The aim of this study was to determine, in the absence of excess dietary salt, the individual effects of excess accumulation of dietary phytosterols and phytostanols on blood pressure in Wistar Kyoto (WKY) inbred rats (10/group) were fed a control diet or a diet containing phytosterols or phytostanols (2.0 g/kg diet) for 5 weeks. The sterol composition of the diets, plasma and tissues were analysed by gas chromatography. Blood pressure was measured by the tail cuff method. mRNA levels of several renal blood pressure regulatory genes were measured by real-time quantitative PCR.Thirty 35-day old male WKY inbred rats (P < 0.05). The phytostanol diet dramatically increased (> 9-fold) the levels of phytostanols in plasma, red blood cells, liver, aorta and kidney of these rats (P < 0.05). The phytosterol diet decreased cholesterol levels by 40%, 31%, and 19% in liver, aorta and kidney, respectively (P < 0.05). The phytostanol diet decreased cholesterol levels by 15%, 16%, 20% and 14% in plasma, liver, aorta and kidney, respectively (P < 0.05). The phytostanol diet also decreased phytosterol levels by 29% to 54% in plasma and tissues (P < 0.05). Both the phytosterol and phytostanol diets produced significant decreases in the ratios of cholesterol to phytosterols and phytostanols in plasma, red blood cells, liver, aorta and kidney. Rats that consumed the phytosterol or phytostanol diets displayed significant increases in systolic and diastolic blood pressure compared to rats that consumed the control diet (P < 0.05). The phytosterol diet increased renal angiotensinogen mRNA levels of these rats.Compared to the control diet, the phytosterol diet resulted in 3- to 4-fold increases in the levels of phytosterols in plasma, red blood cells, liver, aorta and kidney of WKY inbred rats in the absence of excess dietary salt. Therefore, even though phytosterols and phytostanols lower cholesterol levels, prospective clinical studies testing the net beneficial effects of dietary phytosterols and phytostanols on cardiovascular events for subgroups of individuals that have an increased incorporation of these substances are needed.These data suggest that excessive accumulation of dietary phytosterols and phytostanols in plasma and tissues may contribute to the increased blood pressure in WKY  Elevated blood levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) are established risk factors for the development of cardiovascular disease in humans . PhytostNo unexpected side effects have been reported since phytosterol- and phytostanol-enriched food products have been introduced into the food supply . HoweverAlthough phytosterolemia  is a rare autosomal recessive disorder, the prevalence of this disorder is likely underestimated due to misdiagnosis as hyperlipidemia since the standard colorimetric and enzymatic methods for the detection of cholesterol do not distinguish cholesterol from phytosterols and phytostanols. In addition, although homozygosity for a mutation that causes phytosterolemia is rare, heterozygosity is much more common  . These iinbred rats were used because this rat strain is usually used as a 'normotensive' model compared to its 'descendant' SHRSP rat strain [inbred rats have a mutation in the Abcg5 gene that results in increased tissue incorporation of phytosterols and phytostanols [Our previous data showed that dietary phytosterols and phytostanols increased the incorporation of phytosterols and phytostanols in plasma and tissues in diabetic  and saltt strain . Also, wostanols . TherefoPhytosterols were prepared from canola oil deodorizer distillate as described previously by us . DeodoriA portion of the recrystalized phytosterol product was converted to phytostanols via catalytic hydrogenation as described previously by us  at the pThree diets were prepared according to our previous publication  based oninbred rats were obtained from Charles River Laboratories . 35-day old male WKY inbred rats were randomly assigned to one of three diet groups  of the feeding phase of the study by the tail cuff method using a II TC Model 31 Blood Pressure Apparatus  as described previously [Procedures described previously were followed . BrieflyP ≤ 0.05.Data are presented as the means ± standard deviation (SD). Statistical analyses were performed using Statistica 8.0 software . One-way analysis of variance (ANOVA) followed by post-hoc Duncan's multiple range test was used to determine the diet effects and compare differences among group means. All data were evaluated for equality of variance prior to statistical analysis. Variables with skewed distribution were logarithm-transformed. A non-parametric Kruskal-Wallis test followed by Wilcoxon rank sum tests was employed if the data failed to satisfy equality of variance. Differences were considered significant when Body weight of the animals increased steadily during the 5 week feeding phase of the study. There were no effects of diet on body weight gain, food efficiency and total water consumption Table . No signP < 0.05), red blood cells , liver , aorta  and kidney  in WKY inbred rats (Table P < 0.05), red blood cells , liver , aorta  and kidney  in these rats. The phytostanol diet decreased phytosterol incorporation in plasma , red blood cells , liver , aorta  and kidney .In comparison to the control diet, the phytosterol diet increased phytosterol incorporation in plasma , aorta  and kidney  of these rats. The phytostanol diet also decreased cholesterol levels in plasma , liver , aorta  and kidney . The effects of phytosterols and phytostanols on cholesterol lowering in red blood cells did not reach statistical significance , aorta (P < 0.05) and kidney (P < 0.05), but increased total sterols in plasma (P < 0.05) of these rats. The phytostanol diet also decreased total sterol levels in aorta (P < 0.05) and kidney (P < 0.05). However, the phytosterol diet resulted in the lowest ratio of cholesterol to total phytosterols and total phytostanols in plasma, red blood cells, liver, aorta and kidney .Compared to the control diet, the phytosterol diet decreased total sterol levels in liver  and diastolic (P = 0.0001) blood pressure as well as greater increases in systolic (P = 0.0333) and diastolic (P = 0.0021) blood pressure, when compared to the rats fed the control diet. The phytostanol diet caused a greater increase in diastolic blood pressure (P < 0.05) compared to the phytosterol diet.There were no differences in the initial systolic and diastolic blood pressure among groups , angiotensin II receptor type 1a (Agtr1a), nitric oxide synthase 1, 3 , cyclooxygenase 2, Spondin 1 and THUMP domain containing 1 (P > 0.05). There were no effects of phytostanols on mRNA expression of all genes measured (P > 0.05).In comparison to the control diet, the phytosterol diet significantly increased mRNA levels of renal et al. [et al. [Abcg5) female SHR inbred rats. In the absence of salt-loading, our present study found that dietary phytosterols or phytostanols (2.0 g/kg diet) significantly increased systolic and diastolic blood pressure in WKY inbred rats  1, Ace2, angiotensin II receptor 1a (Agtr1a), nitric oxide synthases (Nos) 1, Nos3, Cyclooxygenase 2, Spondin 1 and Thump domain 1 (P > 0.05). These results suggest that Nos, Cyclooxygenase 2, Spondin 1 and Thump domain 1 pathways do not play a critical role in the blood pressure regulation caused by the intake of phytosterols and phytostanols in WKY inbred rats. Also, the phytostanol diet increased blood pressure but did not change the mRNA levels of renal angiotensinogen. Therefore, the renin-angiotensin-aldosterone system may not play a leading role in the hypertensive responses caused by phytosterol and phytostanol diets in the absence of salt-loading in WKY inbred rats.In order to elucidate the molecular mechanism(s) by which intake of phytosterols and phytostanols increased blood pressure in this rat model, the expression of several renal genes known to be involved in the renin-angiotensin-aldosterone system, nitric oxide, and cyclooxygenase-derived prostanoid pathways were investigated Table . SpondinP < 0.05, Table P < 0.05), and to decrease cholesterol levels in liver, aorta, and kidney as well as plasma (only by phytostanols) (P < 0.05)  Table . These ret al. [inbred rats. Therefore, the increased blood pressure caused by phytosterols and phytostanols in WKY inbred rats may be due to increased cell membrane rigidity. Other studies, in WKY rats in the presence of salt and in SHRSP rats in the absence of salt, have proposed that enhanced membrane activity of Na+, K+-ATPase by phytosterols in rapeseed oil may play a role in elevated blood pressure [inbred rats in this study and could be investigated in future studies. The molecular mechanisms of action of dietary phytosterols and phytostanols responsible for the absorption and accumulation of cholesterol, phytosterols and phytostanols have been previously discussed in our recently published paper [Our previous study indicated that a deficiency of membrane cholesterol due to phytosterol intake increases cell membrane rigidity, which might be a factor contributing to the shortened life span of SHRSP rats . Hamano et al.  also reppressure ,22. Othepressure , have noed paper .P < 0.05, Table Interestingly, it is generally speculated that phytostanol supplementation may be safer than phytosterol supplementation because the absorption of phytostanols (1-2%) is less than that of phytosterols 4-13%)  and the -13%  andinbred rats. The renin-angiotensin-aldosterone system, prostanoids system, nitric oxide system, Spondin 1 and THUMP domain containing 1 do not appear to contribute significantly to the increased blood pressure. Increased cell membrane rigidity caused by a decreased ratio of cholesterol to phytosterols and phytostanols may contribute to the increased blood pressure. The net beneficial effect of phytosterols and phytostanols on cardiovascular events for individuals predisposed to over absorption of phytosterols and phytostanols requires further investigation.Our study demonstrated for the first time that, in the absence of salt-loading, dietary phytosterols and phytostanols (2.0 g/kg diet) significantly increase systolic and diastolic blood pressure, and decrease the ratios of cholesterol to phytosterols and phytostanols in plasma, red blood cells, liver, aorta and kidney in WKY Ace1, Ace2: angiotensin I converting enzyme 1, 2; Agtr1a: angiotensin II receptor type 1a; Nos1, Nos3: nitric oxide synthase 1, 3; SHR: spontaneously hypertensive rats; SHRSP: stroke-prone spontaneously hypertensive rats; WKY inbred: Wistar Kyoto inbred.The authors declare that they have no competing interests.QC contributed to the animal feeding phase, blood pressure and gene expression measurements, data analysis as well as the drafting of the paper; HG contributed to the animal feeding phase and blood pressure measurements; ES and KC contributed to gene expression measurements; CP contributed to sterol measurements; WMNR and KAS contributed to the design of the study, data interpretation and drafting the paper. All authors read and approved the final manuscript.


