Epicardial Adipose Tissue Thickness and Preserved Ejection Fraction Heart Failure.

PURPOSE OF THE REVIEW: Preserved ejection fraction heart failure and obesity frequently coexist. Whether obesity plays a consistent role in the pathogenesis of preserved ejection fraction heart failure is unclear. Accumulation of visceral adiposity underlies the pathogenic aftermaths of obesity. However, visceral adiposity imaging is assessed by computed tomography or magnetic resonance and thus not routinely available. In contrast, epicardial adiposity thickness is assessed by echocardiography and thus routinely available. We review the rationale for assessing epicardial adiposity thickness in patients with preserved ejection fraction heart failure and elevated body mass index. RECENT FINDINGS: Body mass index correlates poorly with visceral, and epicardial adiposity. Visceral and epicardial adiposity enlarges as preserved ejection fraction heart failure progresses. Epicardial adiposity may hasten the progression of coronary artery disease and impairs left ventricular sub-endocardial perfusion and diastolic function. Epicardial adiposity thickness may help monitor the therapeutic response in patients with preserved ejection failure heart failure and elevated body mass index.

Practice Facilitation and Peer Coaching for Uncontrolled Hypertension Among Black Individuals: A Randomized Clinical Trial.

Importance: Rural Black participants need effective intervention to achieve better blood pressure (BP) control. Objective: Among Black rural adults with persistently uncontrolled hypertension attending primary care clinics, to determine whether peer coaching (PC), practice facilitation (PF), or both (PCPF) are superior to enhanced usual care (EUC) in improving BP control. Design, Setting, and Participants: A cluster randomized clinical trial was conducted in 69 rural primary care practices across Alabama and North Carolina between September 23, 2016, and September 26, 2019. The participating practices were randomized to 4 groups: PC plus EUC, PF plus EUC, PCPF plus EUC, and EUC alone. The baseline EUC approach included a laptop for each participating practice with hyperlinks to participant education on hypertension, a binder of practice tips, a poster showing an algorithm for stepped care to improve BP, and 25 home BP monitors. The trial was stopped on February 28, 2021, after final data collection. The study included Black participants with persistently uncontrolled hypertension. Data were analyzed from February 28, 2021, to December 13, 2022. Interventions: Practice facilitators helped practices implement at least 4 quality improvement projects designed to improve BP control throughout 1 year. Peer coaches delivered a structured program via telephone on hypertension self-management throughout 1 year. Main Outcomes and Measures: The primary outcome was the proportion of participants in each trial group with BP values of less than 140/90 mm Hg at 6 months and 12 months. The secondary outcome was a change in the systolic BP of participants at 6 months and 12 months. Results: A total of 69 practices were randomized, and 1209 participants' data were included in the analysis. The mean (SD) age of participants was 58 (12) years, and 748 (62%) were women. In the intention-to-treat analyses, neither intervention alone nor in combination improved BP control or BP levels more than EUC (at 12 months, PF vs EUC odds ratio [OR], 0.94 [95% CI, 0.58-1.52]; PC vs EUC OR, 1.30 [95% CI, 0.83-2.04]; PCPF vs EUC OR, 1.02 [95% CI, 0.64-1.64]). In preplanned subgroup analyses, participants younger than 60 years in the PC and PCPF groups experienced a significant 5 mm Hg greater reduction in systolic BP than participants younger than 60 years in the EUC group at 12 months. Practicewide BP control estimates in PF groups suggested that BP control improved from 54% to 61%, a finding that was not observed in the trial's participants. Conclusions and Relevance: The results of this cluster randomized clinical trial demonstrated that neither PC nor PF demonstrated a superior improvement in overall BP control compared with EUC. However, PC led to a significant reduction in systolic BP among younger adults. Trial Registration: ClinicalTrials.gov Identifier: NCT02866669.

Rationale for a New Low-Dose Triple Single Pill Combination for the Treatment of Hypertension.

Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these 'hypertension polypills' were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.

What Is the Current Best Drug Treatment for Hypertensive Heart Failure With Preserved Ejection Fraction? Review of the Totality of Evidence.

