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Primary aldosteronism (PA) is the most common cause of secondary hypertension but is frequently underrecognized and undertreated. Patients with PA are at a markedly increased risk for target organ damage to the heart and kidneys. While patients with unilateral PA can be treated surgically, many patients with PA are not eligible or willing to undergo surgery. Steroidal mineralocorticoid receptor antagonists (MRAs) are highly effective for treating PA and reducing the risk of target organ damage. However, steroidal MRAs are often underprescribed and can be poorly tolerated by some patients due to side effects. Nonsteroidal MRAs reduce adverse renal and cardiovascular outcomes among patients with diabetic kidney disease and are bettertolerated than steroidal MRAs. While their blood pressure–lowering effects remain unclear, these agents may have a potential role in reducing target organ damage in patients with PA. [ABSTRACT FROM AUTHOR]

An editorial is presented discussing the implications of a crossover trial examining individual responses to low-sodium and high-sodium diets, emphasizing the spectrum of responsiveness to sodium reduction and the challenges in interpreting the study's findings. Topics include the longstanding debate on sodium restriction, the mechanistic underpinnings of salt-sensitive hypertension, and the limitations and implications of the trial's design and dietary interventions.

Background: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses. Methods and findings: In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs. non-ARB/ACEI (excluding Veterans with compelling indications to reduce confounding by indication) and (B) ARB vs. ACEI among (1) SARS-CoV-2+ outpatients and (2) COVID-19 hospitalized inpatients. The primary outcome was all-cause hospitalization or mortality (outpatients) and all-cause mortality (inpatients). We estimated hazard ratios (HR) using propensity score-weighted Cox regression. Baseline characteristics were well-balanced between exposure groups after weighting. Among outpatients, there were 5.0 and 6.0 primary outcomes per 100 person-months for ARB/ACEI (n = 2,482) vs. non-ARB/ACEI (n = 2,487) users (HR 0.85, 95% confidence interval [CI] 0.73–0.99, median follow-up 87 days). Among outpatients who were ARB (n = 4,877) vs. ACEI (n = 8,704) users, there were 13.2 and 14.8 primary outcomes per 100 person-months (HR 0.91, 95%CI 0.86–0.97, median follow-up 85 days). Among inpatients who were ARB/ACEI (n = 210) vs. non-ARB/ACEI (n = 275) users, there were 3.4 and 2.0 all-cause deaths per 100 person months (HR 1.25, 95%CI 0.30–5.13, median follow-up 30 days). Among inpatients, ARB (n = 1,164) and ACEI (n = 2,014) users had 21.0 vs. 17.7 all-cause deaths, per 100 person-months (HR 1.13, 95%CI 0.93–1.38, median follow-up 30 days). Conclusions: This observational analysis supports continued ARB or ACEI use for patients already using these medications before SARS-CoV-2 infection. The novel beneficial association observed among outpatients between users of ARBs vs. ACEIs on hospitalization or mortality should be confirmed with randomized trials. [ABSTRACT FROM AUTHOR]

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

In the early months of the coronavirus disease 2019 (COVID-19) pandemic, a hypothesis emerged suggesting that pharmacologic inhibitors of the renin–angiotensin system (RAS) may increase COVID-19 severity. This hypothesis was based on the role of angiotensin-converting enzyme 2 (ACE2), a counterregulatory component of the RAS, as the binding site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), allowing viral entry into host cells. Extrapolations from prior evidence led to speculation that upregulation of ACE2 by RAS blockade may increase the risk of adverse outcomes from COVID-19. However, counterarguments pointed to evidence of potential protective effects of ACE2 and RAS blockade with regard to acute lung injury, as well as substantial risks from discontinuing these commonly used and important medications. Here we provide an overview of classic RAS physiology and the crucial role of ACE2 in systemic pathways affected by COVID-19. Additionally, we critically review the physiologic and epidemiologic evidence surrounding the interactions between RAS blockade and COVID-19. We review recently published trial evidence and propose important future directions to improve upon our understanding of these relationships. [ABSTRACT FROM AUTHOR]

