The Management of Elevated Blood Pressure in the Acute Care Setting: A Scientific Statement From the American Heart Association.

Over the past 3 decades, a substantial body of high-quality evidence has guided the diagnosis and management of elevated blood pressure (BP) in the outpatient setting. In contrast, there is a lack of comparable evidence for guiding the management of elevated BP in the acute care setting, resulting in significant practice variation. Throughout this scientific statement, we use the terms acute care and inpatient to refer to care received in the emergency department and after admission to the hospital. Elevated inpatient BP is common and can manifest either as asymptomatic or with signs of new or worsening target-organ damage, a condition referred to as hypertensive emergency. Hypertensive emergency involves acute target-organ damage and should be treated swiftly, usually with intravenous antihypertensive medications, in a closely monitored setting. However, the risk-benefit ratio of initiating or intensifying antihypertensive medications for asymptomatic elevated inpatient BP is less clear. Despite this ambiguity, clinicians prescribe oral or intravenous antihypertensive medications in approximately one-third of cases of asymptomatic elevated inpatient BP. Recent observational studies have suggested potential harms associated with treating asymptomatic elevated inpatient BP, which brings current practice into question. Despite the ubiquity of elevated inpatient BPs, few position papers, guidelines, or consensus statements have focused on improving BP management in the acute care setting. Therefore, this scientific statement aims to synthesize the available evidence, provide suggestions for best practice based on the available evidence, identify evidence-based gaps in managing elevated inpatient BP (asymptomatic and hypertensive emergency), and highlight areas requiring further research.

Revisiting Hypertension Treatment in Patients With Chronic Kidney Disease.

Despite being the world's top risk factor for death and disability, hypertension awareness and control within the chronic kidney disease (CKD) population have decreased. This is particularly important considering the heightened severity and management challenges of hypertension in CKD patients, whose outcomes are often worse compared with persons with normal kidney function. Therefore, finding novel therapeutics to improve blood pressure control within this vulnerable group is paramount. Although medications that target the renin-angiotensin-aldosterone system remain a mainstay for blood pressure control in most stages of CKD, we discuss novel approaches that may expand their use in advanced CKD. We also review newer tools for blood pressure management that have emerged in recent years, including aldosterone synthase inhibitors, endothelin receptor antagonists, and renal denervation. Overall, the future of hypertension management in CKD appears brighter, with a growing arsenal of tools and a deeper understanding of this complex disease.

Intradialytic Hypotension and Mortality in Adolescents and Young Adults With Kidney Failure Receiving Maintenance Hemodialysis.

Rationale & Objective: Intradialytic hypotension (IDH) is associated with mortality in adults with kidney failure requiring hemodialysis (HD); however, large-scale pediatric studies are lacking. Moreover, there is no evidence-based consensus definition of IDH in pediatric literature. We aimed to examine the association of commonly used definitions of IDH with mortality in adolescents and young adults. Study Design: This was a retrospective observational cohort study. Setting & Participants: In total, 1,199 adolescents and young adults (N = 320, aged 10-18 years and N = 879, aged 19-21 years) who initiated HD in a large dialysis organization were included. Exposures: This study used different definitions of IDH. Outcome: The study outcome was 2-year all-cause mortality. Analytical Approach: Several definitions of IDH were selected a priori based on a literature review. Patients were classified as having IDH if it was present in at least 30% of HD treatments during the first 90 days after dialysis initiation. Cox proportional hazards regression was used to test whether IDH associated with 2-year all-cause mortality. Results: Over a 2-year follow-up period, 54 (4.5%) patients died. Dependent on its definition, IDH was present in 2.9%-61.1% of patients. After the multivariable adjustment for sociodemographic and clinical characteristics, we found no association of IDH with mortality. Results were consistent across subgroups stratified by age (aged <18 and 19-21 years) and predialysis systolic blood pressure (<120, 120-150, and >150 mm Hg). We also examined IDH as occurring in <5%, 5%-29%, 30%-50%, and >50% of baseline treatments, and did not find a dose-response association with mortality (P > 0.05). Limitations: Owing to low event rates, our current sample size may have been too small to detect a difference in mortality. Conclusions: Our study found that IDH was not associated with mortality in adolescents and young adults.

