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Background: Self-management has shown to improve the quality of life in patients with chronic kidney disease (CKD). Readily accessible self-management tools are essential in promoting adherence to self-care behaviors. In recognizing that digital health facilitates efficient access to self-management programs, we developed a digital counseling program, ODYSSEE Kidney Health, to promote self-care behaviors while supporting health-related quality of life., Objective: To present the design and development of ODYSSEE Kidney Health for digital counseling for patients with CKD., Design: The study involved an iterative design process based on user-centered design principles to develop the digital counseling program, ODYSSEE Kidney Health., Setting: A sample of 10 to 15 participants were purposively sampled from nephrology clinics at the University Health Network, Toronto, Canada., Methods: Participants underwent 2 phases in the development process. In each phase, participants were presented with a component of the program, asked to perform goal-oriented tasks, and participate in the "think-aloud" process. Semi-structured interviews followed the first phase to identify feedback about the overall program. Thematic analysis of the interviews identified themes from the usability testing. Descriptive statistics were used to summarize patient demographic data., Results: We enrolled 11 participants (n = 7 males, n = 4 females, ages 30-82). The main themes generated anchored on (1) impact on nephrology care, (2) technical features, and (3) CKD content. Overall, participants reported positive satisfaction toward the navigation, layout, and content of the program. They cited the value of the program in their daily CKD care., Limitations: Study limitations included using a single center to recruit participants, most of the participants having prior technology use, and using one module as a representative of the entire digital platform., Conclusion: The acceptability of a digital counseling program for patients with CKD relies on taking the patients' perspective using a user-centered design process. It is vital in ensuring adoption and adherence to self-management interventions aimed at sustaining behavioral change., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Despite the growing prevalence of people with complex conditions and evidence of the positive impact of telemonitoring for single conditions, little research exists on telemonitoring for this population., Objective: This randomized controlled trial and embedded qualitative study aims to evaluate the impact on and experiences of patients and health care providers (HCPs) using a telemonitoring system with decision support to manage patients with complex conditions, including those with multiple chronic conditions, compared with the standard of care., Methods: A pragmatic, unblinded, 6-month randomized controlled trial sought to recruit 146 patients with ≥1 diagnosis of heart failure (HF), uncontrolled hypertension (HT), and insulin-requiring diabetes mellitus (DM) from outpatient specialty settings in Toronto, Ontario, Canada. Participants were randomized into the control and telemonitoring groups, with the latter being instructed to take readings relevant to their conditions. The telemonitoring system contained an algorithm that generated decision support in the form of actionable self-care directives to patients and alerts to HCPs. The primary outcome was health status (36-Item Short Form Health Survey questionnaire). Secondary outcomes included anxiety and depression, self-efficacy in chronic disease management, and self-reported health service use. HF-related quality of life and self-care measures were also collected from patients followed for HF. Within- and between-group change scores were analyzed for statistical significance (P<.05). A convenience sample of HCPs and patients in the intervention group was interviewed about their experiences., Results: A total of 96 patients were recruited and randomized. Recruitment was terminated early because of implementation challenges and the onset of the COVID-19 pandemic. No significant within- and between-group differences were found for the main primary and secondary outcomes. However, a within-group analysis of patients with HF found improvements in self-care maintenance (P=.04) and physical quality of life (P=.046). Opinions expressed by the 5 HCPs and 13 patients who were interviewed differed based on the monitored conditions. Although patients with HF reported benefitting from actionable self-care guidance and meaningful interactions with their HCPs, patient and HCP users of the DM and HT modules did not think telemonitoring improved the clinical management of those conditions to the same degree. These differing experiences were largely attributed to the siloed nature of specialty care and the design of the decision support, whereby fluctuations in the status of HT and DM typically required less urgent interventions compared with patients with HF., Conclusions: We recommend that future research conceive telemonitoring as a program and that self-management and clinical decision support are necessary but not sufficient components of such programs for patients with complex conditions and lower acuity. We conclude that telemonitoring for patients with complex conditions or within multidisciplinary care settings may be best operationalized through nurse-led models of care., Trial Registration: ClinicalTrials.gov NCT03127852; https://clinicaltrials.gov/ct2/show/NCT03127852., International Registered Report Identifier (irrid): RR2-10.2196/resprot.8367., (©Patrick Ware, Amika Shah, Heather Joan Ross, Alexander Gordon Logan, Phillip Segal, Joseph Antony Cafazzo, Katarzyna Szacun-Shimizu, Myles Resnick, Tessy Vattaparambil, Emily Seto. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 26.01.2022.)

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Background and Objectives: Patients with CKD are at risk for adverse drug reactions, but effective community-based preventive programs remain elusive. In this study, we compared the effectiveness of two digital applications designed to improve outpatient medication safety., Design, Setting, Participants, & Measurements: In a 1-year randomized controlled trial, 182 outpatients with advanced CKD were randomly assigned to receive a smartphone preloaded with either eKidneyCare ( n =89) or MyMedRec ( n =93). The experimental intervention, eKidneyCare, includes a medication feature that prompted patients to review medications monthly and report changes, additions, or medication problems to clinicians for reconciliation and early intervention. The active comparator was MyMedRec, a commercially available, standalone application for storing medication and other health information that can be shared with patients' providers. The primary outcome was the rate of medication discrepancy, defined as differences between the patient's reported history and the clinic's medication record, at exit., Results: At exit, the eKidneyCare group had fewer total medication discrepancies compared with MyMedRec (median, 0.45; interquartile range, 0.33-0.63 versus 0.67; interquartile range, 0.40-1.00; P =0.001), and the change from baseline was 0.13±0.27 in eKidneyCare and 0.30±0.41 in MyMedRec ( P =0.007). eKidneyCare use also reduced the severity of clinically relevant medication discrepancies in all categories, including those with the potential to cause serious harm (estimated rate ratio, 0.40; 95% confidence interval, 0.27 to 0.63). Usage data revealed that 72% of patients randomized to eKidneyCare completed one or more medication reviews per month, whereas only 30% of patients in the MyMedRec group (adjusted for dropouts) kept their medication profile on their phone., Conclusions: In patients who are high risk and have CKD, eKidneyCare significantly reduced the rate and severity of medication discrepancies, the proximal cause of medication errors, compared with the active comparator. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: www.ClinicalTrials.gov, NCT:02905474., (Copyright © 2021 by the American Society of Nephrology.)

Telemedicine allows the remote exchange of medical data between patients and healthcare professionals. It is used to increase patients' access to care and provide effective healthcare services at a distance. During the recent coronavirus disease 2019 (COVID-19) pandemic, telemedicine has thrived and emerged worldwide as an indispensable resource to improve the management of isolated patients due to lockdown or shielding, including those with hypertension. The best proposed healthcare model for telemedicine in hypertension management should include remote monitoring and transmission of vital signs (notably blood pressure) and medication adherence plus education on lifestyle and risk factors, with video consultation as an option. The use of mixed automated feedback services with supervision of a multidisciplinary clinical team (physician, nurse, or pharmacist) is the ideal approach. The indications include screening for suspected hypertension, management of older adults, medically underserved people, high-risk hypertensive patients, patients with multiple diseases, and those isolated due to pandemics or national emergencies.

