Showing papers by "Raymond R. Townsend published in 2014"
University of Iowa1, University of Alabama at Birmingham2, University of Tennessee Health Science Center3, Johns Hopkins University4, Kaiser Permanente5, Medical University of South Carolina6, University of Missouri7, University of Colorado Denver8, New York University9, University of North Carolina at Chapel Hill10, Duke University11, Mayo Clinic12, University of Pennsylvania13, Case Western Reserve University14, National Institutes of Health15
TL;DR: Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.
Abstract: Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.
7,119 citations
TL;DR: This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control.
Abstract: A total of 535 patients underwent randomization. The mean (±SD) change in systolic blood pressure at 6 months was −14.13±23.93 mm Hg in the denervation group as compared with −11.74±25.94 mm Hg in the sham-procedure group (P<0.001 for both comparisons of the change from baseline), for a difference of −2.39 mm Hg (95% confidence interval [CI], −6.89 to 2.12; P = 0.26 for superiority with a margin of 5 mm Hg). The change in 24-hour ambulatory systolic blood pressure was −6.75±15.11 mm Hg in the denervation group and −4.79±17.25 mm Hg in the sham-procedure group, for a difference of −1.96 mm Hg (95% CI, −4.97 to 1.06; P = 0.98 for superiority with a margin of 2 mm Hg). There were no significant differences in safety between the two groups. Conclusions This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control. (Funded by Medtronic; SYMPLICITY HTN-3 ClinicalTrials.gov number, NCT01418261.)
1,793 citations
SUNY Downstate Medical Center1, McGill University2, University of Connecticut3, Cornell University4, Umeå University5, Wayne State University6, University of Iowa7, University of Miami8, University of Pennsylvania9, Mayo Clinic10, University of Sydney11, University of Buenos Aires12, University of Chicago13, Shanghai Jiao Tong University14, North-West University15, University of Rochester16, University of Glasgow17, Virginia Commonwealth University18, University of Melbourne19
TL;DR: Clinical Practice Guidelines for the Management of Hypertension in the Community as mentioned in this paper A Statement by the American Society of hypertension and the International Society of Hyperpharmension (ISH).
Abstract: Clinical Practice Guidelines for the Management of Hypertension in the Community A Statement by the American Society of Hypertension and the International Society of Hypertension
920 citations
State University of New York System1, McGill University2, University of Connecticut3, Cornell University4, Umeå University5, Wayne State University6, University of Iowa7, University of Miami8, University of Pennsylvania9, Mayo Clinic10, University of Sydney11, University of Buenos Aires12, University of Chicago13, Shanghai Jiao Tong University14, North-West University15, University of Rochester16, University of Glasgow17, Virginia Commonwealth University18, University of Melbourne19
TL;DR: Clinical practice guidelines for the management of hypertension in the community a statement by the American Society of Hypertension and the International Society of hypertension as mentioned in this paper, which is based on guidelines from the National Institute of Neurological Disorders and Strochastic Hemorrhage.
Abstract: Clinical practice guidelines for the management of hypertension in the community a statement by the American society of hypertension and the International society of hypertension
665 citations
Broad Institute1, Eli Lilly and Company2, University of Victoria3, Institute for Systems Biology4, University of Washington5, ETH Zurich6, University of California, San Francisco7, University of South Florida8, Vanderbilt University9, Pacific Northwest National Laboratory10, Food and Drug Administration11, Pfizer12, Fred Hutchinson Cancer Research Center13, Purdue University14, National Institutes of Health15, Centers for Disease Control and Prevention16, Johns Hopkins University17, Korea University18, Harvard University19, Emory University20, Washington University in St. Louis21, Leidos22, University of Texas Health Science Center at San Antonio23
TL;DR: A workshop was held at the National Institutes of Health with representatives from the multiple communities developing and employing targeted MS assays and defined three tiers of assays distinguished by their performance and extent of analytical characterization.
476 citations
TL;DR: In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce CRP levels more than either intervention alone, and adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure.
Abstract: Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear. Methods We randomly assigned 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter to receive treatment with continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. We assessed the incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure. Results Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone. Blood pressure was reduced in all three groups. No significant incremental effect on CRP levels was found for the combined interventions as compared with either weight loss or CPAP alone. Reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. In per-protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone. Conclusions In adults with obesity and obstructive sleep apnea, CPAP combined with a weightloss intervention did not reduce CRP levels more than either intervention alone. In secondary analyses, weight loss provided an incremental reduction in insulin resistance and serum triglyceride levels when combined with CPAP. In addition, adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure as compared with either intervention alone. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT0371293.)
390 citations
TL;DR: AML cells with the R882H mutation have severely reduced de novo methyltransferase activity and focal hypomethylation at specific CpGs throughout AML cell genomes.
