Cushing's disease (CD) is remarkably prevalent among females; however, more severe clinical presentation and adverse outcomes have been found in males. The purpose of this study was to investigate the overall clinical profile and biochemical parameters in patients with CD to identify the gender differences. Here we describe our series of CD patients referred to our medical center during 2012-2013. Among 73 cases, females presented a marked preponderance compared to males. Males had significantly higher ACTH, BMI, HbA1c, systolic blood pressure, and hemoglobin than females. For the first time, the incidence of fatty liver and hepatic function was also shown to be elevated in males. Multiple linear regression analysis was performed to further investigate the correlation of risk factors with hypokalemia, HbA1c, and systolic blood pressure. Gender and serum cortisol were associated with hypokalemia. Age, gender, and serum cortisol were significantly associated with HbA1c. Additionally, only gender was significantly associated with systolic blood pressure. Regarding clinical presentation, purple striae seemed to occur more frequently in males than in females. Thus, more severe clinical presentation, biochemical parameters, and complications were found in males than in females. Clinical professionals should pay more attention to the diagnosis and management of males with CD. Cushing's disease (CD) is caused by a corticotroph pituitary adenoma that secretes adrenocorticotroph hormone (ACTH), resulting in chronic overproduction of cortisol by the adrenal glands. This chronic state of hypercortisolism is associated with many metabolic disorders such as central obesity, diabetes mellitus, hypertension, and dyslipidemia.It is well accepted that the incidence of CD is higher among women than among men, with new cases diagnosed at the ratio of 3–8 : 1 . HoweverThe purpose of the present study was to identify the gender differences associated with clinical presentation, biochemical parameters, and complications of CD in patients from a single center. Results of this study may assist clinical physicians with the difficulties in diagnosis and management of this disorder.This retrospective study included 73 patients referred to the Endocrine Department of Huashan Hospital for evaluation and diagnosis of CD from January 2012 to December 2013. Sixty females and thirteen males were enrolled. All subjects had detailed clinical evaluation by the same group of endocrinology specialists to avoid subjective influences.μg/dL after overnight 1 mg DST; and (3) impaired serum cortisol secretion circadian rhythm , as previously described [The 24-hour urinary free cortisol (UFC) excretion, the overnight 1 mg dexamethasone suppression test (DST), and cortisol secretion circadian rhythm were used as first-line screening tests to identify patients with Cushing's syndrome (CS) after exclusion of exogenous glucocorticoids exposure. The diagnostic criteria included (1) elevated levels of 24-hour UFC (average of at least 2 samples); (2) failure of plasma cortisol decrease <5 escribed –12. Plasescribed . Plasma Body mass index (BMI) and blood pressure were measured under the same conditions at diagnosis. Hemoglobin, plasma potassium (plasma K), hepatic function, creatinine (Cr), hemoglobin A1c (HbA1c), lipid profile, and testosterone were evaluated by standard methods. Ultrasound was used to assess fatty liver. Fatty liver was defined by the presence of at least two of three abnormal findings on abdominal ultrasonography including diffusely increased liver near-field ultrasound echo, liver echo greater than kidney; vascular blurring and the gradual attenuation of far-field ultrasound echo .U test. Categorical variables were evaluated with Chi-squared test, as appropriate. Multiple linear regression analysis was used to assess associations between variables. Data were analyzed using the statistical software SPSS 10.0 . A two-tailed P value less than 0.05 was established as statistical significance.Continuous data are shown as median and range  and compared between groups using the nonparametric Mann-Whitney Gender-related patients' characteristics are presented in P < 0.05) . Arterial hypertension was defined as blood pressure >140/90 mmHg or patients were already taking antihypertensive drugs. No significant differences were found in the prevalence of hypertension between genders . Similarly, no differences were found in the frequency of HbA1c above 6.5% between genders . Fatty liver assessed by ultrasound was found to be more prevalent in males than in female patients  .β = −0.522, P = 0.025) and plasma F  were found to be associated with hypokalemia. Age , gender , and plasma F  were significantly associated with HbA1c. However, in multiple linear regression analysis, there did not appear to be a relationship between plasma F and systolic blood pressure. Only gender  was significantly associated with systolic blood pressure.When age, gender, BMI, and plasma F values were included in the multiple linear regression model , gender Regarding clinical presentation, the prevalence of purple striae seemed to occur more frequently in males than in females . MeanwhiIn this study, to establish a better understanding of CD, we retrospectively analyzed the differences in clinical presentation, biochemical parameters, and complications between male and female CD patients. The subject population of our investigation was diagnosed and treated in only one medical center within a two-year period. Although the number of patients was smaller compared to other studies , one strResults of the present study confirmed that, just like many other endocrine disorders, CD was more prevalent in females. Nevertheless, previous studies have shown the opposite results among prepubertal patients , 15. We CD is associated with high levels of cortisol and ACTH. In the present study, the plasma and urine cortisol levels were slightly higher in male patients, but there were no statistically different results between genders. The limited number of male patients may explain the wide range of 24-hour UFC values found in this study. It would be worth assessing cortisol values in larger populations to confirm these findings in the future. In contrast to wide-ranging UFC values, ACTH levels were extremely and consistently higher in males at three different time points of a day, which agrees with results of previous studies. It has been demonstrated that pituitary adenomas in males have a greater secretory capacity, but it is still unclear what the risk factors are for CD. Also, the greater secretory capacity cannot be explained simply by the size of the adenoma. Several factors were observed that could affect the MRI diagnosis, so observations in this area are in conflict with results of other studies –8. ThereThe elevated cortisol levels were combined with several severe clinical presentations. Results of the present study highlight the differences in the clinical profiles between male and female patients at diagnosis. Our observations have confirmed that the purple striae represent a marked male preponderance of this characteristic, which had been previously reported . This fiAs is already well known, the glucocorticoids are important modulators of red blood cell development . Patientβ-hydroxysteroid dehydrogenase type 2, 11β-HSD2) to bind with mineralocorticoid receptors that exhibit mineralocorticoid activity [β-HSD2 activity, which may amplify the actions of cortisol on the mineralocorticoid receptor [Similar to ectopic ACTH secretion, the prevalence of hypokalemia at diagnosis correlated with cortisol levels . This maactivity , 21. Wheactivity , 8. In aactivity , 23. Intactivity , 23. Moractivity , 24–27. activity . Furtheractivity , but alsreceptor . Thus, mGlucose metabolism disorders are a frequent complication of CD , 31. AnoA final gender-related issue of hepatic function is worth mentioning. The glucocorticoids, as well known, have strong effects on the liver that affects the secretion of several hormones. Our findings documented elevated levels of biologic markers for liver function in men, which has not been reported previously. The higher frequency of BMI found in males could be an important factor. Also, the presence of fatty liver might partially explain this result. The diagnosis of fatty liver using ultrasound revealed a higher prevalence in males than in females. However, previous reports showed that only 20% of patients with CS had hepatic steatosis using computed tomography (CT) and there were no gender differences . In thisIn conclusion, the results of this current investigation demonstrated that males with CD were fewer than females but had more severe clinical presentation, biochemical parameters, and complications, including ACTH, systolic blood pressure, HbA1c, BMI, hepatic function, and fatty liver. Results of this study may help to draw physicians' attention to the diagnosis and management of CD in males.