Objective: Apps promoting patient self-management may improve health outcomes. However, methods to secure stored information on mobile devices may adversely affect usability. We tested the reliability and usability of common user authentication techniques in younger and older adults., Methodology: Usability testing was conducted in two age groups, 18 to 30 years and 50 years and older. After completing a demographic questionnaire, each participant tested four authentication options in random order: four-digit personal identification number (PIN), graphical password (GRAPHICAL), Android pattern-lock (PATTERN), and a swipe-style Android fingerprint scanner (FINGERPRINT). Participants rated each option using the Systems Usability Scale (SUS)., Results: A total of 59 older and 43 younger participants completed the study. Overall, PATTERN was the fastest option (3.44s), and PIN had the fewest errors per attempt (0.02). Participants were able to login using PIN, PATTERN, and GRAPHICAL at least 98% of the time. FINGERPRINT was the slowest (26.97s), had an average of 1.46 errors per attempt, and had a successful login rate of 85%. Overall, PIN and PATTERN had higher SUS scores than FINGERPRINT and GRAPHICAL. Compared to younger participants, older participants were also less likely to find PATTERN to be tiring, annoying or time consuming and less likely to consider PIN to be time consuming. Younger participants were more likely to rate GRAPHICAL as annoying, time consuming and tiring than older participants., Conclusions: On mobile devices, PIN and pattern-lock outperformed graphical passwords and swipe-style fingerprints. All participants took longer to authenticate using the swipe-style fingerprint compared to other options. Older participants also took two to three seconds longer to authenticate using the PIN, pattern and graphical passwords though this did not appear to affect perceived usability.

Background: The rising prevalence of chronic illnesses hinders the sustainability of the health care system because of the high cost of frequent hospitalizations of patients with complex chronic conditions. Clinical trials have demonstrated that telemonitoring can improve health outcomes, but they have generally been limited to single conditions such as diabetes, hypertension, or heart failure. Few studies have examined the impact of telemonitoring on complex patients with multiple chronic conditions, although these patients may benefit the most from this technology., Objective: The aim of this study is to investigate the impact of a smartphone-based telemonitoring system on the clinical care and health outcomes of complex patients across several chronic conditions., Methods: A mixed-methods, 6-month randomized controlled trial (RCT) of a smartphone-based telemonitoring system is being conducted in specialty clinics. The study will include patients who have been diagnosed with one or more of any of the following conditions: heart failure, chronic obstructive pulmonary disease, chronic kidney disease, uncontrolled hypertension, or insulin-requiring diabetes. The primary outcome will be the health status of patients as measured with SF-36. Patients will be randomly assigned to either the control group receiving usual care (n=73) or the group using the smartphone-based telemonitoring system in addition to usual care (n=73)., Results: Participants are currently being recruited for the trial. Data collection is anticipated to be completed by the fall of 2018., Conclusions: This RCT will be among the first trials to provide evidence of the impact of telemonitoring on costs and health outcomes of complex patients who may have multiple chronic conditions., Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 41238563; http://www.isrctn.com/ISRCTN41238563 (Archived by WebCite at http://www.webcitation.org/6ug2Sk0af) and Clinicaltrials.gov NCT03127852; https://clinicaltrials.gov/ct2/show/NCT03127852 (Archived by WebCite at http://www.webcitation.org/6uvjNosBC)., (©Emily Seto, Patrick Ware, Alexander G Logan, Joseph A Cafazzo, Kenneth R Chapman, Phillip Segal, Heather J Ross. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 21.11.2017.)

Study Objectives: In heart failure (HF), we observed two patterns of hyperpnea during Cheyne-Stokes respiration with central sleep apnea (CSR-CSA): a positive pattern where end-expiratory lung volume remains at or above functional residual capacity, and a negative pattern where it falls below functional residual capacity. We hypothesized the negative pattern is associated with worse HF., Methods: Patients with HF underwent polysomnography. During CSR-CSA, hyperpnea, apnea-hyperpnea cycle, and lung to finger circulation times (LFCT) were measured. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration and left ventricular ejection fraction (LVEF) were assessed., Results: Of 33 patients with CSR-CSA (31 men, mean age 68 years), 9 had a negative hyperpnea pattern. There was no difference in age, body mass index, and apnea-hypopnea index between groups. Patients with a negative pattern had longer hyperpnea time (39.5 ± 6.4 versus 25.8 ± 5.9 seconds, P < .01), longer cycle time (67.8 ± 15.9 versus 51.7 ± 9.9 seconds, P < .01), higher NT-proBNP concentrations (2740 [6769] versus 570 [864] pg/ml, P = .01), and worse New York Heart Association class ( P = .02) than those with a positive pattern. LFCT and LVEF did not differ between groups., Conclusions: Patients with HF and a negative CSR-CSA pattern have evidence of worse cardiac function than those with a positive pattern. Greater positive expiratory pressure during hyperpnea is likely generated during the negative pattern and might support stroke volume in patients with worse cardiac function., Commentary: A commentary on this article appears in this issue on page 1227., Clinical Trial Registration: The trial is registered with Current Controlled Trials (www.controlled-trials.com; ISRCTN67500535) and Clinical Trials (www.clinicaltrials.gov; NCT01128816)., (© 2017 American Academy of Sleep Medicine)

Introduction: Both types of sleep-disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo-ventilation (ASV) in such patients reduces morbidity and mortality., Aim: ADVENT-HF is designed to assess the effects of treating SDB with ASV on morbidity and mortality in patients with HFrEF., Methods: ADVENT-HF is a multicentre, multinational, randomized, parallel-group, open-label trial with blinded assessment of endpoints of standard medical therapy for HFrEF alone vs. with the addition of ASV in patients with HFrEF and SDB. Patients with a history of HFrEF undergo echocardiography and polysomnography. Those with a left ventricular ejection fraction ≤45% and SDB (apnoea-hypopnoea index ≥15) are eligible. SDB is stratified into OSA with ≥50% of events obstructive or CSA with >50% of events central. Those with OSA must not have excessive daytime sleepiness (Epworth score of ≤10). Patients are then randomized to receive or not receive ASV. The primary outcome is the composite of all-cause mortality, cardiovascular hospital admissions, new-onset atrial fibrillation requiring anti-coagulation but not hospitalization, and delivery of an appropriate discharge from an implantable cardioverter-defibrillator not resulting in hospitalization during a maximum follow-up time of 5 years., Conclusion: The ADVENT-HF trial will help to determine whether treating SDB by ASV in patients with HFrEF improves morbidity and mortality., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

