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Rationale and Objective Concerns about non-adherent behaviors often prevent dialysis patients from entering waitlists for transplantation, despite an inconsistent association with posttransplant outcomes. We examined the association between plausible metrics of non-adherence related to dialysis treatment and posttransplant outcomes. Study Design Retrospective cohort. We linked national dialysis treatment data with transplant registry data. Setting and Participants Adult patients on maintenance hemodialysis from 1/1/2004-12/31/2014 who received a kidney transplant at US centers. Exposures We examined five nonadherence metrics: serum potassium (≥5.2 mEq/L), serum phosphorus (>5.5 mg/dL), intradialytic weight gain (IDWG, ≥5 L), shortened treatments (≥30 minutes) and missed treatments (≥1); missed treatment data was only available for 2004-2009. These metrics were characterized as the proportion of time under observation. Dialysis observation time was divided into 3-month intervals (quarters) and the number of “non-adherent” measurements in each domain was calculated for each quarter. Outcomes Allograft loss; mortality; and acute rejection in the first posttransplant year. Analytical approach Using Cox proportional hazards and logistic regression, we estimated the hazard ratios (HRs) for graft loss and mortality, and odds ratios (OR) for rejection. Results 9543 patients met inclusion criteria. In our primary model, hyperphosphatemia (aHR 1.27, 05% CI 1.08-1.49), IDWG (aHR 1.39, 95% CI 1.23-1.59) and shortened treatments (aHR 1.54, 95% CI 1.12-2.13) were associated with greater rates of allograft loss but hyperkalemia was not. IDWG (aHR 1.49, 95% CI 1.29-1.73) and shortened treatments (aHR 1.34, 95% CI 1.13-1.58) were associated with mortality while hyperkalemia and hyperphosphatemia were not. Only shortened treatments was associated with an increased risk of acute rejection (aOR 3.88, 95% CI 1.98-7.58). In models limited to the years 2004 to 2009 that included missed treatments, missed treatments were only associated with mortality. Limitations Unmeasured confounding (e.g., dietary data); adherence metrics used may have multiple, complex causes. Conclusions Plausible measures of dialysis nonadherence have long-term associations with allograft and patient survival. Behavioral metrics were more closely associated with outcomes than laboratory markers. The implications of non-adherent behaviors for dialysis patients must be carefully considered before excluding patients from transplantation.

Background Treating hypertension with antihypertensive medications combinations, rather than one medication (ie, monotherapy), is underused in the United States, particularly in certain race/ethnic groups. Identifying factors associated with monotherapy use despite uncontrolled blood pressure (BP) overall and within race/ethnic groups may elucidate intervention targets in under-treated populations. Methods Cross-sectional analysis of National Health and Nutrition Examination Surveys (NHANES; 2013-2014 through 2017-2018). We included participants age ≥20 years with hypertension, taking at least one antihypertensive medication, and uncontrolled BP (systolic BP [SBP] ≥ 140 mmHg or diastolic BP [DBP] ≥ 90 mmHg). Demographic, clinical, and healthcare-access factors associated with antihypertensive monotherapy were determined using multivariable-adjusted Poisson regression. Results Among 1,597 participants with hypertension and uncontrolled BP, age- and sex- adjusted prevalence of monotherapy was 42.6% overall, 45.4% among non-Hispanic White, 31.9% among non-Hispanic Black, 39.6% among Hispanic, and 50.9% among non-Hispanic Asian adults. Overall, higher SBP was associated with higher monotherapy use, while older age, having a healthcare visit in the previous year, higher body mass index, and having heart failure were associated with lower monotherapy use. Conclusion Clinical and healthcare-access factors, including a healthcare visit within the previous year and co-morbid conditions were associated with a higher likelihood of combination antihypertensive therapy.

PURPOSE OF REVIEW: Several recent trials and observational studies have identified critical areas that can help to improve the management and measurement of blood pressure in patients with hypertension. RECENT FINDINGS: High quality trial evidence supports intensive systolic blood pressure lowering to 110–130 mmHg in older patients, potassium-based salt substitution in patients without chronic kidney disease, and chlorthalidone for the management of hypertension in patients with chronic kidney disease. Additionally, population-based studies indicate enormous underdiagnosis of primary aldosteronism as well as greater sustained intensification of antihypertensive therapy in older patients by maximizing medication dosage rather than adding new agents. The prevalence of hypertension is stable worldwide, though is generally improving in high-income countries and worsening in low-income countries. Furthermore, while cuffless blood pressure devices have the potential to improve access to blood pressure measurement, they have not yet demonstrated sufficient accuracy for clinical use. SUMMARY: Growing evidence supports intensive blood pressure lowering, sodium reduction, targeted antihypertensive treatment, and appropriate screening for secondary hypertension to optimize blood pressure control and reduce the risk of target organ damage from hypertension. Future studies are needed to identify ways to improve our ability to implement these findings in routine clinical practice.

Rationale & objectiveObservational studies have reported a U-shaped association between blood pressure (BP) before a hemodialysis session and death. In contrast, because a linear association between out-of-dialysis-unit BP and death has been reported, home BP may be a better target for treatment. To test the feasibility of this approach, we conducted a pilot trial of treating home versus predialysis BP in hemodialysis patients.Study designA 4-month, parallel, randomized, controlled trial.Settings & participants50 prevalent hemodialysis patients in San Francisco and Seattle. Participants were randomly assigned using 1:1 block randomization, stratified by site.InterventionsTo target home systolic BP (SBP)of 100-200mm Hg; 0.2% vs 0%) or low (defined as

Concerns over ACE inhibitor or ARB use to treat hypertension during COVID-19 remain unresolved. Although studies using more robust methodologies provided some clarity, sources of bias persist and it remains critical to quickly address this question. In this review, we discuss pernicious sources of bias using a causal model framework, including time-varying confounder, collider, information, and time-dependent bias, in the context of recently published studies. We discuss causal inference methodologies that can address these issues, including causal diagrams, time-to-event analyses, sensitivity analyses, and marginal structural modeling. We discuss effect modification and we propose a role for causal mediation analysis to estimate indirect effects via mediating factors, especially components of the renin--angiotensin system. Thorough knowledge of these sources of bias and the appropriate methodologies to address them is crucial when evaluating observational studies to inform patient management decisions regarding whether ACE inhibitors or ARBs are associated with greater risk from COVID-19.