Keywords: blood pressure; blood pressure monitors; quality improvement EN blood pressure blood pressure monitors quality improvement 94 96 3 01/20/22 20220111 NES 220111 Renal-Electrolyte and Hypertension Division (J.B.C.), Perelman School of Medicine, University of Pennsylvania, Philadelphia. Blood pressure, quality improvement, blood pressure monitors. [Extracted from the article]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus responsible for coronavirus disease 2019 (COVID‐19), is associated with high incidence of multiorgan dysfunction and death. Angiotensin‐converting enzyme 2 (ACE2), which facilitates SARS‐CoV‐2 host cell entry, may be impacted by angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two commonly used antihypertensive classes. In a multicenter, international randomized controlled trial that began enrollment on March 31, 2020, participants are randomized to continuation vs withdrawal of their long‐term outpatient ACEI or ARB upon hospitalization with COVID‐19. The primary outcome is a hierarchical global rank score incorporating time to death, duration of mechanical ventilation, duration of renal replacement or vasopressor therapy, and multiorgan dysfunction severity. Approval for the study has been obtained from the Institutional Review Board of each participating institution, and all participants will provide informed consent. A data safety monitoring board has been assembled to provide independent oversight of the project. [ABSTRACT FROM AUTHOR]

Animal studies have suggested that Erythropoiesis-Stimulating Agents (ESAs) may increase vascular endothelial growth factor (VEGF)-related retinopathies, but this effect is unclear in humans. This study evaluates the risk of vision-threatening diabetic retinopathy (VTDR), defined as either diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), in patients exposed to an ESA. Two analyses were performed. First, a retrospective matched-cohort study was designed using a de-identified commercial and Medicare Advantage medical claims database. The ESA cohort of non-proliferative diabetic retinopathy patients who were new users of an ESA from 2000 to 2022 was matched to controls up to a 3:1 ratio. Exclusion criteria included less than 2 years in the plan, history of VTDR or history of other retinopathy. Multivariable Cox proportional hazards regression with inverse proportional treatment weighting (IPTW) was used to assess the hazard of developing VTDR, DME, and PDR. The second analysis was a self-controlled case series (SCCS) evaluating the incidence rate ratios (IRR) of VTDR during 30-day periods before and after initiating an ESA. After inclusion of 1502 ESA-exposed patients compared with 2656 controls, IPTW-adjusted hazard ratios found the ESA cohort had an increased hazard of progressing to VTDR (HR = 3.0 95%CI:2.3–3.8;p <.001) and DME (HR = 3.4,95%CI:2.6–4.4,p <.001), but not PDR (HR = 1.0,95%CI:0.5–2.3,p =.95). Similar results were found within the SCCS which demonstrated higher IRRs for VTDR (IRRs = 1.09–1.18;p <.001) and DME (IRRs = 1.16–1.18;p <.001), but not increased IRRs in PDR (IRR = 0.92–0.97,p =.02–0.39). ESAs are associated with higher risks for VTDR and DME, but not PDR. Those studying ESAs as adjunctive therapy for DR should be cautious of possible unintended effects. [ABSTRACT FROM AUTHOR]