Total intravenous anaesthesia has received much importance than inhalational anaesthesia in neuroanaesthetic practice. In an effort to determine whether any important clinical differences occur, studies concerning intracranial pressure (ICP), degree of dural tension and degree of brain swelling during intravenous and inhalational based anaesthesia are warranted like the present one.−1) and maintained with propofol (6-10mg.kg−1.hr−1) and fentanyl (2-3mcg.kg−1.hr−1). In Group-II (n=34), anaesthesia was induced with propofol (1-3mg.kg−1) but maintained with isoflurane, nitrous oxide and fentanyl (2-3mcg.kg−1.hr−1). Moderate hypocapnia was applied to maintain arterial carbon dioxide around 30mmHg. Mean arterial blood pressure was stabilized with phenylephrine whenever necessary. Subdural intracranial pressure, mean arterial pressure, cerebral perfusion pressure were monitored before and after 10min period of hyperventilation. Furthermore, the tension of dura before and after of hyperventilation and the degree of brain swelling after opening of dura were also estimated by the neurosurgeon.A total of 68 patients were assigned randomly to one of two groups. In Group-I(n=34), anaesthesia was induced with propofol (1-3mg.kgP<0.05). But after hyperventilation there was no significant difference of ICP and dural tension in between groups. The degree of brain swelling after opening of dura was similar in both groups. There was a positive correlation between measured ICP and brain swelling score.No differences were found between the groups with regards to demographics, neuroradiologic diagnosis, position of head and time of ICP measurement. Before hyperventilation, both ICP and dural tension were significantly lower in Group I compared with Group-II ( Major goals of neurosurgical anaesthesia are maintenance of haemodynamic stability, sufficient cerebral perfusion pressure, relaxed brain to facilitate neurosurgical resection and avoidance of agents or procedures that increase intracranial pressure (ICP).2O) and volatile agents. But so far no study comparing intravenous with volatile based anaesthesia has been able to demonstrate major outcome difference1There has been long standing controversy regarding use of inhalational or intravenous anaesthetic agent for intracranial procedure. Total intravenous anaesthesia has always received much importance to avoid cerebral vasodilating effect of nitrous oxide NO and vol2), ICP have been conducted during isoflurane32O, N2O-fentanyl, propofol-fentanyl) were used for elective supratentorial craniotomy, epidural ICP was measured through burr hole. Though ICP did not differ significantly, more patients with isoflurane- N2O group had ICP greater than 24mmHg as compared to other two groupsSeveral experimental and clinical studies of cerebral haemodynamics including cerebral blood flow (CBF), cerebral metabolism for oxygen CMRO, ICP havDuring craniotomy one of the most critical point is opening of dura where a high ICP may cause some degree of brain swelling13The primary goal of present study was to detect any difference in subdural ICP occured during propofol versus isoflurane-nitrous oxide anaesthesia along with the effect of hyperventilation in patients undergoing elective craniotomy for supratentorial tumour. Degree of dural tension and brain swelling after opening of the dura were also studied as secondary objectives.The study was undertaken at Bangur Institute of Neuroscience and Psychiatry after approval of the protocolby local ethical committee. It was a prospective randomized trial. Verbal and written consent was taken from all patients.Sixty eight patients of age 18 to 65 years, of either sex, American Society of Anesthesiologists physical status I and II, Glasgow Coma Scale (GCS) of 15 undergoing elective craniotomy for supratentorial tumour resection were randomly allocated in one of the two groups. Group I- Propofol (n= 34), Group II-Isoflurane-nitrous oxide (n=34).Patients diagnosed as having supratentorial tumour with midline shift of less than 10mm  were included in this study. Medically controlled hypertension or diabetes mellitus were also included.Patients were excluded if they suffered from ischaemic heart disease, congestive heart failure, renal or hepatic dysfuntion, or severe chronic respiratory disease.2O. Train offour was used to monitor muscular relaxation which was achieved by acontinuous infusion of atracurium. The anaesthetic procedures were as follows.The patients were premedicated with 150mg oral ranitidine one hour prior to anaesthesia. Preoperative corticosteroid, anticonvulsant, antihypertensive were administered as usual. Monitoring before induction consisted of automated noninvasive blood pressure, continuous electrocardiogram and pulse oximetry. After induction of anaesthesia, a radial artery catheter was inserted with zero pressure adjustment at mid-axillary line for continuous blood pressure monitoring and blood sampling. Urine output and rectal temperature were continuously monitored throughout the procedure. Inspired and end-tidaloxygen, carbon dioxide, nitrous oxide and isoflurane were measured. Lungs were mechanically ventilated to maintain an arterial blood carbon-dioxide tension between 30-40 mmHg and inspiratory peak pressure less than 20cm of H−1 propofol over 1min and 2-4mcg.kg−1 fentanyl. Lidocaine 1mg.kg−1 was administered over 1 minute followed by muscle relaxation with 0.5mg.kg−1 atracurium. After 3 minutes of mask ventilation with 100% oxygen, trachea was intubated. Lungs were mechanically ventilated with oxygen in air (fraction of oxygen 0.5). Anaesthesia was maintained with infusion of propofol (6-10mg.kg−1.hr−1) and fentanyl (2-3mcg.kg.−1hr−1). Rate of propofol infusion was adjusted to maintain adequate depth of anaesthesia. Just before skin incision of scalp, fentanyl 1mcg.kg−1 was supplemented. Infusion rate of propofol and fentanyl were kept unchanged during ICP measurement and during estimation of dural tension.Anaesthesia was induced with 1-3mg.kg−1 propofol over 1min and 2-4mcg.kg−1 fentanyl. Lidocaine 1mg.kg−1 was administered over 1minute followed by muscle relaxation with 0.5mg.kg−1 atracurium. After 3 minutes of mask ventilation with 100% oxygen, trachea was intubated. Lungs were mechanically ventilated with 50% nitrous oxide in oxygen (fraction of oxygen 0.5). Isoflurane was added to the inspired gas mixture and concentration was increased in 0.2% increments for maintaining adequate depth of anaesthesia. Fentanyl infusion was administered (2-3mcg.kg−1.hr−1) as in Group-I. Just before skin incision of scalp fentanyl 1mcg.kg−1 was supplemented. Infusion rate of fentanyl and percentage of isoflurane were kept unchanged during ICP measurement and during estimation of dural tension.Anaesthesia was induced with 1-3 mg.kg−1 was administered to all patients while making first burr hole.Intravenous phenylephrine was administered if systolic blood pressure decreased greater than 20mmHg of baseline inspite of normal saline infusion. Mannitol 0.75gm.kgth min after first measurement. Cerebral perfusion pressure (CPP) was calculated as the difference between mean arterial pressure (MAP) and ICP.After removal of bone flap, a 22G/0.8mm venflon cannula was placed under dura and connected to a pressure transducer system via a polyethylene catheter. Zero level of ICP was adjusted with the transducer kept at the level of orbitomeatal line. After 1minute of stabilization mean value of subdural pressure was used as an estimate of ICP. After initial measurement of ICP, pulmonary ventilation was increased by 30%  for 10min. Subdural ICP was again measured at 11Estimation of dural tension was made in a scale of four, using tactile evaluation by neurosurgeon. Neurosurgeons were blinded to anaesthetic technique. The tension was categorized as follows: (1) very slack (2) normal (3) increased tension (4) pronounced increased tension. The degree of brain swelling was evaluated by the neurosurgeon after opening of the dura. Degree of swelling was estimated and categorized as follows (1) no swelling, excellent operating condition (2) minimum swelling (3) moderate swelling and (4) pronounced swelling of the brain.P<0.05, the total sample size (number of patients) was calculated to be 68. Data within groups were tested for normal distribution. Two sample t-test was applied for parametric data . Chi-square test was used for analysis of demographic data, localization, size and histopathologic diagnosis of the tumours, preoperative drug administration between the groups. Difference in dural tension and brain swelling were tested by chi-square test in 2×4 tables. For correlation, Pearson product moment correlation and linear regression were performed. Data were expressed as mean ±SD. P<0.05 was considered statistically significant.Based on a previous study of ICP, given a minimal detectable significant difference of 3.5mmHg, expected SD 5.0mmHg, power of 0.80, and a statistical significance level of A total of 68 patients were enrolled in the study with equal number of 34 patients in each group. Demographic data are shown in Clinical data including time interval between induction and ICP measurement and vasopressor administration are shown in 2 (before and after hyperventilation) was greater in propofol group but reduction in ICP after hyperventilation was significantly smaller as compared to isoflurane-nitrous-oxide group.After removal of bone flap subdural ICP, MAP were measured and CPP was derived and are summarized in The dural tension before and after hyperventilation as estimated by neurosurgeon, are shown in There was a positive correlation between measured ICP and brain swelling score as well as neurological data (tumoursize and midline shift) and brain swelling score.Different anaesthetic agents have different effects on cerebral haemodynamics. For example, propofol decreases CBF, ICP and may decrease cerebral perfusion pressure via its effects on blood pressure.23Despite these concerns, there is no clinical evidence that one particular anaesthetic management regimen is superior to other. The few available comparative trials suggest no important difference between propofol versus isoflurane, nitrous oxide versus no nitrous oxide.226In comparative studies of lumbar CSF pressure in patients without space occupying lesion subjected to desflurane, isoflurane, sevoflurane and propofol anaesthesia, a higher CSF pressure was found during volatile anaesthesia compared with propofol anaesthesia8Subdural pressure is more accurate as a regional estimate102O and propofol/fentanyl groupIn this study, brain swelling after opening of dura was similar in both groups. Neurosurgeons were blinded to anaesthetic technique. In another study no difference was mentioned regarding brain swelling between isoflurane-NIn clinical studies, cerebral autoregulation is preserved with propofol but is impaired during 1.5 MAC isoflurane.282O group. The significantly greater decrease in ICP during isoflurane-nitrous oxide anaesthesia may be due to better carbon dioxide responsiveness. This is in agreement with other clinical studies indicating a preserved carbon dioxide reactivity during anaesthesia with isoflurane43233In this study, the decrease in ICP after hyperven-tilation averaged 1.5mmHg in the propofol group but 3mmHg in isoflurane-NIt is tempting to conclude that one anaesthetic regimen is better than other. Each anaesthetic has advantages and disadvantages. As noted, isoflurane and nitrous oxide are vasodilators and both can increase ICP. In contrast, total intravenous anaesthesia consisting of propofol and fentanyl (without nitrous oxide) should reduce CBF and ICP. But combination of low dose isoflurane with nitrous oxide and fentanyl might cause an intermediate increase in CBF and ICP because concentration of either drug can be decreased than concentration of any agent when using alone to provide an anaesthetic plane required for surgical resection. None of the anaesthetic was associated with any intra operative difficulties.We designed the current trial in such a manner that the subject population was as uniform as possible and we restricted the trial to patients with known supratentorial tumours with midline shift less than 10mm. Although supratentorial surgery in patients with large tumour might reveal differences, in this study, any significant difference in subdural ICP and brain condition for surgery after hyperventilation was not revealed in both groups. Limitation of the study were firstly inability to estimate carbon dioxide reactivity, inability to define absolute end points of anaesthesia in both groups in absence of anaesthetic depth monitor.The current study indicates that during craniotomy for supratentorial cerebral tumours, subdural ICP is lower in patients anaesthetized with propofol than isoflurane-nitrous oxide. After hyper ventilation, there were no significant difference of ICP and dural tension. Degree of brain swelling after opening of dura was similar in both groups. CPP was higher, may be due to better preservation of carbon dioxide responsiveness in isoflurane-nitrous oxide group as compared with propofol group. These results support the view that despite their cerebrovascular effects, institution of hyperventilation makes both anaesthetic regimens equally acceptable for intracranial tumour surgery.


