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Neuroadrenergic function in type 2 diabetic (T2D) patients without neuropathy is poorly characterized. We therefore compared sympathetic nervous system activity at rest and during an oral glucose tolerance test in obese metabolic syndrome (MetS) subjects classified as glucose intolerant (impaired glucose tolerance [IGT]; n = 17) or treatment-naive T2D (n = 17). Untreated subjects, matched for age (mean 59 ± 1 year), sex, BMI (32.4 ± 0.6 kg/m(2)), and family history of diabetes were studied. We measured resting muscle sympathetic nerve activity (MSNA) by microneurography, whole-body norepinephrine kinetics by isotope dilution, insulin sensitivity by euglycemic-hyperinsulinemic clamp (steady-state glucose utilization adjusted for fat-free mass and steady-state insulin concentration [M/I]), and MetS components. T2D subjects had higher resting MSNA burst incidence (67 ± 4 versus 55 ± 3 bursts per 100 heartbeats; P = 0.05) and arterial norepinephrine levels (264 ± 33 versus 167 ± 16 pg/mL; P = 0.02), lower plasma norepinephrine clearance (by 17%; P = 0.03), and reduced neuronal reuptake compared with IGT subjects (by 46%; P = 0.04). Moreover, norepinephrine spillover responses to glucose ingestion were blunted in T2D subjects. The M/I value independently predicted whole-body norepinephrine spillover (r = -0.47; P = 0.008), whereas fasting insulin level related to neuronal norepinephrine reuptake (r = -0.35, P = 0.047). These findings demonstrate that progression to T2D is associated with increased central sympathetic drive, blunted sympathetic responsiveness, and altered norepinephrine disposition. [ABSTRACT FROM AUTHOR]

Objective: To provide an update on the ability of different antihypertensive drugs to reduce left ventricular hypertrophy in essential hypertension. [ABSTRACT FROM PUBLISHER]

Background/objectives: Artificial intelligence can assist with ocular image analysis for screening and diagnosis, but it is not yet capable of autonomous full-spectrum screening. Hypothetically, false-positive results may have unrealized screening potential arising from signals persisting despite training and/or ambiguous signals such as from biomarker overlap or high comorbidity. The study aimed to explore the potential to detect clinically useful incidental ocular biomarkers by screening fundus photographs of hypertensive adults using diabetic deep learning algorithms., Subjects/methods: Patients referred for treatment-resistant hypertension were imaged at a hospital unit in Perth, Australia, between 2016 and 2022. The same 45° colour fundus photograph selected for each of the 433 participants imaged was processed by three deep learning algorithms. Two expert retinal specialists graded all false-positive results for diabetic retinopathy in non-diabetic participants., Results: Of the 29 non-diabetic participants misclassified as positive for diabetic retinopathy, 28 (97%) had clinically useful retinal biomarkers. The models designed to screen for fewer diseases captured more incidental disease. All three algorithms showed a positive correlation between severity of hypertensive retinopathy and misclassified diabetic retinopathy., Conclusions: The results suggest that diabetic deep learning models may be responsive to hypertensive and other clinically useful retinal biomarkers within an at-risk, hypertensive cohort. Observing that models trained for fewer diseases captured more incidental pathology increases confidence in signalling hypotheses aligned with using self-supervised learning to develop autonomous comprehensive screening. Meanwhile, non-referable and false-positive outputs of other deep learning screening models could be explored for immediate clinical use in other populations., (© 2024. The Author(s).)