Background: The long-term cardiovascular risk of isolated elevated office blood pressure (BP) is unclear.Purpose: To summarize the risk for cardiovascular events and all-cause mortality associated with untreated white coat hypertension (WCH) and treated white coat effect (WCE).Data Sources: PubMed and EMBASE, without language restriction, from inception to December 2018.Study Selection: Observational studies with at least 3 years of follow-up evaluating the cardiovascular risk of WCH or WCE compared with normotension.Data Extraction: 2 investigators independently extracted study data and assessed study quality.Data Synthesis: 27 studies were included, comprising 25 786 participants with untreated WCH or treated WCE and 38 487 with normal BP followed for a mean of 3 to 19 years. Compared with normotension, untreated WCH was associated with an increased risk for cardiovascular events (hazard ratio [HR], 1.36 [95% CI, 1.03 to 2.00]), all-cause mortality (HR, 1.33 [CI, 1.07 to 1.67]), and cardiovascular mortality (HR, 2.09 [CI, 1.23 to 4.48]); the risk for WCH was attenuated in studies that included stroke in the definition of cardiovascular events (HR, 1.26 [CI, 1.00 to 1.54]). No significant association was found between treated WCE and cardiovascular events (HR, 1.12 [CI, 0.91 to 1.39]), all-cause mortality (HR, 1.11 [CI, 0.89 to 1.46]), or cardiovascular mortality (HR, 1.04 [CI, 0.65 to 1.66]). The findings persisted across several sensitivity analyses.Limitation: Paucity of studies evaluating isolated cardiac outcomes or reporting participant race/ethnicity.Conclusion: Untreated WCH, but not treated WCE, is associated with an increased risk for cardiovascular events and all-cause mortality. Out-of-office BP monitoring is critical in the diagnosis and management of hypertension.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association between body mass index (BMI) and postoperative outcomes in elective paraesophageal hernia (PEH) repairs.Methods: A retrospective review of patients who underwent elective PEH repair in the ACS NSQIP database (2005-2015) was performed. Patients were stratified into BMI groups (< 18.5, 18.5-24.9, 25.0-29.9, 30.0-34.9, 35-39.9, and ≥ 40.0 kg/m2) according to the World Health Organization classification criteria. A multivariable logistic regression model was developed to characterize the association between BMI class and outcomes, including readmission, reoperation, postoperative complications, and mortality.Results: The median (IQR) age of the 9641 patients who met inclusion criteria was 64 (55-72) and 72.7% were women. Across each BMI class, age, race, gender, type of procedure, frailty index, smoking, and ASA class varied (p < 0.05). Underweight patients (BMI < 18.5 kg/m2) had an increased risk of mortality (OR = 6.35, p < 0.05). Patients with a BMI 35-39.9 kg/m2 (OR = 0.65, p < 0.05) and ≥ 40 kg/m2 (OR = 0.36, p < 0.001) were associated with a decreased risk for readmissions.Conclusion: Underweight patients have an increased risk for postoperative mortality after elective PEH repair. Higher BMI was associated with a diminished risk for readmission, but not for mortality, reoperations, or overall complications. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is common in dialysis patients and renal transplant recipients and has been associated with diminished patient and allograft survival. HCV-positive (HCV+) kidneys have been used in HCV-positive (HCV+) recipients as a means of facilitating transplantation and expanding the organ donor pool; however, the effect of donor HCV serostatus in the modern era is unknown. Methods: Using national transplant registry data, we created a propensity score-matched cohort of HCV+ recipients who received HCV-positive donor kidneys compared to those transplanted with HCV-negative kidneys. Results: Transplantation with an HCV+ kidney was associated with an increased risk of death {hazard ratio [HR] 1.43 [95% confidence interval (CI) 1.18-1.76]; P<0.001} and allograft loss [HR 1.39 (95% CI 1.16-1.67); P<0.001] compared with their propensity score-matched counterparts. However, HCV+ kidneys were not associated with an increased risk of acute rejection [odds ratio 1.16 (95% CI 0.84-1.61); P=0.35]. Conclusions: While use of HCV+ donor kidneys can shorten the wait for renal transplantation and maximize organ utility for all candidates on the waiting list, potential recipients should be counseled about the increased risks associated with HCV+ kidney. [ABSTRACT FROM AUTHOR]

The OMRON HEM-907XL is a commercial oscillometric blood pressure (BP) monitor that was used in the Systolic Blood Pressure Intervention Trial (SPRINT), in which 28% of participants had chronic kidney disease (CKD). This study examined the accuracy of the monitor in nondialytic patients with CKD. Eighty-seven patients met inclusion criteria. The authors used a modified Association for the Advancement of Medical Instrumentation (AAMI) protocol, with one observer recording measurements from the monitor and two blinded physicians obtaining simultaneous aneroid values by auscultation. Using AAMI method 1, there was a 2.5±9.5 mm Hg difference in OMRON and aneroid systolic BP, and a -1.6±6.5 mm Hg difference in diastolic BP. Using AAMI method 2, there was a 5.1±7.4 mm Hg difference in systolic BP and a -0.2±5.4 mm Hg difference in diastolic BP. In patients with CKD, the OMRON HEM-907XL appears to be accurate for measuring diastolic BP, but did not perform as well for systolic BP. [ABSTRACT FROM AUTHOR]

The most notable recommendation in the 2017 American College of Cardiology and American Heart Association hypertension guidelines is the reduced threshold for the diagnosis of hypertension, from ≥140/90 mm Hg to ≥130/80 mm Hg in the general population. This commentary discusses the guidelines and why they create as many questions as they answer. [ABSTRACT FROM AUTHOR]

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

In this paper, the first author's name was incorrectly tagged. [ABSTRACT FROM AUTHOR]