Information on hypertension in the very elderly is sparse. Until recently evidence of benefits from pharmacological treatment was inconclusive. We estimated the prevalence of hypertension in subjects aged 80 or more, the proportion of awareness, treatment and control. Explanatory variables associated with good control were also studied.Cross sectional, population-based study, conducted in Martorell, an urban Spanish municipality, in 2005. By simple random sampling from the census, 323 subjects aged 80 or more were included. Patients were visited at home or in the geriatric institution and after giving informed consent, the study variables were collected. These included: supine and standing blood pressure and information about diagnosis and treatment of hypertension. The estimation and 95% confidence interval were obtained and a logistic regression model was used to study explanatory variables associated with blood pressure below 140/90 mm Hg.The prevalence of hypertension was 72.8% (95%CI: 69.5 – 76.6%) and 93% of the patients were aware of this condition, of whom 96.3% (95%CI: 93.65 – 97.9%) had been prescribed pharmacological treatment and 30.7% (95%CI: 25.8 – 36.1%) had blood pressure below 140/90 mm Hg. Some of the patients (43%) had one antihypertensive drug and 39.5% had two in combination. Explanatory variables associated with blood pressure below 140/90 mm Hg included prescription of a diuretic, OR: 0.31 (95%CI: 0.14 – 0.66), and history of ischemic heart disease, OR: 0.21 (95%CI: 0.1 – 0.47).The prevalence of hypertension in population aged 80 or more was over 70%. Most patients were aware of this condition and they had antihypertensive medication prescribed. Approximately one third of treated patients had blood pressure below 140/90 mm Hg. Patients with heart disease and with diuretics had more frequently blood pressure below this value. In Spain 655,924 men and 1,247,295 women were 80 years of age or more in 2005, which represents 3.8% and 5.5% of total male and female Spanish population [Until very recently evidence that treating patients 80 years of age or older is beneficial was inconclusive -9. Most In our country there is little information available about hypertension in the very elderly. The objectives of the study were to estimate the prevalence of hypertension in subjects aged 80 years or more, awareness, treatment and control. Explanatory variables associated with good control were also studied.The study is cross sectional, population-based and it was conducted in 2005 in Martorell. It is an urban municipality close to Barcelona, Spain, with 25,718 inhabitants (879 aged 80 or more). Inclusion criteria were people aged 80 years or more, living at home or in geriatric institutions, included in the census of the municipality who gave informed consent to participate in the study. Exclusion criteria included disorders that made impossible to measure blood pressure, extreme mobility alteration and terminal patients.By simple random sampling 323 subjects were selected. Sample size was calculated assuming a proportion of 0.7, with 0.05 precision and a confidence level of 95%. Lost subjects were replaced.Randomized patients were contacted and visited at home or in their geriatric institution by a nurse or physician, where data were collected. Except for the first 10 patients visited by a nurse, the subjects were visited by physicians, all of them members of the research team. Measurements were standardized. Patients who gave informed consent were included in the study. Variables studied were: Demographic , Diagnostic blood pressure (DBP) for those who were not previously diagnosed hypertension, control blood pressure (CBP) for previously known hypertensive patients, standing blood pressure (to detect orthostatic hypotension), prescribed antihypertensive medication, cardiovascular risk factors  and cardiovascular disease . The Barthel index was used to rate ability to perform activities of daily living. It is a 10 item scale with a highest possible score of 5 to 15 points on each item . It giveBlood pressure was ascertained under standardized conditions. After a 5 minute-rest blood pressure was measured in the seated position, using appropriately sized cuffs and calibrated and validated automatic devices . Feet were flat on the floor and arm supported at heart level. Contralateral arm was verified.Measurement of Diagnostic blood pressure: patients who were not previously diagnosed hypertension had two measurements separated one another more than 2 minutes, in three different days at least 7 days apart. Diagnostic blood pressure was the mean value. For blood pressure measurements and criteria for definition of hypertension we followed the hypertension guidelines of the Catalan Society of Family and Community Medicine . These cMeasurements of Control blood pressure: patients who were aware of this condition had two blood measurements separated one another more than 2 minutes. Mean value was considered.Hypertension was defined as systolic blood pressure greater than or equal to 140 mm Hg or diastolic blood pressure greater than or equal to 90 mm Hg, or receiving medication specifically for the indication of hypertension. Control was considered acceptable when systolic blood pressure was less than 140 mm Hg and diastolic blood pressure less than 90 mmHg among treated hypertensive patients.Blood pressure was also measured in the standing position. Orthostatic hypotension was considered when a reduction of at least 20 mm Hg in systolic blood pressure or at least 10 mm Hg in diastolic blood pressure was observed within 3 minutes of standing up . Pulse pThe estimation and 95% confidence interval were obtained for the prevalence of hypertension, awareness and control. Logistic regression models with forward stepwise selection of variables were used to study explanatory variables associated with blood pressure below 140/90 mm Hg. Independent variables studied were age, gender, functional status, residence at home or in geriatric institutions and cardiovascular disease.A total of 447 individuals aged 80 and over were randomly selected from the municipal census. The following did not participate in the study for the following reasons: 48 had already died, 35 refused, 30 could not be contacted, 9 did not live in the municipality and 2 because of severe dementia. Response rate was 81% (399 people were contacted and 323 were included).The total number of subjects included was 323. The percentage of women was 62.5%, mean age 84.9 (S.D: 3.6). Most of them lived at home (91.6%) and 8.4% lived in geriatric institutions. According to their functional status 44.3% were independent (scored 100 in Barthel index) and 41.2% had mild dependence (scored 60 to 99).The prevalence of other cardiovascular risk factors was: diabetes mellitus type 2 (20.7% of the subjects), hyperlipidemia (35%) and 3.4% were current smokers. The prevalence of ischemic heart disease was 13%, stroke 17.3% and peripheral vascular disease 11.1%.In table The percentage of patients with hypertension diagnosis with systolic blood pressure below 140 mm Hg and diastolic pressure below 90 mmHg was 30.7% (95% CI: 25.8 – 36.1%). Explanatory variables associated with blood pressure below 140/90 mm Hg: there was good control in 35.4% of patients who were prescribed a diuretic and in 21.6% of patients without this medication . The percentage of patients with ischemic heart disease with good control was higher (57.6%) than that of patients without this condition (26.6%), odds ratio: 0.21 (95%CI: 0.1 – 0.47). Age and sex were not statistically significant.Pulse pressure was 65 mm Hg or higher in 65% of subjects (95% CI: 60.5 – 69.3%); in 72.3% (95% CI: 67.3 – 76.9%) of patients with hypertension and in 45.4% of people without this condition (95% CI: 60.5 – 69.3%). Orthostatic hypotension was present in 9.6% of patients (95% CI: 7.2 – 12.6%); in 8.3% (5.7 – 11.9%) of patients with hypertension and 12.4% (8–18.7%) of patients without it.The prevalence of hypertension in this population aged 80 or more is very high, it exceeds 70% and most of the patients (93%) are aware of this condition. Most subjects known to be hypertensive have pharmacological treatment (96%), even though at the time data were collected there was no clear evidence of the benefits in this age group. However, only 31% of the patients aware of this condition had blood pressure below 140/90 mmHg.Another study in elderly population conducted in Spain has a similar prevalence of hypertension . HoweverThe very old have been under-represented in many past randomized clinical trials . As a reResults from HYVET are probably not enough to answer all questions about treatment of the very elderly with hypertension. There should be caution to extrapolate results to patients in this age group who are more frail than those in the trial, and also to other antihypertensive drugs than those used in the study. Thiazide diuretics in the very elderly may be more prone to metabolic alterations, such as hypokalemia, which can predispose patients to arrhythmias and possibly sudden death. Results from HYVET support a target blood pressure of 150/80 mmHg, whether further reduction is beneficial still needs to be established.The percentage of elderly hypertensive patients with blood pressure below 140/90 mm Hg is also around 30% in other studies conducted in Spain ,19 and iThe frequency of orthostatic hypotension in hypertensive patients increases with advancing age and with systolic blood pressure. It may be present in 5% to 14.6% of patients with hypertension, although a minority has orthostatic symptoms . It is aOur study is population-based, and it includes both people who live in their home and also in geriatric institutions. However an important number of randomized people had already died when they were contacted or refused to take part in the study. This limits to some extent the extrapolation of our results.The sample was obtained from an urban municipality, Martorell. So data are valid for this municipality. However, similar results might be obtained in other urban populations in Spain. For rural areas, prevalence of hypertension in this age group might be similar, but awareness, treatment and control may be different because of differences in access to health services.Although regression models were used to identify independent factors for blood pressure control, it was a secondary endpoint of the study. Sample size calculations were based to estimate prevalence of hypertension. Statistical power might be insufficient to identify some factors. Some factors that might be relevant were not considered, such as dementia because some patients with this condition were excluded. Renal failure is often undetected in primary care  and for The prevalence of hypertension in population aged 80 or more is over 70%. Most of the people are aware of this condition. Even though at the time data were collected there was no clear evidence of the benefits from antihypertensive medication in this age group, most of the patients had pharmacological treatment. Half of the subjects had two or more drug products and the most common treatment included diuretic combined with angiotensin converting enzyme inhibitors. Approximately one third of treated patients had blood pressure below 140/90 mm Hg and patients with heart disease and receiving diuretics had better control of hypertension.The authors declare that they have no competing interests.AA designed the study, analyzed the data and drafted the manuscript, FL and SM coordinated the field work and prepared the databases. PO, TB, MF, BH, LE and JP conducted the field work.All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