Introduction Cardiovascular disease (CVD) is the leading cause of mortality among individuals with chronic kidney disease (CKD). Cardiac biomarkers of myocardial distention, injury, and inflammation may signal unique pathways underlying CVD in CKD. In this analysis, we studied the association of baseline levels and changes in 4 traditional and novel cardiac biomarkers with risk of all-cause, CV, and non-CV mortality in a large cohort of patients with CKD. Methods Among 3664 adults with CKD enrolled in the Chronic Renal Insufficiency Cohort Study, we conducted a cohort study to examine the associations of baseline levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac high-sensitivity troponin T (hsTnT), growth differentiation factor−15 (GDF-15), and soluble ST-2 (sST-2) with risks of all-cause and cardiovascular (CV) mortality. Among a subcohort of 842 participants, we further examined the associations between change in biomarker levels over 2 years with risk of all-cause mortality. We used Cox proportional hazards regression models and adjusted for demographics, kidney function measures, cardiovascular risk factors, and medication use. Results After adjustment, elevated baseline levels of each cardiac biomarker were associated with increased risk of all-cause mortality: NT-proBNP (hazard ratio [HR] = 1.92, 95% confidence interval [CI] = 1.73−2.12); hsTnT (HR = 1.62, 95% CI = 1.48, 1.78]); GDF-15 (HR = 1.61, 95% CI = 1.46−1.78]); and sST-2 (HR = 1.26, CI = 1.16−1.37). Higher baseline levels of all 4 cardiac biomarkers were also associated with increased risk of CV. Declines in NT-proBNP (adjusted HR = 0.55, 95% CI = 0.36−0.86) and sST2 (HR = 0.55, 95% CI = 0.36−0.86]) over 2 years were associated with lower risk of all-cause mortality. Conclusion In a large cohort of CKD participants, elevations of NT-proBNP, hsTnT, GDF-15, and sST-2 were independently associated with greater risks of all-cause and CV mortality., Graphical abstract

Background Whether ambulatory BP monitoring is of value in evaluating risk for outcomes in patients with CKD is not clear. Methods We followed 1502 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study for a mean of 6.72 years. We evaluated, as exposures, ambulatory BP monitoring profiles (masked uncontrolled hypertension, white-coat effect, sustained hypertension, and controlled BP), mean ambulatory BP monitoring and clinic BPs, and diurnal variation in BP-reverse dipper (higher at nighttime), nondipper, and dipper (lower at nighttime). Outcomes included cardiovascular disease (a composite of myocardial infarction, cerebrovascular accident, heart failure, and peripheral arterial disease), kidney disease (a composite of ESKD or halving of the eGFR), and mortality. Results Compared with having controlled BP, the presence of masked uncontrolled hypertension independently associated with higher risk of the cardiovascular outcome and the kidney outcome, but not with all-cause mortality. Higher mean 24-hour systolic BP associated with higher risk of cardiovascular outcome, kidney outcome, and mortality, independent of clinic BP. Participants with the reverse-dipper profile of diurnal BP variation were at higher risk of the kidney outcome. Conclusions In this cohort of participants with CKD, BP metrics derived from ambulatory BP monitoring are associated with cardiovascular outcomes, kidney outcomes, and mortality, independent of clinic BP. Masked uncontrolled hypertension and mean 24-hour BP associated with high risk of cardiovascular disease and progression of kidney disease. Alterations of diurnal variation in BP are associated with high risk of progression of kidney disease, stroke, and peripheral arterial disease. These data support the wider use of ambulatory BP monitoring in the evaluation of hypertension in patients with CKD. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/JASN/2020_09_24_JASN2020030236.mp3.

Objectives This study sought to assess if clinical phenogroups differ in comprehensive biomarker profiles, cardiac and arterial structure/function, and responses to spironolactone therapy. Background Previous studies identified distinct subgroups (phenogroups) of patients with heart failure with preserved ejection fraction (HFpEF). Methods Among TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial) participants, we performed latent-class analysis to identify HFpEF phenogroups based on standard clinical features and assessed differences in multiple biomarkers measured from frozen plasma; cardiac and arterial structure/function measured with echocardiography and arterial tonometry; prognosis; and response to spironolactone. Results Three HFpEF phenogroups were identified. Phenogroup 1 (n = 1,214) exhibited younger age, higher prevalence of smoking, preserved functional class, and the least evidence of left ventricular (LV) hypertrophy and arterial stiffness. Phenogroup 2 (n = 1,329) was older, with normotrophic concentric LV remodeling, atrial fibrillation, left atrial enlargement, large-artery stiffening, and biomarkers of innate immunity and vascular calcification. Phenogroup 3 (n = 899) demonstrated more functional impairment, obesity, diabetes, chronic kidney disease, concentric LV hypertrophy, high renin, and biomarkers of tumor necrosis factor-alpha–mediated inflammation, liver fibrosis, and tissue remodeling. Compared with phenogroup 1, phenogroup 3 exhibited the highest risk of the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest (hazard ratio [HR]: 3.44; 95% confidence interval [CI]: 2.79 to 4.24); phenogroups 2 and 3 demonstrated similar all-cause mortality (phenotype 2 HR: 2.36; 95% CI: 1.89 to 2.95; phenotype 3 HR: 2.26, 95% CI: 1.77 to 2.87). Spironolactone randomized therapy was associated with a more pronounced reduction in the risk of the primary endpoint in phenogroup 3 (HR: 0.75; 95% CI: 0.59 to 0.95; p for interaction = 0.016). Results were similar after excluding participants from Eastern Europe. Conclusions We identified important differences in circulating biomarkers, cardiac/arterial characteristics, prognosis, and response to spironolactone across clinical HFpEF phenogroups. These findings suggest distinct underlying mechanisms across clinically identifiable phenogroups of HFpEF that may benefit from different targeted interventions.

