Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses.

The SARS-CoV-2 pandemic has resulted in millions of infections, yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By investigating 17 acute and 24 convalescent patients, we found that acute SARS-CoV-2 infection resulted in broad immune cell reduction including T, natural killer, monocyte, and dendritic cells (DCs). DCs were significantly reduced with functional impairment, and ratios of conventional DCs to plasmacytoid DCs were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks after symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 T cells than CD8 T cells. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, could contribute to acute COVID-19 pathogenesis and have implications for vaccine development.

Hypertension Related Co-Morbidities and Complications in Women of Sub-Saharan Africa: A Brief Review.

Hypertension is the leading cause of cardiovascular disease in women, and sub-Saharan African (SSA) countries have some of the highest rates of hypertension in the world. Expanding knowledge of causes, management, and awareness of hypertension and its co-morbidities worldwide is an effective strategy to mitigate its harms, decrease morbidities and mortality, and improve individual quality of life. Hypertensive disorders of pregnancy (HDPs) are a particularly important subset of hypertension, as pregnancy is a major stress test of the cardiovascular system and can be the first instance in which cardiovascular disease is clinically apparent. In SSA, women experience a higher incidence of HDP compared with other African regions. However, the region has yet to adopt treatment and preventative strategies for HDP. This delay stems from insufficient awareness, lack of clinical screening for hypertension, and lack of prevention programs. In this brief literature review, we will address the long-term consequences of hypertension and HDP in women. We evaluate the effects of uncontrolled hypertension in SSA by including research on heart disease, stroke, kidney disease, peripheral arterial disease, and HDP. Limitations exist in the number of studies from SSA; therefore, we will use data from countries across the globe, comparing and contrasting approaches in similar and dissimilar populations. Our review highlights an urgent need to prioritize public health, clinical, and bench research to discover cost-effective preventative and treatment strategies that will improve the lives of women living with hypertension in SSA.

Equitable Care for Hypertension: Blood Pressure and Patient-Reported Outcomes of the RICH LIFE Cluster Randomized Trial.

BACKGROUND: Disparities in hypertension control are well documented but underaddressed. METHODS: RICH LIFE (Reducing Inequities in Care of Hypertension: Lifestyle Improvement for Everyone) was a 2-arm, cluster randomized trial comparing the effect on blood pressure (BP) control (systolic BP ≤140 mm Hg, diastolic BP ≤90 mm Hg), patient activation, and disparities in BP control of 2 multilevel interventions, standard of care plus (SCP) and collaborative care/stepped care (CC/SC). SCP included BP measurement standardization, audit and feedback, and equity-leadership training. CC/SC added roles to address social or medical needs. Primary outcomes were BP control and patient activation at 12 months. Generalized estimating equations and mixed-effects regression models with fixed effects of time, intervention, and their interaction compared change in outcomes at 12 months from baseline. RESULTS: A total of 1820 adults with uncontrolled BP and ≥1 other risk factors enrolled in the study. Their mean age was 60.3 years, and baseline BP was 152.3/85.5 mm Hg; 59.4% were women; 57.4% were Black, 33.2% were White, and 9.4% were Hispanic; 74% had hyperlipidemia; and 45.1% had type 2 diabetes. CC/SC did not improve BP control rates more than SCP. Both groups achieved statistically and clinically significant BP control rates at 12 months (CC/SC: 57.3% [95% CI, 52.7%-62.0%]; SCP: 56.7% [95% CI, 51.9%-61.5%]). Pairwise comparisons between racial and ethnic groups showed overall no significant differences in BP control at 12 months. Patients with coronary heart disease showed greater achievement of BP control in CC/SC than in SCP (64.0% [95% CI, 54.1%-73.9%] versus 50.8% [95% CI, 42.6%-59.0%]; P=0.04), as did patients in rural areas (67.3% [95% CI, 49.8%-84.8%] versus 47.8% [95% CI, 32.4%-63.2%]; P=0.01). Individuals in both arms experienced statistically and clinically significant reductions in mean systolic BP (CC/SC: -13.8 mm Hg [95% CI, -15.2 to -12.5]; SCP: -14.6 mm Hg [95% CI, -15.9 to -13.2]) and diastolic BP (CC/SC: -6.9 mm Hg [95% CI, -7.8 to -6.1]; SCP: -5.5 mm Hg [95% CI, -6.4 to -4.6]) over time. The difference in diastolic BP reduction between CC/SC and SCP over time was statistically significant (-1.4 mm Hg [95% CI, -2.6 to -0.2). Patient activation did not differ between arms. CC/SC showed greater improvements in patient ratings of chronic illness care (Patient Assessment of Chronic Illness Care score) over 12 months (0.12 [95% CI, 0.02-0.22]). CONCLUSIONS: Adding a collaborative care team to enhanced standard of care did not improve BP control but did improve patient ratings of chronic illness care.