To study the effect of nebivolol 5 mg once daily versus (S)-atenolol 25 mg once daily in patients with essential hypertension.A prospective study was conducted at RLJH and Research Centre which included 30 patients in each group with essential hypertension. The sex, age, presenting illness, and family history of the patients were recorded. Investigations such as blood sugar, urine analysis, kidney function test, lipid profile, and ECG were performed before starting the treatment. Any adverse effects during the treatment were noted. Blood pressure and heart rate were recorded at baseline and during follow-up. One group received nebivolol 5 mg once daily and other group (S)atenolol 25 mg once daily. Patients were followed-up every 15 days for 3 months.P <·0001) in systolic (SBP), diastolic blood pressure (DBP), and heart rate at the end of first, second, and third month when compared to baseline. The difference in fall in SBP and DBP was insignificant between the groups, but fall in heart rate was significant (P <·0001). Adverse effects such as headache, dizziness, and fatigue were reported with both drugs.Nebivolol group had 18 males and 12 females with mean age 50.6 ± 9.5 years, (S)-atenolol had 16 males and 14 females with mean age 54.4 ± 9 years. Patients receiving nebivolol and (S)-atenolol showed a significant fall (Reduction of blood pressure with nebivolol and (S)atenolol was similar, but fall in blood pressure from baseline was highly significant in both groups. Hypertension is a major public health problem, being one of the leading causes of death and disability worldwide and a major risk factor for cardiovascular diseases.–3 The poEssential hypertension is a condition where the cause for rise in blood pressure is not known. It is so1-lipophilic blocker,[S)-atenolol is a hydrophilic β1-blocker which is an optically pure enantiomer of atenolol.[S)-atenolol is equivalent to 100 mg of racemic atenolol in its efficacy.[S)-atenolol on blood pressure and heart rate in patients with essential hypertension, hence this study was done.Beta-blockers are widely accepted as the first-line treatment for hypertension.8 Nebivol blocker, it also atenolol. Fifty miefficacy. To the bS)-atenolol. The study was conducted in the Medicine and Cardiology Department of R. L. Jalappa Hospital and Research Centre, attached to Sri Devaraj Urs Medical College, Tamaka, Kolar.A prospective study was conducted from 01.04.2004 to 31.03.2005 in patients with essential hypertension. Sixty patients were included in the study, of which 30 patients received nebivolol and 30 received (S)-atenolol, suffering from asthma or liver dysfunction, heart block, peripheral artery disease, pregnant, and lactating women and those who had received antihypertensive treatment were excluded from the study. The patients above 65 years had associated diseases such as diabetes mellitus, asthma, and liver dysfunction, so they were excluded from the study. Only newly diagnosed hypertensive patients without prior antihypertensive treatment and without any associated diseases mentioned earlier were included.A proforma containing detailed information on each patient was prepared according to the protocol designed for the study. Ethics clearance was obtained from Institutional Ethics Committee. Informed consent was taken from all the patients included in the study. Patients of either sex in the age group of 30–80 years with blood pressure of ≥140/90 mmHg were included in the study. The upper limit of blood pressure in both groups was 180/110 mmHg. Patients belonging to both stage 1 and stage 2 hypertension were selected as per JNC VIIth report. Patients with secondary hypertension, diabetes mellitus, allergic to nebivolol, and (S)-atenolol 25 mg once daily were given to respective patients in each group. The patients were advised to report for follow-up every 15 days for 3 months. On each visit, blood pressure and heart rate were recorded. Blood sugar, urine analysis, renal function test, lipid profile, and ECG were assessed before starting the treatment. Lipid profile was repeated at the end of 3 months. The data obtained were analyzed using descriptive statistics and paired and unpaired Student’s “t” test to compare results within the group and between groups, respectively.Blood pressure and heart rate were measured in sitting posture using the standard mercury sphygmomanometer. Blood pressure was recorded after giving rest of 15 min to patients in sitting position. Two recordings of blood pressure were taken at an interval of 5 min. Before administering the drug, the baseline blood pressure and heart rate were recorded. Nebivolol 5 mg once daily and (S)-atenolol 25 mg once daily. All the patients completed the study.Sixty patients were included in the study, of which 30 received nebivolol 5 mg once daily and the other 30 patients received (S)-atenolol, 53% were males and 47% females with mean age 54.4 ± 9 years. Ten male patients and five female patients of nebivolol group, nine male and nine female patients of (S)-atenolol group had family history of hypertension. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) (at baseline) of patients with history of smoking and alcoholism in both the groups were the same as that of other patients included in the study. Therefore, these patients were included in the study. The most common presenting symptoms in both the groups were headache and giddiness. Seven patients in each group presented with epistaxis. These patients had blood pressure in the range of 140/90 to 160/100 mmHg, and they had no other bleeding disorders.The patients were followed up at 15 days, but when the data were analyzed at the interval of 15 days the results were statistically insignificant. Therefore, the data were assessed at monthly intervals.P < 0·0001) in SBP at the end of each month  as compared to the baseline (158 ± 17 mmHg) [P < 0·0001) fall in diastolic blood pressure (DBP) at the end of 1, 2, and 3 months as compared to the baseline. There was gross reduction in heart rate at the end of first, second, and third months as compared to the baseline [17 mmHg) , respectbaseline .S)-atenolol on SBP. The mean SBP at the baseline was 160 ± 16 mmHg was reduced to 142 ± 15, 131 ± 13, 115 ±7 mmHg at the end of 1, 2, and 3 months of treatment, respectively, (P < 0·0001). Mean DBP as shown P < 0·0001). S)-atenolol on heart rate which was reduced from 85 ± 5 to 73 ± 5, 66 ± 4, 61 ± 2 at the end of first, second, and third month, respectively, (P < 0·0001).S)-atenolol on SBP, DBP, and heart rate at baseline and at the end of 3 months of treatment. The mean SBP at baseline in nebivolol group was 158 ± 17 mmHg and in (S)-atenolol group, 160 ± 16 mmHg. At the end of 3 months, it was reduced to 118 ± 8 mmHg in nebivolol group and 115 ± 7 mmHg in (S)-atenolol group. The fall in blood pressure between groups after 3 months was almost similar (P < 0·2). Similarly, mean DBP at baseline in nebivolol and (S)-atenolol group was 97 ± 10 mmHg and 99 ± 10 mmHg and at the end of 3 months of treatment the fall in blood pressure in both the groups was 71 ± 3 mmHg (P < 0·9).Figures P < 0·0001).The effect of nebivolol and (S)-atenolol on heart rate is depicted in The common adverse effects seen with both the drugs were headache, dizziness, and fatigue. Lipid profile was done as one of the laboratory tests because nebivolol has shown to decrease total cholesterol levels when compared with atenolol. There was no change in the lipid profile observed in both the groups at the end of 3 months of treatment with these drugs.Hypertension remains a major health problem being one of the leading causes of death and disability. Prevalence of hypertension among Indians is 26.78% in males and 27.65% in females. Cardiova19S)-atenolol 25 mg once daily in hypertensive patients. The patients were in the age group of 50–54 years in both groups. Literature search has revealed comparison of effect of nebivolol 5 mg once daily with racemic mixture of atenolol 100 mg once daily on blood pressure, heart rate, and oxidative stress in essential hypertensive patients.[S)-atenolol 25 mg were lacking, hence this study was carried out. In our study, we have observed a reduction of SBP and DBP and heart rate in patients who received nebivolol 5 mg once daily. The effect was observed at the end of 1 month of treatment and was maintained till the end of 3 months. These results are similar to the other studies.[S)-atenolol reduced SBP as well as DBP and heart rate. In this study, (S)-atenolol 25 mg once daily reduced SBP, DBP, and heart rate significantly after the patients were treated for a period of 1 month and subsequently till the end of 3 months. Studies[S)-enantiomer of atenolol contributes to the β-blocking activity of currently used rac-atenolol 100 mg, but the same effect was achieved with half dose (50 mg) of optically pure (S)-atenolol alone. In our study, we have observed that 25 mg of (S)-atenolol alone could reduce SBP, DBP, and HR significantly (P < 0·0001) at the end of 1 month of treatment and it was maintained throughout our study. Incidentally, the cost of one tablet of racemic mixture atenolol 100 mg ranges from Rs. 1.80 to 3.30 and that of 25 mg (S)-atenolol is Rs. 2.50.[In our study, we have analyzed the effect of nebivolol 5 mg once daily and (patients. Studies  studies.22 In one studies. 100 mg o. Studies24 have sS)-atenolol reduced SBP, DBP, and HR, but the reduction of SBP and DBP when compared between the groups at the end of 3 months was not statistically significant. Similarly, DBP was similar in both the groups. The reduction was similar in both the groups. When heart rate was compared between nebivolol-treated and (S)-atenolol-treated patients, there was significant fall (P < 0·0001) in the heart rate in (S)-atenolol group, this could be because (S)-atenolol blocks β1-receptors in the heart while nebivolol because of its vasodilator property can produce reflex increase in heart rate. Similar findings, i.e., reduction in SBP, DBP, and heart rate were observed in two other studies.[In this study both the drugs nebivolol and  studies.24S-atenoloS)-atenolol 25 mg had similar antihypertensive effect. Although there was no difference between the groups with respect to reduction of SBP and DBP, decrease in HR was significantly greater in patients receiving (S)-atenolol. The cost of nebivolol 5 mg is Rs. 5 per tablet and that of (S)-atenolol is Rs. 2.50 per tablet, thus (S)-atenolol being more cost-effective. The important clinical implication is that nebivolol though costly can improve nitric-oxide availability, thus prevent the endothelial dysfunction that predisposes to essential hypertension. Though this appears to offer more benefit based on its pharmacodynamics, clinically significant data were not evident in this study. Further studies with higher doses of nebivolol may throw more light on this particular aspect. Adverse effects in both the groups were similar, and no change in lipid profile was observed at the end of 3 months with either drugs.The results of this study showed that nebivolol 5 mg and (