Having a usual source of care increases use of preventive services and is associated with improved survival in the general population. We evaluated this association in adults with chronic kidney disease (CKD).Prospective, observational cohort study.Adults with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.Usual source of care was self-reported as: 1) clinic, 2) emergency department (ED)/urgent care, 3) other.Primary outcomes included incident end-stage kidney disease (ESKD), atherosclerotic events (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, hospitalization events, and all-cause death.Multivariable regression analyses to evaluate the association between usual source of care (ED/urgent care vs clinic) and primary outcomes.Among 3,140 participants, mean age was 65 years, 44% female, 45% non-Hispanic White, 43% non-Hispanic Black, and 9% Hispanic, mean estimated glomerular filtration rate 50 mL/min/1.73 mCannot be generalized to all patients with CKD. Causal relationships cannot be established.In this large, diverse cohort of adults with moderate-to-severe CKD, those identifying ED/urgent care as usual source of care were at increased risk for death and hospitalizations. These findings highlight the need to develop strategies to improve health care access for this high-risk population.

BACKGROUND: In the Systolic Blood Pressure (SBP) Intervention Trial (SPRINT), intensive BP treatment reduced acute decompensated heart failure (ADHF) events. Here we report the effect on HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF) and their subsequent outcomes. METHODS: Incident ADHF was defined as hospitalization or emergency department visit, confirmed, and formally adjudicated by a blinded events committee using standardized protocols. HFpEF was defined as EF≥ 45%, and HFrEF was EF

Accurate blood pressure measurement is crucial for proper screening, diagnosis, and monitoring of high blood pressure. However, providers are not aware of proper blood pressure measurement skills, do not master all the appropriate skills, or miss key steps in the process, leading to inconsistent or inaccurate readings. Training in blood pressure measurement for most providers is usually limited to a one-time brief demonstration during professional education coursework. The American Medical Association and the American Heart Association developed a 30-minute e-Learning module designed to refresh and improve existing blood pressure measurement knowledge and clinical skills among practicing providers. One hundred seventy-seven practicing providers, which included medical assistants, nurses, advanced practice providers, and physicians, participated in a multi-site randomized educational study designed to assess the effect of this e-Learning module on blood pressure measurement knowledge and skills. Participants were randomized 1:1 to either the intervention or control group. The intervention group followed a pre-post assessment approach, and the control group followed a test-retest approach. The initial assessment showed that participants in both the intervention and control groups correctly performed less than half of the 14 skills considered necessary to obtain an accurate blood pressure measurement (mean scores 5.5 and 5.9, respectively). Following the e-Learning module, the intervention group performed on average of 3.4 more skills correctly vs 1.4 in the control group (P .01). Our findings reinforce existing evidence that errors in provider blood pressure measurements are highly prevalent and provide novel evidence that refresher training improves measurement accuracy.

Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.

BACKGROUND: The association between socioeconomic factors and development of peripheral artery disease (PAD) has not been as well characterized compared to other cardiovascular diseases (CVD). We sought to define how annual income, sex, race, and education level are associated with newly diagnosed PAD in a well-characterized, diverse set of adults with CKD. METHODS: The Chronic Renal Insufficiency Cohort Study (CRIC) is a multicenter, prospective cohort study designed to examine risk factors for progression of CKD and cardiovascular disease. Demographic and clinical data including ankle brachial index (ABI) and interventions were collected at baseline, as well as yearly during follow-up visits. Annual income was categorized as: < $25,000, $25,000–50,000, $50,000–100,000, or above $100,000. We excluded those with pre-existing PAD, defined as enrollment ABI of 1.4, or missing income data. Cox proportional hazards regression was used to estimate the risk for incident PAD during CRIC enrollment, defined as a drop in ABI to < 0.90 or a confirmed PAD intervention, including revascularization or amputation. RESULTS: A total of 3,313 patients met inclusion criteria, the mean age was 58.7 yrs, 56% were male, and 42% were Black. Over a median follow-up of 10.1 years, 639 participants (19%) were newly diagnosed with PAD. After adjusting for cardiovascular risk factors, all lower levels of annual household income were associated with increased incidence of PAD (income $100,000 (overall p-value=0.02). In the multivariable model, there was no association between education level and PAD incidence (p=0.80). Black race (HR 1.2, 95% CI 1.0–1.5, p=0.023) and female sex (HR 1.7, 95% CI 1.4–2.0, p

Introduction: Hypertension associates with both kidney and cardiovascular (CV) disease risk. Time-in-target range (TTR) associates with CV risk independent of mean SBP and SBP variability. We hypothesized that SBP TTR predicts both adverse kidney and CV outcomes. Methods: ACCORD BP and SPRINT trial participants with >=2 SBP measurements were eligible, except ACCORD standard BP lowering participants due fewer SBP measurements. SBP TTR for months 0-3 was calculated using Rosendaal linear interpolation with target ranges of 110-130 mm Hg and 120-140 mm Hg for participants in the intensive or standard arms, respectively. Adverse kidney outcomes included dialysis, kidney transplant, serum creatinine > 3.3 mg/dL, sustained eGFR of < 15 mL/min per 1.73 m 2 or sustained eGFR decline >40% after month 3. Adverse CV outcomes included myocardial infarction, stroke, heart failure and CV death. Cox proportional hazards regression models were used to estimate the association between TTR and adverse outcomes after demographics, clinical risk factors and baseline SBP adjustment Results: Participants with higher TTR were younger, less likely to have preexisting CV disease and had less albuminuria, higher eGFR and lower baseline SBP. In fully adjusted models accounting for baseline SBP, higher TTR independently associated with a lower risk of adverse kidney and CV outcomes (P-trend < .001 for each). Whereas the relationship between TTR and CV risk increased monotonically with higher TTR, the TTR association with kidney risk was greatest at the extremes of TTR ( Figure ). Conclusions: Further reductions in adverse kidney and CV outcomes may be achievable through sustained SBP control.