Using Genetics to Inform Interventions Related to Sodium and Potassium in Hypertension.

BACKGROUND: Hypertension is a key risk factor for major adverse cardiovascular events but remains difficult to treat in many individuals. Dietary interventions are an effective approach to lower blood pressure (BP) but are not equally effective across all individuals. BP is heritable, and genetics may be a useful tool to overcome treatment response heterogeneity. We investigated whether the genetics of BP could be used to identify individuals with hypertension who may receive a particular benefit from lowering sodium intake and boosting potassium levels. METHODS: In this observational genetic study, we leveraged cross-sectional data from up to 296 475 genotyped individuals drawn from the UK Biobank cohort for whom BP and urinary electrolytes (sodium and potassium), biomarkers of sodium and potassium intake, were measured. Biologically directed genetic scores for BP were constructed specifically among pathways related to sodium and potassium biology (pharmagenic enrichment scores), as well as unannotated genome-wide scores (conventional polygenic scores). We then tested whether there was a gene-by-environment interaction between urinary electrolytes and these genetic scores on BP. RESULTS: Genetic risk and urinary electrolytes both independently correlated with BP. However, urinary sodium was associated with a larger BP increase among individuals with higher genetic risk in sodium- and potassium-related pathways than in those with comparatively lower genetic risk. For example, each SD in urinary sodium was associated with a 1.47-mm Hg increase in systolic BP for those in the top 10% of the distribution of genetic risk in sodium and potassium transport pathways versus a 0.97-mm Hg systolic BP increase in the lowest 10% (P=1.95×10-3). This interaction with urinary sodium remained when considering estimated glomerular filtration rate and indexing sodium to urinary creatinine. There was no strong evidence of an interaction between urinary sodium and a standard genome-wide polygenic score of BP. CONCLUSIONS: The data suggest that genetic risk in sodium and potassium pathways could be used in a precision medicine model to direct interventions more specifically in the management of hypertension. Intervention studies are warranted.

Systolic Blood Pressure and Survival to Very Old Age: Results From the Women's Health Initiative.

BACKGROUND: The relationship between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine which SBP levels in women ≥65 years of age with or without blood pressure medication were associated with the highest probability of surviving to 90 years of age. METHODS: The study population consisted of 16 570 participants enrolled in the Women's Health Initiative who were eligible to survive to 90 years of age by February 28, 2020, without a history of cardiovascular disease, diabetes, or cancer. Blood pressure was measured at baseline (1993 through 1998) and then annually through 2005. The outcome was defined as survival to 90 years of age with follow-up. Absolute probabilities of surviving to 90 years of age were estimated for all combinations of SBP and age using generalized additive logistic regression modeling. The SBP that maximized survival was estimated for each age, and a 95% CI was generated. RESULTS: During a median follow-up of 19.8 years, 9723 of 16 570 women (59%) survived to 90 years of age. Women with an SBP between 110 and 130 mm Hg at attained ages of 65, 70, 75, and 80 years had a 38% (95% CI, 34%-48%), 54% (52%-56%), 66% (64%-67%), or 75% (73%-78%) absolute probability to survive to 90 years of age, respectively. The probability of surviving to 90 years of age was lower for greater SBP levels. Women at the attained age of 80 years with 0%, 20%, 40%, 60%, 80%, or 100% time in therapeutic range (defined as an SBP between 110 and 130 mm Hg) had a 66% (64%-69%), 68% (67%-70%), 71% (69%-72%), 73% (71%-74%), 75% (72%-77%), or 77% (74%-79%) absolute survival probability to 90 years of age. CONCLUSIONS: For women >65 years of age with low cardiovascular disease and other chronic disease risk, an SBP level <130 mm Hg was found to be associated with longevity. These findings reinforce current guidelines targeting an SBP target <130 mm Hg in older women.

Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program.

BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.

Hypertension as Cardiovascular Risk Factor in Chronic Kidney Disease.

Hypertension is the leading modifiable cause of premature death and hence one of the global targets of World Health Organization for prevention. Hypertension also affects the great majority of patients with chronic kidney disease (CKD). Both hypertension and CKD are intrinsically related, as hypertension is a strong determinant of worse renal and cardiovascular outcomes and renal function decline aggravates hypertension. This bidirectional relationship is well documented by the high prevalence of hypertension across CKD stages and the dual benefits of effective antihypertensive treatments on renal and cardiovascular risk reduction. Achieving an optimal blood pressure (BP) target is mandatory and requires several pharmacological and lifestyle measures. However, it also requires a correct diagnosis based on reliable BP measurements (eg, 24-hour ambulatory BP monitoring, home BP), especially for populations like patients with CKD where reduced or reverse dipping patterns or masked and resistant hypertension are frequent and associated with a poor cardiovascular and renal prognosis. Even after achieving BP targets, which remain debated in CKD, the residual cardiovascular risk remains high. Current antihypertensive options have been enriched with novel agents that enable to lower the existing renal and cardiovascular risks, such as SGLT2 (sodium-glucose cotransporter-2) inhibitors and novel nonsteroidal mineralocorticoid receptor antagonists. Although their beneficial effects may be driven mostly from actions beyond BP control, recent evidence underline potential improvements on abnormal 24-hour BP phenotypes such as nondipping. Other promising novelties are still to come for the management of hypertension in CKD. In the present review, we shall discuss the existing evidence of hypertension as a cardiovascular risk factor in CKD, the importance of identifying hypertension phenotypes among patients with CKD, and the traditional and novel aspects of the management of hypertensives with CKD.

Resistant Hypertension in Dialysis: Epidemiology, Diagnosis, and Management.

Apparent treatment-resistant hypertension is defined as an elevated BP despite the use of ≥3 antihypertensive medications from different classes or the use of ≥4 antihypertensives regardless of BP levels. Among patients receiving maintenance hemodialysis or peritoneal dialysis, using this definition, the prevalence of apparent treatment-resistant hypertension is estimated to be between 18% and 42%. Owing to the lack of a rigorous assessment of some common causes of pseudoresistance, the burden of true resistant hypertension in the dialysis population remains unknown. What distinguishes apparent treatment-resistance from true resistance is white-coat hypertension and adherence to medications. Accordingly, the diagnostic workup of a dialysis patient with apparent treatment-resistant hypertension on dialysis includes the accurate determination of BP control status with the use of home or ambulatory BP monitoring and exclusion of nonadherence to the prescribed antihypertensive regimen. In a patient on dialysis with inadequately controlled BP, despite adherence to therapy with maximally tolerated doses of a ß -blocker, a long-acting dihydropyridine calcium channel blocker, and a renin-angiotensin system inhibitor, volume-mediated hypertension is the most important treatable cause of resistance. In daily clinical practice, such patients are often managed with intensification of antihypertensive therapy. However, this therapeutic strategy is likely to fail if volume overload is not adequately recognized or treated. Instead of increasing the number of prescribed BP-lowering medications, we recommend diet and dialysate restricted in sodium to facilitate achievement of dry weight. The achievement of dry weight is facilitated by an adequate time on dialysis of at least 4 hours for delivering an adequate dialysis dose. In this article, we review the epidemiology, diagnosis, and management of resistant hypertension among patients on dialysis.

Mind the gap in kidney care: translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Integrating essence of "time" for blood pressure control in nephrology care.

Controlling blood pressure (BP) is essential in the management of patients with chronic kidney disease. Reflecting the intrinsic variability of BP, several parameters of BP over time have been shown to predict adverse outcomes. Systolic BP time in target range has been recently proposed as a new promising parameter. Park et al. confirmed its prognostic value in patients with chronic kidney disease. We review the potential clinical usefulness and challenges of this parameter in nephrology care.