Intradialytic hypotension (IDH), or hypotension experienced during dialysis, is common among children and young adults with kidney failure requiring hemodialysis. We examined the association of commonly used definitions of IDH with death in adolescents and young adults with kidney failure receiving hemodialysis. Intradialytic hypotension was present in 2.9%-61.1% of patients, depending on the definition, and over a 2-year follow-up period, 4.5% of the patients died. We found no association of IDH with mortality.

Design and Implementation of an Electronic Health Record-Integrated Hypertension Management Application.

BACKGROUND: High blood pressure affects approximately 116 million adults in the United States. It is the leading risk factor for death and disability across the world. Unfortunately, over the past decade, hypertension control rates have decreased across the United States. Prediction models and clinical studies have shown that reducing clinician inertia alone is sufficient to reach the target of ≥80% blood pressure control. Digital health tools containing evidence-based algorithms that are able to reduce clinician inertia are a good fit for turning the tide in blood pressure control, but careful consideration should be taken in the design process to integrate digital health interventions into the clinical workflow. METHODS: We describe the development of a provider-facing hypertension management platform. We enumerate key steps of the development process, including needs finding, clinical workflow analysis, treatment algorithm creation, platform design and electronic health record integration. We interviewed and surveyed 5 Stanford clinicians from primary care, cardiology, and their clinical care team members (including nurses, advanced practice providers, medical assistants) to identify needs and break down the steps of clinician workflow analysis. The application design and development stage were aided by a team of approximately 15 specialists in the fields of primary care, hypertension, bioinformatics, and software development. CONCLUSIONS: Digital monitoring holds immense potential for revolutionizing chronic disease management. Our team developed a hypertension management platform at an academic medical center to address some of the top barriers to adoption and achieving clinical outcomes. The frameworks and processes described in this article may be used for the development of a diverse range of digital health tools in the cardiovascular space.

Preoperative proteinuria is independently associated with mortality after fenestrated endovascular aneurysm repair.

OBJECTIVE: Fenestrated endovascular aneurysm repair (FEVAR) has become a mainstay in treating complex aortic aneurysms, though baseline patient factors predicting long-term outcomes remain poorly understood. Proteinuria is an early marker for chronic kidney disease and associated with adverse cardiovascular outcomes, but its utility in patients with aortic aneurysms is unknown. We aimed to determine whether preoperative proteinuria impacts long-term survival after FEVAR. METHODS: A single-institution, retrospective review of all elective FEVAR was performed. Preoperative proteinuria was assessed by urinalysis: negative (0-29 mg/dL), 1+ (30-100 mg/dL), 2+ (101-299 mg/dL), and 3+ (≥300 mg/dL). The cohort was stratified by patients with proteinuria (≥30 mg/dL) vs those without (<30 mg/dL). Baseline, perioperative, and long-term outcomes were compared. The primary outcome, all-cause mortality, was evaluated by Kaplan-Meier analysis and independent predictors with Cox proportional hazards modeling. RESULTS: Among 181 patients who underwent standard FEVAR from 2012 to 2022 (mean follow-up 33 months), any proteinuria was noted in 30 patients (16.6%). Patients with proteinuria were more likely to be Black (10.0% vs 1.3%) with a lower estimated glomerular filtration rate (eGFR) (52.7 ± 24.7 vs 67.7 ± 20.5 mL/min/1.73 m2), higher Society for Vascular Surgery comorbidity score (10.9 ± 4.3 vs 8.2 ± 4.7) and calcium channel blocker therapy (50.0% vs 29.1%), and larger maximal aneurysm diameter (67.2 ± 16.9 vs 59.8 ± 9.8 mm) (all P < .05). Thirty-day mortality was higher in the proteinuria group (10.0% vs 1.3%; P = .03). Overall survival at 1 and 5 years was significantly lower for those with proteinuria (71.5% vs 92.3% and 29.5% vs 68.1%; log-rank P < .001). On multivariable analysis, preoperative proteinuria was independently associated with over threefold higher hazard of mortality (hazard ratio [HR]: 3.21, 95% confidence interval [CI]: 1.66-6.20; P < .001), whereas preoperative eGFR was not predictive (HR: 0.99, 95% CI: 0.98-1.01; P = .28). Additional significant predictors included chronic obstructive pulmonary disease (HR: 2.04), older age (HR: 1.05), and larger maximal aneurysm diameter (HR: 1.03; all P < .05). CONCLUSIONS: In our 10-year experience with FEVAR, preoperative proteinuria was observed in 17% of patients and was significantly associated with worse survival. In this cohort, proteinuria was independently associated with all-cause mortality, whereas eGFR was not, suggesting that urinalysis may provide an additional simple metric for risk-stratifying patients before FEVAR.

