Catha edulis) contain Cathinone, an amphetamine like alkaloid responsible for its pharmacological action. Chewing of Khat has been associated with a transient rise in blood pressure and heart rate in experimental studies. Few studies examined the effect of regular or frequent Khat chewing on blood pressure at the population level. This study was conducted to examine the association of regular Khat chewing with blood pressure among adults.Fresh leaves and buds of the Khat plant  and non-chewers (330), were identified from among the general population through a house-to-house visit using a screening questionnaire. They were frequency-matched for sex and age within a five-year range. Data were collected through structured interviews and physical measurements including blood pressure, weight and height.The prevalence of hypertension was significantly higher among Khat chewers (13.4%) than non-chewers (10.7%), odds ratio (OR) = 1.66  1.05, 3.13). A considerably high proportion of chewers (29.9%) than non-chewers (20.6%) had sub-optimal diastolic blood pressure (> 80 mmHg). The mean (sd) diastolic blood pressure was significantly higher among Khat chewers [75.0 (11.6)] than non-chewers [72.9 (11.7)], P < 0.05. Similarly, Khat chewers had significantly higher mean (sd) heart rate [76.3 (11.5)] than non-chewers [73.9 (12.6)], P < 0.05. There was no significant difference in mean systolic blood pressure between the two groups.Regular chewing of Khat is associated with elevated mean diastolic blood pressure, which is consistent with the peripheral vasoconstrictor effect of Cathinone. Regular Khat chewing may have sustained effects on the cardiovascular system that can contribute to elevated blood pressure at the population level. Hypertension is a growing public health problem, with remarkable contribution to cardiovascular diseases (CVD) morbidity. Worldwide, an estimated 1 billion individuals have hypertension, and approximately 7.1 million deaths per year are attributable to hypertension . In EthiElevated blood pressure has many risk factors that are of behavioral, dietary or genetic origin. Among the main modifiable risk factors of hypertension are overweight and obesity, cigarette smoking, physical inactivity, unhealthy diet, stress, dietary salt intake, and alcohol use ,4. RegulCatha edulis. It is indigenous to Ethiopia, Kenya, and Yemen [Khat is found in the flowering evergreen tree or large shrub of Celastracea family. It consists of whole fresh leaves and buds of a plant known as nd Yemen . More thnd Yemen . Cathinond Yemen -11.The use of Khat is an established cultural tradition for many social situations in the areas of primary cultivation, East Africa and the Arabian Peninsula. Several million people may be chewing Khat worldwide, with an estimated 10 million people chewing Khat leaf daily . The preKhat typically is ingested while chewing the leaves. After ingesting Khat, the chewer experiences an immediate increase in blood pressure and heart rate ,14. VariStudies on the effect of substance abuse and their health effects are scarce despite the ever-growing rate of substance use behaviors . Some st2. The topography ranges between dry lowlands at altitudes around 1,500 m  to cool mountainous areas of up to 3,500 m above mean sea level (temperate climate). Farming is the main occupation in rural areas while petty trading is common in the town [This study was conducted in Meskan District of Gurage Zone, Ethiopia. Meskan District is located 130 km to the south of Addis Ababa. The district population was estimated at 260,000 in 2005, of which 87% live in rural areas. The district covers an area of 797 kmthe town . Khat isthe town .A demographic surveillance system, the Butajira Rural Health Program (BRHP), has been operational in the area since 1987 . The BRHThe selection of kebeles or households was not intended to generate a representative sample of the district population. As the primary purpose of the study was the comparison of blood pressure between Khat chewers and non-chewers, efforts were made to ensure that the two groups were selected using the same procedure.The sample size was estimated using the general formula for comparison of two means . The meaOnce a household was selected, all individuals residing in the household that fulfilled the criteria as either Khat chewer or non chewer were enrolled into the study, until the number of participants assigned to each of the four kebeles  was attained. In the event that there was no eligible individual in the selected household, the next closest household was visited.Adults between 35 and 65 years of age who chewed Khat for four or more days in a week during the past five years (chewers) or those who never chewed Khat during the past five years (non-chewers), were included in the two groups. Adults younger than 35 year of age were excluded from the study as elevated blood pressure is less common in this age group ,24, and M4 digital blood pressure measuring device.A semi-structured questionnaire, modified from the World Health Organization instrument for stepwise surveillance (WHO STEPS) of chronic disease risk factors ,26 was uTwelve data collectors, six male and six female, who have experience in data collection and measurements were recruited and trained on the administration of survey instruments using training manual, developed for the survey based on the WHO training and practical guide ,25.Physical measurements of height, weight, hip, and waist circumferences and BP were carried out after the socio-demographic questions have been completed. The interview and physical measurements were conducted during the day, between 8:30 am and 6:30 pm, independent from the time of Khat chewing. Before BP measurement, each study participant was advised to sit and take rest for at least five minutes. Three consecutive measurements were taken on the left arm at 3-5 minutes interval. Average of the second and third measurements was used to describe the mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP), and heart rate (HR) of study participants as recommended in the WHO STEPS method ,26.Data were entered and analyzed using EPI-Info version 6.04d and Statistical Package for Social Sciences (SPSS) version 13.0 software. Proportions and percentages were utilized to describe some characteristics of the study participants. Multiple linear regression analysis was performed in order to identify determinants of DBP and to estimate their corresponding coefficients of variability. Odds ratio (OR) was used to measure association of dependent and independent variables where 95% confidence interval (CI) and P-value were utilized to determine statistical significance.Ethical clearance for the study was obtained from the Ethics Review Committee of the School of Pharmacy, Addis Ababa University (AAU). Informed and written consent was obtained from each study participant. The survey did not involve any invasive procedure which could cause harm to the study participant or to the community. Individuals with high blood pressure identified during the survey were advised to seek BP measurement service at the local health facilities.A total of 667 adults who met the eligibility criteria were interviewed, of which 664 participants have completed both the interview and measurements making the response rate of 99.5%. Among the 664 study participants, 50.3% were Khat chewers and 49.7% were non-chewers. Of the Khat chewers, 53.0% were males, 55.4% were rural residents, 99.4% were married, and 92.5% were Moslem. While the two groups were comparable in most socio demographic characteristics, the non-chewers were less likely to be Moslems (41.5% vs. 92.5%), odds ratio (OR) = 0.07. There was no significant difference in mean (sd) age of chewers (43.67) and non-chewers (43.51) , of chewers chew Khat four days a week. The median duration (years) of chewing was 20 years. The mean (sd) duration of chewing in a day was 2.4 (± 1.2) hours. About half (51.8%) of the Khat chewers chewed Khat for a duration of three hours at a time.The reported reasons for chewing Khat include religious prayer, to pass time, to accompany or socialize with family members, and to get more concentration at work. Only 30 (9.0%) chewers reported that they might be addicted to Khat, while another 45% claim that they might have some habit of chewing, but no addiction. The remaining 44.4% believed that they have neither addiction nor habituation.The proportion of smokers was significantly (P < 0.05) higher among Khat chewers (10.8%) than non-chewers (4.8%). The mean (sd) duration of smoking was 16.2 (± 10.5) years; where chewers smoked for mean (sd) of 15.2 (± 9.3) years and non-chewers for 18.5 (± 12.9) years. Similarly, Khat chewers were significantly (P < 0.05) more likely to be drinking coffee, and to be adding salt in their coffee. On the other hand, alcohol drinking was significantly (P < 0.001) more common among non-chewers (30.9%) than Khat chewers (7.8%) (Table Table Significantly more Khat chewers (30%) had sub-optimal diastolic blood pressure (DBP > 80 mmHg) than the non-chewers (21%); Chi-square = 7.65, P < 0.01. Whereas, 47% of Khat chewers and 45% on the non-chewers had sub-optimal systolic blood pressure (SBP > 120 mmHg). The difference in the proportion with sub-optimal systolic blood pressure was not significant (P > 0.05).The prevalence of hypertension (SBP > = 140 mmHg or DBP > = 90 mmHg or reported use of antihypertensive drugs) was significantly higher among Khat chewers (13.4%) than non-chewers (10.7%), OR = 1.66 . Similarly, 30.9% of chewers and 28.5% of non-chewers were found to have pre-hypertension, which is a designation that helps to identify individuals at high risk of developing hypertension.Multiple linear regression analysis was conducted in order to examine the independent effect of the behavioral characteristics  that were found to vary significantly across Khat chewers and non-chewers. The analysis Table  revealedThis study compared mean systolic and diastolic blood pressure between adults in Butajira district who are Khat chewers and non-chewers. We demonstrated the association of Khat chewing with mean diastolic blood pressure, which suggests that Cathinone may have a more pronounced effect on diastolic blood pressure. Earlier studies have also suggested that chronic use of Khat predisposes to high blood pressure and other cardiovascular morbidity ,20,27.Our study suggests for the first time, using a comparative study design that long-term Khat chewing contributes to an isolated increase in diastolic blood pressure at the population level. The present finding confirms an earlier report of association between Khat chewing and elevated blood pressure from a cross sectional study in a similar population . Our finThe potency of Khat leaves varies depending on freshness, origin or type, and the chewing pattern . Amount The concomitant use of other classical cardiovascular risk factors, such as smoking, alcohol, or dietary salt intake along with Khat may modify the extent of association between Khat chewing and blood pressure . ReporteThe ideal method of determining salt consumption at the population level would be through the measurement of 24 hour urinary sodium excretion. However, this was not possible in the present study largely due to logistics limitations. In the absence of such laboratory methods, a qualitative assessment of the salt use behavior may offer important clues on salt intake. However, as indicated in Table Although previous studies commonly reported association between Khat chewing and alcohol consumption ,28,29, oOther studies ,31 have Our findings suggest sustained effects of regular Khat chewing on blood pressures, beyond the transient rise in blood pressure and heart rate that have been demonstrated in experimental studies ,8,14,20.The mean diastolic blood pressure and heart rate of Khat chewers in our study were significantly higher than that of non-chewers, (p < 0.05). On the other hand, the difference in mean SBP between the two groups was not statistically significant. The reason for a less marked effect of Khat chewing on systolic blood pressure in contrast to diastolic blood pressure needs further investigation.Use of self reported age and Khat chewing data in a setting where record of vital statistics are not available, may be subject to recall bias. No mechanism was designed to countercheck the reported age or consumption behavior. The effect of other contributing factors and associated health problems such as Diabetes, kidney diseases, heart diseases, level of cholesterol etc, that require additional input was not assessed."a large number of people exposed to a small risk