BACKGROUND: More than 90% of patients developing heart failure (HF) have an epidemiological background of hypertension. The most frequent concomitant conditions are type 2 diabetes mellitus, obesity, atrial fibrillation, and coronary disease, all disorders/diseases closely related to hypertension. METHODS: HF outcome research focuses on decreasing mortality and preventing hospitalization for worsening HF syndrome. All drugs that decrease these HF endpoints lower blood pressure. Current drug treatments for HF are (i) angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor neprilysin inhibitors, (ii) selected beta-blockers, (iii) steroidal and nonsteroidal mineralocorticoid receptor antagonists, and (iv) sodium-glucose cotransporter 2 inhibitors. RESULTS: For various reasons, these drug treatments were first studied in HF patients with a reduced ejection fraction (HFrEF). However, subsequently, they have been investigated and, as we see it, documented as beneficial in HF patients with a preserved left ventricular ejection fraction (LVEF, HFpEF) and mostly hypertensive etiology, with effect estimates assessed partly on top of background treatment with the drugs already proven effective in HFrEF. Additionally, diuretics are given on symptomatic indications. CONCLUSIONS: Considering the totality of evidence and the overall need for antihypertensive treatment and/or treatment of hypertensive complications in almost all HF patients, the principal drug treatment of HF appears to be the same regardless of LVEF. Rather than LVEF-guided treatment of HF, treatment of HF should be directed by symptoms (related to the level of fluid retention), signs (tachycardia), severity (NYHA functional class), and concomitant diseases and conditions. All HF patients should be given all the drug classes mentioned above if well tolerated.

The current best drug treatment for hypertensive heart failure with preserved ejection fraction.

More than 90 % of patients developing heart failure (HF) have hypertension. The most frequent concomitant conditions are type-2 diabetes mellitus, obesity, atrial fibrillation, and coronary disease. HF outcome research focuses on decreasing mortality and preventing hospitalization for worsening HF syndrome. All drugs that decrease these HF endpoints lower blood pressure. Current drug treatments for HF are (i) angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, (ii) selected beta-blockers, (iii) steroidal and non-steroidal mineralocorticoid receptor antagonists, and (iv) sodium-glucose cotransporter 2 inhibitors. For various reasons, these drug treatments were first studied in HF patients with a reduced ejection fraction (HFrEF). Subsequently, they have been investigated in HF patients with a preserved left ventricular ejection fraction (LVEF, HFpEF) of mostly hypertensive etiology, and with modest benefits largely assessed on top of background treatment with the drugs already proven effective in HFrEF. Additionally, diuretics are given on symptomatic indications. Patients with HFpEF may have diastolic dysfunction but also systolic dysfunction visualized by lack of longitudinal shortening. Considering the totality of evidence and the overall need for antihypertensive treatment and/or treatment of hypertensive complications in almost all HF patients, the principal drug treatment of HF appears to be the same regardless of LVEF. Rather than LVEF-guided treatment of HF, treatment of HF should be directed by symptoms (related to the level of fluid retention), signs (tachycardia), severity (NYHA functional class), and concomitant diseases and conditions. All HF patients should be given all the drug classes mentioned above if well tolerated.

Spironolactone improves left atrial function and atrioventricular coupling in patients with resistant hypertension.

To determine the blood pressure independent effects of spironolactone on left atrial (LA) size and function in patients with resistant hypertension (RHTN). Patients with RHTN (n = 36, mean age 55 ± 7) were prospectively recruited. Spironolactone was initiated at 25 mg/day and increased to 50 mg/day after 4 weeks. Other antihypertensives were withdrawn to maintain constant blood pressure. Cardiac magnetic resonance imaging was performed at baseline and after 6 months of spironolactone treatment and changes in LA functional metrics were assessed. LA size and function parameters were improved (p < 0.05) from baseline to month-6: LA volumes indexed to body surface area (LAVI) were reduced (LAVImaximum 41.4 ± 12 vs. 33.2±9.7 mL/m2; LAVIpre-A 32.6 ± 9.8 vs. 25.6 ± 8.1 mL/m2; median LAVIminimum 18.5 [13.9-24.8] vs. 14.1 [10.9-19.2] mL/m2); left atrioventricular coupling index was reduced (28.2 ± 11.5 vs. 22.7 ± 9.2%); LA emptying fractions (LAEF) were increased (median total LAEF 52.4 [48.7-60.3] vs. 55.9 [50.3-61.1] %; active LAEF 40.2 ± 8.6 vs. 43.1 ± 7.8%). LA global longitudinal strain in the active phase was increased (16.3 ± 4.1 vs. 17.8 ± 4.2%). The effect of spironolactone was similar in patients with high (N = 18) and normal (N = 18) aldosterone status (defined by plasma renin activity and 24-h urine aldosterone). Treatment of RHTN with spironolactone is associated with improvements in LA size and function, and atrioventricular coupling, regardless of whether aldosterone levels were normal or high at baseline. This study suggests the need for larger prospective studies examining effects of mineralocorticoid receptor antagonists on atrial function and atrioventricular coupling.

Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT.

BACKGROUND: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values. METHODS: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively. RESULTS: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70). CONCLUSIONS: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase.

Perinatal Outcomes Associated With Management of Stage 1 Hypertension.

OBJECTIVE: To evaluate the association between maternal blood pressure (BP) below 130/80 mm Hg compared with 130-139/80-89 mm Hg and pregnancy outcomes. METHODS: We conducted a planned secondary analysis of CHAP (Chronic Hypertension and Pregnancy), an open label, multicenter, randomized controlled trial. Participants with mean BP below 140/90 mm Hg were grouped as below 130/80 mm Hg compared with 130-139/80-89 mm Hg by averaging postrandomization clinic BP throughout pregnancy. The primary composite outcome was preeclampsia with severe features, indicated preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The secondary outcome was small for gestational age (SGA). RESULTS: Of 2,408 patients in CHAP, 2,096 met study criteria; 1,328 had mean BP 130-139/80-89 mm Hg and 768 had mean BP below 130/80 mm Hg. Participants with mean BP below 130/80 mm Hg were more likely to be older, on antihypertensive medication, in the active treatment arm, and to have lower BP at enrollment. Mean clinic BP below 130/80 mm Hg was associated with lower frequency of the primary outcome (16.0% vs 35.8%, adjusted relative risk 0.45; 95% CI 0.38-0.54) as well as lower risk of severe preeclampsia and indicated birth before 35 weeks of gestation. There was no association with SGA. CONCLUSION: In pregnant patients with mild chronic hypertension, mean BP below 130/80 mm Hg was associated with improved pregnancy outcomes without increased risk of SGA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Breastfeeding initiation and duration among people with mild chronic hypertension: a secondary analysis of the Chronic Hypertension and Pregnancy trial.

BACKGROUND: Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown. OBJECTIVE: This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg). STUDY DESIGN: We performed a secondary analysis of the Chronic Hypertension and Pregnancy trial. This was an open-label, multicenter, randomized trial where pregnant participants with mild chronic hypertension were randomized to receive antihypertensive medications with goal blood pressure <140/90 mm Hg (active treatment) or deferred treatment until blood pressure ≥160/105 mm Hg (control). The primary outcome was initiation and duration of breastfeeding, assessed at the postpartum clinic visit. We performed bivariate analyses and log-binomial and cumulative logit regression models, adjusting models for variables that were unbalanced in bivariate analyses. We performed additional analyses to explore the relationship between breastfeeding duration and blood pressure measurements at the postpartum visit. RESULTS: Of the 2408 participants from the Chronic Hypertension and Pregnancy trial, 1444 (60%) attended the postpartum study visit and provided breastfeeding information. Participants in the active treatment group had different body mass index class distribution and earlier gestational age at enrollment, and (by design) were more often discharged on antihypertensives. Breastfeeding outcomes did not differ significantly by treatment group. In the active and control treatment groups, 563 (77.5%) and 561 (78.1%) initiated breastfeeding, and mean durations of breastfeeding were 6.5±2.3 and 6.3±2.1 weeks, respectively. The probability of ever breastfeeding (adjusted relative risk, 0.99; 95% confidence interval, 0.93-1.05), current breastfeeding at postpartum visit (adjusted relative risk, 1.01; 95% confidence interval, 0.94-1.10), and weeks of breastfeeding (adjusted odds ratio, 0.87; 95% confidence interval, 0.68-1.12) did not differ by treatment group. Increased duration (≥2 vs <2 weeks) of breastfeeding was associated with slightly lower blood pressure measurements at the postpartum visit, but these differences were not significant in adjusted models. CONCLUSION: In a secondary analysis of the cohort of Chronic Hypertension and Pregnancy trial participants who attended the postpartum study visit and provided breastfeeding information (60% of original trial participants), breastfeeding outcomes did not differ significantly by treatment group. This suggests that maintaining goal blood pressure <140/90 mm Hg throughout the perinatal period is associated with neither harm nor benefit for short-term breastfeeding goals. Further study is needed to understand long-term breastfeeding outcomes among individuals with chronic hypertension and how to support this population in achieving their breastfeeding goals.