Sir,Hanging is a common mode of suicide worldwide. However, almost 80% survive, often with permanent neurosequelae due to parenchymal brain damage. We tried to correlate clinical parameters and results of noncontrast magnetic resonance imaging (MRI) of brain with development of neurologic deficits in patient presenting post hanging. Neurodeficits studied were the delayed development of seizure, hemiparesis or movement disorders within a period of 6 months post discharge from the hospital.We included 19 cases in our study . Data regarding Glasgow Coma Scale (GCS), systolic and diastolic blood pressure, pulse rate, respiratory rate, plantar and pupillary reflex were collected retrospectively from patient charts on all the 19 patients. Noncontrast MRI of brain was done within 48 hours of incidence of hanging, irrespective of duration of hanging on all the patients. We excluded patients with a past history of seizure, stroke or movement disorder. Out of the 19 patients, 7 (36.8%) developed delayed neurosequelae. Two patients (28.57%) developed hemiparesis, four patients (57.14%) developed seizure disorder, while one patient (14.28%) developed hemichorea. The interesting part about these patients was that all of them had a normal noncontrast MRI of brain done within 48 hours of admission.P = 0.035). Abnormal plantar reflex, defined as unilateral or bilateral equivocal or extensor response, strongly correlated with neurosequelae development (P = 0.015). Pulse rate (P = 0.516), respiratory rate P = 0.340), systolic blood pressure P = 0.336), diastolic blood pressure (P = 0.912), pupil size (P = 0.054) and pupillary reaction to light had insignificant association with future neurosequelae as was the case with non-contrast MRI.GCS value below 10 at admission was associated with adverse neurological outcome (In hanging, the brain parenchymal damage results from either venous congestion in brain leading to hypoxic neuronal injury or hemorrhage from rupture of vessels. Hypoxia can also occur from bilateral carotid compression at neck with severe constriction pressure. This ultimately results in damage to the basal ganglia, thalamus and cortex of the brain, with development of motor neurosequelae. It is clear from our study that in case of hanging, clinical parameters at presentation, in particular GCS score below 10 and upgoing or nonresponsive plantar reflex, have significant correlation in predicting future neurosequelae. Pupil si4


The aims of this study were to find out whether Postprandial hypotension (PPH) occurs more frequently in patients admitted to a geriatric ward than in healthy elderly individuals, what the optimal interval between blood pressure measurements is in order to diagnose PPH and how often it is associated with symptoms.The result of this study indicates that PPH is present in a high number of frail elderly, but also in a few healthy older persons. Measuring blood pressure at least every 10 minutes for 60 minutes after breakfast will adequately diagnose PPH, defined as >20 mmHg systolic fall, in most patients. However with definition of PPH as >30 mmHg systolic fall, measuring blood pressure every 10 minutes will miss PPH in one of three patients. With the latter definition of PPH the presence of postprandial complaints is not associated with the existence of PPH. Postprandial hypotension (PPH) was defined in the past as a fall in systolic blood pressure of ≥20 mmHg within 2 hours of eating a meal, comparable with the definition of postural hypotension . A recenThe pathophysiology of PPH is probably multifactorial, possibly involving an attenuated baroreflex, an attenuated reflex increase in sympathetic activity by activation of stretch receptors in the stomach (gastrovascular reflex) , sympathThe aims of this study were to establish the prevalence, duration, and association with symptoms of PPH in patients admitted to a geriatric ward, compared with healthy elderly individuals. Patients were provided with a continental breakfast. We measured beat-to-beat blood pressure and tested different intervals between blood pressure measurements to diagnose postprandial hypotension adequately.Consecutive patients admitted to the geriatric ward of the University Medical Center Utrecht over 6 months were eligible for inclusion. This ward serves elderly patients with a wide range of acute and chronic diseases and referrals for diagnostic work-up or therapy. Most patients are referred by general practitioners or geriatricians. Inclusion criteria were being able to give informed consent and to walk . Exclusion criteria were myocardial infarction less than 3 months earlier, any acute illness, uncontrolled metabolic disease, resting systolic blood pressure more than 200 mmHg, cardiovascular disease , dysphagia, life expectancy less than 3 months, and use of medication that affects blood pressure and which could not be discontinued for 24 hours. All subjects were studied in the week prior to discharge. All participants gave written informed consent prior to the examination. Healthy elderly individuals, recruited by advertisement in a weekly newspaper, were screened by telephone and underwent a physical examination before being matched for age with the geriatric patients. All subjects were healthy according to modified exclusion criteria defining medically stable elderly subjects for exercise studies [Blood pressure was recorded using Portapres . Portapres is a non-invasive method to record beat-to-beat blood pressure alternately from two adjacent fingers and is accurate for measuring changes over time, but not for measuring absolute values . The metTwenty-four hours before the measurements, all medication that affects blood pressure was withdrawn. After an overnight fast, the subjects were allowed to take their regular medication (with the above exception) with some water 2 hours before breakfast. They could select the ingredients of their continental breakfast, to mimic normal conditions as closely as possible, but were offered weak tea, because caffeine in coffee might affect blood pressure . After bU test. The chi-square and Fisher exact tests were used for comparison of the presence of PPH with PPH-related symptoms. Differences between the groups at baseline and maximum changes from baseline were determined with a Mann-Whitney In this study, PPH was defined as a decline in systolic blood pressure of at least 20 mmHg, determined by calculating the difference between the minimum systolic blood pressure values before and within 120 minutes after the start of breakfast. According to the results of a recent study [Because we were not interested in beat-to-beat blood pressure variations, we calculated mean values over 2-minute periods. The start of PPH and the time of maximal fall in blood pressure are expressed in minutes after the completion of breakfast. To determine the minimum interval between blood pressure measurements for diagnosis of PPH, the maximum decrease in blood pressure was calculated for different intervals between measurements, which was done by omitting 1 or more of the 2-minute blood pressure measurements from calculations. The number of patients diagnosed with PPH was calculated, using these different intervals.P < .05. Data are expressed as means ± standard deviation (SD) unless otherwise specified.Differences were considered significant with a During the study period, 101 patients were admitted to the geriatric ward, 68 of whom were excluded because they met one or more of the exclusion criteria (in most cases because they suffered form an acute illness). Five patients did not give consent, and five others could not participate because of technical difficulties. The remaining 22 patients  were studied. They were admitted because of metabolic disorders (4 patients), mobility disorders (4), anemia (3), Parkinsonism (3), delirium (2), syncope (2), or miscellaneous (4). Mean age was 84 years . Resting blood pressure was 140/65 mm Hg  and heart rate 67/min . Of these patients, 45% had a history of cardiovascular disease (other than hypertension), 32% had a history of hypertension , 27% had Parkinson's disease , 18% had a history of cerebrovascular disease, and 14% had diabetes mellitus.Of the 53 healthy elderly subjects who responded to the advertisement, 20 were excluded because they met one or more of the exclusion criteria, 2 did not give consent after reading the patient information, and 11 were excluded because of age mismatching. The remaining 20 healthy elderly were compared with the 22 geriatric patients. There were no differences in baseline characteristics between the two groups . Of the P = .05 and P = .13, resp.). After the meal, systolic and diastolic blood pressure decreased below baseline values in both groups, but the fall in systolic blood pressure was significantly greater in the patient group . Thus PPH, defined as a systolic fall of 20 mmHg or more, occurred in 20 (91%) of 22 patients and in 8 of 20 (40%) healthy elderly individuals . PPH defined as a fall of 30 mmHg or more was