The influences of obstructive sleep apnea hypopnea syndrome (OSAHS) on blood pressure and C-reactive protein (CRP) were observed, and the underlying mechanism was investigated.Respiratory sleep monitoring was performed on 188 male patients who were newly diagnosed with hypertension. Based on the apnea hypopnea index (AHI) results, patients were divided into a normal control group , a mild OSAHS group , a moderate OSAHS group , and a severe OSAHS group . Ambulatory blood pressure monitoring was conducted on patients in each group, and blood samples were collected to detect indicators, including fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and high-sensitivity CRP (hs-CRP).2 = 0.46) and nDBP (adjusted R2 = 0.38) and negatively correlated with the nocturnal blood pressure reduction percentage (adjusted R2 = 0.48).TG and hs-CRP in patients in the moderate and severe OSAHS groups were higher than those in the normal control group . Additionally, their mean nocturnal systolic blood pressure (nSBP) and nocturnal diastolic blood pressure (nDBP) were higher than those in the normal control group . However, the percentage of blood pressure reduction at night was significantly lower than that in the normal control group (P < 0.01). AHI and hs-CRP positively correlated with nSBP (adjusted RModerate and severe OSAHS induced increases in nocturnal blood pressure and CRP content in the body, resulting in further damage to the circadian rhythms of blood pressure. Hypertension is one of the most important risk factors for patients with cardiovascular and cerebrovascular diseases. Achieving blood pressure control within the standard range has important significance for the reduction of cardiovascular mortality. However, studies have shown that when hypertension patients also had obstructive sleep apnea hypopnea syndrome (OSAHS), their blood pressure fluctuations were more obvious than those in general hypertension patients, and they had difficultly achieving control within the standard range . CurrentA total of 188 male hypertension patients diagnosed and treated in our department from June 2014 to May 2015 who all conformed to the diagnostic criteria of the “2014 evidence-based guideline for the management of high blood pressure in adults” (JNC8) [2 (m2).The patients’ ages, heights, and body weights were recorded. The body mass index (BMI) was calculated for each patient according to the formula: BMI = body weight (kg)/heightTM, ResMed, Australia). On the first day of admission, the recording time was longer than 7 h. On the examination day, drinking alcohol and coffee and taking sedatives and sleeping pills were prohibited to avoid interfering with the assessments. The monitoring items included posture, nasal airflow, thoracoabdominal movement, and the minimum blood oxygen saturation (SpO2). On the next day, the sleep monitoring results of all patients were analyzed according to the 2003 Chinese OSAHS treatment guidelines (draft), of which the apnea hypopnea index (AHI) = ((number of apnea events + number of hypopnea events)/sleep time (min)) × 60. Based on the detected AHI values, the 188 patients were divided into 35 cases in the normal control group (AHI ≤ 5), 28 cases in the mild OSAHS group (5 < AHI ≤ 15), 57 cases in the moderate OSAHS group (15 < AHI ≤ 30), and 68 cases in the severe OSAHS group (AHI > 30).All study subjects received examinations using a portable sleep apnea recording device  was conducted on all subjects. During the monitoring period, patients resumed their normal daily lives. The effective recording time of blood pressure monitoring had to be longer than 20 h. The effective reading of blood pressure > 85% of the time was regarded as qualified; otherwise, the readings had to be taken again. Computers automatically performed statistical analyses of ambulatory blood pressure monitoring data. The observation parameters included mean daytime systolic blood pressure (dSBP), mean daytime diastolic blood pressure (dDBP), mean nocturnal SBP (nSBP), and mean nocturnal DBP (nDBP). In addition, the nocturnal blood pressure reduction percentage was calculated using the formula (dSBP - nSBP)/dSBP × 100%, which represented the amplitudes of circadian blood pressure changes in patients.Starting from 8:00 - 9:00, 24-h ambulatory blood pressure monitoring using a portable type 90217 non-invasive cuff automatic blood pressure monitor , patients’ cubital vein blood samples were collected to detect fasting blood glucose (FBG), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and high-sensitivity CRP (hs-CRP). FBG, TG, HDL-C and LDL-C were measured using the 7200 automatic biochemical analyzer (Japan), and hs-CRP was measured using an enzyme-linked immunosorbent assay (ELISA); the reagent kit was purchased from Shanghai Senxiong BioTechnology Co., Ltd. The detection procedure and calculation were performed strictly according to the instructional manual.χ ± s. Comparison of mean values between groups was performed using the F test. Factors that affected blood pressure were obtained using a stepwise multiple linear regression analysis. P < 0.05 indicated that the difference was statistically significant.Statistical analysis was performed using the software SPSS version 17.0. Measurement data were presented as According to the respiratory sleep monitoring results, the numbers of cases in each group were 35 cases in the normal control group, 28 cases in the mild OSAHS group, 57 cases in the moderate OSAHS group, and 68 cases in the severe OSAHS group. Compared to the normal control group, patients in the OSAHS groups had increased BMIs and TG and hs-CRP levels; of these measurements, the changes in patients in the moderate and severe groups were significantly different . Other indicators did not have changes (P > 0.05) .The dSBP and dDBP values of hypertension patients among the different groups were not significantly different (P > 0.05). However, the nSBP and nDBP values in patients in the three OSAHS groups were all higher than those in the normal control group. The nocturnal blood pressure reduction percentage significantly decreased; when the degree of OSAHS was more serious, the percentage of the reduction of nocturnal blood pressure was lower, and the difference between the moderate and severe OSAHS groups and the normal control group was statistically significant (P < 0.01). In addition, compared to the mild OSAHS group, the nSBP and nDBP values in patients in the moderate and severe OSAHS groups also significantly increased , and the nocturnal blood pressure reduction percentage significantly decreased (P < 0.01), while other indicators did not change (P > 0.05) .2 = 0.46) and nDBP (adjusted R2 = 0.38) and an independent negative correlation with the nocturnal blood pressure reduction percentage (adjusted R2 = 0.48)  .OSAHS is an airway obstruction and sleep apnea phenomenon with several causative factors. The main manifestations are daytime sleepiness and recurrent airway obstruction during sleep at night. OSAHS mainly occurs in obese and older people. More and more studies have discovered and confirmed that OSAHS is an independent risk factor for hypertension and is closely associated with hypertension . ResultsThe main pathological feature of OSAHS is intermittent hypoxia. During sleep, the recurrent hypoxemia and hypercapnia in OSAHS patients can stimulate the central nervous system and the peripheral chemoreceptors, which already have increased sensitivity, to increase the activity of the sympathetic nervous system, thus increasing blood pressure. In addition, repeated awakening can further stimulate sympathetic nerve excitation to increase plasma levels of catecholamine, renin, and angiotensin II, thus causing peripheral blood vessel constriction and eventually causing an increase in nocturnal blood pressure.In addition to its influence on the sympathetic nervous system, hypoxia can also induce oxidative imbalances in the body. In recent years, scholars proposed the concept that OSAHS was an oxidative stress disorder , which mIn summary, intermittent hypoxia induced by OSAHS increases blood pressure through its influences on the sympathetic nervous system. In addition, OSAHS also influences the oxidative stress balance and increases inflammatory factor CRP levels in the body to further change the circadian rhythm of blood pressure. Therefore, an effective improvement of OSAHS has important significance in the control of blood pressure within the standard range.


The relationship between diastolic dysfunction and P-wave dispersion (PWD) in the electrocardiogram has been studied for some time. In this regard, echocardiography is emerging as a diagnostic tool to improve risk stratification for mild hypertension. To determine the dependence of PWD on the electrocardiogram and on echocardiographic variables in a pediatric population. 515 children from three elementary schools were studied from a total of 565 children. Those whose parents did not want them to take part in the study, as well as those with known congenital diseases, were excluded. Tests including 12-lead surface ECGs and 4 blood pressure (BP) measurements were performed. Maximum and minimum P-values were measured, and the PWD on the electrocardiogram was calculated. Echocardiography for structural measurements and the pulsed Doppler of mitral flow were also performed.p <0.01 and r = 0.33, p <0.01, respectively. There was a significant correlation found between PWD and the left atrial area (r = 0.45 and p <0.01). A significant correlation in statistical variables was found between PWD and mean BP for pre-hypertensive and hypertensive children, i.e., r = 0.32,  We highlight the dependency between PWD, the electrocardiogram and mean blood pressure. We also draw attention to the dependence of PWD on the duration of the mitral inflow A-wave. This result provides an explanation for earlier changes in atrial electrophysiological and hemodynamic characteristics in pediatric patients. Atrial Fibrillation (AF) is a paradigm of atrial arrhythmic heterogeneity with an anatomical and electrophysiological complex quality It has been suggested that one of the mechanisms involved in AF pathogenesis is the presence of multiple random re-entrant wavelets that propagate and become extinct or fractionate within the atrial tissue. The correlation between the presence of abnormalities in atrial conduction and paroxysmal AF induction is well documented Intra- and interatrial conduction prolongation and the homogeneous propagation of sinus impulses are electrophysiological characteristics of patients with paroxysmal AF, Concerning hypertension, researchers have demonstrated a significant relationship between changes in the left ventricular geometry and PWDThe objective of this paper is to determine the association between PWD and mean blood pressure (BP) in children between 8 and 11 years of age.515 school children, between the ages of 8 and 11 years and without known congenital cardiovascular diseases, were studied from 2008 to 2010. Excluded from the study were children whose parents did not want them to be included, and children with congenital cardiovascular diseases, either previously known or diagnosed during the study. The main element of the physical examination was the way in which BP measurements were obtained. The conventional method for measurement was used by means of a calibrated oscillometric sphygmomanometer. Measurements were always taken under similar conditions by the same staff utilizing an appropriate-sized cuff with the cuff bladder covering at least 80% of the child's arm. It was measured at the midpoint between the acromion and the olecranon with a pediatric-sized stethoscopeBP measurements were taken with the child in a seated position with the forearm resting on a table, and after remaining at rest for at least 10 minutes. An unwrinkled cuff was placed at the level of the heart. Four BP measurements were taken on different days. The cuff was inflated to 20 mm Hg above the abolition level of the radial pulse, and it deflated at a rate of approximately 2 mm Hg per second. The systolic BP was determined to be the pressure at which the first sound was heard (Korotkoff phase I) and the diastolic BP were defined by the change of the arterial tone or by the point of noise cessation (Korotkoff phase IV). The sample was classified according to the diagnosis of normotensive blood pressure, i.e. with BP below the 90th percentile; pre-hypertensive, by a BP between the 90th and 95th percentiles, and hypertension by a BP higher than the 95th percentile for age, sex and height in all cases. This procedure is consistent with those established in the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and AdolescentsP-waves were measured for each lead. The maximum P value was taken as the highest measured P-wave value; the minimum P value was noted as the lowest measured value; and the P-wave dispersion (PWD) was identified as the difference between the maximum P value and the minimum P value.A 12-lead surface electrocardiogram was performed with Nyhom Kodem equipment standardized at a paper speed of 50 mm/second. Echocardiography also was performed with Aloka 5000 equipment, using a 3.5 MHz transducer. The existence of structurally normal hearts for the entire sample was confirmed through echocardiography. Mitral inflow was determined by Doppler pulse in an apical four-chamber view. A normal pattern of left ventricular relaxation was identified for all of the 515 children under study. The following echocardiography variables were also obtained: left ventricular diameter (diastolic and systolic diameters), inter-ventricular septum thickness, posterior wall thickness, fractional shortening, ejection fraction, left atrial diameter, velocity and mitral inflow A-wave duration (AWD), respectively given in millimetres per second and milliseconds. These values were used to calculate the left ventricular mass, according to the Deveroux equationLeft Ventricular Mass (g) = 0.8 x 1.04 x(LVD+ IVS+ WP) x + 0 6 (1)Where: LVD = left ventricular diameter (mm) IVS = inter-ventricular septum (mm) WP = posterior wall (mm)The left ventricular mass index (LVMI) g/cm was calculated by equation 2.LVMI = Left ventricular mass/size Data were analyzed using the SPSS 17.0 software, and the means and standard deviations were calculated. The differences in continuous variables among 3 diagnosis-related groups and 2 sex-related groups were evaluated by parametric tests. Additionally, a multivariate linear regression was performed to identify the most influential variable from an independent perspective on PWD as the dependent variable. In all cases, a 95% confidence interval was used along with partial correlations for age, weight and height. An ANOVA with the Scheffé test was used to compare means.p < 0.01), as well as between normotensive and hypertensive children (p < 0.01). No significant differences were found between pre-hypertensive and hypertensive children (p = 0.411).The echocardiographic variables studied included: velocity and mitral inflow Awave duration, left atrium diameter, left and right atrial area and left ventricular mass index. The systolic blood pressure, diastolic blood pressure and mean blood pressure (MBP) were all determined, as were the weight, height, age and body surface area. p = 0.118); however, there was a significant difference (p = 0.026) between normotensive and hypertensive children. LVMI mean values for pre-hypertensive and hypertensive children were not significantly different (p = 0.256). The AWD value decreased from 138.2 ms in normotensive children to 131.6 ms in hypertensive children, and the standard deviation likewise decreased. No significant differences between AWD means were observed in the comparison using an ANOVA with the Scheffé Test and a 95-percent confidence interval (inter-group). Echocardiographic variables are also shown in p < 0.01), normotensive and hypertensive (p <0.01), and pre-hypertensive and hypertensive (p <0.01). A multivariate linear regression analysis was also performed with a 95% confidence interval that adjusted for age, weight and height. The purpose was to identify MBP as an independent variable among variables having a greater influence on PWD. p <0.01 and r = 0.33, p <0.01) respectively. There was significant correlation found between PWD and the left atrial area.The most important results are the following: a significant correlation in statistical variables was found between PWD and mean BP for pre-hypertensive and hypertensive children  and in LVMI, have been associated with increased PWD. PWD, in particular, has been independently associated with LVMI.. This knowledge could lead to the pathophysiological argument that despite the absence of altered echocardiographic patterns, this study found a pathophysiological negative influence due to increases in the systemic pressure on left ventricular relaxation. DD is frequent in patients with hypertension17. Thet al,Gunduz H, et al, Several authorsBeevers G et al, et alSeveral studies indicate that the relationship between PWD and MBP also guarantees that arrhythmia risk decreases when the BP was normalized. It is shown by the regression of PWD values and decrease of heterogeneity in impulse conduction  . We hold the belief that these advanced inflammatory changes are not present in early childhood.Higher r correlation coefficients and p-wave dispersions can be found in the literature. In our opinion, it is important to consider that these values relate to adults with hypertension, heart failure and other inflammatory secondary changes to the activity of the renin-angiotensin-aldosterone system 24 . WWe highlighted the dependence between PWD, the electrocardiogram and mean blood pressure and drew attention to the dependence of PWD on the duration of the mitral inflow A-wave. Perhaps these results will provide a satisfactory explanation for the earlier changes in the characteristics of the hemodynamics and atrial electrophysiology in pediatric patients.