364 citations
TL;DR: Existing literature regarding inflammation and arterial stiffness is summarized, including a discussion of the potential mechanisms by which inflammation may lead to arterial stiffening and potential opportunities to assess the impact of anti-inflammatory interventions on arterIAL stiffness in subjects without primary inflammatory conditions.
181 citations
TL;DR: This trial did not demonstrate a benefit of renal artery denervation on reduction in ambulatory BP in either the 24-h or day and night periods compared with sham.
170 citations
TL;DR: Large artery stiffness is an independent predictor of incident HF in chronic kidney disease, an association with strong biological plausibility given the known effects of large artery stiffening of left ventricular pulsatile load.
Abstract: Background—Chronic kidney disease is associated with an increased risk of heart failure (HF). We aimed to evaluate the role of large artery stiffness, brachial, and central blood pressure as predictors of incident hospitalized HF in the Chronic Renal Insufficiency Cohort (CRIC), a multiethnic, multicenter prospective observational study of patients with chronic kidney disease. Methods and Results—We studied 2602 participants who were free of HF at baseline. Carotid-femoral pulse wave velocity (CF-PWV; the gold standard index of large artery stiffness), brachial, and central pressures (estimated via radial tonometry and a generalized transfer function) were assessed at baseline. Participants were prospectively followed up to assess the development of new-onset hospitalized HF. During 3.5 years of follow-up, 154 participants had a first hospital admission for HF. CF-PWV was a significant independent predictor of incident hospitalized HF. When compared with the lowest tertile, the hazard ratios among subject...
87 citations
TL;DR: A cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study found that carefully selected older kidney donors do not face a higher risk of death or CVD.
TL;DR: Reflection magnitude is independently associated with all-cause mortality in a multiethnic population initially free of clinically evident cardiovascular disease.
Abstract: Arterial wave reflections have been associated with mortality in an ethnically homogenous Asian population. It is unknown whether this association is present in a multiethnic population or whether it is independent of subclinical atherosclerosis. We hypothesized that reflection magnitude (defined as the ratio of the amplitude of the backward wave [Pb] to that of the forward wave [Pf]) is associated with all-cause mortality in a large multiethnic adult community-based sample. We studied 5984 participants enrolled in the Multi-Ethnic Study of Atherosclerosis who had analyzable arterial tonometry waveforms. During 9.8±1.7 years of follow-up, 617 deaths occurred, of which 134 (22%) were adjudicated cardiovascular deaths. In Cox proportional hazards models, each 10% increase in reflection magnitude was associated with a 31% increased risk for all-cause mortality (hazard ratio [HR]=1.31; 95% confidence interval [CI]=1.11-1.55; P=0.001). This relationship persisted after adjustment for various confounders and for markers of subclinical atherosclerosis (HR=1.23; 95% CI=1.01-1.51; P=0.04), including the coronary calcium score, ankle-brachial index, common carotid intima-media thickness, and ascending thoracic aortic Agatston score. Pb was independently associated with all-cause mortality in a similarly adjusted model (HR per 10 mm Hg increase in P(b)=2.18; 95% CI=1.21-3.92; P=0.009). Reflection magnitude (HR=1.71; 95% CI=1.06-2.77; P=0.03) and P(b) (HR=5.02; 95% CI=1.29-19.42; P=0.02) were mainly associated with cardiovascular mortality. In conclusion, reflection magnitude is independently associated with all-cause mortality in a multiethnic population initially free of clinically evident cardiovascular disease. This relationship persists after adjustment for a comprehensive set of markers of subclinical atherosclerosis.
TL;DR: Among a cohort of individuals with CKD, lower UCr is associated with death and ESRD independent of FFM as assessed by bioelectrical impedance analysis.
Abstract: Background and objectives Previous studies in chronic disease states have demonstrated an association between lower urinary creatinine excretion (UCr) and increased mortality, a finding presumed to reflect the effect of low muscle mass on clinical outcomes. Little is known about the relationship between UCr and other measures of body composition in terms of the ability to predict outcomes of interest. Design, setting, participants, & measurements Using data from the Chronic Renal Insufficiency Cohort (CRIC), the relationship between UCr, fat free mass (FFM) as estimated by bioelectrical impedance analysis, and (in a subpopulation) whole-body dual-energy x-ray absorptiometry assessment of appendicular lean mass were characterized. The associations of UCr and FFM with mortality and ESRD were compared using Cox proportional hazards models. Results A total of 3604 CRIC participants (91% of the full CRIC cohort) with both a baseline UCr and FFM measurement were included; of these, 232 had contemporaneous dual-energy x-ray absorptiometry measurements. Participants were recruited between July 2003 and March 2007. UCr and FFM were modestly correlated (rho=0.50; P Conclusions Among a cohort of individuals with CKD, lower UCr is associated with death and ESRD independent of FFM as assessed by bioelectrical impedance analysis.