Background: Single-pill combinations of 3 or more low-dose blood pressure (BP)-lowering drugs hold promise for initial or early treatment of hypertension., Objectives: We conducted a placebo-controlled trial of a new single-pill combination containing low doses of telmisartan, amlodipine, and indapamide in 2 dose options to assess efficacy and safety., Methods: This international, randomized, double-blind, placebo-controlled, parallel-group trial enrolled adults with hypertension receiving 0 to 1 BP-lowering drugs. After a 2-week placebo run-in during which any BP-lowering medication was stopped, participants were eligible if home systolic BP (SBP) was 130 to 154 mm Hg. Participants were randomized in a 2:2:1 ratio to GMRx2 ¼ dose (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), GMRx2 ½ dose (telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg), or placebo. The primary efficacy outcome was difference in change in home SBP from randomization to week 4, and primary safety outcome was treatment discontinuation due to an adverse event., Results: From June 14, 2021 to October 18, 2023, a total of 295 participants (mean age: 51 years; 56% female) were randomized and 96% completed the trial. Baseline mean home BP was 139/86 mm Hg and clinic BP was 138/86 mm Hg after placebo run-in. The placebo-corrected least square mean differences in home SBP at Week 4 were -7.3 mm Hg (95% CI: -4.5 to -10.2) for GMRx2 ¼ dose and -8.2 mm Hg (95% CI: -5.2 to -11.3) for GMRx2 ½ dose; reductions for clinic BP were 8.0/4.0 and 9.5/4.9 mm Hg. At Week 4, clinic BP control (<140/90 mm Hg) was 37%, 65%, and 70% for placebo, GMRx2 ¼ dose, and GMRx2 ½ dose, respectively (both doses P < 0.001 vs placebo). Placebo, GMRx2-triple ¼, and GMRx2 ½ treatment discontinuation due to an adverse event occurred in 1 (1.6%), 0, and 6 (5.1%), respectively; out of normal range serum sodium or potassium was observed in 4 (6.3%), 12 (10.6%), and 12 (10.1%), respectively, but no participant had a serum sodium <130/>150 mmol/L or potassium <3.0/>6.0 mmol/L. Serious adverse events were reported by 2 participants in the placebo and GMRx2 ½ groups and none in the GMRx2 ¼ group., Conclusions: In a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo. (Efficacy and Safety of GRMx2 Compared to Placebo for the Treatment of Hypertension: NCT04518306)., Competing Interests: Funding Support and Author Disclosures This trial was funded by George Medicines Pty Ltd (GM). The trial was designed by The Steering Committee, who were responsible for the study protocol. The funder of the study consulted with the U.S. Food and Drug Administration to ensure the trial design was suitable to inform an application for regulatory approval; the funder GM provided comments on a draft of the publication. The Steering Committee had full access to all the data, wrote and had final responsibility for the publication. Prof Rodgers, Dr Salam, Prof Schutte, C. ianacas, M. Shanthakumar, Dr Liu, and Dr Wang are employed at The George Institute for Global Health (TGI), which holds an interest in GM via its social enterprise arm, George Institute Ventures. None of the TGI staff have any personal financial interest in GM. Prof Rodgers is seconded part-time to GM. TGI holds patents for ultra -low-dose fixed-dose combination products for the treatment of hypertension and diabetes, and Prof Rodgers is listed as one of the inventors (granted: U.S. 10,369,156; U.S. 10,799,487; U.S. 10,322,117; U.S. 11,033,544; U.S. 11,478,462; pending: U.S. 17/932,982; U.S. 18/446,268; U.S. 17/ 598,122; U.S. 17/317,614; U.S. 17/527,084; U.S. 17/527,085; U.S. 17/ 527,087). Prof Rodgers does not have a financial interest in these patents. None of the other authors have a financial interest in GM or have received funding for their independent contribution to the GMRx2 program. Dr Schutte has received consulting fees and/or speaker honoraria from Omron Healthcare, Aktiia, Medtronic, Servier, Abbott, Sanofi, Sun Pharmaceuticals, Novartis, and Skylabs; is co-chair of the National Hypertension Taskforce of Australia; is a board member of Hypertension Australia, and Australian Cardiovascular Alliance; and is supported by an investigator grant from the National Health and Medical Research Council of Australia (GNT 2017504). Dr Ojji has received speaker honoraria from Novartis, AstraZeneca, Servier, Swipha, and Boehringer Ingelheim for speaking at educational meetings. Dr Narkiewicz has received speaker and consulting honoraria from Bausch Health, Berlin-Chemie/Menarini, Egis, Gedeon Richter, Gilead, Idorsia, Janssen, Krka, Novo Nordisk, Polpharma, Recordati, Sandoz, Servier, and Zentiva. Dr Schlaich has received consulting fees, and/or travel fees and research support from Medtronic, Abbott, ReCor, Novartis, Servier, Pfizer, and Boehringer Ingelheim; and is the current president of Hypertension Australia and Treasurer of the World Hypertension League. Dr Cushman has received institutional grants from Recor Medical and George Medicines; and has received consulting fees from Alnylam Pharmaceuticals. Dr Poulter has received financial support from several pharmaceutical companies that manufacture BP-lowering agents; has received consultancy fees from Servier and Aktiia; has received consultancy fees for research projects and staff from Servier and Pfizer; has received consultancy fees for arranging and speaking at educational meetings from AstraZeneca, Lri Therapharma, Napi, Servier, Sanofi, Eva Pharma, Pfizer, Emcure India, Dr Reddy's Laboratories, and Zydus; and has received support from the National Institute for Health Research Senior Investigator Awards, Biomedical Research Centre funding, and the British Heart Foundation Research Centre Excellence Award. Dr Wright has received support from NIH, Ohio Department of Medicaid, Agency for Health Care Research and Quality, Medtronic, Inc, and the Northeast Ohio Neighborhood Health Center Community Board of Directors. Dr Grobbee receives funding to his department as part of the EU Horizon Hypermarker project. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A recent call-to-action highlighted that Australia is lagging behind high-income countries regarding hypertension control rates., Methods: We performed a systematic literature search of reports on prevalence, awareness, treatment and control rates since 2010. We also undertook an individual participant data meta-analysis of six population-based studies in the general population from 1980 to 2018 to understand the size of the problem and trajectories over time., Results: The aggregated data showed that after 2010, hypertension prevalence was 31% ]95% confidence interval (CI) 27-34%], and awareness, treatment, and control rates among people with hypertension were 56% (41-71%), 54% (46-62%) and 34% (22-47%), respectively. Since 1980, these figures have shown slight improvement. However, we noted a low availability of quality nationwide randomized databases for Australia., Conclusions: We require critical action to improve the prevention, detection and treatment of hypertension, and highlight the need for large-scale investment in tracking population health in order to produce vital health statistics for the nation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The strong relationship between blood pressure (BP) and age is well known. Limited evidence suggests that a steeper age-BP slope may be associated with an increased risk of adverse outcomes. The May Measurement Month campaign enables an investigation of geographic, socioeconomic, and sex differences in age-BP gradients and their association with public-health outcomes., Methods: Cross-sectional, annual global BP May Measurement Month screening data were analyzed. Average systolic BP and age-related BP slopes across different age groups were calculated to assess regional, socioeconomic, and sex-stratified variations. The association of BP slopes derived from adjusted linear regression models with country-level health metrics was investigated., Results: Age-related systolic BP gradients differed distinctly across global geographic regions, income levels, and between sexes. The steepest age gradients of BP were observed in populations from Africa and Europe. Women had lower BP levels than men at younger ages (20s and 30s) but subsequently experienced more pronounced age-related BP gradients. Geographically divergent age-related BP gradients were significantly associated with major national public health indicators. Globally, steeper age-related BP slopes were associated with poor BP control, increased disability-adjusted life years, and death rates. A steeper population age-BP slope of 1 mm Hg per 10 years was associated with a decrease in life expectancy of 3.3 years in this population (95% CI, -5.1 to -1.4; P =0.0007)., Conclusions: Age-related BP gradients vary considerably across global populations and are associated with variability in BP-related risks and adverse outcomes across regions. Effective public health strategies may require region-specific targeting of adverse BP gradients to improve health outcomes.

