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Intimal hyperplasia (IH) remains a significant clinical problem, causing vascular intervention failure. This study aimed to elucidate whether gangliosides GA2 accumulated in atherosclerotic mouse aortae and plasma promote the development of IH. We identified that GA2 was remarkably accumulated in both artery and plasma of atherosclerotic patients and mice. Injected GA2 exacerbated IH and mainly co-stained with macrophages after mouse carotid arterial injury model. Intracellular GA2 induced pyroptosis accompanying the IL-1α release, which was blocked by caspase-11 knockout. Mechanistically, GA2 directly activated caspase-4 as a new ligand. And then, activated caspase-4/11 combined and cleaved BID, promoting the cytochrome C release to cytoplasm, which derived gasdermin E-medicated pyroptosis through activation of caspase-9-caspase-3 pathway. Mice transplanted with caspase-11 deficient bone marrow or mice with caspase-11 knockdown in macrophages exhibited an improvement of the IH aggravated by GA2. These findings suggest GA2-mediated caspase-4/11 activation drives macrophage pyroptosis, contributing to IH. Our results provide a potential diagnostic and therapeutic target in IH., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Cardiovascular diseases (CVD) continue to be the leading cause of deaths and disability worldwide and the major contributor is hypertension. Despite all the improvements in detecting hypertension together with technological advances and affordable, efficacious and relatively free of adverse effects anti-hypertensive agents, we continue to struggle to prevent the onset of hypertension and to control blood pressure (BP) to acceptable targets. The poor control of hypertension is commonly due to non-adherence to medications. Another reason is the failure to adopt diet and lifestyle changes. Reduction of dietary salt intake is important for lowering BP but the role of potassium intake is also important. Globally the intake of sodium is double that of the recommended 2 gm per day (equivalent to 5 gm of sodium chloride/salt) and half that of the daily recommended intake of potassium of 3500 mg/day, giving a sodium-to-potassium ratio of >1, when ideally it should be <1. Many studies have shown that a higher potassium intake is associated with lower BPs, particularly when coupled concurrently with a lower sodium intake giving a lower sodium to potassium ratio. Most hypertension guidelines, while recommending reduction of salt intake to a set target, do not specifically recommend a target for potassium intake nor potassium supplementation. Here we review the role of potassium and salt substitution with potassium in the management of hypertension. Hence, the focus of dietary changes to lower BP and improve BP control should not be on reduction of salt intake alone but more importantly should include an increase in potassium intake., Competing Interests: Compliance with ethical standards. Conflict of interest: YCC has received Research grants from Pfizer and Omron, Speaker honorarium from Astra-Zeneca, Medtronic, MIMS, Omron, Xepa-Sol, Viatris, Duopharma and Unrestricted educational grants on behalf of HOPE-Asia Network from Viatris and on behalf of the Malaysian Society for World Action on Salt, Sugar and Health (MyWASSH) from Medtronic. FJH is an unpaid member of Action on Salt and World Action on Salt, Sugar and Health (WASSH). All other authors report no potential conflicts of interest in relation to this article., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Whether left ventricular structure and function is associated with sodium dietary intake and renal handling while considering blood pressure (BP) remains unclear. Consecutive untreated patients referred for ambulatory BP monitoring were recruited. Standard echocardiography was performed to measure left ventricular structure and function. Fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa) were calculated as markers of proximal and distal tubular sodium handling, respectively. The 952 participants (51.0% women; mean age, 50.8 years) included 614 (64.5%) ambulatory hypertension and 103 (10.8%) left ventricular hypertrophy. There were significant interactions of urinary sodium excretion with FELi (P ≤ 0.045), but not FDRNa (P ≥ 0.36), in relation to left ventricular posterior wall thickness (LVPW), mass (LVM) and mass index (LVMI), but not functional measurements. Only in tertile 1 of FELi, the multivariate-adjusted regression coefficients for urinary sodium excretion reached statistical significance (P ≤ 0.049), being 0.16 ± 0.05 mm, 4.32 ± 1.48 g, and 1.64 ± 0.83 g/m 2 for LVPW, LVM and LVMI, respectively. In mutually adjusted analyses, the regression coefficient for LVMI was statistically significant for FELi, FDRNa and 24-h systolic BP, being -2.17 ± 0.49, -1.95 ± 0.54, and 2.99 ± 0.51 g/m 2 , respectively (P < 0.001). Multivariable analysis of variance showed that sodium renal handling indexes (P ≥ 0.14), but not sodium urinary excretion (P = 0.007), were similarly as 24-h BP associated with LVMI. Heat maps on left ventricular hypertrophy provided a graphical confirmation of the findings. Sodium dietary intake and renal handling interact to be associated with left ventricular structure. Renal handling indexes were similarly in size as, jointly in action with and independently of 24-h BP., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Aims: β3-Adrenergic receptor (β3-AR) is essential for cardiovascular homoeostasis through regulating adipose tissue function. Perivascular adipose tissue (PVAT) has been implicated in the pathogenesis of aortic dissection and aneurysm (AD/AA). Here, we aim to investigate β3-AR activation-mediated PVAT function in AD/AA., Methods and Results: Aortas from patients with thoracic aortic dissection (TAD) were collected to detect β3-AR expression in PVAT. ApoE-/- and β-aminopropionitrile monofumarate (BAPN)-treated C57BL/6 mice were induced with Angiotensin II (AngII) to simulate AD/AA and subsequently received either placebo or mirabegron, a β3-AR agonist. The results demonstrated an up-regulation