TL;DR: Analyses of controlled clinical trial data from future trials with novel designs will be of critical importance to determine the effectiveness of device therapy for patients with severe and resistant hypertension and will allow for proper determination of patient selection and whether it will be acceptable for clinical practice.
Abstract: The epidemiology, evaluation, and management of severe and resistant hypertension in the United States (US) are evolving. The American Society of Hypertension held a multi-disciplinary forum in October 2013 to review the available evidence related to the management of resistant hypertension with both drug and device therapies. There is strong evidence that resistant hypertension is an important clinical problem in the US and many other regions of the world. Complex drug therapy is effective in most of the patients with severe and resistant hypertension, but there are certain individuals who may be refractory to multiple-drug regimens or have adverse effects that make adherence to the regimen difficult. When secondary forms of hypertension and pseudo-resistance, such as medication nonadherence, or white-coat hypertension based on marked differences between clinic and 24-hour ambulatory blood pressure monitoring, have been excluded, the impact of device therapy is under evaluation through clinical trials in the US and from clinical practice registries in Europe and Australia. Clinical trial data have been obtained primarily in patients whose resistant hypertension is defined as systolic clinic blood pressures of ≥160 mm Hg (or ≥ 150 mm Hg in type 2 diabetes) despite pharmacologic treatment with at least three antihypertensive drugs (one of which is a thiazide or loop diuretic). Baroreceptor stimulation therapy has shown modest benefit in a moderately sized sham-controlled study in drug-resistant hypertension. Patients selected for renal denervation have typically been restricted to those with preserved kidney function (estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2). The first sham-controlled safety and efficacy trial for renal denervation (SYMPLICITY HTN-3) did not show benefit in this population when used in addition to an average of five antihypertensive medications. Analyses of controlled clinical trial data from future trials with novel designs will be of critical importance to determine the effectiveness of device therapy for patients with severe and resistant hypertension and will allow for proper determination of patient selection and whether it will be acceptable for clinical practice. At present, the focus on the management of severe and resistant hypertension will be through careful evaluation for pseudo-resistance and secondary forms of hypertension, appropriate use of combination pharmacologic therapy, and greater utility of specialists in hypertension.
TL;DR: Self-reported heart failure was an independent risk factor for the development of the endpoint of ESRD or 50% decline in GFR in a cohort of patients with chronic kidney disease.
Abstract: Background and Aims: There is limited information on the risk of progression of chronic kidney disease (CKD) among individuals with CVD (cardiovascular disease). We studied the association between prevalent CVD and the risk of progression of CKD among persons enrolled in a long-term observational study. Methods: A prospective cohort study of 3,939 women and men with CKD enrolled in the chronic renal insufficiency cohort (CRIC) study between June 2003 and June 2008. Prevalent cardiovascular disease (myocardial infarction/revascularization, heart failure, stroke, and peripheral vascular disease) was determined by self-report at baseline. The primary outcome was a composite of either end-stage renal disease or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline. Results: One-third (1,316 of 3,939, 33.4%) of the study participants reported a history of any cardiovascular disease, and 9.6% (n = 382) a history of heart failure at baseline. After a median follow up of 6.63 years, 1,028 patients experienced the primary outcome. The composite of any CVD at baseline was not independently associated with the primary outcome (Hazard Ratio 1.04 95% CI (0.91, 1.19)). However, a history of heart failure was independently associated with a 29% higher risk of the primary outcome (Hazard Ratio 1.29 95% CI (1.06, 1.57)). The relationship between heart failure and risk of CKD progression was consistent in subgroups defined by age, race, gender, baseline eGFR, and diabetes. Neither the composite measure of any CVD or heart failure was associated with the rate of decline in eGFR. Conclusions: Self-reported heart failure was an independent risk factor for the development of the endpoint of ESRD or 50% decline in GFR in a cohort of patients with chronic kidney disease. i 2014 S. Karger AG, Basel
National Institutes of Health1, University of Massachusetts Amherst2, University of Pennsylvania3, Los Angeles Biomedical Research Institute4, Tulane University5, Kaiser Permanente6, George Washington University7, Temple University8, Children's Hospital of Philadelphia9, Cleveland Clinic10, Veterans Health Administration11, Edward Hines, Jr. VA Hospital12
TL;DR: Higher plasma CXCL12 was associated with CVD risk factors and prevalent CVD as well as the hazard of incident MI and death in chronic kidney disease patients.
Abstract: Aims Genome-wide association studies revealed an association between a locus at 10q11, downstream from CXCL12, and myocardial infarction (MI). However, the relationship among plasma CXCL12, cardiovascular disease (CVD) risk factors, incident MI, and death is unknown.