may generate many more cases than a small number exposed to high risk" [The mean diastolic blood pressure among Khat chewers was significantly higher than that of the non-chewers, by 2.1 mmHg. A blood pressure variation of 2.1 mmHg may appear insignificant at an individual level, but can be regarded as an important difference at a population level. It takes much effort to lower (shift to the left) the mean blood pressure distribution of a given population by 2.1 mmHg. Such reduction would also have a significant contribution to lowering the risk of morbidity and mortality related to cardiovascular diseases at the population level. It has been well established that gh risk" . Populatgh risk" .The quantitative measurement of Cathinone and its metabolic products in the urine, as well as the measurement of 24-hour urinary excretion of Sodium was beyond the scope of the present study. It is suggested that future studies in the area of Khat chewing and cardiovascular health may allow a more quantitative analysis by conducting such measurements.Our study revealed that Khat chewing may contribute to elevated blood pressure, with a more pronounced effect on diastolic blood pressure. A considerably higher proportion of Khat chewers have sub-optimal DBP. The findings suggest that Cathinone might have a sustained effect as peripheral vasoconstrictor among regular Khat chewers.The association of regular Khat chewing and elevated blood pressure levels in the population has significant relevance for public health. Programs for the prevention and control of high blood pressure in the population need to devise strategies to counter the expansion of Khat chewing and other substance use behaviors.The authors declare that they have no competing interests.WG, drafted the study proposal, developed survey instruments and collected and processed data. FT and TG conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors participated in data analysis. WG drafted the manuscript. FT and TG reviewed and revised the manuscript, and approved the final form.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/390/prepub


The Alberta Kidney Disease Network is a collaborative nephrology research organization based on a central repository of laboratory and administrative data from the Canadian province of Alberta.The laboratory data within the Alberta Kidney Disease Network can be used to define patient populations, such as individuals with chronic kidney disease (using serum creatinine measurements to estimate kidney function) or anemia (using hemoglobin measurements). The administrative data within the Alberta Kidney Disease Network can also be used to define cohorts with common medical conditions such as hypertension and diabetes. Linkage of data sources permits assessment of socio-demographic information, clinical variables including comorbidity, as well as ascertainment of relevant outcomes such as health service encounters and events, the occurrence of new specified clinical outcomes and mortality.The unique ability to combine laboratory and administrative data for a large geographically defined population provides a rich data source not only for research purposes but for policy development and to guide the delivery of health care. This research model based on computerized laboratory data could serve as a prototype for the study of other chronic conditions. The Alberta Kidney Disease Network (AKDN) is a collaborative group of nephrology researchers located in Calgary and Edmonton, Alberta, Canada, with a mission to undertake clinical research and offer research training in kidney disease. The flagship initiative of the AKDN is a unique data collection initiative of routine laboratory tests on all patients in the province of Alberta, resulting in a geographically inclusive database. Patients identified from laboratory data are linked to administrative and other computerized sources to obtain detailed information including socio-demographic data, clinical data including comorbidities, health care encounters, health care costs, death, and kidney-related outcomes.As the initiative grows the AKDN research findings and activities are beginning to appear more frequently in peer-reviewed literature and health policy circles -3. HowevThe AKDN objectives are focused around key research methodologies: clinical epidemiology; health services research; clinical trials; systematic review and meta-analysis; and health economics. Five specific aims relevant to the AKDN dataset were initially identified:1. To determine the prevalence and identify those at high risk for chronic kidney disease in Alberta, Canada.2. To determine rates of progression of chronic kidney disease.3. To determine if access to/quality of specialized medical care and/or rates of progression of kidney disease differs by gender, age, location of residence or ethnic background.4. To determine the health care costs of caring for patients with chronic kidney disease.5. To determine optimal treatments for patients with chronic kidney disease.This is not an exhaustive list, and as the Network grows more objectives and research questions are being addressed. The examples of on-going research projects outlined below demonstrate the potential of this data source.http://www.AKDN.info was established to facilitate knowledge translation activities, as well as to provide information regarding team members, training opportunities and research activities.The AKDN has also developed a plan to facilitate implementation of its research findings. These knowledge translation activities target patients, health care providers, researchers and health policy-makers. These activities aim to provide information to patients regarding kidney function and disease in general, health care providers to assist with investigation and management of patients with chronic kidney disease, and policy makers to guide evaluation and planning of health service delivery for patients with chronic kidney disease. A website The core component of the AKDN database is the central repository of laboratory data. Through the AKDN, and in collaboration with laboratories across the province of Alberta (population 3.5 million), we have developed a process for retrieval, storage and maintenance of computerized laboratory data and relevant laboratory tests for all patients who have these measurements obtained throughout the province. To permit complete collection of specific tests, and in accordance with privacy laws and ethics board regulations, we were required to limit the number of laboratory tests retrieved and maintained in the database. As such we selected tests which are routinely ordered for patients with common medical conditions to guide ongoing patient assessment, monitor disease progression and identify relevant outcomes Table . The datThe serum creatinine is used to obtain an estimate of glomerular filtration rate (eGFR). Serum creatinine measurements < 25 umol/L are excluded as they are physiologically implausible. We initially used the non-isotope dilution mass spectrometry traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation . AlthougTo reduce the effect of regression to the mean, a statistical phenomenon that occurs when repeated measurements with wide variability are made on the same subject , baselinProteinuria, an important predictor of outcomes for patients with kidney disease, is captured by qualitative (urine dipstick) as well as quantitative measures Table . There iLinkage of laboratory data to administrative and other computerized data sources provides a rich source of information for assessment of socio-demographic characteristics, clinical variables and health outcomes Figure . The uniAHW administrative data includes all residents of the province of Alberta, and contains data sources which permit determination of disease incidence and prevalence using validated algorithms for common medical conditions such as hypertension, diabetes, acute myocardial infarction, congestive heart failure and stroke -15, as wAlberta Blue Cross administers extended health benefits paid by AHW on behalf of eligible individuals, including residents aged 65 and older, for services which include formulary drugs, permitting evaluation of drug use and its impact on outcomes ,22. DetaFollow-up and capture of outcomes of particular relevance for the study of kidney disease, including dialysis initiation or kidney transplantation, is possible by linkage with the Northern and Southern Alberta Renal Program databases . These tAs outlined in Figure Laboratory data can be used for case identification and for assessment of disease control, including the use of hemoglobin A1C among patients with diabetes, cholesterol levels among patients at risk for cardiovascular disease, and hemoglobin levels among patients with chronic diseases. It can also be used to identify adverse outcomes related to a treatment or procedure, such as the development of hyperkalemia among patients initiating an angiotensin converting enzyme inhibitor or angiotensin receptor blocker medication. Importantly the serum creatinine measurement can be used to estimate kidney function and define chronic kidney disease, and thus can be used for ongoing surveillance (defined as the ongoing systematic and population-based collection of data).Surveillance is important for the purposes of disease detection, assessment of trends, identification of service needs for program and policy development, and research. Recently efforts have been directed towards enhanced surveillance for specific chronic medical conditions, including diabetes, cardiovascular disease, and chronic kidney disease. However, the ability to implement a comprehensive surveillance system is limited by the availability of data, and sources currently used often include outcome measures only , or are limited by incomplete assessment of comorbidity. The computerized laboratory data within the AKDN provides the potential for both case identification and ongoing monitoring of chronic medical conditions such as chronic kidney disease (using the serum creatinine to estimate glomerular filtration rate), and can be enhanced to obtain an assessment of comorbidity through linkage with administrative data.Notwithstanding its strengths, there are important limitations which must be recognized when using the AKDN data. First, the use of laboratory data to define a study cohort by definition will limit the study to subjects who have sought medical care and had a laboratory test undertaken. Although the reasons for measurement are unknown and selected patients may differ from patients without these measurements, this is unlikely to invalidate study findings which are based upon a large proportion of patients from the source population and reflect standard clinical practices in a defined geographic location with universal access to health care. Furthermore a cohort identified by laboratory-based case finding is easily generalized to primary care practice. Second, use of administrative data limits access to certain clinical variables such as blood pressure control and lifestyle factors , which may be potential confounders. However other important confounders such as diabetes, hypertension and the Charlson comorbidity index are captured using the computerized data sources.The AKDN has used this database to gain a more in-depth understand of chronic kidney disease at the community level, including prevalence and progression of kidney dysfunction ,25 and aThe AKDN has developed a unique repository of laboratory data which can be used for health services and health policy research. Although originally developed by nephrology researchers, the AKDN database includes information on all patients who have obtained routine laboratory investigations (not just those with kidney disease), and therefore could also be used for the study of other chronic medical conditions.The authors declare that they have no competing interests.All authors have made substantial contributions to the conception and design of the Alberta Kidney Disease Network (AKDN). All authors have been involved in revising the manuscript for important intellectual content, and all authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/10/30/prepub