To determine the relationship between renal function and visit-to-visit blood pressure (BP) variability in a cohort of primary care patients.Retrospective cohort study from routinely collected healthcare data.Primary care in Nijmegen, the Netherlands, from 2007 to 2012.19 175 patients who had a measure of renal function, and 7 separate visits with BP readings in the primary care record.Visit-to-visit variability in systolic BP, calculated from the first 7 office measurements, including SD, successive variation, absolute real variation and metrics of variability shown to be independent of mean. Multiple linear regression was used to analyse the influence of estimated glomerular filtration rate (eGFR) on BP variability measures with adjustment for age, sex, diabetes, mean BP, proteinuria, cardiovascular disease, time interval between measures and antihypertensive use.2 and SD systolic BP 148.3 (21.4) mm Hg. All BP variability measures were negatively correlated with eGFR and positively correlated with age. However, multiple linear regressions demonstrated consistent, small magnitude negative relationships between eGFR and all measures of BP variability adjusting for confounding variables.In the patient cohort, 57% were women, mean (SD) age was 65.5 (12.3) years, mean (SD) eGFR was 75.6 (18.0) mL/min/1.73mWorsening renal function is associated with small increases in measures of visit-to-visit BP variability after adjustment for confounding factors. This is seen across the spectrum of renal function in the population, and provides a mechanism whereby chronic kidney disease may raise the risk of cardiovascular events. We studied blood pressure (BP) variability in a patient cohort generalisable to primary care where the majority of patients with chronic kidney disease are diagnosed and monitored, as previously BP variability in chronic kidney disease (CKD) has only been studied in patients with advanced renal disease under specialist care.We examined measures of BP variability that are independent of mean BP, which have been shown to have greater prognostic significance than mean BP alone.We were not able to assess the effect of different exposures to antihypertensive medication.We did not have access to data on cardiovascular outcomes to test the clinical significance of visit-to-visit variability in this patient cohort.Hypertension is a major vascular risk factor, and average blood pressure (BP) correlates with cardiovascular disease and death.5Increased BP variability has been observed in small groups of patients with relatively advanced renal disease under specialist hospital care. In a small hospital cohort, visit-to-visit BP variability was independently associated with albuminuria and with increased renal vascular resistance as assessed by Doppler ultrasound.11However, as BP variability increases with mean BP, and renal disease is associated with increased mean BP, the relationship between BP variability and renal impairment can only be established using metrics of BP variability that have been shown to be independent of mean BP.It is important to establish whether there is a real relationship between renal impairment and increased BP variability because the link might be causal and have important implications for therapy in CKD. Analysis of large sets of routinely collected healthcare data has demonstrated that CKD is an important independent risk factor for cardiovascular disease even after controlling for other known risk factors.We therefore sought to determine whether renal function was associated with visit-to-visit BP variability using a large dataset of routinely collected healthcare data.We retrospectively defined a patient cohort (age ≥18 years) using routinely collected healthcare data from 47 primary care practices in the Nijmegen region, the Netherlands, with a combined registered population of 207 468 people, as part of the CONTACT study , Netherlands Trial Registration code 2368, with approval from the Medical Research Ethics Committee Arnhem/Nijmegen, registration number 2010/187.Data included demographic details, medical history with conditions diagnosed in the course of routine clinical practice, BP measurements, antihypertensive prescribing and renal function between 1 January 2008 and 1 January 2011. We did not seek to include patients receiving dialysis in this study population. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was used to calculate estimated glomerular filtration rates (eGFRs) using the first creatinine measurements in the time period, which were either standardised to isotope dilution-mass spectrometry (IDMS), or subject to the appropriate correction factor for laboratories using the Jaffé technique.Given that blood pressure variability is associated with mean BP, we calculated BP variability independent of mean (VIM) BP using standard formulae for measures that have prognostic significance for cardiovascular events.10.1136/bmjopen-2015-010702.supp1Supplementary data2 and a mean systolic BP of 148.3 mm Hg.Among the 207 468 total registered population, 162 562 were over the age of 18 years, of whom 63 073 (39%) had renal function measured during the study period. Of these, 19 175 (30%) had at least seven BP measurements recorded at different visits. The mean time interval from the first to the final seventh BP measurement was 22 months (SD 11 months). Mean systolic BP rose with age  and with falling eGFR . Correlation analysis of transformed BP variability measures was consistent with their independence from mean BP  −0.009, p=0.23; SV independent of mean (SVIM) −0.009, p=0.22; ARV independent of mean (ARVIM) −0.01, p=0.15). Online The relationships of eGFR and age with SDIM, as an exemplar of the associations with VIM, are shown in Multiple stepwise regression analysis was performed to examine the association between renal function and BP variability. Lower eGFR was consistently associated with increasing measures of BP variability (both with and without transformation to be independent of mean BP), as evidenced by the significant negative standardised β coefficients across the regressions in the presence of potential confounders. Although the presence of proteinuria was not associated with any measure of BP variability, a history of cardiovascular disease was positively associated with increased BP variability. All classes of antihypertensive medication were positively associated with measures of BP variability where significant relationships were observed  in eGFR ranges corresponding to CKD stage 4 in this study are similar to those seen in cohorts of patients with transient ischaemic attack (TIA) in the UK-TIA trial and the European Carotid Surgery Trial.22Our study has some limitations. The population studied exists in a healthcare context where the value of treating hypertension is recognised, and this is likely to reduce the slope of the relationship between mean systolic BP and eGFR. In addition, the variability associated with the estimation of renal function,Our results demonstrate that the relationship between eGFR and BP variability exists across the spectrum of eGFR which corresponds to different stages of CKD. This relationship is consistent with a causative relationship between diminished eGFR and BP variability, but causation cannot be established in an observational study. Nevertheless, this may prove to have clinical usefulness in determining vascular risk and prognosis, as we have demonstrated that BP variability is readily detectable and quantifiable in retrospective data in the non-specialist setting.Studies of the prognostic significance of BP variability in general CKD populations are required as monitoring BP variability may refine the prediction of cardiovascular risk. The correlations that we have identified are of small magnitude, but they are independent, and given the population prevalence of CKD, this correlation will have consequences for cardiovascular risk at the population level. Clinical trials are needed in CKD to establish the value or otherwise for renal and cardiovascular outcomes of tailoring antihypertensive therapy to minimise BP variability.