of β3-AR in PVAT of TAD patients and AD/AA mice. Moreover, activation of β3-AR by mirabegron significantly prevented AngII-induced AD/AA formation in mice. RNA-sequencing analysis of adipocytes from PVAT revealed a notable increase of the lymphangiogenic factor, vascular endothelial growth factor C (VEGF-C), in mirabegron-treated mice. Consistently, enhanced lymphangiogenesis was found in PVAT with mirabegron treatment. Mechanistically, the number of CD4+/CD8+ T cells and CD11c+ cells was reduced in PVAT but increased in adjacent draining lymph nodes of mirabegron-treated mice, indicating the improved draining and clearance of inflammatory cells in PVAT by lymphangiogenesis. Importantly, adipocyte-specific VEGF-C knockdown by the adeno-associated virus system restrained lymphangiogenesis and exacerbated inflammatory cell infiltration in PVAT, which ultimately abolished the protection of mirabegron on AD/AA. In addition, the conditional medium derived from mirabegron-treated adipocytes activated the proliferation and tube formation of LECs, which was abrogated by the silencing of VEGF-C in adipocytes., Conclusion: Our findings illustrated the therapeutic potential of β3-AR activation by mirabegron on AD/AA, which promoted lymphangiogenesis by increasing adipocyte-derived VEGF-C and, therefore, ameliorated PVAT inflammation., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: In a post-hoc analysis of a multinational, randomized trial, we investigated whether the efficacy and safety of nifedipine gastrointestinal therapeutic system (GITS) and ramipril differed between Chinese and European patients with hypertension., Methods: Previously treated (after 2-week washout) and untreated patients with clinic blood pressure (BP) ≥140/90 mmHg (systolic/diastolic), daytime ambulatory BP ≥135/85 mmHg and standard deviation of home systolic BP >7 mmHg and/or daytime BP >12 mmHg were randomly assigned to treatment based on nifedipine GITS 30 mg or ramipril 10 mg for 12 months. Clinic, ambulatory and home BP were measured at baseline, 10 weeks and 12 months after randomization., Results: A total of 67 Chinese and 101 European patients were analyzed and they differed in age (50.9 vs. 54.6 years, respectively), body mass index (24.5 vs. 27.0 kg/m2), clinic diastolic BP (87.9 vs. 92.5 mmHg), heart rate (75.0 vs. 70.8 beats/minute) and nighttime diastolic BP (79.3 vs. 75.9 mmHg) (all P<0.05). However, within each ethnicity, patients were comparable for clinical characteristics between the nifedipine GITS and ramipril groups (P>0.05). In both the Chinese and European patients, BP was similarly reduced with nifedipine GITS and ramipril, except that daytime systolic/diastolic BP reductions were 7.4/4.1 mmHg greater in the ramipril than nifedipine GITS group in Chinese (P=0.02). The safety profile differed between the Chinese and European patients (P for drug*ethnicity interaction ≤0.05) for all adverse events (lower incidence on nifedipine GITS in Chinese), ankle edema (higher on nifedipine GITS in Europeans) and dry cough (higher on ramipril in Chinese)., Conclusion: In the Chinese and European patients with hypertension, nifedipine GITS and ramipril had similar BP lowering efficacy, but different safety profile and tolerability., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Competing interests: None declared.

Both hypertension and type 2 diabetes are attributable to premature death, cardiovascular and kidney diseases with largely overlapping population. Followed the GRADE approach, this expert consensus aimed to reduce the cardiovascular and kidney death and disability due to hypertension and minimize the treatment burden in adults with type 2 diabetes. Through online survey and discussion, a multidisciplinary team comprehensively prioritized seven key guideline questions. Informed by the evidence synthesis and online discussion, the team developed 12 recommendations under the GRADE Evidence-to-decision (EtD) framework. The recommendations covered the screening of hypertension in adults diagnosed with type 2 diabetes but not hypertension and the monitoring, lifestyle interventions, and medications in those diagnosed with type 2 diabetes and hypertension., (© 2024 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are a new class of agents for the treatment of anemia in chronic kidney disease (CKD). Unlike traditional treatments such as erythropoiesis-stimulating agents (ESAs), HIF-PH inhibitors are orally administered drugs and may increase endogenous erythropoietin and improve iron homeostasis. However, a significant concern is their possible side effect on blood pressure. The current mini-review summarizes the data of 26 randomized controlled (placebo or ESAs) trials on six different HIF-PH inhibitors with regard to their potential influence on blood pressure and hypertension in the management of anemia in CKD. Overall, the use of HIF-PH inhibitors was associated with a higher risk of hypertension than placebo (pooled risk ratio 1.36, 95% confidence interval [CI] 1.16-1.59), but a lower risk of hypertension than ESA treatment (pooled risk ratio 0.92, 95% CI 0.86-0.98), especially in CKD patients not undergoing dialysis (pooled risk ratio 0.85, 95% CI 0.73-0.98). This review highlights the importance of blood pressure monitoring during the treatment of HIF-PH inhibitors, especially out-of-office blood pressure measurement., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Objective: We aimed to evaluate the influences of cardiovascular disease (CVD) on the relationship between baseline systolic blood pressure (SBP) and outcomes in community populations with diabetes., Methods: This is an observational study of 16,431 community adults with diabetes. The relationship between SBP with major adverse cardiovascular event (MACE) and all-cause death were evaluated using multivariable-adjusted Cox proportional hazard models and restricted cubic spline., Results: After a median follow-up of 3.4 (IQR 2.6, 4.3) years, 2145 (13.1 %) MACE and 1025 (6.2 %) all-cause death occurred. In participants free of CVD, in reference to SBP < 120 mmHg group, the risks for MACE increased as SBP