Wrist blood pressure (BP) devices have physiological limits with regards to accuracy, therefore they were not preferred for home BP monitoring. However some wrist devices have been successfully validated using etablished validation protocols. Therefore this study assessed the reproducibility of wrist home BP measurement with position sensor and automatic data storage.To compare the reproducibility of three different(BP) measurement methods: 1) office BP, 2) home BP (Omron wrist device HEM- 637 IT with position sensor), 3) 24-hour ambulatory BP(24-h ABPM) conventional sphygmomanometric office BP was measured on study days 1 and 7, 24-h ABPM on study days 7 and 14 and home BP between study days 1 and 7 and between study days 8 and 14 in 69 hypertensive and 28 normotensive subjects. The correlation coeffcient of each BP measurement method with echocardiographic left ventricular mass index was analyzed. The schedule of home readings was performed according to recently published European Society of Hypertension (ESH)- guidelines.The reproducibility of home BP measurement analyzed by the standard deviation as well as the squared differeces of mean individual differences between the respective BP measurements was significantly higher than the reproducibility of office BP (p < 0.001 for systolic and diastolic BP) and the reproducibility of 24-h ABPM . The reproducibility of systolic and diastolic office versus 24-h ABPM was not significantly different . The correlation coefficient of 24-h ABMP (r = 0.52) with left ventricular mass index was significantly higher than with office BP (r = 0.31). The difference between 24-h ABPM and home BP (r = 0.46) was not significant.The short-term reproducibility of home BP measurement with the Omron HEM-637 IT wrist device was superior to the reproducibility of office BP and 24- h ABPM measurement. Furthermore, home BP with the wrist device showed similar correlations to targed organ damage as recently reported for upper arm devices. Although wrist devices have to be used cautious and with defined limitations, the use of validated devices with position sensor according to recently recommended measurement schedules might have the potential to be used for therapy monitoring. The reproducibility of office blood pressure (office BP) measurement in clinical studies as well as in doctor's offices is very limited for various reasons. These include for example observer bias, the white-coat and placebo effects . The pooIt has so far been unclear whether the reproducibility of home BP measurement on the wrist is comparable with that of 24-hour on the upper arm. Moreover, there have been as yet not been any studies investigating the correlation of wrist measurements with end organ damage such as left ventricular hypertrophy.In the present study, the following questions were therefore investigated with the Omron wrist instrument HEM-637 IT with a position sensor:1. To what extent is the short-term reproducibility of wrist measurements with a position sensor comparable with that of 24-h ABPM and office BP measurement?2. How do multiple wrist measurements correlate with left ventricular mass index (LVMI) as compared to 24-h ABPM and office BP measurement?The objective of the study was to investigate the reproducibility of office BP, home BP and 24-h ABPM over a period of one week. For this purpose, an office BP measurement was taken on study days 1 and 7 in 101 patients and an ambulatory 24-h ABPM was carried out on study days 7 and 14. In the time intervals between study days 1 and 7 and between study days 8 and 14, the patients measured their home BP themselves with an oscillometric wrist instrument.One hundred and one participants were included in the study. All subjects were consecutively recruited from the outpatients of Medical Policlinic of the University of Bonn.The data of 97 patients with complete data sets  were included in the statistical analysis. Hypertensive subjects measured home BP before taking antihypertensive medication. The antihypertensive treatment regime (frequency and timing) was not changed during the study period. 4 patients were excluded. The inclusion criteria were aged between 18 and 75 years and the presence of written consent to participate in the study. The exclusion criteria were significant arrhythmias, pregnancy and lactation. The University of Bonn issued a positive ethical vote on the study.The blood pressure was measured in the doctor's office in accordance with the recommendations of the American Heart Association (AHA) and the European Society of Hypertension (ESH) after the participant had rested for five minutes in a sitting position ,8. On stThe patients measured their blood pressure themselves with the oscillometric wrist instrument from Omron (wrist instrument HEM- 637 IT with position sensor). Between study days 1 and 7 and study days 8 and 14, the participants took two measurements on the left wrist each day in the morning between 6 and 9 a.m. and in the evening between 8 and 9 p.m. after sitting for five minutes with a two-minute interval between the two consecutive measurements. Hypertensive subjects measured home BP before taking antihypertensive medication. The antihypertensive treatment regime was not changed during the study period. Patients were instructed how to correctly use the oscillometric Omron wrist device for home BP measurement with a standardized 30 min. teaching program. The blood pressure parameters of the first week (day 1 to day 7) were compared with the results of the second week (day 8 to day 14). The HEM- 637 IT wrist device is validated according to the international protocol of the European Society of Hypertension [The ambulatory 24-h blood pressure was performed according to AHA and ESH guidelines and measured with the ABPM 04 instrument of the company Meditech, Hungary, on the left upper arm on study day 7 and 14. In the period between 6 a.m. and 10 p.m., an oscillometric blood pressure measurement was taken automatically at intervals of 20 minutes, and at intervals of 45 minutes in the period between 10 p.m. and 6 a.m. The CardioTens is validated according to the BHS (British Hypertension Society) protocol [2 body surface was calculated in accordance with the corrected Devereaux formula. LVMI was analysed by an investigator blinded to the results of the BP measurements.On study day 1, a cardiac ultrasonographic investigation was conducted in all patients with the Hewlett Packard instrument  with a 2.5 MHz transducer. The left ventricular muscle mass index (LVMI) in g/mThe parameters investigated were anthroprometric data such as age, gender, height, body weight, body mass index, circumference of the wrist and of the upper arm. The parameters of office BP were systolic and diastolic blood pressure and pulse pressure. The parameters of home BP were systolic and diastolic blood pressure, heart rate as well as pulse pressure. The parameters of the ambulatory 24-h ABPM were systolic and diastolic blood pressure, heart rate, and pulse pressure measured, for the total ambulatory 24 hour period, for the daytime (6 a.m. to 10 p.m.) and for the nighttime (10 p.m. to 6 a.m.).Before the evaluation, the systolic and diastolic blood pressure values were averaged for each method of measurement  over the respective visit to the doctor's office, day of measurement or the respective week of measurement. Consequently, two values  were available for each of the methods. These had been measured at an interval of about one week. The mean values determined in this way were the basis for the descriptive evaluation of the values measured with the different methods.In order to be able to compare the reproducibility of the three measurement strategies, the standard deviation of mean differences were compared. Student's t-test was used to statistically compare the SD of mean difference between measurement methods. Furthermore, the squared differences between the first and second set of BP measurements was calculated for office, home and 24-h ABPM.The left ventricular mass was used as a measure for the extent of end organ damage and the correlation coefficient of the blood pressure parameters obtained with various methods of measurement with the left ventricular mass index was calculated.For each BP measurement method, the number of patients needed to detect a two-sided α risk of 5% and a statistical power of 80% to detect a systolic and diastolic blood pressure difference of 5 mm Hg was calculated.The data from 97 patients were evaluated to compare the reproducibility of blood pressure measurements. The correlation analysis of blood pressure parameters with the left ventricular mass index could only be carried out with a subgroup of 74 patients in whom satisfactory sonography was possible. The patients' characteristics are shown in Table Compared to study days 1 and 7, there was no difference in the office BP values. There was also no difference in the home BP values, compared to week 1 and week 2, and no diference in the 24-h ABPM values compared to study 7 and 14. The blood pressure values obtained with the different methods are shown in table The standard deviation of mean differences of the respective measurement method is shown in Table For the three methods of blood pressure measurement, the standard deviation of mean differences reveals that home BP shows the least variability both for systolic and diastolic BP. The reproducibility of systolic and diastolic home BP was significantly higher than the reproducibility of office BP  and the reproducibility of 24-h ABPM . The reproducibility of systolic and diastolic office and 24-h ABPM was not significantly different .The squared differences for office, home BP and the 24-h ABPM was analyzed as a further parameter for appraising the reproducibility of the different methods of BP measurement. The results are shown in figure The results for reproducibility did not change, if a separate analysis was performed for treated or untreated patients.The correlation coefficient of the BP parameters of different methods of measuring BP with the left ventricular mass index is shown in figure For each blood pressure measurement method the number of patients needed to detect a two-sided α risk of 5% and a statistical power of 80% a systolic and diastolic blood pressure difference of 5 mm Hg is shown in table In the present study, it could be shown that home BP measurements at the wrist using a validated instrument with activated position sensor show very much better reproducibility not only compared to conventional office BP measurements, but also compared to standardized 24-h ABPM. Moreover, the coefficients of correlation with left ventricular mass index as an indirect parameter of hypertensive end organ damage were comparable with those of home BP recently carried out on the upper arm and did not differ significantly from those of 24-h ABPM.As shown by earlier studies, the reproducibility of BP measurements can be substantially increased by 24-h ABPM compared to office BP ,2,11. HoAlso in the present study, for each BP measurement method, we have calculated the number of patients needed to detect a two-sided α risk of 5% and a statistical power of 80% to detect a systolic and diastolic blood pressure difference of 5 mm Hg table . The resThe present study was carried out with a validated wrist blood pressure instrument with an activated position sensor -19. AccoThe standard deviations for the mean differences are between 5 and 8 mmHg systolic and 4 and 6 mmHg diastolic for home BP with upper-arm instruments. A recently published study of Stergiou demonstrated that the reproducibility was indeed even better with a newer validated upper-arm instrument with digital print-outs and standardized measurement than with a standardized 24-h ABPM [The absolute number of values measured does not provide a cogent explanation for the better reproducibility of home BP, since both in the first and in the second week an average of 31 ± 7 and 31 ± 9 measurement values were obtained of home BP as compared to 52+8 and 51 ± 8 measurement values in 24-h ABPM. It is more likely that the largely standardized wrist measurement with automatic recording of the values measured, activated position sensor and measurements and defined times of day have contributed to the very good reproducibility. Moreover, fluctuations in BP which are not seen in 24-h ABPM but might contribute to a raised variability are also detected over a week with home BP. In our investigation, we have also deliberately included the first day of home BP in the analysis, since the patients were already familiar with the instrument as a result of prior thorough instruction in self-measurement at the wrist. However, the inclusion of the first day in the measurement analysis did not affect the reproducibility owing to the large number of measurements.Besides the reproducibility, the correlation of the different methods of BP measurement with hypertensive end organ damage measured with the left ventricular mass index was also investigated in the present study. According to the study results available so far, the 