{"title":"Cardiac Sympathetic Nerve Activity Is Not Elevated in Ovine Hypertensive HFpEF.","authors":"Joshua W-H Chang,Bindu George,Mridula Pachen,Julia Shanks,Rohit Ramchandra","doi":"10.1161/hypertensionaha.125.24884","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.24884","url":null,"abstract":"BACKGROUNDThe sympathetic nervous system is a crucial mediator of cardiovascular variables during exercise. However, its role in heart failure with preserved ejection fraction (HFpEF), where exercise intolerance is a cardinal feature, is poorly understood. Currently, there is scant and no clear evidence of heightened cardiac sympathetic nerve activity (CSNA) in HFpEF, which might explain why β-blockers lack convincing prognostic benefit in this syndrome. Accordingly, we utilized gold standard direct recordings to test the hypothesis that resting levels of CSNA are not elevated in HFpEF. We also tested whether β-blockers in HFpEF cause further impairments in the hemodynamic determinants of exercise capacity.METHODSExperiments were conducted in a conscious large animal (ovine) model of hypertensive HFpEF that exhibits similarly impaired exercise hemodynamics as patients with HFpEF. Direct recordings of CSNA were made in this model and compared with non-HFpEF sheep. In addition, hemodynamic responses to graded treadmill exercise testing were compared before and after β-blocker administration.RESULTSGold standard direct recordings of resting CSNA were not elevated in HFpEF sheep. Inhibition of this activity using a β-blocker further impaired exercise hemodynamics (cardiac output, heart rate and pulmonary capillary wedge pressure) in HFpEF sheep. In addition, non-HFpEF and HFpEF sheep exhibited differential exercise hemodynamic responses to β-blockers.CONCLUSIONSOur data demonstrates that CSNA is not elevated in an ovine model of hypertensive HFpEF and suggests that favorable exercise hemodynamics in HFpEF are reliant upon β-adrenergic activation. Our findings provide a mechanistic rationale for why β-blockers should be avoided in patients with HFpEF.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"17 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HypertensionPub Date : 2025-06-25DOI: 10.1161/hypertensionaha.125.25104
Luigi Marzano,Francesca Zoccatelli,Francesca Pizzolo,Simonetta Friso
{"title":"Adrenalectomy Versus Medical Therapy in Primary Aldosteronism: A Meta-Analysis of Long-Term Cardiac Remodeling and Function: Medical Versus Adrenalectomy Treatment Compared in Hyperaldosteronism (MATCH) Study.","authors":"Luigi Marzano,Francesca Zoccatelli,Francesca Pizzolo,Simonetta Friso","doi":"10.1161/hypertensionaha.125.25104","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25104","url":null,"abstract":"BACKGROUNDPrimary aldosteronism (PA) is a common curable cause of secondary hypertension that significantly increases left ventricular mass (LVM) and predisposes patients to adverse cardiovascular outcomes. Although adrenalectomy and medical therapy with mineralocorticoid receptor antagonists (MRAs) are both used to treat PA, their long-term comparative efficacy in reversing cardiac structural changes remains debated.METHODSWe systematically searched MEDLINE and Embase for prospective and retrospective clinical trials published up to November 22, 2024, with a minimum follow-up of 6 months that reported changes in LVM in patients with PA treated with adrenalectomy or MRAs. Data were independently extracted by 2 reviewers, and risk-of-bias assessments were conducted using standardized tools. The primary outcome was the percentage reduction in indexed LVM; secondary outcomes included changes in cardiac remodeling, and systolic and diastolic function parameters.RESULTSSeventeen studies comprising 1696 patients (49% adrenalectomy, 51% MRA therapy) were analyzed. Adrenalectomy yielded a significantly greater indexed LVM reduction (mean difference, -3.5% [95% CI, -4.9% to -2.2%]; P<0.0001) and a 32% reduction in left ventricular hypertrophy risk ratio, compared with a 19% reduction with MRAs. Meta-regression revealed that shorter hypertension duration predicted greater LVM regression following adrenalectomy, whereas high dietary sodium attenuated MRA effects. In addition, left ventricular ejection fraction improved modestly after adrenalectomy.CONCLUSIONSAdrenalectomy provides superior long-term regression of LVM and left ventricular hypertrophy compared with MRAs in PA, supporting its use as the first-line treatment for unilateral PA. Future research should compare emerging nonsteroidal MRAs and aldosterone synthase inhibitors to further optimize cardiac remodeling outcomes.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"639 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HypertensionPub Date : 2025-06-24DOI: 10.1161/hypertensionaha.125.24751