Background: We recently demonstrated how orthostatic hypotension might be used to identify out-of-office blood pressure phenotypes, including white coat effects and nocturnal non-dipping patterns. However, these findings have not been replicated in a population with chronic kidney disease (CKD). Objective: To examine the association between orthostatic hypotension (OH) or hypertension (OHTN) with ambulatory BP in adults with CKD. Methods: CRIC is a prospective multicenter observation cohort study of participants with CKD. Standing BP at 1 minute and ABPM were obtained on 1467 participants. OH was defined as a 20mmHg drop in systolic BP (SBP) or 10 mmHg drop in diastolic BP (DBP) when changing from seated to standing positions. OHTN was defined as a 20 mmHg or 10mmHg rise in SBP or DBP respectively when changing from seated to standing position. White coat effects, based on ABPM, was defined as the difference between seated clinic and ambulatory BP. Systolic and diastolic night to day ratio was also calculated. Results: Of the 1467 participants (age: 58 ± 10 yrs, 44% female, 39% black) 73 had OH and 165 had OHTN). OH was positively associated with systolic and diastolic white coat effect (β=5.9 [0.9, 10.9] and 4.2 [1.3, 7.1]). OHTN was negatively associated with diastolic white coat effect (-4.9 [-6.9, -3]). OH was positively associated with systolic and diastolic night-to-day ratio (0.03 [0.01, 0.05] and 0.03 [0.01, 0.06] respectively). Conclusions: Clinic-based assessments of OH and OHTN may be useful for identifying BP phenotypes often missed with seated office BP measurements in CKD patients.

Author(s): Turgeon, Ricky D; Althouse, Andrew D; Cohen, Jordana B; Enache, Bogdan; Hogenesch, John B; Johansen, Michael E; Mehta, Raj; Meyerowitz-Katz, Gideon; Ziaeian, Boback; Hiremath, Swapnil

Cancer patients and survivors of cancer have a greater burden of cardiovascular disease compared with the general population. Much of the elevated cardiovascular risk in these individuals is likely attributable to hypertension, because individuals with cancer have a particularly high incidence of hypertension following cancer diagnosis. Treatment with chemotherapy is an independent risk factor for hypertension due to direct effects of many agents on endothelial function, sympathetic activity, and renin-angiotensin system activity, as well as nephrotoxicity. Diagnosis and management of hypertension in cancer patients requires accurate blood pressure measurement and consideration of potential confounding factors, such as adjuvant treatments and acute pain, that can temporarily elevate blood pressure readings. Home blood pressure monitoring can be a useful tool to facilitate longitudinal blood pressure monitoring for titration of antihypertensive medications. Selection of antihypertensive agents in cancer patients should account for treatment-specific morbidities and target organ damage.

Few population-based studies have examined bleeding associated with clopidogrel drug-drug interactions (DDIs). We sought to identify precipitant drugs taken concomitantly with clopidogrel (an object drug) that increased serious bleeding rates. We screened 2000-2015 Optum commercial health insurance claims to identify DDI signals. We performed self-controlled case series studies for clopidogrel plus precipitant pairs, examining associations with gastrointestinal bleeding or intracranial hemorrhage. To distinguish native bleeding effects of a precipitant, we reexamined associations using pravastatin as a negative control object drug. Among 431 analyses, 28 clopidogrel plus precipitant pairs were statistically significantly positively associated with serious bleeding. Ratios of rate ratios ranged from 1.13-3.94. Among these pairs, 13 were expected given precipitant drugs alone increased and/or were harbingers of serious bleeding. The remaining 15 pairs constituted new DDI signals, none of which are currently listed in two major DDI knowledge bases.

Rationale & Objective Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus. Study Design Retrospective cohort study. Setting & Participants Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014. Exposure HCV antibody serostatus obtained as part of clinical data from a national dialysis provider. Outcomes Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist. Analytical Approach After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals. Results Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney. Limitations No data for HCV viral load or liver biopsy. Conclusions HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.

BACKGROUND Heart failure (HF) is a leading contributor of cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. HF risk prediction tools that utilize readily available clinical parameters to risk stratify individuals with CKD are needed. METHODS We included Black and White participants aged 30 to 79 years with CKD stages 2-4 enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study and without self-reported cardiovascular disease. We assessed model performance of the Pooled Cohort Equations to Prevent Heart Failure (PCP-HF) to predict incident HF hospitalizations and refit the PCP-HF in the CKD population using CRIC data-derived coefficients and survival from CRIC Study participants in the CKD population (PCP-HFCKD). We investigated the improvement in HF prediction with inclusion of estimated glomerular filtration rate [eGFR] and urine albumin to creatinine ratio [UACR] into the PCP-HFCKD equations by change in C-statistic, net reclassification improvement (NRI) and integrated discrimination improvement index (IDI). We validated the PCP-HFCKD with and without eGFR and UACR in Multi-Ethnic Study of Atherosclerosis (MESA) participants with CKD. RESULTS Among 2328 CRIC Study participants, 340 incident HF hospitalizations occurred over a mean follow-up of 9.5 years. The PCP-HF equations did not perform well in most participants with CKD and had inadequate discrimination and insufficient calibration (C-statistic 0.64-0.71, GND chi-square statistic p value 0.05). Addition of UACR, but not eGFR, to the refit PCP-HFCKD improved model performance in all race-sex groups (C-statistic [0.73-0.81], GND chi-square p value > 0.05, delta C-statistic ranging from 0.03-0.11 and NRI and IDI p values