24-h ABPM shows correlation coefficients with the left ventricular mass index of 0.52 for systolic and 0.46 for diastolic values ,25,26. SIn this study, we attempted to include as large as possible a spectrum of BP values in the range between optimal BP values and hypertension of severity grade III. For this purpose, we considered it necessary also to include in the investigation patients under antihypertensive treatment who were referred to our hospital because of hypertension that was refractory to treatment. However, since the antihypertensive medication remained unchanged over the investigation period in all patients, an effect on one of the methods of BP measurement would not have been expected.The present study did not address the question whether home BP measurement with a wrist device with position sensor is more or less reproducibile compared to an upper arm device. In our view, the study design for such a study would be very difficult to handle. Therefore, this question may be evaluated in future studiesFurthermore, it was not our purpose to advocate the general use of wrist devices. Such devices have physiological limits with regards to accuracy and only devices with a position sensor may be considered for clinical use . Even thTo summarize, the present study showed that the wrist measurement of home BP with a validated system comprising an activated position sensor was superior in respect of reproducibility both to office BP and 24-h ABPM. Moreover, a correlation of the wrist measurement with hypertensive end organ damage similar to that with 24-h ABPM was revealed. Although wrist devices have to be used cautious and with defined limitations, the use of validated devices with position sensor according to recently recommended measurement schedules  might haThis study was supported by Omron Company, Japan.The article-processing charge will be financed by Omron CompanyAll authors declare that they have no competing interestsSU conceived of the study and its coordination, performed the echocardiography, RF performed the statistical analysis. MB recruited the patients, supplied blood pressure measurements. GN drafted the manuscript, TM evaluated the echocardiography and drafted the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Increased arterial stiffness is associated with mortality in patients with chronic kidney disease. Cardiovascular magnetic resonance (CMR) permits assessment of the central arteries to measure aortic function.We studied the relationship between central haemodynamics and outcome using CMR in 144 chronic kidney disease patients with estimated glomerular filtration rate <15 ml/min . Aortic distensibilty and volumetric arterial strain were calculated from cross sectional aortic volume and pulse pressure measured during the scan.Median follow up after the scan was 24 months. There were no significant differences in aortic distensibilty or aortic volumetric arterial strain between pre-dialysis and dialysis patients. Aortic distensibilty and volumetric arterial strain negatively correlated with age. Aortic distensibilty and volumetric arterial strain were lower in diabetics, patients with ischaemic heart disease and peripheral vascular disease. During follow up there were 20 deaths. Patients who died had lower aortic distensibilty than survivors. In a survival analysis, diabetes, systolic blood pressure and aortic distensibilty were independent predictors of mortality. There were 12 non-fatal cardiovascular events during follow up. Analysing the combined end point of death or a vascular event, diabetes, aortic distensibilty and volumetric arterial strain were predictors of events.Deranged vascular function measured with CMR correlates with cardiovascular risk factors and predicts outcome. CMR measures of vascular function are potential targets for interventions to reduce cardiovascular risk. Premature cardiovascular disease is the leading cause of death in patients with end stage renal disease (ESRD) treated with dialysis. The relationship between cardiovascular (CV) risk factors and CV events is less clear in ESRD than in the general population, with paradoxical relationships between both cholesterol and blood pressure and CV risk,2. The pTo date however, the relationship between aortic distensibilty (AD), as measured with CMR and long term outcome has not been assessed. Thus, we assessed the relationship between CMR measures of vascular function and conventional CV risk factors in ESRD patients and studied the long term prognostic implications of CMR measures of vascular function.Studies were performed on 144 patients with chronic kidney disease (CKD) stage 5. All patCMR was performed using a 1.5 Tesla MR scanner . In haemodialysis patients imaging was performed on the post-dialysis day whereas peritoneal dialysis patients were studied at their "dry weight". Aortic volume was acquired from cine CMR images in the transverse plane of the ascending aorta, obtained at the level of the main pulmonary artery, using a steady-state free precession (true FISP) sequence, TR = 3.2 ms, TE = 1.6 ms, FA = 60°, FoV 276 × 340 mm, pixel dimensions 2.3 × 1.3 mm, slice thickness = 7 mm  mass and function were measured using a true FISP sequence to acquire cine images in long axis planes  followed by sequential short axis LV cine loops  from the atrio-ventricular ring to the apex. LV mass index (LVMI) was calculated by normalising LV mass to the body surface area. Overall, scan time was approximately 30 minutes.All CMR analyses were performed using conventional analysis software . Cross sectional aortic contours were defined by manual planimetry throughout the cardiac cycle, with resulting aortic volume defined as the measured cross sectional area multiplied by the slice thickness. This calculation was performed automatically by the analysis program.Aortic distensibilty (AD) was calculated from change in aortic volume and simultaneous brachial blood pressure using the formula:max and (Aortic volume)min are the maximal and minimal calculated aortic volumes during the cardiac cycle. Additionally, aortic volumetric arterial strain (VAS), which is non-pressure dependent, was calculated from the formula:where (Aortic volume)As a ratio of change in aortic volume, VAS does not have any units.All patients underwent conventional cardiovascular risk factor assessment including history, clinical examination, ECG as well as routine haematology, biochemical, and lipid profile. A history of ischaemic heart disease (IHD) was defined as previous clinically documented myocardial infarction/angina pectoris or previous coronary revascularisation procedure. Peripheral vascular disease was defined by clinically documented intermittent claudication with prior consultation by a vascular surgeon or the need for a previous peripheral vessel revascularisation procedure. Blood was drawn at the time of scanning for lipids and C – reactive protein, with other haematological and biochemical parameters  assessed from the mean of readings taken on the three consecutive months preceding the scan.Follow up data was collected from date of the CMR scan using electronic patient records. Death and cardiovascular events  were collected as end points.Correlations between cardiac dimensions, measures of arterial function and continuous clinical variables were assessed with Pearson and Spearman co-efficients. Differences between groups were tested by student's t-test and Mann-Whitney-U test. Measures of vascular function were compared between patients who died or had a vascular event during the follow up period with these measures divided into tertiles or quartiles and subjected to an unadjusted survival analysis by the Kaplan-Meier method. Statistical significance was determined by the log-rank test. Cox survival analysis was performed to assess the influence of multiple variables on outcome. Variables identified as possibly influential on outcome by univariate analysis were then entered into a forward stepwise regression model. As exponential values logarithmic transformation was used for AD and VAS values to simplify interpretation of values in the regression analyses. Analyses were performed using SPSS 13.0 software package .Patient demographics at the time of scan are shown in Table All scans were analysed by a single observer (P.B.M). No significant differences in patient demographics or vascular function were exhibited between patients with advanced renal failure not yet on dialysis therapy  and those established on dialysis (110 patients) and therefore patients were combined as a single group. AD and VAS demonstrated a negative correlation with age .-3 vs. non-diabetics 2.8 × 10-3 mmHg-1, p = 0.001; VAS 0.11 vs. 0.15, p = 0.001), patients with a history of ischaemic heart disease  or peripheral vascular disease . No significant differences in AD or VAS were demonstrated between patients treated with statins or requiring antihypertensive therapy. There were no significant differences between AD between dialysis modalities. 58 patients (40.3%) had a functioning arteriovenous fistula or graft at the time of scanning. There were no significant differences in AD or VAS between patients with an arteriovenous fistula or graft and those without.There were no significant correlations between haemoglobin, dialysis adequacy , time on dialysis, lipid parameters, C-reactive protein, calcium, phosphate or calcium phosphate product and AD or VAS. There were no significant differences in AD or VAS between genders. AD and VAS were reduced in patients with diabetes mellitus  and end systolic volume  but no other LV dimension. Aortic VAS correlated with markers of cardiac function – left ventricular ejection fraction  and stroke volume .Follow up data were available for all 144 patients. Overall survival data was analysed for the whole cohort including analyses of the relationship between VAS and outcome. For analyses of the relationship between AD and outcome, only the 120 patients who only results of AD available were studied. The median follow up period was 719 days (interquartile range 375 days). There were 20 deaths, giving an overall mean death rate of 76.2 per 1000 patient years. Patients who died had significantly lower AD than those who where alive at the end of follow up. There were no significant differences in VAS between survivors and patients who died. Patients who died had significantly higher systolic and pulse pressure than survivors . These patients had significantly lower AD and VAS than those who remained event free , VAS  and higher systolic blood pressure  and pulse pressure  than those who did not. There were no significant differences in diastolic blood pressure  between those who reached the combined end point and those who did not.Combining death with non fatal CV events as a combined CV end point, patients who reached this combined end point had significantly lower AD  -22. OtheAside from the issue of use of brachial blood pressure to calculate central haemodynamics, our study has some other limitations. Although direct comparison between CMR and calcification is not possible, CMR has emerged as a technique for imaging atheroma. A direct comparison between vascular function and dark blood imaging looking at aortic wall thickness and atheroma would be of interest but unfortunately was not performed. Measurement of AD is still a relatively novel technique and its widespread reproducibility is yet to be established. In house blinded analysis has demonstrated an inter-observer variability of 4.6%, although this needs to be reproduced in other centres, particularly as there are potential sources of error in both data acquisition and analysis as well as in blood pressure measurements. As we have previously used CMR with late gadolinium enhancement (LGE) to analyse myocardial tissue composition in ESRD, it woulThis study has demonstrated that vascular function can be measured using CMR in ESRD. Increased aortic stiffness, indicated by reduced AD and reduced VAS are associated with risk factors for CV disease. Both AD and VAS were independent predictors of combined vascular events and mortality. AD predicted all cause mortality. Therefore, CMR offers a novel non-invasive tool to assess vascular function in patients ESRD. AD and VAS are potential targets for therapeutic intervention to reduce cardiovascular risk in ESRD.The authors declare that they have no competing interests.Guarantor of integrity of entire study PBM, study concepts/study design PBM, AD, KGB, TS, JEF, HJD, AGJ data collection and analysis PBM, AD, KGB, RKP, RAPW, TS, JE, AGJ, statistical analysis PBM, RKP, AGJ, manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors.