To determine whether clinical outcomes differed by occurrence of severe hypertension in the international CHIPS trial (Control of Hypertension in Pregnancy Study), adjusting for the interventions of "less tight" (target diastolic blood pressure [dBP] 100 mm Hg) versus "tight" control (target dBP 85 mm Hg). In this post-hoc analysis of CHIPS data from 987 women with nonsevere nonproteinuric preexisting or gestational hypertension, mixed effects logistic regression was used to compare the following outcomes according to occurrence of severe hypertension, adjusting for allocated group and the influence of baseline factors: CHIPS primary (perinatal loss or high-level neonatal care for >48 hours) and secondary outcomes (serious maternal complications), birth weight <10th percentile, preeclampsia, delivery at <34 or <37 weeks, platelets <100×10 9 /L, elevated liver enzymes with symptoms, maternal length of stay ≥10 days, and maternal readmission before 6 weeks postpartum. Three hundred and thirty-four (34.1%) women in CHIPS developed severe hypertension that was associated with all outcomes examined except for maternal readmission (P=0.20): CHIPS primary outcome, birth weight <10th percentile, preeclampsia, preterm delivery, elevated liver enzymes (all P<0.001), platelets <100×10 9 /L (P=0.006), and prolonged hospital stay (P=0.03). The association between severe hypertension and serious maternal complications was seen only in less tight control (P=0.02). Adjustment for preeclampsia (464, 47.3%) did not negate the relationship between severe hypertension and the CHIPS primary outcome (P<0.001), birth weight <10th percentile (P=0.005), delivery at <37 (P<0.001) or <34 weeks (P<0.001), or elevated liver enzymes with symptoms (P=0.02). Severe hypertension is a risk marker for adverse maternal and perinatal outcomes, independent of BP control or preeclampsia co-occurrence., Clinical Trial Registration: URL: http://pre-empt.cfri.ca/. Unique identifier: ISRCTN 71416914. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01192412., (© 2016 The Authors.)

Unlabelled: The CHIPS randomized controlled trial (Control of Hypertension in Pregnancy Study) found no difference in the primary perinatal or secondary maternal outcomes between planned "less tight" (target diastolic 100 mm Hg) and "tight" (target diastolic 85 mm Hg) blood pressure management strategies among women with chronic or gestational hypertension. This study examined which of these management strategies is more or less costly from a third-party payer perspective. A total of 981 women with singleton pregnancies and nonsevere, nonproteinuric chronic or gestational hypertension were randomized at 14 to 33 weeks to less tight or tight control. Resources used were collected from 94 centers in 15 countries and costed as if the trial took place in each of 3 Canadian provinces as a cost-sensitivity analysis. Eleven hospital ward and 24 health service costs were obtained from a similar trial and provincial government health insurance schedules of medical benefits. The mean total cost per woman-infant dyad was higher in less tight versus tight control, but the difference in mean total cost (DM) was not statistically significant in any province: Ontario ($30 191.62 versus $24 469.06; DM $5723, 95% confidence interval, -$296 to $12 272; P=0.0725); British Columbia ($30 593.69 versus $24 776.51; DM $5817; 95% confidence interval, -$385 to $12 349; P=0.0725); or Alberta ($31 510.72 versus $25 510.49; DM $6000.23; 95% confidence interval, -$154 to $12 781; P=0.0637). Tight control may benefit women without increasing risk to neonates (as shown in the main CHIPS trial), without additional (and possibly lower) cost to the healthcare system., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01192412., (© 2016 The Authors.)

Competing events (or risks) preclude the observation of an event of interest or alter the probability of the event's occurrence and are commonly encountered in transplant outcomes research. Transplantation, for example, is a competing event for death on the waiting list because receiving a transplant may significantly decrease the risk of long-term mortality. In a typical analysis of time-to-event data, competing events may be censored or incorporated into composite end points; however, the presence of competing events violates the assumption of "independent censoring," which is the basis of standard survival analysis techniques. The use of composite end points disregards the possibility that competing events may be related to the exposure in a way that is different from the other components of the composite. Using data from the Scientific Registry of Transplant Recipients, this paper reviews the principles of competing risks analysis; outlines approaches for analyzing data with competing events (cause-specific and subdistribution hazards models); compares the estimates obtained from standard survival analysis, which handle competing events as censoring events; discusses the appropriate settings in which each of the two approaches could be used; and contrasts their interpretation., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background and Objectives: Patient self-management has been shown to improve health outcomes. We developed a smartphone-based system to boost self-care by patients with CKD and integrated its use into usual CKD care. We determined its acceptability and examined changes in several clinical parameters., Design, Setting, Participants, & Measurements: We recruited patients with stage 4 or 5 CKD attending outpatient renal clinics who responded to a general information newsletter about this 6-month proof-of-principle study. The smartphone application targeted four behavioral elements: monitoring BP, medication management, symptom assessment, and tracking laboratory results. Prebuilt customizable algorithms provided real-time personalized patient feedback and alerts to providers when predefined treatment thresholds were crossed or critical changes occurred. Those who died or started RRT within the first 2 months were replaced. Only participants followed for 6 months after recruitment were included in assessing changes in clinical measures., Results: In total, 47 patients (26 men; mean age =59 years old; 33% were ≥65 years old) were enrolled; 60% had never used a smartphone. User adherence was high (>80% performed ≥80% of recommended assessments) and sustained. The mean reductions in home BP readings between baseline and exit were statistically significant (systolic BP, -3.4 mmHg; 95% confidence interval, -5.0 to -1.8 and diastolic BP, -2.1 mmHg; 95% confidence interval, -2.9 to -1.2); 27% with normal clinic BP readings had newly identified masked hypertension. One hundred twenty-seven medication discrepancies were identified; 59% were medication errors that required an intervention to prevent harm. In exit interviews, patients indicated feeling more confident and in control of their condition; clinicians perceived patients to be better informed and more engaged., Conclusions: Integrating a smartphone-based self-management system into usual care of patients with advanced CKD proved feasible and acceptable, and it appeared to be clinically useful. The results provide a strong rationale for a randomized, controlled trial., (Copyright © 2016 by the American Society of Nephrology.)

Cardiovascular mortality is the leading cause of death in ESRD. Whereas innate and adaptive immunity have established roles in cardiovascular disease, the role of humoral immunity is unknown. We conducted a retrospective cohort study in first-time adult kidney transplant candidates (N=161,308) using data from the Scientific Registry of Transplant Recipients and the Centers for Medicare and Medicaid Services to evaluate whether anti-human leukocyte antigen antibodies, measured as panel reactive antibodies (PRAs), are related to mortality in ESRD. Relationships between time-varying PRAs and all-cause or cardiovascular mortality were assessed using Cox proportional hazards models. The analysis was repeated in subcohorts of candidates at lower risk for significant comorbidities, activated on the waiting list after 2007, or unsensitized at activation. Competing risks analyses were also conducted. Fully adjusted models showed increased hazard ratios (HRs [95% confidence intervals]) for all-cause mortality (HR, 1.02 [95% CI, 0.99 to 1.06]; HR, 1.11 [95% CI,1.07 to 1.16]; and HR,1.21 [95% CI,1.15 to 1.27]) and cardiovascular mortality (HR, 1.05 [95% CI,1.00 to 1.10]; HR,1.11 [95% CI,1.05 to 1.18]; and HR,1.21 [95% CI,1.12 to 1.31]) in PRA 1%-19%, PRA 20%-79%, and PRA 80%-100% categories compared with PRA 0%, respectively. Associations between PRA and the study outcomes were accentuated in competing risks models and in lower-risk patients and persisted in other subcohorts. Our findings suggest that PRA is an independent predictor of mortality in wait-listed kidney transplant candidates. The mechanisms by which PRA confers an incremental mortality risk in sensitized patients, and the role of transplantation in modifying this risk, warrant further study., (Copyright © 2016 by the American Society of Nephrology.)