Background: Despite a survival benefit from transplantation and acceptable outcomes, patients with human immunodeficiency virus (HIV+) face barriers to kidney transplantation. Little is known about the acceptance or decline of organ offers on their behalf because waitlist registry data do not include HIV serostatus. Methods: We performed a retrospective cohort study using match run data from the Organ Procurement and Transplantation Network, including every kidney offer from May 1, 2007, to July 3, 2013. HIV and hepatitis C virus (HCV) serostatus were obtained by merging the match run with clinical data from a large dialysis provider. We used Cox proportional hazards modeling to evaluate differences in time to the first organ offer and to transplantation. A total of 35 646 uninfected, 2213 HCV+, 418 HIV+, and 71 HIV+/HCV+ candidates received organ offers during the study period. Results: Compared to uninfected candidates, HIV+ candidates had a significantly lower likelihood of receiving a first offer (adjusted hazard ratio [aHR] 0.88, 95% confidence interval [CI] 0.79‐0.99) and undergoing transplantation (aHR 0.82, 95% CI: 0.68‐0.98) after receiving a first offer; HCV+ candidates had a similar likelihood of receiving a first offer (aHR 0.98, 95% CI: 0.92‐1.03) and greater likelihood of transplantation after receiving a first offer (aHR 1.23, 95% CI: 1.12‐1.36). Conclusions: HIV+ candidates had a significantly longer wait until their first organ offer and to transplantation. Efforts to increase their access to transplantation are needed. [ABSTRACT FROM AUTHOR]

Algorithms are used in health care to calculate organ function and predict patient risk or future outcomes, and, subsequently, for treatment decisions, further diagnostic procedures, or referral for further care. Inputs to algorithms and how they are calculated may result in racial or ethnic disparities in access to care, quality of care, and disparities in health outcomes. This paper systematically reviews studies that have evaluated the impact of algorithms on racial or ethnic disparities and what strategies have been used to mitigate such disparities. Background: There is increasing concern for the potential impact of health care algorithms on racial and ethnic disparities. Purpose: To examine the evidence on how health care algorithms and associated mitigation strategies affect racial and ethnic disparities. Data Sources: Several databases were searched for relevant studies published from 1 January 2011 to 30 September 2023. Study Selection: Using predefined criteria and dual review, studies were screened and selected to determine: 1) the effect of algorithms on racial and ethnic disparities in health and health care outcomes and 2) the effect of strategies or approaches to mitigate racial and ethnic bias in the development, validation, dissemination, and implementation of algorithms. Data Extraction: Outcomes of interest (that is, access to health care, quality of care, and health outcomes) were extracted with risk-of-bias assessment using the ROBINS-I (Risk Of Bias In Non-randomised Studies – of Interventions) tool and adapted CARE-CPM (Critical Appraisal for Racial and Ethnic Equity in Clinical Prediction Models) equity extension. Data Synthesis: Sixty-three studies (51 modeling, 4 retrospective, 2 prospective, 5 prepost studies, and 1 randomized controlled trial) were included. Heterogenous evidence on algorithms was found to: a) reduce disparities (for example, the revised kidney allocation system), b) perpetuate or exacerbate disparities (for example, severity-of-illness scores applied to critical care resource allocation), and/or c) have no statistically significant effect on select outcomes (for example, the HEART Pathway [history, electrocardiogram, age, risk factors, and troponin]). To mitigate disparities, 7 strategies were identified: removing an input variable, replacing a variable, adding race, adding a non–race-based variable, changing the racial and ethnic composition of the population used in model development, creating separate thresholds for subpopulations, and modifying algorithmic analytic techniques. Limitation: Results are mostly based on modeling studies and may be highly context-specific. Conclusion: Algorithms can mitigate, perpetuate, and exacerbate racial and ethnic disparities, regardless of the explicit use of race and ethnicity, but evidence is heterogeneous. Intentionality and implementation of the algorithm can impact the effect on disparities, and there may be tradeoffs in outcomes. Primary Funding Source: Agency for Healthcare Quality and Research. [ABSTRACT FROM AUTHOR]

