Home blood pressure monitoring (HBPM) is gaining popularity among hypertensive patients. This study aimed to explore the influence of self-initiated HBPM on primary care patients with hypertension.Six in-depth interviews and two focus group discussions were conducted, taking into consideration the experiences of 24 primary care patients with hypertension. These patients had been using HBPM as part of their hypertension management. The overriding influences were grouped under themes which emerged from analyzing the data using the grounded theory approach.There are both positive and negative influences of self-initiated HBPM. Patients used the readings of their HBPM to decide on many aspects of their hypertension management. The HBPM readings both influenced their adherence to diet and exercise and provided certain reassurance when they experienced symptoms. In addition, the act of discussing their HBPM readings with their health care providers resulted in an enhanced doctor-patient therapeutic relationship. Nevertheless, HBPM created confusion at times in some patients, particularly with regard to the target blood pressure level and the need for medication. This led to some patients making their own medical decisions based on their own standards.HBPM is becoming an integral part of hypertension management. Primary care patients who self-initiated HBPM reported being more self-efficacious, but lack of participation and guidance from their doctors created confusion, and hindered the true benefit of HBPM. The use of HBPM as an adjunct to office blood pressure readings in the management of hypertension is advocated by the Malaysian National Hypertension Guideline  as well Globally, the use of HBPM by patients is gaining popularity. The prevalence of use ranges from 24% to 66% ,14. In tPatients with hypertension found it acceptable to monitor their blood pressure at home . PrimaryThe effect of purchasing and using HBPM at patients' own initiative has not been studied before. This study aimed to explore the practices and experiences of these patients. Using the qualitative approach, the study hoped to understand the influences of HBPM on these patients. The findings of this study will be useful for healthcare providers when faced with patients who self-initiated the use of HBPM as part of their hypertension management.2, with an estimated population of a little over 450,000 inhabitants (2003 figures). The clinic served patients from all walks of life, ranging from the affluent middle class to patients from a lower socioeconomic status. As it is attached to a tertiary referral hospital, the clinic also sees patients from outside the district and state. Ethical approval for the study was obtained from the UMMC Ethics Committee on 22 April 2009, as per letter dated 24 April 2009 with MEC Ref. No: 715.2.The study was carried out at an urban primary care clinic, located within the University Malaya Medical Centre in Petaling Jaya, Selangor. Petaling Jaya covers an area of 51.4 kmThe populations sampled were primary care patients diagnosed with hypertension, who had experience owning and using home blood pressure monitors as part of their hypertension management. Purposive sampling methods were used to recruit patients who self-initiated the use of HBPM. Patients were informed of the study by their healthcare providers and through posters. Those who were interested gave their contact numbers to a member of the research team. Patients were then invited to attend either an in-depth interview session or a focus group discussion, based on their availability. Informed consent and simple demographic data including age, gender, who initiated the purchase and duration of HBPM usage were obtained prior to each data collection session.Table Patients' accounts with regards to HBPM were captured by two methods of data collection: in-depth interview and focus group discussions.Six in-depth interviews were conducted to explore patients' practices and beliefs using HBPM as part of their hypertension management. A rough topic guide was used to act as a reminder of areas to be covered in the interviews  acted as the moderator, and there was a research assistant who took notes from the discussions. The patients were asked general questions regarding their experience in using HBPM, and intra-group discussions were encouraged. The discussions were conducted in both English and Bahasa Malaysia. All interviews were digitally recorded, and field notes were also taken.The data from the interviews and focus groups were transcribed verbatim. Data was analysed by the primary investigator (AA) using thematic analysis. The transcriptions were large, and had to be stored and managed accordingly whilst simultaneously ensuring confidentiality. Thus the qualitative software, NVivo 8 program was used for this purpose, as well as to assist in the handling of massive data and streamlining of the coding process . The traThis study identified several influences of HBPM on patients' management of hypertension. These influences could be divided into positive and negative influences, depending on their potential effect on blood pressure control. Those that could improve blood pressure control were placed under positive influences, and those that could lead to worsening of blood pressure control placed under negative influences. From analysis of patients' responses, this study was able to identify five themes under positive influences and two themes under negative influences.Patients universally believed that their diet and exercise regime have an influence on their blood pressure readings. The readings they obtained from HBPM were frequently used as a form of feedback, to gauge the adequacy of their lifestyle changes. Patients reported altering their diet and increasing their frequency of exercise in response to high home blood pressure readings.What do I do? I will note down what food I eat and what activity I did. That was during the holidays. I will note down today what did I eat, then I said maybe this food is good for me then I will note down whether I go for a walk in the morning, whether I sweat. I noticed when I sweat the pressure goes better(IDI2/53-year-old/10 years of HBPM usage)When its high, then I know it's either my diet or I've not been exercising. So when it's high I'll take my walks. I'll do my aerobics and then cut down on meats, go vegetarian.(FGD2/68-year-old/3 years of HBPM usage)Patients in this study seemed knowledgeable about their hypertension treatment. Patients comfortably used medication names and dosages when discussing their medications. By using HBPM, they were able to see the effect of pharmacological treatment, and as a result were able to comment on the efficacy of different hypertension medications.My pressure is still high, so I wonder whether the pressure pills (is not effective). Because I was on Atenolol then changed to Coversyl. Now (I am) on Cozaar.(FGD2/63-year-old/10 years of HBPM usage)It is better (with HBPM) because you can see whether the medicine is effective. Even now when I am on medicine already, before taking the medicine I will go and measure, after taking the medicine I will also measure. That's why I notice that Coversyl is more effective for me(IDI2/53-year-old/10 years of HBPM usage)This awareness and interest resulted in patients reporting improved adherence to their antihypertensive medications.What causes the change in my blood pressure? I will relax and will observe the readings. I realized that I do need to take the medications because if I don't, the blood pressure will go up(FGD1/54-year-old/1 year of HBPM usage)Patients felt reassured with their ability to continue monitoring their blood pressure at home. Many felt that the without it, duration until their next clinic follow-up appointment was too long, regardless of the actual duration. Home monitoring gave them a sense of confidence that their blood pressure readings were satisfactory between appointments.Why we need the machine in the house? I think it's an important thing to have if we can afford because our visit to the doctor (is infrequent). Duration between visits is about three months(FGD2/68-year-old/3 years of HBPM usage)The doctor gave me 8 months appointment; I might have died by then(FGD1/53-year-old/5 years of HBPM usage)I can say this machine can give patient immediate psychological relaxation. It is very important. If you are not feeling well and the blood pressure reading is still normal. So feeling psychologically relax(FGD1/66-year-old/20 years of HBPM usage)Eighteen patients also obtained home blood pressure readings for reassurance when they experienced symptoms. These symptoms varied between patients, but they felt relieved with the ability to measure their blood pressure readings when symptoms occurred.So usually it's like that (checking irregularly). Except when I feel very bad, like something is wrong. Sometimes I may feel some chest pains then I'll go and check(FGD1/40-year-old/3 years of HBPM usage)Aiyo, the days when I get the reading one two zero (120 mmHg), ahh so happy. That's like striking the first prize in lottery you know(FGD2/63-year-old/7 years of HBPM usage)The patients reported on-going discussions regarding their hypertension management with their healthcare providers, especially with regards to the home blood pressure readings. The processes had strengthened the therapeutic alliance, and increased trust between patient and healthcare providers.The doctor told me to take the readings early morning after waking up from sleep, then at noon after being active and before bed time . Then the readings I brought to show to the doctor(FGD1/54-year-old/1 year of HBPM usage)One patient noted his readings at home to be lower than the ones recorded in the clinic by his cardiologist. So he was asked by his healthcare providers to bring his home monitors to clinic for validation of accuracy.I said that the doctor's manual blood pressure readings are incorrect. When I argued with him, he said bring your machine and check it against his manual machine(FGD2/71-year-old/10 years of HBPM usage)Many patients wanted to be told about blood pressure readings that are recorded in the clinic, and wanted more time with their doctors to discuss their home blood pressure readings and subsequent management.But when we went for check-up, the doctor rarely tell us the actual blood pressure reading. He did not tell us the readings he just said it's okay. Actually we would like to know, the actual reading of the diastolic blood pressure(FGD1/63-year-old/3 years of HBPM usage)Some patients related that they had shared the use of home blood pressure machine with their spouse, parents and siblings. This led to enhanced awareness and support from their family members.I have the machine in the house since 1998, because my husband is a diabetic. He and my mother both have diabetes and high blood pressure, so we decided to buy one (home blood pressure monitor). So when I check their blood pressures, I will also check mine(FGD2/57-year-old/5 years of HBPM usage)Definitely useful, that's why I taught my mum to use the meter. My meter is very easy to use, so she had been using it diligently(IDI1/53-year-old/10 years of HBPM usage)Many patients expressed concern regarding the reliability of the home blood pressure readings and ultimately the accuracy of the digital blood pressure monitors. They noted variability in the blood pressure readings, and therefore showed a tendency to regard or disregard the values according to their own judgements.That's why. I am also very suspicious, I mean, (the readings are) so variable within two weeks you know. Up and down, never consistent. So, we wonder whether I should be taking tablets. Is it worth of taking tablets or is it worth of using the machine at all, you see(FGD2/75-year-old/10 years of HBPM usage)Its measurement fluctuates, every moment of the day. (In the) morning will be 140 (and) later 120. Then I said why it is such a variation?(FGD2/67-year-old/9 months of HBPM usage)One of the younger patients tried to clear his confusion by discussing his home blood pressure readings with his doctor. He mentioned that this variation could be minimised by increasing the number of measurements taken at one time. This technique was taught to him by his healthcare provider.Take two readings and repeat again. It could be quite accurate la, quite accurate. Take the average(FGD2/30-year-old/5 years of HBPM usage)Confusion also arose regarding the acceptable target blood pressure levels and the frequency of monitoring. One participant had uncontrolled hypertension for many years and had recently suffered from stroke. He believed that his target blood pressure must be compared against his previous blood pressure reading, and target value should be individualised.Because my previous readings (systolic blood pressure (SBP)) are 179, 180(mmHg) and the lower reading 110 (mmHg). So when I get reading of (SBP) 159 (mmHg) and occasionally the lower reading (diastolic blood pressure) 90 (mmHg), I felt happy. So for me when I occasionally get the reading (SBP) 140 (mmHg), that is already very good for me(FGD1/54-year-old/1 year of HBPM usage)The frequency of checking blood pressure also varied. Some measured their blood pressure daily without fail. Others did it only when they had symptoms or when it was convenient. None had written the readings down in a record book.I checked mine every day, without miss. One time before going to sleep(FGD1/66-year-old/3 years of HBPM usage)Some patients made their own decision as to whether to comply with medical advice based on the home blood pressure readings. These included starting or stopping of medications, as well as advice on lifestyle changes.Based on home blood pressure readings, two patients delayed in taking hypertension medications although prescribed by their healthcare providers. One patient had diabetes, and her office blood pressure was off target (> 130/80 mmHg), but because her home blood pressure readings were around 125/80 mmHg, she decided not to take her medications.But if you check, normally it doesn't go more than one twenty five on my machine. So when I come here they say it's high. That's why I begin to (doubt). But I never took the medication (given) but I exercise(FGD2/57-year-old/5 years of HBPM usage)Another patient said she was rushing when she arrived at the clinic room, which could explain the high office reading. When she rechecked the blood pressure reading at home, she felt this was acceptable and therefore she didn't take the medications added by her doctor for her hypertension.Yesterday morning I checked (my BP) was alright. When I came  was higher the systolic. Then the evening I didn't started the medication yesterday. Last night I checked twice again, the readings were 150 over and 83 something. Of course I didn't start the medication(FGD1/70-year-old/10 years of HBPM usage)The variable blood pressure readings at home at times hindered some patients' adherence to medical advice. One patient had been struggling to come to terms with his diagnosis of hypertension. He noted that his blood pressure readings at home seemed to vary widely and did not change much despite medication. He began to question the need to take the medication.But I have to take the same type (of antihypertensive medication). I checked my reading..... not different from what it was. Then should I stop?(FGD2/75 years old/using for 10 years)This study assessed the influence of HBPM on hypertensive patients who self-initiated its use. In-depth exploration of patients' experiences and practices showed that self-initiation of HBPM is associated with both positive and negative implications.The positive influences included being more reflective, especially concerning lifestyle changes, having an increased interest in the management of their hypertension and giving users feelings of reassurance. All these positive influences lead to improved patient's self-efficacy. Self-efficacy is defined as a person's confidence to carry out behaviour necessary to reach a desired goal . It is aThis study found that dealing with a disease that is mostly asymptomatic raised a great deal of anxiety and uncertainty on the part of the patients. The tangible readings from home blood pressure monitors turned this largely asymptomatic disease onto a condition that is measurable in patients' own homes. These readings became the patients' cue for action to take the necessary actions. Furthermore, patients in this study reported first hand observations of the effect of unhealthy practices such as a salty diet and sedentary lifestyle on their blood pressure readings. The HBPM readings reinforced advice given by healthcare practitioners on the appropriate lifestyle changes and the need for compliance.This study also found that patients who self-monitor were eager to be more involved in discussions about their blood pressure control, especially when there is discrepancy between home and clinic blood pressure readings. Similar findings were also reported in a qualitative study looking at primary care patients' experiences of home blood pressure measurement in the United Kingdom . When paThe importance of HBPM as a mode of hypertension screening in the community was revealed in this study. Patients reported sharing the use of HBPM with their immediate family, and occasionally even neighbours. In fact, some of the patients involved in this study reported using HBPM prior to being diagnosed with hypertension. With wider use of HBP monitors in the community, potentially more people with hypertension could be diagnosed. This is provided that patients are given greater knowledge regarding HBPM readings that could indicate diagnosis of hypertension and the HBP monitors used are accurate and validated.Despite the benefits of HBPM, this study also found some negative influences of self-initiated HBPM on these patients. Patients reported feeling confused and unsure of the true meaning of HBP readings. They noted the values seemed to be fluctuating, and sometimes differed significantly from clinic readings. Since these patients self-initiated the purchase and use of HBPM, the machine purchased might not have been validated, and thus may not be completely accurate. In Turkey, only 40.7% of the HBP monitors used by patients were accurate, when checked in a campaign run at a University Hospital .Only some of the patients in this study reported telling their doctors about their HBPM. Lack of time and doctor's lack of interest were some of the reasons given for not consulting their doctors. For those lacking guidance, the variability of HBPM readings led them to regard and disregard HBPM readings according to their own standard. The lack of guidance seemed to stem not only from lack of awareness, as some patients reported telling their doctors about their HBPM. Low level of acceptance by doctors could be another reason. A study in Canada noted that only 19% of the primary physicians surveyed used the home readings to guide therapy . These dFrom the findings in this study, primary care providers need to increase their participation, and give guidance to patients who self-initiated owning and using HBPM. As patients in this study reported using HBPM readings to decide on various aspects of their hypertension management, most critically whether to start taking new medication started by their doctors, doctors managing these patients need to discuss the significance of the HBPM readings and the target HBP reading which is different from the clinic reading. Other areas to cover in counselling sessions are information regarding validated brand names and models, correct techniques of measurement and actions to take when high readings are experienced. It is also important to be aware that people other than the patients may ultimately use the monitors. Advice on how to tackle these situations should also be given to patients.The aspect of self-doctoring in patients using HBPM also needs to be regulated. It is impossible to eliminate all aspects of patient self management of their disease using home monitoring. From this study it is important to lay down ground rules concerning self-doctoring, such as discussions on the limitations of the home blood pressure readings, the importance of long term control and not just one off reading, and the concept of a risk continuum, where the aim is to reduce the overall cardiovascular risk and not just the blood pressure numbers. It is through the concerted effort of doctors and patients that the true potential of HBPM could be realised and its negative implications minimised.This study is not without limitations. Although this study had a fair representation of primary care patients with hypertension, selecting the study population from a university-based urban primary care clinic limits the findings. Many of the patients are from the middle to high-income group, as well as coming from a more educated background. The findings may be more representative of more knowledgeable and interested patients. The voluntary nature of recruitment also may have led to over-representation of hypertensive patients who have greater motivation. This may lead to the increased interest in the involvement of hypertension management in this group of patients.HBPM is becoming an integral part of hypertension management. Primary care patients who self-initiated HBPM use need their doctors' participation and guidance especially regarding target blood pressure level, frequency of monitoring and measures to deal with aberrant blood pressure readings. Without which, the true benefits of this important self-management tool may not be realized.The authors declare that they have no competing interests.AA designed the study, conducted the interviews, analysed the data and drafted the manuscript. SO conducted one focus group discussion, analysed the data and provided overall supervision of the study. All authors were responsible with redrafting the final version of the manuscript. All authors read and approved the final manuscript.1. The purchasea. Impetusb. Relationship with diseasec. Encouragement/triggering eventd. Discussion/encouragement from doctor2. The choicea. Factors in consideration: price, accuracy, validationb. Use of other health related monitors3. The usagea. Intended useb. Actual usec. Explanation of techniqued. Frequency of use/influencing factors4. The readingsa. What is considered normal?b. What do they do with the readings?c. How did the readings influence the management of hypertension?d. What do they do if the readings deemed too high/low?e. Any discussion of the readings with the doctor?5. The valuea. Perceived valueb. Actual valuec. Any barrier to maximize the valued. Any potential harm6. The difficultiesa. Any difficulties with useb. How?c. Calibration/durability issuesThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/12/143/prepubAppendix 1: Topic Guide: In-Depth Interview and Focus Group Discussion.Click here for file


There is emerging evidence for the presence of an extensive microbiota in human lungs. It is not known whether variations in the prevalence of species of microbiota in the lungs may have aetiological significance in respiratory conditions such as asthma. The aim of the study was to undertake semi-quantitative analysis of the differences in fungal species in pooled sputum samples from asthma patients and controls.Induced sputum samples were collected in a case control study of asthma patients and control subjects drawn from the community in Wandsworth, London. Samples from both groups were pooled and then tested for eukaryotes. DNA was amplified using standard PCR techniques, followed by pyrosequencing and comparison of reads to databases of known sequences to determine in a semi-quantitative way the percentage of DNA from known species in each of the two pooled samples.Psathyrella candolleana, Malassezia pachydermatis, Termitomyces clypeatus and Grifola sordulenta showed a higher percentage of reads in the sputum of asthma patients and Eremothecium sinecaudum, Systenostrema alba, Cladosporium cladosporioides and Vanderwaltozyma polyspora showed a higher percentage of reads in the sputum of control subjects. A statistically significant difference in the pattern of fungi that were present in the respective samples was demonstrated using the Phylogenetic (P) test (P < 0.0001).A total of 136 fungal species were identified in the induced sputum samples, with 90 species more common in asthma patients and 46 species more common in control subjects. Malassezia pachydermatis, which is known to be associated with atopic dermatitis.This study is novel in providing evidence for the widespread nature of fungi in the sputum of healthy and asthmatic individuals. Differences in the pattern of fungi present in asthma patients and controls merit further investigation. Of particular interest was the presence of  On aver2, some ofHistorically, healthy lungs were believed to be free of bacteria and that during infection organisms “gain a foothold in the normally sterile lung tissue” . HoweverProteobacteria more frequently found in the bronchi of asthmatics patients than in controls [There is relatively little literature examining microbiota in human lungs. Tunney et al.  showed tcontrols .The current study further examines the role of atypical microbiota in respiratory disease. The study used molecular techniques to identify eukaryote species that were present in induced sputum samples taken from asthma patients and controls, living in Wandsworth, London. The aim of the study was to undertake semi-quantitative analysis of the differences in fungal species present in pooled sputum samples from asthma patients and controls.The study protocol was approved by Camden and Islington community local research ethics committee (ref 08/H0722/540). All patients participating in the study supplied informed consent. This case control study from which the induced sputum samples were drawn has previously been described. Further information on the characteristics of the subjects in this study has been provided in that paper . In summ2 areas were excised from each microscope slide. The samples were combined to yield two pooled samples for subsequent DNA extraction and PCR: asthma patients and control subjects. (A sample from one asthma patient was inadvertently included in the control set). DNA was subsequently extracted using the Zymo research pinpoint system  in accordance with manufacturer’s instructions. The samples were taken from 30 asthma patients and 13 non-atopic control subjects involved in the case control study.Participants inhaled isotonic saline via an ultrasonic nebuliser. Globules of sputum were coughed up into petri dishes, spread on microscope slides and stained for microscopic examination. Approximately 5 mmExtracted DNA was amplified using a PCR protocol for the partial 18S rRNA gene using the primer pair (Euk1a (5’ CTG GTT GAT CCT GCC AG 3’) and Euk516r (5’ ACC AGA CTT GCC CTC C 3’)) in accordance with previously described protocols ,14. The The difference between the pattern of fungal species in each of the two pooled samples was compared using Unifrac ,16. ThisPatients had a mean age of 41.6 years  and control participants a mean age of 35.7 years . The patient group was 40% male and the control group was 46% male.A positive answer to at least one of the four questions regarding possible mould in the home was recorded in 30% (9/30) asthma patients and 15.4% (2/13) of control subjects. Due to the small sample size, this relatively large difference was not statistically significant.The differences based on the percent of total DNA reads of in the pooled samples from asthma patients and non-atopic controls are shown in Tables Psathyrella candolleana, Malassezia pachydermatis, Termitomyces clypeatus and Grifola sordulenta were particularly prevalent in the sputum of asthma patients and Eremothecium sinecaudum, Systenostrema alba, Cladosporium cladosporioides and Vanderwaltozyma polyspora were particularly prevalent in the sputum of control subjects. No other eukaryote species were identified in the sputum samples.A total of 136 fungal species were identified in the induced sputum samples, with 90 species more common in asthma patients and 46 species more common in control subjects, based on the percent of total DNA reads  represent members of the basidiomycete family [The range of fungal species present in both asthma patients and control subjects was larger than expected. There were also clear differences in the pattern of fungal species between asthma patients and control subjects. The fungi rmatitis . Howevere family . The late family  and one Cladosporium, the species identified in induced sputum are not commonly found in air samples examined using standard culture techniques [Except for chniques . AnalysiHomo sapiens’ 18S rRNA gene 100% [We used universal primers for the eukaryotic 18S rRNA gene and were surprised that no eukaryotes other than fungi were identified in cases or controls. We have considered a number of potential reasons why this may be the case and the most likely was that levels of non-fungal eukaryotic DNA, present in the samples, was below the limits of detection. The PCR primers were chosen after considerable deliberation and a probeCheck test showed that they were universal and matched ene 100% . HoweverIndividual level analysis of samples was considered, but rejected as it was anticipated that, if the samples from each individual were analysed separately, the number of eukaryotes in each sample would be below the threshold of detection. Samples for this study were therefore pooled to maximise the number of copies of each species in the pooled samples and consequently maximise the probability of detecting all the species that were present.Malassezia pachydermatis in the sputum of the research subjects, as this organism has been identified as a commensal on the skin of dogs and have could contaminated air in the homes of some of the research participants.The study has a number of weaknesses. The sputum was not fresh when it was examined and although every effort was made to prevent contamination of samples by spores in the air, this is a possibility. The sample size is small and therefore may not be representative of asthma patients. Unfortunately, information on pets was not collected in this study and therefore could not be correlated with the presence of absence of particular fungi. It is possible to speculate that the presence of a pet (particularly a dog) in the subjects' house might be associated with the presence of The potential significance of these fungi is unclear. There is tentative emerging evidence that microbiota may form part of a complex causal web that results in disease, for example, by their effects on the immune system, without becoming pathogenic in the classical sense. For example, microbial compounds present in sputum may play a role as adjuvant factors and encourage a Th2-biased allergic response ,23.This study provides emerging evidence for the widespread presence of fungi in the sputum of asthma patients and control subjects. Significant differences have been identified in the pattern of fungi present in asthma patients and control subjects drawn from the same community. Although this method demonstrates the possibility of using microscopy samples, further investigation is warranted which applies these techniques to fresh sputum samples. This method may in itself be applicable to analysis of historical samples and may in turn prove of interest in evaluating the microbiome of the lung demographically and between generations.The authors declare that they have no competing interests.HCVW obtained the initial funding, designed the case control study, obtained ethical and NHS R&D permission and wrote the first draft of the paper. CG, RG and JM undertook analysis of the sputum samples. All authors have contributed to, read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/69/prepub


Patients with COPD have an increased risk of cardiovascular disease. Whilst pulmonary rehabilitation has proven benefit for exercise tolerance and quality of life, any effect on cardiovascular risk has not been fully investigated. We hypothesised that pulmonary rehabilitation, through the exercise and nutritional intervention, would address these factors.Thirty-two stable patients with COPD commenced rehabilitation, and were compared with 20 age and gender matched controls at baseline assessment. In all subjects, aortic pulse wave velocity (PWV) an independent non-invasive predictor of cardiovascular risk, blood pressure (BP), interleukin-6 (IL-6) and fasting glucose and lipids were determined. These measures, and the incremental shuttle walk test (ISWT) were repeated in the patients who completed pulmonary rehabilitation.On commencement of rehabilitation aortic PWV was increased in patients compared with controls (p < 0.05), despite mean BP, age and gender being similar. The IL-6 was also increased (p < 0.05). Twenty-two patients completed study assessments. In these subjects, rehabilitation reduced mean (SD) aortic PWV (9.8 (3.0) to 9.3 (2.7) m/s (p < 0.05)), and systolic and diastolic BP by 10 mmHg and 5 mmHg respectively (p < 0.01). Total cholesterol and ISWT also improved (p < 0.05). On linear regression analysis, the reduction in aortic PWV was attributed to reducing the BP.Cardiovascular risk factors including blood pressure and thereby aortic stiffness were improved following a course of standard multidisciplinary pulmonary rehabilitation in patients with COPD. Chronic obstructive pulmonary disease (COPD) is an increasing cause of global morbidity and mortality  of whichIn the general population, addressing physical activity and nutritional optimisation, both components of multidisciplinary pulmonary rehabilitation, are associated with reducing the CV risks such as blood pressure (BP) and cholesterol . ExercisDemonstrable improvements in aortic PWV have been shown in non-COPD populations with short-term aerobic exercise training ,10, howeMultidisciplinary pulmonary rehabilitation is integral to the management of patients with COPD. Although the programme is short term, encompassing exercise, education and nutritional advice, its aim is to address lifestyle modification and several endeavours are currently addressing how benefits can be maintained. Demonstrable benefits in exercise capacity and quality of life are evident with improvements seen at 1 or 2 years following the course, even without a maintenance arm ,14. WhilThe design was a prospective cohort study. Patients meeting the inclusion and exclusion criteria were recruited consecutively from the routine rehabilitation referral list at University Hospital Llandough. At baseline they were compared with control subjects who attended for one assessment only.Thirty-two patients with confirmed COPD, accepted for rehabilitation were recruited. Patients were clinically stable, defined as no change in dyspnoea, cough or sputum beyond day-to-day variability; or requirement for antibiotic or oral corticosteroid therapy in the preceding month. Subjects were excluded from the study (but not rehabilitation) if they had known ischaemic heart disease, cardiac failure, diabetes mellitus, malignancy, or any other inflammatory or metabolic condition, or were receiving oral corticosteroids, disease modifying or weight loss drugs. Twenty age- and sex-matched sedentary controls free from respiratory disease and other exclusions as above, but with a history of cigarette smoking were also recruited. Controls were spouses of patients or past volunteers who had agreed to consider future research. All subjects gave written, informed consent and the study had South East Wales Research Ethics Committee approval: 07/WSE04/05.2 peak [The multidisciplinary pulmonary rehabilitation programme has been detailed previously . Briefly2 peak . Patient1), forced vital capacity (FVC) and their ratio (FEV1/FVC) according to guidelines [For all participants, height (m) and weight (kg) were measured barefoot, wearing lightweight clothing and body mass index (BMI) was calculated. All participants performed spirometry  to determine forced expiratory volume in 1 second  and pulse pressure (PP) . Applanation tonometry using a high fidelity micromanometer (Millar Instruments Texas) was used to measure pulse waveforms at the radial, carotid and femoral sites, in relation to the R wave of a simultaneous ECG recording . The radial pulse wave was used to generate a central arterial waveform, and augmentation index (AIx) was calculated as the difference between the first and reflected systolic peak as a percentage of pulse pressure, corrected to a heart rate of 75 beats per minute. Using integral software aortic  and brachial  PWV was calculated as the speed of the pulse wave travelling between the 2 sites. Increased PWV and AIx indicate increased stiffness of blood vessels with aortic PWV being the preferable measure in this age group [Subjects were assessed having fasted and abstained from caffeine, tobacco and inhaled short-acting βA sample of venous blood was taken following the haemodynamic assessment, but prior to any exertion. Fasting glucose and cholesterol were determined within the Trust biochemistry laboratory according to standard procedure. Interleukin (IL)-6 was determined by ELISA  with a minimum detectable limit of less than 0.70 pg/mL .10 transformed and checked for normality prior to analysis. Data are presented as mean and standard deviation (SD) unless stated. Patients and controls were compared using an unpaired t test and the chi squared test for categorical data. Relationships were investigated using Pearson's correlations.Data analysis was performed using the Statistical Package for the Social Sciences , version 16.0. Skewed data were logt test for parametric data and linear regression was used evaluate the contribution of change in blood pressure to change in aortic PWV. The significance level for all statistical tests was set at p < 0.05. The sample size was based on previous published work from the department in patients with COPD [Assessments pre and post rehabilitation were analysed using the paired ith COPD . For an 2 in patients at room air was 70 (10)mmHg, 4 patients were on LTOT and had been stabilised on this prior to commencement of rehabilitation. Thirteen patients classified as GOLD stage II and 19 patients were stage III/IV [Patients and controls were similar with respect to age, sex and BMI Table . All parr was 70 0mmHg, 4 2-agonist, 5 (16%) were taking a long-acting β-agonist alone, 25 (78%) were on combination inhaled therapy (long-acting β-agonist & corticosteroid), 30 (94%) were taking an anticholinergic bronchodilator.Of the 32 patients recruited at baseline, 31 (97%) of patients were taking a short-acting βEight patients (25%) and four control subjects (20%) were taking antihypertensive medication, while five patients (16%) and six controls (30%) had been prescribed statins for hypercholesterolaemia. There were no other cardiac medication and there was no change to CV or respiratory maintenance medication was made during rehabilitation.Patients with COPD had greater aortic PWV than controls (p < 0.05) despite having similar MAP. There were 13 (41%) patients, 4 of whom were on prior treatment had a BP greater than the recommended, with either a systolic >140 or diastolic >90 mmHg. In parallel, 5 25%) controls, 2 on treatment, also had elevated BP. Heart rate and IL-6 were also greater in patients than controls (Table 5% contro2), and 8 patients (3 controls) were obese (BMI ≥30 kg/m2) [Although mean BMI was similar in patients with COPD and control subjects, BMI was more heterogeneous in the patients. Six patients (no controls) were underweight (BMI <20 kg/m0 kg/m2) .1, oxygen saturations or smoking pack-years. Although patients reported less physical activity in the preceding month than controls this was not related to aortic PWV.In all subjects and in patients alone, as expected, aortic PWV was related to age ; as well as aortic PWV related to central and peripheral systolic BP and peripheral MAP . Aortic PWV did not relate to other clinical variables; FEVOf the 32 patients, 22 completed rehabilitation - for this group of completers, median (range) number of attendances was 18 (14-20) out of 20. There was no difference in age, gender, baseline lung function, haemodynamic variables or body composition between patients who completed study assessments and those who did not. Reasons for non-completion were illness, personal constraints or exclusion from the study due to commencement of oral corticosteroids. One of the five patients who smoked at baseline stopped smoking during rehabilitation.Following rehabilitation aortic PWV reduced from 9.8 3.0) to 9.3 (2.7) m/s (p < 0.05) Figure  and peri.0 to 9.3Overall there was no change in glucose, IL-6 or BMI. However as expected, traditional rehabilitation outcome measures - ISWT and SGRQ improved, although these did not relate to change in aortic PWV. There were 19/22 patients who exceeded the minimum clinically significant improvement of 47.5 m  and 17 pThis is the first study to evaluate the effect of a standardised multidisciplinary pulmonary rehabilitation programme on central arterial haemodynamic risk factors in patients with COPD. Pulmonary rehabilitation improved several cardiovascular risk factors including aortic PWV, an independent predictor of CV risk in the general population, blood pressure and cholesterol ,5. A recThe clinical relevance of the change in aortic PWV in this study is uncertain as a clinically significant reduction has yet to be fully established. Certainly, an increase in aortic PWV of 1 m/s corresponds to an adjusted risk increase of 15% in CV mortality , but theAlthough limited data exists in subjects with COPD, the haemodynamic benefits of aerobic exercise have been demonstrated in non-respiratory conditions. In subjects with hypertension 4 weeks of exercise resulted in a 9% reduction in aortic PWV . This isThe mechanism of improved haemodynamics following exercise has not been established, but may include increased shear stress with improved structural compliance, nitric oxide related vasodilation and reduced sympathetic drive . The latWe and others have previously reported increased arterial stiffness in patients with COPD compared to controls ,33,34. IAortic PWV has previously been associated with impaired lung function in both COPD subjects  and a geThe limitations of this study include the small sample size and a high rate of drop out from the study over the course of pulmonary rehabilitation. Whilst we still met our sample size, the mean aortic PWV at baseline was lower than previously reported and which was used in our power calculation , perhapsThis study confirms the presence of multiple cardiovascular risk factors in patients with COPD undergoing multi-disciplinary pulmonary rehabilitation, and is the first to show that a standardised programme appears to improve the cardiovascular risk profile. Pulmonary rehabilitation may be an opportunity to identify and treat cardiovascular and metabolic dysfunction and therefore may provide additional benefit lead to patients. Further research is required to corroborate and determine the longer term implications of these haemodynamic changes. The clinical impact of the findings reported is potentially transferable across rehabilitation programmes and reinforces the known functional and health status improvements that pulmonary rehabilitation already delivers.1: forced expiratory volume in 1s; FVC: forced vital capacity; GOLD: Global Initiative for Chronic Obstructive Lung Disease; HDL: high density lipoprotein; ISWT: incremental shuttle walk test; IL-6: interleukin; LDL: low density lipoprotein; LTOT: long-term oxygen therapy; MAP: mean arterial pressure; PaO2: arterial partial pressure of oxygen; PP: pulse pressure; PWV: pulse wave velocity; SBP: systolic blood pressure; SGRQ: St Georges respiratory questionnaire; SD: standard deviation; SpO2: peripheral oxygen saturation; VO2 peak: peak oxygen consumption.AIx: augmentation index; BMI: body mass index; BP: blood pressure; COPD: chronic obstructive pulmonary disease; CV: cardiovascular; DBP: diastolic blood pressure; FEVThe authors declare that they have no competing interests.NG helped design the study, conducted the clinical assessments, analysed and drafted the manuscript; JD contributed to the clinical evaluation of subjects, interpretation and writing; SE contributed to the interpretation and writing and provided academic support to NG; JC helped design the study, interpret and contributed to the writing; DS helped design the study, assisted with interpretation and contributed to the writing; CB helped design the study, assisted with conduct of study, analysis and interpretation and helped write the manuscript. All authors read and approved of the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2466/11/20/prepub


A non-dipper blood pressure (BP) pattern is very common in chronic kidney disease (CKD) patients and affects the progression and development of cardiovascular disease. However, data on the reversed dipper BP pattern on target-organ damage in Chinese CKD patients are lacking.A total of 540 CKD patients were enrolled. Ambulatory blood pressure monitoring (ABPM), clinical BP, ultrasonographic assessment and other clinical data were collected. Univariate and multivariate analyses were used to ascertain the relationship between ABPM results and clinical parameters.A total of 21.9% CKD patients had a reversed dipper BP pattern, 42% of patients had a non-dipper BP pattern and 36.1% of patients had a dipper BP pattern. Patients with reversed dipper BP pattern had the worst renal function and most severe cardiovascular damages among these CKD patients (p<0.05). The estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMI) correlated significantly with the rate of decline of nocturnal BP. A reversed dipper BP pattern was an independent factor affecting kidney damage and left ventricular hypertrophy. Age, lower hemoglobin level, higher 24-h systolic BP from ABPM, and higher serum phosphate levels were independent associated with a reversed dipper BP pattern after multivariate logistic regression analyses.The reversed dipper BP pattern is closely related to severe renal damage and cardiovascular injuries in CKD patients, and special attention should be given to these CKD patients. The rising prevalence and associated morbidity of chronic kidney disease (CKD) has resulted in significant disease burden and became a major public health problem in many countries Accurate measurement of BP is very important for CKD patients, whereas the traditional Perloff method has limitations  All patients in our division diagnosed with CKD from May 2010 to May 2012 were enrolled this study. The exclusion criteria were subjects who: (i) had undergone treatment with corticosteroids or hormones; (ii) had acute changes in the estimated glomerular filtration rate (eGFR) >30% in the previous 3 months; (iii) were pregnant; (iv) had a history of abuse of drugs or alcohol; (v) had night-work or shift-work employment; (vi) had acquired immunodeficiency syndrome (AIDS); (vii) had cardiovascular disorders ; (viii) could not tolerate ABPM; (ix) could not communicate and comply with all of the study requirements.The study protocol was approved by the Ethics Committee of the third hospital of Sun Yat-sen University . All study participants provided written informed consent before enrolling in the study.CKD patients were diagnosed using clinical practice guidelines set by National Kidney Foundation Disease Outcomes Quality Initiative (NKF-K/DOQI) Patients underwent 24-h ABPM using a TM-2430 monitor . Cuff size was chosen on the basis of arm circumference, and the cuff fixed to the non-dominant arm. Three BP readings were obtained in the morning (7∶00 to 10∶00 am) concomitant with sphygmomanometric measurements to ensure that the mean of the two sets of values differed by <5 mmHg. BP was recorded every 15 min from 7∶00 am to 10∶00 pm, and every 30 min from 10∶00 pm to 7∶00 am. The daytime and night-time periods were derived from diaries recorded by the patients during ABPM. Monitoring was always undertaken on a working day. Patients did not have access to values of ABP. Strenuous physical activity was discouraged in all patients during the monitoring period. Their daily activities were comparable. BP series were eliminated from the analysis if: >30% of the measurements were missing; data were missing for >3-h spans; they were collected from subjects while they were experiencing an irregular rest–activity schedule or a night-time sleep span <6 h or >12 h during monitoring.During a visit to the physician (8∶00 to 11∶00 am), BP was measured for each patient 2.72.7 (man) and >45 g/m2.7 (woman) were diagnosed as left ventricular hypertrophy (LVH) The volume, mass, systolic function and diastolic function of the left ventricle were assessed using two-dimensional echocardiography. Left ventricular mass was calculated using the Duvereux method Carotid intima-media thickness (CIMT) was determined by averaging three measurements taken on each carotid artery , measuring the distance between the leading edge of the lumen–intima interface, and the leading edge of the collagenous upper layer of the adventitia using high-resolution B mode ultrasonography. Measurements were taken in areas free of obvious atherosclerotic plaques around the level of the carotid bifurcation.We collected 24-h urine samples within a 7-day period of ABPM and measured levels of urinary protein, creatinine, and sodium excretion. We also collected urine samples at 7∶00 am to 10∶00 pm and 10∶00 pm to 7∶00 am to detect proteinuria and sodium excretion . Patients were asked to void their bladders at 7∶00 am and 10∶00 pm to ensure valid results. In addition, medical history, including demographic and laboratory data , high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), fasting glucose), and current therapy were obtained at the initial study visit.t test, analysis of variance (ANOVA), or non-parametric test. The relationship between two continuous variables was assessed by a bivariate correlation method (Pearson’s correlation).Data were analyzed using SPSS ver15.0 . Descriptive statistics are presented as percentages for discrete variables and as means (standard deviation) for continuous variables. Non-parametric variables are expressed as median and interquartile range. Comparisons for continuous variables between groups were tested by the Student’s 2vs eGFR ≥60 mLl/min/1.73 m2), 24-h proteinuria (≥1 g/24 h vs <1 g/24 h) and LVH (no LVH vs LVH) and reversed dipper status. CKD outcomes were treated as dependent variables. Sex, age, clinical variables, all BP values from the clinic BP and ABPM, and dipping status  were treated as independent variables. Logistic regression analyses were also used to identify the factors associated with dipper status (non-reversed dipper vs reversed dipper) (dependent variables) and age, sex, clinical variables, clinic- SBP and DBP and 24-h SBP and DBP (independent variables). To explore the potential confounding factors, all those variables mentioned above which significantly correlated with dependent variables were tested further in multiple logistic regression models with the forward likelihood method. Univariate linear regression model was employed to examine the association between E/A ratio (dependent variable) and age, sex, eGFR, levels of hemoglobin, serum calcium, phosphate and intact parathyroid hormone (iPTH), clinic BP and ABPM, and dipper status  (independent variables). Those variables with significant associations with the E/A ratio were tested further in multiple linear regression analyses with the forward likelihood method. All values are two-tailed, and significance was defined as p<0.05.Logistic regression analyses were used to explore the associations of three types of CKD outcomes: eGFR  was higher than that in patients with an eGFR ≥60 mL/min/1.73 m2 (patients in CKD stages I and II) (31.3% vs 11.1% p<0.05).A total of 118 patients (21.9%) had a reversed dipper BP pattern. A total of 227 patients (42%) had a non-dipper BP pattern, and 195 patients (36.1%) had a dipper BP pattern. The prevalence of the reversed dipper BP pattern in CKD stage I, II, III, IV and V was 12.3%, 8.6%, 18.8%, 36.1% and 35.7% respectively. The prevalence of the reversed dipper BP pattern in patients with an eGFR <60 mL/min/1.73 mCompared with patients with dipper BP pattern, subjects with reversed dipper BP pattern were older and had: higher clinical SBP, 24-h-SBP, awakening SBP and bedtime BP; a higher ratio of bedtime/awakening time of proteinuria and urinary sodium excretion; lower eGFR; lower hemoglobin, higher serum phosphate, iPTH and uric acid; higher LVMI, lower E/A ratio, higher CIMT and percentage of atherosclerotic plaques around the level of the carotid bifurcation (p<0.05).More importantly, when we compared patients with reverse dipper BP pattern with patients with a non-dipper BP pattern, we found that patients with reversed dipper BP pattern also had: higher clinical SBP, 24-h SBP, awakening SBP and bedtime BP; higher ratio of bedtime/awakening time of proteinuria and urinary sodium excretion; lower eGFR; lower hemoglobin level, higher serum phosphate and iPTH; higher LVMI and lower E/A ratio (p<0.05). Patients with a reversed dipper BP pattern have the lowest eGFR, highest LVMI and lowest E/A ratio among these CKD patients .Bivariate correlation analysis revealed that eGFR was positively correlated with the rate of decline of nocturnal SBP and DBP, whereas proteinuria of 24 h was not significantly related to the rate of decline of nocturnal SBP and DBP. LVMI was negatively related to the rate of decline of nocturnal SBP and DBP. The E/A ratio was positively correlated with the rate of decline of nocturnal SBP and DBP. CIMT only negatively correlated with rate of decline of nocturnal DBP  and 2.mL/min/1.73 m2  and DBP from AMBP  to be independent factors for affecting the E/A ratio by multivariate linear regression analyses.Age, sex, eGFR, levels of hemoglobin, serum calcium, phosphate and iPTH, all BP values from the clinic and ABPM, and reversed BP patterns were significantly correlated with the LVH by univariate analyses. Multivariate regression analyses revealed that female sex, lower eGFR, higher serum iPTH level, awakening SBP and reversed dipper DBP were independently correlated with LVH . Data we2, lower hemoglobin level, and higher serum levels of calcium, phosphate and iPTH to be significantly correlated with a reversed BP pattern. However, we found only older age, higher 24-h SBP from ABPM, lower hemoglobin and higher serum phosphate levels to be independently correlated with the reversed BP pattern after multivariate regression analyses , size (540 vs 190) and target (reversed dipper BP pattern vs non-dipper patten). However these two studies undoubtedly indicated that serum phosphate levels might affect the rate of decline of nocturnal BP. More studies are needed to explore the real mechanism.The mechanism of reversed or non-dipper BP patterns remains unknown. It could be a consequence of autonomic dysfunction, relative nocturnal volume overload, and abnormal handling of sodium. One study has shown that hypertension  is associated with increased night-time sodium excretion, and that the correlation between night-time sodium excretion and night-time BP is stronger than the correlation between daytime sodium excretion and daytime BP The present study had several strengths. We are the first to report the prevalence of reverse BP patterns in Chinese CKD patients and their close relationship with target-organ damage. Secondly, the sample size was large considering that CKD patients were our selected cohort. Finally, we reported ABPM results, renal damage and cardiovascular damage in Chinese CKD patients. However, some limitations should be considered when evaluating our results. Firstly, this was an observational study and we did not provide a standard clinical trial to change the reversed dipper blood pressure pattern. Secondly, long-term follow-up data were not provided. Finally, we can not get the cause-effect relationship between BP pattern and target organ damages.A reversed dipper BP pattern is closely correlated with severe renal damage and cardiovascular injuries in Chinese CKD patients, and special attention should be given to subjects with a reversed dipper BP pattern. More clinical trials are needed to confirm the role of a reverse dipper pattern and high nocturnal BP on CKD progression.


The Patient Protection and Affordable Care Act (ACA) galvanised debate in the United States (US) over universal health coverage. Comparison with countries providing universal coverage may illustrate whether the ACA can improve health outcomes and reduce disparities. We aimed to compare quality and disparities in hypertension management by socio-economic position in the US and England, the latter of which has universal health care.We used data from the Health and Retirement Survey in the US, and the English Longitudinal Study for Aging from England, including non-Hispanic White respondents aged 50–64 years (US market-based v NHS) and >65 years (US-Medicare v NHS) with diagnosed hypertension. We compared blood pressure control to clinical guideline (140/90 mmHg) and audit (150/90 mmHg) targets; mean systolic and diastolic blood pressure and antihypertensive prescribing, and disparities in each by educational attainment, income and wealth, using regression models.There were no significant differences in aggregate achievement of clinical targets aged 50 to 65 years (US market-based vs. NHS- 62.3% vs. 61.3% [p = 0.835]). There was, however, greater control in the US in patients aged 65 years and over (US Medicare vs. NHS- 53.5% vs. 58.2% [p = 0.043]). England had no significant socioeconomic disparity in blood pressure control . The US had socioeconomic differences in the 50–64 years group ; these were attenuated but not abolished in Medicare beneficiaries.Moves towards universal health coverage in the US may reduce disparities in hypertension management. The current situation, providing universal coverage for residents aged 65 years and over, may not be sufficient for equality in care. Given the growing global burden of chronic diseases, effective and equitable management of diseases such as hypertension is a core requirement of any health system Cross-country analysis can examine relationships between health system structures and outcomes Finally, England offers universal health coverage with care free at the point of delivery. Medication in England costs a standard prescription charge (£7.10 (∼$13.90) in April 2008), although exemptions mean that approximately 60 percent of the population, and 90 percent of items dispensed are free of charge We aim to determine whether health system differences between the US and England influence the quality of hypertension management and disparities across socio-economic position (SEP), characterised by income, wealth and education We analysed data from two national longitudinal surveys, the English Longitudinal Study of Aging (ELSA), and the Health and Retirement Survey (HRS) from the US. These provide comparable data on aging, with similar sampling techniques and content ELSA, a biennial survey, began in 2002, sampling respondents aged 50 years and over We used data from Wave 4 of ELSA, conducted during 2008 and 2009, which contained 11,050 respondents (response rate 74.3%). We included respondents aged 50 years and over, with valid blood pressure readings  from the survey nurse visit . To control for differences in ethnic mix between samples, and ensure that we compared differences between health systems – not biological differences in control between samples, we restricted analyses to non-Hispanic Whites (excluding 225 from ELSA). We exclude respondents with missing SEP  and clinical data (body mass index (BMI), co-morbidities and smoking status; n = 900 – latter two not mutually exclusive), leaving 4,910 respondents.For comparison we used data from Wave 9 of the HRS, administered in 2008, with 17,217 respondents (response rate 88.6%). We include respondents aged 50 years and over, with valid blood pressure readings . We excluded 3,049 non-white and Hispanic respondents, 304 with no BMI record (there were no missing SEP data), leaving 4,920 respondents.Has a doctor ever told you that you have hypertension?” Though this method may underestimate hypertension rates compared with measures based on actual blood pressure values From the samples defined above, we include respondents with a self-reported physician's diagnosis of hypertension, leaving 2,318 ELSA and 2,855 HRS respondents. Both surveys included a question similar to “We used three measures of SEP that are comparable between countries: education, household income and wealth. We divided education into three groups defined using years of continuous education; in England 0–11 years, 12–13 and ≥14; in the USA 0–12, 13–15 and ≥16 years. These cut-offs are widely used We used mean systolic and diastolic blood pressure (from two or more measures), defined controlled hypertension as blood pressure lower than 140/90 mmHg, in line with clinical guidelines We controlled for the following potentially confounding variables: age and sex of respondents; smoking status (current/non-smoker); BMI; and concordant vascular co-morbidities. All except BMI were self-reported, which was recorded by study nurses. We defined the latter as the sum of patient reported doctor diagnoses out of coronary heart disease, stroke/transient ischaemic attack, diabetes or chronic kidney disease.We conducted analyses separately in the groups aged 50 to 64 years and 65 years and over. We present the prevalence of hypertension, standardized for age and sex, along with summaries of covariates across indicators of SEP , in patients with hypertension in each country, testing for statistical significance.w4nurwt in ELSA and lwgtr in the HRS), which we conducted using Stata 11.2SE.In patients with hypertension, we modelled blood pressure control  and anti-hypertensive medication using logistic regression The unadjusted prevalence of hypertension in England and the US was 38.2% and 45.1% in respondents aged 50–64 years and 52.9% and 63.6% in those aged >65 years, respectively. There are significant disparities in prevalence, especially by education and wealth, which were greatest in US respondents aged 50–64 years. The characteristics of respondents with hypertension are presented in There was significantly higher aggregate blood pressure (BP) control in US respondents aged >65 years using clinical  but not audit targets  . Mean syThe lowest SEP groups had poorer control to clinical targets in the US, which reached statistical significance for income , but not in England . There wThere was higher prescribing of anti-hypertensive medication in the US across all SEP groups compared with England. In England there was no SEP disparity in prescribing, whereas the US had lower prescribing in lowest SEP groups, which was statistically significant for wealth .In patients with hypertension aged 50–64 years, there were no significant differences in the control of blood pressure to 140/90 mm Hg between countries . RespondDespite no overall difference between countries in the 50–64 years age group, Americans in the highest wealth groups had significantly better control to the clinical target than their English counterparts  ; total American = 131.2 (p = 0.007 vs. England)): Diastolic blood pressure was lower in the English sample, compared with both from the US ; total American = 84.8 (p<0.001 vs. England)).English patients with hypertension were less often prescribed anti-hypertensive medication than insured Americans and Americans in total  and 80.2% (p<0.001 vs. England), respectively). There were no SEP disparities in prescribing in the US Sample, but there was statistically significantly lower prescribing in the lowest wealth group in the total US sample compared with the lowest . There were no prescribing disparities in the US sample reporting health insurance.Patients with hypertension in America eligible for Medicare are, overall, more likely than their English counterparts to have their blood pressure controlled to the clinical guideline target, but not to the English audit target. Patients aged 50 to 64 years, with insurance coverage through the NHS or under the market-based US health system, have similar control to both targets, even limiting the comparison to US patients reporting health insurance. The US has significantly more prescribing of anti-hypertensive medication across all levels of SEP. We found no evidence of disparities in English patients, while significant wealth and income disparities in blood pressure control and prescribing among younger US patients. Disparities in both were generally attenuated but not abolished in insured patients aged under-65 and older patients eligible for Medicare.The US is enacting some of its most significant health care reforms since the formation of Medicare in 1965 While health insurance may reduce health disparities through improved access to care, the US and UK health systems differ in other ways. Primary care plays a significantly greater role in England, which itself may reduce disparities fundamental cause of raised blood pressure That said, disparities in blood pressure control are absent in older English patients but some remain in Medicare-eligible Americans . Universal coverage alone may not eliminate disparities. The strength of English primary care may increase equity in hypertension control In addition to more equitable care, the NHS matches the US in absolute levels of blood pressure control in the sample aged 50 to 64 years. Given greater health care spending in the US per se. Other factors, including use of appropriate combination therapy and life-style interventions, are important One interesting finding is that anti-hypertensive medications are more far more frequently prescribed in the US sample aged 50 to 64 years, but control remains comparable. The control of blood pressure in hypertensive patients is not solely determined by the prescribing of pharmacological agents Our study has potential limitations. We used patient-reported diagnoses of hypertension. While this definition may underestimate prevalence Hypertension control in both countries remains suboptimal; blood pressure is controlled to clinical targets in just over a half of patients aged 65 years and over. Given the association between blood pressure control and good health outcomes The English and American health care systems differ in many ways, including the provision of universal coverage and overall levels of expenditure. Our study demonstrates that hypertension control in England matches that in the US in a sample without universal health insurance, despite the evidence elsewhere of lower overall expenditure. The two study samples covered by universal health insurance had the lowest disparities in hypertension control, and in one – in England – were entirely absent. The ACA's vision of improving access to healthcare may promote equitable care. Interestingly, while there were no indications of health care disparities in the English system, some persisted in the US, even when patients had insurance (either private insurance for patients under 65 years or Medicare for older patients). The introduction of universal coverage at the age of 65 years may not eliminate disparities that become too entrenched; although may reduce them. Again, the ACA's expansion of Medicare and its individual mandate – expanding private insurance coverage – may increase equity. Alternately, other country-level differences, such as the underlying structures or subtle challenges to care access, including co-payment, may perpetuate disparities: If so, further system-level changes may be required, which the ACA only begins to tackle.Characteristics of both a single-payer health service and universal health insurance coverage may facilitate high-quality, equitable treatment. The expansion of Medicaid eligibility and widening private insurance coverage under the ACA, indeed the promotion of universal health coverage globally


The present study was designed to evaluate which arterial stiffness parameter - AASI or the home arterial stiffness index (HASI) - correlates best with vascular, cardiac and renal damage in hypertensive individuals.A cross-sectional study was carried out involving 258 hypertensive patients. AASI and HASI were defined as the 1-regression slope of diastolic over systolic blood pressure readings obtained from 24-hour recordings and home blood pressure over 6 days. Renal damage was evaluated by glomerular filtration rate (GFR) and microalbuminuria; vascular damage by carotid intima-media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index (ABI); and left ventricular hypertrophy by the Cornell voltage-duration product (VDP) and the Novacode index.AASI and HASI were not correlated with microalbuminuria, however AASI and HASI- blood pressure variability ratio (BPVR) showed negative correlation with GRF. The Cornell PDV was positively correlated with AASI- BPVR-Sleep  and the left ventricular mass index with HASI-BPVR . Carotid IMT and PWV were positively correlated with all the parameters except the HASI, while ABI was negatively correlated with AASI and Awake-AASI. After adjusting for age, gender and 24 hours heart rate, statistical significance remains of the IMT with AASI, Awake AASI and AASI-BPVR. PWV with the AASI, Awake-AASI and Sleep-AASI. ABI with AASI and Awake-AASI. Odd Ratio to presence target organ damage was for AASI: 10.47(IC95% 1.29 to 65.34), Awake-AASI: 8.85(IC95% 1.10 to 71.04), Sleep-AASI: 2.19(IC95% 1.10 to 4.38) and AASI-BPVR-night: 4.09 (IC95% 1.12 to 14.92).After adjusting for age, gender and 24-hour heart, the variables that best associated with the variability of IMT, PWV and ABI were AASI and Awake-AASI, and with GFR was HASI-BPVR. The ambulatory arterial stiffness index (AASI) is related to cardiovascular morbidity-mortality ,2 and toTaking into account the above, home blood pressure monitoring (HBP) also offers a range of measures of blood pressure in the usual environment of the individual, with a good correlation to cardiovascular morbidity-mortality  and the The relationship between the home arterial stiffness index (HASI) and AASI has not been well established. A study has concluded that HASI may serve as a useful surrogate measure of arterial stiffness , while oThe present study was designed to evaluate which arterial stiffness parameter - AASI or the home arterial stiffness index (HASI) - correlates best with vascular, cardiac and renal damage in hypertensive individuals.A cross-sectional study was carried out in a primary care setting. We consecutively included all hypertensive subjects visiting primary care clinics between January 2008 and January 2011, and referred to the research unit for the assessment of cardiovascular risk. Hypertension was diagnosed when the mean of three recordings in the clinic under basal conditions and separated in time revealed systolic blood pressure (SBP) ≥ 140 and/or diastolic blood pressure (DBP) ≥ 90 mmHg. On each visit at least two recordings were made, spaced more than one minute apart. The included patients were aged 30-80 years, and individuals with a history of cardiovascular disease (ischemic heart disease or stroke) or diabetes mellitus were excluded. The sample size to detect a minimum correlation coefficient of 0.2 with two-sided type I error rate of 5% and 80% power was estimated to be 194 individuals The sample of 258 subjects was therefore considered to be sufficient for this study, which adhered to the principles of the Declaration of Helsinki, and was approved by an independent ethics committee of Salamanca University Hospital (Spain). Written informed consent to participation in the study was obtained in all cases.Office blood pressure measurement involves three measurements of SBP and DBP, using the average of the last two measurements, with a validated OMRON model M7 sphygmomanometer , and following the recommendations of the European Society of Hypertension . The offThree measurements were made in the morning (between 6:00 and 9:00 a.m.), and three in the afternoon/evening (between 18:00 and 21:00 p.m.), over a period of 7 days, with a minimum interval of one minute between measurements, and excluding the first measurement and the values corresponding to the first day of measurement . Twenty-ABPM was performed on a day of standard activity, with an adequate cuff for the size of the patient's arm. A control system , validated according to the protocol of the British Hypertension Society, was used . The recCarotid ultrasonography to assess IMT was performed by two investigators trained for this purpose before starting the study. A Sonosite Micromax ultrasound device paired with a 5-10 MHz multifrequency high-resolution linear transducer with Sonocal software was used for performing automatic measurements of IMT, in order to optimize reproducibility. Measurements were made of the common carotid artery after the examination of a longitudinal section of 10 mm at a distance of 1 cm from the bifurcation, performing measurements in the proximal wall, and in the distal wall in the lateral, anterior and posterior projections, following an axis perpendicular to the artery to discriminate two lines (one for the intima-blood interface and the other for the media-adventitia interface). A total of 6 measurements were obtained of the right carotid and another 6 of the left carotid. The measurements were obtained, following the recommendations of the Manheim Carotid Intima-Media Thickness Consensus . The aveThis was evaluated using the ankle/brachial index (ABI). The blood pressure in the upper and lower extremities was measured using a portable Doppler system Minidop Es-100Vx , applying the probe at the posterior tibial artery at an angle of approximately 60° to the direction of blood flowThe ABI was calculated separately for each foot by dividing the higher of the two systolic pressures in the ankle by the higher of the two systolic pressures in the arm. TOD was considered if the ABI was lower than 0.9 .Pulse wave velocity (PWV) was estimated with the SphygmoCor System , with the patient in the supine position. The pulse waves of the carotid and femoral arteries were analyzed, estimating the delay with respect to the ECG wave and calculating PWV. PWV is calculed as the ratio of the distance travelled  and the foot-to-foot time delay between the pulse waves and expressed in meters per second (m/sec). TOD was considered if the PWV was higher than 12 m/sec  in 24-hour blood pressure -25, and The individuals performing the different tests were blinded to the clinical data of the patient. All organ damage assessment measures were made within a period of 10 days.Continuous variables were expressed as the mean ± standard deviation (SD), while frequency distributions were used for qualitative variables. Mean of AASI and HASI were adjusted by age and gender based on analysis of covariance (ANCOVA). Pearson's correlation coefficient was used to estimate the relationship between quantitative variables, while the chi-squared test was used to associate qualitative variables. We performed multiple linear regression analysis using carotid IMT, PWV, ABI, Cornell PDV and glomerular filtration as dependent variables. The enter method was used in a first step to include as adjustment variables patient age, gender  and 24-hour heart rate, and then we included one by one the independent variables  to avoid collinearity. Logistic regression analysis by the enter method was performed to evaluate the association between ambulatory arterial stiffness measures as independent variables, included one by one, and TOD as the dependent variable (1 with TOD and 0 without TOD), adjusted by age and gender. The data were analyzed using the SPSS version 18.0 statistical package .The demographic and clinical characteristics, office and ambulatory blood pressure parameters used to evaluate TOD, and the arterial stiffness indices are reported in Tables Table The correlation of PWV with office PP was: ; with PP ABPM 24 h ; and with PP HOME BP .The observed correlations between AASI with TOD indices were greater (p < 0.05) than those of HASI in GFR, carotid IMT, PWV and ABI. The results were not modified on excluding from the analysis those patients with white coat hypertension, or on separately analyzing those receiving drug treatment and those receiving no drug treatment.After adjusting for age, gender and 24 hours heart rate (table Figure The present study shows that the behavior of the two approaches for measuring stiffness through home blood pressure monitoring and its relation to TOD differs. Thus, while HASI is not correlated to any of the parameters used to evaluate the presence of TOD in hypertensive patients, HASI-BPVR is positively correlated with IMT and PWV, and shows a negative correlation with GFR, in the same way as the AASI indices except Sleep-AASI, which shows a negative correlation with GFR. In turn, AASI-BPVR-Sleep and which shows a positively correlation with Cornell-PDV and HASI-BPVR which shows a positively correlation with LVMI.These results indicate that stiffness arterial assessed with HASI-BPVR to detect the presence of vascular, renal or cardiac damage associated to hypertensive patients is better than HASI.In previous studies, Qureshi et al.  reportedThe correlations found between HASI and the AASI measures have an r-value of close to 0.18, while the values reported by Stergiou  were r =The positive association between AASI and TOD has already been reported by Leoncini et at.  in 188 sOur findings on evaluating renal TOD confirm those published by Ratto et al.  and MulèSchillaci et al. and JerrThe main limitation of our study is its cross-sectional design, which precludes the definition of a causal relationship between AASI and different parameters in evaluating TOD. Another limitation is the fact that ours was not a randomized sample, and so we cannot extrapolate the results to all hypertensive patients. In order to correctly interpret the 24-hour, Awake-AASI and Sleep-AASI values, it must be taken into account that the waking/sleeping measurements ratio is 3 - as a result of which the waking values are over-dimensioned with respect to the sleeping values.The ambulatory arterial stiffness measures, except HASI were positively correlated with IMT and PWV, and negatively correlated with glomerular filtration. After adjusting for age, gender and 24-hour heart, the variables that best associated to the variability of IMT, PWV and ABI were AASI and Awake-AASI, and with CKDEPI was HASI-BPVR. HASI-BPVR shows greater correlation with the studied target organ damage parameters than HASI.Lastly, new prospective studies would be needed in order to confirm the usefulness of HASI-BPVR in assessing arterial stiffness with home blood pressure monitoring.The authors declare that they have no competing interests.MAGM devised the study, designed the protocol, participated in fund raising, interpretation of results, prepared the manuscript draft and corrected the final version of the manuscript. JIRR and CAC participated in the study design, data collection and manuscript review. MCPA performed all analytical methods, interpretation of results, and manuscript review. ERS, LGS and MGS participated in the study design, interpretation of results, and manuscript review. LGO participated in the protocol design, fund raising, analysis of results, and final review of the manuscript. Finally, all authors reviewed and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/12/1/prepub


Renin-angiotensin-aldosterone system (RAAS) is the most important endocrine blood pressure control mechanism in our body, genes encoding components of this system have been strong candidates for the investigation of the genetic basis of hypertension. However, previous studies mainly focused on limited polymorphisms, thus we carried out a case-control study in the Han Chinese population to systemically investigate the association between polymorphisms in the RAAS genes and essential hypertension.905 essential hypertensive cases and 905 normotensive controls were recruited based on stringent inclusion and exclusion criteria. All 41 tagSNPs within RAAS genes were retrieved from HapMap, and the genotyping was performed using the GenomeLab SNPstream Genotyping System. Logistic regression analysis, Multifactor dimensionality reduction (MDR), stratified analysis and crossover analysis were used to identify and characterize interactions among the SNPs and the non-genetic factors.AGT, rs4305 within ACE, rs275645 within AGTR1, rs3802230 and rs10086846 within CYP11B2 were shown to associate with hypertension. The MDR analysis demonstrated that the interaction between BMI and rs4305 increased the susceptibility to hypertension. Crossover analysis and stratified analysis further indicated that BMI has a major effect, and rs4305 has a minor effect.Serum levels of total cholesterol (TC) and triglyceride (TG), and body mass index (BMI) were significantly higher in the hypertensive group than in the control group. Of 41 SNPs genotyped, rs3789678 and rs2493132 within These novel findings indicated that together with non-genetic factors, these genetic variants in the RAAS may play an important role in determining an individual’s susceptibility to hypertension in the Han Chinese. Essential hypertension, defined as high blood pressure (BP) with no identifiable cause, affecting 95% of hypertensive patients REN), angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin type 1 receptor (AGTR1) and aldosterone synthase gene (CYP11B2) have been widely investigated in different ethnic populations, and dozens of single nucleotide polymorphisms (SNPs) within RAAS genes have been reported to be significantly associated with essential hypertension AGT M235T, AGT A6G, AGT T174M, ACE I/D, AGTR1 A1166C, and CYP11B2 C3344T, and the results are often inconsistent RAAS genes encoding renin  and hypertension. Thus, we first conducted a case-control study in the Han Chinese population and genotyped all tagSNPs within RAAS genes. Subsequently, we analyze the interaction among different SNPs and non-genetic risk factors for hypertension, which may give more information on the roles of genetic factors.Given these limitations, this study was designed and conducted in a large, homogeneous sample of Han Chinese, which would minimize the potential influence of mixed factors on hypertension. The objective of the present study was to systemically examine the association between polymorphisms in the RAAS candidate genes  for at least three generations without migration history. Finally, 905 essential hypertensive cases and 905 normotensive controls were chosen from this database, which were matched for age and sex. In addition, participants without cardiovascular diseases, diabetes, kidney diseases, or other major chronic illnesses according to their health records were recruited as controls.Blood pressure was measured in the morning after the participants had been in sitting position for 10 minutes. Three readings were taken 5 minutes apart using standard mercury sphygmomanometer and the average of last two measurements was recorded. Hypertension in this study was defined as sitting systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg, or self-reported use of anti-hypertensive medication. Patients with secondary hypertension were excluded. Normal blood pressure was defined with SBP≤120 mmHg and DBP≤80 mmHg.With informed written consent, two milliliter of venous blood was collected with ethylene diamine tetraacetic acid (EDTA) as anticoagulant. Subsequently, serum levels of total cholesterol (TC), high-density lipoprotein (HDL), triglyceride (TG) were measured enzymatically on a Hitachi automatic biochemistry analyzer 7100. Clinical information including body mass index (BMI), and weekly alcohol and cigarettes consumption were also obtained. In this study, who consumed ≥70 g of alcohol per week for more than 1 year were defined as individuals with alcohol abuse. Moreover, who smoked ≥70 cigarettes per week for more than 1 year were defined as individuals with smoking habit.http://hapmap.ncbi.nlm.nih.gov/), with tagger pairwise method in CHB: R2 cut off = 0.8 and minor allele frequency (MAF) cut off = 0.1 (All 41 tagSNPs were retrieved from HapMap (ff = 0.1 . The genhttp://www.sph.umich.edu/csg/abecasis/). Multifactor dimensionality reduction (MDR), stratified analysis and crossover analysis were used to identify and characterize interactions among the SNPs and the non-genetic factors http://www.epistasis.org/mdr.html).Continuous variables were presented as the mean ± SD and analyzed by t-test between two groups. Statistical analysis of allele and genotype frequencies between case and control groups were compared by chi-squared test. Effect of confounding variables were identified by logistic regression . Hardy-Weinberg equilibrium (HWE) was calculated in controls by the software PEDSTATS V0.6.8 .All tests were two-sided, and P<0.01).The baseline characteristics of our study participants are summarized in P value of 41 tagSNPs within RAAS genes were shown in AGTR1 and rs6414 within CYP11B2 were failed in genotyping, and the genotyping success rate of other 39 SNPs was 99%. Two of 39 SNPs, rs3789678 and rs10086846, deviated from Hardy-Weinberg equilibrium (P<0.05). However, the genotype distribution and MAF of these two SNPs were similar to those of HapMap CHB. To exclude the genotyping error, we randomly regenotyped 20% of the samples for these two SNPs by Tm-shift genotyping method http://pngu.mgh.harvard.edu/~purcell/gpc/) indicated that the sample size is big enough to do case-control analysis with 80% power P values (P<0.05) and odds ratios, rs3789678 and rs2493132 within AGT, rs4305 within ACE, rs275645 within AGTR1, rs3802230 and rs10086846 within CYP11B2 were shown to associate with hypertension  = 0.81–1.30]   , which aAGT, rs4305 within ACE, rs275645 within AGTR1, rs3802230 within CYP11B2 were shown to associate with hypertension.Since RAAS is the most important mechanism regulates blood pressure in our body P = 3.0×10−5), and associated with SBP (P = 4.6×10−4) and DBP (P = 6.0×10−5) in a study compromising 23 cohorts of three independent studies  and a total of 86,588 participants P = 3.0×10−25), and the mean ACE activity among subjects with G allele of rs4343 increased by 3.5 IU/L per copy of the allele 2 = 0.80), suggesting a potential common link between the studies. In the present study, A allele of rs4305 increases the susceptibility to hypertension, which might be associated with increased ACE activity.Similar to this study, some of the susceptibility SNPs were also found to be associated with hypertensive traits in previous studies. The rs4305 has been related to the risk of hypertension  and K173R (rs4539) polymorphisms that previous studies were mostly interested, were also selected for the study. The result showed that among the six SNPs, only the C allele of rs3802230 was significantly more prevalent in the hypertension subjects than in the control subjects . Since the results of both studies were similar, we further calculated the pooled P value and OR. The combined P = 0.001, OR = 1.20, 95% CI = 1.08–1.34, I2 = 0.0% (P = 0.39), which means no heterogeneity existed between two studies, and the C allele of rs3802230 might be a risk factor for essential hypertension in the Han Chinese population. Chen et al. also analyzed these SNPs in Yi and Hani Minorities of China, and found rs4536 was significantly associated with hypertension in the Hani minority, however, no association was found in the Yi minority Prior to our study, Chen MMP3 gene polymorphism rs679620 and BMI in predicting blood pressure in African-American women with hypertension Pickering and colleagues have initially suggested that hypertension and blood pressure are complex traits In conclusion, we identified several genetic variants in the RAAS genes that were significantly associated with hypertension in the Han Chinese population. Most notable, the interaction between BMI and rs4305 increased the susceptibility to hypertension, meanwhile BMI has a major effect, and rs4305 has a minor effect.Table S1All 41 tagSNPs within genes coding for RAAS.(DOC)Click here for additional data file.Table S2Genotype distributions of 35 SNPs not associated with hypertension.(DOC)Click here for additional data file.


An estimated up to 7% of high-risk cardiac surgery patients return to the operating room for bleeding. Aprotinin was used extensively as an antifibrinolytic agent in cardiac surgery patients for over 15 years and it showed efficacy in reducing bleeding. Aprotinin was removed from the market by the U.S. Food and Drug Administration after a large prospective, randomized clinical trial documented an increased mortality risk associated with the drug. Further debate arose when a meta-analysis of 211 randomized controlled trials showed no risk of renal failure or death associated with aprotinin. However, only patients with normal kidney function have been studied.In this study, we look at a single center clinical trial using patients with varying degrees of baseline kidney function to answer the question: Does aprotinin increase odds of death given varying levels of preoperative kidney dysfunction?Based on our model, aprotinin use was associated with a 3.8-fold increase in odds of death one year later compared to no aprotinin use with p-value = 0.0018, regardless of level of preoperative kidney dysfunction after adjusting for other perioperative variables.Lessons learned from our experience using aprotinin in the perioperative setting as an antifibrinolytic during open cardiac surgery should guide us in testing future antifibrinolytic drugs for not only efficacy of preventing bleeding, but for overall safety to the whole organism using long-term clinical outcome studies, including those with varying degree of baseline kidney function. Approximately one million cardiac surgeries are performed in the United States every year. Of these, about 200,000 can be classified as complex procedures, such as repeat coronary artery bypass grafting (CABG), valve replacements, and combined CABG with valve repairs/replacements. One of the reasons these procedures are labeled as complex is because they carry a significant increased risk of perioperative bleeding. An estimated 2.98% to 6.96% of high-risk cardiac operation patients return to the operating room due to bleeding . AprotinThe safety of aprotinin was brought into question in 2006 when a study revealed an increased risk of renal failure, myocardial infarction, and stroke . In 2008This retrospective, single-center study compared aprotinin versus no aprotinin use during complex cardiac surgery between October 2003 and October 2005. The study was conducted at The Ohio State University Medical Center in Columbus, Ohio. A total of 1,644 complex cardiac procedures were done during this two-year period, which included repeat CABG, valve replacements, and combined CABG with valve repairs/replacements. Non-complex cases, such as primary coronary artery bypass surgery, were specifically excluded in an attempt to avoid the statistical bias that aprotinin tends to be used in more complex surgeries, which inherently carry a greater morbidity and mortality risk . The patAfter obtaining approval from our institutional review board, we retrieved perioperative data from our institution's thoracic surgery, perfusion, and general electronic medical record databases. From the 1,644 cases, the Center for Biostatistics randomly selected 251 with varying degrees of renal dysfunction for analysis.Twenty data points per patient were collected, including preoperative and postoperative kidney function, patient demographics, medical comorbidities, intraoperative variables, aprotinin administration, postoperative hemodialysis requirements, and one-year mortality Table . Glomerut tests or Wilcoxon rank sum test where appropriate. The relationship between one-year mortality as the outcome variable and aprotinin treatment was analyzed using a multivariate logistic regression model that adjusted for other variables determined to be significantly related to mortality. Additional variables were checked for potential confounding or effect modification but did not make it into the final model as their effect on the relationship between aprotinin treatment and the outcome was minimal. We also adhered to the general guideline to include no more than one variable per 10 patients in the group that experienced the outcome event of interest. All statistical analyses were performed using SAS 9.2 .Categorical demographic and clinical characteristics of patients were compared between the treatment and control groups using Chi-squared or Fisher exact tests as appropriate Table . ContinuA total of 1,644 patients underwent complex cardiac surgery between 2003 and 2005. From this population, 251 were randomly selected for analysis. From this group, 39 were excluded from the final model because of incomplete data sets. A total of 212 subjects were included in our final statistical model.Statistical analysis revealed three factors, other than aprotinin, that were significantly associated with mortality Table . These fAs expected, patients had varying levels of kidney dysfunction preoperatively, though level of kidney dysfunction did not differ significantly between the two groups. In our model, preoperative kidney function as a continuous or categorical variable did not significantly interact with aprotinin. This indicates that the increased odds of death in aprotinin-treated patients were the same across each level of kidney function.The rates of postoperative hemodialysis were low for both drug and no drug groups. Only one patient in the no drug group and two patients in the aprotinin group required postoperative hemodialysis.The primary new finding in our study is that aprotinin use, irrespective of the level of preoperative renal dysfunction, was associated with a 3.8-fold increase in odds ratio of death one year postoperatively. While previous studies have documented an increase in mortality associated with worsening preoperative kidney dysfunction , our modThis finding coincides with the Blood Conservation Using Antifibrinolytics in a Randomized Trial  and furtThere has been a certain degree of controversy over aprotinin's effect on kidney function postoperatively. Several previous retrospective studies have shown aprotinin to be associated with an increased risk of postoperative renal failure ,12. In cThere were several other variables that were found to be significantly associated with mortality. We discuss these, as it was necessary to include them in our final statistical model. We found that the presence of diabetes, increased blood transfusions on bypass, and decreased eGFR all were associated with increased mortality. These findings are not surprising, and similar mortality associations have been demonstrated in the literature for diabetes -19 and rOur findings, while significant and new, have some limitations. The most significant of these limitations is the retrospective nature of the study. Also, the small number of deaths and our inability to document a cause of death may have potentially masked an increased risk of renal dysfunction as well as any other major organ system failures. In addition, our preoperative baseline of acute kidney dysfunction is non-standardized since there is no agreed upon definition of grades of acute renal dysfunction . The aprThe exact mechanism of increased mortality associated with aprotinin is unknown; however, it has been speculated that it may be related to its systemic effect on inflammation, oxidative stress, and bioactive molecules in addition to the complex interaction between the homeostatic, complement, and cytokine pathways in the setting of ischemia and reperfusion ,28. Ray CABG: coronary artery bypass grafting; eGFR: estimated glomerular filtration rateThe authors declare that they have no competing interests.BS analyzed the data and wrote the manuscript. PG, LY, MA, and WO analyzed the data. JV analyzed the data and wrote the manuscript. HA designed the study, analyzed the data and wrote the manuscript.All authors read and approved the final manuscript.