Dialysis Modality, Transplant Characteristics, and Incident Atrial Fibrillation After Kidney Transplant: An Observational Study Using USRDS Data.

Rationale & Objective: Atrial fibrillation is the most common arrhythmia and is increasing in prevalence. The prevalence of atrial fibrillation is high among patients receiving dialysis, affecting ∼21.3% of the patients receiving hemodialysis and 15.5% of those receiving peritoneal dialysis. The association of previous dialysis modality with incident atrial fibrillation in patients after receiving their first kidney transplant has not been studied. Study Design: We used the United States Renal Data System to retrospectively identify adult, Medicare-insured patients who received their first kidney transplant between January 1, 2005, and September 30, 2012 and who had not previously been diagnosed with atrial fibrillation. Setting & Participants: The study included 43,621 patients who were aged 18 years older when receiving a first kidney transplant between January 1, 2005, and September 30, 2012 and whose primary payer was Medicare (parts A and B) at the time of transplantation and the 6 months preceding it. Exposure: Dialysis modality used before transplant. Outcome: Time to incidence of atrial fibrillation up to 3 years posttransplant. Analytical Approach: Multivariable Cox regression was used to estimate HRs. Results: Of 43,621 patients, 84.9% received hemodialysis and 15.1% received peritoneal dialysis before transplant. The mean ± SD age was 51 ± 13.6 years; 60.8% were male, 55.6% White, and 35.8% Black race. The mean dialysis vintage was 4.3 ± 2.8 years. Newly diagnosed atrial fibrillation after kidney transplant occurred in 286 patients (during 15,363 person-years) who had received peritoneal dialysis and in 2,315 patients (during 83,536 person-years) who had received hemodialysis. After multivariable adjustment, atrial fibrillation was 20% (95% CI, 4%-38%) more likely in those who had been receiving hemodialysis versus peritoneal dialysis, regardless of whether death was considered a competing risk or a censoring event. Each year of pretransplant dialysis vintage increased the risk of posttransplant atrial fibrillation by 6% (95% CI, 3%-9%). Limitations: Residual confounding; data from billing claims does not specify the duration of atrial fibrillation or whether it is valvular. Conclusions: Pretransplant hemodialysis, as compared with peritoneal dialysis, was associated with higher risk of newly diagnosed atrial fibrillation after a first kidney transplant. Plain-Language Summary: New-onset atrial fibrillation (AF) occurs in 7% of kidney transplant recipients in the first 3 years posttransplantation. We conducted this study to determine whether pretransplant dialysis modality was associated with posttransplant AF. We identified 43,621 patients; 84.9% used hemodialysis and 15.1% used peritoneal dialysis pretransplant. Multivariable Cox regression was used to estimate hazard ratios. We found that patients receiving hemodialysis pretransplant were at 20% increased risk of developing posttransplant AF as compared with patients receiving peritoneal dialysis. As our understanding of transplant-specific risk factors for AF increases, we may be able to better risk-stratify transplant patients and develop monitoring and management strategies that can improve outcomes.

Endovascular versus Surgical Lower Extremity Revascularization among Patients with Chronic Kidney Disease.