Rationale. The goal of antihypertensive treatment is to reduce risk of cardiovascular morbidity and mortality. Apart from blood pressure lowering per se, also reducing the activities of the renin-angiotensin system and sympathetic nervous system appears to be important. Angiotensin II receptor blocker drugs (ARBs) have provided a useful class of anti-hypertensive drugs. Eprosartan is a relatively new ARB which is chemically distinct  from all other ARBs (biphenyl tetrazoles). An analysis has been made on available experimental and clinical data on eprosartan which not only is an effective and well tolerated antihypertensive agent, but also lowers the activities of the renin-angiotensin system and sympathetic nervous system. Experimental and pharmacokinetic studies on eprosartan have shown differences with the other ARBs. The distinct properties of this non-biphenyl, non-tetrazole ARB might be relevant in the effort to reduce cardiovascular risk, also beyond its blood pressure lowering capacity.                      The purpose of treating patients with increased cardiovascular risk is to reduce that risk. It is well established that blood pressure lowering per se substantially reduces cardiovascular risk. Both the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) play an important role in the pathogenesis of various forms of hypertension. Independent of their effect on blood pressure, these systems also contribute to the pathophysiology of both structural and functional cardiovascular abnormalities. As a consequence, counteracting the mechanisms involved in the pathogenesis of cardiovascular organ damage is also important, independent of any direct blood pressure lowering effect.1). These therapies also appear to have sympatholytic properties, which may be particularly important in determining the efficacy of these agents in reducing cardiovascular risk, since there is abundant evidence that sympathetic hyperactivity is associated with poor clinical outcome.There is conclusive evidence that the RAS and SNS systems do not operate independently, but that there are multiple interactions on different levels of the cardiovascular system. It is well established that angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) reduce the effects of angiotensin II Fig. . Further, angiotensin II exerts inhibitory effects on baroreflex modulation of the heart rate and sympathetic drive. The idea that AngII directly stimulates centrally originated sympathetic outflow in humans was tested in an elegant study. Intravenous infusion of AngII raised blood pressure and suppressed muscle sympathetic nerve activity. But during simultaneously infusion of nitroprusside to control blood pressure rise, MSNA increased. An identical experiment with phenylephrine infusion showed no effect on MSNA [RAS/SNS interactions appear bi-directional and occur at different sites in the chain of events leading to angiotensin II and noradrenaline release, the two major transmitters of these two systems . There iVarious pathological conditions are associated with hyperactivity of both the RAS and SNS systems, including hypertension, heart failure, kidney disease, hypertension associated with obesity and obstructive sleep apnea syndrome amongst others. In the majority of these conditions both the RAS and the SNS are activated. Because circulating renin is  exclusively produced by the kidneys, it is logical to question how the kidneys might contribute to the increased activities of the two pressor systems in the above-mentioned conditions. The precise role of a local i.e. tissue RAS is much more difficult to quantify and evaluate. Experimental studies have shown several pathophysiological mechanisms through which the diseased kidneys can be involved. Inappropriate renin secretion in relation to the state of sodium-volume balance has long been recognized. In humans, intravenous infusion of angiotensin II stimulates central sympathetic outflow.via the afferent renal nerves to the central nervous system Fig. (3). Renal ischemia can lead to sympathetic activation. During renal ischemia, adenosine is released and adenosine evokes an increase in afferent renal nerve traffic, as can be shown during adenosine infusion in the renal artery of uninephrectomized dogs. Even a small injury in one kidney caused by intrarenal injection of phenol, which does not affect glomerular filtration rate, leads to hypertension in association with an increased central sympathetic activity. In these animal models renal denervation results in a reduction or total prevention of hypertension. Additionally, in the phenol hypertension model nephrectomy of the injured kidney several weeks after the induction of renal damage results in normalisation of blood pressure. Thus kidney injury in experimental conditions can lead to sympathetic hyperactivity and hypertension and this hyperactivity is associated with activation of renal afferent nerves. The signal from the diseased kidneys travels 3). Given the importance of sympathetic activity in determining cardiovascular morbidity and mortality, it is important to quantity the ability of agents that affect the RAS to reduce sympathetic activity.Some forms of essential hypertension, hypertension associated with chronic kidney disease, renovascular hypertension, heart failure, and obesity/metabolic syndrome are all associated with both an activated RAS and an activated SNS. Agents that interfere with the RAS are particularly effective in reducing sympathetic activity when the RAS is activated. The apparent marked parallelism in the activities of these two systems may be interpreted as indicating a cause and effect relation or a common origin, i.e. kidney ischemia Fig. (4). The antagonistic properties of eprosartan on the angiotensin II receptor type 1 (AT1) have been extensively documented [Eprosartan is chemically-distinct from the other ARBs in its class , 4. It icumented . Unlike 2). Consequently, ARBs can block this stimulatory effect of angiotensin II at these different levels. The effects of eprosartan on sympathetic activity have been studied in experimental conditions. Eprosartan induces dual blockade of angiotensin II receptors both pre- and post-synaptically Fig. (2). Importantly, it has been shown that eprosartan crosses the blood-brain barrier, which pro-bably contributes to its antihypertensive efficacy [et al. [et al. [et al. [et al. [Angiotensin II may stimulate the SNS on various levels Fig  presented similar reductions during eprosartan (600 mg od) and atenolol (50 mg od) in peripheral blood pressure after 6 weeks. Both agents reduced central systolic pressure, albeit eprosartan more so than atenolol, but only eprosartan reduced wave reflections. Central pressures more closely relate to clinical outcome than peripheral pressures, suggesting an advantage of eprosartan over atenolol . These fet al. showed that in mild to moderate essential hypertension ARB treatment  did not affect muscle sympathetic nerve activity, which is the centrally originated postganglionic sympathetic activity [In patients with mild hypertension and type 2 diabetes once daily eprosartan (600 mg od) and telmisartan (40 mg od) were equally effective in reducing blood pressure during a 12 months study . Obesityactivity . There is clear evidence that chronic renal disease is often characterised by the presence of sympathetic hyperactivity and that sympathetic activity is associated with poor cardiovascular outcomes in chronic renal failure patients -30. It iCurrent evidence suggests there is no accumulation of eprosartan at the recommended dose of 600 mg, regardless of renal function. Chronic treatment (> 6 weeks) with enalapril (20 mg od) and losartan (100 mg od) significantly reduced but do not normalized muscle sympathetic nerve activity in patients with hypertensive chronic renal failure , 33. Epret al. [et al. [Experimental studies with eprosartan suggest that it might have a benefit in the prevention or delay of renal damage in hypertensive patients with renal impairment , 35. Fraet al.  showed t [et al.  noted anIsolated systolic hypertension is the most common form of hypertension in the elderly , 39. Epret al. study, eprosartan (600 mg od for 16 weeks) in the primary care setting was well tolerated and effective in over 600 patients (mean age 63 y) in reducing blood pressure  as well as pulse pressure . Also the pulse pressure / mean arterial pressure ratio decreased  [In the ETAPA (Estudio de la Efectividad del Tratamiento antihipertensivo sobre la Presion de Pulso en adultos) study from Spain involving approximately 4,000 hypertensive patients (mean age 67 y), eprosartan (600 mg) alone (87%) or in combination with a diuretic decreased systolic, diastolic and mean  blood pressure in hypertensive patients and was associated with a reduction in pulse pressure / mean blood pressure ratio  . Also in< 0.001) .The MOSES study  is a large, prospective, randomised outcome study comparing the addition of 600 mg eprosartan or 10 mg nitrendipine to existing therapy in patients with a history of proven stroke or transient ischaemic attack . BackgroAlthough different in terms of structure and mode of action, eprosartan has, to date, been seen as one of many sartans. Ongoing studies are now focusing in other areas where reduction of sympathetic activity might be expected to show benefit. The STARLET study (Stress-induced Hypertension at the Workplace) will examine the prevalence of ‘job-strain’ hypertension and cardiovascular outcomes. Job-strain hypertension is defined as a difference of at least 5mm diastolic blood pressure and/or 8mm Hg systolic blood pressure between work and weekend mean daytime ambulatory blood pressure. First results show that eprosartan effectively reduced blood pressure .The OSCAR study will be a long-term, open-label, study examining the effects of eprosartan-based therapy (600 mg od) on systolic blood pressure and cognitive function. Results from this study are also awaited with interest , 53. The goal of antihypertensive treatment is not only to lower blood pressure but also to reduce risk of cardiovascular morbidity and mortality. It is important not only to quantify the blood pressure lowering effect of antihypertensive compounds, but also to assess their ability to counteract mechanisms involved in the pathogenesis of cardiovascular morbidity and mortality, such as the hyperactivities of the renin-angiotensin system and the sympathetic nervous system. Eprosartan is an effective antihypertensive agent and clearly belongs to the class of ARBs, reversing effects of the renin and the sympathetic system. Experimental and pharmacokinetic studies have shown differences with the other ARBs. Since direct comparison of effects of eprosartan and other ARBs on meaningful clinical endpoints is not available, the clinical relevance of these differences has to be judged as unclear.