Sympathetic activation and renin-angiotensin system are essential for development and sustenance of hypertension. However, the status of these systems has not been well evaluated among patients in an African setting. This study therefore set out to assess the angiotensin II status and sympathetic activation among hypertensive patients in Uganda.In this cross sectional study conducted at Mulago, the national referral hospital, blood samples were taken to measure angiotensin II, metanephrines and normetanephrines. Urine samples were also taken for measuring urine creatinine and sodium. The angiotensin II categories were defined using the Mosby’s Diagnostic and Laboratory Test References. 9th ed while the metanephrines and normetanephrine categories were defined using the Makerere University Biosafety II Immunology Laboratory reference values.162 patients were consented and enrolled into the study, of these 136 (84 %) had low, 15 (9 %) had normal, while, 11 (7 %) had high angiotensin II levels. 142 (88 %) participants had normal levels of metanephrine, while 20 (12 %) had high levels. Only 88 were assessed for metanephrines and of these 85 (97 %) had normal, while 3 (3 %) had raised levels. Urine sodium was associated with low and normal angiotensin II levels . Female gender and diastolic blood pressure were associated with a protective effect against high normetanephrines , 80–89 mmHg , above 100 mmHg . Current smoking status was associated with high risk for abnormal normetanephrines  while former smoking was associated with high risk for abnormal metanephrines . After multivariate analysis, all the significant variables at bivariate analysis were still significant except those who stopped smoking and those with a BP at 80–89 which were not significant.Hypertensive patients in this setting have predominantly low angiotensin II hypertension as a result of high salt intake. Sympathetic activation is not a significant mechanism of hypertension in this study population, more so in the females, with the exception of smokers who have a highly activated sympathetic system. Therefore, the use of agents targeting renin angiotensin and sympathetic systems as single first line antihypertensive agents in this setting should be re-evaluated if such patients are to be treated effectively. Hypertension is one of the most prevalent and major contributors to atherosclerotic cerebral and cardiovascular disease, increasing the risk by two to threefold . TreatmeHypertension is a result of the interaction between genetic and environmental factors. This interaction influences intermediary phenotypes such as sympathetic nervous activity, renin angiotensin aldosterone, renin-kallikrein—kinin systems, and endothelial factors . These p+/H+ exchanger 3 in the proximal tubule is also key in maintaining basal blood pressure and the development of angiotensin II hypertension [More than 70 % of hypertensive patients have renin related mechanisms as the aetiology of their hypertension. About 20 % of these have inappropriately normal or high renin values, and 30 % have low renin values, with the remaining half distributed between these two extremes . Angiotertension .Sympathetic neural mechanisms are also important in the development and progression of hypertension. The magnitude of sympathetic activation is proportional to the degree of elevation in blood pressure and development of hypertension-related target organ damage . It has Much has been studied about the renin angiotensin and sympathetic nervous systems’ role in the pathophysiology of hypertension. Despite this, data on this subject in an African setting is limited. The closest data often cited for black populations is from the African Americans who may be genetically and environmentally distinct from blacks in an African setting. There is a need to fill this knowledge gap with data from an appropriate population. We therefore set out to assess the angiotensin II status and sympathetic activation of hypertensive patients in Uganda attending the national referral hospital. Such information is extremely useful, especially in our low resource settings, where appropriate treatment of chronic conditions, basing on scientific evidence, is prudent. We also sought to seek for any factors associated with the prevailing status of these parameters.This was a cross sectional study conducted at Mulago, the only National referral hospital in Uganda.All study participants were recruited from the Mulago Hospital hypertension clinic. We recruited both newly diagnosed adult hypertensive patients (with no history of antihypertensive medication) and previously treated hypertensive patients but who had defaulted their medication for at least 1 week. Exclusion criteria included; pregnant women, patients currently or within 1 week of using oral contraceptive therapy or adrenaline, patients with deranged renal function tests and urinalysis, patients with diabetes mellitus and confirmed pheochromocytoma.A formula by Eng  was usedThe study participants were consecutively recruited from the waiting area in the hypertension clinic and screened using the study eligibility criteria. Those eligible were informed about the study and requested to give a written informed consent to participate in the study.Study participants responded to a pre-coded, pre-tested and standardized questionnaire which covered demographic details, duration of hypertension, duration off antihypertensives, type of antihypertensives that were being taken before defaulting, alcohol consumption, salt intake and smoking. They then underwent measurement of height, weight and blood pressure, and then gave an arterial blood and urine sample as elaborated below.2) and then categorized into underweight (<18.5), Normal weight (18.5–24.9), overweight (25–29.9) and obese (>30) using the world health organisation criteria of categorization of BMI, 2004 [The body mass index (BMI) was calculated using the formula; weight (kg)/height  oscillometric blood pressure monitoring sphygmomanometer with the subject in the sitting position, legs uncrossed, the arm resting on a table and the ante-cubital fossa at the level of the lower sternum. The Omron M7 (HEM-780-E) is validated according to the British hypertension Society protocol and is recommended for professional and home use .An appropriate cuff (with bladder length >80 % of the arm circumference) was used. Two readings were taken 3 min apart and the average was used to describe the blood pressure of the patient. If the readings differed by 10 mmHg, a third reading was taken and the blood pressure was then taken to be the average of the closest two. Blood pressure was then categorized using the JNC 7 .The participant was laid on the examination couch in supine position for at least 15 min before the blood sample was drawn. Using a 10 ml syringe and observing aseptic conditions, 6 ml of blood was drawn from the femoral artery. Pressure was applied to the puncture site for 7 min to stop any bleeding. Four ml was introduced into an iced pre-labelled EDTA vacutainer, mixed gently by tilting the vacutainer top to bottom and vice versa eight times to mix the blood with the anticoagulant.The sample was kept under ice in an ice box carrier immediately. It was then transported within 1 h to the laboratory where it was centrifuged at 4500 rotations per minute at 4 °C for 5 min to separate the plasma. The plasma was stored at −80 °C till analysis. The remaining ml were used for determination of plasma creatinine and sodium at the Mulago Hospital clinical chemistry laboratory.All the samples were analysed within 5 months from the time of collection at the Makerere University Biosafety II Immunology Laboratory, using the AssayMax Human Angiotensin II Elisa Kit from ASSAYPRO, Germany and 2-MET Plasma Elisa fast track from Labor Diagnostic Nord, Germany.The Mosby’s Diagnostic and Laboratory Test References. 9th ed angiotensin II reference ranges (0.01–0.06 ng/ml) and the Makerere University Biosafety II Immunology Laboratory reference values for metanephrine (<90 pg/ml) and normetanephrine <180 pg/ml) were used to categorise these measurements into low, normal, and high 0 pg/ml w.Patients were instructed to collect a mid-stream urine sample after washing with soap the head of the penis and the retracted foreskin (for men) or the separated skin folds covering the urinary opening . The urine sample was transported within 1 h to the laboratory for determination of urine sodium and creatinine.Data analysis was done with the assistance of a statistician. Data were double entered using EPI-INFO 6.0 and then exported to STATA version 12.0  for analysis.The independent variables which included: social demographics, alcohol intake, smoking history, salt intake, treatment history of hypertension, physical measurements, and fraction excretion of sodium were organised into categories. The outcomes of interest in this study were percentages and their confidence intervals of the participants with low, moderate and high angiotensin II, metanephrine and normetanephrines levels.P value of ≤0.05 was considered to be statistically significant.Logistics regression model was used to assess for factors associated with the three parameters outcomes by estimating the odds ratio and accompanying 95 % confidence interval. Only variables that were significant in the bivariate analysis  were considered for multivariate analysis, and a forward fitting regression model was used to assess for effect modification and confounders. In all analyses, a The full dataset for this study is available on Zenodo data repository. DOI 10.5281/Zenodo.31479.Written informed consent was obtained from all study participants. The study protocol was approved by the Makerere University School of Medicine Research and Ethics Committee, and Uganda National Council of Science and Technology.162 Patients were recruited for the study as shown in Fig. There were more senior citizens, 122 (75 %), above 45 years and 61 (38 %) above 60 years with hypertension compared to the younger participants 40 (25 %) below 45 years and 6 (4 %) participants below 30 years (Table Sixty-seven (42 %) of the participant added raw salt to their food. Among the 162 participants, majority 64 (40 %) of them added one table spoon to their food as they prepared it, closely followed by 54 (33 %) who added half a table spoon.Majority of the participants, 136 (84 %) had normal pulse rates and majority had a systolic blood pressure of more than 160 mmHg and a diastolic blood pressure of more than 100 mmHg, 108 (67 %) and 89 (55 %) respectively. Twenty-nine (18 %) participants had grade one obesity while 9 (6 %) were morbidly obese. See Table Sixteen (10 %) participants were recently diagnosed with hypertension compared to 146 (90 %) who had a known diagnosis of hypertension but had defaulted taking their medications. Among the 146 previously treated defaulting participants, 34 (23 %) of them had been on single drug therapy while 112 (77 %) had been on combination therapy. The most commonly used class of single drug therapy was calcium channel blockers, 13 (38 %) while the most commonly used combination therapy was a diuretic with a calcium channel blocker and either an ACEI or ARB 27 (24 %). See Table The smoking rates in this study were very low, with 3 (1.9 %) and 12 (7 %) being current and former smokers respectively. The participants currently taking alcohol were 35 (22 %). Among the 35 participants, 18 (51 %) were taking beer, followed by local gin (waragi) at 12 (34 %). Among the 31 who took quantifiable amounts of alcohol, the majority took 1–6 bottles of beer per week while only one participant took a glass of wine daily.Eighty-four percent (136) of the participants had low angiotensin II levels. This represented a proportion of 78–90 % of the reference population as shown by the 95 % confidence interval. Among the participants with low angiotensin II levels, 130 (97 %) had normal, 4 (3 %) had low while none had high urine excretion of sodium. In contrast however, majority with low angiotensin II levels, 120 (90 %), had a fractional excretion of sodium of less than 1 %. Urine sodium was the only factor significantly associated with low and normal angiotensin II levels, P value = 0.007 as illustrated in Table Majority of the participants, 142 (88 %) had normal normetanephrine levels representing a range of 83–93 % in the reference population as shown by the 95 % confidence intervals. A similar proportion, 85 of the 88 (97 %) participants with metanephrine results had normal metanephrine levels representing 92–100 % of the reference population as shown by the 95 % confidence intervals.Among the participants with normal metanephrines, 60 (71 %) had a systolic blood pressure of more than 160 mmHg compared to 94 (66 %) with normal normetanephrines. The percentage of participants with normal metanephrines and normetanephrines who had a diastolic blood pressure of more than 100 mmHg was similar, 55 and 56 % respectively.Distribution by the other variable is shown in Table Being female was associated with a significant protective effect from high normetanephrine OR 0.29 (0.11–0.79), P = 0.015 and so was diastolic blood pressure of 80–89 mmHg OR 0.19 (0.03–1.02), p = 0.053, 90–99 mmHg OR 0.86 (0.01–0.77), P = 0.028 and >100 mmHg OR 0.27 , P value −0.022, while former smoking status was associated with increased risk of elevated metanephrines OR 18.75 (1.53–230.42), P = 0.022, as shown in Table After multivariate analysis, all the significant variables at bivariate analysis were still significant except those who stopped smoking and those with a BP at 80–89 which were not significant Table .Table 7MThe major finding in this study was that majority of the participants had low angiotensin II levels, which, correlated with the finding that majority of participants had a fractional excretion of sodium of less than 1 %. This clinical state is similar to patients with pre-renal azotemia whereby they are highly conserving sodium and water leading to a high effective circulatory volume. It is possible that high salt intake in this population suppresses angiotensin II release as majority of the participants reported taking salt in their diet, especially raw salt and urine sodium was associated with low angiotensin II levels. It would have been important to correlate the angiotensin II levels with renin levels as previous studies have shown majority of blacks to have a low renin hypertension  as a resFindings from this study suggest that sympathetic nervous activation may not be a dominant mechanism in the pathophysiology of hypertension in this study population. This is in contrast to previous studies that have shown increased sympathetic nervous out flow in patients with accelerated or malignant hypertension, where, the sympathetic out flow is due to the increased endogenous renin-angiotensin axis which stimulates it at the sympathetic ganglia  and centMore to the above, current smoking status was associated with increased stimulation of the sympathetic nervous activation meaning that smoking may be a contributing mechanism to developing hypertension in smokers. This finding is similar to results of other studies which showed that smoking has a direct peripheral and a centrally mediated effect on both blood pressure and pulse through stimulation of the sympathetic nervous system . HoweverIt was also seen in this study that increase in diastolic blood pressure showed dampening or protection against increased sympathetic nervous activity. The diastolic blood pressure is related to relaxation of the cardiac muscle which occurs with reduced sympathetic outflow and sustained by residual pressure retained by the elasticity of the arterial system . The symHypertensive patients in this setting have predominantly low angiotensin II hypertension as a result of high salt intake. Sympathetic nervous activation is not a significant mechanism of hypertension in patients in this setting, more so in the females, but may be exaggerated in current smokers. Use of agents targeting renin angiotensin and sympathetic systems as single first line antihypertensive agents in this setting needs to be re-evaluated for better management of patients in this setting.


