronic cigarettes (ECs) are battery-operated devices designed to vaporise nicotine, which may help smokers with quitting or reducing their tobacco consumption. No data is available regarding the health effects of ECs use among smokers with arterial hypertension and whether regular use results in blood pressure (BP) changes. We investigated long-term changes in resting BP and level of BP control in hypertensive smokers who quit or reduced substantially their tobacco consumption by switching to ECs. A medical records review of patients with hypertension was conducted to identify patients reporting regular daily use of ECs on at least two consecutive follow-up visits. Regularly smoking hypertensive patients were included as a reference group. A marked reduction in cigarette consumption was observed in ECs users ( Smoking is the leading cause of preventable premature mortality in the world. Death is mainly caused by ischemic heart disease, stroke, lung cancer, and the catastrophic complications of advanced stage chronic obstructive pulmonary disease . It has The interaction between smoking and blood pressure (BP) is complex. Despite the strong relationship between smoking and elevated risk for cardiovascular disease ,10, therElectronic cigarettes (ECs) are battery-operated devices designed to vaporise nicotine without burning tobacco. These consumer products share many similarities with smoking in the behavioural aspect of their use . Users aData from clinical trials of “healthy” smokers ,19,20 anHere we report, for the first time, long-term improvement in resting BP as well as in level of BP control in smokers with a diagnosis of hypertension who quit or reduced substantially their tobacco consumption by switching to ECs.We conducted a medical records review of patients with arterial hypertension regularly followed-up at the outpatient clinics of our institution. Patients reporting regular daily use of ECs on at least two consecutive follow-up visits were eligible to be included in our study. Data from a second group of age-, sex-matched patients who reported to be regular smokers on at least two consecutive follow-up visits was included as a reference group. Patients in both study groups had to have similar weight (<5 kg) and systolic BP (<10 mmHg) fluctuations between pre-baseline and baseline visits. Any patients with a known cause of secondary hypertension were excluded. The study was approved by the local institutional ethics review board (Protocol registered No. 675).From chart review, we extracted patient data from the clinic visit immediately preceding [baseline visit] the first of the two consecutive follow-up visits (follow-up visit 1 and 2). We also included data from the clinic visit immediately prior to the baseline visit [pre-baseline visit] to substantiate disease stability. In brief, data from four visits were collected and analysed. Pre-baseline visits were carried out at 6–12 months prior to baseline visits. Follow-up visit 1 and 2 were carried out at 6 (±1) and 12 (±2) months after baseline visits, respectively. At each routine outpatient clinic visit patients were assessed using a standard approach consisting of clinical examination, review of smoking history, and measurement of blood pressure (BP), heart rate (HR), and body weight. Systolic (SBP) and diastolic BP (DBP) measurements were conducted according to the recommendations of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure  with patFor the purposes of this study, patients’ data at the time of the outpatient visits were later extracted from their medical record and entered into an electronic spreadsheet prior to statistical computation.Our routine approach to anti-hypertensive treatment is to evaluate and optimize patients’ drug regimens to include a combination of drugs that work on different pathophysiological pathways in order to maximize BP control . Where aThe primary outcome of interest was the change in resting SBP and DBP from baseline to the final follow-up visit at about one year. Secondary outcomes of interest were changes from baseline to the final follow-up visit in: (a) proportion of blood pressure grading; (b) proportion of patients with good BP control, defined as an office SBP < 140 mmHg and a DBP < 90 mmHg  ; (c) HR;t-test and Wilcoxon-signed rank test depending on whether the data was parametric or not, respectively. Similar statistical analyses were conducted for dual and single users within groups from baseline. Missing measurements were not included in the analyses. Repeated measures analysis of variance (ANOVA) between baseline and 12 months and between the two study groups were also conducted. A two-tailed p value of less than 0.05 was considered to indicate statistical significance. Odds ratios (OR) were computed to compare changes in BP control. All analyses were performed with the Statistical Package for Social Science . Data were expressed as mean (±standard deviation (SD)) if parametric and median (interquartile range (IQR)) if non-parametric. We also delineated data for single (ECs use only) and dual users . Statistical comparisons of change from baseline between and within the two groups in the parameters assessed were carried out using student’s A total of 89  regular smokers with a diagnosis of hypertension and on anti-hypertensive drugs at baseline were studied. They had either pre-hypertension, or grade 1 or 2 hypertension according to 2013 ESH/ESC criteria  despite p < 0.001 for both visits) (p < 0.001 for both visits)  cigarettes/day use decreasing from 20.2 (±5.0) at baseline to 2.6 (±2.9) at follow-up visit 1 and to 1.8 (±2.0) at follow-up visit 2, respectively ( visits) . As expe visits) . A signi visits) . More thp < 0.001) and DBP (p = 0.006) from baseline was observed at follow-up visit 2 in the EC group. In contrast, no significant change in BP was observed in the reference group. The observed reductions in SBP and DBP were significant  when comparing the EC group to the reference group at 12 months. Changes in SBP and DBP from baseline in smokers with arterial hypertension who switched to ECs and between the two study groups are illustrated and reported in No significant change in HR from baseline was noted in both patients’ groups during the course of the study . A signiThe overall proportion of patients in the EC group with good BP control at baseline increased from 25.6% to 37.2% and 48.8% at follow-up visit 1 and 2, respectively ; Table 4Overall, all patients remained on a stable number of anti-hypertensives throughout the study period with minor adjustments in medications’ class and dosage . No severe adverse reactions or acute decompensation in BP were reported with EC use throughout the entire follow-up duration. Overall, EC use appeared to be well tolerated in these hypertensive patients with dry mouth and throat irritation being occasionally reported.Smoking is known to act synergistically to elevate the risk of myocardial infarction in patients with established hypertension . MoreoveHere we illustrate for the first time the utility of ECs as a bridge in reducing cigarette consumption in smokers with arterial hypertension. Adoption of regular long-term ECs use in this group led to a marked and stable reduction in conventional cigarette consumption, with about 50% of them abstaining completely from tobacco smoking by the end of the observation period. The success rate observed in these patients with arterial hypertension is similar to that recently reported in asthmatics  and may As a result of the substantial reduction in cigarette consumption, decreased systolic and diastolic BP as well as improved BP control was also reported. In the EC group, systolic and diastolic BP fell by 10 mmHg and 6 mmHg, respectively. Improvement in systolic (but not diastolic) BP was also observed in dual users at 12 (but not 6) months. These findings are in agreement with the 8.8 mmHg reduction in systolic BP at week-52 in a prospective randomised control trial looking at the effect of smoking cessation by using ECs in subjects with high BP at baseline . PredictGiven the well-established acute effect of smoking on immediate vasopressor and tachycardic responses ,32 and iIn agreement with the findings from other research groups ,39, posiThe observed improvement in systolic and diastolic BP as well as in BP control in hypertensive smokers who switched to regular ECs use suggests that the harmful effects of cigarette smoke on the vascular system can potentially be reversed. By substantially reducing exposure to conventional cigarettes’ hazardous toxicants and achieving clinically relevant BP reductions, EC use may not only improve the cardiovascular risk profile but also confer an overall health advantage in smokers unable or unwilling to quit who are also at risk of developing arterial hypertension compared to continuing smoking. The use of low risk nicotine-containing products (including ECs) should be investigated as a safer alternative approach to harm-reversal  and, in general, to harm-reduction .There are some limitations in our study. First, the sample size is small; hence the results must be interpreted with caution. However, despite being small, significant results were reported for several study endpoints. Standard concerns associated with retrospective studies  need consideration. Nonetheless, a clear advantage conducting this type of study is the generation of hypotheses that can be tested prospectively under controlled conditions. Secondly, patients in this study may represent a self-selected sample, which is not representative of all smokers with arterial hypertension . Thirdly, although careful extraction from patients’ medical records allowed systematic assessment of anti-hypertensive medication prescriptions, this alone may not reflect true usage due to lack of rigorous adherence checks. Carbon monoxide measurements are not routinely performed in patients who are followed-up for elevated blood pressure at outpatient clinics and their smoking abstinence was self-reported. However, self-reported number of cigarettes smoked per day in studies of this type is not subjected to the kind of biases observed in clinical trials where there is the tendency to claim abstinence . MoreoveThat ECs may help also smokers with arterial hypertension to reduce their cigarette consumption or remain abstinent is a novel and important message of the study. As a result of this, we have observed substantial long-term improvements in systolic and diastolic BP as well as greater BP control. Large prospective studies are now warranted to confirm and expand the potential role of the e-vapor category for smoking cessation and/or reversal of harm in hypertensive patients who smoke. Substitution of conventional cigarettes with EC is unlikely to raise significant health concerns and may achieve better BP control. This can improve counseling between physicians and their patients with high BP using or intending to use ECs .