category (120-129, 130-139, and ≥ 140 mmHg) advanced (P-trend < 0.001), and there was a linear relationship (P-nonlinear = 0.75). The risks for all-cause death were lower in SBP of 120-139 mmHg and 140-159 mmHg groups but higher in SBP ≥ 160 mmHg group, and there was a U-shaped relationship (P-nonlinear < 0.001). In participants with existing CVD the relationship between baseline SBP with MACE and all-cause death did not show any specific pattern., Conclusion: Results of the current study suggest that the relationship between baseline SBP with MACE and all-cause death varied significantly by baseline CVD status., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hyperuricemia is a common comorbidity of hypertension and probably has a causal relationship with hypertension. Alpha-mangostin (α-MG) has been reported to have uric acid lowering effect. This study aimed to investigate the dual effects of α-MG on blood pressure (BP) and uric acid levels in angiotensin II (Ang II)-infused hypertensive mice. Male C57BL/6 mice were randomized into five groups: control, Ang II infusion (500 ng/kg/min for 2 weeks), Ang II infusion with gavage administration of α-MG 4.0 and 8.0 mg/kg and benzbromarone (25 mg/kg) respectively. BP, uric acid levels, vascular structure and function, and renin-Ang II system expressions in the aorta were assessed. Treatment with α-MG reduced BP, improved endothelial relaxation, and reversed aortic wall thickening and collagen deposition in Ang II-induced hypertensive mice. It also downregulated Ang II receptor 1 (AT1R) and angiotensin converting enzyme (ACE) expression, while upregulating ACE2, Mas receptor (MasR), and angiotensin (1-7) in the aorta. Moreover, α-MG demonstrated a significant enhancement in uric acid clearance and reduction in serum uric acid levels. Conversely, benzbromarone did not result in a decrease in BP, indicating that the hypotensive effect of α-MG may not be necessarily dependent on its urate-lowering properties. α-MG can attenuate Ang II-induced hypertension and reverse vascular remodeling, potentially by balancing the ACE/Ang II/AT1R axis and the ACE2/Ang-(1-7)/MasR axis. Our findings provide insights into α-MG as a novel anti-hypertensive drug especially in patients with hyperuricemia., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Aims: Few randomized trials assessed the changes over time in the chronotropic heart rate (HR) reactivity (CHR), HR recovery (HRR) and exercise endurance (EE) in response to the incremental shuttle walk test (ISWT). We addressed this issue by analysing the open HOMAGE (Heart OMics in Aging) trial., Methods: In HOMAGE, 527 patients prone to heart failure were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current sub-study included 113 controls and 114 patients assigned spironolactone (~70% on beta-blockers), who all completed the ISWT at baseline and at Months 1 and 9. Within-group changes over time (follow-up minus baseline) and between-group differences at each time point (spironolactone minus control) were analysed by repeated measures ANOVA, unadjusted or adjusted for sex, age and body mass index, and additionally for baseline for testing 1 and 9 month data., Results: Irrespective of randomization, the resting HR and CHR did not change from baseline to follow-up, with the exception of a small decrease in the HR immediately post-exercise (-3.11 b.p.m.) in controls at Month 9. In within-group analyses, HR decline over the 5 min post-exercise followed a slightly lower course at the 1 month visit in controls and at the 9 month visits in both groups, but not at the 1 month visit in the spironolactone group. Compared with baseline, EE increased by two to three shuttles at Months 1 and 9 in the spironolactone group but remained unchanged in the control group. In the between-group analyses, irrespective of adjustment, there were no HR differences at any time point from rest up to 5 min post-exercise or in EE. Subgroup analyses by sex or categorized by the medians of age, left ventricular ejection fraction or glomerular filtration rate were confirmatory. Combining baseline and Months 1 and 9 data in both treatment groups, the resting HR, CHR and HRR at 1 and 5 min averaged 61.5, 20.0, 9.07 and 13.8 b.p.m. and EE 48.3 shuttles., Conclusions: Spironolactone on top of usual treatment compared with usual treatment alone did not change resting HR, CHR, HRR and EE in response to ISWT. Beta-blockade might have concealed the effects of spironolactone. The current findings demonstrate that the ISWT, already used in a wide variety of pathological conditions, is a practical instrument to measure symptom-limited exercise capacity in patients prone to developing heart failure because of coronary heart disease., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Hypertension remains the world's leading cause of premature death. Interventions such as exercise, diet modification, and pharmacological therapy remain the mainstay of hypertension treatment. Numerous systematic reviews and meta-analyses demonstrated the effectiveness of western exercises, such as aerobic exercise and resistance exercise, in reducing blood pressure in hypertensive patients. There is recently emerging evidence of blood pressure reduction with Chinese exercises, such as Tai Chi, Baduanjin, and Qigong. The current overview of systematic reviews aims to evaluate the quality and descriptively summarize the evidence for the effectiveness of western and Chinese exercises for hypertension management. Thirty-nine systematic reviews were included in this overview, with 15 of those being on Chinese exercise. Evidence suggests that exercise training, regardless of Western or Chinese exercise, generally reduced both systolic and diastolic blood pressure. High-intensity intermittent training did not further reduce blood pressure when compared to moderate-intensity continuous training. Conflicting results on the effectiveness of blood pressure reduction when comparing Chinese and Western exercise training were observed. This suggests the comparable effectiveness of Chinese exercise training, in particularly Tai Chi, to general or aerobic exercise training in terms of blood pressure reduction. The Chinese exercise modality and intensity may be more suitable for the middle-aged and elderly population., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