Findings from the KNOW-CKD Study indicate that higher systolic blood pressure time in target range is associated with a lower risk of chronic kidney disease progression.

Time-in-target range (TTR) of systolic blood pressure (SBP) is determined by the proportion of time during which SBP remains within a defined optimal range. TTR has emerged as a useful metric for assessing SBP control over time. However, it is uncertain if SBP-TTR can predict the progression of chronic kidney disease (CKD). Here, we investigated the association between SBP-TTR during the first year of enrollment and CKD progression among 1758 participants from the KNOW-CKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). Baseline median estimated glomerular filtration rate (eGFR) was 51.7 ml/min per 1.73 m2. Participants were categorized into four SBP-TTR groups (0%, 1-50%, 51-99%, and 100%). The primary outcome was CKD progression defined as 50% or more decline in eGFR from baseline measurement or the initiation of kidney replacement therapy. During the follow-up period (9212 person-years over a median 5.4 years), the composite outcome occurred in 710 participants. In the multivariate cause-specific hazard model, a one-standard deviation increase in SBP-TTR was associated with an 11% lower risk of the composite outcome with hazard ratio, 0.89 (95% confidence interval, 0.82-0.97). Additionally, compared to patients with SBP-TTR 0%, the respective hazard ratios for those with SBP-TTR 1-50%, 51-99%, and 100% were 0.85 (0.68-1.07), 0.76 (0.60-0.96), and 0.72 (0.55-0.94), and the respective corresponding slopes of eGFR decline were -3.17 (-3.66 to -2.69), -3.02 (-3.35 to -2.68), -2.62 (-2.89 to - 2.36), and -2.33 (-2.62 to -2.04) ml/min/1.73 m2. Thus, higher SBP-TTR was associated with a decreased risk of CKD progression in patients with CKD.

Identifying an acceptable number of ambulatory blood pressure measurements for accuracy of average blood pressure and nocturnal dipping status.

We aimed to identify the minimum number of ambulatory blood pressure (ABP) measures to accurately determine daytime and nighttime systolic blood pressure (BP) averages and nocturnal dipping status (i.e., relative daytime:nighttime change). A total of 43 midlife participants wore an ABP monitor for 24 h with measurements every 20/30 min during the daytime/nighttime, as identified by a sleep diary. We calculated daytime/nighttime systolic BP average and dipping status from all available measurements per participant (i.e., normative data). We then calculated daytime and nighttime BP per participant based on a random selection of 8-20 and 4-10 measurements and replicated random selections 1,000 times. We calculated accuracy by checking the proportion from 1,000 different randomly selected samples for a particular number of measurements that systolic BP was ±5 mmHg of normative data, and dipping status remained unchanged for each participant compared with the normative value. The best fit for the regression model estimated the minimal number of measurements for an accuracy of 95% in BP averages. For a 95% accuracy in estimating daytime and nighttime systolic BP, 11 daytime and 8 nighttime measurements were required. The highest accuracy for dipping status was 91.6 ± 13.4% using 20 daytime and 10 nighttime measures, while the lowest was (83.4 ± 15.1%) using 8 daytime and 4 nighttime measures. In midlife adults, 11 daytime and 8 nighttime measurements are likely enough to calculate average systolic BPs accurately. However, no minimum number is suggested to accurately calculate dipping status.NEW & NOTEWORTHY We found that a minimum of 11 blood pressure (BP) measures are necessary to calculate an accurate average daytime BP, and 8 nighttime measures are necessary to calculate an accurate nighttime average if 95% accuracy is acceptable. Regarding BP dipping status, the current recommendations (20 daytime/7 nighttime) inaccurately classified the dipping status 10.5% of the time, suggesting that guidelines may need to be updated to classify patients as nocturnal dippers or nondippers correctly.

Relation between frailty and hypertension is partially mediated by physical activity among males and females in the Canadian Longitudinal Study on Aging.