Background: Nonadherence is common in children with chronic kidney disease (CKD). This may contribute to inadequate blood pressure control and adverse outcomes. This study examined associations between antihypertensive medication nonadherence, ambulatory blood pressure monitoring (ABPM) parameters, kidney function, and cardiac structure among children with CKD. Methods: We performed secondary analyses of data from the CKD in Children (CKiD) study, including participants with treated hypertension who underwent ABPM, laboratory testing, and echocardiography biannually. Nonadherence was defined by self-report of any missed antihypertensive medication 7 days prior to the study visit. Linear regression and mixed-effects models were used to assess the association of nonadherence with baseline and time-updated ABPM profiles, estimated glomerular filtration rate (eGFR), urine protein to creatinine ratio (UPCR), and left ventricular mass index (LVMI). Results: Five-hundred and eight participants met inclusion criteria, followed for a median of 2.9 years; 212 (42%) were female, with median age 13 years (IQR 10–16), median baseline eGFR 49 (33–64) ml/min/1.73 m2 and median UPCR 0.4 (0.1–1.0) g/g. Nonadherence occurred in 71 (14%) participants. Baseline nonadherence was not significantly associated with baseline 24-h ABPM parameters (for example, mean 24-h SBP [β − 0.1, 95% CI − 2.7, 2.5]), eGFR (β 1.0, 95% CI − 0.9, 1.2), UCPR (β 1.1, 95% CI − 0.8, 1.5), or LVMI (β 0.6, 95% CI − 1.6, 2.9). Similarly, there were no associations between baseline nonadherence and time-updated outcome measures. Conclusions: Self-reported antihypertensive medication nonadherence occurred in 1 in 7 children with CKD. We found no associations between nonadherence and kidney function or cardiac structure over time. [ABSTRACT FROM AUTHOR]

Background: Viral infection is associated with a significant rewire of the host metabolic pathways, presenting attractive metabolic targets for intervention. Methods: We chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples and perform in vitro metabolism-focused drug screen on primary lung epithelial cells infected with different strains of the virus. We perform observational analysis of Israeli patients hospitalized due to COVID-19 and comparative epidemiological analysis from cohorts in Italy and the Veteran's Health Administration in the United States. In addition, we perform a prospective non-randomized interventional open-label study in which 15 patients hospitalized with severe COVID-19 were given 145 mg/day of nanocrystallized fenofibrate added to the standard of care. Results: SARS-CoV-2 infection produced transcriptional changes associated with increased glycolysis and lipid accumulation. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication through a PPARa-dependent mechanism in both alpha and delta variants. Analysis of 3233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective non-randomized interventional open-label study was carried out on 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to patients admitted during the same period. Conclusions: Taken together, our data suggest that pharmacological modulation of PPARa should be strongly considered as a potential therapeutic approach for SARS-CoV-2 infection and emphasizes the need to complete the study of fenofibrate in large randomized controlled clinical trials. Funding: Funding was provided by European Research Council Consolidator Grants OCLD (project no. 681870) and generous gifts from the Nikoh Foundation and the Sam and Rina Frankel Foundation (YN). The interventional study was supported by Abbott (project FENOC0003). [ABSTRACT FROM AUTHOR]

Background The effect of renin–angiotensin system (RAS) blockade either by angiotensin-converting enzyme inhibitors (ACEis) or angiotensin-receptor blockers (ARBs) on coronavirus disease 2019 (COVID-19) susceptibility, mortality and severity is inadequately described. We examined the association between RAS blockade and COVID-19 diagnosis and prognosis in a large population-based cohort of patients with hypertension (HTN). Methods This is a cohort study using regional health records. We identified all individuals aged 18–95 years from 87 healthcare reference areas of the main health provider in Catalonia (Spain), with a history of HTN from primary care records. Data were linked to COVID-19 test results, hospital, pharmacy and mortality records from 1 March 2020 to 14 August 2020. We defined exposure to RAS blockers as the dispensation of ACEi/ARBs during the 3 months before COVID-19 diagnosis or 1 March 2020. Primary outcomes were: COVID-19 infection and severe progression in hospitalized patients with COVID-19 (the composite of need for invasive respiratory support or death). For both outcomes and for each exposure of interest (RAS blockade, ACEi or ARB) we estimated associations in age-, sex-, healthcare area- and propensity score-matched samples. Results From a cohort of 1 365 215 inhabitants we identified 305 972 patients with HTN history. Recent use of ACEi/ARBs in patients with HTN was associated with a lower 6-month cumulative incidence of COVID-19 diagnosis {3.78% [95% confidence interval (CI) 3.69–3.86%] versus 4.53% (95% CI 4.40–4.65%); P < 0.001}. In the 12 344 patients with COVID-19 infection, the use of ACEi/ARBs was not associated with a higher risk of hospitalization with need for invasive respiratory support or death [OR = 0.91 (0.71–1.15); P = 0.426]. Conclusions RAS blockade in patients with HTN is not associated with higher risk of COVID-19 infection or with a worse progression of the disease. [ABSTRACT FROM AUTHOR]