May Measurement Month (MMM) is a global and national blood pressure (BP) screening campaign initiated by the International Society of Hypertension to improve awareness of BP worldwide. This study reports on the findings of the MMM21 campaign in Australia. Adult participants (≥18 years) were screened through opportunistic sampling across Australia between 1 May and 30 November 2021. Trained volunteers recorded standardized BP measurements from community volunteer participants along with demographic data, lifestyle factors, comorbidities, and history of COVID-19 infection and vaccination. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg and/or taking antihypertensive medication. Data were collated and analysed centrally using the current MMM protocol and presented after the imputation of missing BP readings. A total of 1307 participants were screened in 2021, comprising 652 (49.9%) females and 654 (50.0%) males with a mean age of 48 years (SD 20.1). Of all 1307 participants, 524 (40.1%) had hypertension. Of participants with hypertension, 65.4% were aware and 59.3% were on antihypertensive medication. Of 311 participants on antihypertensive medication, 54.7% had controlled BP. Of all 524 participants with hypertension, 32.5% had controlled BP. The current 2021 data may indicate some progress in creating BP awareness; however, consecutive Australian data obtained since 2017 demonstrated stagnating treatment, and control rates compared with global rates and those in other high-income countries. Concerted efforts from all stakeholders will be required to further improve BP awareness, treatment, and control rates in Australia., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Conflict of interest: none declared.

Resistant hypertension is characterized by the inability of guideline-recommended triple combination therapy to control blood pressure (BP) to target. It is associated with a significantly increased risk of adverse outcomes. Despite abundant preclinical evidence supporting the critical role of the endothelin pathway in resistant hypertension (RH), clinical implementation of endothelin antagonists for the treatment of hypertension was hindered by various factors. Recently, the novel dual endothelin-receptor antagonist aprocitentan was tested in individuals with resistant hypertension in the PRECISION trial and provided compelling evidence supporting both short and longer-term safety and clinically meaningful and sustained BP lowering efficacy. These findings resulted in the recent regulatory approval of aprocitentan by the FDA. Aprocitentan may be a particularly useful antihypertensive option for individuals with advanced age, chronic kidney disease, and albuminuria.