P < 0.001). Among hypertensive patients, frail elderly were more likely to be treated than pre-frail or robust elderly (P < 0.001), but the proportion of patients whose blood pressure was under control ( < 150/90 mmHg) was lower in frail elderly (P = 0.005). Considering the adverse cardiovascular outcomes associated with frailty, more attention should be paid to the blood pressure control of the frail elderly.Frailty is a common geriatric syndrome characterized by increased risk of disability, hospitalization, and mortality. Hypertension (HTN) is one of the most common chronic medical conditions in the elderly. However, there have been few studies regarding the association between frailty and HTN prevalence, treatment, and control rates. We analyzed data of 4,352 older adults (age ≥ 65 years) from the fifth Korea National Health and Nutrition Examination Survey. We constructed a frailty index based on 42 items and classified participants as robust, pre-frail, or frail. Of the subjects, 2,697 (62.0%) had HTN and 926 (21.3%) had pre-HTN. Regarding frailty status, 721 (16.6%), 1,707 (39.2%), and 1,924 (44.2%) individuals were classified as robust, pre-frail and frail, respectively. HTN prevalence was higher in frail elderly (67.8%) than pre-frail (60.8%) or robust elderly (49.2%) ( However, there remains controversy regarding the optimal treatment of HTN in the elderly, especially the oldest old age group3.Hypertension (HTN) prevalence increases with aging. HTN is an important risk factor of cerebro-cardiovascular disease, and it has a critical impact on quality of life and maintenance of activities of daily living (ADL) among the elderly. Antihypertensive treatment has been shown to reduce stroke, cardiovascular events, and mortality5. However, an inverse association between blood pressure and cardiovascular risk was found in the oldest age groups among the elderly9. In particular, the effect of antihypertensive treatment and the ideal blood pressure goal of treatment were not clear in the frail elderly10.Many large-scale trials have proven the necessity of antihypertensive treatment in the elderly. Meta-analyses of large-scale trials for elderly hypertensive patients have revealed significant reductions in cardiovascular morbidity and mortality with antihypertensive treatment11. Frailty assessments are clinically useful to address the heterogeneity of health status among the elderly. Frailty, as a reflection of decreased physiologic reserve, is closely associated with biological age12, concurrent medical conditions, morbidity, and decreased survival in the elderly13.Older hypertensive patients are highly heterogeneous, and physiological ability and vulnerability varies widely even for individuals of the same age11. However, other studies showed that antihypertensive treatment has been beneficial both frailer and healthier hypertensive elderly patients. For example, the HYVET  study showed that there was no evidence of an interaction between treatment effect and frailty14. Recently, the Systolic Blood Pressure Intervention Trial (SPRINT) study revealed the benefit of strict HTN control even in the frail elderly, with respect to lowering the rate of cardiovascular events and all-cause mortality15.Previous studies suggested that antihypertensive treatment was not safe in the frail elderlyFew studies have examined the effect of frailty on HTN prevalence, treatment, and control in the elderly. Frail elderly are especially vulnerable to cardiovascular disease, and blood pressure control is an effective way to decrease risk of such disease. Therefore, it is important to study the epidemiology of HTN according to frailty status of the elderly people. Analyzing the association between frailty and HTN prevalence, treatment, and control will be helpful for guiding therapeutic decisions for HTN control among the elderly patients.16.This cross-sectional study was based on data acquired in the fifth Korea National Health and Nutrition Examination Survey (KNHANES V), conducted from 2010 to 2012. These surveys have been conducted periodically since 1998 to assess the health and nutritional status of Koreans, monitor trends in health risk factors and the prevalence of major chronic diseases, and provide data for the development and evaluation of health policies and programs in KoreaTwenty households were selected throughout 192 regions for each of the years, and 10,000 individuals aged 1 year and over were targeted for KNHANES. To reduce the limitation of seasonal variations, KNHANES V was conducted continuously year round. The KNHANES has been conducted by the Korean Centers for Disease Control & Prevention since 2007. There were 4,557 older adults (age ≥ 65) in the KNHANES V. After excluding 10 participants with missing blood pressure data, and 195 participants with missing questionnaire data about HTN, 4,352 participants were included in the study. This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No. B-1610-365-101), which waived the requirement for informed consent. In addition to this, all methods were performed in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology Statement and regulation of the institutional review board.Blood pressure was measured on the right arm, by trained nurses, using a mercury sphygmomanometer  with an appropriately sized cuff after participants remained still for at least 5 minutes in a sitting posture. During the measurement period, participants were seated leaning against the back of a chair, while their feet remained flat on the floor. The right arm of participant was located at the middle of the cuff to be at the level of the heart. Blood pressure was measured 3 times, and the mean blood pressure of the second and third measured value was used to determine the final systolic and diastolic blood pressure.2 (m2). Waist circumference was measured at the narrowest point from the lower border of the rib cage to the iliac crest. Information about household income, level of education, and life style factors was derived from a self–reported questionnaire. A nutrition survey was conducted by the survey team via interview.Blood samples were collected from each participant during the survey. Body mass index (BMI) was calculated by dividing body weight (kg) by height18.HTN was defined as blood pressure ≥ 140/90 mmHg or taking antihypertensive medications. Pre-HTN was defined as 120 mmHg ≤ systolic blood pressure < 140 mmHg and 80 mmHg ≤ diastolic blood pressure < 90 mmHg. HTN treatment was defined if patients took antihypertensive medication 20 days or more in a month. We analyzed our data with the blood pressure target of 150/90 mmHg according to current guidelinesDiabetes was defined as fasting blood sugar ≥ 7 mmol/L (126 mg/dL), taking an oral hypoglycemic agent or insulin, or diagnosed with diabetes by a medical doctor.19. Chronic kidney disease (CKD) was defined as estimated GFR < 60 mL/min per 1.73 m2.Glomerular filtration rate (GFR) was calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equationSmokers were defined as those who smoked 5 packs of cigarettes in a lifetime or more, or they were current smokers. Exercise was defined as either 3 times or more per week of 20 minutes or longer strenuous physical activity, 5 times or more per week of 30 minutes or longer moderate physical activity or walking exercise.20. The frailty index, calculated as a ratio of deficits present out of the total number of possible deficits, gives a continuous score from total fitness (0) to total frailty (1). This means that the more deficits an individual has, the frailer they will be21.We developed the frailty index using a cumulative deficit model, including symptoms, signs, abnormal laboratory values, disease status, and disabilitiesOur frailty index consists of 42 items from the KNHANES V. The items used to calculate the index value included comorbidities, functional abilities, signs and symptoms, and laboratory values. Comorbidities included bronchial asthma, chronic obstructive pulmonary disease (COPD), diabetes, dyslipidemia, cataract, cardiovascular disease, stroke, arthritis, anemia, cancer, and depression. Functional abilities consisted of inactivity, exercise capacity, ADL limitation, social activity limitation, self-care ability, difficulty in chewing hard foods, hearing impairment, and anosmia. Signs and symptoms consisted of pain or discomfort, back pain, weight loss, dyspnea, depression or anxiety, fatigue, suicidal ideation, and stress. Laboratory values consisted of systolic blood pressure, diastolic blood pressure, heart rate regularity, pulmonary function test, hemoglobin, blood urea nitrogen, creatinine, vitamin D, total cholesterol, triglyceride, high density lipoprotein (HDL)-cholesterol, fasting glucose, and urine protein. Additional items were current smoking and obesity.21.We classified the study participants as robust (frailty index ≤ 0.10), pre-frail (0.10 < frailty index ≤ 0.21), or frail (frailty index > 0.21) according to previous criteriat-test