Frailty reflects the heterogeneity in aging and may lead to the development of hypertension and heart disease, but the frailty-cardiovascular relationship and whether physical activity modifies this relationship in males and females are unclear. We tested whether higher frailty was positively associated with hypertension and heart disease in males and females and whether habitual movement mediated this relationship. The relationship between baseline frailty with follow-up hypertension and heart disease was investigated using the Canadian Longitudinal Study on Aging at 3-year follow-up data (males: n = 13,095; females: n = 13,601). Frailty at baseline was determined via a 73-item deficit-based index, activity at follow-up was determined via the Physical Activity Scale for the Elderly, and cardiovascular function was self-reported. Higher baseline frailty level was associated with a greater likelihood of hypertension and heart disease at follow-up, with covariate-adjusted odds ratios of 1.08-1.09 (all, P < 0.001) for a 0.01 increase in frailty index score. Among males and females, sitting time and strenuous physical activity were independently associated with hypertension, with these activity behaviors being partial mediators (except male-sitting time) for the frailty-hypertension relationship (explained 5-10% of relationship). The strength of this relationship was stronger among females. Only light-moderate activity partially mediated the relationship (∼6%) between frailty and heart disease in females, but no activity measure was a mediator for males. Higher frailty levels were associated with a greater incidence of hypertension and heart disease, and strategies that target increases in physical activity and reducing sitting may partially uncouple this relationship with hypertension, particularly among females.NEW & NOTEWORTHY Longitudinally, our study demonstrates that higher baseline frailty levels are associated with an increased risk of hypertension and heart disease in a large sample of Canadian males and females. Movement partially mediated this relationship, particularly among females.

Laboratory Testing for Endocrine Hypertension: Current and Future Perspectives.

BACKGROUND: Secondary hypertension (SH) is a form of high blood pressure caused by an identifiable underlying condition. Although, it accounts for a small fraction of the overall hypertensive population, detection and management of SH is of utmost importance, because SH phenotypes carry a high cardiovascular risk and can possibly be cured by timely treatment. CONTENT: This review focuses on the endocrine causes of SH, such as primary aldosteronism, Cushing syndrome, thyroid disease, pheochromocytoma and paraganglioma, acromegaly, and rare monogenic forms. It discusses current biomarkers, analytical methods, and diagnostic strategies, highlighting advantages and limitations of each approach. It also explores the emerging -omics technologies that can provide a comprehensive and multidimensional assessment of SH and its underlying mechanisms. SUMMARY: Endocrine SH is a heterogeneous and complex condition that requires proper screening and confirmatory tests to avoid diagnostic delays and improve patient outcomes. Careful biomarker interpretation is essential due to potential interferences, variability, and method-dependent differences. Liquid chromatography-tandem mass spectrometry is a superior method for measuring low-concentration hormones and metabolites involved in SH, but it requires expertise. Omics approaches have great potential to identify novel biomarkers, pathways, and targets for SH diagnosis and treatment, especially considering its multifactorial nature.

A paradigm shift from office to home-based blood pressure measurement approaches in kidney transplant recipients.

PURPOSE OF REVIEW: The unattended blood pressure (BP) readings from home blood pressure (HBP) monitoring should provide more accurate BP readings than attended BP obtained from office blood pressure (OBP). Here, we review evidence supporting the clinical utility of HBP and automatic remote monitoring of blood pressure (ARM-BP) in kidney transplant recipients (KTR). RECENT FINDINGS: BP from 24-h ambulatory blood pressure monitoring (24-h ABPM) is higher than but better associated with kidney and cardiovascular outcomes compared to OBP and HBP. While there is discordance of BP readings across different BP measurement methods causing BP misclassification, HBP provides BP readings closer to the readings from the 24-h ABPM than those from OBP. Systolic and diastolic BP is better controlled within 30 days after utilizing ARM-BP. SUMMARY: Compared to OBP, HBP minimizes the attended effect of OBP, and its readings are closer to the gold standard 24-h ABPM. ARM-BP improves BP control in the short term and trials of longer follow-up duration are required to evaluate sustained clinical benefits in KTR. The paradigm of BP monitoring may shift toward HBP, while OBP may be utilized primarily for KTR who cannot perform HBP for hypertension diagnosis and management.

Revisiting resistant hypertension in kidney disease.