Methods and results We analysed study-entry plasma CXCL12 levels in 3687 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective study of cardiovascular and kidney outcomes in chronic kidney disease (CKD) patients. Mean follow-up was 6 years for incident MI or death. Plasma CXCL12 levels were positively associated with several cardiovascular risk factors (age, hypertension, diabetes, hypercholesterolaemia), lower estimated glomerular filtration rate (eGFR), and higher inflammatory cytokine levels ( P < 0.05). In fully adjusted models, higher study-entry CXCL12 was associated with increased odds of prevalent CVD (OR 1.23; 95% confidence interval 1.14, 1.33, P < 0.001) for one standard deviation (SD) increase in CXCL12. Similarly, one SD higher CXCL12 increased the hazard of incident MI (1.26; 1.09,1.45, P < 0.001), death (1.20; 1.09,1.33, P < 0.001), and combined MI/death (1.23; 1.13–1.34, P < 0.001) adjusting for demographic factors, known CVD risk factors, and inflammatory markers and remained significant for MI (1.19; 1.03,1.39, P = 0.01) and the combined MI/death (1.13; 1.03,1.24, P = 0.01) after further controlling for eGFR and urinary albumin:creatinine ratio.
Conclusions In CKD, higher plasma CXCL12 was associated with CVD risk factors and prevalent CVD as well as the hazard of incident MI and death. Further studies are required to establish if plasma CXCL12 reflect causal actions at the vessel wall and is a tool for genomic and therapeutic trials.
TL;DR: The data suggest that NAD(P)H oxidase is a source of reactive oxygen species and contributes to microvascular dysfunction in patients with CKD.
Abstract: Oxidative stress promotes vascular dysfunction in chronic kidney disease (CKD). We utilized the cutaneous circulation to test the hypothesis that reactive oxygen species derived from NADPH oxidase ...
Stanford University1, Veterans Health Administration2, Kaiser Permanente3, University of California, San Francisco4, University of Pennsylvania5, Tulane University6, National Institutes of Health7, University of Illinois at Chicago8, University of Michigan9, Case Western Reserve University10, Wayne State University11
TL;DR: The objective was to determine the association between cognition and levels of cystatin C in persons with chronic kidney disease (CKD) and to establish a cause-and-effect relationship.
Abstract: Objectives: To determine the association between cognition and levels of cystatin C in persons with chronic kidney disease (CKD).
Design: Prospective observational study.
Setting: Chronic Renal Insufficiency Cohort Cognitive Study.
Participants: Individuals with a baseline cognitive assessment completed at the same visit as serum cystatin C measurement (N = 821; mean age 64.9, 50.6% male, 48.6% white).
Measurements: Levels of serum cystatin C were categorized into tertiles; cognitive function was assessed using six neuropsychological tests. Scores on these tests were compared across tertiles of cystatin C using linear regression and logistic regression to examine the association between cystatin C level and cognitive performance (1 standard deviation difference from the mean).
Results: After multivariable adjustment for age, race, education, and medical comorbidities in linear models, higher levels of cystatin C were associated with worse cognition on the modified Mini-Mental State Examination, Buschke Delayed Recall, Trail-Making Test Part (Trails) A and Part B, and Boston Naming (P < .05 for all). This association remained statistically significant for Buschke Delayed Recall (P = .01) and Trails A (P = .03) after additional adjustment for estimated glomerular filtration rate (eGFR). The highest tertile of cystatin C was associated with greater likelihood of poor performance on Trails A (odds ratio (OR) = 2.17, 95% confidence interval (CI) = 1.16–4.06), Trails B (OR = 1.89, 95% CI = 1.09–3.27), and Boston Naming (OR = 1.85, 95% CI = 1.07–3.19) than the lowest tertile after multivariate adjustment in logistic models.
Conclusion: In individuals with CKD, higher serum cystatin C levels were associated with worse cognition and greater likelihood of poor cognitive performance on attention, executive function, and naming. Cystatin C is a marker of cognitive impairment and may be associated with cognition independent of eGFR.
TL;DR: Home BP monitoring provides more data than conventional clinic or dialysis-unit BP measurements and is relatively easy to accomplish, is cost-effective, and has been shown to have an increasing role in the management of BP in the CKD population.
TL;DR: Changes in the abundance of hemoglobin and histones with the loss of normal α-crystallin chaperone function suggest that these proteins also play important roles in the biochemical mechanisms of hereditary cataracts.