Given unique pathways contributing to hypertension among people with HIV, we sought to determine whether antihypertensive class was associated with cardiovascular disease (CVD) events among people with HIV. Among veterans with HIV and incident hypertension (2000–2018), we used propensity-score matching to evaluate risk of (1) incident/recurrent CVD or death, (2) incident CVD, and (3) incident heart failure by antihypertensive class. In supplementary analyses, we performed stratified analyses by race and chronic kidney disease status. Among 8041 veterans, 24% were initiated on ACE (angiotensin-converting enzyme) inhibitor/ARB (angiotensin receptor blocker) monotherapy, 23% on thiazide/thiazide-like diuretic monotherapy, 13% on β-blocker monotherapy, and 11% on calcium channel blocker monotherapy. Over a median of 6.5 years, 25% experienced a CVD event. β-blockers, but not calcium channel blockers or diuretics, were associated with an increased risk of incident CVD compared with ACEs/ARBs (hazard ratio [95% CI], β-blockers 1.90 [1.24–2.89]; calcium channel blockers 1.02 [0.77–1.34]; diuretics 1.06 [0.86–1.31]); similar hazard ratio were noted for incident/recurrent CVD or death. In veterans without chronic kidney disease, ACE inhibitor/ARBs were associated with a lower risk of incident heart failure compared with all other classes (hazard ratio [95% CI]: β-blockers, 1.52 [1.11–2.09]; calcium channel blockers 1.48 [1.00–2.19]; diuretics 1.52 [1.07–2.16]). In conclusion, we observed high rates of CVD events in people with HIV with hypertension and a high prevalence of β-blocker use for initial hypertension management, even among those without indications. Our findings highlight the potential harm associated with β-blockers and the possible benefit associated with ACE inhibitor/ARBs for hypertension management in people with HIV. Prospective and randomized trials are needed to confirm these findings.

Background: Biological considerations suggest that renin–angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin–angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19. Methods: The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin–angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin–angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin–angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009. Findings: Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin–angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin–angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40–110] for continuation vs 81 [38–117] for discontinuation; β-coefficient 8 [95% CI −13 to 29]). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups. Interpretation: Consistent with international society recommendations, renin–angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19. Funding: REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants. Fil: Cohen, Jordana B.. State University of Pennsylvania; Estados Unidos Fil: Hanff, Thomas C.. State University of Pennsylvania; Estados Unidos Fil: William, Preethi. University of Arizona; Estados Unidos Fil: Sweitzer, Nancy. University of Arizona; Estados Unidos Fil: Rosado Santander, Nelson R.. Hospital Nacional Carlos Alberto Seguin Escobedo; Perú Fil: Medina, Carola. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Rodriguez-Mori, Juan E. Hospital Nacional Alberto Sabogal Sologuren; Perú Fil: Renna, Nicolas Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; Argentina Fil: Chang, Tara I.. University of Stanford; Estados Unidos Fil: Corrales Medina, Vicente. Ottawa Hospital Research Institute; Canadá Fil: Andrade Villanueva, Jaime F.. Hospital Civil de Guadalajara; México Fil: Barbagelata, Alejandro. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. University of Duke; Estados Unidos Fil: Cristodulo Cortez, Roberto. No especifíca; Fil: Díaz-Cucho, Omar A. Hospital Alberto Leopoldo Barton Thompson; Perú Fil: Spaak, Jonas. Danderyd University Hospital; Suecia Fil: Alfonso, Carlos E.. University of Miami; Estados Unidos Fil: Valdivia Vega, Renzo. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Villavicencio Carranza, Mirko. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Ayala García, Ricardo J.. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Castro Callirgos, Carlos A.. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: González Hernández, Luz A.. Hospital Civil de Guadalajara; México Fil: Bernales Salas, Eduardo F.. Hospital Nacional Carlos Alberto Seguin Escobedo; Perú Fil: Coacalla Guerra, Johanna C.. Hospital Nacional Carlos Alberto Seguin Escobedo; Perú Fil: Salinas Herrera, Cynthia D.. Hospital Nacional Carlos Alberto Seguin Escobedo; Perú Fil: Nicolosi, Liliana. Hospital Espanol; Argentina Fil: Basconcel, Mauro. Hospital Espanol; Argentina Fil: Byrd, James B.. University of Michigan; Estados Unidos Fil: Sharkoski, Tiffany. University of Pennsylvania; Estados Unidos Fil: Bendezú Huasasquiche, Luis E.. Hospital Alberto Leopoldo Barton Thompson; Perú Fil: Chittams, Jesse. University of Pennsylvania; Estados Unidos Fil: Edmonston, Daniel L.. University of Duke; Estados Unidos Fil: Vasquez, Charles R.. University of Pennsylvania; Estados Unidos Fil: Chirinos, Julio A.. University of Pennsylvania; Estados Unidos

Visual Abstract, Highlights • DM is a significant risk factor for major adverse cardiovascular events in patients with HFpEF. • Patients with diabetes with HFpEF have a distinct proteome compared with patients without diabetes with HFpEF. • Proteomics analysis identified higher levels of alpha-1-microglobulin/bikunin precursor protein in patients with diabetes with HFpEF and lower levels of CILP2 and Apo M. • Lower Apo M levels mediate most of the association between diabetes and major adverse cardiovascular events in HFpEF., Summary Diabetes mellitus (DM) is associated with a higher risk of heart failure hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Using SomaScan assays and proteomics analysis of plasma from participants in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial and the Penn Heart Failure Study, this study identified 10 proteins with significantly different expression in patients with HFpEF and DM. Of these, apolipoprotein M was found to mediate 72% (95% CI: 36% to 100%; p

Background Primary aldosteronism is a common cause of treatment-resistant hypertension. However, evidence from local health systems suggests low rates of testing for primary aldosteronism. Objective To evaluate testing rates for primary aldosteronism and evidence-based hypertension management in patients with treatment-resistant hypertension. Design Retrospective cohort study. Setting U.S. Veterans Health Administration. Participants Veterans with apparent treatment-resistant hypertension (n = 269 010) from 2000 to 2017, defined as either 2 blood pressures (BPs) of at least 140 mm Hg (systolic) or 90 mm Hg (diastolic) at least 1 month apart during use of 3 antihypertensive agents (including a diuretic), or hypertension requiring 4 antihypertensive classes. Measurements Rates of primary aldosteronism testing (plasma aldosterone-renin) and the association of testing with evidence-based treatment using a mineralocorticoid receptor antagonist (MRA) and with longitudinal systolic BP. Results 4277 (1.6%) patients who were tested for primary aldosteronism were identified. An index visit with a nephrologist (hazard ratio [HR], 2.05 [95% CI, 1.66 to 2.52]) or an endocrinologist (HR, 2.48 [CI, 1.69 to 3.63]) was associated with a higher likelihood of testing compared with primary care. Testing was associated with a 4-fold higher likelihood of initiating MRA therapy (HR, 4.10 [CI, 3.68 to 4.55]) and with better BP control over time. Limitations Predominantly male cohort, retrospective design, susceptibility of office BPs to misclassification, and lack of confirmatory testing for primary aldosteronism. Conclusion In a nationally distributed cohort of veterans with apparent treatment-resistant hypertension, testing for primary aldosteronism was rare and was associated with higher rates of evidence-based treatment with MRAs and better longitudinal BP control. The findings reinforce prior observations of low adherence to guideline-recommended practices in smaller health systems and underscore the urgent need for improved management of patients with treatment-resistant hypertension. Primary funding source National Institutes of Health.