or one-way analysis of variance (One-way ANOVA). Discrete variables were expressed as counts and percentages, and the proportions were compared by using the Chi-square test. We used binary logistic regression analysis to estimate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for factors that were considered to potentially influence the results. All statistical analyses were two-tailed, and P-values < 0.05 were taken as statistically significant.All statistical analyses were performed using the SPSS version 19.0 statistical package . Continuous variables were expressed as mean ± standard deviation, and were compared by either the unpaired Student’s https://knhanes.cdc.go.kr/.All data are available at The mean age of the study population was 72.6 ± 5.4 years and 1,855 (42.6%) participants were men. Of all subjects, 2,697 (62.0%) had HTN and 926 (21.3%) had pre-HTN. Among hypertensive patients, 2,159 patients (80.1% of the HTN patients) were treated. Among treated hypertensive patients, the blood pressure of 1,744 patients (80.8% of the treated HTN patients) was controlled under 150/90 mmHg. . Among hypertensive patients, frail elderly are more likely to be treated than pre-frail or robust elderly (P < 0.001). However, the proportion of patients whose blood pressure was controlled under 150/90 mmHg was lower in frail elderly (P = 0.005) , and the proportion of patients whose diastolic blood pressure was controlled under 90 mmHg was also lower in frail elderly (P = 0.032) , however, diastolic blood pressure was lower in frail patients (73.0 ± 10.6 mmHg) than pre-frail (74.2 ± 9.6 mmHg) or robust (74.1 ± 8.1 mmHg) patients (P = 0.019). When we analyzed the association between frailty index and systolic or diastolic blood pressure of the entire study population, there was U-shape relationship between them. In other words, the mean frailty index was higher in patients with high or low blood pressure  than pre-frail (60.8%) or robust elderly (49.2%) (05) Fig. . Among t32) Fig. . There wP = 0.005 [pre-frail], P < 0.001 [frail]) was significantly related to poor blood pressure control   Table .Table 2UIn this study, we showed that HTN prevalence and treatment rate was higher, but control rate was lower among the frail elderly people. Furthermore, frailty status was an independent factor associated with poor blood pressure control. In addition, uncontrolled blood pressure was associated with pre-frail or frail status of the study population. Interestingly, the mean frailty index was greater in elderly patients who had high or low systolic and diastolic blood pressure. Considering the significance of frailty on future cardiovascular events and mortality, more attention should be paid to frail hypertensive patients for the better management of HTN and improvement of prognosis.24. Maybe the reason for the association is that frailty is a condition associated with problems across multiple physiological systems. HTN treatment rate was significantly higher among the frail elderly. Because frailty is associated with comorbidity, frail elderly tend to use medical treatment more frequently, and as accessibility to healthcare institutions has increased, the HTN treatment rate may be increasing accordingly.Frailty statuses  were meaningfully associated with prevalence of HTN. The association has been published in the previous studies25, an injurious fall or syncope potentially. As a result, clinicians have not consistently and strictly controlled blood pressure of frail elderly. Third, frailty was associated with an unhealthy lifestyle. In this study, frail elderly had high BMI, large waist circumference, high smoking rate, and low physical activity rate. High BMI and large waist circumference are associated with poor dietary habits. Because lifestyle modification is also important in blood pressure control, it is difficult to treat HTN in frail elderly. Lastly, we have to consider comorbidities such as diabetes, dyslipidemia, renal impairment, stroke, and cardiovascular disease in frail elderly. It is possible that their general physical condition and polypharmacy had a considerable influence on the effects of antihypertensive drugs.But we observed that HTN control rate was low in frail elderly. There were several reasons that may explain why the control rate was low in frail elderly. First, the target level for blood pressure control has been unclear in frail elderly, and, until recently, clinicians considered individual tolerability in setting up treatment regimens. Second, isolated systolic HTN is common in elderly hypertensive patients. In such cases, many clinicians are concerned that strict systolic blood pressure control using antihypertensive drugs might cause excessively low diastolic blood pressure. Too low diastolic blood pressure might increase the risk of adverse events, such as a stroke15. Additionally, the overall rate of serious adverse events and absolute rates of adverse events, such as hypotension, syncope, electrolyte abnormalities, acute kidney injury, and injurious fall, were not significantly different between treatment groups15. Uncontrolled HTN is the cause of serious cardiovascular events. In addition, previous studies showed that HTN is associated with future ADL/IADL limitation or disability even in patients without stroke27. Blood pressure control helps prevent the occurrence of additional morbidity and consequently helps maintain the current quality of life and ADL/IADL of elderly people.Although, there have been concerns regarding strict blood pressure control for frail older adults, but SPRINT study revealed the benefit of strict HTN control for the patients. There was a significantly lower rate of cardiovascular events and all-cause mortality in the intensive treatment group whose systolic blood pressure was controlled less than 120 mmHg, even the frail elderlyIn this study, frail elderly had lower blood pressure control rate. Additionally, there was a U-shaped relationship between systolic or diastolic blood pressure and frailty index. In other words, frail elderly people consist of two distinct groups, people with high blood pressure and low blood pressure. Accordingly, for the better control of blood pressure of the frail elderly people, we should pay attention to the frail elderly people who have high blood pressure.28. This study has strengths and limitations. First, the study population was drawn from nationally representative samples of older adults in Korea. Therefore, the results of this study are easily generalizable. Second, statistically significant results were attained after adjusting for multiple covariates. Limitations of this study are as follows. First, we cannot know the causal and temporal relationship between frailty and HTN because of limitations of cross-sectional study design. Second, data from the KNHANES V were based on self-reported questionnaires, which present the limitation of recall bias. Third, KNHANES V contains questionnaires about the use of HTN medication and the number of doses per month, but does not include questionnaires about the type of HTN medication and the number of concomitant use. In conclusion, considering frailty status is an independent risk factor for poor blood pressure control, more attention should be paid to control blood pressure in frail elderly.For the frail elderly, blood pressure monitoring and drug side effect confirmation are required through additional early visits to confirm tolerability, when we start a new HTN drug. Once these assessments confirm the intolerance of HTN medication, individualized management, such as drug modification and dose titration, will be required. Especially proper management is necessary to prevent falls when a new HTN drug is started in elderly, because antihypertensive drug initiation during the first 45 days of treatment was associated with an increased risk of falls in community-dwelling elderly