To report the outcome of children with life-threatening asthma (LTA) admitted to a university Pediatric Intensive Care Unit (PICU).Retrospective study between October 2002 and May 2010 was carried out. Every child with LTA and bronchospasm was included.2 levels  and longer PICU stay  The majority of patients received systemic corticosteroids, intravenous or inhaled bronchodilators. There was one pneumothorax but no death in this series.30 admissions of 28 patients  were identified which accounted for 3% of total PICU admissions (n = 1033) over the study period. The majority of patients were toddlers (median age 3.1 years). Few had past history of prematurity, lung diseases, or neuro-developmental conditions. Approximately half had previous admissions for asthma and one-forth with history of non-compliance to recommended treatment for asthma. One patient had parainfluenza virus and one had rhinovirus isolated. None of these factors were associated with need for mechanical ventilation (n = 6 admissions). Comparing with patients who did not receive mechanical ventilation, ventilated children had significantly higher PIM2 score , higher PCOLTA accounted for a small percentage of PICU admissions. Previous hospital admissions for asthma and history of non-compliance were common. Approximately one quarters required ventilatory supports. Regardless of the need for mechanical ventilation, all patients survived with prompt treatment. Asthma is a very common childhood condition worldwide and in Hong Kong. Acute asthmatic attacks cause significant morbidity and account for a significant number of emergency department consultations and hospital admissions-4. Most 2 or Fisher exact test. All comparisons were made two-tailed, and p-values less than 0.05 considered statistically significant.We retrospectively reviewed the medical records and analyzed data from all children with LTA admitted to the PICU of a tertiary care university hospital  in Hong Kong during the period October 2002 and May 2010. LTA was defined as all children with asthma who required ICU admission and care. The initial diagnosis was made clinically by the admitting physicians. Final diagnosis was confirmed on chart review and subsequent evaluations. The hospital provides PICU care to a catchment population of approximately 1.1 million. The following data were collected: age, sex, duration of admission, treatment of the LTA, clinical condition, blood gases, the incidence of barotrauma, and outcome. Respiratory viruses and bacterial pathogens were routinely screened for by standard examination of nasopharyngeal aspirate and cultures. The Pediatric Index of Mortality 2 (PIM2) score based on admission data was used as severity score. NumericThere were 30 admissions  and longer PICU stay  but no differences in other factors evaluated in Table In terms of risk factors, 'smoker(s) at home' were present in 5 of the admissions, 'history of atopy in 1 st degree relative' in 11 admissions, and 'personal history of atopy' in 20 admissions. Few had past history of prematurity (n = 4 admissions), lung diseases , neuro-developmental condition . Half had previous admissions for asthma and one-fourth with history of non-compliance to recommended treatment for asthma. In the ventilated group, three patients were on inhaled corticosteroid but compliance to corticosteroid was reportedly poor in two. In the non-ventilated group, 9 patients were on inhaled corticosteroid. One patient also received oral montelukast. Poor-compliance to asthma management was reported in 5 patients. One patient had parainfluenza virus and one had rhinovirus isolated. None of these factors were associated with need for mechanical ventilation which was required in 6 patients. Ventilator modes included Synchronized Intermittent Mandatory Ventilation (SIMV) or Pressure Regulated Volume Control mode (PRVC), with low Positive End-Expiratory Pressure (PEEP) and low inspiratory to expiratory (I:E) ratios. Comparing with patients who did not receive mechanical ventilation, ventilated children had significantly higher PIM2 score , higher first PaCOAsthma is a common disease and its frequency of occurrence sometimes detracts from its potential seriousness. Severe 2 retention. LTA can be associated with metabolic acidosis, which reduces the effectiveness of ß-agonists[Status asthmaticus is severe asthma that does not respond well to immediate care and is a life-threatening medical emergency. Ensuing-agonists. In a pr-agonists. In seve-agonists. Mechani-agonists. Noninva-agonists.One of the clinical problems facing pediatric intensivists is the differentiation between viral and bacterial infections when an acutely ill child with LTA is admitted. Empirical course of antibiotics were often used in the initial management in order to avoid missing any treatable bacterial co-infections. Rapid diagnosis of respiratory viral infections in children is important because prompt diagnosis may result in significantly reduced antibiotic use and unnecessary strict isolation for respiratory viruses. In this study, there was no bacterial isolation and viral co-infection was only found in two cases (parainfluenza and rhinovirus).Status asthmaticus is one of the most common causes of admission to a pediatric intensive care unit (PICU). There have been published data examining the complications associated with the treatment of status asthmaticus in children in the PICU. In one study of children admitted to PICU, there was a 22% complication rate, increased by intubation. The risNear-fatal asthma continues to be a significant problem despite the decline in overall asthma mortality. Two distinctive phenotypes of near-fatal asthma have been identified: one with eosinophilic inflammation associated with a gradual onset and a slow response to therapy and a second phenotype with neutrophilic inflammation that has a rapid onset and rapid response to therapy. In stable condition, near-fatal asthma frequently cannot be distinguished from mild asthma. Diminished perception of dyspnea plays a relevant role in treatment delay, near-fatal events, and death in patients with severe asthma. Reduced compliance with anti-inflammatory therapy has also been associated with fatal or near-fatal asthma. The sudprn-basis and had been asymptomatic for a number of months, but some were non-compliant to prescribed therapy. The limitation of this study is the small sample size and there was high chance of type II error with regard to different parameters studied.Approximately one third of patients were on maintenance inhaled corticosteroid; many of these patients were on inhaled salbutamol on a 2 and longer PICU stays. Regardless of the need for mechanical ventilation, all patients survived with prompt treatment, and only required brief PICU stays.In conclusion, LTA and bronchospasm accounted for a small percentage of PICU admissions following initial stabilization at the emergency department. Approximately 20% required ventilatory supports. Ventilated patients appeared to have higher PIM2 severity score, higher PCOThe authors declare that they have no competing interests.KLH is the principal author, WSWT is involved with data review, TFL provides statistical assistance, KLC is involved in patient care and provides inputs and audit for the manuscript, PCN is involved in review of the manuscript. All authors read and approved the final manuscript.