For adopting recently introduced hypertension phenotypes categorized using office and out of office blood pressure (BP) for the diagnosis of hypertension and antihypertension drug therapy, it is mandatory to define the corresponding out of office BP with the specific target BP recommended by the major guidelines. Such conditions include white-coat hypertension (WCH), masked hypertension (MH), white-coat uncontrolled hypertension (WUCH), and masked uncontrolled hypertension (MUCH). Here, the authors review the relevant literature and discuss the related issue to facilitate the use of corresponding BPs for proper diagnosis of WCH, MH, WUCH, and MUCH in the setting of standard target BP as well as intensive target BP. The methodology of deriving the corresponding BP has evolved from statistical methods such as standard deviation, percentile value, and regression to an outcome-based approach using pooled international cohort study data and comparative analysis in randomized clinical trials for target BPs such as the SPRINT and STEP studies. Corresponding BPs to 140/90 and 130/80 mm Hg in office BP is important for safe and strict achievement of intensive BP targets. The corresponding home, daytime, and 24-h BPs to 130/80 mm Hg in office BP are 130/80, 130/80, and 125/75 mm Hg, respectively. However, researchers have found some discrepancies among the home corresponding BPs. As tentative criterion for de-escalation of antihypertensive therapy as shown in European guidelines was 120 mm Hg in office BP, corresponding home, daytime, and 24-h systolic BPs to 120 mm Hg in office systolic BP are 120, 120, and 115 mm Hg, respectively., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Hypertension is a leading risk factor for disability and deaths worldwide. Evidence indicates that alpha-mangostin(α-MG) can reduce blood pressure and improve target organ damage. Nonetheless, its pharmacological targets and potential mechanisms of action remain inadequately elucidated., Method: We used SwissTargetPrediction to identify α-MG's drug targets and DisGeNET, GeneCards, CTD, and GEO databases for hypertension-related targets, and then determined antihypertensive therapeutic targets of α-MG by intersecting these targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were conducted using the DAVID database and R package "clusterprofile", visualized with Cytoscape software. The binding affinity of α-MG to identified targets was confirmed through molecular docking using Autodock Vina v.1.2.2 software. The impact of α-MG on target genes was validated using an Angiotensin II-induced hypertensive mouse model and RT-qPCR., Results: A total of 51 potential antihypertensive therapeutic targets for α-MG were identified by intersecting 109 drug targets with 821 disease targets. Furthermore, 10 cellular component terms, 10 disease terms, and the top 20 enriched biological processes, molecular functions, and KEGG pathways related to α-MG's antihypertensive effects were documented. Molecular docking studies indicated a strong binding affinity of α-MG with the HSP90AA1 domain. In Ang II-induced hypertensive mice aorta, treatment with α-MG effectively reversed the aberrant mRNA expression of TNF, HSP90AA1, NFKB1, PPARG, SIRT1, PTGS2, and RELA., Conclusion: Our analyses showed that TNF, HSP90AA1, NFKB1, PPARG, SIRT1, PTGS2, and RELA might be α-MG's potential therapeutic targets for hypertension, laying groundwork for further investigation into its pharmacological mechanisms and clinical uses., Competing Interests: Declarations. Ethical approval and consent to participate: The animal experimental protocols were approved by the Animal Care and Use Committee of Shanghai Jiaotong University (China). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Blacks are more prone to salt-sensitive hypertension than Whites. This cross-sectional analysis of a multi-ethnic cohort aimed to search for proteins potentially involved in the susceptibility to salt sensitivity, hypertension, and hypertension-related complications. The study included individuals enrolled in African Prospective Study on the Early Detection and Identification of Cardiovascular Disease and Hypertension (African-PREDICT), Flemish Study of the Environment, Genes and Health Outcomes (FLEMENGHO), Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers (PROVALID)-Austria, and Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform Trial (UPRIGHT-HTM). Sequenced urinary peptides detectable in 70% of participants allowed the identification of parental proteins and were compared between Blacks and Whites. Of 513 urinary peptides, 300 had significantly different levels among healthy Black (n = 476) and White (n = 483) South Africans sharing the same environment. Analyses contrasting 582 Blacks versus 1731 Whites, and Sub-Saharan Blacks versus European Whites replicated the findings. COL4A1, COL4A2, FGA, PROC, MGP, MYOCD, FYXD2, and UMOD were identified as the most likely candidates underlying the racially different susceptibility to salt sensitivity, hypertension, and related complications. Enriched pathways included hemostasis, platelet activity, collagens, biology of the extracellular matrix, and protein digestion and absorption. Our study suggests that MGP and MYOCD being involved in cardiovascular function, FGA and PROC in coagulation, FYXD2 and UMOD in salt homeostasis, and COL4A1 and COL4A2 as major components of the glomerular basement membrane are among the many proteins potentially incriminated in the higher susceptibility of Blacks compared to Whites to salt sensitivity, hypertension, and its complication. Nevertheless, these eight proteins and their associated pathways deserve further exploration in molecular and human studies as potential targets for intervention to reduce the excess risk of hypertension and cardiovascular complications in Blacks versus Whites., (© 2024 The Author(s). PROTEOMICS published by Wiley‐VCH GmbH.)