Currently there is limited research documenting the changes in blood parameters, following Flexible Ureterorenoscopy. This study aims to determine whether there are any changes in haematology and biochemistry parameters, following Flexible Ureterorenoscopy for the treatment of kidney stones.40 consecutive patients aged between 27–87 years (median 49 years) undergoing Flexible Ureterorenoscopy for the treatment of kidney stones were recruited . Blood samples were collected from each patient at four time points: baseline (pre-operatively) followed by 30 minutes, 120 minutes and 240 minutes post-operatively. On these samples, routine haematological and biochemistry tests were carried out. In addition to the assessment of clinical parameters prospectively from the medical notes.There was a significant decrease observed following Flexible Ureterorenoscopy in the following parameters: lymphocytes (p = 0.007), eosinophils (p = 0.001), basophils (p = 0.001), haemoglobin (p = 0.002), red blood cells (p = 0.001), platelet count (p = 0.001), fibrinogen concentration (p = 0.001), von Willebrand factor (p = 0.046), C reactive protein (p = 0.01), total protein (p = 0.001), albumin (p = 0.001), globulin (p = 0.001) and alkaline phosphatase (p = 0.001). In addition, there was a significant increase observed in the following parameters: white blood cells (p = 0.001), neutrophils (p = 0.001), activated partial thromboplastin time (p = 0.001), total bilirubin (p = 0.012), creatinine (p = 0.008), sodium (p = 0.002) and potassium (p = 0.001). Limiting factors for this study were the sample size, and restriction on the recruitment time points.Significant changes were noted to occur in haematology and biochemistry parameters following Flexible Ureterorenoscopy. Some of the data presented in this study may represent the ‘normal’ post-operative response following FURS, as no major complications occurred, in the majority of our patients. This data on the ‘normal response’ will need to be validated but may ultimately aid clinicians in distinguishing patients at risk of complications, if reproduced in larger multi-centre studies. Kidney stones are increasing in prevalence and are recognised as a significant health issue , affectiIn the current European Association of Urology guidelines, Shock Wave Lithotripsy (SWL) and Flexible Ureterorenoscopy (FURS) are considered equally suitable treatments for stones between 11–20mm . The CliThe overall complication rate after FURS is 9–25% , with thThe aim of this study was to evaluate haematological and biochemistry changes in patients undergoing FURS for the treatment of kidney stones. It was our expectation to enhance the current urological literature by adding evidence based insight on this topic, and to provide findings that may ultimately aid clinicians in distinguishing patients at risk of complications such as bleeding or infection following FURS.Ethical approval for this pilot study was received from the Welsh Research Ethics Service (REC) 4 committee (REC4: 12/WA/0117). Forty consecutive patients scheduled for elective FURS for the treatment of kidney stones were recruited at their pre-operative assessment after providing written informed consent (n = 40). The patients  were aged between 27–87 years (median 49 years). Of the 40 patients, 27 had a single stone, 10 had two stones and 3 patients had 3 stones in the target kidney. The median stone size was 7.0 mm (range: 2.0 mm—25.0 mm). The median Hounsfield unit was 976 (range: 153–2224). The location of the stones was upper pole (n = 15), mid-pole (n = 8) and lower pole (n = 17). Treatment was given as per standardised protocol in our institution using the Olympus P5 Flexible Ureterorenoscope whilst under general anaesthesia using Propofol, with 75% (30/40) of the patients receiving laser lithotripsy during the procedure for a median duration of 14.58 minutes (range: 30 seconds– 54.02 minutes), at an average energy of 3232.7 J, and a mean pulse of 6272.76. The median operative time for the FURS procedure was 49 minutes (range: 22–104 minutes). Complete stone clearance was achieved in all patients (n = 40) with 25/40 of the patients requiring post-operative stent insertion. Stone samples for biochemical analysis were collected where possible, and the composition was analysed using infrared spectroscopy at the Leicester Royal Infirmary.°C, in accordance to the manufacturers protocol. Subject plasma was obtained by centrifuging whole blood samples at 450g for 15 minutes.On the day of their intervention, each patient had a venous blood sample collected from the arm, prior to the FURS procedure, which stood as a baseline (control) measurement. Following FURS, additional blood samples were collected at 30, 120 and 240 minutes post-operatively. Three vacutainers of blood were collected at each interval (di-potassium ethylene diamine tetra-aceticacid (EDTA), tri-sodium citrate and serum separator tube). All haematological and biochemical analysis was carried out on the day of the procedure on fresh whole blood/plasma, with exception of vWF analysis which was carried out in batches every 6 months on frozen patient plasma, stored at -809/L.Complete blood counts were performed using a Sysmex XE-5000 automated cell counter and platelets measured in units x10aPTT (seconds), PT (seconds) and Fibrinogen (g/L) concentrations were measured using citrated samples using the Sysmex CS2100 analyser. Plasma vWF concentrations (IU/dL) were measured in the frozen samples, using a two-step sandwich method, enzyme immunoassay (ELISA) using rabbit anti-human vWF and rabbit anti-human vWF peroxidase conjugate.Plasma viscosity (mPa/second) was measured using a Benson BV200 viscometer.Biochemistry parameters were measured using the Beckman Coulter AU5800 and AU680 analyser.All results were presented as mean ± standard error (SE) or median ± min/max. Where data was normally distributed, repeated measures one-way analysis of variance (ANOVA) between samples test was employed, adopting a 5% level of significance. Post hoc testing was conducted using the Bonferroni test for pairwise comparisons between means. Data that did not comply with normality was analysed using the Friedman test. Where the Friedman test resulted in statistical significance, subsequent tests were performed using the Wilcoxon test. Statistical significance was accepted when p ≤ 0.05.““One female (participant 12) and two males (participants 9 and 10) developed a post-operative UTI, and participant 32  developed urosepsis. “Figs “204.H20 -calcium oxalate monohydrate) stones, 8 had Apatite (Ca10(PO4)6-(OH)2—calcium phosphate) stones, 4 had Cystine stones [SCH2CH(NH2)COOH]2, 4 had Carbonite apatite (Ca5(PO3)3(OH) -calcium hydroxyl phosphate) stones and 3 had Wheddelite  stones.Stone samples were collected during the FURS procedure from 27 participants. Post-operative calculus analysis found that 21 participants had Whewellite . Although they do not comment on routine haematological or biochemistry based parameters, their findings do report on changes seen in norepinephrine, epinephrine and cortisol; which all increase during surgery and may have an effect on haemostasis . Increas16. AlthoLeukocytes play an integral role during an inflammatory response . A decreUğuz S et al, (2016) explored the effect on ozone therapy in reducing lithotripsy induced renal injury on rats during SWL and found that administering ozone resulted in significant changes to biochemical results, notably a reduction is AST and ALP, as well as ameliorating nitro-oxide stress [One of the participants in our study who developed a post-operative infection (Participant 9), interestingly had a ‘normal’ CRP level “e stress . TherefoTo date there are very few reports on the effect of FURS, for the treatment of kidney stones, on haematology and biochemistry parameters in human subjects. We therefore believe that the results from this study are a welcome addition to the urological literature. However, in order to fully understand the changes within the peripheral circulatory system, further studies involving larger cohorts and longer post-operative monitoring and blood sampling (eg. 24hours +) is needed. The lack of a control arm in this study due to ethical restrictions is also recognised as a limitation, baseline measurements were implemented to overcome this, however sampling procedures my need some revision in future to overcome the potential effects of sampling pre-operatively whilst patients are in a non-physiological state and to fully understand the attributing effects of anaesthesia on patients’ blood parameters.Furthermore, it is acknowledged that a limiting factor of this pilot-study is the relatively small number of participants recruited (n = 40). Nevertheless, we feel that these initial results provide encouragement for further exploration into the inflammatory and phagocytic leukocyte reactions and its correlation with clinical outcome measures (e.g. bleeding and infection), in larger cohorts following FURS. Ultimately, if changes to haematology and biochemistry markers following FURS can identify or predict those patients at increased risk, future directions of this study may offer the potential to guide practice, with the introduction of point of care testing to predict those patients at risk of complications allowing for ‘pre-emptive’ interventions to be implemented; such as pharmacological intervention using anti-inflammatory or anti-haemorrhagic agents to improve patient outcome, in those ‘at risk’ undergoing FURS for kidney stones.In conclusion, in this study we have shown several changes to haematology and biochemistry parameters following FURS. Informed examination of these parameters, in the future, could provide valuable data to aid clinicians in distinguishing a ‘normal’ response after FURS to those that are ‘abnormal’. The ultimate goal is to be able to predict those patients at risk of complications, such as bleeding or infection following FURS. The validation and reliability needs to be assessed through larger cohort studies.S1 File(XLSX)Click here for additional data file.