Sympathetic Neural Mechanisms in Hypertension: Recent Insights.

PURPOSE OF REVIEW: To examine published and unpublished data documenting the role of sympathetic neural factors in the pathogenesis of different hypertensive phenotypes. These phenotypes relate to attended or unattended blood pressure measurements, to nighttime blood pressure profile alterations, and to resistant, pseudoresistant, and refractory hypertension. Results of original clinical studies as well as of recent meta-analyses based on the behavior of different sympathetic biomarkers in various hypertensive forms will be also discussed. RECENT FINDINGS: Studies performed in the past decade have shown that office blood pressure measurements, including in recent years those characterizing unattended or attended blood pressure assessment, are associated with profound changes in the behavior of different sympathetic biomarkers. This is the case for the clinical hypertensive phenotypes characterized by alterations in the nocturnal blood pressure profile and by sleep duration abnormalities. This is also the case for the clinical conditions defined as resistant, refractory, and pseudoresistant hypertension. Data reviewed in the present paper highlight the relevance of sympathetic neural factors in the development and progression of different clinical hypertensive phenotypes. This suggests that a common hallmark of the majority of the essential hypertensive states detectable in current clinical practice is represented by the alteration in the sympathetic blood pressure control.

Disparities in Postdischarge Ambulatory Care Follow-Up Among Medicaid Beneficiaries With Diabetes, Hospitalized for Heart Failure.

Background Ambulatory follow-up for all patients with heart failure (HF) is recommended within 7 to 14 days after hospital discharge to improve HF outcomes. We examined postdischarge ambulatory follow-up of patients with comorbid diabetes and HF from a low-income population in primary and specialty care. Methods and Results Adults with diabetes and first hospitalizations for HF, covered by Alabama Medicaid in 2010 to 2019, were included and the claims analyzed for ambulatory care use (any, primary care, cardiology, or endocrinology) within 60 days after discharge using restricted mean survival time regression and negative binomial regression. Among 9859 Medicaid-covered adults with diabetes and first hospitalization for HF (mean age, 53.7 years; SD, 9.2 years; 47.3% Black; 41.8% non-Hispanic White; 10.9% Hispanic/Other [Other included non-White Hispanic, American Indian, Pacific Islander and Asian adults]; 65.4% women, 34.6% men), 26.7% had an ambulatory visit within 0 to 7 days, 15.2% within 8 to 14 days, 31.3% within 15 to 60 days, and 26.8% had no visit; 71% saw a primary care physician and 12% a cardiology physician. Black and Hispanic/Other adults were less likely to have any postdischarge ambulatory visit (P<0.0001) or the visit was delayed (by 1.8 days, P=0.0006 and by 2.8 days, P=0.0016, respectively) and were less likely to see a primary care physician than non-Hispanic White adults (adjusted incidence rate ratio, 0.96 [95% CI, 0.91-1.00] and 0.91 [95% CI, 0.89-0.98]; respectively). Conclusions More than half of Medicaid-covered adults with diabetes and HF in Alabama did not receive guideline-concordant postdischarge care. Black and Hispanic/Other adults were less likely to receive recommended postdischarge care for comorbid diabetes and HF.

Association of cancer with the risk of developing hypertension.

BACKGROUND AND AIMS: Although the importance of hypertension in patients with cancer is widely recognized, little is known about the risk of developing hypertension in patients with a history of cancer. METHODS: This retrospective observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2022, including 78,162 patients with a history of cancer and 3,692,654 individuals without cancer. The primary endpoint was the incidence of hypertension. RESULTS: During a mean follow-up period of 1,208 ± 966 days, 311,197 participants developed hypertension. The incidence of hypertension was 364.6 (95% CI 357.0-372.2) per 10000 person-years among those with a history of cancer, and 247.2 (95% CI 246.3-248.1) per 10000 person-years in those without cancer. Individuals with a history of cancer had an elevated risk of developing hypertension according to multivariable Cox regression analyses (HR 1.17, 95% CI 1.15-1.20). Both cancer patients requiring active antineoplastic therapy (HR 2.01, 95% CI 1.85-2.20), and those who did not require active antineoplastic therapy (HR 1.14, 95% CI 1.12-1.17) had an increased risk of hypertension. A multitude of sensitivity analyses confirmed the robustness of the relationship between cancer and incident hypertension. Patients with certain types of cancer were found to have a higher risk of developing hypertension than those without cancer, with varying risks dependent on the type of cancer. CONCLUSIONS: Our analysis of a nationwide epidemiological database revealed that individuals with a history of cancer have a higher risk of developing hypertension, and that this finding applies to both cancer patients who require active antineoplastic therapy and those who do not.