Obstructive sleep apnoea (OSA) is highly prevalent in hypertensive patients, particularly those with drug resistance. Evidence from animal experiments, epidemiologic studies and clinical trials strongly suggest a causal link. Mechanistic studies argue for increased sympathetic neural activity and endothelial dysfunction. However, disturbances in fluid volume regulation and distribution may also be involved in the pathogenesis of these two conditions. Several studies have shown a high prevalence of OSA in fluid-retaining states including hypertension, a direct relationship between the severity of OSA and the volume of fluid displaced from the legs to the neck during sleep, and a decrease in upper airway cross-sectional area in response to graded lower body positive pressure. Treatments targeting fluid retention and redistribution, including diuretics, mineralocorticoid antagonists, exercise, and possibly renal denervation lower blood pressure and reduce the apnoea-hypopnoea index, a measure of OSA severity. From these observations, it has been postulated that during the daytime, excess fluid collects in the lower extremities due to gravity, and on lying down overnight is redistributed rostrally to the neck, where it may narrow the upper airway and increase its collapsibility, predisposing to OSA when pharyngeal dilator muscle activity decreases during sleep. This article discusses the associations between OSA and hypertension and reviews the evidence for fluid accumulation and its nocturnal rostral redistribution in the pathogenesis of OSA in hypertensive patients.

We conducted a nested case-control study from a cohort of adult kidney transplant recipients to assess the risk of transplant glomerulopathy (TG) as a function of donor and recipient HLA-DR and -DQ incompatibility at the eplet level. Cases (n = 52) were defined as patients diagnosed with transplant glomerulopathy based on biopsies showing glomerular basement membrane duplication without immune complex deposition. Controls (n = 104) with a similar follow-up from transplantation were randomly selected from the remaining cohort. HLAMatchmaker was used to ascertain the number of DRB1/3/4/5, DQA1 and DQB1 related eplet mismatches (eplet load). Multivariable conditional logistic regression models demonstrated an increase in the odds of TG (odds ratios [OR] of 2.84 [95% confidence interval (CI): 1.03, 7.84] and 4.62 [95% CI: 1.51, 14.14]) in the presence of 27-43 and >43 HLA-DR + DQ related eplet mismatches versus <27 eplet mismatches, respectively. When the eplet load was modeled as a continuous variable, the OR for TG was 1.25 (95% CI: 1.04, 1.50) for every 10 additional HLA-DR + DQ eplet mismatches. Our study suggests that minimization of HLA-DR + DQ eplet mismatches may decrease the incidence of transplant glomerulopathy diagnosed by indication biopsies. The role of eplet immunogenicity/antigenicity as determinants of allograft outcomes requires further study., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

In this study, we conducted a systematic review of the literature to re-evaluate the role of C4d in the diagnosis of acute antibody-mediated rejection of kidney allografts. Electronic databases were searched until September 2013. Eligible studies allowed derivation of diagnostic tables for the performance of C4d by immunofluorescence or immunohistochemistry with comparison to histopathological features of acute antibody-mediated rejection and/or donor-specific antibody (DSA) assays. Of 3492 unique abstracts, 29 studies encompassing 3485 indication and 868 surveillance biopsies were identified. Assessment of C4d by immunofluorescence and immunohistochemistry exhibited slight to moderate agreement with glomerulitis, peritubular capillaritis, solid-phase DSA assays, DSA with glomerulitis, and DSA with peritubular capillaritis. The sensitivity and specificity of C4d varied as a function of C4d and comparator test thresholds. Prognostically, the presence of C4d was associated with inferior allograft survival compared with DSA or histopathology alone. Thus, our findings support the presence of complement-dependent and -independent phenotypes of acute antibody-mediated rejection. Whether the presence of C4d in combination with histopathology or DSA should be considered for the diagnosis of acute antibody-mediated rejection warrants further study.

We previously showed that in hypertensive patients the amount of fluid displaced from the legs overnight is directly related to the severity of obstructive sleep apnea and that the rostral fluid shift was greater in drug-resistant hypertensive patients. The findings suggested that this fluid redistribution increases upper airway collapsibility, yet more direct evidence is lacking. The present study examines the effects of graded lower body positive pressure on leg fluid volume, upper airway cross-sectional area, and neck circumference in patients with drug-resistant hypertension (n=25) and controlled hypertension (n=15). In both groups, the reduction in mean upper airway cross-sectional area and oropharyngeal junction area, assessed by acoustic pharyngometry, and the increase in neck circumference, determined by mercury strain gauge plethysmography, were related to the amount of fluid displaced from the legs (R(2)=0.41, P<0.0001; R(2)=0.42, P<0.0001; and R(2)=0.47, P<0.0001, respectively). Displacement of leg fluid volume was significantly greater in patients with drug-resistant hypertension than in controlled hypertension (P<0.0001), and as a consequence, the former experienced greater reductions in mean upper airway cross-sectional area and oropharyngeal junction area (P=0.001 and P<0.0001, respectively). The findings support the concept that in hypertensive subjects, rostral fluid displacement may participate in the pathogenesis of obstructive sleep apnea by narrowing the upper airway and making it more susceptible to collapse during sleep. The exaggerated fluid volume displacement from the legs and upper airway response to lower body positive pressure in patients with drug-resistant hypertension provide additional evidence of an important link between drug-resistant hypertension and obstructive sleep apnea.

Lowering blood pressure reduces cardiovascular risk, yet hypertension is poorly controlled in diabetic patients. In a pilot study we demonstrated that a home blood pressure telemonitoring system, which provided self-care messages on the smartphone of hypertensive diabetic patients immediately after each reading, improved blood pressure control. Messages were based on care paths defined by running averages of transmitted readings. The present study tests the system's effectiveness in a randomized, controlled trial in diabetic patients with uncontrolled systolic hypertension. Of 244 subjects screened for eligibility, 110 (45%) were randomly allocated to the intervention (n = 55) or control (n = 55) group, and 105 (95.5%) completed the 1-year outcome visit. In the intention-to-treat analysis, mean daytime ambulatory systolic blood pressure, the primary end point, decreased significantly only in the intervention group by 9.1 ± 15.6 mmHg (SD; P < 0.0001), and the mean between-group difference was 7.1 ± 2.3 mmHg (SE; P < 0.005). Furthermore, 51% of intervention subjects achieved the guideline recommended target of <130/80 mmHg compared with 31% of control subjects (P < 0.05). These improvements were obtained without the use of more or different antihypertensive medications or additional clinic visits to physicians. Providing self-care support did not affect anxiety but worsened depression on the Hospital Anxiety and Depression Scale (baseline, 4.1 ± 3.76; exit, 5.2 ± 4.30; P = 0.014). This study demonstrated that home blood pressure telemonitoring combined with automated self-care support reduced the blood pressure of diabetic patients with uncontrolled systolic hypertension and improved hypertension control. Home blood pressure monitoring alone had no effect on blood pressure. Promoting patient self-care may have negative psychological effects.