Oxygen was first described by Carl Wilhelm Scheele as “Fire air” since it supported combustion. He obtained oxygen by heating mercuric oxide, silver carbonate, and nitrate salts. Scheele communicated his findings to Lavoisier, who realized the significance of this finding. Scheele's discovery of oxygen (ca. 1771) was chronologically earlier than the corresponding work of Priestley and Lavoisier, but he did not publish this discovery until 1777, after both of his rivals had already published their findings West, . BecauseOxygen is essential for aerobic metabolism, a fundamental mechanism for energy production. The delivery of optimal levels of oxygen to tissues is tightly regulated as both hypoxia and hyperoxia are detrimental for cellular function. Indeed, tissue hypoxia has been found during pathological conditions such as cancer  in pre-clinical and clinical studies in diabetic and hypertensive CKD along with the underlying mechanisms and potential therapeutic options. The novel hypothesis by Patinha et al. on the cooperative oxygen sensing by the kidney and carotid body in blood pressure control, could further explain the role of kidney hypoxia in hypertension. This is relevant for the pursuit of novel ways to treat associated with sympathetic overdrive. Indeed, Hering et al. reduced sympathetic nerve activity and lowered blood pressure in CKD patients using 100% oxygen  did not allow for the detection of any possible subtle effects of kidney specific oxygenation on sympathetic outflow.Maekawa et al. describes that elevated levels of the uremic toxin indoxyl sulfate (IS) in CKD can induce endoplasmatic reticulum (ER) stress and subsequent hypoxia through suppression of erythropoiesis and exacerbation of tubular fibrosis. They propose that the removal of IS, blockage of aryl hydrocarbon receptor (mediator of IS-induced suppression of erythropoietin production), inhibition of hepcidin production (controls iron homeostasis) and mediation of the ER unfolded protein pathway could be therapeutic targets in ameliorating hypoxia and subsequent CKD progression. Preserving mitochondrial uncoupling might be a potential treatment target. Indeed, kidney hypoxia per se, caused by mitochondrial uncoupling, without confounding factors such as uraemia, hyperglycaemia or hypertension results in albuminuria and tubulointerstitial damage  has the potential to detect several pathophysiological mechanisms involved in kidney allograft dysfunction, making it a promising tool in long-term follow-up of kidney transplantation patients. In addition, Cox et al. showed in a pilot study that multiparametric MRI could assess renal structure, hemodynamics and oxygenation in healthy participants and CKD patients. Renal blood flow and renal cortex perfusion was lower in CKD patients compared with healthy participants. Longitudinal relaxation time , an MRI parameter that increases with reduced perfusion/filtration and/or progressive scarring, were increased in both renal cortex and medulla compared to healthy participants, though primarily in cortex, resulting in a loss of corticomedullary differentiation. Finally, Laustsen describes how the introduction of dissolution dynamic nuclear polarization technology has enabled a new paradigm for renal MRI. They describe the utility of hyperpolarized MRI in preclinical research in which the real-time interrogation of metabolic turnover has already aided the physiological and pathophysiological metabolic and functional effects in ex vivo and in vivo models, and discus its potential translation to renal patients.This research topic highlights the important role of hypoxia in kidney disease and what progress has been made to address its importance. We conclude that it is imperative to further advance our understanding about the sequence of events leading to intrarenal tissue hypoxia, its regulation and consequences in both acute and CKD. If we do that, we might be able to end Scheele's “hard-luck” and have a major impact of patient care and reduce the poor quality of life often associated with kidney disease.MK: conceived the content and drafted the manuscript; MK and FP: revised and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Arterial blood pressure (BP) can be measured directly using an invasive intra-arterial method. This method is considered a gold standard, however it is potentially hazardous and requires expensive equipment and professional skills. Therefore, two non-invasive methods–Doppler ultrasonic sphygmomanometry and oscillometry–have been introduced in veterinary medicine. Their accuracy has so far been reliably evaluated in various animal species, however only one study included a small group of goats. Therefore, we carried out a large-scale study which aimed to evaluate agreement between the two non-invasive methods and invasive intra-arterial BP measurement in anesthetized goats at various age. The study included 122 goats of two Polish local breeds (Polish White Improved and Polish Fawn Improved): 67 adult females, 35 adult males, and 20 two-month-old female kids. Goats were anesthetized with the intravenous mixture of xylazine and ketamine. BP was measured simultaneously with the three methods in each goat with 7 measurements on average taken. The study showed that according to the criteria of the American College of Veterinary Internal Medicine (ACVIM) oscillometric method yielded BP measurements sufficiently consistent with invasive intra-arterial method in anesthetized adult goats– 95% of oscillometric BP measurements were expected to differ from invasive BP measurements by at most ±20–25 mmHg. The agreement was worse in goat kids–oscillometry significantly overestimated invasive BP measurements, which resulted in highly asymmetrical 95% limits of agreement. Doppler systolic BP very poorly conformed to invasive systolic BP both in adult goats and in kids and all the ACVIM criteria were violated. Concluding, oscillometry, but not Doppler ultrasonic sphygmomanometry, may be regarded as an alternative to invasive BP measurement in large-scale scientific studies involving adult goats, however, individual oscillometric BP measurements should be treated with caution as estimated 95% limits of agreement were wide. Arterial blood pressure (BP) measurement on a peripheral artery provides a vital piece of medical information. Four BP measurements are used in human medicine: systolic (SBP), diastolic (DBP), mean (MBP) and pulse pressure (PP). Their routine use in veterinary is hindered by anxiety of animal patients, which precludes obtaining accurate and reliable records . This haDoppler ultrasonic method was the first non-invasive method widely applied in veterinary medicine, and technically is the closest to the cuff/stethoscope auscultatory method. Recently, it has been found consistent with invasive BP measurement in anesthetized rabbits , but preOscillometry has proven to be acceptably consistent with invasive BP measurement in anesthetized dogs , 16, catThe goat has been used as an experimental in vivo model of various orthopedic conditions and surgical procedures in human medicine –24. ThisData were collected from 122 goats of two Polish local breeds (Polish White Improved and Polish Fawn Improved): 67 adult females  aged from 1 to 12 years with the median of 4 years and IQR from 3 to 7 years, 35 adult males  aged 2 years (n = 19) or 3 years (n = 15), and 20 two-month-old female kids (16%). Body weight of adult goats ranged from 20 to 70 kg, and kids weighed between 7 and 10 kg.Goats came from four dairy herds and all were intended for culling due to symptomatic caprine arthritis-encephalitis (adult goats) or chronic arthritis of unknown origin (kids). BP measurements were taken during general anesthesia directly preceding euthanasia. The study was approved by the II Local Commission for Experiments in Animals in Warsaw (WAW2/67/2016).Neither food nor water was withheld before anesthesia. A catheter was placed in the cephalic vein and mixture of xylazine  at dose of 0.05 mg/kg and ketamine  at dose of 5 mg/kg in one syringe was given intravenously. No tracheal tube was inserted, only visual monitoring of respiration was used. An animal was placed in right lateral recumbency. A 20 gauge catheter was placed in the right femoral artery after shaving of hair, cleansing of the skin and making a 1 cm incision of the skin above the palpable pulse of the artery. The catheter was connected via saline-filled non-compliant tubing with a 3-way stopcock to a pressure transducer . The transducer was placed at the level of the right atrium of the heart and the system was electronically calibrated and zeroed to atmospheric pressure according to manufacturer’s recommendations (GE Dash 4000). The system was connected to a bag containing heparinized saline and was periodically flushed to maintain patency. The tubing was constantly checked for the presence of air bubble which were removed if present.Oscillometric blood pressure was measured using PetTrust Veterinary blood pressure monitor for cat and dog . The cuff was placed in the middle of the left forearm and its width was fitted using the measure attached to the device. Doppler blood pressure was measured using Doppler Ultrasonic Flow Detector Model 811-B was used . Doppler blood pressure cuff was placed above the left hock. The limb circumference was measured and a cuff that was approximately 40% of the circumference of the limb was chosen . The proInvasive mean blood pressure was used to classify goats into blood pressure classes of normotensive (MBP for 65 to 100 mmHg), hypotensive (MBP <65mmHg), and hypertensive (MBP >100mmHg). Pulse pNumerical variables were presented as the arithmetic mean and standard deviation (SD) or as the median and interquartile range (IQR), if SD exceeded one-half the arithmetic mean . The range was presented in all cases. Comparisons between groups of unpaired observations were performed using the one-way analysis of variance (ANOVA) with the Tukey’s HSD post-hoc test for unequal group sizes, or Kruskal-Wallis H test with Dunn’s post-hoc procedure. Paired groups were compared using paired-sample Student’s t-test or Wilcoxon signed-rank test, the latter with a Bonferroni correction if more than 2 groups were analyzed. All statistical test were two-sided and the significance level (α) was set at 0.05.Among measurements taken from each goat the outliers were identified according to Tukey’s rule with fences set at 3 interquartile ranges (IQR) above the upper quartile (Q3) or below the lower quartiles (Q1). Then variability of measurements obtained from a goat was calculated as the coefficient of variation (CV% = 100% × SD / arithmetic mean). Outliers were dropped from further analysis only if raised CV% above 20% . RemainiAgreement between blood pressure by invasive (I), oscillometric (O) and Doppler (D) method was determined by calculating the arithmetic mean of difference between pairs of methods (henceforth referred to as bias) ± SD (precision). Relationship between BPs and HR was determined using the Pearson’s product-moment correlation coefficient (r). Invasive method was regarded as a reference gold standard, and oscillometric and Doppler method as alternative tests. The 95% confidence interval (95% CI) for the bias was also calculated and if it fell entirely above or below 0 the results obtained using an alternative method were considered as significantly biased i.e. they were found to non-coincidently over- or underestimate the true blood pressure. To evaluate the clinical importance of the discrepancies the cumulative percentage of oscillometric and Doppler readings falling within ±10 mmHg and ±20 mmHg of the invasive reference method were determined. Furthermore, paired measurements were plotted on the scatter diagram (O vs. I and D vs. I) with the line of equality and then their differences  were plotted against invasive BP measurements (not against the averages of the two methods as invasive method was considered a gold standard  to show The measures of agreement obtained were compared with ACVIM guidelines . Power oUsing each of the three methods between 5 and 9 measurements (median of 7) were taken from each goat. In 35 adult goats (34%) and 3 kids (15%), despite repeated attempts lasting at least half an hour, we were unable to obtain Doppler blood pressure measurements since we could not localize the dorsal metatarsal artery with the Doppler probe. Median CV% ranged from 3.2% in invasive MBP to 8.8% in oscillometric DBP and in general variability of measurements was lower in invasive than in oscillometric and Doppler method, and was the highest in DBP . Only onKids had significantly lower SBP, DBP and MBP than adults when measured using invasive method, however this difference was not observed in oscillometry. Blood pressure did not differ between adult males and females regardless of the method used .Significant bias was observed between invasive and oscillometric blood pressure both in adults and in kids, however the direction and magnitude of the bias was different: in kids SBP, DBP and MBP were overestimated by oscillometry by 7–11 mmHg on average, whereas in adults oscillometry underestimated DBP and MBP significantly but only by 2–3 mmHg on average. In turn, oscillometric SBP and PP in adults were not significantly biased . OscilloOscillometry satisfied all the criteria of ACVIM in adults and in kids, except for the bias of SBP which was by 1.5 mmHg too high than accepted by ACVIM  as well LoAs indicated that 95% of oscillometric SBP measurements in adult goats were expected to be from 22 mmHg higher to 23 mmHg lower than invasive measurements, while in kids from 33 mmHg higher to only 10 mmHg lower than invasive measurements . SimilarDoppler SBP poorly conformed to invasive SBP both in adult goats and in kids . LoAs weOscillometric and invasive HR was differed on average by -0.8±5.2 bpm and the bias was not significantly different from 0 . LoAs were from -11  to 10  bpm. No significant correlation was observed between any of BPs and HR .We showed in our study that oscillometric method yielded BP measurements sufficiently consistent with invasive intra-arterial method in anesthetized adult goats according to ACVIM criteria. The ACVIM criteria were satisfied also in each of blood pressure classes except for SBP in hypertension, whose SD was, however, only slightly above 15 mmHg (16.3 mmHg). Ninety five per cent of oscillometric BP measurements are expected to differ from invasive BP measurements by at most 20–25 mmHg, which is less than allowed by ACVIM guidelines . AgreemThe agreement was worse in goat kids, in which presented LoAs must be treated with even higher caution as the sample of kids was much smaller than adult goats. Oscillometry significantly overestimated invasive BP measurements (contrary to the bias observed in DBP and MBP in adults), which resulted in highly asymmetrical LoAs. This may indicate that the cuff used was undersized. As we used a tape measure provided by the manufacturer of the oscillometric device to determine the cuff size to be used, it appears that perhaps in goat kids wider cuff than recommended should be chosen by default.It ought to be stressed that the maximum difference between 95% of BP measurements of ±30 mmHg is twofold more than AAMI allows in terms of automatic devices used in human medicine (1.96 × SD of 8 mmHg is 16 mmHg) , and hypOur study undoubtedly disqualifies Doppler ultrasonic sphygmomanometry as an accurate method of SBP measurement in anesthetized goats. It is not because we could not localize pulse on the dorsal metacarpal artery and measure SBP in a considerable proportion of goats as switching to another vessel might have perhaps solved this problem. However, LoAs were significantly beyond the ACVIM acceptable range and Doppler tended to overestimate SBP considerably both in adults and kids. Large number of adult goats enrolled in the study makes this conclusion highly trustworthy, however the discrepancies observed were so big that even the sample size of 17 kids resulted in the probability of error below 10% . Along with our previous results showing large disparities between oscillometric and Doppler BP measurements in conscious goat , this obThis is the first study to evaluate BP measurements in a group of males which was large enough to fulfil AAMI requirements , and to compare BP between sexes. BP proved not to differ between males and females, contrary to previous observations in dogs , but in In our study a different artery  was used for invasive BP measurement compared to previous studies in small ruminants (auricular). The femoral artery is more central artery than auricular, so it could perform slightly better as an indicator of aortal BP, as MBP measurements from the auricular artery have been shown to be lower than those obtained from the carotid artery in rabbits . NeverthInvasive method proved to yield significantly more repeatable BP measurements (as indicated by significantly lower CV%) than oscillometry and Doppler. Generally, the range of CV% observed was wide although quite similar to previously obtained  and DBP Concluding, oscillometry, but not Doppler ultrasonic sphygmomanometry, may be regarded as an alternative to invasive BP measurement in large-scale scientific studies involving adult goats, however, individual oscillometric BP measurements should be treated with caution.S1 FigDiagonal line on the scatter plot (A) is a line of equality. Upper and lower solid horizontal lines on Bland-Altman plots (B) signify the upper and lower limits of agreement, respectively while the broken lines show the mean difference (i.e. bias) between invasive and oscillometric SBP measurements.(TIF)Click here for additional data file.S2 FigDiagonal line on the scatter plot (A) is a line of equality. Upper and lower solid horizontal lines on Bland-Altman plots (B) signify the upper and lower limits of agreement, respectively, while the broken lines show the mean difference (i.e. bias) between invasive and oscillometric DBP measurements.(TIF)Click here for additional data file.S3 FigDiagonal line on the scatter plot (A) is a line of equality. Upper and lower solid horizontal lines on Bland-Altman plots (B) signify the upper and lower limits of agreement, respectively while the broken lines show the mean difference (i.e. bias) between invasive and oscillometric MBP measurements.(TIF)Click here for additional data file.S4 FigDiagonal line on the scatter plot (A) is a line of equality. Upper and lower solid horizontal lines on Bland-Altman plots (B) signify the upper and lower limits of agreement, respectively while the broken lines show the mean difference (i.e. bias) between invasive and Doppler PP measurements.(TIF)Click here for additional data file.S5 FigDiagonal line on the scatter plot (A) is a line of equality. Upper and lower solid horizontal lines on Bland-Altman plots (B) signify the upper and lower limits of agreement, respectively while the broken lines show the mean difference (i.e. bias) between invasive and Doppler SBP measurements.(TIF)Click here for additional data file.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.