Once-daily phosphodiesterase type-5 (PDE5) inhibitors improve both sexual function and vascular measures of cavernous arteries by improving surrogate markers of endothelial dysfunction, that is, plasma endothelin-1 and adrenomedullin levels, which may play a potential role in preventing progression of penile fibrosis and ED. Also, the beneficial effect of long-term PDE5i add-on therapy to SSc therapy in the treatment of Raynaud's phenomenon is described.Systemic Sclerosis (SSc) is a connective tissue disorder featuring vascular alterations and an immunological activation leading to a progressive and widespread fibrosis of several organs such as the skin, lung, gastrointestinal tract, heart, and kidney. Men with SSc are at increased risk of developing erectile dysfunction (ED) because of the evolution of early microvascular tissutal damage into corporeal fibrosis. The entity of penile vascular damage in SSc patients has been demonstrated by using Duplex ultrasonography and functional infra-red imaging and it is now clear that this is a true clinical entity invariably occurring irrespective of age and disease duration and constituting the ‘‘ Systemic Sclerosis (SSc) is a connective tissue disorder featured by vascular alterations and immunological activation leading to progressive and widespread fibrosis of several organs such as skin, lung, gastrointestinal tract, heart, and kidney , 2. The sclerodermic penis”. In fact, the prevalence of ED in men with SSc has been reported as high as 80% [ Similarly, at the penile level, there occurs a consistent vascular damage that almost invariably determines, as a consequence of both endothelium damage –16 and ih as 80%  and it cβ1), platelet-derived growth factor (PDGF) and its receptors are overexpressed in the corpora cavernosa [β1 and PDGF have both been identified as important regulators of the collagen and extracellular matrix synthesis by smooth muscle cells and also act as smooth muscle mitogens. Under hypoxic conditions, human penile smooth muscle cells also release ET-1 and induce ET-B receptor expression, processes that in turn are strongly increased by TGFβ1 and ET-1 itself [Hormonal derangement is a common finding in SSc patients even if a hormonal basis for impotence, that is, abnormalities in serum testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, and oestradiol, has never been demonstrated. Neurological causes could also be excluded. In contrast, penile blood pressure, but not ankle blood pressure indices, were found to be diminished . Duplex avernosa . TGFβ1 a1 itself . These r1 itself . The hyp Contradictory attitudes exist about the mechanisms of the vasospastic arteriolar paroxysms—from hyperactivity of the sympathetic nervous system and “local defect” with receptor and nerve endings' dysfunctions, endothelial dysregulation and blood cells' activation to statements of primary central nervous mechanism. The venoarteriolar reflex is a local mechanism protecting the capillary bed against high hydrostatic pressure and therefore the tissue against edema. The underlying mechanism of the venoarteriolar reflex is still debated, although it is commonly believed to depend on an intact innervations of the arterioles by sympathetic vasoconstrictor fibers . The modThe diagnosis of scleroderma is not always easy. If scleroderma is suspected, tests should be ordered to confirm the diagnosis, as well as to determine the severity of the disease. Major body changes determined by SSc are often responsible for increased morbidity and mortality, and may contribute to the occurrence of psychological disturbances such as anxiety and depression, whereas the incidence of psychotic symptoms is very low in SSc patients . It is kED should always be investigated with appropriate questionnaires and dynamic penile Duplex ultrasound. In fact, penile vascular damage occurs in almost all SSc patients, regardless of clinical symptoms and we have suggested that investigation of these patients with Duplex ultrasound is mandatory for documenting the degree of vascular involvement since the self-administered International Index of Erectile Function questionnaire does not often match with vascular findings . In addisclerodermic penis”. With the progression of micromacrovascular damage in the natural course of the disease, a concomitant penile fibrosis and venocclusive dysfunction occur leading to difficult-to-treat ED.  After careful review of clinical and instrumental data already published in our previous papers, we suggest that there is a relationship between ED and SSc vascular damage evaluated by capillaroscopic pattern and vascular domain of Medsger Disease Severity Scale (DSS) . In our  For these reasons, a multidisciplinary approach to SSc patients would involve the rheumatologist, the uro/andrologist and the psychiatrist to comprehensively evaluate all diagnostic aspects.The treatment of ED in SSc suggest to modify or revert risk factors for ED, including lifestyle, psychological or drug-related factors, but such treatments are often unsatisfactory and limited by frequent side effects in the long-term. Three different phosphodiesterase type-5 (PDE5) inhibitors are currently available: sildenafil, vardenafil and tadalafil. Several randomized trials have demonstrated the efficacy of this class of medications, but there are no compelling data to support the superiority of one PDE5 inhibitor over another in non-SSc patients. The three PDE5 inhibitors share many pharmacological and clinical characteristics. Initial studies involving animal models, data from open-label, uncontrolled trials involving patients with pulmonary arterial hypertension, and a small randomized, controlled studies involving patients with idiopathic pulmonary arterial hypertension suggest that PDE5 inhibitors are beneficial in the treatment of pulmonary arterial hypertension –33. Rece In the era of PDE5 inhibitors, we believe that the implantation of a penile prosthesis may be considered only in patients who fail pharmacotherapy or who prefer a permanent solution of their problem. The choice of prosthesis is depends from patients' preference and his manual dexterity. This solution may have an high satisfaction rate as in the non-SSc population but must take into account that it is not reversible. Finally, mechanical failures and infection has the same occurrence (1%–3%) than the general population .Long-standing SSc is almost always associated with the presence of some degree of ED, because of micro and macrovascular disseminated damage through cavernosal penile arteries and capillaries and subsequent cavernosal fibrosis. As a consequence, ED should be systematically questioned and counselled in any patient presenting with SSc by a specialized team. Although robust data on treatment options for ED in the SSc population are not yet available, empirical treatment should be started with a daily or alternate day regimen of a long-acting PDE5i after addressing modifiable risk factors for ED. Second-line treatment decisions require the cooperation between expert specialists in order to maximize medical therapy benefits for underlying conditions.


In vivo and in vitro evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans.We hypothesised that a low-dose adenosine infusion could reduce the ischemic burden evoked by physical exercise and improve the regional left ventricular (LV) systolic function.We studied nine severely symptomatic male patients with severe coronary artery disease. Myocardial ischemia was induced by exercise on two separate occasions and quantified by Tissue Doppler Echocardiography. Prior to the exercise test, intravenous low-dose adenosine or placebo was infused over ten minutes according to a randomized, double blind, cross-over protocol. The LV walls were defined as ischemic if a reduction, no increment, or an increment of < 15% in peak systolic velocity (PSV) was observed during maximal exercise compared to the baseline values observed prior to placebo-infusion. Otherwise, the LV walls were defined as non-ischemic.P = 0.0001) and low-dose adenosine infusion (P = 0.0009). However, in the ischemic walls, PSV increased only during low-dose adenosine infusion (P = 0.001), while no changes in PSV occurred during placebo infusion (P = NS).PSV increased from baseline to maximal exercise in non-ischemic walls both during placebo (Low-dose adenosine infusion reduced the ischemic burden and improved LV regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia, confirming that adenosine is a potential preconditioning agent in humans. Ischemic preconditioning protects the heart through brief episodes of ischemia and renders the myocardium resistant to subsequent ischemic insults. The potential beneficial effects of ischemic preconditioning include the preservation of the left ventricular (LV) systolic and diastolic functions, the prede novo protein synthesis[ATP channels either on the cardiac sarcolemmal or mitochondrial membrane [Ischemic preconditioning is triggered by the binding of several humoral factors such as adenosine, bradykinin, and opioids to their cardiac receptors,4, theresynthesis,4. The mmembrane -7.The aim of this study was to explore whether low-dose adenosine infusion exerts an ischemic preconditioning effect in severely symptomatic patients with advanced coronary artery disease.We studied nine male patients, mean age 74 years, (range 58-79 years), with severe coronary artery disease (eight with three-vessel and one with two-vessel disease) and severely symptomatic . Except for one patient who had dynpnea, the rest suffered from daily angina. Eight of the patients underwent later coronary bypass grafting (CABG) and one patient with earlier CABG underwent percutanous coronary intervention. All patients had normal global LV systolic function at rest except for one patient who had mildly depressed global LV systolic function (LV ejection fraction ≈ 45%). Three patients had a history of myocardial infarction, three had a history of systemic arterial hypertension, three had a history of paroxysmal atrial fibrillation, three had a mild form of chronic renal failure, and none had a history of diabetes mellitus. All patients were treated with aspirin, beta-blockers, long acting nitrates and calcium channel blockers and seven with either angiotensine converting enzyme inhibitors or angiotensine II receptors blockers.We obtained a baseline two-dimensional echocardiography with superimposed Tissue Doppler Echocardiography (TDE) images using a multi-Hertz transducer with commercially available equipment  for all patients prior to bicycle exercise stress echocardiography test. Standard parasternal short and long axis views, as well as apical two, three, and four chamber views, were digitized during three consecutive cardiac cycles in cine loop format for off-line analysis.The patients underwent two separate exercise stress echocardiography test in semi-supine position on a specially designed, table-mounted bicycle ergometer. The initial workload was 25 Watts with increments of 10 Watts added every minute. At each stage, the heart rate, systolic blood pressure, and a 12-lead ECG were recorded. We obtained standard echocardiographic images of five consecutive cardiac cycles containing TDE information at rest, sub-maximal workload , maximal workload, and recovery phases (one to two minutes after the exercise); all measurements were digitally recorded and stored. Stopping criteria for exercise test was either severe chest pain or achieved 85% of maximal expected heart rate (220-age).An intravenous infusion of either low-dose adenosine (35 μg/kg/min) or placebo  was given in a double-blind fashion over 10 minutes prior to the start of the exercise test. The order of the drug administration was randomly selected and the sequence of infusions was inverted on the second occasion; the first and second occasions occurred at least one day apart, median 3 days (range 1 to 5 days)  blinded to the sequence of drug administration. However, the images corresponding to each stage of the protocol were known as the heart rate at rest and at peak exercise were clearly discernible. A sample volume was positioned on the region of interest at the basal segment of the four LV walls  to obtain a myocardial velocity profile Figure . We analIn order to assess the LV regional systolic function and to detect the presence of regional myocardial ischemia, the LV walls were categorized as ischemic or non-ischemic: a LV wall was defined as ischemic if a reduction, no increment, or an increment of <15% in PSV, was observed during maximal work load compared to baseline preceding