Social Determinants of Health and Uncontrolled Blood Pressure in a National Cohort of Black and White US Adults: the REGARDS Study.

BACKGROUND: Determining the contribution of social determinants of health (SDOH) to the higher proportion of Black adults with uncontrolled blood pressure (BP) could inform interventions to improve BP control and reduce cardiovascular disease. METHODS: We analyzed data from 7306 White and 7497 Black US adults taking antihypertensive medication from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study (2003-2007). SDOH were defined using the Healthy People 2030 domains of education, economic stability, social context, neighborhood environment, and health care access. Uncontrolled BP was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg. RESULTS: Among participants taking antihypertensive medication, 25.4% of White and 33.7% of Black participants had uncontrolled BP. The SDOH included in the current analysis mediated the Black-White difference in uncontrolled BP by 33.0% (95% CI, 22.1%-46.8%). SDOH that contributed to excess uncontrolled BP among Black compared with White adults included low annual household income (percent-mediated 15.8% [95% CI, 10.8%-22.8%]), low education (10.5% [5.6%-15.4%]), living in a health professional shortage area (10.4% [6.5%-14.7%]), disadvantaged neighborhood (11.0% [4.4%-18.0%]), and high-poverty zip code (9.7% [3.8%-15.5%]). Together, the neighborhood-domain accounted for 14.1% (95% CI, 5.9%-22.9%), the health care domain accounted for 12.7% (95% CI, 8.4%-17.3%), and the social-context-domain accounted for 3.8% (95% CI, 1.2%-6.6%) of the excess likelihood of uncontrolled BP among Black compared with White adults, respectively. CONCLUSIONS: SDOH including low education, low income, living in a health professional shortage area, disadvantaged neighborhood, and high-poverty zip code contributed to the excess likelihood of uncontrolled BP among Black compared with White adults.

The design and rationale of a multicenter real-world trial: The Southeastern Collaboration to Improve Blood Pressure Control in the US Black Belt - Addressing the Triple Threat.

BACKGROUND: Impoverished African Americans (AA) with hypertension face poor health outcomes. PURPOSE: To conduct a cluster-randomized trial testing two interventions, alone and in combination, to improve blood pressure (BP) control in AA with persistently uncontrolled hypertension. METHODS: We engaged primary care practices serving rural Alabama and North Carolina residents, and in each practice we recruited approximately 25 AA adults with persistently uncontrolled hypertension (mean systolic BP >140 mmHg over the year prior to enrollment plus enrollment day BP assessed by research assistants ≥140/90 mmHg). Practices were randomized to peer coaching (PC), practice facilitation (PF), both PC and PF (PC + PF), or enhanced usual care (EUC). Coaches met with participants from PC and PC + PF practices weekly for 8 weeks then monthly over one year, discussing lifestyle changes, medication adherence, home monitoring, and communication with the healthcare team. Facilitators met with PF and PC + PF practices monthly to implement ≥1 quality improvement intervention in each of four domains. Data were collected at 0, 6, and 12 months. RESULTS: We recruited 69 practices and 1596 participants; 18 practices (408 participants) were randomized to EUC, 16 (384 participants) to PF, 19 (424 participants) to PC, and 16 (380 participants) to PC + PF. Participants had mean age 57 years, 61% were women, and 56% reported annual income <$20,000. LIMITATIONS: The PF intervention acts at the practice level, possibly missing intervention effects in trial participants. Neither PC nor PF currently has established clinical reimbursement mechanisms. CONCLUSIONS: This trial will fill evidence gaps regarding practice-level vs. patient-level interventions for rural impoverished AA with uncontrolled hypertension.