Obstructive sleep apnea occurs frequently in patients with drug-resistant hypertension. The factors accounting for this observation, however, are unclear. Both conditions demonstrate clinical features suggestive of extracellular fluid volume overload. The aims of this study were to examine whether the spontaneous overnight fluid shift from the legs to the upper body is associated with obstructive sleep apnea in hypertensive subjects and whether its magnitude is greater in drug-resistant hypertension. Leg fluid volume and the circumference of the calf and neck were measured before and after sleep in drug-resistant hypertensive (n = 25) and controlled hypertensive (n=15) subjects undergoing overnight polysomnography. The severity of obstructive sleep apnea was greater in the drug-resistant hypertensive group than in the controlled hypertensive group (apnea-hypopnea index: 43.0 ± 5.4 versus 18.1 ± 4.2 events per hour of sleep; P = 0.02, case-mix adjusted). In both groups, the apnea-hypopnea index strongly related to the amount of leg fluid volume displaced (R² = 0.56; P < 0.0001), although the magnitude of change was greater in the drug-resistant hypertensive group (346.7 ± 24.1 versus 175.8 ± 31.3 mL; P = 0.01, propensity-score adjusted). The overnight reduction in calf circumference and increase in neck circumference were also greater in drug-resistant hypertension (both P ≤ 0.02). In hypertensive subjects, rostral fluid displacement strongly relates to the severity of obstructive sleep apnea with its magnitude being greater in drug-resistant hypertension. Our findings support the concept that fluid redistribution centrally during sleep accounts for the high prevalence of obstructive sleep apnea in drug-resistant hypertension.

In patients with heart failure (HF), the predominant type of sleep apnoea can change over time in association with alterations in circulation time. The aim of this study was to determine whether, in some patients with HF, a spontaneous shift from mainly central (>50% central events) to mainly obstructive (>50% obstructive events) sleep apnoea (CSA and OSA, respectively) over time coincides with improvement in left ventricular ejection fraction (LVEF). Therefore, sleep studies and LVEFs of HF patients with CSA from the control arm of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure (CANPAP) trial were examined to determine whether some converted to mainly OSA and, if so, whether this was associated with an increase in LVEF. Of 98 patients with follow-up sleep studies and LVEFs, 18 converted spontaneously to predominantly OSA. Compared with those in the nonconversion group, those in the conversion group had a significantly greater increase in the LVEF (2.8% versus -0.07%) and a significantly greater fall in the lung-to-ear circulation time (-7.6 s versus 0.6 s). In patients with HF, spontaneous conversion from predominantly CSA to OSA is associated with an improvement in left ventricular systolic function. Future studies will be necessary to further examine this relationship.

Background: Nocturnal blood pressure abnormalities are independently associated with an increased risk of death and cardiovascular disease. It is unclear, however, whether they are related to the presence or severity of hypertension., Objectives: To determine and compare the prevalence of sleep pattern disturbances in normotensive (NT) and hypertensive patients., Methods: The present cross-sectional study assessed the nocturnal blood pressure profiles from 24 h ambulatory blood pressure monitoring of refractory hypertensive (RH) (n=26), controlled hypertensive (CH) (n=52) and NT (n=52) subjects who were matched for age, sex and body mass index. Results are expressed as mean +/- SD or proportion, as appropriate., Results: During sleep, the percentage fall in mean arterial pressure was 15.1+/-6.1% in the NT group, 11.5+/-7.0% in the CH group and 7.7+/-7.7% in the RH group (P<0.0001). The corresponding proportions of nondipping were 25.0%, 42.3% and 61.5%, respectively (P=0.006), and those of nocturnal hypertension were 9.6%, 23.1% and 84.6%, respectively (P<0.0001). All pairwise comparisons of nocturnal blood pressure fall were significant. The proportion of subjects in the RH group who experienced a rise in nocturnal blood pressure (19.2%) was significantly greater than the proportions in the NT and CH groups (P=0.001), as was the proportion of subjects with nocturnal hypertension (P<0.0001). There was less extreme dipping in RH, although the difference was not statistically significant (P=0.08)., Conclusions: A significantly higher prevalence of nondipping, nocturnal hypertension and nocturnal blood pressure rising in RH was demonstrated. These sleep disturbances or independently, their cause, may account for the difficulties in attaining blood pressure control.

Poor eating habits, a strong predictor of health outcomes, are not objectively assessed in routine clinical practice. In this study, we evaluated the use of urinary potassium (K(+)) as a means to identify people consuming a poor quality diet. Consecutive patients with kidney stones (n = 220), aged 18-50 y, from a population-based lithotripsy unit, collected a single 24-h urine sample to assess urinary K(+). They also completed a FFQ to derive the recommended foods score (RFS), an index of overall diet quality, and had their blood pressure, heart rate, weight, and height measured. Urinary K(+) was related positively with the intake of recommended food items, including vegetables, fruit, whole grains, low-fat dairy products, fish and poultry, and wine and negatively to those not recommended by current dietary guidelines, including red meat, fast food, and high-energy drinks. Urinary K(+) was also correlated with the RFS (r = 0.226; P < 0.001). Using a receiver operating characteristic curve, K(+) excretion values below the gender-specific median (men, 60 mmol/d; women, 41 mmol/d) were identified as the optimal cutoff values for a poor quality diet, indicated by the RFS. Higher urinary K(+) was inversely related to adjusted BMI (P-trend = 0.03), diastolic blood pressure (P-trend = 0.04) and heart rate (P-trend = 0.006), after controlling for potential confounders. Urinary K(+) provides a summary measure of diet quality, is significantly related to BMI, blood pressure, and heart rate, and may be useful clinically to detect poor dietary habits and monitor response to dietary interventions.

Nocturnal hypertension and non-dipping of blood pressure during sleep are distinct entities that often occur together and are regarded as important harbingers of poor cardiovascular prognosis. This review addresses several aspects related to these blood pressure abnormalities including definitions, diagnostic limitations, pathogenesis and associated patient profiles, prognostic significance, and therapeutic strategies. Taken together, persistent nocturnal hypertension and non-dipping blood pressure pattern, perhaps secondary to abnormal renal sodium handling and/or altered nocturnal sympathovagal balance, are strongly associated with deaths, cardiovascular events, and progressive loss of renal function, independent of daytime and 24-hour blood pressure. Several pharmacological and non-pharmacological approaches may restore nocturnal blood pressure and circadian blood pressure rhythm to normal; however, whether this translates to a clinically meaningful reduction in unfavorable cardiovascular and renal consequences remains to be seen.

Background: Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in haemodialysis patients. The link between OPG and aortic stiffening--a consequence of arterial calcification--has not been previously evaluated in this population, and it is not known whether OPG-related mortality risk is mediated by arterial stiffening., Methods: At baseline, OPG and aortic pulse wave velocity (PWV) were measured in 98 chronic haemodialysis patients who were followed for a median of 24 months. The relationship between OPG and PWV was assessed by multivariate linear regression. The role of PWV in mediating OPG related cardiovascular mortality was evaluated by including both OPG and PWV in the same survival model., Results: At baseline mean (standard deviation) PWV was 11.2 (3.3) m/s and median OPG (interquartile range) was 11.1 (7.5-15.9) pmol/L. There was a strong, positive, linear relationship between PWV and lnOPG (P = 0.009, model R(2) = 0.540) independent of covariates. During follow-up 23 patients died of cardiovascular causes. In separate univariate survival models both PWV and lnOPG were related to cardiovascular mortality [hazard ratios 1.31 (1.14-1.50) and 8.96 (3.07-26.16), respectively]. When both PWV and lnOPG were entered into the same model, only lnOPG remained significantly associated with cardiovascular mortality [hazard ratio 1.11 (0.93-1.33) and 7.18 (1.89-27.25), respectively)., Conclusion: In haemodialysis patients OPG is strongly related to PWV and OPG related cardiovascular mortality risk is, in part, mediated by increased PWV.