Background: In the general population, genetic risk for elevated blood pressure has been associated with cardiovascular disease but not kidney function or incident chronic kidney disease. These relationships have not been studied longitudinally in participants with chronic kidney disease. We examined whether blood pressure genetic risk predicts cardiovascular disease and kidney disease progression in patients with chronic kidney disease. Methods: We included 1,493 African and 1,581 European ancestry participants from the Chronic Renal Insufficiency Cohort who were followed for 12 years. We examined associations of blood pressure genetic risk scores with development of cardiovascular disease (myocardial infarction, congestive heart failure, or stroke) and chronic kidney disease progression (incident end stage kidney disease or halving of estimated glomerular filtration rate) using Cox proportional hazards models. Analyses were stratified by race and included adjustment for age, sex, study site, and ancestry principal components. Results: Each standard deviation increase in systolic blood pressure and pulse pressure genetic risk score conferred respective 15% [95% confidence interval: 4%, 27%] and 11% (95% confidence interval: 1%, 23%) higher risks of cardiovascular disease, with a similar marginally significant trend for diastolic blood pressure, among European ancestry participants. Among African ancestry participants, each standard deviation increase in systolic and diastolic blood pressure genetic risk score conferred 10% (95% confidence interval: 1%, 20%) and 9% (95% confidence interval: 0%, 18%) higher risk of cardiovascular disease. Higher genetic risk was not associated with chronic kidney disease progression. Conclusions: Genetic risk for elevation in blood pressure was associated with increased risk of cardiovascular disease but not chronic kidney disease progression.

Introduction: Heart failure (HF) is a leading contributor of cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. While risk equations such as the pooled cohort equations to prevent HF (PCP-HF) have been validated in the general population, no such tools have been evaluated in CKD-specific cohorts. Strategies for identification of individuals with CKD at higher risk of HF are needed. Methods: Among black and white participants with CKD stages 2-4 enrolled in the CRIC Study, we included individuals between the ages of 30-79 without baseline cardiovascular disease. We assessed model performance of the PCP-HF to predict incident HF and recalibrated the PCP-HF in the CKD population (PCP-HF CKD ). Given that indices of kidney function are associated with HF, we examined the contribution of estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) to PCP-HF CKD by change in C-statistic, net reclassification index (NRI) and integrated discrimination index (IDI). Results: Among 2328 participants, mean (SD) baseline eGFR was 46 (15) ml/min/1.73m2 and median (IQR) UACR was 37 (7, 381) mg/g. Over 9.5 years of follow-up, 336 incident HF events occurred. The PCP-HF equations systematically under-predicted HF risk in participants with CKD (C-statistic CKD had good discrimination and calibration (C-statistic 0.75-0.78), except in black women (0.61). Addition of UACR, but not eGFR, to the PCP-HF CKD improved model calibration (Figure) and performance in all race-sex groups (delta C-statistic 0.03-0.11, NRI and IDI values p Conclusions: Routinely available clinical data in patients with CKD can reliably predict incident HF. Further study is needed to examine whether implementation of the modified PCP-HF CKD risk prediction equation into clinical practice can improve HF prevention and patient outcomes.

Rationale & Objective Evaluating repeated measures of estimated glomerular filtration rate (eGFR) and urinary protein-creatinine ratio (UPCR) over time may enhance our ability to understand the association between changes in kidney parameters and cardiovascular disease risk. Study Design Prospective cohort study. Setting & Participants Annual visit data from 2,438 participants in the Chronic Renal Insufficiency Cohort (CRIC). Exposures Average and slope of eGFR and UPCR in time-updated, 1-year exposure windows. Outcomes Incident heart failure, atherosclerotic cardiovascular disease events, death, and a composite of incident heart failure, atherosclerotic cardiovascular disease events, and death. Analytical Approach A landmark analysis, a dynamic approach to survival modeling that leverages longitudinal, iterative profiles of laboratory and clinical information to assess the time-updated 3-year risk of adverse cardiovascular outcomes. Results Adjusting for baseline and time-updated covariates, every standard deviation lower mean eGFR (19 mL/min/1.73 m2) and declining slope of eGFR (8 mL/min/1.73 m2 per year) were independently associated with higher risks of heart failure (hazard ratios [HRs] of 1.82 [95% CI, 1.39-2.44] and 1.28 [95% CI, 1.12-1.45], respectively) and the composite outcome (HRs of 1.32 [95% CI, 1.11-1.54] and 1.11 [95% CI, 1.03-1.20], respectively). Every standard deviation higher mean UPCR (136 mg/g) and increasing UPCR (240 mg/g per year) were also independently associated with higher risks of heart failure (HRs of 1.58 [95% CI, 1.28-1.97] and 1.20 [95% CI, 1.10-1.29], respectively) and the composite outcome (HRs of 1.33 [95% CI, 1.17-1.50] and 1.12 [95% CI, 1.06-1.18], respectively). Limitations Limited generalizability of annual eGFR and UPCR assessments; several biomarkers for cardiovascular disease risk were not available annually. Conclusions Using the landmark approach to account for time-updated patterns of kidney function, average and slope of eGFR and proteinuria were independently associated with 3-year cardiovascular risk. Short-term changes in kidney function provide information about cardiovascular risk incremental to level of kidney function, representing possible opportunities for more effective management of patients with chronic kidney disease.

ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.