Adverse cardiac remodeling is absent in patients with true controlled resistant hypertension.

Resistant hypertension (RHTN), defined as blood pressure (BP) that is uncontrolled with ≥3 medications, including a long-acting thiazide diuretic, also includes a subset with BP that is controlled with ≥4 medications, so-called controlled RHTN. This resistance is attributed to intravascular volume excess. Patients with RHTN overall have a higher prevalence of left ventricular hypertrophy (LVH) and diastolic dysfunction compared to patients with non-RHTN. We tested the hypothesis that patients with controlled RHTN due to the intravascular volume excess have higher left ventricular mass index (LVMI), higher prevalence of LVH, larger intracardiac volumes, and more diastolic dysfunction compared to patients with controlled non-resistant hypertension (CHTN), defined as BP controlled with ≤3 anti-hypertensive medications. Patients with controlled RHTN (n = 69) or CHTN (n = 63) who were treated at the University of Alabama at Birmingham were offered enrollment and underwent cardiac magnetic resonance imaging. Diastolic function was assessed by peak filling rate, time needed in diastole to recover 80% of stroke volume, E:A ratios and left atrial volume. LVMI was higher in patients with controlled RHTN (64.4 ± 22.5 vs 56.9 ± 11.5; P = .017). Intracardiac volumes were similar in both groups. Diastolic function parameters were not significantly different between groups. There were no significant differences in age, gender, race, body mass index, dyslipidemia between the two groups. The findings show that patients with controlled RHTN have higher LVMI, but comparable diastolic function to those of patients with CHTN.

Endothelial cells overexpressing CXCR1/2 are renoprotective in rats with acute kidney injury.

Inflammation that develops with the release of chemokines and cytokines during acute kidney injury (AKI) has been shown to participate in functional renal recovery. Although a major research focus has been on the role of macrophages, the family of C-X-C motif chemokines that promote neutrophil adherence and activation also increases with kidney ischemia-reperfusion (I/R) injury. This study tested the hypothesis that intravenous delivery of endothelial cells (ECs) that overexpress (C-X-C motif) chemokine receptors 1 and 2 (CXCR1 and CXCR2, respectively) improves outcomes in kidney I/R injury. Overexpression of CXCR1/2 enhanced homing of endothelial cells to I/R-injured kidneys and limited interstitial fibrosis, capillary rarefaction, and tissue injury biomarkers (serum creatinine concentration and urinary kidney injury molecule-1) following AKI and also reduced expression of P-selectin and the rodent (C-X-C motif) chemokine cytokine-induced neutrophil chemoattractant (CINC)-2ß as well as the number of myeloperoxidase-positive cells in the postischemic kidney. The serum chemokine/cytokine profile, including CINC-1, showed similar reductions. These findings were not observed in rats given endothelial cells transduced with an empty adenoviral vector (null-ECs) or a vehicle alone. These data indicate that extrarenal endothelial cells that overexpress CXCR1 and CXCR2, but not null-ECs or vehicle alone, reduce I/R kidney injury and preserve kidney function in a rat model of AKI.NEW & NOTEWORTHY Inflammation facilitates kidney ischemia-reperfusion (I/R) injury. Endothelial cells (ECs) that were modified to overexpress (C-X-C motif) chemokine receptor (CXCR)1/2 (CXCR1/2-ECs) were injected immediately following kidney I/R injury. The interaction of CXCR1/2-ECs, but not ECs transduced with an empty adenoviral vector, with injured kidney tissue preserved kidney function and reduced production of inflammatory markers, capillary rarefaction, and interstitial fibrosis. The study highlights a functional role for the C-X-C chemokine pathway in kidney damage following I/R injury.

Validation of a Remote Monitoring Blood Pressure Device in Pregnancy.