present in 10 (45%) patients and three (15%) healthy persons (P < .001). The characteristics of the blood pressure fall in the subjects with PPH are shown in We determined the interval between blood pressure measurements that was most appropriate for detecting PPH in the individuals with PPH in the group of patients that were admitted to the geriatric ward. PPH lasted 2 minutes in two patients, 6 minutes in one patient, and 8 minutes in two patients. It lasted between 14 and 108 minutes in the remaining 15 patients see . Eight pP < .001). However with PPH defined as a systolic fall of >30 mmHg, an association could not be found. The sensitivity of PPH-related symptoms for a significant decrease in blood pressure was 7/13 = 0.53, the specificity was 18/29 = 0.62, the positive predictive value was 7/18 = 0.39, and the negative predictive value was 18/24 = 0.75. Also an association between supine systolic hypertension >160 mmHg in rest and PPH could not be found. Only four patients and one healthy subject had a supine blood pressure >160 mmHg after 15 minutes rest; three of them had PPH.Of the 42 included subjects, 18 developed PPH-related symptoms and 24 had no complaints . SeventeWe found PPH to be present in a high number of frail elderly patients, but also in a considerable number of healthy elderly. The prevalence of PPH we found in elderly patients (91%) is higher than previously reported , 7, 30. Despite this variability, PPH started within an hour of eating breakfast in 18 of 20 patients (90%). Assuming that changes in systolic blood pressure measured with a sphygmomanometric device are similar to the 2-minute mean Portapres values that were used in this study, blood pressure measured at 6-minute intervals would have identified at least 18 patients with PPH (90%); measurement with 10-minute intervals would have identified at least 17 patients (85%) with PPH . HoweverBeat-to-beat measurements will increase the number of short-lasting falls in postprandial blood pressure detected relative to the number detected when blood pressure is measured with a sphygmomanometer. However, in general practice, this method is not attractive because continuous blood pressure measurements are comprehensive, require skill to get reliable results, and require relatively expensive equipment. For this reason, automatic sphygmomanometer measurements, with devices such as Spacelab, are preferred .In this study, the subjects ate a continental breakfast, in which the release of glucose is quite constant whereas other studies used standardized liquid meals, in which the release of glucose is rapid. We chose a standardized continental breakfast as being more representative of the normal situation. Moreover, we hypothesize that differences in the severity of PPH observed with high and low carbohydrate-containing meals can be explained by differences in the rate of glucose uptake rather than by differences in the total number of calories consumed, a hypothesis that is supported by the findings of O'Donovan et al. . They foOur study had some potential limitations. We chose to withdraw medication that affects blood pressure for 24 hours to eliminate transient effects of medication that could occur directly after ingestion. However, we cannot rule out the possibility that these medications affect the mechanism of PPH. We calculated mean values of blood pressure over 2-minute periods and may thus have missed a short-lasting fall (less than 2 minutes) in blood pressure. However, such a short-lasting fall in blood pressure may not be of clinical relevance. It was our goal to mimic the normal physiological condition by using a continental breakfast instead of standardized meal and to allow subjects to choose their breakfast. Because subjects were not active after they finished their breakfast, we cannot rule out that the fall in blood pressure was the effect of drowsiness or even sleep as might occur during the period of inactivity after the meal, adding to the occurring hypotension, although a researcher was constantly in the room and a symptom-questionnaire was evaluated every 15 minutes, limiting the presence of drowsiness and its potential influence. There is currently no standardized clinically meaningful definition of PPH .In the current study, it is surprising that blood pressure fall up to more than 30 mm Hg is still well tolerated in six subjects  without any symptoms. The mechanism(s) mediating the effects of meal on the hypotensive response remain uncertain, and there are a number of possibilities which warrant further exploration. Symptoms due to reduced cerebral perfusion can be manifested as dizziness, light-headedness, weakness, dyspnea, sweating, or syncope. Cerebral hypoperfusion develops when cerebral autoregulation fails. The autoregulated range is known, typically 70–140 mmHg. Cerebral autoregulation is ineffective when the blood pressure falls to <70 mmHg, and here the cerebral perfusion might be severely compromised. However, patients with chronic orthostatic hypotension may have an expansion of their autoregulated range to lower BP . Such paAs neurogenic orthostatic hypotension, severely afflicted patients are unable to stand without experiencing symptoms. We cannot, however, exclude the possibility that there is some kind of autonomic dysfunction in this very elderly group. Aging, leading to abnormalities of parasympathetic and sympathetic control of heart rate and blood pressure, may be associated with concomitant autonomic afferent sensory fiber neuropathy. Degeneration or dysfunction of these afferent fibers may result in interruption of pain or other autonomic disorders sensations . ReducedFrom the clinical perspective, it is important to measure blood pressure following a meal in patients who have unexplained syncope and whose orthostatic stress test result is normal. Old age is associated with diminished homeostatic regulation of many physiological functions. Reduced fluid and food intake and common medical conditions in the elderly, such as gastrointestinal disease , can cause dehydration. Dehydration and the use of diuretics or other agents may reduce the cardiac output in the elderly. In subjects with PPH, these factors might induce severe hypotension, and this is a potential trigger for ischemic stroke or acute myocardial infarction.In conclusion, PPH occurs in a high number of frail elderly patients admitted to a geriatric ward. PPH was also present in a few relatively healthy elderly. Measuring blood pressure every 10 minutes, starting from 15 minutes before until 60 minutes after the end of a regular breakfast, using a sphygmomanometer, will detect about 70% of geriatric patients with PPH. This seems a patient friendly, practical, and adequate way to evaluate PPH in clinical practice. The presence of postprandial complaints during the measurement is not a good indicator of the existence of PPH.


We aimed to investigate the effects of nebivolol and quinapril treatments on P-wave duration and dispersion in hypertensive patients. Hypertensive patients who were in sinus rhythm were assigned to the two treatment groups and received either 20 mg quinapril/day or 5 mg nebivolol/day. P-Wave dispersion (PWD) was measured at baseline and after four weeks of treatment and defined as the difference between the maximum (Pmax) and the minimum (Pmin) P-wave duration. The study group consisted of 54 patients  with 27 patients in each group. At 4-week follow up both treatment groups showed a significant reduction (p< 0.001) in systolic (SBP) and diastolic blood pressure (DBP). Heart rate (HR) reduction was significant in patients receiving nebivolol (P=0.001). Both groups showed a similar  but significant reduction in PWD  and Pmax . A 2 (Time) x 2 (Group) mixed-model repeated-measures analysis of variance revealed that the main effect of Time was significant for Pmax (P=0.002) and PWD (P=0.008) after controlling for changes in SBP, DBP and HR. However, the main effect of Group and Time x Group interaction was not significant for both variables . In conclusion, short-term treatment with nebivolol and quinapril produces a similar but significant reduction in Pmax and PWD in hypertensive patients. This effect is independent of blood pressure and heart rate changes. The surface electrocardiogram (ECG) is the most common non-invasive method used for cardiovascular evaluations. Increased P-wave dispersion (PWD) and maximum P-wave duration (Pmax) are considered to be the non-invasive indicators of prolonged and heterogeneous atrial conduction  . Accordi2; (11) technically insufficient echocardiographic images; (12) left ventricular ejection fraction (LVEF) < 55%; (12) QRS duration ≥  120 millisecond (ms); (13) unrecognized P-wave in ≥  3 leads; (14) any  contraindication to beta-blockers or ACE inhibitors. Eligible patients were approached for study participation and informed consent was obtained from all participants. The recruitment of the patients was completed prospectively in 6 months between December 1st, 2005 and May 31st, 2006.The study included newly diagnosed hypertensive patients who were in sinus rhythm. Blood pressure measurements were done in the morning for the 3 consecutive days with an appropriate sized cuff mercury sphygmomanometer . The patients were allowed to take a rest at least 10 minutes before each blood pressure measurement, without tea and coffee intake or smoking at least 30 minutes prior to the measurement. Patients who had a blood pressure value of ≥ 140/90 mm Hg and < 180/110 mmHg were included. We applied the following exclusion criteria: presence of (1) malignant or secondary hypertension; (2) ischemic or valvular heart disease; (3) heart failure; (4) renal dysfunction; (5) sustain atrial or ventricular arrhythmias; (6) antiarrhythmic treatment; (7) chronic obstructive lung disease or pulmonary hypertension; (8) neurological, oncological or rheumatological disease; (9) pregnancy; (10) a body mass index (BMI)  ≥ 35 kg/mElectrocardiograms were obtained using a 3-channel standard 12-lead synchronous electrocardiography apparatus  with a rate of 50 mm/seconds and amplitude of 10 mV including at least 3 QRS complexes for each derivation. During recordings, the patients were allowed to breathe freely, but not to speak. The P-wave durations for each derivation was manually analyzed through a x10 magnifying glass. The beginning of P-wave was considered as intersection point of isoelectric line with the P-wave while the end point was the intersection of isoelectric line with the last point of P-wave. The difference between the longest and shortest P-waves was defined as PWD. All measurements were done by the same cardiologist who was blinded to clinical characteristics of the participants.3 - (LVEDD)3} + 0.6. The LVM index was calculated as LVM divided by body surface area (BSA). Left ventricular hypertrophy was considered present when the LVM index was > 125g/m2 in men, and > 110g/m2 in women [A transthoracic echocardiography was performed in all patients using a 3.2 MHz probe . Parasternal long- and short-axis, apical four chamber and two chamber views were obtained, and left ventricular systolic and diastolic functions were evaluated. Left atrium diameter, posterior wall thickness (PWT), interventricular septal thickness (IVST), left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) were measured for each patient. The left ventricular muscle mass (LVM) was calculated with the Devereux formula ; LVM= 0.2 were defined as obese. All patients were reevaluated at 4-weeks follow up. No other antihypertensive drugs or any other drugs with effects on cardiovascular system were allowed during the study period.  The study was conducted in accordance to the Helsinki Declaration with the permission of the local ethical board.The recruited patients were assigned to the two treatment groups in a sequential order and received either 20 mg quinapril/day or 5 mg nebivolol/day treatment. A brochure explaining life style changes  was given to all patients. Lipid profile and renal function tests were performed for each patient, including the measurement of height and weight. BMI was calculated as weight in kilograms divided by height in square meters. The patients who had a BMI ≥  30 kg/mContinuous data were expressed as the mean ±  standard deviation; categorical data were expressed as numbers with percentages. The Shapiro-Wilk test was used to assess the normality of the continuous data. Differences in continuous data were analyzed by using the Students' t or Mann-Whitney U test in two independent groups. Categorical data were compared by using the Chi-square test or Fisher's Exact test in two independent groups. T or Wilcoxon test for paired samples was used to assess changes in the variables over time within each group. A 2 (Time) x 2 (Group) mixed-model repeated-measures analysis of variance (ANOVA) was performed to compare between-group differences .Changes in P-wave parameters were adjusted for the changes in blood pressure and heart rate in this ANOVA model. A two tailed p value < 0.05 was considered statistically significant. All statistical analyses were performed using the SPSS  statistical software package .A total of 62 consecutive patients, 31 in each group, were recruited. Two patients who didn't comply with the treatment regimen , and three patients who didn't attend the control visit at week 4  and three patients who failed to follow the instructions  were excluded. Thus, the study group consisted of 54 patients  with 27 patients in each group. The baseline characteristics of the two study groups were comparable . Mean blBoth groups showed a similar but significant reduction in PWD and Pmax . The delA 2 (Time) x 2 (Group) mixed-model repeated ANOVA revealed that the main effect of Time was still significant for Pmax (P=0.002) and PWD (P=0.008) after controlling for delta SBP, delta DBP and delta HR . HoweverDuring the study period, cough occurred only in one patient in the quinapril group. In the nebivolol group, one patient experienced headache, and one patient experienced weakness. No other clinical side effect or laboratory abnormality observed during the study period.To our knowledge, this is the first study to compare the effect of beta- blockers and ACE inhibitors on the P-wave duration and dispersion. We showed that nebivolol and quinapril treatment produce a similar but significant reduction in Pmax and PWD in patients with newly diagnosed hypertension. Moreover, this effect was independent of blood pressure and heart rate changes.Increased Pmax and PWD are believed to reflect heterogeneous and prolonged atrial conduction . IndepenThe density of angiotensin (Ang)-II receptors in the atria is generally greater than in the ventricles  and Ang-There are several possible direct or indirect mechanisms by which nebivolol might reduce the prolongation of the maximum duration and dispersion of the P-wave. Beta-blockers lengthen duration of diastole, enhance ventricular filling, decrease atrial pressure, and dilatation and thereby may improve stretch related arrhythmogenic mechanisms ,24,25. IIn conclusion, antihypertensive treatment with nebivolol and quinapril produces a similar but significant reduction in PWD and Pmax. Our results also suggest that reduction of Pmax and PWD cannot be solely attributed to a better blood pressure control since effect of both quinapril and nebivolol on Pmax and PWD was independent of blood pressure and heart rate changes. Further studies are required to assess clinical utility of Pmax and PWD reduction after the administration of anti-hypertensive treatment for the prevention of AF.Several limitations should be considered. This study is subject to the limitations inherent to a nonrandomized study. A second limitation of the study is the small sample size. P-wave measurements were performed manually on the standard paper ECG. A digitized measurement method for P-Wave parameters would be more accurate.


Postural orthostatic tachycardia syndrome (POTS) commonly affects women of childbearing age. We report on a 37-year-old woman who developed symptoms of recurrent syncope in the postpartum period. Her head up tilt test and clinical presentation was consistent with POTS. Recurrent unexpected syncope may have severe consequences and can result in serious injury, especially in a postpartum period when the maternal syncope can have the disastrous effect on the newborn infant as well as the mother. Postpartum syncope has been reported to result in death due to dropping of the infants . We repoA 37-year-old woman with a past medical history of migraine headache and reflux esophagitis was seen in our autonomic clinic for evaluation of recurrent syncope. In the last nine years, she had experienced episodes of debilitating recurrent syncope. Her first episode occurred six months after she gave birth to her daughter. At that time, she described an episode that occurred while standing at work during which she became “fuzzy”, lightheaded, and subsequently suffered from an episode of syncope with a brief loss of consciousness. She had no convulsive activity during this episode. She continued to experience episodes of lightheadedness without frank syncope. Six years after her first episode the symptoms and the frequency of episodes progressed to the point where she experienced approximately eight episodes of lightheadedness and palpitations over a period of six months, occasionally resulting in syncope. In the interim, multiple neurologists evaluated her. Ultimately, a cardiologist sent her for head up tilt test (HUTT). Upon the assumption of upright posture during the tilt test, her heart rate increased from 86 beats per minute (bpm) (baseline) to 126 bpm within 5 minutes, and her blood pressure dropped from 126 mm Hg (baseline) to 90 mm Hg, associated with symptoms of lightheadedness, palpitations and loss of consciousness. She was initially treated with fludrocortisone, which failed to relieve her symptoms. Midodrine  and methylphenidate (noncatecholamine sympathomimetic) were also tried but ineffective. She suffered multiple injuries (including head injuries) during these episodes of syncope, and her quality of life had markedly decreased. During one traumatic syncopal episode, she fell while attending physical therapy. In addition, she also suffered from loss of memory and balance problems.In our clinic, she presented with a blood pressure of 100/80 sitting and 90/64 standing. Her supine heart rate was 70 beats per minute and immediately upon standing rose to 111 beats per minute. The rest of the physical examination was normal except for the presence of joint hypermobility in the bilateral wrists, thumbs, fingers, elbows, and ankles. After review of her history, physical exam, and the extensive evaluation, the diagnostic impression was autonomic dysfunction and orthostatic intolerance most consistent with new onset postpartum postural orthostatic tachycardia syndrome. Her overall clinical picture of orthostatic intolerance and joint findings were most consistent with joint hypermobility. The initial core management choices here were reasonable; indeed the prior management was essentially exactly as our center would recommend. She was commenced on Duloxetine, a serotonin/norepinephrine reuptake inhibitor. During her next clinic visit, she reported marked improvement in symptoms, except for headache and mild cognitive impairment. She was started on Cerefolin to help the memory loss .Multiple cardiovascular adaptations occur during pregnancy, which are essential for successful completion of pregnancy. These include an increase in cardiac output, sodium, and water retention with increase in expansion of blood volume and a reduction in peripheral vascular resistance and diastolic blood pressure . These c In patients with POTS, the main mechanism is the consistent failure of the peripheral vascular system to increase resistance during upright posture. Patients with joint hypermobility syndrome even have more difficulty owing to loss of supporting connective tissues in the vessels. Orthostatic intolerance develops in these patients due to the presence of abnormally elastic connective tissue in the vasculature. This results in an increase in vessel distensibility in response to the augmented hydrostatic pressure that occurs during orthostatic stress. Consequently, there is excessive peripheral venous pooling with a resultant compensatory tachycardia. About 70% of patients with hypermobility syndrome may suffer from some form of orthostatic intolerance due to sympathetic dys-regulation . These patients are usually treated with fludrocortisone  midodrinIn our experience, we have found that use of combined selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors has been more effective in POTS than in neurocardiogenic syncope .POTS in the postpartum period can have serious consequences; indeed the risks associated with syncope can be life threatening not only to mother but also to the child as well. Early recognition and proper management of these patients are essential to prevent serious morbidity and mortality associated with this clinical entity. Long-term outcomes in patients with postpartum POTS are unknown.


Blood pressure (BP) lowering in people who have had a stroke or transient ischaemic attack (TIA) leads to reduced risk of further stroke. However, it is not clear what the target BP should be, since intensification of therapy may lead to additional adverse effects. PAST BP will determine whether more intensive BP targets can be achieved in a primary care setting, and whether more intensive therapy is associated with adverse effects on quality of life.This is a randomised controlled trial (RCT) in patients with a past history of stroke or TIA. Patients will be randomised to two groups and will either have their blood pressure (BP) lowered intensively to a target of 130 mmHg systolic, (or by 10 mmHg if the baseline systolic pressure is between 125 and 140 mmHg) compared to a standard group where the BP will be reduced to a target of 140 mmHg systolic. Patients will be managed by their practice at 1-3 month intervals depending on level of BP and followed-up by the research team at six monthly intervals for 12 months.610 patients will be recruited from approximately 50 general practices. The following exclusion criteria will be applied: systolic BP <125 mmHg at baseline, 3 or more anti-hypertensive agents, orthostatic hypotension, diabetes mellitus with microalbuminuria or other condition requiring a lower treatment target or terminal illness.The primary outcome will be change in systolic BP over twelve months. Secondary outcomes include quality of life, adverse events and cardiovascular events.In-depth interviews with 30 patients and 20 health care practitioners will be undertaken to investigate patient and healthcare professionals understanding and views of BP management.The results of this trial will inform whether intensive blood pressure targets can be achieved in people who have had a stroke or TIA in primary care, and help determine whether or not further research is required before recommending such targets for this population.ISRCTN29062286 Stroke is the third largest cause of death in England, and the single largest cause of adult disability. A NatioThe PROGRESS trial demonstrated that blood pressure lowering is beneficial in reducing risk of stroke amongst both hypertensive and non-hypertensive individuals with a history of stroke or TIA recruited in secondary care immediately after their cerebrovascular event. In this trial, patients were randomised to either a combination of an ACE inhibitor and thiazide diuretic against double placebo, or an ACE inhibitor alone against single placebo. The decision to randomise to one or two agents was made by the supervising physician on the basis of whether or not they thought it was safe to randomise an individual patient to two agents. Mean blood pressure in the intervention arm was reduced from 147 mmHg systolic by 9 mmHg (SE 0.3), and this was associated with a 28% reduction in stroke risk . The posLong term management of blood pressure following stroke and TIA is predominantly carried out in primary care. Recent studies of blood pressure control in this setting paint a mixed picture of implementation of guidelines. In a study of seven general practices in South Birmingham in 2002, 63% of patients with a previous stroke or TIA had BP above the 140 mmHg target, and 80% above the 130 mmHg target . 68% of In summary, although there is some evidence that blood pressure lowering in people who have had a stroke or TIA is beneficial, there is no clear guidance on what the target BP should be. Furthermore, data collected from primary care suggest that guidelines from the British Hypertension Society and Intercollegiate Stroke Working Party are not being fully implemented. This research is designed to support implementation of the guidelines by both addressing the gaps in the underlying evidence base, and testing a specific mechanism for implementation of blood pressure lowering.The primary aim of Past BP is to determine whether a more intensive target BP for people with stroke or TIA in a pragmatic primary care setting will lead to a lower BP.Secondary aims of the research are to:• determine the impact of a more intensive BP target on patient quality of life;• identify the barriers to implementation of more intensive blood pressure lowering;• to explore whether the potential benefits associated with intensive blood pressure lowering might be outweighed by potential adverse effects on quality of life and costs.The latter point will be explored by economic modelling. If there is uncertainty as to whether there is net benefit from intensive blood pressure lowering, then there would be a case for a trial of different targets for BP lowering in primary care that is powered to detect differences in clinical end-points.The study will also investigate patients' understanding and beliefs about the relationship between blood pressure and stroke, and patients and healthcare professionals experience of participating in the study, which may contribute to the success or otherwise of the intervention.Past BP is a primary care based pragmatic randomised controlled trial (RCT) in which people with stroke or TIA are randomised to an intensive blood pressure (BP) target group  or a standard BP target group (target 140 mmHg systolic).We will also use qualitative methodologies to investigate patient and healthcare professionals understanding and views of BP management. Grounded theory methods will guide sampling, data collection and data analysis ,16. SampFull ethical approval for this study has been obtained from Warwickshire Research Ethics Committee, reference 08/H1211/121. A Data Monitoring Committee and a Trial Steering Committee will monitor the progress of the RCT.Management of both treatment groups will follow study specific treatment protocols that reflect the current NICE guidelines . HoweverEligible patients will be identified from general practices from the Central England Primary Care Research Network and from the Midlands Research Practice Consortium (MidReC). Each practice will run a search of their clinical computer system to identify all patients on the stroke/TIA register. Where possible, the computer search will exclude patients with clear exclusion criteria , sex, diabetes mellitus, atrial fibrillation (because of the difficulties of obtaining accurate BP measurements in this group), baseline systolic BP and practice.Patients will be followed up from trial entry for 12 months. Follow up will be carried out in several ways. Firstly, practice nurses (PNs) will see patients at 1-3 monthly intervals, depending on BP and treatment allocation. (see figure th and 6th readings (by which time any accommodation effect is likely to have worn off), enabling us to determine whether accommodation has a significant effect in this study. 24 hour blood pressure recordings using an ambulatory sphygmomanometer will be recorded at baseline and at twelve months. 24 hour ambulatory measurement will be unaffected by accommodation, so will provide further evidence as to whether or not this was significant in this study.The primary outcome measure is a change in systolic blood pressure between baseline and 12 months. Blood pressure measurements are performed in a standardised way, using BHS validated automated electronic monitors supplied and validated for the study. The patient will be seated for 5 minutes and then 6 measurements will be taken at minute intervals. The second and third measurements are averaged to give the reading. As the intensive target group have their BP monitored more frequently than those in the standard group, there may be some diminution of the 'white coat' effect in this group; the mean of readings 2 to 6 and the mean of 5 and 6 will be used to monitor for this. Any differences between the groups in the primary outcome should be sustained in the mean of the 5A variety of secondary outcome measures are also assessed during the RN follow up appointments. (see table Randomisation of 610 patients 305 per arm), with 12 months of follow-up, will detect a 5 mmHg difference in systolic BP between groups with 90% power and at a significance level of 5% assuming a standard deviation of 17.5 mmHg  will detect a 4 mmHg difference in systolic BP between groups with 90% power and at a significance level of 5% assuming a standard deviation of 11.7 mmHg . This caTo recruit patients from primary care, an estimate of the number of practices is required. Approximately 50 practices with an average list size of 7,500 will be needed in order to recruit the required number of patients. This will generate 5,625 patients on practice TIA/stroke registers . From our analysis of South Birmingham data , we antiThe principal analyses will use generalised linear models, accounting for baseline BP as a patient level covariate, and practices as random effects and compare differences in systolic BP (primary outcome), and differences in diastolic BP, quality of life, adherence and frequency of adverse effects (secondary outcomes). We will look at effect on systolic BP lowering in pre-specified sub-groups: diabetes; atrial fibrillation; and age group. Clinical event rates will be monitored by treatment allocation by the Data Monitoring & Ethics Committee, but only aggregated rates will be made available to the investigators.Decision analytical modelling will be undertaken to synthesise data from the trial and the literature in order to determine whether potential benefits of intensive blood pressure lowering (by lowering the risk of stroke) are outweighed by potential adverse effects on quality of life. Ultimately the model analyses will inform whether a further trial, powered to detect differences in clinical end-points, is required.A Markov model will be constructed to consider intensive target and standard target strategies for blood pressure lowering in patients with a history of stroke or TIA. The clinical events of importance in the model are further stroke events, myocardial infarction (MI) and other cardiovascular related mortality. Data from the trial and literature will inform the probability of these events occurring and the risk reduction afforded by the alternative strategies. Attached to each health state will be associated health state utility values  in order that quality-adjusted life years (QALYs) can be calculated. Quality of life on each treatment strategy will be obtained from the trial data on EQ-5 D, and previous studies will inform post-stroke and post-MI values. In addition, in order that cost-effectiveness analyses can be undertaken, the model will be populated with costs of the therapies prescribed in each strategy and acute and long term costs of further cardiovascular events.In order to explore uncertainties in the analyses, deterministic sensitivity analysis is proposed to test the robustness of the model when varying key model parameters and structural assumptions. Probabilistic sensitivity analysis will be undertaken to incorporate the uncertainty around parameter values and quantify the overall decision uncertainty, and inform whether further research is required.A purposively selected sample of 30 patients (10 each from intervention and control and 10 patients who declined the invitation to participate), and 20 healthcare professionals , nurses and GPs) will be selected for interview.Sampling will be carried out on the basis of study arm (intervention or control), with a further group of people who did not consent to participate in the trial also being invited to attend for an interview. Within each group, participants will be selected on the basis of: age (tertiles); socio-economic status (using IMD scores); number of different classes of medications; and whether they have had a stroke or a TIA. A researcher will randomly select patients from these categories, ensuring that similar numbers of patients in all categories are included.Practices participating in the study were selected to ensure a range of practice characteristics are represented, including practice size and socio-economic status. A researcher will randomly select 20 practitioners from these practices and send an invitation letter and information sheet, inviting them to take part in an interview.Patients and practitioners who fail to respond to invitation or who do not wish to participate will be replaced by another patient/practitioner with similar characteristics. This process will continue until theoretical saturation is achieved and interviews cease.Semi-structured, face-to-face, in-depth interviews will be carried out in patients' own homes or in other suitable locations, or with healthcare professionals in the surgery, and will be conducted by a researcher trained in qualitative interviewing techniques. Fully informed consent will be obtained from interviewees at the start of the interview, and a consent form signed. An interview topic guide will be used  have been recruited into the trial. Interviews will commence in January 2010 and are expected to be completed by February 2011.The results of this trial and the health economic analysis will provide insight into the role of intensive blood pressure targets for people who have had a stroke or TIA. If the trial is negative and a significant difference in systolic blood pressure is not observed between the two study arms, then the embedded qualitative work will be of importance to determine why low blood pressure targets did not lead to lower blood pressure. If the trial is positive, then the critical question remains as to whether striving for lower blood pressure targets is appropriate. If we observe no difference in adverse event rates or quality of life between the two arms of the trial, then it is likely that aiming for lower blood pressure targets will be worthwhile, given the benefits of reduced stroke risk that were observed in the PROGRESS trial . This wiGF or his institution has received payment for educational, advisory and research activities related to BP lowering drugs in the last 12 months from the following pharmaceutical companies: Boehringer Ingelheim, Servier.FDRH has received limited research support in terms of BP devices from Microlife and BpTRU and occasional sponsorship or speaker fees from a number of pharmaceutical companies that market anti-hypertensives.RJM is funded by an NIHR Career Development Fellowship and has no conflicts with respect to this paper.NF has received funding for research and consulting from several companies who manufacture treatments for cardiovascular disease.None of the remaining authors have any conflicts of interest.JM conceived the study. JM, KF, SC, GF, RH, RM and UM designed the RCT; KF, SV and SG were responsible for the design of the qualitative element; SJ, JM, CT and RM participated in the design of the health economics; JB, CT, and JM designed the treatment algorithm and NF participated in the design of the statistics. KF drafted the manuscript and all authors contributed to its revision. All authors have given final approval of the version to be published. JM is the study guarantor.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/10/37/prepubInterview guides. This file contains a copy of the interview guides for Patients and Health Care Professionals.Click here for file