Objective: To provide updated, evidence-based recommendations for the prevention and management of hypertension in adults., Options and Outcomes: For lifestyle and pharmacological interventions, evidence was reviewed from randomized controlled trials and systematic reviews of trials. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. For treatment of patients with kidney disease, the progression of kidney dysfunction was also accepted as a clinically relevant primary outcome., Evidence: A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to update the 2006 Canadian Hypertension Education Program recommendations. In addition, reference lists were scanned and experts were contacted to identify additional published studies. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence., Recommendations: Dietary lifestyle modifications for prevention of hypertension, in addition to a well-balanced diet, include a dietary sodium intake of less than 100 mmol/day. In hypertensive patients, the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day. Other lifestyle modifications for both normotensive and hypertensive patients include: performing 30 min to 60 min of aerobic exercise four to seven days per week; maintaining a healthy body weight (body mass index of 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (less than 102 cm in men and less than 88 cm in women); limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women; following a diet reduced in saturated fat and cholesterol, and one that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and considering stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and any comorbid conditions: blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients require more than one agent to achieve these blood pressure targets. In adults without compelling indications for other agents, initial therapy should include thiazide diuretics; other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (except in black patients), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction, or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor plus diuretic combination is preferred; in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered., Validation: All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.

Background: Prevalence surveys have consistently found that the blood pressure control rate among people with hypertension is less than 25%. Studies of telemedicine as a means of providing care to hypertensive patients have shown that this approach is effective in lowering blood pressure. Major design flaws and high operating costs, however, have hindered its adoption by physicians and patients., Objectives: In the present commentary, the field of telemedicine, as it pertains to hypertension management, is reviewed, and the investigators' experiences in developing a new telemedicine system are outlined., Methods: An applied qualitative case study approach was used to determine the information needs for the design of a telemedicine system. Opinions were elicited separately from type 2 diabetic patients with hypertension (n=24) and family practitioners in active clinical practice (n=18)., Results: Physician and patient focus group meetings provided key information that led to changes in the prototype system. The low level of computer and Internet use by patients in everyday life and by physicians in practice-related activities precluded their inclusion in the design of the system for information retrieval and receiving clinical alerts. For patients, the mobile phone appeared to be an acceptable alternative. The only practical, automated means to disseminate reports and alerts to physicians was by fax, which was the most universally available device in a doctor's office., Conclusion: This tightly focused qualitative study led to the development of design principles for a prototype system, increasing the likelihood of user acceptance and improving its effectiveness.

Objective: To provide updated, evidence-based recommendations for the management of hypertension in adults., Options and Outcomes: For lifestyle and pharmacological interventions, evidence from randomized, controlled trials and systematic reviews of trials was preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. For lifestyle interventions, blood pressure (BP) lowering was accepted as a primary outcome given the lack of long-term morbidity/mortality data in this field. For treatment of patients with kidney disease, the development of proteinuria or worsening of kidney function was also accepted as a clinically relevant primary outcome., Evidence: MEDLINE searches were conducted from November 2004 to October 2005 to update the 2005 recommendations. In addition, reference lists were scanned and experts were contacted to identify additional published studies. All relevant articles were reviewed and appraised independently by content and methodological experts using prespecified levels of evidence., Recommendations: Lifestyle modifications to prevent and/or treat hypertension include the following: perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index of 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (less than 102 cm for men and less than 88 cm for women); limit alcohol consumption to no more than 14 standard drinks per week in men or nine standard drinks per week in women; follow a diet that is reduced in saturated fat and cholesterol and that emphasizes fruits, vegetables and low-fat dairy products; restrict salt intake; and consider stress management in selected individuals. Treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and comorbid conditions. BP should be lowered to less than 140/90 mmHg in all patients, and to less than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease (regardless of the degree of proteinuria). Most adults with hypertension require more than one agent to achieve these target BPs. For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic hypertension with or without systolic hypertension include beta-blockers (in those younger than 60 years), angiotensin-converting enzyme (ACE) inhibitors (in nonblack patients), long-acting calcium channel blockers or angiotensin receptor antagonists. Other agents for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine calcium channel blockers or angiotensin receptor antagonists. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with diabetes mellitus, ACE inhibitors or angiotensin receptor antagonists (or in patients without albuminuria, thiazides or dihydropyridine calcium channel blockers) are appropriate first-line therapies; and in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended. All hypertensive patients should have their fasting lipids screened, and those with dyslipidemia should be treated using the thresholds, targets and agents recommended by the Canadian Hypertension Education Program Working Group on the management of dyslipidemia and the prevention of cardiovascular disease. Selected patients with hypertension, but without dyslipidemia, should also receive statin therapy and/or acetylsalicylic acid therapy., Validation: All recommendations were graded according to strength of the evidence and voted on by the 45 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.

Background: Variance of peak bone mass has a substantial genetic component, as has been shown with twin studies examining quantitative measures such as bone mineral density (BMD) and quantitative ultrasound (QUS). Evidence implicating single nucleotide polymorphisms (SNPs) of the transforming growth factor beta-1 (TGFB1) gene is steadily accumulating. However, a comprehensive look at multiple SNPs at this locus for their association with indices of peak bone mass has not been reported., Methods: A cohort of 653 healthy Caucasian females 18 to 35 years old was genotyped for seven TGFB1 SNPs. Polymorphisms were detected by restriction endonuclease digestion of amplified DNA segments., Results: The frequencies of the least common allele at G-800A, C-509T, codon 10 (L10P), codon 25 (R25P), codon 263 (T263I), C861-20T, and 713-8 delC loci were 0.07, 0.33, 0.41, 0.08, 0.04, 0.25 and 0.01, respectively. A significant association was seen between QUS Stiffness Index (QUS-SI) and the SNP at codon 10 and the linked promoter SNP, C-509T. This association remained significant after multiple regression was used to incorporate important clinical covariates--age, BMI, level of activity, family history, and caffeine intake--into the model., Conclusion: The association of QUS-SI with -509T is consistent with a gene-dose effect, while only individuals homozygous for the codon 10P allele showed a significant increase. In this cohort of young healthy Caucasian females, the T allele at position -509 is associated with greater bone mass as measured by calcaneal ultrasound.