Objectives: Greater vulnerability of Black vs. White individuals to cardiovascular disease (CVD) and chronic kidney disease (CKD) is well charted in the United States, but studies involving sub-Saharan blacks are scarce., Methods: Baseline data (2021-2024) were collected in 168 sub-Saharan Blacks and 93 European Whites in an ongoing clinical trial (NCT04299529), using standardized patient selection criteria. Data included clinical and biochemical risk factors, ECG and echocardiographic traits, Framingham CVD risk, CKD grades (KDIGO 2024), self-assessed symptoms (WHO questionnaire), and urinary proteomic profiles predictive of left ventricular dysfunction (LVD) and CKD, HF1, and CKD273, respectively. Racial comparisons rested on unadjusted and multivariable-adjusted analyses., Results: Despite being younger (60.4 vs. 68.3 years), blacks had a worse risk profile, as evidenced by higher diabetes prevalence, higher BMI, faster heart rate, unfavourable serum cholesterol fractions, lower estimated glomerular filtration rate, microalbuminuria, and sedentary lifestyle. This resulted in blacks having higher 10-year CVD risk, higher heart age (index of vascular ageing with chronological age as reference), and a worse CKD grades. In both races, CKD273 increased with CKD grade, but CKD273 and HF1 were not different by race. These observations were robust in subgroup and adjusted analyses., Conclusion: This study did not differentiate host (genetic, molecular, and pathogenic) from environmental drivers of disease. Nonetheless, the findings call for a multipronged and comprehensive implementation of innovative health policies in sub-Saharan countries. Education, research, empowerment of stakeholders, and international learned societies connecting experts from a wide array of disciplines should vigorously sustain this effort., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The aim of this study was to investigate the association of macular microcirculation with renal function and the feasibility of using macular microcirculatory parameters to monitor renal function in Chinese non-diabetic patients with hypertension., Methods: This case-control study included 62 non-diabetic patients with hypertension, including 31 with renal dysfunction (estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m 2 ) and 31 with normal renal function (eGFR ≥90 mL/min/1.73 m 2 ). Age, sex and clinic blood pressure were matched between groups. Macular microcirculatory parameters of 124 eyes of the 62 patients were evaluated by optical coherence tomography (OCT) and OCT angiography (OCTA)., Results: In comparison with the patients with normal renal function, patients with renal dysfunction had lower macular superficial parafovea vessel density (18.6 vs. 19.4%, P = 0.029), macular cube average thickness (273.0 vs. 280.2 µm, P = 0.003), and average ganglion cell layer and inner plexiform layer (GCL-IPL) thickness (79.5 vs. 82.8 µm, P = 0.006), but similar macular central fovea vessel density and central fovea thickness (P ≥ 0.54). After adjustment for confounders, eGFR was significantly associated with macular superficial parafovea vessel density, cube average thickness and GCL-IPL thickness (P < 0.02). In detecting renal dysfunction, areas under the curve were 0.61, 0.66 and 0.65 for macular superficial parafovea vessel density, cube average thickness and GCL-IPL thickness., Conclusion: In non-diabetic patients with hypertension, macular superficial parafovea vessel density, cube average thickness and GCL-IPL thickness were significantly worse in patients with renal dysfunction than those with normal renal function. Using macular parameters to monitor renal function is feasible., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Patients with primary aldosteronism present with renal function decline after unilateral adrenalectomies. Our study aimed to assess the evolution of renal function after adrenalectomy in patients with primary aldosteronism across different age groups and to identify risk factors for postoperative renal function deterioration., Methods: We included 210 patients with primary aldosteronism categorized into three age groups: <40, 40-60, and ≥60 years old. We followed up the patients for 1 month, 1 year, and 5 years after adrenalectomy to assess outcomes. Multivariate analyses were performed to identify predictors of renal function deterioration, and a univariate logistic regression analysis was used to assess the relationship between KCNJ5 mutation status and the decline in renal function., Results: Patients aged <40 years had a shorter duration of hypertension, higher preoperative diastolic blood pressure, and higher preoperative estimated glomerular filtration rate (eGFR) than did those in the other age groups. This group also exhibited the highest rate of complete clinical success, although there were no significant differences in complete biochemical success among age groups. Renal function declined in all three groups after adrenalectomy. However, changes in blood pressure and eGFR in the short- or long-term after adrenalectomy showed no significant differences among the three groups. Hypertension duration, preoperative systolic blood pressure (SBP), and plasma aldosterone concentration (PAC) were predictors of postoperative renal function deterioration. KCNJ5 wild-type status was significantly correlated with the occurrence of chronic kidney disease after adrenalectomy., Conclusions: Unilateral adrenalectomy demonstrates favorable biochemical and clinical outcomes in patients with primary aldosteronism, irrespective of age. Long-term eGFR decline is similar among the different age groups. KCNJ5 mutation exhibits a protective effect against the risk of chronic kidney disease after unilateral adrenalectomy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Tang, Ge, Xu, Gao, Wang and Zhu.)