Although α-klotho is known as an anti-aging, antioxidant, and cardio-renal protective protein, the clinical implications of soluble α-klotho levels in patients with diabetes have not been evaluated. Therefore, this study evaluated whether plasma and urinary α-klotho levels are associated with albuminuria in kidney disease in diabetes.A total of 147 patients with type 2 diabetes and 25 healthy control subjects were enrolled. The plasma and urine concentrations of α-klotho were analyzed by enzyme-linked immunosorbent assay.vs. 476.9 pg/mL ) and urinary α-klotho levels  were significantly higher in diabetic patients than non-diabetic controls. Among diabetic patients, plasma α-klotho concentration was inversely associated with albuminuria stages , while urinary α-klotho levels were remained constantly high with increasing urinary albumin excretion.Plasma α-klotho (572.4 pg/mL  Soluble α-klotho levels in plasma and urine may be novel and useful early markers of diabetic renal injury. Although α-klotho was first described as an anti-aging factor, recent experimental and clinical studies suggest α-klotho also has important pleotroic effects on the kidneys However, with regard to diabetic nephropathy, the role of α-klotho in the pathogenesis of kidney injury has not been fully studied. Renal α-klotho expression is markedly decreased in diabetic nephropathy in humans and mice This study determined whether diabetes influences soluble circulating or urinary α-klotho level and investigated the relationship between these soluble α-klotho levels and albuminuria in patients with type 2 diabetes.This study was carried out in accordance with the Declaration of Helsinki and study protocol was approved by the Institutional Review Board of Pusan National University Hospital . All patients provided their written informed consent before entering the study. Data are available to all interested researchers on request to the Institutional Review Board of Pusan National University Hospital.−1 1.73 m−2, serum creatinine <1.2 mg/dL, stable renal function status without 2-fold elevation of serum creatinine for at least 5 months, and no history of administration of RAS inhibitors. If patients took RAS inhibitors, these medications were withdrawn and replaced with other antihypertensive agents for at least 2 months before enrollment in this study. A random spot urine sample and a blood sample were obtained from each patient at the clinic visit. Medical histories and anthropometric measurements were also recorded on the same day. The eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) Study formula as follows: MDRD  = 186× (serum creatinine [mg/dL])−1.154 × age [years]−0.203A total of 147 consecutive patients with type 2 diabetes were enrolled at outpatient clinics between February 2010 and February 2012. All patients met the following inclusion criteria: age ≥18 years and estimated GFR (eGFR) ≥60 mL min−1 1.73 m−2 and had no prior history of diabetes, renal disease or cardiovascular diseases including hypertension and dyslipidemia.Patients with active urinary tract infection; renal disease other than diabetic nephropathy; neoplastic disorders; severe liver dysfunction; active or chronic infection or inflammatory disorders; pregnancy; or a recent  history of acute myocardial infarction, stroke, or occlusive peripheral vascular disease were excluded. Nondiabetic control subjects were randomly selected from the Center for Health Promotion at Pusan National University Hospital for a comprehensive medical check-up. They were enrolled in this study if they had fasting plasma glucose levels of <100 mg/dL after an overnight fasting, eGFR of ≥60 mL minPlasma samples were centrifuged for 15 minutes at 3,000 rpm within 30 minutes of collection; plasma was removed and stored at −70°C until analysis. Urine samples were centrifuged for 10 minutes at 3,000 rpm to remove particulate matter and stored at −70°C until analysis. The plasma and urine concentrations of α-klotho were analyzed by human soluble α-klotho immunoassay kits  according to the manufacturer's protocol. All samples were run in duplicate and were within the range of the standard curve . Values below the detection limit (6.15 pg/mL) were approximated using the mean value between zero and the lower limit of detection. The intra- and inter-assay coefficients of variation were less than 10%. The levels of urinary α-klotho were expressed as the ratio of urinary α-klotho to urinary creatinine in order to assess the hydration states and renal functions of the patients.2χ test. Pearson correlation analysis was used to determine the correlations between individual variables. Multivariate regression analyses were used to determine the associations of plasma α-klotho with several parameters. All statistical analyses were performed using SPSS version 15.0 . The level of significance was set at p<0.05. All hypothesis tests were 2-sided.Categorical variables, continuous variables with a normal distribution, and non-normally distributed variables are presented as number (percentage), mean ± SD, and median (interquartile range), respectively. Statistical analyses were performed after log-transforming the data of all skewed variables. Geometric means  are presented with 95% CIs. The significance of differences between continuous variables was tested by ANOVA or the Kruskal–Wallis test, with polynomial contrasts for linear trends or Tukey's multiple comparison test where appropriate. Categorical variables were analyzed using the Pearson vs. 476.9 pg/mL , p = 0.016). Urinary α-klotho levels were also significantly higher in diabetic patients than in non-diabetic controls .A total of 172 subjects were enrolled in this study; their mean age was 55.8±10.4 years , and there were 77 men and 95 women. Age, systolic, diastolic blood pressure, alanine aminotransferase, insulin, and eGFR were significantly higher in diabetic patients than non-diabetic control. Meanwhile, hemoglobin, total bilirubin, and direct bilirubin were significantly lower in diabetic patients than in non-diabetic controls. Other parameters did not differ significantly between the diabetes group and non-diabetic controls . Plasma n = 75), ACR 30–299 mg/g creatinine , and ACR ≥300 mg/g creatinine  : ACR <30 mg/g creatinine  . Age, sep for linear trend  = 0.008). In contrast to plasma α-klotho levels, no albuminuria level was significantly associated with urinary α-klotho creatinine ratio . ne ratio D.P<0.05). However, there were no significant correlations between plasma α-klotho and HbA1C, eGFR, or urine α-klotho. We performed multivariate regression analyses for the associations of plasma α-klotho with several parameters. In a multiple linear regression analysis, plasma α-klotho was significantly associated with hemoglobin  and urine ACR  and they never mentioned the albuminuria status of their diabetic patients Zhao Both acute kidney injury and chronic kidney disease exhibit renal and systemic α-klotho deficiency. Levels of α-klotho plummet very early and severely in acute kidney injury, representing a pathogenic factor that exacerbates acute kidney damage Recent studies indicate the potential contribution of absolute α-klotho deficiency to acute and chronic kidney injury It is worth noting that the significance of urine α-klotho concentration as an early biomarker has not been evaluated in chronic kidney disease. The most important finding of the present study is that for the first time, high urine α-klotho levels were found to be associated with diabetes in humans even in the normoalbuminuria stage.1c or glycated albumin with soluble α-klotho concentrations in the present study also corroborates previous observations. Insulin can increase soluble α-klotho concentration through the cleavage and release of the extracellular domain of α-klotho et al.+ excretion in rat by ROMK channel activation which is expressed in apical membrane. Interestingly, epitope-tagged klotho was appeared in urine at 2 hr after intravenous administration Nevertheless, the underlying mechanisms explaining the present results require further investigation. The present results may be explained by increased α-klotho synthesis or its cleavage process, although requires further study. The extracellular domain of α-klotho protein is subject to ectodomain shedding and is released into the blood and urine We found an interesting decrease in hemoglobin concentration from 13.6 g/dL in patients with normoalbuminuria to 13.3 g/dL in patients with microalbuminuria and then low to 12.7 g/dL in macroalbuminuria . The decPlasma and urinary α-klotho were not correlated in a previous study Exogenous supplementation or stimulation of endogenous α-klotho may prevent and/or ameliorate kidney injury and mitigate chronic kidney disease development. The correction of α-klotho deficiency may delay the progression and forestall the development of extrarenal complications in chronic kidney disease. Angiotensin II receptor blocker treatment was recently shown to increase blood α-klotho levels while reducing albuminuria in type 2 diabetes with nephropathy r = 0.726, p<0.01) The results of this study are subject to some limitations. First, the sample size was relatively small. We measured the urinary levels of α-klotho with single random spot urine samples, although urine samples were collected at the outpatient clinic from patients without illness or renal diseases besides diabetic nephropathy; moreover, a moderate linear association was observed between the amount of urine α-klotho in 24 hours and urinary α-klotho/creatinine ratio in random urine specimens (In conclusion, the results of the present study suggest plasma and urinary α-klotho may be the early markers for predicting renal injury in patients with type 2 diabetes and we need to do long-term prospective study in order to elucidate the role of α-klotho in the pathophysiological mechanisms of the development and progression of albuminuria in type 2 diabetes.