The 2017 American College of Cardiology / American Heart Association blood pressure guideline recommends ambulatory blood pressure monitoring to detect masked hypertension. Data on the short-term reproducibility of masked hypertension are scarce. The Improving the Detection of Hypertension study enrolled 408 adults not taking antihypertensive medication from 2011–2013. Office blood pressure and 24-hour ambulatory blood pressure monitoring were performed on two occasions, a median of 29 days apart. After excluding participants with office hypertension (mean systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 80 mm Hg), the analytical sample included 254 participants. Using the Kappa statistic, we evaluated the reproducibility of masked awake hypertension (awake systolic/diastolic blood pressure ≥ 130/80 mm Hg) defined by the 2017 blood pressure guideline thresholds, as well as masked 24-hour (24-hour systolic/diastolic blood pressure ≥ 125/75 mm Hg), masked asleep (asleep systolic/diastolic blood pressure ≥ 110/65 mm Hg), and any masked hypertension (high awake, 24-hour, and/or asleep blood pressure). The mean (SD) age of participants was 38.0 (12.3) years and 65.7% were female. Based on the first and second ambulatory blood pressure recordings, 24.0% and 26.4% of participants, respectively, had masked awake hypertension. The Kappa statistic (95% CI) was 0.50 (0.38 to 0.62) for masked awake, 0.57 (0.46 to 0.69) for masked 24-hour, 0.57 (0.47 to 0.68) for masked asleep, and 0.58 (0.47 to 0.68) for any masked hypertension. Clinicians should consider the moderate short-term reproducibility of masked hypertension when interpreting the results from a single ambulatory blood pressure recording.

Introduction: Apparent treatment resistant hypertension (aTRH) affects 10-20% of hypertensive adults and increases risk of cardiovascular events and mortality. Fewer than half of these patients have true resistant hypertension. The majority experience pseudo-resistant hypertension due to inadequate medication adherence, white coat hypertension, and secondary causes of hypertension. We hypothesize that electronic health records can be leveraged to identify aTRH patients who would benefit from targeted counseling, medication reconciliation, and screening for secondary causes of hypertension. Methods: We studied electronic health record (EHR) data from 395 hypertensive adults in our primary care population who received longitudinal care between 2007 and 2017. Patients who met the 2008 AHA definition of resistant hypertension by chart review were considered to have aTRH. We also included 100 patients identified by heuristics targeting secondary hypertension. We extracted from the EHR demographics, vitals, laboratory results, diagnosis codes, and medications. Results outside of physiologic range were excluded and median imputation was used to handle missing data. Random forest model performance was assessed by 5-fold cross validation. Model discrimination was evaluated at an estimated positive predictive value of 75%. Results: The prevalence of aTRH in our randomly selected and full cohorts was 20.3% (n=295) and 25.8% (n=395), respectively. In cross-validation, the random forest model demonstrated a median sensitivity of 65% (IQR: 60% - 65%) and a median AUROC of 0.92 (IQR: 0.90 - 0.92). The most influential variables were related to the prescription of three or more hypertension medications; number of days on diuretics, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers; systolic blood pressure measurements; and hypertension or diabetes diagnosis codes. Conclusion: EHR data can be used to accurately identify patients with aTRH. We expect the implementation of a clinical decision support system leveraging such models could lead to the improved care for aTRH patients.

Purpose of the Review Angiotensin-converting enzyme 2 (ACE2) is a key counter-regulatory component of the renin-angiotensin system. Here, we briefly review the mechanistic and target organ effects related to ACE2 activity, and the importance of ACE2 in SARS-CoV-2 infection. Recent Findings ACE2 converts angiotensin (Ang) II to Ang-(1–7), which directly opposes the vasoconstrictive, proinflammatory, and prothrombotic effects of Ang II. ACE2 also facilitates SARS-CoV-2 viral entry into host cells. Drugs that interact with the renin-angiotensin system may impact ACE2 expression and COVID-19 pathogenesis; however, the magnitude and direction of these effects are unknown at this time. Summary High quality research is needed to improve our understanding of how agents that act on the renin-angiotensin system impact ACE2 and COVID-19-related disease outcomes.

Background Slopes of eGFR have been associated with increased risks of death and cardiovascular events in a U-shaped fashion. Poor outcomes in individuals with rising eGFR are potentially attributable to sarcopenia, hemodilution, and other indicators of clinical deterioration. Methods To investigate the association between eGFR slopes and risks of death or cardiovascular events, accounting for multiple confounders, we studied 2738 individuals with moderate to severe CKD participating in the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study. We used linear, mixed-effects models to estimate slopes with up to four annual eGFR assessments, and Cox proportional hazards models to investigate the association between slopes and the risks of death and cardiovascular events. Results Slopes of eGFR had a bell-shaped distribution (mean [SD], -1.5 [-2] ml/min per 1.73 m2 per year). Declines of eGFR that were steeper than the average decline associated with progressively increasing risks of death (hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 1.09 to 1.39; for a slope 1 SD below the average) and cardiovascular events (HR, 1.19; 95% CI, 1.03 to 1.38). Rises of eGFR or declines lower than the average decline were not associated with the risk of death or cardiovascular events. Conclusions In a cohort of individuals with moderate to severe CKD, we observed steep declines of eGFR were associated with progressively increasing risks of death and cardiovascular events; however, we found no increased risks associated with eGFR improvement. These findings support the potential value of eGFR slopes in clinical assessment of adults with CKD.