Atherosclerosis begins in youth and is associated with the presence of numerous modifiable cardiovascular (CV) risk factors, including hypertension. Pediatric hypertension has increased in prevalence since the 1980s but has plateaued in recent years. Elevated blood pressure levels are associated with impairments to cardiac and vascular structure and both systolic and diastolic function. Blood pressure-related increases in left ventricular mass (LVM) and abnormalities in cardiac function are associated with hard CV events in adulthood. In addition to cardiac changes, key vascular changes occur in hypertensive youth and adults. These include thickening of the arteries, increased arterial stiffness, and decreased endothelial function. This review summarizes the epidemiologic burden of pediatric hypertension, its associations with target organ damage (TOD) of the cardiac and vascular systems, and the impact of these adverse CV changes on morbidity and mortality in adulthood. Internationally, ischemic heart disease and stroke is the leading cause of death  and it iData from the National Health and Nutrition Examination Survey (NHANES) demonstrate that BP levels in the pediatric population rose from 1988 to 1999  and haveHypertension is more common in boys aged 8–17 than girls, and is more prevalent in African American and Hispanic children and in older children .Routine measurement of BP beginning at age 3 at well-child visits is recommended to allow for the early detection of both primary and secondary hypertension . DespiteChildren and adolescents with elevated BP are at risk for progressing to sustained hypertension. A longitudinal assessment of 13–15 year olds from the National Childhood Blood Pressure database demonstrated that, of youth with elevated (pre-hypertensive) BP measurements initially, 14% of boys and 12% of girls developed sustained hypertension 2 years later. The rate of progression from elevated BP to hypertension was determined to be about 7% per year –23. In aA new Clinical Practice Guideline (CPG) was published by the American Academy of Pediatrics on the screening and management of elevated BP in children and adolescents in 2017  and servAtherosclerosis begins in childhood , 32, and2.7. Although LVM >51 g/m2.7 predicts hard adulthood CV events (2.7 and reserve ≥51 g/m2.7 as an indication of significant LV hypertrophy (LVH) requiring more urgent treatment , as opposed to ongoing efforts to improve lifestyle habits (diet and exercise), as supported by the CPG  results in increased LVM that may, over time, result in impaired diastolic and eventually, systolic function. The first measure of diastolic function developed was the ratio of the Doppler velocity of the early flow through the mitral valve “E-wave” to the velocity created by atrial contraction, the “A-wave” (E/A ratio) . This paSystolic function is assessed via the shortening fraction (percentage by which the LV decreases in dimension during systole) or ejection fraction (percentage change in LV volume during systole)  or cardiFortunately, antihypertensive treatment can reduce LVH in both children , 76 and Vascular testing may include measures of vascular structure, arterial stiffness, or endothelial function. These tests are related but assess different properties of the arterial tree and may be affected by risk factors and treatments in different ways. Therefore, ideal assessments of a patient's vasculature involve a combination of techniques.“Hardening of the arteries” is a frequently employed lay term for atherosclerosis. The vascular changes associated with atherosclerosis eventually result in TOD and CV morbidity and mortality. Therefore, it is important to note that a direct relationship exists between sub-clinical measures of atherosclerosis such as increased cIMT  or increcIMT is most commonly measured with “B-mode” ultrasound imaging of the common carotid, carotid bulb, and internal carotid artery at end diastole . While mElevated cIMT is associated with CV events in adults  and pediArterial stiffness is associated with CV events in adults , 101 andDuring assessment of cIMT, M-mode  of the common carotid artery is performed to obtain the maximal (during systole) and minimal (during diastole) diameters to calculate carotid stiffness . IncreasNon-ultrasound-based methods for evaluating arterial stiffness have also been developed. One such method, brachial dispensability (BrachD), involves the use of a cuff-based BP device. Similar to carotid stiffness, BrachD is lower (stiffer vessel) in youth with pre- or sustained hypertension  and in yPWV is the speed by which blood moves along the arterial tree. It is typically measured from an ECG-gated arterial pulse at a proximal (carotid) and distal artery  using a pressure tonometer allowing for determination of the pulse transit time Figure  5). PWV. PWV5). Augmentation index (AIx) is an assessment of arterial stiffness that involves assessing wave reflections through tonometry. As blood moves through the arterial system, each pulse comes in contact with various branch points in the body, allowing for wave reflections back to the heart. The cardiac afterload to the heart is therefore a summation of the outgoing and reflected waves . AIx is Arterial stiffness can also be calculated from 24-h ambulatory BP recordings. The ambulatory arterial stiffness index (AASI) is calculated as 1 minus the regression of the 24-h systolic on diastolic BP readings. As it is dependent on both cardiac output and arterial function (pulse pressure), it may serve as an indicator of ventricular-arterial coupling . Given tIn contrast to arterial stiffness which measures intrinsic arterial wall function, endothelial function evaluates the response of the endothelium to a stress . CurrentA non-ultrasound assessment of endothelial function is provided by the EndoPAT  device. A small cuff is placed on one finger of each hand and the reactive hyperemic index (percentage increase in blood flow) is measured following an ischemic stimulus from an inflated cuff above the patient's systolic BP for 5 min .Laser Flow Doppler (LFD) may be appropriate for evaluating endothelial function in younger children as one may avoid an ischemic insult by using a heating stimulus on the forearm to evaluate the microvascular. Adults with hypertension have been shown to have a reduced response to localized heating . While LVenous plethysmography uses a strap placed around the mid forearm and inflatable BP cuffs on the upper arms and wrist to allow arterial inflow without venous outflow. A stimulus  is applied and the change in limb circumference is measured by a strain gauge. By confining the study to a limb, plethysmography avoids counter-regulatory systems such as increases in heart rate that may occur with vasodilation. Using this technique, endothelial function was lower in obese 10 year-old children with handgrip and mental stress testing compared with their lean counterparts .Primordial prevention, or the prevention of acquisition of CV risk factors is the first step for preventing accelerated vascular aging. Data from the Bogalusa Heart Study  and the Secondary prevention (aggressive treatment in high risk youth) also results in improvement in vascular function including slower progression of cIMT in youth with pediatric familial hypercholesterolemia treated with statins , 140. InBefore vascular assessment can be used clinically, normative data are required across age, body size, and race/ethnicity. Although some epidemiologic studies using PWV have included some healthy children –146, andHypertension is a prevalent CV risk factor in children and adults and is associated with increased vascular thickness and stiffness, reduced endothelial function, and adverse changes to cardiac structure and function. These changes are strongly associated with the occurrence of hard CVD end-points in adulthood. Fortunately, lifestyle and pharmacologic intervention studies have demonstrated improvements in vascular and cardiac health in both hypertensive patients and those with other CV risk factors. However, much more work remains to be done, particularly with respect to normative data for vascular assessments in the pediatric population and evaluations of treatments to improve CV structure and function in an effort to reduce the significant burden of CV diseases around the world.MK and EU made substantial contributions to the conception or design of the work, drafting the work and revising it critically for important intellectual content. MK and EU provided approval for publication of the content and agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.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.


The title should have appeared as “Nonspecific ST-T changes associated with unsatisfactory blood pressure control among adults with hypertension in China: Evidence from the CSPPT study.”In the article, “Nonspecific ST-T changes associated with unsatisfactory blood pressure control among adults with hypertension in China: Evidence from the CSPTT study”,


The purpose of the present study was to investigate the association between the number of natural teeth and measures of kidney dysfunction, such as urinary albumin/creatinine ratio (ACR) and estimated glomerular filtration (eGFR) rate, using nationally representative data.The data used were from the Korea National Health and Nutrition Examination Survey with cross-sectional design, which was conducted between 2011 and 2012; the sample analyzed in this study consisted of a total of 10,388 respondents, each of whom was 19 years or older and had no missing outcome variables. The association between the number of natural teeth and kidney function was assessed by multiple logistic regression and model was adjusted for age, sex, waist conference, smoking, drinking, exercise, education, income, frequency of tooth brushing per day, diabetes, metabolic syndrome, urinary ACR, and eGFR.2). Urinary ACR and eGFR were associated with loss of natural teeth. As urinary ACR increased, the number of natural teeth decreased accordingly. Conversely, the number of natural teeth increased with an increase in eGFR.The mean age, body mass index, and waist circumference were significantly higher among those with lower kidney function (urinary ACR ≥30 mg/g and eGFR <60 mL/min/1.73mThis study showed that the number of natural teeth is inversely associated with the presence of kidney disease. Severity of tooth loss may be considered an independent risk indicator for kidney disease among Koreans. More epidemiological studies are warranted to investigate the role of tooth loss in kidney disease, to confirm this relationship and to test possible underlying mechanisms. It was suggested that periodontal disease is associated with increased risk of cardiovascular disease. In the previous study, severe periodontitis was associated with compromised glycemic control and periodontal treatment was associated with improvements in glycemic control in diabetic patients.Observational studies have shown an association between poor oral health and systemic diseases. The incidence of periodontal disease  was significantly higher among people with renal disease than among controls. Recently, it was reported that periodontitis was associated with increased prevalence of inflammatory markers in end-stage renal disease patients. Recent epidemiological studies have suggested that periodontitis is a major risk factor for renal failure.,10 Within the authors’ knowledge, there is no known report to evaluate the association between the number of natural teeth and eGFR with nationally