placebo-infusion; otherwise, the LV walls were defined as non-ischemic.Data are presented as mean ± standard deviation (SD). Statistical comparisons were performed by analysis of variance (ANOVA) with repeated measures. Post hoc comparisons between groups were performed using the Tukey test.The local Ethics Committee at the Karolinska University Hospital, Huddinge, approved the study. All participants gave written informed consent.There were no significant differences in maximal work capacity, hemodynamic parameters including heart rate and blood pressure or ST-depression Table . We obseAccording to the pre-defined criteria, 12 of the 36 LV walls in the nine patients were found to be ischemic during the placebo infusion. When milder criteria were used to define LV wall ischemia, i.e. a reduction, no increment, or an increment of <25% in peak systolic velocity, 15 of the 36 LV walls were found to be ischemic.P < 0.001; Figure In the ischemic walls, the increment in PSV was higher during adenosine infusion as compared to placebo (In this study, a low-dose infusion of adenosine preserved the regional systolic function of LV walls subjected to an exercise-induced ischemic burden. We observed a higher PSV at peak exercise in LV walls rendered ischemic during adenosine infusion than during placebo infusion, suggesting a preconditioning effect of adenosine. The main idea of the study was to investigate the possible preconditioning effect of adenosine infusion in a quantitative manner and thus avoiding any possible bias induced by subjective analysis of wall motion analysis. Therefore, we did not use wall motion score in the diagnosis of myocardial ischemia. The concordance between wall motion core and tissue Doppler imaging in this respect has been reported elsewhere . Having Alternative mechanisms for preserving the regional systolic function may have been achieved by adenosine-mediated vasodilatation or by the possible unloading effects of adenosine; however, these are unlikely mechanisms because myocardial ischemia would already have caused maximal vasodilatation and the low-dose adenosine infusion was stopped before the exercise stress test, by which time any previously infused adenosine would have been metabolised and could not have had a vasodilatory effect. In addition, heart rate and blood pressure responses did not differ between the two treatments, excluding the possible unloading effect of adenosine.1 and A3 receptors; however, some of the protective effects of adenosine might occur via an antiplatelet effect or an anti-inflammatory effect that is totally independent of preconditioning. Clinical trials suggest that some preconditioning mimetics reduce myocardial infarct size when given in conjunction with reperfusion [Adenosine has been suggested to induce preconditioning by agonierfusion ,13, and erfusion . It shouIn the present experimental model of exercise induced myocardial ischemia detected by TDE technique in humans, it is impossible to be sure that the reported findings were caused by ischemic preconditioning mediated by the activation of adenosine receptors; however excluding the vascular and unloading effects and considering that infusion of 35 μg/kg/min of adenosine give rise to activation of adenosine receptors, the hypNumerous studies have shown that pre-infarction angina pectoris protects patients who develop acute myocardial infarction -19, and The small size of this study precludes the extrapolation of our results to all patients with ischemic heart disease, especially to those with mild forms of exercise-induced ischemia. The positive pre-conditioning effects of adenosine were not observed for all parameters reflecting the regional LV systolic function. In fact, strain rate, a measure of "pure" myocardial contractility, was not affected by adenosine. This result could be explained by the low reproducibility of this measure when assessed during exercise.Certainly, some degree of ischemic preconditioning induced by angina pectoris did exist among all the patients. However, we do not believe that this fact compromised the results of the study, considering the placebo/controlled and the cross-over character of the study. We used high ischemic limit criteria to define myocardial ischemia by tissue Doppler echocardiography, and when milder criteria that allow for the detection of less severe forms of ischemia were applied, the results were the same. However, if we applied the same ischemic criteria as are used in clinical practice, almost The present results may open the possibilities of testing new therapeutic agents for the treatment of not only high risk patients with preconditioning mimetics that stimulate the biochemistry of preconditioning without actually causing ischemia but also of a vast number of patients with stable angina pectoris with mild to severe symptom in whom coronary revascularisation is impossible or not achievable.Low-dose adenosine infusion reduced the ischemic burden and improved the left ventricular regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia, confirming the possible preconditioning effect of adenosine in humans.The authors declare that they have no competing interests.BS selected the patients. MQ carried out the stress tests and MQ and BS analysed the data and statistical measurements. MB participated in the stress tests. CS participated in the design of the study and contributed to the manuscript. All authors read and approved the final manuscript.


A growing body of evidence suggests that effective blood pressure reduction may inhibit the progression of microvascular damage in patients with essential arterial hypertension. However, the potential influence of anti-hypertensive drugs on ocular circulation has not been studied sufficiently.The aim of our study was to evaluate the effects of anti-hypertensive therapy on blood flow in the central retinal artery in patients with systemic arterial hypertension.Twenty patients with essential arterial hypertension, aged 32–46 years, were examined with Doppler ultrasonography (10 MHz ultrasound probe). Blood flow velocities, pulsatility, and vascular resistance were determined before and 3 hours after systemic application of either bisoprolol 5 mg or cilazapril 2.5 mg.P < 0.05) and minimum  velocity, increased the Pourcellot's index  in central retinal artery. There were no statistically significant changes in central retinal artery blood flow after administration of cilazapril.Administered bisoprolol significantly decreased maximum (9.8 ± 0.5 cm/s versus 8.5 ± 0.6 cm/s; Systemic application of beta-blockers may unfavourably disturb the ocular blood flow. Systemic arterial hypertension gradually contributes to progressive damage of arterial vessels. Chronic increases in blood pressure cause several responses within the microvasculature, including endothelial dysfunction, impaired vessel relaxation, enhanced contractile response, and complex intima-media thickening. Finally, hypertrophy and proliferation of vascular smooth muscle cells decrease lumen diameter, which is accompanied by an increase in vessel resistance . It is wAccording to our knowledge, data concerning influence of different anti-hypertensive drugs applied systemically on ocular blood flow in humans are very scarce. Therefore the aim of our study was to evaluate the influence of BB (bisoprolol) and ACEI (cilazapril) on central retinal artery (CRA) flow assessed with Doppler ultrasonography in patients with systemic arterial hypertension.We enrolled 20 patients (aged 32–46 years) with a newly diagnosed essential arterial hypertension requiring monotherapy with one of the anti-hypertensive drugs. Patients were divided into two study groups consisting of 10 patients each and were given orally once (one single dose) either cilazapril 2.5 mg  in group 1, or bisoprolol 5 mg  in group 2. The main exclusion criteria were: any ophthalmic disorders (including glaucoma) and any systemic diseases requiring vasoactive pharmacotherapy or affecting IOP. Additionally, the blood pressure before Doppler examination must have been lower than 140/90 mmHg. The evaluation of the CRA flow was carried out twice: before and 3 hours after taking the examined hypotensive drug. All Doppler measurements were performed in the vertical position. After an application of ultrasound gel, a 10 MHz probe  was positioned over the upper eyelid temporally to the optical axis of the eye, avoiding pressure to the eye-ball. Further analysis included: maximum (systolic) and minimum (diastolic) velocity, and Pourcellot's index of resistance (RI). Additionally, we examined the visual acuity, tonometry, and arterial blood pressure. The results were analysed with Wilcoxon's paired test. All text and table results are expressed as means ± SE. The study was performed in the Department of Ophthalmology, Medical University of Silesia in Katowice. The study was approved by the local ethics committee, and all patients gave written informed consent prior to enrolment.There were no statistically significant differences in base-line values of blood pressure between the study groups. Administration of both study drugs resulted in a substantial systolic and diastolic blood pressure decrease . While aOur preliminary observations showed a different influence of BB and ACEI on the blood flow parameters within the CRA. Moreover, the obtained comparable values of blood pressure before and after both study drugs administration suggest that those effects are dependent on distinct mechanisms of action rather than blood pressure reduction degree. To the best of our knowledge, there are only a few small and inconsistent studies evaluating the influence on ocular circulation parameters of a short-term therapy or a single administration of an anti-hypertensive drug in patients with hypertension. Steigerwalt et al. and others observed an improvement in central retinal artery flow velocity in hypertensive patients after a 1-week treatment with trandolapril, but it did not reach flow parameters observed in healthy individuals . HoweverThe above-described effects might be related to the different impact of anti-hypertensive drugs on microcirculation and endothelium function. Apart from the third-generation agents, studies on beta-blocker effects on endothelial function showed inconsistent results. The majority of studies demonstrated that ACEIs improve microcirculation endothelial function. ACEIs, especially agents with affinity to tissue RAS (cilazapril), not only efficiently inhibit angiotensin II influence on endothelium, but also enhance bradykinin-induced vasodilatation . In a doAll major components of RAS have been identified within the retina of humans and rodents. However, the influence of systemically used ACEIs on CRA flow parameters has hardly been evaluated. The small and non-significant increase of velocity and decrease of vascular resistance suggest similar effects to systemic circulation.Isolated human posterior ciliary arteries and monkeys' ophthalmic and ciliary arteries have been shown to contract mainly in response to noradrenaline and alpha-1 adrenoreceptor agonists with a lack of response to beta-agonists. However, using radioligand binding and auto-radiographic techniques Elena et al. and others localized beta-adrenoreceptors in the ocular circulation, particularly around the ciliary body and also in bovine retinal arteries . Acting via alpha-1 receptors, norepinephrine causes vasoconstriction of posterior ciliary and ophthalmic arteries. Bisoprolol-induced beta-receptor blockade may enhance alpha-1 receptor activation and finally increase the vascular resistance and decrease the flow velocity. Additionally, heart rate suppression caused by beta-blockers may intensify these effects .The above results are based on a small study of a single administration of a hypotensive drug; they constitute preliminary observations and need to be verified in a larger population with a longer treatment period. Anyhow, the influence of different hypotensive drugs on ocular circulation parameters in hypertensive patients without glaucoma has not been evaluated sufficiently.Our results suggest that ACEIs do not disturb or may slightly improve the blood flow in retinal vessels. Unfortunately, BBs may cause unfavourable changes in retinal microcirculation. Those additional effects might be very important in hypertensive patients with any pre-existing ocular disorders. Moreover, considering similarities between ocular and brain vessels, favourable effects on ocular circulation might also suggest improvements in brain circulation and contribute to stroke prevention.