PURPOSE OF REVIEW: As compared to controlled or uncontrolled hypertension, resistant hypertension in patients with chronic kidney disease (CKD) poses a significantly increased healthcare burden due to greater target end-organ damage including cardiovascular disease and CKD progression. Patients with CKD have two to three times higher risk of developing resistant hypertension. True resistant hypertension needs to be distinguished from apparent treatment resistant hypertension (aTRH); however, it is usually not possible in epidemiological studies. Moreover, impact of contemporary guidelines changes in the target blood pressure (BP) goal to less than 130/80 mmHg remains to be determined. RECENT FINDINGS: Up to half of patients with CKD meet aTRH criteria using 2017 ACC/AHA target BP less than 130/80 mmHg. Excess sodium retention in extracellular and tissue compartment remains the cornerstone cause of resistance to the treatment in CKD. Maximizing and optimizing the diuretic regimen in addition to dietary sodium restriction plays a critical role in these patients. Management requires a trustworthy provider-patient relationship facilitating identification and intervention for the barriers restricting the uptake of lifestyle modifications and medications. Recently, renal denervation has been approved and many other novel agents are on the horizon for treatment of true resistant hypertension associated with CKD. SUMMARY: This review discusses the latest in the pathophysiology, definition, identification and treatment strategies of resistant hypertension in individuals with CKD. Further investigations are required to identify the prevalence, future implication and treatment outcome data for true resistant hypertension associated with CKD.

Blood Pressure Outcomes in NICU-Admitted Infants with Neonatal Hypertension: A Pediatric Nephrology Research Consortium Study.

OBJECTIVE: To describe the blood pressure outcomes of infants admitted to the neonatal intensive care unit (NICU) with idiopathic (nonsecondary) hypertension (HTN) who were discharged on antihypertensive therapy. STUDY DESIGN: Retrospective, multicenter study of 14 centers within the Pediatric Nephrology Research Consortium. We included all infants with a diagnosis of idiopathic HTN discharged from the NICU on antihypertensive treatment. The primary outcome was time to discontinuation of antihypertensive therapy, grouped into (≤6 months, >6 months to 1 year, and >1 year). Comparisons between groups were made with χ2 tests, Fisher's exact tests, and ANOVA. RESULTS: Data from 118 infants (66% male) were included. Calcium channel blockers were the most prescribed class of antihypertensives (56%) in the cohort. The percentages remaining on antihypertensives after NICU discharge were 60% at 6 months, 26% at 1 year, and 7% at 2 years. Antenatal steroid treatment was associated with decreased likelihood of antihypertensive therapy >1 year after discharge. CONCLUSIONS: This multicenter study reports that most infants admitted to the NICU diagnosed with idiopathic HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data provide important insights into the outcome of neonatal HTN, but should be confirmed prospectively.

Accuracy and Performance of Triage Blood Pressure Measurements in A Real-World Clinic Setting.

OBJECTIVES: To investigate the agreement and accuracy of triage blood pressure (BP) in a real-world clinic setting, compared with the reference standard. STUDY DESIGN: Paired triage and standardized BP measurements from patients 4 through 21 years old evaluated in an obesity-related hypertension clinic were obtained via chart-review. Triage BPs were measured by a medical assistant or nurse, often by automated device. Triplicate manual BPs were obtained by the clinic physician. Bland-Altman analyses determined mean differences between paired triage and mean standardized BPs. GEE-based multivariable relative risk (RR) regression determined the RR of triage BP overestimation by ≥ 5 mmHg. Overall agreement, sensitivity, specificity, positive predictive value, and negative predictive value of triage BP measurements identifying hypertensive BP were determined. RESULTS: One hundred thirty participants with 347 clinic encounters were included. Mean age was 13.3 years (SD 3.94), 76% were Black, and 58% were male. Overall mean systolic and diastolic BP difference was 8.7 mmHg (95% limits on agreement: -16.66, 34.07) and 4.1 mmHg (95% limits on agreement: -18.56, 26.68), respectively. Triage systolic BP was more likely overestimated by ≥ 5 mmHg when a large adult (RR = 1.49; 95% CI: 1.00, 2.21) or thigh cuff (RR = 1.94; 95% CI: 1.08, 3.51) was required compared with when a child/adult cuff was required. Overall agreement in identifying hypertensive BP was 57.6%. Sensitivity (52.6%), specificity (63.4%), positive predictive value (60.8%), and negative predictive value (55.3%) were low across all cuffs. CONCLUSIONS: There was poor agreement between usual triage and standardized BP measurements, with potential for significant clinical implications. CLINICAL TRIAL REGISTRATION: ReNEW Clinic Cohort Study (ReNEW), NCT03816462, https://clinicaltrials.gov/ct2/show/NCT03816462.