BACKGROUND AND OBJECTIVES: Hypertension is highly prevalent in patients with CKD as is cognitive impairment and frailty, but the link between them is understudied. Our objective was to determine the association between ambulatory BP patterns, cognitive function, physical function, and frailty among patients with nondialysis-dependent CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Ambulatory BP readings were obtained on 1502 participants of the Chronic Renal Insufficiency Cohort. We evaluated the following exposures: (1) BP patterns (white coat, masked, sustained versus controlled hypertension) and (2) dipping patterns (reverse, extreme, nondippers versus normal dippers). Outcomes included the following: (1) cognitive impairment scores from the Modified Mini Mental Status Examination of

BACKGROUND: Incident rates of ESRD are much higher among black and Hispanic patients than white patients. Access to nephrology care before progression to ESRD is associated with better clinical outcomes among patients with CKD. However, it is unknown whether black or Hispanic patients with CKD experience lower pre-ESRD nephrology consultation rates compared with their white counterparts, or whether such a disparity contributes to worse outcomes among minorities. METHODS: We assembled a retrospective cohort of patients with CKD who received care through the Veterans Health Administration from 2003 to 2015, focusing on individuals with incident CKD stage 4 who had an initial eGFR≥60 ml/min per 1.73 m(2) followed by two consecutive eGFRs

To evaluate the association between body mass index (BMI) and postoperative outcomes in elective paraesophageal hernia (PEH) repairs. A retrospective review of patients who underwent elective PEH repair in the ACS NSQIP database (2005–2015) was performed. Patients were stratified into BMI groups (

The optimal treatment for the monoclonal gammopathies of renal significance is not known, but there is consensus among experts that treatment should be specific for the underlying clone. The majority of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) do not have an identifiable clone, and prior studies have found poor renal outcomes for patients with PGNMID treated with a variety of regimens. Here we present a retrospective case series of 19 patients with PGNMID with a more uniform, clone-directed approach. A circulating paraprotein was detected in 37% of patients, and the overall clone detection rate was 32%. Treatment was directed at the underlying clone or, for patients without a detectable clone, empirically prescribed to target the hypothesized underlying clone. Of the 16 patients who underwent treatment, the overall renal response rate was 88%, and 38% of patients experienced complete renal response (proteinuria reduction to under 0.5 gm/24 hours) with initial treatment. All patients were End Stage Renal Disease-free at last follow-up (median 693 days after diagnosis), and treatment was well tolerated. Thus, a clone-directed approach may lead to novel, targeted treatment strategies that could significantly improve outcomes for patients with PGNMID.

Individuals with HIV infection are at elevated risk of developing end-stage renal disease. However, their outcomes after starting chronic dialysis in the contemporary era of widespread antiretroviral therapy are not well described. Using detailed data from a national dialysis provider, we determined HIV status by administrative codes and antiretroviral medication prescriptions, with hepatitis C virus (HCV) co-infection status provided by routinely measured serology. The survival on dialysis among 5348 individuals in the HIV + group and 1863 HIV + /HCV + individuals to a HIV - /HCV - reference cohort was compared. Race significantly modified the effect of HIV and HIV/HCV infection on mortality. In a multivariable model, HIV infection was not associated with an increased risk of death among Caucasians (hazard ratio 1.03, 95% confidence interval 0.91-1.16) but HIV/HCV co-infection (1.48, 1.18-1.87) was. In the same model for non-Caucasians, both HIV infection (1.44, 1.37-1.52) and HIV/HCV co-infection (1.71, 1.60-1.84) were significantly associated with higher mortality. A secondary analysis using propensity scores yielded similar results. Median follow-up for the reference group was 645 days (interquartile range 230-1323), 772 days (276-1623) for the HIV + group and 777 days (334-1665) for the co-infected group. Thus, in the contemporary era of widespread antiretroviral use, HIV infection remains associated with a significant reduction in dialysis survival for non-Caucasians while HIV/HCV co-infection is associated with impaired survival regardless of race or ethnicity. Hence, interventions to improve the care for these vulnerable populations are needed.

Given the rising prevalence of obstructive sleep apnea (OSA), we aimed to review the epidemiologic and pathophysiologic relationship of OSA, hypertension, and cardiovascular disease, and to summarize recent advances in the treatment of OSA. OSA is associated with an elevated risk of hypertension and cardiovascular disease. Several pathophysiologic factors contribute to the relationship between OSA and vascular risk, including neurohormonal dysregulation, endothelial dysfunction, and inflammation. While CPAP reduces blood pressure, it has not been demonstrated to reduce cardiovascular risk. The combination of CPAP and weight loss has a synergistic effect on blood pressure and several metabolic parameters. Adherence to CPAP is poor across studies, potentially contributing to the attenuation of perceived cardiovascular benefit from CPAP therapy. A greater emphasis on adherence to CPAP and the combination of CPAP and weight loss are central to reducing cardiovascular risk among individuals with OSA.

This systematic review and meta-analysis examines cardiovascular and mortality risks associated with untreated white coat hypertension and treated white coat effect.

Background and aims Outcomes with anticoagulation (AC) are understudied in advanced liver disease. We investigated effects of AC with warfarin and direct oral anticoagulants (DOACs) on all-cause mortality and hepatic decompensation as well as ischemic stroke, major adverse cardiovascular events, splanchnic vein thrombosis, and bleeding in a cohort with cirrhosis and atrial fibrillation (AF). Approach and results This was a retrospective, longitudinal study using national data of U.S. veterans with cirrhosis at 128 medical centers, including patients with cirrhosis with incident AF, from January 1, 2012 to December 31, 2017 followed through December 31, 2018. To assess the effects of AC on outcomes, we applied propensity score (PS) matching and marginal structural models (MSMs) to account for confounding by indication and time-dependent confounding. The final cohort included 2,694 veterans with cirrhosis with AF (n = 1,694 and n = 704 in the warfarin and DOAC cohorts after PS matching, respectively) with a median of 4.6 years of follow-up. All-cause mortality was lower with warfarin versus no AC (PS matched: hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.55-0.76; MSM models: HR, 0.54; 95% CI, 0.40-0.73) and DOACs versus no AC (PS matched: HR, 0.68; 95% CI, 0.50-0.93; MSM models: HR, 0.50; 95% CI, 0.31-0.81). In MSM models, warfarin (HR, 0.29; 95% CI, 0.09-0.90) and DOACs (HR, 0.23; 95% CI, 0.07-0.79) were associated with reduced ischemic stroke. In secondary analyses, bleeding was lower with DOACs compared to warfarin (HR, 0.49; 95% CI, 0.26-0.94). Conclusions Warfarin and DOACs were associated with reduced all-cause mortality. Warfarin was associated with more bleeding compared to no AC. DOACs had a lower incidence of bleeding compared to warfarin in exploratory analyses. Future studies should prospectively investigate these observed associations.