Blood pressure (BP) is a key contributor to the lifetime risk of preclinical organ damage and cardiovascular disease. Traditional clinic-based BP readings are typically measured infrequently and under standardized/resting conditions and therefore do not capture BP values during normal everyday activity. Therefore, current hypertension guidelines emphasize the importance of incorporating out-of-office BP measurement into strategies for hypertension diagnosis and management. However, conventional home and ambulatory BP monitoring devices use the upper-arm cuff oscillometric method and only provide intermittent BP readings under static conditions or in a limited number of situations. New innovations include technologies for BP estimation based on processing of sensor signals supported by artificial intelligence tools, technologies for remote monitoring, reporting and storage of BP data, and technologies for BP data interpretation and patient interaction designed to improve hypertension management ("digital therapeutics"). The number and volume of data relating to new devices/technologies is increasing rapidly and will continue to grow. This International Society of Hypertension position paper describes the new devices/technologies, presents evidence relating to new BP measurement techniques and related indices, highlights standard for the validation of new devices/technologies, discusses the reliability and utility of novel BP monitoring devices, the association of these metrics with clinical outcomes, and the use of digital therapeutics. It also highlights the challenges and evidence gaps that need to be overcome before these new technologies can be considered as a user-friendly and accurate source of novel BP data to inform clinical hypertension management strategies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

None of the spironolactone trials in heart failure (HF) assessed the blood pressure (BP) responses to exercise, while conflicting results were reported for exercise capacity. In the HOMAGE trial, 527 patients at increased HF risk were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current substudy included 113 controls and 114 patients assigned spironolactone, who all completed the incremental shuttle walk test at baseline and months 1 and 9. Quality of life (QoL) was assessed by EQ5D questionnaire. Between-group differences (spironolactone minus control [Δs]) were analyzed by repeated measures ANOVA with adjustment for baseline and, if appropriate, additionally for sex, age and body mass index. Δs in the pre-exercise systolic/diastolic BP were -8.00 mm Hg (95% CI, -11.6 to -4.43)/-0.85 mm Hg (-2.96 to 1.26) at month 1 and -9.58 mm Hg (-14.0 to -5.19)/-3.84 mm Hg (-6.22 to -1.47) at month 9. Δs in the post-exercise systolic/diastolic BP were -8.08 mm Hg (-14.2 to -2.01)/-2.07 mm Hg (-5.79 to 1.65) and -13.3 mm Hg (-19.9 to -6.75)/-4.62 mm Hg (-8.07 to -1.17), respectively. For completed shuttles, Δs at months 1 and 9 were 2.15 (-0.10 to 4.40) and 2.49 (-0.79 to 5.67), respectively. Δs in QoL were not significant. The correlations between the exercise-induced BP increases and the number of completed shuttles were similar in both groups. In conclusion, in patients at increased risk of developing HF, spironolactone reduced the pre- and post-exercise BP, but did not improve exercise capacity or QoL., (© 2024. The Author(s).)

We investigated the control rate of hypertension across months of year and hours of day in a real-world database. The study participants were hypertensive patients from 142 community health centers across 16 districts in Shanghai, China, who measured their blood pressure with an automatic office blood pressure measurement platform between 2018 and 2023. The 343,400 hypertensive patients included 53.7% of women, and had average age of 70.2 (±8.1) years (range 50-90 years). For months of year, the control rate of hypertension was lowest in February and highest in August (51.9% vs 71.8%). For hours of day, the control rate of hypertension was lowest at 7:00 AM and highest at 12:00 PM (52.1% vs 76.0%). When the months of year and hour of day were considered together, the control rate was lowest at 7 AM in February (42.1%), and highest at 12 PM in July (86.8%). In 8516 patients who had uncontrolled blood pressure in the early morning and had their blood pressure also measured around noon, 45.7% had masked uncontrolled morning hypertension, with higher rates in spring and summer, and in women, those aged 50-69 years, and non-diabetic patients. The control rate of hypertension varies greatly across months of year and hours of day, suggesting that the evaluation of blood pressure control has to take into full consideration the measurement time in terms of months and hours., (© 2024. The Author(s).)