Japan has four seasons and many chances of low atmospheric pressure or approaches of typhoon, therefore it has been empirically known that the fluctuation of weather induces migraine in people. Generally, its mechanism has been interpreted as follows: physical loading, attributed by atmospheric pressure to human bodies, compresses or dilates human blood vessels, which leads to abnormality in blood flow and induces migraine. We report our examination of the stage in which migraine tends to be induced focusing on the variation of atmospheric pressure.Subjects were 34 patients with migraine, who were treated in our hospital. The patients included 31 females and three males, whose mean age was 32 ± 6.7. 22 patients had migraine with aura and 12 patients had migraine without aura. All of patients with migraine maintained a headache diary to record atmospheric pressures when they developed a migraine. The standard atmospheric pressure was defined as 1013 hPa, and with this value as the criterion, we investigated slight fluctuations in the atmospheric pressure when they developed a migraine. It was found that the atmospheric pressure when the patients developed a migraine was within 1003–1007 hPa in the approach of low atmospheric pressure and that the patients developed a migraine when the atmospheric pressure decreased by 6–10 hPa, slightly less than the standard atmospheric pressure.Small decreases of 6–10 hPa relative to the standard atmospheric pressure of 1013 hPa induced migraine attacks most frequently in patients with migraine. The triggers of migraine are multi-factorial  age of 32 (±6.7) years. Twenty-two patients had migraine with aura (MA), whereas 12 had migraine without aura (MOA). In addition, a group of 28 patients with tension-type headache (TTH) were included as controls  formed, approached, and passed across the Japanese archipelago. The central atmospheric pressure of this tropical cyclone ranged from 920 to 1008 hPa during the period. The patients were instructed to carry with them a headache diary to record the time of migraine attack and to check weather data released by the Japan Meteorological Agency and record the atmospheric pressure at the time of migraine onset. Standard atmospheric pressure was defined as 1013 hPa, and deviations from this value at the time of onset were calculated. The relationship between the onset of migraine and barometric pressure levels resulting from the approach of the tropical cyclone was examined using the Mann–Whitney U test.The subjects were asked to refrain as much as possible from consuming alcoholic beverages and foods containing known migraine triggers during the study period.p values were <0.05). Migraine occurred most frequently when the atmospheric pressure decreased by 6–10 hPa relative to the standard pressure. There was no significant difference between MA and MOA patients in the incidence of migraine attacks during atmospheric pressure decrease.The proportions of patients who developed migraine in association with atmospheric pressure decrease were as follows: 72.7 % 16/22) of MA patients, 75.0 % (9/12) of MOA patients, and 21.4 % (6/28) of TTH patients. Thus, patients with migraine experienced headaches associated with atmospheric pressure decrease at a significantly greater rate than patients with TTH. In addition, most of these migraines developed during periods of quite small pressure decreases from the standard atmospheric pressure  on frequency of migraine attacks in patients with migraine, and found that decreases of 6–10 hPa are most frequently associated with migraine. We recommend that when cyclones are forecast, patients with migraine should ensure that they have medication on hand.


Dynamic left ventricular (LV) outflow tract (LVOT) obstruction (DLVOTO) is not infrequently observed in older individuals without overt hypertrophic cardiomyopathy (HCM). We sought to investigate associated geometric changes and then evaluate their clinical characteristics.A total of 168 patients with DLVOTO, which was defined as a trans-LVOT peak pressure gradient (PG) higher than 30 mmHg at rest or provoked by Valsalva maneuver (latent LVOTO) without fixed stenosis, were studied. Patients with classical HCM, acute myocardial infarction, stress induced cardiomyopathy or unstable hemodynamics which potentially induce transient-DLVOTO were excluded.Their mean age was 71 ± 11 years and 98 (58%) patients were women. Patients were classified as pure sigmoid septum (n = 14) if they have basal septal bulging but diastolic thickness less than 15 mm, sigmoid septum with basal septal hypertrophy for a thickness ≥15 mm (n = 85), prominent papillary muscle (PM) (n = 20) defined by visually large PMs which occluded the LV cavity during systole or 1/2 LVESD, or as having a small LV cavity with concentric remodelling or hypertrophy (n = 49). The prominent PM group was younger, had a higher S’ and lower E/e’ than other groups. In all groups, a higher peak trans-LVOT PG was related (p < 0.10) to higher E/e’, systolic blood pressure, relative wall thickness, and pulmonary arterial systolic pressure. In multivariate analysis, resting trans-LVOT PG correlated to pulmonary arterial pressure  after adjustment for systolic blood pressure, relative wall thickness, and E/e’.DLVOTO develops from various reasons, and patients with prominent PMs have distinct characteristics. We suggest to use DLVOTO-relieving medication might reduce pulmonary pressure in this group of patients. Dynamic left ventricular (LV) outflow tract (LVOT) obstruction (DLVOTO) is not uncommonly observed in aged individuals without overt hypertrophic cardiomyopathy (HCM) . Any conWe retrospectively analysed echocardiographic images diagnosed as DLVOTO with imaging obtained during Valsalva maneuver from 2008 to 2012 in a single tertiary referral hospital. DLVOTO was defined as a trans-LVOT peak PG higher than 30 mmHg at resting or provoked by a Valsalva maneuver, i.e., latent DLVOTO, in patients without fixed structural stenosis  at the end of systole was calculated as (1.35)*(Pes)*(Des)/(4 )*(hes)*[l + (hes///Des)], where Pes is the left ventricular pressure (mm Hg) at end-systole determined by the end-systolic blood pressure plus the end-systolic peak PG across the LVOT, Des and h are the LV internal dimension and posterior wall thickness (cm) at end-systole, respectively, 1.35 is a conversion factor (mm Hg to g/cm), and 4 is a geometric factor that results from conversion of the radius to the internal dimension [Before echocardiography, all the patients underwent blood pressure measurements in the upper arm with an automatic sphygmomanometer . End-systolic systemic pressure was calculated as (2х systolic blood pressure + diastolic blood pressure)/3. The left ventricular end-systolic meridional wall stress was calculated by the method of Grossman et al.  Left venimension .Interventricular basal septal thickness was measured at end-diastole in apical 3-chamber view images. The angle between the ascending aorta and the plane of the mitral valvular orifice was measured at both end-diastole and end-systole from 3-chamber views Figure . Size ofp < 0.10 in univariate analysis were included in the multivariable regression analysis. All the analyses were performed using SPSS , and p values less than 0.05 were considered significant.Clinical characteristics and echocardiographic parameters are presented as mean ± standard deviation for continuous variables and number (percentage) for categorical variables. Correlation analysis was performed between continuous variables using the Pearson correlation coefficient. Comparisons of echocardiographic findings between controls and study group were performed by independent t-test. Comparison of clinical and echocardiographic variables among subgroups was performed by ANOVA with post-hoc analysis via Bonferroni correction. The trans-LVOT-PG before and after a Valsalva maneuver was compared using the paired t-test. Variables with 2 vs. 26.7 ± 2.9 mm/m2, p < 0.001) and end-systolic dimensional index  were significantly lower than those of age- and sex- matched controls (n = 30). Relative wall thickness was significantly higher than controls , suggesting significant concentric remodelling. Baseline clinical and echocardiographic variables are described in Table Among 33,060 primary transthoracic echo reports, total of 168 patients  were studied after exclusion of cases with any exclusion criteria. Referral reasons for echocardiography were evaluations for chest pain or previous coronary artery disease in 27 (16%), ECG abnormalities in 15 (9%), dyspnea on exertion in 21 (13%), and evaluation for origin of cardiac murmur in 5 (3%), evaluation for target organ damage in hypertension or diabetes in 93 (55%) or evaluation for cause of syncope or dizziness in 7 (4%). Among them, 135 (80%) had latent DLVOTO. Mean age was 71 ± 11 years and 98 (58%) patients were women. One hundred thirty-six patients (81%) had a history of hypertension and 54 (32%) had diabetes. The mean LV end-diastolic dimension and ejection fraction were 39.3 ± 4.6 mm and 69.0 ± 5.7%, respectively. The patients almost had no regional wall motion abnormality except for few patients (n = 2). The body surface area corrected LV end-diastolic dimensional index (24.1 ± 3.1 mm/mPatients with resting DLVOTO had higher LVESWS (p = 0.007), lower S’ (p = 0.048) and a higher pulmonary arterial systolic pressure (p = 0.007) than those with latent DLVOTO. However, the prevalence of concomitant hypertension, diabetes and anti-hypertensive medications were not different. In the latent DLVOTO group, the indexed LV end-diastolic dimension was inversely and significantly correlated with an increase of the PG between the resting state and the Valsalva maneuver . However, other parameters such as angle and basal septal thickness were not significantly correlated with peak PG change.Study patients were classified as either having a pure sigmoid septum, defined as basal septal bulging but diastolic thickness ≤ 15 mm (n = 14); a sigmoid septum with basal septal hypertrophy higher than 15 mm (n = 85); a prominent papillary muscle (PM) n = 20), defined as a visually large PM which occlude the LV cavity during systole or >1/2 LV end-systolic dimension and maximal thickness of PM in short axis view higher than 11.2 mm or longer than 2.6 cm in 2, 3 or 4 chamber view; or a small LV cavity with concentric remodelling or hypertrophy (n = 49) , pulmonary arterial systolic pressure , systolic blood pressure  and relative wall thickness . In multivariate analysis, resting trans-LVOT PG correlated to PASP  after adjustment for systolic blood pressure, relative wall thickness, and E/e’.In this study, we found that, even in patients without overt HCM, DLVOTO, especially the latent form, is not infrequently seen in the absence of acute volume depletion or hemodynamic instability. This group of patients mainly has basal septal bulging and concentric remodelling that is classically assumed to be an aging-related change ,12. HoweThis group of patients had a small LV cavity and increased basal septal thickness with a more angulated ascending aorta compared to age- and sex-matched controls. Classically, basal septal bulging due to focally increased wall thickness or increased septal to ascending aorta angle  with conElderly people frequently complain of dyspnea on exertion due to diastolic dysfunction and reactive pulmonary venous hypertension. Therefore, aging is thought to be the leading cause of heart failure with a preserved ejection fraction . The usuThis study has several limitations. First, due to the nature of this retrospective study performed in a tertiary referral hospital, there may be some referral bias, and the actual prevalence of concomitant risk factors could not be truly measured. Additionally, Valsalva maneuver was not routinely done in all patients but only in patients with color flow turbulence or acceleration at rest in our echo-lab, the actual prevalence of latent DLVOTO might be underestimated. Secondly, although patients with secondary DLVOTO related to HCM or other conditions were excluded, complete evaluation by invasive hemodynamic status was not performed. Thirdly, classification based on basal septum thickness, LV concentric remodelling and visually assessed PM morphology is somewhat arbitrary. However, individual subtypes have been reported in previous studies ,11,14, sDLVOTO can develop due to various geometric changes, but patients with a prominent PM have distinct characteristics suggestive of atypical HCM rather than age-related changes. A higher trans-LVOT PG results in a higher pulmonary arterial pressure through diastolic dysfunction. Therefore, LVOTO-relieving medication might reduce the occurrence or severity of symptoms by reducing pulmonary pressure in this group of patients.The authors declare that they have no competing interest.EYC and JJC made the study design. JJC, HC and YWY analysed echocardiography images. EYC, JJC and HC collected the echocardiographic and clinical data. EYC and JJC analysed and interpreted the data. HC made a proposal and did IRB processing job. JJC, HC, YWY and EYC wrote manuscript. JHY, YWY, JYK, BKL, PKM, BKH, SJR and HMK collected the clinical data and gave comments on the manuscript. All authors read and approved the final manuscript.