Introduction: Patients with chronic kidney disease (CKD) have a high prevalence of peripheral artery disease. How best to manage lower extremity peripheral artery disease remains unclear in this patient population. We therefore sought to compare the outcomes after endovascular versus surgical lower extremity revascularization among patients with CKD. Methods: We used data from Optum's de-identifed Clinformatics® Data Mart Database, a nationwide database of commercially insured persons in the United States to study patients with CKD who underwent lower extremity endovascular or surgical revascularization. We used inverse probability of treatment weighting to balance covariates. We employed proportional hazard regression to study the primary outcome of major adverse limb events (MALE), defined as a repeat revascularization or amputation. We also studied each of these events separately and death from any cause. Results: In our cohort, 60,057 patients underwent endovascular revascularization and 9,338 patients underwent surgical revascularization. Endovascular revascularization compared with surgical revascularization was associated with a higher adjusted hazard of MALE (hazard ratio (HR) 1.52; 95% confidence interval (CI) 1.46-1.59). Endovascular revascularization was also associated with a higher adjusted hazard of repeat revascularization (HR 1.65; 95% CI 1.57-1.72) but a lower adjusted risk of amputation (HR 0.71; CI 0.73-0.89). Patients undergoing endovascular revascularization also had a lower adjusted hazard for death from any cause (0.85; CI 0.82-0.88). Conclusions: In this analysis of patients with CKD undergoing lower extremity revascularization, an endovascular approach was associated with a higher rate of repeated revascularization but a lower risk of subsequent amputation and death compared with surgical revascularization. Multiple factors must be considered when counseling patients with CKD, who have a high burden of comorbid conditions. Clinical trials should include more patients with kidney disease, who are often otherwise excluded from participation, to better understand the most effective treatment strategies for this vulnerable patient population.

Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials.

Background Sodium glucose cotransporter-2 inhibitors reduce systolic blood pressure (SBP), but whether they affect SBP variability is unknown. There also remains uncertainty regarding the prognostic value of SBP variability for different clinical outcomes. Methods and Results Using individual participant data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, we assessed the effect of canagliflozin on SBP variability in people with type 2 diabetes across 4 study visits over 1.5 years as measured by standard deviation, coefficient of variation, and variability independent of the mean. We used multivariable Cox regression models to estimate associations of SBP variability with cardiovascular, kidney, and mortality outcomes. In 11 551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (-0.25 mm Hg [95% CI, -0.44 to -0.06]), but there was no effect on coefficient of variation (0.02% [95% CI, -0.12 to 0.16]) or variability independent of the mean (0.08 U [95% CI, -0.11 to 0.26]) when adjusting for correlation with mean SBP. Each 1 standard deviation increase in standard deviation of SBP variability was independently associated with higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19 [95% CI, 1.02-1.38]) and all-cause mortality (HR, 1.12 [95% CI, 1.01-1.25]), with consistent results observed for coefficient of variation and variability independent of the mean. Increases in SBP variability were not associated with kidney outcomes. Conclusions In people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease, higher visit-to-visit SBP variability is independently associated with risks of hospitalization for heart failure and all-cause mortality. Canagliflozin has little to no effect on SBP variability, independent of its established SBP-lowering effect. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01032629, NCT01989754, NCT02065791.

Associations of Serum and Dialysate Potassium Concentrations With Incident Atrial Fibrillation in a Cohort Study of Older US Persons Initiating Hemodialysis for Kidney Failure.