Background: This study aims to compare the differences between unattended and conventional blood pressure measurements in hospitalized hypertensive patients., Methods: In fall of 2019, hypertensive patients at Ruijin Hospital underwent two rounds of unattended and conventional (nurse-monitored) blood pressure measurement. Both rounds used the same electronic blood pressure monitor with measurements taken three times, 30 s apart. Comparison was made using intra-class correlation coefficients, Bland-Altman plots, paired t -tests, etc., Results: Among the 92 subjects in the study, the median age was 50 years old, with women accounting for 33.7%. Among the subjects, the median duration of hypertension was 8.0 years. The prevalence of diabetes, coronary heart disease, and stroke were 26.1%, 5.4%, and 6.5%, respectively. Whether unattended or conventional measurements were taken first, the average blood pressure measured first was slightly higher than the one measured later, but the difference was within 1-2 mmHg. Except that the average DBP during the round of conventional blood pressure measurements was significantly reduced by 1.6 mmHg compared to the conventional DBP, there were no other significant differences. Subgroup analysis by age, gender, BMI, and diabetes showed no significant difference in blood pressure measurement results between unattended and conventional methods., Conclusion: No significant difference was observed between unattended and conventional methods of blood pressure measurement in hospitalized hypertensive patients. Unattended blood pressure measurement can be adopted as the current standard for blood pressure management in hospitalized patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We reported the blood pressure data obtained in the May Measurement Month (MMM) China project in 2020 during the COVID-19 control period. The study participants were adults (≥ 18 years), ideally in whom blood pressure had not been measured in the previous year. Blood pressure was measured three times consecutively with a 1-min interval in the sitting position, using a validated automated BP monitor (Omron HEM-7081IT), and transmitted to a central database via a smartphone app. The measurement was performed at 136 sites across 29 China provinces. The 100 728 participants had a mean (±SD) age of 45.6 (±18.3) years and included 56 097 (55.7%) women. The mean systolic/diastolic blood pressure was 120.0/76.9 mm Hg. The proportion of hypertension was 28.9% (n  =  29 135), and the awareness, treatment, and control rates of hypertension were 45.3% (n = 13 212), 39.7% (n =  1573), and 24.4% (n = 7101), respectively. After adjustment for age, gender, and use of antihypertensive medication, systolic/diastolic BP were significantly higher with cigarette smoking (n = 8070, +0.5/+1.0 mm Hg, p < 0.05), mild (n = 4369, +1.2/+1.3 mm Hg, p < 0.001) and moderate or heavy alcohol drinking (n = 3871, +0.4/+0.7 mm Hg, p < 0.05), and overweight (+1.8/+1.4 mm Hg, p < 0.001) and obesity (+2.3/+1.5 mm Hg, p < 0.001). In conclusion, our study provided unique blood pressure data during the COVID-19 period, and suggested that hypertension management might have been even more challenging when the medical professionals had to shift their focus on other urgencies., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: There is no consensus on optimal time points or systolic blood pressure (SBP) ranges for calculating SBP time in target range (TTR)., Objectives: The purpose of this study was to examine the association between various SBP TTR metrics and long-term major adverse cardiovascular events (MACEs)., Methods: This post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) included participants with complete SBP records and excluded those with events in the initial 2 years. SBP TTR indices were calculated using 3 distinct time points and 3 SBP ranges. The SBP TTR index was the percentage of BP segments within the target SBP ranges. MACE, a composite of heart attack, stroke, heart failure, and cardiovascular death, was the primary outcome., Results: The study included 7,134 participants, of which 280 had a MACE. The median follow-up was 3.91 years. The SBP TTR 110-140 mm Hg in the initial 3 months (3-month TTR 110-140) had the optimal association with incident MACEs (HR per SD increase: 0.898 [95% CI: 0.788-1.022], relative informativeness = 24,398%). Furthermore, a cutoff value of 0.65 for 3-month TTR 110 to 140 index was identified by threshold saturation analysis and used to evaluate early SBP control. No difference in MACE was seen between different mean SBP subgroups in those with good early control (3-month TTR >0.65) ( P  = 0.88), but in those with poor early control (3-month TTR ≤0.65), a higher mean SBP of 130 to 140 mm Hg was related to increased MACEs risk ( P  = 0.019)., Conclusions: In nondiabetic hypertensive patients, the 3-month TTR 110 to 140 mm Hg index was independently associated with 2-year MACEs. A cutoff of TTR index as 0.65 indicated that the patient was within BP target range 65% of the time, combined with mean SBP, could potentially be used as a metric for early control stability and late cardiovascular risks. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062)., Competing Interests: This study was financially supported by the Health Youth Talent Project of Shanghai Municipal Health Commission (2022YQ023), Shanghai Municipal Health Commission Clinical Research Project (Youth, 20214Y0152), the 10.13039/501100001809National Nature Science Foundation of China (82170388, 82370300), Shanghai Technology Research Leader Program (21XD1434700), the cardiac rehabilitation fund by the International Medical Exchange Foundation (Z-2019-42-1908-3), and Grant for the construction of Innovative Flagship Hospital for Integrated Traditional Chinese and Western Medicine (No. ZY (2021-2023)-0205-05). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Mild asymptomatic intracranial atherosclerotic stenosis (aICAS) is common in Chinese patients with hypertension. However, there are no data on its prognostic value in this population. The aim of the present study was to clarify the prevalence and associated cardiovascular risk factors of mild aICAS and determine its prognostic value for overall and cardiovascular mortality in patients with hypertension., Methods: In total, 1,813 participants were evaluated for aICAS using computed tomographic angiography. The predictive effect of mild to severe aICAS on all-cause and cardiovascular mortality was evaluated using Kaplan-Meier survival curves and Cox regression analyses., Results: The prevalence rate of mild aICAS was 35.7%. Poorly controlled hypertension, in combination with diabetes and dyslipidemia, was associated with aICAS. Patients with aICAS had an independently significant increase in the risk of all-cause and cardiovascular death, with adjusted hazard ratios (HRs) for mild to severe stenosis ranging from 1.56 to 3.30 for all-cause death and from 2.48 to 6.38 for cardiovascular death. Among the patients with mild aICAS, only those with more than two stenoses had increased mortality after adjustment, with an HR of 2.44 (95% CI: 1.42-4.18) for total death and 4.49 (95% CI: 1.82-11.05) for cardiovascular death., Conclusions: A significant association between mild aICAS and mortality in stroke-free patients with hypertension was revealed. The results indicate that mild aICAS might be an imaging marker for cerebrovascular lesions in patients with hypertension and poor control of blood pressure and lipids in this population requires further research., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The increasing incidence and high mortality rate of Candida glabrata infection in ICU patients is an important issue. Therefore, it is imperative to investigate the antifungal susceptibility profiles and epidemiological characteristics in local regions., Methods: Herein, antifungal susceptibility testing was conducted to determine the minimum inhibitory concentrations (MICs) of eight antifungal drugs. Multilocus sequence typing (MLST) was used to study the strain genotype, geographical distribution, and susceptibility to antifungal agents among C. glabrata isolates. The mechanism of echinocandin resistance was explored by sequencing the FKS1 and FKS2 genes (encoding 1,3-β-D-glucan synthases) of echinocandin-resistant C. glabrata strains. Moreover, we further investigated the clinical manifestations and the various risk factors of patients infected with C. glabrata in the ICU., Results: We selected 234 C . glabrata isolates from 234 patients in the ICU randomly for the follow-up study. Cross-resistance was found among the ICU C. glabrata isolates. Analysis using MLST showed that the genetic diversity among the C. glabrata isolates was low. Furthermore, sequence type showed no correlation with the antifungal resistance profiles, but was associated with geographical distribution. We also revealed novel mutations in FKS1 (S629P) and FKS2 (W1497stop) that mediated high-level echinocandin resistance (MIC >8 µg/mL). More than 14 days' stay in ICU (P=0.007), Acute Physiology and Chronic Health Evaluation II (APACHE-II) score (P=0.024), prior antifungal exposure (P=0.039) and lung disease (P=0.036) were significantly associated with antifungal resistant/non-wild-type C. glabrata infection., Conclusion: Our study shed light on the antifungal susceptibility, molecular epidemiology, and clinical risk factors of C. glabrata in the ICU of a Chinese Tertiary Hospital. Importantly, we revealed the molecular mechanism of echinocandin resistance. These results highlight the significance of continued surveillance in ICUs and provide data support for the treatment of C. glabrata in clinics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Lv, Song, Zhao, Liu, Wang and Xiang.)

Objectives: To determine the independent effect of high-sensitivity C-reactive protein (hs-CRP) and the combined effects of hs-CRP and other traditional risk factors on microalbuminuria in hypertensive patients during the 3-year follow-up period., Methods and Results: Baseline hs-CRP levels and other risk factors were measured in 280 adults in 2007. In the third year of examination, 199 patients (mean age 62.5 ± 9.5, men 59.3%) were approached for the measurement of microalbuminuria. The subjects were classified into two groups by the median of baseline hs-CRP. Compared to the patients with baseline hs-CRP below the median group ( n  = 99, 50%), the group with baseline hs-CRP above the median ( n  = 100, 50%) had higher urinary albumin-to-creatinine ratio (ACR) ( P  = 0.007) at the end of follow-up period. ACR at the end of follow-up period was significantly correlated with baseline diabetes ( β  = 0.342; P  < 0.001), baseline SBP ( β  = 0.148; P  = 0.02), and baseline log-transformed hs-CRP ( β  = 0.169; P  = 0.01), while adversely correlated with baseline estimated glomerular filtration rate (eGFR) ( β  = -0.163; P  = 0.02) in multivariate stepwise linear analysis. In addition, ACR change during follow-up period was significantly correlated with baseline diabetes ( β  = 0.359; P  < 0.001) and baseline log-transformed hs-CRP ( β  = 0.190; P  = 0.004) in multivariate stepwise linear analysis. The combined effects of baseline hs-CRP and conventional risk factors, such as male sex, diabetes, smoking status, hyperlipidemia, hyperuricemia, and mildly reduced eGFR had a greater risk for microalbuminuria progression. There was no difference in eGFR changes during the follow-up period between two groups., Conclusion: Our findings offer a new piece of evidence on the predictive value of baseline hs-CRP for microalbuminuria progression in essential hypertensive patients, and highlight those who combined with traditional cardiovascular risk factors had a greater risk for developing microalbuminuria., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)