Abstract: αA-crystallin and αB-crystallin are members of the small heat shock protein family and function as molecular chaperones and major lens structural proteins. Although numerous studies have examined their chaperone-like activities in vitro, little is known about the proteins they protect in vivo. To elucidate the relationships between chaperone function, substrate binding, and human cataract formation, we used proteomic and mass spectrometric methods to analyze the effect of mutations associated with hereditary human cataract formation on protein abundance in αA-R49C and αB-R120G knock-in mutant lenses. Compared with age-matched wild type lenses, 2-day-old αA-R49C heterozygous lenses demonstrated the following: increased crosslinking (15-fold) and degradation (2.6-fold) of αA-crystallin; increased association between αA-crystallin and filensin, actin, or creatine kinase B; increased acidification of βB1-crystallin; increased levels of grifin; and an association between βA3/A1-crystallin and αA-crystallin. Homozygous αA-R49C mutant lenses exhibited increased associations between αA-crystallin and βB3-, βA4-, βA2-crystallins, and grifin, whereas levels of βB1-crystallin, gelsolin, and calpain 3 decreased. The amount of degraded glutamate dehydrogenase, α-enolase, and cytochrome c increased more than 50-fold in homozygous αA-R49C mutant lenses. In αB-R120G mouse lenses, our analyses identified decreased abundance of phosphoglycerate mutase, several β- and γ-crystallins, and degradation of αA- and αB-crystallin early in cataract development. Changes in the abundance of hemoglobin and histones with the loss of normal α-crystallin chaperone function suggest that these proteins also play important roles in the biochemical mechanisms of hereditary cataracts. Together, these studies offer a novel insight into the putative in vivo substrates of αA- and αB-crystallin.
TL;DR: In this article, the authors investigated the association between serum aldosterone and death and end-stage renal disease in 3866 participants from the Chronic Renal Insufficiency Cohort, and the Cox proportional hazards models were used to evaluate independent associations between elevated aldrone concentrations and each outcome.
Abstract: Prior studies have demonstrated that elevated aldosterone concentrations are an independent risk factor for death in patients with cardiovascular disease. Limited studies, however, have evaluated systematically the association between serum aldosterone and adverse events in the setting of chronic kidney disease. We investigated the association between serum aldosterone and death and end-stage renal disease in 3866 participants from the Chronic Renal Insufficiency Cohort. We also evaluated the association between aldosterone and incident congestive heart failure and atherosclerotic events in participants without baseline cardiovascular disease. Cox proportional hazards models were used to evaluate independent associations between elevated aldosterone concentrations and each outcome. Interactions were hypothesized and explored between aldosterone and sex, race, and the use of loop diuretics and renin-angiotensin-aldosterone system inhibitors. During a median follow-up period of 5.4 years, 587 participants died, 743 developed end-stage renal disease, 187 developed congestive heart failure, and 177 experienced an atherosclerotic event. Aldosterone concentrations (per SD of the log-transformed aldosterone) were not an independent risk factor for death (adjusted hazard ratio, 1.00; 95% confidence interval, 0.93-1.12), end-stage renal disease (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.17), or atherosclerotic events (adjusted hazard ratio, 1.04; 95% confidence interval, 0.85-1.18). Aldosterone was associated with congestive heart failure (adjusted hazard ratio, 1.21; 95% confidence interval, 1.02-1.35). Among participants with chronic kidney disease, higher aldosterone concentrations were independently associated with the development of congestive heart failure but not for death, end-stage renal disease, or atherosclerotic events. Further studies should evaluate whether mineralocorticoid receptor antagonists may reduce adverse events in individuals with chronic kidney disease because elevated cortisol levels may activate the mineralocorticoid receptor.
TL;DR: The results showed a nonlinear relationship between mean ratio of arteriole/vein calibers and the risk of progression to ESRD and decline in eGFR after taking into account established risk factors.
Abstract: Background and objectives Retinal abnormalities may be associated with changes in the renal vasculature. This study assessed the association between retinopathy and progression of kidney disease in participants of the Chronic Renal Insufficiency Cohort (CRIC) study. Design, setting, participants, & measurements This was a prospective study in which patients with CKD enrolled in CRIC had nonmydriatic fundus photographs of both eyes. All CRIC participants in six clinical sites in which fundus cameras were deployed were offered participation. Photographs were reviewed at a reading center. The presence and severity of retinopathy and vessel calibers were assessed using standard protocols by graders masked to clinical information. The associations of retinal features with changes in eGFR and the need for RRT (ESRD) were assessed. Results Retinal images and renal progression outcomes were obtained from 1852 of the 2605 participants (71.1%) approached. During follow-up (median 2.3 years), 152 participants (8.2%) developed ESRD. Presence and severity of retinopathy at baseline were strongly associated with the risk of subsequent progression to ESRD and reductions in eGFR in unadjusted analyses. For example, participants with retinopathy were 4.4 times (95% confidence interval [95% CI], 3.12 to 6.31) more likely to develop ESRD than those without retinopathy ( P P Conclusions The presence and severity of retinopathy were not associated with ESRD and decline in eGFR after taking into account established risk factors.
TL;DR: The transcriptome, proteome and immunolome of adult P. kellicotti represent a major advance in the study of Paragonimus species and provide a powerful foundation for translational research to develop improved diagnostic tests.