Objective: To determine the proportion of births complicated by either a pre-existing or a gestational non-proteinuric hypertension, presenting at <34 weeks' gestation, and the associated incidence with 1 or more serious perinatal complications or birth weight <3rd centile for gestational age., Methods: A retrospective chart review was conducted in 5 international centres, from 1998 to 2002, where "tight" control (normalization) of blood pressure (BP) is the norm. International Classification of Diseases (ICD) codes were used to identify women who delivered at > or =20 weeks' gestation, with any hypertensive disorder of pregnancy. Women were included if they had a diastolic blood pressure (dBP) of 90 to 109 mm Hg, due to either a pre-existing or a gestational non-proteinuric hypertension, presenting at <34 weeks' gestation. Women were excluded if they had ongoing severe hypertension, or if at presentation with dBP of 90 to 109 mm Hg, they had 1 or more of the following: proteinuria, an indication for "tight" control of BP or imminent delivery, or a known intrauterine fetal death or lethal fetal anomaly. Data were collected on paper forms, scanned into an electronic database, and summarized descriptively by type of hypertension., Results: There were 305 eligible women (0.7% deliveries, 12.8% hypertensive deliveries) identified with non-proteinuric hypertension that was either pre-existing (133 [43.6%]) or gestational (172 [56.4%]). Regardless of hypertension type, 16.4% (n = 50) of pregnancies were complicated by birth weight <3rd centile or 1 or more serious perinatal complications, 34.3% (n = 100) by preterm birth, 30.8% (n = 94) by preeclampsia, and 2.0% (n = 6) by serious maternal complications., Conclusion: Non-proteinuric pre-existing or gestational hypertension, presenting before 34 weeks' gestation, identifies a subpopulation of hypertensive pregnant women at both substantial perinatal risk and maternal risk. The CHIPS (Control of Hypertension In Pregnancy Study) trial is designed to determine how best to manage the hypertension of such women in order to optimize perinatal outcome.

This study was undertaken to determine whether abolition of obstructive sleep apnoea (OSA) by continuous positive airway pressure (CPAP) could reduce blood pressure (BP) in patients with refractory hypertension. In 11 refractory hypertensive patients with OSA, the acute effects of CPAP on nocturnal BP were studied during sleep and its longer term effects on 24-h ambulatory BP after 2 months. During a single night's application, CPAP abolished OSA and reduced systolic BP in stage 2 sleep from 138.3 +/- 6.8 to 126.0 +/- 6.3 mmHg. There was also a trend towards a reduction in average diastolic BP (from 77.7 +/- 4.5 to 72.9 +/- 4.5). CPAP usage for 2 months was accompanied by an 11.0 +/- 4.4 mmHg reduction in 24-h systolic BP. In addition, both the nocturnal and daytime components of systolic BP fell significantly by 14.4 +/- 4.4 and 9.3 +/- 3.9 mmHg, respectively. Diastolic BP was reduced significantly at night by 7.8 +/- 3.0 mmHg. In patients with refractory hypertension, acute abolition of obstructive sleep apnoea by continuous positive airway pressure reduces nocturnal blood pressure. These data also suggest that continuous positive airway pressure may reduce nocturnal and daytime systolic blood pressure chronically. Randomised trials are needed to confirm the latter results.

Background: Atherosclerotic renal artery stenosis is the most common cause of secondary hypertension. Balloon angioplasty is widely used for the treatment of hypertensive patients with renal artery stenosis., Objectives: The objective of this systematic review was to compare the effectiveness of balloon angioplasty (with and without stenting) with medical therapy on blood pressure control, renal function, frequency of renovascular complications, and side effects in hypertensive patients with atherosclerotic renal artery stenosis., Search Strategy: The reviewers performed a search of MEDLINE from 1966 to December 2002, EMBASE from 1980 to 2002, Science Citation Index from 1990 to 2002, the Cochrane Central Register of Controlled Trials and personal files to identify randomised controlled trials comparing balloon angioplasty with medical therapy in hypertensive patients with renal artery stenosis. In addition, reference lists of papers resulting from this search were hand-searched, and authors of published trials were contacted to enquire if they were aware of any eligible unpublished trials., Selection Criteria: Randomised and quasi-randomised controlled trials comparing balloon angioplasty with medical therapy in hypertensive patients with haemodynamically significant renal artery stenosis (greater than 50 per cent reduction in luminal diameter and minimal follow-up of six months)., Data Collection and Analysis: Two investigators independently extracted data on trial design, characteristics of trial participants, types of interventions, and outcome measures. The quality of the available data precluded a formal meta-analysis to assess the effect on blood pressure, renal function, and number and defined daily doses of antihypertensive drugs. Peto's odds ratios and corresponding 95% confidence intervals (CI) were calculated for dichotomous outcomes such as the presence or absence of patent vessels and renovascular complications., Main Results: Three randomised controlled trials involving 210 patients met the inclusion criteria. In unselected patients there was a consistent, but statistically non significant trend towards lower blood pressure in the balloon angioplasty group. Patients treated with balloon angioplasty required less antihypertensive drugs in two of three trials, and were more likely to have patent renal arteries after 12 months (OR 4.2, 95% CI 1.8 to 9.8). There were no differences in renal function. There were significantly fewer cardiovascular and renovascular complications in patients treated with angioplasty (OR 0.32, 95% CI 0.15 to 0.70, test for heterogeneity p > 0.1)., Reviewer's Conclusions: Available data are insufficient to conclude that balloon angioplasty is superior to medical therapy in lowering blood pressure of patients with renal artery stenosis in whom blood pressure can be controlled with medical therapy. In patients with hypertension refractory to medical therapy, there is some weak evidence that balloon angioplasty lowers blood pressure more effectively than medical therapy. Balloon angioplasty appears to be safe and leads to fewer cardiovascular and renovascular complications. There is a need for randomised controlled trials comparing the effect of balloon angioplasty and medical therapy on the preservation of renal function in the long term.

Familial aggregation of diseases potentially associated with metabolic syndrome (diabetes mellitus, hypertension, and cardiovascular diseases) was assessed in a colonoscopy-based case-control study of colorectal neoplasia in Toronto and Ottawa, Canada, in 1993-1996. Each familial disease was analyzed by logistic regression using generalized estimating equations. Case probands had incident adenomatous polyps (n = 172) or incident (n = 25) or prevalent (n = 132) colorectal cancer (CRC), while control probands (n = 282) had a negative colonoscopy and no history of CRC or polyps. Significant effect modification was evident in the data, with the strongest positive associations between familial diabetes and colorectal neoplasia among older probands with symptoms (parents: odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.2, 4.8; siblings: OR = 5.8, 95% CI: 2.6, 13.3). Familial hypertension was also associated with colorectal neoplasia among probands with symptoms (OR = 1.7, 95% CI: 1.1, 2.6). In stratified analyses, familial diabetes, hypertension, and stroke were positively associated with adenomatous polyps in subgroups of probands who were older and/or had symptoms, while only familial diabetes was possibly associated with CRC. Associations in other proband groups may have been obscured by high cumulative incidence of parental CRC. Family studies are needed to understand the contribution of specific environmental and genetic factors in accounting for the disease aggregations.