Asher Y Rosinger,Amanda McGrosky,Hannah Jacobson,Elena Hinz,Srishti Sadhir,Faith Wambua,Tom Otube,Lilian Baker,Alison Sherwood,Tiffany Chrissy-Mbeng,Lauren Broyles,Carey Musumeci,Natalie Meriwether,Nicole Bobbie,Zoë Farrar,Madeleine Todd,Zee Nguyen,Gabriella Berger,Leslie B Ford,David R Braun,Michael D Hunter,Matthew Douglass,William Farquhar,W Larry Kenney,Jeff M Sands,Rosemary Nzunza,Emmanuel Ndiema,Herman Pontzer
{"title":"Drinking Water NaCl Is Associated With Hypertension and Albuminuria: A Panel Study.","authors":"Asher Y Rosinger,Amanda McGrosky,Hannah Jacobson,Elena Hinz,Srishti Sadhir,Faith Wambua,Tom Otube,Lilian Baker,Alison Sherwood,Tiffany Chrissy-Mbeng,Lauren Broyles,Carey Musumeci,Natalie Meriwether,Nicole Bobbie,Zoë Farrar,Madeleine Todd,Zee Nguyen,Gabriella Berger,Leslie B Ford,David R Braun,Michael D Hunter,Matthew Douglass,William Farquhar,W Larry Kenney,Jeff M Sands,Rosemary Nzunza,Emmanuel Ndiema,Herman Pontzer","doi":"10.1161/hypertensionaha.125.24751","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.24751","url":null,"abstract":"BACKGROUNDSalt leaching into freshwater is an emerging global environmental health concern. We tested the associations between drinking water salinity and blood pressure, hypertension, and albuminuria.METHODSWe conducted a 2-year panel study in 2022 and 2023 with 434 observations among 327 Daasanach adults aged >18 years in northern Kenya. Water sources were analyzed for overall salinity and ionic composition (sodium-chloride; calcium, potassium, magnesium). We measured resting blood pressure and classified hypertension stage 1 and stage 2. Urine samples were analyzed for albuminuria (≥30 mg/g albumin-to-creatinine ratio).RESULTSDrinking water salinity was driven by sodium-chloride (mean=162.6 mg/L, SD=77.1), with low concentrations of calcium, potassium, and magnesium (mean=45 mg/L, SD=13.5). Across 2022 and 2023, 40.1% of adults had at least hypertension stage 1, 13.5% had hypertension stage 2, and 42.2% had albuminuria. Using random effects linear and logistic panel regressions fully adjusted for confounders, each 100 mg/L of drinking water sodium-chloride was associated with 4.5 mm Hg (95% CI, 2.4-6.6) and 3.3 mm Hg (95% CI, 2.2-4.5) increases in systolic and diastolic blood pressure, 3.0× the odds of at least hypertension stage 1 (95% CI, 1.49-5.83), 3.6× the odds of hypertension stage 2 (95% CI, 1.93-6.81), and 2.0× the odds of albuminuria (95% CI, 1.28-3.06). Calcium, potassium, and magnesium were unassociated with any outcomes. Hypertension stage 2 (but not hypertension stage 1) was associated with 2.6× (95% CI, 1.19-5.77) the odds of albuminuria.CONCLUSIONSDrinking water sodium-chloride was associated with resting blood pressure, hypertension, and albuminuria in a population with few traditional lifestyle risk factors for chronic disease. Measuring specific salts in water helps untangle associations with hypertension.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"16 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HypertensionPub Date : 2025-06-23DOI: 10.1161/HYPERTENSIONAHA.124.24548
Jie Zhou, Zhenzhen Xu, Dao-Bo Peng, Xiaoting Li, Sheng Chang, Ke Duan, Yating Jiang, Cihang Gu, Xiaojia Peng, Wei-Bing Xie
{"title":"Macrophage-Derived LCN2 Promotes Methamphetamine-Induced Pulmonary Hypertension.","authors":"Jie Zhou, Zhenzhen Xu, Dao-Bo Peng, Xiaoting Li, Sheng Chang, Ke Duan, Yating Jiang, Cihang Gu, Xiaojia Peng, Wei-Bing Xie","doi":"10.1161/HYPERTENSIONAHA.124.24548","DOIUrl":"10.1161/HYPERTENSIONAHA.124.24548","url":null,"abstract":"<p><strong>Background: </strong>Methamphetamine (METH), a novel amphetamine-type psychostimulant, is recognized as a risk factor for pulmonary hypertension (PH). Macrophage activation is a key event in pulmonary vascular remodeling and PH progression, but the specific mechanisms of METH-induced PH (METH-PH) remain unclear.</p><p><strong>Methods: </strong>A METH-PH mouse model was constructed using wild-type and Lipocalin 2 (LCN2) knockout (LCN2<sup>-/-</sup>) mice. The involvement and underlying mechanism of LCN2 in METH-PH formation were explored using a METH-PH mouse model and a coculture system of macrophages and pulmonary artery smooth muscle cells.</p><p><strong>Results: </strong>In this study, LCN2 was identified as a key regulator of perivascular inflammation and pulmonary vascular remodeling in PH. In the METH-PH mouse model, LCN2 expression was elevated in macrophages within lung tissues. Compared with wild-type mice, LCN2<sup>-/-</sup> mice were protected from METH-PH, exhibiting reduced pulmonary vascular remodeling and right ventricular pressure. Mechanistically, LCN2 regulates IL-1β (interleukin-1β) production and secretion through NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation. In pulmonary artery smooth muscle cells, macrophage-derived LCN2 upregulates the expression of SLC7A11 (solute carrier family 7 member 11) and GPX4 (glutathione peroxidase 4), thereby reducing reactive oxygen species production and preventing ferroptosis.</p><p><strong>Conclusions: </strong>Our data revealed a novel mechanism linking LCN2 to macrophages, inflammatory responses, vascular remodeling, and intercellular interactions, indicating that LCN2 could serve as a therapeutic target for METH-induced PH.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HypertensionPub Date : 2025-06-18DOI: 10.1161/hypertensionaha.125.25020