representative data. Thus, this study was performed to investigate the association between the number of natural teeth and both urinary ACR and eGFR using nationally representative data.Chronic kidney diseases were shown to affect the oral health status of patients by inducing xerostomia, delayed eruption of teeth, calcification of root canals, and gingival hyperplasia.22.1The data from the Korea National Health and Nutrition Examination Survey (KNHANES), which was performed between 2011 and 2012, were used for the study. KNHANES is conducted to evaluate the health and nutritional status for the Korean people and KNHANES is an ongoing surveillance system in the Republic of Korea that assesses the health and nutritional status of Koreans, monitors trends in health risk factors and the prevalence of major chronic diseases, and provides data for the development and evaluation of health policies and programs in Korea. The KNHANES uses a stratified and multistage probability-sampling design with a rolling survey-sampling model. The sample weights were used to calculate all the statistics in this survey. A total of 16,576 patients initially participated in the survey. The analysis in this study was confined to a total of 10,388 respondents who were 19 years or older and who had no missing values for the outcome variables  and by estimated glomerular filtration rate (eGFR).2) = 186.3 × (serum creatinine−1.154) × (age−0.203); this result was then multiplied by the constant 0.742 if the patient was female. The equation was developed from the Modification of Diet in Renal Disease (MDRD) formula. Participants with eGFR <60 mL/min/1.73m2 were considered to have kidney disease. For this study, chronic kidney disease was ascertained if a patient's eGFR was <60 mL/min/1.73m2.,14The level of kidney function was also determined by eGFR using an abbreviated equation: eGFR . If the monthly house income was <$1092.40, it was considered the lowest quartile. The participants were categorized by those with at least a high school degree and those with less education. Sleep duration and stress recognition were self-reported. Daily energy, fat, protein, and calcium intake were calculated based on the survey.Participants were regarded as regular physical exercisers if the participants performed vigorous exercise at least 3 times per week for at least 20 minutes per session or moderate exercise at least 5 times per week for at least 30 minutes per session.2.5Blood pressure measurements were performed using a standard mercury sphygmomanometer . Systolic and diastolic blood pressures were measured 2 times at intervals of 5 minutes, and the analysis used the average values. A gamma counter  and a 25-hydroxyvitamin D 125I radioimmunoassay kit  were utilized to measure serum 25-hydroxyvitamin D levels.A blood sample was collected from each participant's antecubital vein after the individual had fasted for >8 hours to measure concentrations of serum-fasting plasma glucose, glycated hemoglobin (HbA1c), total, low-density lipoprotein, high-density lipoprotein cholesterol, triglycerides; white blood cell count, and serum 25-hydroxyvitamin D. The blood samples were analyzed within 24 hours of transportation. Levels of serum-fasting plasma glucose, HbA1c, cholesterol, and triglycerides were measured with the analyzer  using enzymatic methods and commercially available kits .2.6 Diabetes was diagnosed when fasting blood sugar was >126 mg/dL or when the individual was currently using antidiabetic medications. Metabolic syndrome was defined according to the criteria for Asians in the American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Three or more of the following criteria must be met to be diagnosed with metabolic syndrome: waist circumference of at least 90 cm in men or 80 cm in women; fasting triglycerides of at least 150 mg/dL (or use of lipid-lowering medication); high-density lipoprotein cholesterol of <40 mg/dL in men or 50 mg/dL in women (or use of medication); blood pressure of at least 130 mmHg systolic blood pressure and 85 mmHg diastolic pressure (or use of antihypertensive medication); and fasting blood glucose of at least 100 mg/dL (or use of antidiabetic medication).If participant had a systolic blood pressure of >160 mmHg, a diastolic blood pressure of >90 mmHg, or currently used systemic antihypertensive drugs, the individuals were considered having hypertension.2.7The time of day of patients’ tooth brushing was noted as part of their oral health behavior and the frequency of daily tooth brushing was calculated from the oral health behavior.The survey also recorded patients’ secondary oral product use, return dental checkup timing , and self-reported oral status.In this study, the natural tooth was considered to be present if the permanent tooth was present or primary tooth was present. The total number of natural teeth was calculated from the examination. Training was provided to each examiner to minimize measurement errors during the examination as part of quality control.2.8t test or a χ2 test was used to investigate the differences as categorized by urinary ACR or eGFR. The association between the number of natural teeth and kidney function was assessed by multiple logistic regression. Model 1 was adjusted for age, sex, and waist conference. Model 2 was adjusted for the same variables as Model 1 plus smoking, drinking, exercise, education, income, and frequency of tooth brushing per day. Model 3 was adjusted for the variables in Model 2 plus diabetes, metabolic syndrome, urinary ACR, and eGFR. The survey procedure of a statistical program  was used for statistical analysis to account for the complex sampling design. Two-sided P values of 0.05 were used for the statistical significance.The data were presented as mean ± standard error or as a percent (standard error). To achieve normal distribution, a logarithmic transformation was performed when necessary. Either Student 32). The mean age, body mass index, and waist circumference were significantly higher among those with lower kidney function. Systolic and diastolic blood pressure, glucose, HbA1c, and triglycerides were also statistically higher among those with kidney diseases. High-density lipoprotein levels were significantly lower among those with kidney diseases. The percentage of individuals in the lowest-income quartile was higher among those with lower kidney function. The percentage of patients with at least a high school degree was lower among those with kidney disease. The prevalence of hypertension, diabetes, and metabolic syndrome was significantly higher among those with kidney disease. The subgroup analysis  is shown in Table P < 0.01). Similarly, the number of natural teeth was lower among the participants with hypertension, diabetes, or metabolic syndrome (P < 0.01).Table Figure 2) according to the number of natural teeth. The odds ratios increased in the individuals with urinary ACR ≥30 mg/g. The adjusted odds ratios  among participants with urinary ACR ≥30 mg/g were 1 [reference] for individuals with 28 natural teeth, 1.298 (0.989–1.703) for those with 20 to 27 teeth, and 1.758 (1.302–2.375) among those with ≤19 teeth. The adjusted odds ratios  for participants with eGFR <60 mL/min/1.73m2 were 1 [reference] for individuals with 28 natural teeth, 1.329 (0.691–2.557) for those with 20 to 27 teeth, and 1.287 (0.659–2.513) for those with ≤19 teeth.Table 42).This study clearly showed that the odd ratios for having fewer natural teeth tended to increase among the participants with lower kidney function  may be associated with periodontitis. International recommendations suggest that the measurement of serum creatinine should be supplemented with eGFR using the MDRD study's equation.,32 This previous report showed that the MDRD equation provided reasonably accurate GFR estimates in patients with chronic kidney disease. The lack of standardization of commercially available creatinine assays, which resulted in varying estimates of GFR, was considered to be problematic, and another study suggested the use of isotope dilution mass spectrometry without the requirement of standardization to the MDRD laboratory. Renal function may be estimated using the Chronic Kidney Disease Epidemiology Collaboration equation.,26Kidney function may be determined using various methods. Poor oral health behavior may worsen inflammation; a previous report showed that poor oral hygiene was related to higher inflammatory markers.,35 Periodontitis is a chronic inflammatory disease that results from a microbial infection within the subgingival dental plaque biofilm; the resulting inflammatory response may facilitate intravascular dissemination of microorganisms and their products throughout the body. This disease destroys tooth-supporting tissues and may lead to loss of teeth. Periodontitis leading to tooth loss has been labeled as an important potential risk factor for noncommunicable diseases, including diabetes mellitus, cardiovascular diseases, pulmonary diseases, and osteoporosis. A higher percentage of periodontal disease among patients with renal disease was noted when these patients were compared with healthy individuals. The prevalence and severity of chronic periodontitis in the previous cohort of chronic kidney disease patients was markedly higher than it was in a geographically matched control population in Europe. In another report, poor oral health, which includes chronic periodontitis, was a common finding in patients undergoing hemodialysis, and chronic periodontitis was considered a continuous, reversible source of inflammation and this has a potential impact on mortality in patients undergoing hemodialysis. The authors suggested intervention trials to test the hypothesis that treatment of chronic periodontitis may improve survival in patients undergoing hemodialysis.The mechanisms behind the association between kidney function and the number of natural teeth may be explained partially by the following. Inflammation can be considered to be the intermediate factor between oral health behavior and systemic diseases. However, some limitations should be considered regarding this study, as it used a cross-sectional design, which makes it difficult to determine whether there is a direct relationship between the exposure and the outcome. Another limitation of this study is that individuals’ energy intake and oral health behavior were obtained self-reported and were under recall basis.,43 Data regarding the inflammatory markers  were not available, so the study's explanation of inflammation and kidney disease is limited.The most important strength of this study is that it is based on a nationally representative sample of Koreans. KNHANES is a nationwide survey of noninstitutionalized civilians; it uses sample participants and sample weights to represent the Korean population and considers survey nonresponse, complex survey design, and poststratification.2), the adjusted odds ratios for the group with 28 natural teeth were lower than the ratios for those with fewer natural teeth. Tooth loss may be considered an independent risk indicator for kidney disease in Korean people. More epidemiological studies are warranted to investigate the role of tooth loss in participants with kidney disease, to confirm this relationship, and to test possible underlying mechanisms.This study showed that the number of natural teeth is inversely associated with the presence of kidney disease. Among those with reduced kidney function (eGFR <60 mL/min/1.73mThe authors acknowledge the Korea Centers for Disease Control and Prevention for providing the data.