Abstract: Background: Paragonimiasis is a food-borne trematode infection acquired by eating raw or undercooked crustaceans. It is a major public health problem in the far East, but it also occurs in South Asia, Africa, and in the Americas. Paragonimus worms cause chronic lung disease with cough, fever and hemoptysis that can be confused with tuberculosis or other non-parasitic diseases. Treatment is straightforward, but diagnosis is often delayed due to a lack of reliable parasitological or serodiagnostic tests. Hence, the purpose of this study was to use a systems biology approach to identify key parasite proteins that may be useful for development of improved diagnostic tests. Methodology/Principal Findings: The transcriptome of adult Paragonimus kellicotti was sequenced with Illumina technology. Raw reads were pre-processed and assembled into 78,674 unique transcripts derived from 54,622 genetic loci, and 77,123 unique protein translations were predicted. A total of 2,555 predicted proteins (from 1,863 genetic loci) were verified by mass spectrometric analysis of total worm homogenate, including 63 proteins lacking homology to previously characterized sequences. Parasite proteins encoded by 321 transcripts (227 genetic loci) were reactive with antibodies from infected patients, as demonstrated by immunoaffinity purification and high-resolution liquid chromatography-mass spectrometry. Serodiagnostic candidates were prioritized based on several criteria, especially low conservation with proteins in other trematodes. Cysteine proteases, MFP6 proteins and myoglobins were abundant among the immunoreactive proteins, and these warrant further study as diagnostic candidates. Conclusions: The transcriptome, proteome and immunolome of adult P. kellicotti represent a major advance in the study of Paragonimus species. These data provide a powerful foundation for translational research to develop improved diagnostic tests. Similar integrated approaches may be useful for identifying novel targets for drugs and vaccines in the future.
TL;DR: For the first time, the WHO has specific targets to address noncommunicable diseases and raised BP, in particular, as a worldwide health priority and the introduction of a global standardized treatment approach has great potential to enhance BP treatment and control worldwide.
Abstract: The World Health Organization (WHO) Global Monitoring Framework includes a set of nine voluntary noncommunicable disease goals for 2025. It was endorsed by the World Health Assembly in 2013 and includes for the first time a shared target to reduce the prevalence of raised blood pressure (BP; ≥140/ 90 mm Hg) globally by 25% by 2025. Other related priorities include reducing salt intake by 30% and physical inactivity by 10%. Hypertension affects 1 billion people worldwide and one third of adults have the condition. In addition to a significant increase in morbidity and mortality, the economic impact of suboptimal BP control is substantial. Reasons for poor BP control are many, ranging from poor medication adherence as a result of drug cost and complex medication regimens, to an inability to deliver effective treatment because of inadequate patient medical care, initial access, and follow-up, to complicated treatment algorithms for providers to follow. To address these issues, the Centers for Disease Control and Prevention (CDC), Pan American Health Organization, and other major stakeholder organizations are collaborating on the Global Standardized Hypertension Treatment Project. The Project aims to standardize and simplify the treatment of hypertension through the development of a framework that is flexible and has worldwide applicability. In Latin America and the Caribbean, regional workshop participants developed a primary core set of medications appropriate for the treatment of most adults with the condition. They include a diuretic (chlorthalidone), angiotensin-converting enzyme inhibitor (lisinopril), angiotensin receptor blocker (losartan), calcium channel blocker (amlodipine), b-blocker (bisoprolol), and a mineralocorticoid antagonist (spironolactone). Additional combination pharmacologic regimens were developed as well. Mechanisms to increase the availability and affordability of these medications in the region are also being pursued. Other Project aims are to identify and promote the integration of specific key evidence–based healthcare delivery elements that are central to improving hypertension control. Examples are patient registries, standardized treatment protocols, the promotion of multidisciplinary team–based care, and patient selfmanagement. For the first time, the WHO has specific targets to address noncommunicable diseases and raised BP, in particular, as a worldwide health priority. Towards this end, the introduction of a global standardized treatment approach to hypertension has great potential to enhance BP treatment and control worldwide.
TL;DR: Findings suggest that reduced endothelial function may be detected 1 year after HDP, and large prospective studies are needed to further understand the contribution of arterial stiffness and endothelial dysfunction in the evolution of CVD after these complicated pregnancies.
Abstract: Hypertensive disorders of pregnancy (HDP) are associated with cardiovascular disease (CVD) later in life. We investigated the association of HDP with blood pressure (BP) and arterial stiffness 1-year postpartum. Seventy-four participants, 33 with an HDP and 41 with uncomplicated pregnancies, were examined using applanation tonometry to measure BP, carotid-femoral pulse-wave velocity (cfPWV) and augmentation index (AIx). On average, women with HDP had a 9 mm higher systolic BP (p<.01), 0.8 m/s faster cfPWV (p=.09), and 5.4% greater AIx (p=.09) at the 1-year exam. After adjustment for covariates, there was no significant difference in cfPWV between groups, while a 7.3% greater AIx (p<.05) remained. These findings suggest reduced endothelial function may be detected 1 year after HDP. Large prospective studies are needed to further understand of the contribution of arterial stiffness and endothelial dysfunction to the evolution of CVD disease after these complicated pregnancies.