Normal blood pressure (BP) follows a circadian rhythm, with dipping of BP at night. However, knowledge is limited in how the nocturnal dipping in hypertensive patients changes with the seasons. The study aims to examine the pattern of seasonal changes of nocturnal dip in an Irish population and furthermore, to compare it to the pattern observed near the equator where such seasonal variations are minimal, by also studying a Singaporean population.Ambulatory Blood Pressure Monitor recordings were obtained from 220 patients, half were from Mercy University Hospital, Cork, Ireland and half from the National Heart Centre, Singapore during the summer period from May to June and the winter period from October to December.Irish seasonal changes resulted in an increase in nocturnal dipping in the hypertensive patients, especially for diastolic pressure  and a change in the duration of dipping at night . In Singapore, slight differences in dipping in systolic pressure were apparent despite the presence of only minor alterations in temperature  or duration of daylight.Seasonal changes not only affected the daily blood pressure but also the night time dipping status in hypertensive patients by mean value of 1.99mmHg and 3.38mmHg for systolic and diastolic pressure dip respectively. This has implications on how hypertensive patients should be treated during different seasons and when they are traveling to countries of different climatic environment. Various studies have demonstrated the presence of seasonal variations in BP –4. AlterThis night time dipping is thought to be affected by an inability to excrete sodium during the daytime . Night tBrennan et al. accurately mapped out the changes in blood pressure due to acclimatization in mildly hypertensive people . They deThis study aims to elucidate the seasonal pattern of nocturnal dipping in patients with a clinical diagnosis, or suspicion of hypertension. The research also attempted to take into consideration any secondary features such as seasonal affective disorder and physical exertion both of which vary more in Ireland than Singapore.By exploring the effect of seasonal variations on the duration of the nocturnal dip we will not only provide clinicians with a better appreciation of the factors that influence the successful control of hypertension but also explore any forms of secondary features such as Seasonal Affective Disorder and physical exertion both of which are affected by the daylight shift.Patients who were referred to Mercy University Hospital, Cork, Ireland and National Heart Centre, Singapore were considered for the study. Hypertensive patients that were selected for inclusion in the study were randomly selected by a non-stratified method. Those that were shown to be taking any other forms of non-anti-hypertensive medications that might alter the BP were excluded from the study.The data being collected have been ethically approved by the Clinical Research Ethical Committee (CREC) of UCC and the Centralised Institutional Review Board (CIRB) of Singapore. The data were collected from May to October 2014.Data on systolic blood pressure and diastolic blood pressure are recorded by 24h Ambulatory Blood Pressure Monitor (ABPM). Race, age, gender, Body Mass Index (BMI), any present diagnosis, family history, anti-hypertensive or diuretic drugs that affects blood were recorded from the Citrix system and medical reports in Singapore and Ireland. The Ambulatory Blood Pressure Monitor used in Singapore was a Spacelabs Model 90217 while those used in Ireland were Meditech LTD ABPM-04, Medtech LTD ABPM-05 and Spacelabs model 90207. The MUH ABPM data were analyzed using the DABL software system, DABL Health, Dublin, Ireland. The ABPMs were programmed to record BP at thirty minute intervals over the day time and the night time. Systolic and diastolic ABP and heart rate (HR) values were averaged to each hour of the recording, over the daytime (from 08:00–20:00h), over the night time (from 01:00–06:00h), and over the entire 24-h periods .The retrospective data were collected from the period of May to July as the summer season and October to December as the winter season from 2013. 110 patients’ details were collected from each season amounting to 220 patients per country.Patients were further divided into hypertensive, which includes, and non-hypertensive patients. Hypertensive patients refers to patients who have a systolic pressure greater than 135mmHg and diastolic pressure of 85mmHg on ABPM. The diagnosis is made according to National Institute for Health and Care Excellence (NICE) guidelines .Data are also expressed in terms of means with standard deviations using descriptive statistics or paired sample T test or independent sample T test is used. The different numbers of each dippers in both countries are compared amongst themselves to find out whether there was any change by using the paired sample T test in SPSS Statistics 20 to obtain the p-value.Data on temperature, humidity and other meteorological data will be obtained from the Irish Meteorological Service (MET) and from the National Environment Agency (NEA) of the Singapore government.Data on the electricity consumption by household in Singapore was taken from the Energy Market Authority (EMA) of Singapore.A total of 220 patients were studied in Ireland and in Singapore. There were a total of 62 males and 43 females, 82 males and 28 females in Singapore during the summer and winter seasons respectively. In Ireland, there were 64 males and 46 females, 58 males and 52 females during summer and winter seasons respectively. The mean age, in years, in Singapore was 52.29 in summer and 46.37 in winter, In Ireland the mean age in summer was 57.64 and in winter was 55.63. Unlike Ireland, Singapore experienced a relative stability of temperature from May to December . This isDuring the different seasons, there were changes in mean systolic and diastolic pressure dipping for both Ireland and Singapore as summarized in However, when the average sleeping blood pressure between the two countries in the two seasons were compared  and 2, iThe results of this study show that there was a seasonal link with the nocturnal dip in hypertensive patients. As seen in However, the systolic dip at night in Singapore was an unexpected change (p < 0.05). In fact, the mean systolic dip changed a total of 2.6% as compared to 1.99% of Ireland. This could be due to many other variables which might have a greater effect on the systolic pressure. In the Irish population, there is an overall decrease in pulse pressure from 56.23 to 56.15mmHg while that in Singapore increased from 53.12 to 53.9mmHg.In addition, the duration of night time dipping between the two seasons in Ireland changed from 2.99 to 3.52h while that in Singapore was only from 2.57 to 2.97h. The result could also be an underestimation of the true value of the dipping as the average age in the Irish population is slightly higher. The average age for the Irish population is 58 and 56 between summer and winter while that in Singapore is 52 and 46. Age is one of the key factor which will increase the frequency of arousal from sleep . This miInterestingly, even though there are no changes in seasons in Singapore, both Ireland and Singapore seem to show an overall drop in the number of reverse dippers and increase in the other group of dippers . This woThis study is unique in the inclusion of two countries, Ireland and Singapore, one of which has no seasonal changes. It allows the use of a single country to act as a form of control. Many present studies in similar field only use a single country as a form of comparison. This study thus, allowed us to further test the hypothesis.Some limitation of the study involves the fact that as data are being collected from different countries, the Ambulatory Blood Pressure Monitor (ABPM) being used is different which might give rise to systematic errors. However, both centers used systems of ABPM monitoring that are well validated and should minimize observer bias in the collection of individual blood pressure values.Both countries are very different in terms of culture, demographics as well as dieting style and that the Asian population tends to be lower in BMI as compared to the Caucasian population. In Singapore, the food consumed is generally healthier and tend to be less salty which might result in a lowering of blood pressure as compared to that of the Irish population. Unlike Ireland, Singapore does not have winter season, thus the amount of food consumption are also generally more constant as people tend to consume greater amount and saltier food during the winter as compared to summer. This would inevitably affect the overall blood pressure as well.However, despite the differences in diet, race and culture, the difference in BMI between both countries was modest. This will allow the exclusion of these difference affecting any changes in blood pressure between the two populations. This is further enhanced by the similarity in the sexes group being used with males being the predominant one due to the fact males are more susceptible to hypertension and cardiovascular diseases.The population of hypertensive subjects studied in the summer and winter cohorts in each country differed. This is a reflection of the collection of this data from a real world population. Although it would be preferable to study the same population in both phases this was not practical in view of the clinical demand for ABPM and the need to apply it in an environment of routine care. As the comparison of an entire cohort in the two countries seems to show how the season will affect the dipping status in people, this would perhaps, be amplified if the same cohort were used.Another limitation will stem from the fact that Singaporeans in general are mostly indoors in air-conditioned areas. During a hotter weather the air-conditioners will be used to reduce temperature. Irish on the other hand, will use heaters during the winter season and reduce the change in temperature due to any seasonal changes. In our population of non-night shift works the nocturnal BP recordings will almost exclusively be recorded in the patients’ homes. As a result, the changes in blood pressure might not accurately reflect the actual changes in the temperature changes due to different seasons as the air-conditioning and heating might lower the difference in changes of temperature due to the changes of weather. This might cause an underestimation of the actual change in blood pressure.In summary, it is difficult to obtain a single variable from two separate countries with different cultural influences. However, this research shows a clinical significance in the seasonal changes in nocturnal dip and should be taken into consideration during the treatment of diastolic pressure of hypertensive patients. In the usual practice now, not much of an attention is given to the fact that how the seasonal changes will affect the usual blood pressure changes. By taking the changes into consideration, clinicians will be able to control the changes in blood pressure more effectively especially even when the seasons change through the control of dosages of medications prescribed. The change in blood pressure should also be taken into considerations when the patient travels into countries with different climatic environment.


Linear mixed effects model showed that drinking tea, family history of hypertension (FHH), higher blood glucose, triglyceride and low density lipoprotein were related with elevated diastolic blood pressure (DBP) (p < 0.01); HFH, blood glucose, creatinine and BMI have positive effect on systolic blood pressure (SBP) (p < 0.05). Conclusions: Drinking tea, FHH, high levels of triglyceride, high density lipoprotein, blood glucose and BMI are associated with IDH among young and middle-aged Chinese.Objective: To explore potential risk factors of isolated diastolic hypertension (IDH) among young and middle-aged Chinese. Methods: A community-based cross-sectional study was conducted among 338 subjects, aged 25 years and above, using random sampling technique. There were 68 cases of IDH, 46 cases of isolated systolic hypertension (ISH), 89 cases of systolic and diastolic hypertension (SDH), and 135 of subjects with normal blood pressure. Cases and controls were matched on sex by frequency matching. Demographic characteristics, blood pressure and other relevant information were collected.Results: Compared with controls, patients with IDH and ISH had significant higher level of triglyceride, high density lipoprotein, blood glucose and body mass index (BMI) ( Isolated diastolic hypertension (IDH), as unrecognized subtype of hypertension, is defined as DBP more than 90 mmHg and systolic BP less than 140 mmHg . Althouget al. found that unreasonable diet structure was the main risk factor for IDH in exploring the differences between ISH and IDH risk factors among 20,364 patients (>35 years) [et al. studied 5968 of people aged above 18 and found that in untreated, while at the same time in patients with hypertension and metabolic syndrome, IDH patients with metabolic syndrome risk ratio (14.7) was higher than that of ISH (10.2) and SDH (12.2) (p < 0.01), the probability of the metabolic syndrome is nearly 15 times as large as the ideal blood pressure [Previous study indicated that higher levels of BMI, glucose, and uric acid concentrations were potential risk factors for IDH . However5 years) , while t5 years) . FrankliSymptoms of IDH are less likely to be addressed by doctors or patients in China . Thus, mTherefore, we conducted a community-based study and used linear mixed effect model to explore the risk factors of newly diagnosed IDH among young and middle-aged Chinese.Participants were recruited from March to June in 2014 among a hospital physical examination population among whom 66.3% came from the community of Ma’anshan City, Auhui Province, China. Two hundred and three cases  were selected from all of the hypertension patients according to the inclusion criteria, and 135 controls with normal blood pressure matched on sex by frequency matching were sampled by simple random sampling in the same certain period of time. All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Wanna Medical College (NO.: 2014023). (1) Questionnaire survey: A self-administered questionnaire was used to collect information on demographic characteristics, including medical history, family history of hypertension, health-related knowledge, dietary pattern, exercise, alcohol consumption, smoking, drinking tea status, socioeconomic status, etc. Trained investigators disseminated questionnaire to participants and provided instructions to them. (2) Physical examination: height, body weight and blood pressure were measured according the standard protocol. Blood pressure was recorded using an aneroid sphygmomanometer, the participants were in a quiet and warm room. Two readings taken at least 5 minutes apart were obtained for each participant, and the average blood pressure was calculated.(3) Laboratory examination: 5 mL of fasting venous blood was used to measure fasting blood glucose (FBG), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglyceride (TG),uric acid (UA) and creatinine (Cr) .(1) Hypertension group: according to the 2010 guideline of hypertension prevention and control: hypertension is defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg without administrating any antihypertensive drugs . (2) Sub2 is defined as normal, 24.0–27.9 kg/m2 as overweight, greater than or equal to 28 kg/m2 as obesity [BMI category: body mass index (BMI) < 24.0 kg/m obesity . Intensip < 0.05.Data was entered into database established using Epi Data 3.02 with double entry. SPSS 13.0 was used for statistical analysis. Chi-square test and analysis of variance were used to test the differences of the demographic characteristic of subjects. The Student-Newman-Keuls analysis of variance was conducted to compare differences of serum lipid, renal function, blood glucose BMI, physical and behavioral factors among IDH, ISH, SDH and control group. In order to explore the impact factors of different types of hypertension, especially the IDH, we used multivariable analysis of linear mixed effect model; Statistical significance was defined as p > 0.05), and details have been presented in A total of 68 IDH cases, 46 ISH cases, 89 SDH cases and 135 controls were included in the current study with male: female ratio of 2.29:1. The average age were 41.97 ± 7.87, 43.98 ± 9.09, 45.12 ± 7.45 and 41.14 ± 9.71 in the IDH, ISH, SDH and control group, respectively. The proportion of genders was comparable across the four groups. No significant difference was detected in marital status, household registration and educational background among IDH, ISH, SDH and control groups (p < 0.05 or p < 0.01), while TC, TG, FBG and BMI level in SDH group were significantly higher compared with control group (p < 0.05 or p < 0.01); there were no significant differences of LDL UA and Cr among four groups.We tested the distribution of serum lipid, renal function, blood glucose, and BMI among people with different types of hypertension. p < 0.05), while there were more participants with overweight in ISH group than in control group (p < 0.05). In addition, the percent of FHH, and tea drinkers were significantly higher in SDH group than in the control group (p < 0.05 or p < 0.01).p < 0.05 or p < 0.01); FHH, FBG and BMI had positive effect on SBP (p < 0.05 or p < 0.01); and Cr had negative effect on SBP (p < 0.05) and it is the protective factor of SBP.In linear mixed effect model, the different types of hypertension were treated as dependent variable, and those statistically significant variables in In summary, drinking tea, HFH, blood glucose, triglyceride and low density lipoprotein were associated with elevated diastolic blood pressure (DBP); HFH, blood glucose, Cr and BMI had positive effect on systolic blood pressure (SBP). Meanwhile, different type of hypertension had different risk factors, of particular interest, drinking tea was a risk factor for IDH.The target population of this study is young and middle-aged adults with an average age of 45 years old. Biologically, large artery elasticity functions well and only peripheral vascular resistance can increase diastolic blood pressure for population of this age .etc. [The high incidence of IDH among the population could be partly result from stress from people’s career and life, as well as, high prevalence of IDH risk factors including high TC, overweight, smoking, and drinking, etc. . Of noteThe linear mixed effects model analysis indicated that tea drinking history, FHH, blood glucose, TC, LDL, UA and Cr are factors associated with blood pressure. Although the linear mixed effects model analysis of blood pressure was rarely reported in hypertension-related studies, family history, blood glucose, blood lipid have been frequently reported as impact factors for blood pressure . The anaConsistently, it is observed that compared with the control group, TC, HDL, blood glucose and BMI were statistically significantly higher among IDH group, ISH group and SDH group, which is consistent with other findings on IDH risk factors ,22,23. TTo our knowledge, our study is the first report on a positive relationship of tea drinking and IDH, although the effect size is small. However, our study has several limitations. For example, accurate information about the tea type, frequency, time, and quantity consumed are not available in present study. However, Anhui Province is the main production area of green tea, and the green tea is the most popular drink in the study setting. A survey in Tongcheng City (a neighboring city in Auhui Province) showed that more than 90% of the residents drink green tea . Of noteDifferent type of hypertension had different risk factors, drinking tea, family history of hypertension, high levels of triglyceride, high density lipoprotein, blood glucose and BMI are risk factors of isolated diastolic hypertension among young and middle-aged Chinese.