BACKGROUND: The Ideal Life Blood Pressure Manager measures blood pressure (BP) and automatically transmits results to the patient's medical record independent of internet access, but has not been validated. Our objective was to conduct a validation study of the Ideal Life BP Manager in pregnant women using a validation protocol. METHODS: Pregnant participants were enrolled into three subgroups per the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization protocol: normotensive (systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90), hypertensive without proteinuria (SBP ≥ 140 or DBP ≥ 90), and preeclampsia (SBP ≥ 140 or DBP ≥ 90 with proteinuria). Two trained research staff used a mercury sphygmomanometer to validate the device, alternating sphygmomanometer, and device readings for a total of 9 measurements. RESULTS: Among 51 participants, the mean SBP and DBP differences and standard deviations between the device and the mean staff measurements for all participants were 1.7 ± 7.1 and 1.5 ± 7.0 mm Hg, respectively. The standard deviations of the individual participant's paired device and mean staff SBP and DBP measurements were 6.0 and 6.4 mm Hg, respectively. The device was more likely to overestimate rather than underestimate BP (SBP: mean difference = 1.67, 95% CI [-12.15 to 15.49]; DBP: mean difference = 1.51, 95% CI [-12.26 to 15.28]). Most paired readings had a difference of less than 10 mm Hg across averaged paired readings. CONCLUSION: The Ideal Life BP Manager met internationally recognized validity criteria in this sample of pregnant women.

Outcomes of shared institutional review board compared with multiple individual site institutional review board models in a multisite clinical trial.

BACKGROUND: Institutional review boards play a crucial role in initiating clinical trials. Although many multicenter clinical trials use an individual institutional review board model, where each institution uses their local institutional review board, it is unknown if a shared (single institutional review board) model would reduce the time required to approve a standard institutional review board protocol. OBJECTIVE: This study aimed to compare processing times and other processing characteristics between sites using a single institutional review board model and those using their individual site institutional review board model in a multicenter clinical trial. STUDY DESIGN: This was a retrospective study of sites in an open-label, multicenter randomized control trial from 2014 to 2021. Participating sites in the multicenter Chronic Hypertension and Pregnancy trial were asked to complete a survey collecting data describing their institutional review board approval process. RESULTS: A total of 45 sites participated in the survey (7 used a shared institutional review board model and 38 used their individual institutional review board model). Most sites (86%) using the shared institutional review board model did not require a full-board institutional review board meeting before protocol approval, compared with 1 site (3%) using the individual institutional review board model (P<.001). Median total approval times (41 vs 56 days; P=.42), numbers of submission rounds (1 vs 2; P=.09), and numbers of institutional review board stipulations (1 vs 4; P=.12) were lower for the group using the shared institutional review board model than those using the individual site institutional review board model; however, these differences were not statistically significant. CONCLUSION: The findings supported the hypothesis that the shared institutional review board model for multicenter studies may be more efficient in terms of cumulative time and effort required to obtain approval of an institutional review board protocol than the individual institutional review board model. Given that these data have important implications for multicenter clinical trials, future research should evaluate these findings using larger or multiple multicenter trials.

The association of BP with cardiovascular outcomes in patients with dipstick proteinuria and preserved kidney function.

Little is known about the relationship between blood pressure (BP) and incident cardiovascular disease (CVD) in people with proteinuria and a preserved estimated glomerular filtration rate (eGFR). This study sought to investigate the association of BP with CVD risk in adults with proteinuria and preserved eGFR. We studied 188,837 individuals with proteinuria and preserved eGFR ≥60 mL/min/1.73 m2. We categorized individuals who were not taking BP-lowering medications into four groups based on the 2017 American College of Cardiology/American Heart Association BP guideline and categorized those who were taking BP-lowering medications using the same BP ranges. The primary outcome was a composite CVD endpoint that included myocardial infarction, angina pectoris, stroke, and heart failure. Over a mean follow-up of 1,050 days, 7,039 CVD events were identified. Compared with normal BP, stage 1 hypertension (hazard ratio [HR]: 1.30, 95% confidence interval [95% CI]: 1.21-1.40) and stage 2 hypertension (HR: 2.17, 95% CI: 2.01-2.34) were associated with an increased risk for CVD events among medication-naïve individuals. Only stage 2 hypertension range (HR: 1.19, 95% CI: 1.02-1.38) was associated with an increased CVD event risk among people taking BP-lowering medications. Restricted cubic spline analysis showed that the risk of CVD events increased monotonically with BP at an SBP/DBP > 120/80 mmHg among medication-naïve individuals, but risk increased only at an SBP/DBP > 140/90 mmHg among individuals taking BP-lowering medications. In conclusion, among people with proteinuria and preserved eGFR, stage 1 and stage 2 hypertension were associated with a greater risk of CVD among medication-naïve individuals, whereas only stage 2 hypertension was associated with an increased CVD risk among those taking BP-lowering medications.