TL;DR: The authors found that RRI increases with age, serum creatinine, albuminuria, and diabetes mellitus and with increasing serum levels of ADMA and is also associated with carotid atherosclerosis, although whether this association is independent of large artery stiffness is unclear.
Abstract: The RRI was initially proposed for the diagnosis of various forms of renal disease. One of the earliest prospective uses of the RRI was in the prediction of kidney function outcomes following intervention for renal artery stenosis. In this study, an RRI >80 was associated with poorer outcomes, whether surgery or angioplasty was used to correct renal artery stenosis. However, accumulating evidence indicates that the RRI provides important information about the systemic vasculature as well. In this issue of The Journal of Clinical Hypertension, Calabia and colleagues add to our existing knowledge about the relationship between RRI and systemic arterial properties. The authors studied 202 hypertensive and 16 healthy adults and assessed the relationship between the RRI and various systemic arterial phenotypes, including carotid-femoral pulse wave velocity (a measure of large artery stiffness), pulse pressure, the aortic augmentation index (a surrogate of arterial wave reflections), 24-hour blood pressure (BP) measurements, ankle-brachial index, carotid intima-media thickness, and the presence of carotid plaques. They also assessed the relationship between RRI, classic cardiovascular risk factors, and circulating concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (NOS) that is independently associated with the presence of carotid atherosclerosis in the general population. The authors found that RRI increases with age, serum creatinine, albuminuria, and diabetes mellitus and with increasing serum levels of ADMA. In multivariable analysis, greater RRI values were independently associated with increasing age, increasing hemoglobin A1c, lower 24-hour diastolic BP, lower glomerular filtration rate, and greater carotid-femoral pulse wave velocity (or ambulatory arterial stiffness index). These findings add to the growing literature that demonstrates that the RRI is associated with aging, large artery stiffness, BP variability, and left ventricular remodeling and diastolic dysfunction. The RRI is also associated with carotid atherosclerosis, although whether this association is independent of large artery stiffness is unclear. In order to interpret existing literature about RRI, it is essential to assess its hemodynamic determinants. This is a highly relevant issue, since it is often assumed that the RRI reflects properties predominantly of the renal vasculature, in particular, intra-renal vascular resistance, as its name would indicate. Indeed, in many papers, the terms resistive index and renal vascular resistance are used interchangeably. Under the assumption that RRI is indeed a measure of intra-renal vascular resistance, associations reported by Calabia and coworkers and others could be interpreted as supportive of a relationship between the large arteries and the small renal vessels. However, strong evidence exists demonstrating that the RRI has hemodynamic determinants different from intra-renal vascular resistance, and that the latter has little influence on the RRI within physiologic ranges. In vitro experiments showed that the RRI is dependent on vascular compliance and resistance, becoming less and less dependent on resistance as compliance decreases, and being completely independent of vascular resistance when compliance is zero. In a different set of experiments, rabbit kidneys were perfused ex vivo using a pulsatile perfusion system in which renal vascular resistance and systolic, diastolic, and pulse pressure were controlled. In these experiments, the RRI increased only with marked, likely nonphysiologic, increases in renal vascular resistance. Indeed, changes in the RRI in response to marked renal vasoconstriction were only marginally greater than RRI measurement variability. However, the RRI was markedly affected by changes in pulse pressure. These in vitro and ex vivo experiments above are supported by in vivo experiments and human observations. Using an infusion of L-NGmonomethyl arginine (L-NMMA), which, like ADMA, is an inhibitor of endothelial NOS, Raff and colleagues showed that neither baseline nor the changes in RRI were correlated with renal vascular resistance or renal perfusion, assessed with para-aminohippuric acid and inulin clearance. In contrast, RRI correlated with central pulse pressure at baseline and during L-NMMA infusion, whereas renal vascular resistance did not correlate with central pulse pressure. Studies in kidney transplant recipients in which a consistent relationship Address for correspondence: Julio A. Chirinos, MD, PhD, Rm-8B111, University & Woodland Avenue, Philadelphia, PA 19104 E-mail: julio.chirinos@uphs.upenn.edu
Duke University1, Wake Forest University2, University of Chicago3, Harvard University4, Advocate Lutheran General Hospital5, Veterans Health Administration6, Tulane University7, Wayne State University8, National Institutes of Health9, University of Medicine and Dentistry of New Jersey10, University of Alabama at Birmingham11, University of Florida12, Montefiore Medical Center13, St. John's Hospital14, University of Pennsylvania15
TL;DR: A multistakeholder think tank was convened to discuss the current state of knowledge, improve the care of these patients, and identify appropriate study populations for future observational and randomized trials in the field of apparent treatment resistant hypertension.