Introduction: Atrial fibrillation (AF) disproportionally affects persons on maintenance hemodialysis (HD). Associations of serum and dialysate potassium concentrations [K+] with AF incidence are poorly understood. Methods: We conducted a cohort study using Medicare claims merged with clinical data from a dialysis provider to determine whether serum-[K+] and/or dialysate-[K+] independently associated with AF incidence. Persons insured by fee-for-service Medicare aged ≥67 years at dialysis initiation and free from diagnosed AF prior to day 120 of dialysis were eligible. Serum-[K+] and dialysate-[K+] were assessed in 30-day intervals and patients were followed-up with for AF incidence in subsequent 30-day intervals. Results: During 2006 to 2011, 15,190 persons (mean age = 76.3 years) initiating HD had no prior AF diagnosis. Mean serum-[K+] was 4.5 mEq/l; dialysate-[K+] was 3 mEq/l in 34% and 2 mEq/l in 52% of patients. Followed-up over 21,907 person-years, 2869 persons had incident AF (incidence/100 person-years, 13.1 [95% confidence interval [CI], 12.6-13.6]). The multivariable-adjusted association of serum-[K+] with incident AF was J-shaped as follows: relative to a serum-[K+] of 4.5 mEq/l, lower serum-[K+] associated with increased AF risk, whereas confidence bands for higher serum-[K+] indicated no association. Dialysis against a dialysate-[K+] of 3 mEq/l versus 2 mEq/l independently associated with a 14% (95% CI, 5%-24%) lower incidence of AF. No effect modification between serum-[K+] and dialysate-[K+] was detected (P = 0.34). Conclusion: Lower serum-[K+] was independently associated with incident AF whereas elevated serum-[K+] was not. The findings support adoption of dialysate solutions with a dialysate-[K+] of 3 mEq/l, regardless of patients' serum-[K+], and elimination of lower dialysate-[K+] solutions from practice. Clinical trials randomizing patients to different dialysate-[K+] are warranted to establish causality.

Antihypertensive Medication Regimens Used in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Describing the antihypertensive medication regimens used in the SPRINT (Systolic Blood Pressure Intervention Trial) would contextualize the standard and intensive systolic blood pressure (SBP) interventions and may inform future implementation efforts to achieve population-wide intensive SBP goals. METHODS: We included SPRINT participants with complete medication data at the prerandomization and 12-month visits. Regimens were categorized by antihypertensive medication class. Analyses were stratified by treatment group (standard goal SBP <140 mm Hg versus intensive goal SBP <120 mm Hg). RESULTS: Among 7860 participants (83.7% of 9361 randomized), the median number of classes used at the prerandomization visit was 2.0 and 2.0 in the standard and intensive groups (P=0.559). At 12-months, the median number of classes used was 3.0 and 2.0 in the intensive and standard groups (P<0.001). Prerandomization, angiotensin-converting enzyme inhibitor (ACE), or angiotensin-II receptor blocker (ARB) monotherapy was the most common regimen in the intensive and standard groups (12.6% versus 12.2%). At 12-months, ACE/ARB monotherapy was still the most common regimen among standard group participants (14.7%) and was used by 5.3% of intensive group participants. Multidrug regimens used by the intensive and standard participants at 12 months were as follows: an ACE/ARB with thiazide (12.2% and 7.9%); an ACE/ARB with calcium channel blocker (6.2% and 6.8%); an ACE/ARB, thiazide, and calcium channel blocker (11.4% and 4.3%); and an ACE/ARB, thiazide, calcium channel blocker, and beta-blocker (6.5% and 1.2%). CONCLUSIONS: SPRINT investigators favored combining ACEs or ARBs, thiazide diuretics, and calcium channel blockers to target SBP <120 mm Hg, compared to ACE/ARB monotherapy to target SBP <140 mm Hg. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT01206062.

Association Between Preoperative Hemodialysis Timing and Postoperative Mortality in Patients With End-stage Kidney Disease.