John A Baugh,Paul McLoughlin
{"title":"TGFβ Superfamily in Pulmonary Vascular Disease: The Role of SMAD4.","authors":"John A Baugh,Paul McLoughlin","doi":"10.1161/hypertensionaha.125.25020","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25020","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"3 1","pages":"1192-1194"},"PeriodicalIF":8.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HypertensionPub Date : 2025-06-18DOI: 10.1161/hyp.0000000000000246
Megan M McLaughlin,Neda Ghaffari,Catherine Lee,Malamo E Countouris,Phoebe Ashley,Amanda Schnell Heringer
{"title":"Correction to: Disparities in Postpartum Care After a Hypertensive Disorder of Pregnancy in the United States.","authors":"Megan M McLaughlin,Neda Ghaffari,Catherine Lee,Malamo E Countouris,Phoebe Ashley,Amanda Schnell Heringer","doi":"10.1161/hyp.0000000000000246","DOIUrl":"https://doi.org/10.1161/hyp.0000000000000246","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"44 1","pages":"e141"},"PeriodicalIF":8.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HypertensionPub Date : 2025-06-18DOI: 10.1161/hypertensionaha.124.24394
Christos Chatzakis,Laura A Magee,Renata Castello,Gerardo Miranda,Peter von Dadelszen,Kypros H Nicolaides,Marietta Charakida
{"title":"Vascular Assessment Stratifying Preeclampsia Risk in Overweight/Obese Women.","authors":"Christos Chatzakis,Laura A Magee,Renata Castello,Gerardo Miranda,Peter von Dadelszen,Kypros H Nicolaides,Marietta Charakida","doi":"10.1161/hypertensionaha.124.24394","DOIUrl":"https://doi.org/10.1161/hypertensionaha.124.24394","url":null,"abstract":"BACKGROUNDOverweight and obesity greatly increase the risk of preeclampsia. There is a need to better risk-stratify these women in pregnancy and channel resources to those who can benefit most.METHODSProspective observational study of 11 962 women with singleton pregnancies attending a routine assessment at 35+0 to 36+6 weeks' gestation at King's College Hospital, London, United Kingdom. Women were categorized by their body mass index at 11 to 13 weeks' gestation as normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), or obese (≥30 kg/m2). We recorded maternal demographics, assessed uterine artery pulsatility index and ophthalmic artery peak systolic velocity ratio, and measured carotid-to-femoral pulse-wave velocity. Preeclampsia development was retrieved from medical records. Multivariable logistic regression was undertaken to examine determinants of preeclampsia. Mediation analysis was performed to assess causal relationships.RESULTSIn this cohort, 28.4% were overweight and 17.9% were obese. Preeclampsia developed more often in overweight/obese (versus normal weight) women (6.0% versus 1.7%, respectively; P<0.001); women of Black and South Asian ethnicity were at particularly increased risk (P=0.02 and 0.004, respectively). Determinants of preeclampsia development did not differ by body mass index. Mediation analysis suggested that the effect of overweight/obesity on preeclampsia development may be mediated partly by changes in maternal cardiovascular indices, particularly aortic stiffness (as reflected by carotid-to-femoral pulse-wave velocity, proportion mediated=72.6%).CONCLUSIONSRisk factors for term preeclampsia are largely similar between overweight/obese and normal-weight women, except for Black and South Asian women, who face a particularly high risk within the overweight/obese group. Maternal vascular assessment may serve as a valuable tool for stratifying the risk for term preeclampsia in these populations.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"12 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HypertensionPub Date : 2025-06-18DOI: 10.1161/hyp.0000000000000245
Bonita Falkner,Barbara T Alexander,Anne-Monique Nuyt,Andrew M South,Julie Ingelfinger
{"title":"Correction to: Cardiovascular Health Starts in the Womb.","authors":"Bonita Falkner,Barbara T Alexander,Anne-Monique Nuyt,Andrew M South,Julie Ingelfinger","doi":"10.1161/hyp.0000000000000245","DOIUrl":"https://doi.org/10.1161/hyp.0000000000000245","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"46 1","pages":"e140"},"PeriodicalIF":8.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}