Reclassification of Adolescent Ambulatory Prehypertension and Unclassified Blood Pressures by 2022 American Heart Association Pediatric Ambulatory Blood Pressure Monitoring Guidelines.

OBJECTIVE: To describe the epidemiology of reclassification of prehypertensive and unclassified adolescents by 2022 American Heart Association pediatric ambulatory blood pressure monitoring (ABPM) guidelines, and to evaluate the association of the new diagnostic categories with left ventricular hypertrophy (LVH). STUDY DESIGN: A single-center, retrospective review of ABPM reports from adolescents 13-21 years old, from 2015 through 2022, was performed. Adolescents with prehypertension or unclassified by 2014 guidelines were reclassified by 2022 definitions. Logistic regression models evaluated the association of reclassification phenotypes with LVH. RESULTS: A majority of prehypertensive adolescents reclassified to hypertension (70%, n = 49/70). More than one-half (57%, n = 28/49) of the hypertension was isolated nocturnal hypertension, and 80% was systolic hypertension. Reclassification to hypertension was more common in males. The majority (55.6%) of unclassified adolescents were reclassified to normotension. No demographic or clinical variables were associated with reclassification categories. LVH was not associated with hypertension in the reclassified prehypertensive or unclassified groups. CONCLUSIONS: The 2022 ABPM guidelines clearly define blood pressure phenotypes. However, reclassification to hypertension was not associated with an increased odds of LVH. Because most prehypertensive adolescents reclassified as hypertensive by nighttime BPs alone, this study highlights the lowered threshold for nocturnal hypertension. Prospective studies in larger, well-defined cohorts are needed to describe better the predictive value of 2022 BP phenotypes for target organ damage.

The neutrophil-to-lymphocyte ratio is associated with all-cause and cardiovascular mortality among individuals with hypertension.

BACKGROUND: Identifying reliable prognostic markers is crucial for the effective management of hypertension. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential inflammatory marker linked to cardiovascular outcomes. This study aims to investigate the association of NLR with all-cause and cardiovascular mortality among patients with hypertension. METHODS: This study analyzed data from 3067 hypertensive adults in the National Health and Nutritional Examination Surveys (NHANES) from 2009 to 2014. Mortality details were obtained from the National Death Index (NDI). Restricted cubic spline (RCS) was deployed to visualize the association of the NLR with mortality risk. Weighted Cox proportional hazards models were employed to assess the independent association of NLR with mortality risk. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to access the predictive ability of NLR for survival. Mediation analysis was used to explore the indirect impact of NLR on mortality mediated through eGFR. RESULTS: Over a median 92.0-months follow-up, 538 deaths occurred, including 114 cardiovascular deaths. RCS analysis revealed a positive association between NLR and both all-cause and cardiovascular mortality. Participants were stratified into higher (> 3.5) and lower (≤ 3.5) NLR groups. Weighted Cox proportional hazards models demonstrated that individuals with higher NLR had a significantly increased risk of all-cause (HR 1.96, 95% confidence interval (CI) 1.52-2.52, p < 0.0001) and cardiovascular mortality (HR 2.33, 95% CI 1.54-3.51, p < 0.0001). Stratified and interaction analysis confirmed the stability of the core results. Notably, eGFR partially mediated the association between NLR and both all-cause and cardiovascular mortality by a 5.4% and 4.7% proportion, respectively. Additionally, the areas under the curve (AUC) of the 3-, 5- and 10- year survival was 0.68, 0.65 and 0.64 for all-cause mortality and 0.68, 0.70 and 0.69 for cardiovascular mortality, respectively. CONCLUSION: Elevated NLR independently confers an increased risk for both all-cause and cardiovascular mortality in individuals with hypertension.