Importance: For patients with end-stage kidney disease treated with hemodialysis, the optimal timing of hemodialysis prior to elective surgical procedures is unknown. Objective: To assess whether a longer interval between hemodialysis and subsequent surgery is associated with higher postoperative mortality in patients with end-stage kidney disease treated with hemodialysis. Design, Setting, and Participants: Retrospective cohort study of 1 147 846 procedures among 346 828 Medicare beneficiaries with end-stage kidney disease treated with hemodialysis who underwent surgical procedures between January 1, 2011, and September 30, 2018. Follow-up ended on December 31, 2018. Exposures: One-, two-, or three-day intervals between the most recent hemodialysis treatment and the surgical procedure. Hemodialysis on the day of the surgical procedure vs no hemodialysis on the day of the surgical procedure. Main Outcomes and Measures: The primary outcome was 90-day postoperative mortality. The relationship between the dialysis-to-procedure interval and the primary outcome was modeled using a Cox proportional hazards model. Results: Of the 1 147 846 surgical procedures among 346 828 patients (median age, 65 years [IQR, 56-73 years]; 495 126 procedures [43.1%] in female patients), 750 163 (65.4%) were performed when the last hemodialysis session occurred 1 day prior to surgery, 285 939 (24.9%) when the last hemodialysis session occurred 2 days prior to surgery, and 111 744 (9.7%) when the last hemodialysis session occurred 3 days prior to surgery. Hemodialysis was also performed on the day of surgery for 193 277 procedures (16.8%). Ninety-day postoperative mortality occurred after 34 944 procedures (3.0%). Longer intervals between the last hemodialysis session and surgery were significantly associated with higher risk of 90-day mortality in a dose-dependent manner (2 days vs 1 day: absolute risk, 4.7% vs 4.2%, absolute risk difference, 0.6% [95% CI, 0.4% to 0.8%], adjusted hazard ratio [HR], 1.14 [95% CI, 1.10 to 1.18]; 3 days vs 1 day: absolute risk, 5.2% vs 4.2%, absolute risk difference, 1.0% [95% CI, 0.8% to 1.2%], adjusted HR, 1.25 [95% CI, 1.19 to 1.31]; and 3 days vs 2 days: absolute risk, 5.2% vs 4.7%, absolute risk difference, 0.4% [95% CI, 0.2% to 0.6%], adjusted HR, 1.09 [95% CI, 1.04 to 1.13]). Undergoing hemodialysis on the same day as surgery was associated with a significantly lower hazard of mortality vs no same-day hemodialysis (absolute risk, 4.0% for same-day hemodialysis vs 4.5% for no same-day hemodialysis; absolute risk difference, -0.5% [95% CI, -0.7% to -0.3%]; adjusted HR, 0.88 [95% CI, 0.84-0.91]). In the analyses that evaluated the interaction between the hemodialysis-to-procedure interval and same-day hemodialysis, undergoing hemodialysis on the day of the procedure significantly attenuated the risk associated with a longer hemodialysis-to-procedure interval (P<.001 for interaction). Conclusions and Relevance: Among Medicare beneficiaries with end-stage kidney disease, longer intervals between hemodialysis and surgery were significantly associated with higher risk of postoperative mortality, mainly among those who did not receive hemodialysis on the day of surgery. However, the magnitude of the absolute risk differences was small, and the findings are susceptible to residual confounding.

Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist.

Overactivation of the renin-angiotensin-aldosterone system (RAAS) has been shown to be pathologic in heart failure and albuminuric chronic kidney disease (CKD), triggering pro-inflammatory and pro-fibrotic cellular pathways. The standard of care in these disease states includes treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. Mineralocorticoid receptor antagonists (MRAs) are also a mainstay in the treatment of heart failure with reduced ejection fraction; however, therapy is often limited by treatment-related hyperkalemia. In albuminuric CKD, the risk of hyperkalemia, acute kidney injury (AKI), and hypotension also remains significant. Finerenone is a novel non-steroidal MRA that may obviate some of these concerns and have therapeutic potential in additional patient populations. Finerenone was developed using the chemical structure of a dihydropyridine channel blocker but optimized to create a bulky MRA without any activity at the L-type calcium channel. It has several novel cellular mechanisms that may account for its ability to reduce cardiac hypertrophy and proteinuria more efficiently than an equinatriuretic dose of a steroidal MRA, while retaining anti-inflammatory and anti-fibrotic properties. Finerenone also has a lower rate of treatment-related hyperkalemia and AKI than steroidal MRAs with a smaller effect on systolic blood pressure, greatly expanding its therapeutic utility. The recently published FIGARO-DKD and FIDELIO-DKD trials demonstrate that treatment with finerenone in patients with type II diabetes and albuminuric CKD results in improved cardiovascular outcomes and a lower risk of CKD progression. Patients enrolled in these studies were already on maximally tolerated ACE inhibitor or angiotensin receptor blocker therapy. Trials investigating finerenone's therapeutic effect in patients with heart failure with preserved ejection fraction (HFpEF) and non-diabetic CKD, as well sodium-glucose cotransporter 2 (SGLT2) and finerenone combination therapy in patients with diabetic nephropathy, are ongoing.