Aims: Enhanced risk stratification of patients with aortic stenosis (AS) is necessary to identify patients at high risk for adverse outcomes, and may allow for better management of patient subgroups at high risk of myocardial damage. The objective of this study was to identify plasma biomarkers and multimarker profiles associated with adverse outcomes in AS. Methods and results: We studied 708 patients with calcific AS and measured 49 biomarkers using a Luminex platform. We studied the correlation between biomarkers and the risk of (i) death and (ii) death or heart failure‐related hospital admission (DHFA). We also utilized machine‐learning methods (a tree‐based pipeline optimizer platform) to develop multimarker models associated with the risk of death and DHFA. In this cohort with a median follow‐up of 2.8 years, multiple biomarkers were significantly predictive of death in analyses adjusted for clinical confounders, including tumour necrosis factor (TNF)‐α [hazard ratio (HR) 1.28, P < 0.0001], TNF receptor 1 (TNFRSF1A; HR 1.38, P < 0.0001), fibroblast growth factor (FGF)‐23 (HR 1.22, P < 0.0001), N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) (HR 1.58, P < 0.0001), matrix metalloproteinase‐7 (HR 1.24, P = 0.0002), syndecan‐1 (HR 1.27, P = 0.0002), suppression of tumorigenicity‐2 (ST2) (IL1RL1; HR 1.22, P = 0.0002), interleukin (IL)‐8 (CXCL8; HR 1.22, P = 0.0005), pentraxin (PTX)‐3 (HR 1.17, P = 0.001), neutrophil gelatinase‐associated lipocalin (LCN2; HR 1.18, P < 0.0001), osteoprotegerin (OPG) (TNFRSF11B; HR 1.26, P = 0.0002), and endostatin (COL18A1; HR 1.28, P = 0.0012). Several biomarkers were also significantly predictive of DHFA in adjusted analyses including FGF‐23 (HR 1.36, P < 0.0001), TNF‐α (HR 1.26, P < 0.0001), TNFR1 (HR 1.34, P < 0.0001), angiopoietin‐2 (HR 1.26, P < 0.0001), syndecan‐1 (HR 1.23, P = 0.0006), ST2 (HR 1.27, P < 0.0001), IL‐8 (HR 1.18, P = 0.0009), PTX‐3 (HR 1.18, P = 0.0002), OPG (HR 1.20, P = 0.0013), and NT‐proBNP (HR 1.63, P < 0.0001). Machine‐learning multimarker models were strongly associated with adverse outcomes (mean 1‐year probability of death of 0%, 2%, and 60%; mean 1‐year probability of DHFA of 0%, 4%, 97%; P < 0.0001). In these models, IL‐6 (a biomarker of inflammation) and FGF‐23 (a biomarker of calcification) emerged as the biomarkers of highest importance. Conclusions: Plasma biomarkers are strongly associated with the risk of adverse outcomes in patients with AS. Biomarkers of inflammation and calcification were most strongly related to prognosis. [ABSTRACT FROM AUTHOR]

Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension. These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful. In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis. RAS inhibition could mitigate this effect. With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community. [ABSTRACT FROM AUTHOR]

Short sleep duration has been widely linked to increased cardiovascular morbidity and mortality. We performed a post hoc analysis of 24-hour ambulatory blood pressure monitoring (ABPM) in the Lifestyle Modification in Blood Pressure Lowering Study (LIMBS) and Penn Icelandic Sleep Apnea (PISA) Study. The 24-hour mean systolic blood pressure (BP) was 12.7 mm Hg higher in LIMBS (P < 0.001; n = 66) and 4.7 mm Hg higher in PISA (P = 0.005; n = 153) among participants with shorter sleep duration (less than 7 hours) compared to those with longer sleep duration (at least 7 hours). In multivariable adjusted models, shorter sleep duration was strongly associated with higher systolic BP on 24-hour ABPM, independent of nocturnal BP and in-office BP. There was no effect modification by obstructive sleep apnea. Adults with shorter sleep duration may benefit from screening with 24-hour ABPM to promote earlier detection of hypertension and potentially mitigate their increased risk for future cardiovascular disease. [ABSTRACT FROM AUTHOR]