01 Jan 2014
TL;DR: The PharmaSmart PS-2000 closely approximated mean daytime ambulatory BP, supporting the use of serial readings from this device in the assessment of BP, and in-pharmacy device results were similar to automated office results.
Abstract: The objective of this study was to compare serial readings from an in‐pharmacy automated blood pressure (BP) kiosk to mean daytime ambulatory BP. A total of 100 community‐dwelling adults with hypertension underwent (1) three baseline automated office readings; (2) three in‐pharmacy readings on each of four visits (12 total) using the PharmaSmart PS‐ 2000 kiosk; and (3) 24‐hour ambulatory BP monitoring between in‐pharmacy visits two and three. Paired t‐tests, Bland‐ Altman plots, and Pearson correlation coefficients were used for analysis. Mean BPs were 137.8 ! 13.7/81.9 ! 12.2 mm Hg for in‐pharmacy and 135.5 ! 11.7/79.7 ! 10.0 mm Hg for daytime ambulatory (difference of 2.3 ! 9.5/
01 Jan 2014
TL;DR: Analyses of controlled clinical trial data from future trials with novel designs will be of critical importance to determine the effectiveness of device therapy for patients with severe and resistant hypertension and will allow for proper determination of patient selection and whether it will be acceptable for treatment.
Abstract: The epidemiology, evaluation, and management of severe and resistant hypertension in the United States (US) are evolving. The American Society of Hypertension held a multi-disciplinary forum in October 2013 to review the available evidence related to the management of resistant hypertension with both drug and device therapies. There is strong evidence that resistant hypertension is an important clinical problem in the US and many other regions of the world. Complex drug therapy is effective in most of the patients with severe and resistant hypertension, but there are certain individuals who may be refractory to multiple-drug regimens or have adverse effects that make adherence to the regimen difficult. When secondary forms of hypertension and pseudo-resistance, such as medication nonadherence, or white-coat hypertension based on marked differences between clinic and 24-hour ambulatory blood pressure monitoring, have been excluded, the impact of device therapy is under evaluation through clinical trials in the US and from clinical practice registries in Europe and Australia. Clinical trial data have been obtained primarily in patients whose resistant hypertension is defined as systolic clinic blood pressures of � 160 mm Hg (or � 150 mm Hg in type 2 diabetes) despite pharmacologic treatment with at least three antihypertensive drugs (one of which is a thiazide or loop diuretic). Baroreceptor stimulation therapy has shown modest benefit in a moderately sized sham-controlled study in drug-resistant hypertension. Patients selected for renal denervation have typically been restricted to those with preserved kidney function (estimated glomerular filtration rate � 45 mL/min/1.73 m 2 ). The first shamcontrolled safety and efficacy trial for renal denervation (SYMPLICITY HTN-3) did not show benefit in this population when used in addition to an average of five antihypertensive medications. Analyses of controlled clinical trial data from future trials with novel designs will be of critical importance to determine the effectiveness of device therapy for patients with severe and resistant hypertension and will allow for proper determination of patient selection and whether it will be acceptable for
TL;DR: The mechanisms underlying the association between arterial stiffness/central hemodynamics and the short-term development of hypertension appear to differ from those underlying the relationship between kidney function and theShort-term Development of hypertension.
Abstract: OBJECTIVES: We examined the following: whether the estimated glomerular filtration rate calculated from the serum cystatin C levels (eGFRcys) and the brachial-ankle pulse wave velocity (baPWV) might be independent predictors of the development of hypertension over the short term, without any interaction; whether the baPWV may be directly associated with the development of hypertension without the mediation of the arterial stiffness-related acceleration of renal functional decline; whether the second peak of the radial pressure waveform (SP2) might also be a significant independent predictor of the development of hypertension. METHODS: In 1229 middle-aged normotensive Japanese men with preserved renal function, the baPWV, SP2 and eGFRcys were measured at the baseline and at the end of the 3-year study period. RESULTS: Hypertension was detected at the end of the 3-year study period in 127 men. The logistic regression analysis with adjustments demonstrated significant independent odds ratios of the baPWV and eGFRcys for the presence of hypertension at the end of the 3-year study period, without any interaction. When entered simultaneously in this model, the SP2 also showed a significant odds ratio. General linear model analysis revealed that none of the baPWV or SP2 measured at the baseline was related to the renal function assessed at the end of the 3-year study period. CONCLUSIONS: The mechanisms underlying the association between arterial stiffness/central hemodynamics and the short-term development of hypertension appear to differ from those underlying the association between kidney function and the short-term development of hypertension.