Background: Past studies identified an association between kidney stone disease (KSD) and hypertension. We recently reported a high occurrence of hypertension in families of patients with hyperuricosuric KSD. As hypercalciura frequently coexists with hyperuricosuria and high urinary excretion of calcium is found in patients with hypertension, we hypothesized that hyperuricosuria that is accompanied by hypercalciuria better describes the familial association between KSD and hypertension., Methods: Four hundred and eighty-six KSD patients, aged 18-50 years, attending a lithotripsy unit collected a 24-h urine sample for metabolic analysis and provided information on family history of hypertension. The familial occurrence of hypertension was compared among four groups of patients: those who had combined elevation of both urinary calcium and uric acid excretions ("combined" abnormality, n=56), those who had hyperuricosuria without concomitant hypercalciuria ("pure" hyperuricosuria, n=67), those who had hypercalciuria without concomitant hyperuricosuira ("pure" hypercalciuria, n=52), and a control KSD patient group ("other" abnormality, n=311). The prevalence of treated hypertension in patients from the four groups was 16%, 12%, 2%, 10%, respectively., Results: Thirty-four per cent of the patients with the "combined" abnormality had a positive family history of hypertension, defined as two or more first-degree relatives with treated hypertension, that was significantly higher than in patients with either "pure" hyperuricosuira (15%, P<0.02), "pure" hypercalciuria (8%, P<0.001), or patients with "other" abnormality (10%, P<0.001). The adjusted OR for positive family history of hypertension in the "combined" abnormality group compared to the control KSD patient group was 5.6 (2.39-13.30). The prevalence of hypertension in siblings of patients with the "combined" abnormality (13%) was significantly higher than in siblings of patients with either "pure" hyperuricosuria (3%, P<0.001), "pure" hypercalciuria (1%, P<0.001), or siblings of control patients with "other" abnormality (4%, P<0.001). The adjusted OR for hypertension in siblings of a patient with "combined" abnormality compared to a control KSD patient was 3.4 (1.97-5.91). Patients in the "combined" abnormality group were also characterized by significantly elevated urinary sodium, phosphorus, citrate and potassium excretions., Conclusions: Our data suggest that there is a strong, independent association between familial occurrence of hypertension and the phenotype characterized by combined elevation of both urinary uric acid and calcium excretions. The association is not present in those with "pure" hyperuricosuria or "pure" hypercalciuria. Ascertainment of patients based on this phenotype may identify more homogeneous populations for genetic analysis of hypertension.

In a meta-analysis of randomized trials of the effects of dietary sodium interventions on blood pressure, we found substantial heterogeneity among the studies. We were interested in evaluating whether measurement error, known to be a problem for dietary sodium measures, publication bias, or confounding factors could be responsible for the heterogeneity. A measurement error correction was developed that corrects both the slope and the intercept and takes into account the sample size of each study and the number of measurements taken on an individual. The measurement error correction had a minimal effect on the estimates, although it performed well in simulated data. A smoothed scatter plot was used to assess publication bias. Metaregressions provide a convenient way to jointly assess the effects of several factors, but care must be taken to fit an appropriate model.

Objective: To provide updated, evidence-based recommendations for health care professionals on the management of hypertension in adults., Options: For patients with hypertension, there are both lifestyle options and pharmacological therapy options that may control blood pressure. For those patients who are using pharmacological therapy, a range of antihypertensive drugs is available. The choice of a specific antihypertensive drug is dependent upon the severity of the hypertension and the presence of other cardiovascular risk factors and concurrent diseases., Outcomes: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered., Evidence: MEDLINE searches were conducted from the period of the last revision of the Canadian Recommendations for the Management of Hypertension (January 1993 to May 1998). Reference lists were scanned, experts were polled and the personal files of the authors were used to identify other studies. All relevant articles were reviewed, classified according to study design and graded according to levels of evidence., Values: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension., Benefits: Harms and costs: The diagnosis and treatment of hypertension with pharmacological therapy will reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and mortality., Recommendations: This document contains detailed recommendations pertaining to all aspects of the diagnosis and pharmacological therapy of hypertensive patients. With respect to diagnosis, the recommendations endorse the greater use of non-office-based measures of blood pressure control (i.e., using home blood pressure and automatic ambulatory blood pressure monitoring equipment) and greater emphasis on the identification of other cardiovascular risk factors, both in the assessment of prognosis in hypertension and in the choice of therapy. On the treatment side, lower targets for blood pressure control are advocated for some subgroups of hypertensive patients, in particular, those with diabetes and renal disease. Implicit in the recommendations for therapy is the principle that for the vast majority of hypertensive patients treated pharmacologically, practitioners should not follow a stepped-care approach. Instead, therapy should be individualized, based on consideration of concurrent diseases, both cardiovascular and noncardiovascular., Validation: All recommendations were graded according to the strength of the evidence and the consensus of all relevant stakeholders., Sponsors: The Canadian Hypertension Society and the Canadian Coalition for High Blood Pressure Prevention and Control.

Hyperinsulinemia and insulin resistance are implicated in the etiology of hypertension, but the mechanisms involved have not been established. The objectives of this study were to determine whether untreated essential hypertensive patients are more sensitive to the antinatriuretic action of insulin and more resistant to the counteracting natriuretic effect of atrial natriuretic peptide in contrast to age- and sex-matched normotensive control subjects. Urinary sodium excretion was measured at baseline, during hyperinsulinemic euglycemic clamp, and during coadministration of insulin and atrial natriuretic peptide. Baseline urinary sodium excretion was not significantly different in the normotensive subjects (415 +/- 47 mumol/min, n = 12) and hypertensive patients (381 +/- 18 mumol/min, n = 10); with the institution of insulin infusion, there was a similar and significant decline from baseline (P < .001) to 289 +/- 35 mumol/min in normotensive subjects and 235 +/- 17 mumol/min in hypertensive patients. Atrial natriuretic peptide was able to oppose the antinatriuretic action of insulin in normotensive subjects, increasing urinary sodium excretion significantly to a mean level of 352 +/- 31 mumol/min (P < .05), which did not differ significantly from baseline. In the hypertensive group, atrial natriuretic peptide infusion had no effect on urinary sodium excretion (238 +/- 18 mumol/min), and the difference from baseline remained highly significant (P < .001). The hypertensive patients were significantly less insulin sensitive than their normotensive counterparts, as reflected by a lower glucose utilization rate and higher mean baseline plasma insulin level (P < .05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To update recommendations for the diagnosis of mild hypertension in adults and to assess the role of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring., Data Sources: Literature reviews of previous consensus conferences were updated with searches of MEDLINE for the period Jan. 1, 1988, to Nov. 15, 1991, and supplemented by reference lists and personal files., Study Selection: Panel members selected relevant articles and rated them according to methodologic criteria., Data Extraction: The data extracted concerned the measurement of blood pressure, the diagnosis of hypertension, the treatment of mild hypertension, and the reliability and validity of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring in the diagnosis of mild hypertension. The recommendations made were graded according to the level of evidence available, circulated to many experts and approved at a consensus conference., Main Results: Previous recommendations for the accurate measurement of blood pressure remain mostly unchanged. Antihypertensive treatment should be prescribed for patients (including the elderly) with an average diastolic blood pressure of at least 100 mm Hg, for those with isolated systolic hypertension (systolic blood pressure of at least 160 mm Hg and diastolic blood pressure of less than 90 mm Hg) and for patients with a diastolic blood pressure of 90 to 99 mm Hg and target-organ damage. Clinical judgement is required in treating patients with a diastolic blood pressure of 90 to 99 mm Hg without target-organ damage, and individual risk for cardiovascular disease must be taken into account. There is insufficient evidence to warrant the routine use of echocardiography, self-measurement of blood pressure or ambulatory blood pressure monitoring in diagnosis., Conclusions: Recent high-quality evidence supports several new recommendations for the diagnosis of mild hypertension in adults. Additional research is needed to determine the role of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring.