BACKGROUNDPreeclampsia, a life-threatening hypertensive disorder of pregnancy, has been linked to iron dysregulation, though mechanistic insights remain limited.METHODSWe integrated clinical data, a reduced uterine perfusion pressure mouse model, in vitro trophoblast cell experiments, and placental organoids derived from patients with preeclampsia. Iron metabolism was assessed via mass spectrometry, quantitative polymerase chain reaction, Peris' Prussian blue staining and immunohistochemistry. Ferroptosis markers and iron transporters were analyzed. Interventions included the iron chelator deferoxamine, antioxidant MitoQ, ferroptosis inhibitor Fer-1 (ferrostatin-1), and the apoptosis inhibitor Z-VAD.RESULTSPatients with preeclampsia exhibited elevated hemoglobin, ferritin, and serum iron levels from the second trimester, alongside placental iron overload. Single-cell/nucleus RNA sequencing revealed dysregulated iron transporters (TFRC↑, DMT1↑, FPN↓) in preeclampsia trophoblasts. Iron overload induced ferroptosis and apoptosis in trophoblasts, evidenced by increased lipid peroxidation (4HNE↑, Gpx4↓), ROS, Tunnel staining positive and cell death, while suppressing PlGF and progesterone secretion. Both deferoxamine and MitoQ rescued these effects in vitro (similar to Ferr-1) and in preeclampsia-derived organoids. The reduced uterine perfusion pressure model confirmed the preservation of iron dyshomeostasis and ferroptosis in preeclamptic placentas, while oral administration of MitoQ was found to reduce 4-hydroxynonenal and malondialdehyde expression in placenta.CONCLUSIONSOur findings reveal that iron overload and subsequent ferroptosis contribute to placental damage in preeclampsia, suggesting that iron metabolism dysregulation is a critical feature of the disease. This highlights the need to reevaluate iron supplementation protocols in high-risk pregnancies and to consider individualized iron management strategies that balance maternal-fetal iron requirements while minimizing oxidative stress.
{"title":"Iron Overload-Induced Ferroptosis Drives Placental Dysfunction in Preeclampsia.","authors":"Yike Yang,Haoyu Zuo,Xiaojuan Ma,Wei Chen,Mengxing Sun,Qianqian Xiang,Yuan Wei,Yangyu Zhao,Hongbo Qi,Tong Liu","doi":"10.1161/hypertensionaha.125.26344","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.26344","url":null,"abstract":"BACKGROUNDPreeclampsia, a life-threatening hypertensive disorder of pregnancy, has been linked to iron dysregulation, though mechanistic insights remain limited.METHODSWe integrated clinical data, a reduced uterine perfusion pressure mouse model, in vitro trophoblast cell experiments, and placental organoids derived from patients with preeclampsia. Iron metabolism was assessed via mass spectrometry, quantitative polymerase chain reaction, Peris' Prussian blue staining and immunohistochemistry. Ferroptosis markers and iron transporters were analyzed. Interventions included the iron chelator deferoxamine, antioxidant MitoQ, ferroptosis inhibitor Fer-1 (ferrostatin-1), and the apoptosis inhibitor Z-VAD.RESULTSPatients with preeclampsia exhibited elevated hemoglobin, ferritin, and serum iron levels from the second trimester, alongside placental iron overload. Single-cell/nucleus RNA sequencing revealed dysregulated iron transporters (TFRC↑, DMT1↑, FPN↓) in preeclampsia trophoblasts. Iron overload induced ferroptosis and apoptosis in trophoblasts, evidenced by increased lipid peroxidation (4HNE↑, Gpx4↓), ROS, Tunnel staining positive and cell death, while suppressing PlGF and progesterone secretion. Both deferoxamine and MitoQ rescued these effects in vitro (similar to Ferr-1) and in preeclampsia-derived organoids. The reduced uterine perfusion pressure model confirmed the preservation of iron dyshomeostasis and ferroptosis in preeclamptic placentas, while oral administration of MitoQ was found to reduce 4-hydroxynonenal and malondialdehyde expression in placenta.CONCLUSIONSOur findings reveal that iron overload and subsequent ferroptosis contribute to placental damage in preeclampsia, suggesting that iron metabolism dysregulation is a critical feature of the disease. This highlights the need to reevaluate iron supplementation protocols in high-risk pregnancies and to consider individualized iron management strategies that balance maternal-fetal iron requirements while minimizing oxidative stress.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"10 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069977","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}
Pub Date : 2026-01-28DOI: 10.1161/hypertensionaha.125.24344
Laura Mayeda,Nisha Bansal
Hypertension is a highly prevalent and modifiable risk factor, affecting >80% of patients undergoing dialysis. Its pathophysiology is complex and differs from that of the general population, driven by factors such as volume overload, arterial stiffness, overactivation of the sympathetic and renin-angiotensin-aldosterone systems, and endothelial dysfunction. Achieving optimal blood pressure and volume control is central to dialysis care, with significant implications for cardiovascular outcomes and patient quality of life. Despite its importance, evidence guiding hypertension management in this population remains limited. Furthermore, reliable, objective methods to assess extracellular volume are lacking. This review examines current approaches to the assessment and management of hypertension in maintenance hemodialysis, summarizing existing evidence, clinical guidelines, and ongoing challenges in blood pressure and volume control.
{"title":"Hypertension in Patients With End-Stage Kidney Disease Requiring Dialysis: Bridging the Divide Between Evidence and Practice.","authors":"Laura Mayeda,Nisha Bansal","doi":"10.1161/hypertensionaha.125.24344","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.24344","url":null,"abstract":"Hypertension is a highly prevalent and modifiable risk factor, affecting >80% of patients undergoing dialysis. Its pathophysiology is complex and differs from that of the general population, driven by factors such as volume overload, arterial stiffness, overactivation of the sympathetic and renin-angiotensin-aldosterone systems, and endothelial dysfunction. Achieving optimal blood pressure and volume control is central to dialysis care, with significant implications for cardiovascular outcomes and patient quality of life. Despite its importance, evidence guiding hypertension management in this population remains limited. Furthermore, reliable, objective methods to assess extracellular volume are lacking. This review examines current approaches to the assessment and management of hypertension in maintenance hemodialysis, summarizing existing evidence, clinical guidelines, and ongoing challenges in blood pressure and volume control.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"7 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056847","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}
{"title":"From French Gastronomy to Cardiovascular Health: Cutting Salt in the Baguette Has Saved Thousands of Lives in France.","authors":"Clémence Grave,Laure Carcaillon-Bentata,Christophe Bonaldi,Jacques Blacher,Valérie Olié","doi":"10.1161/hypertensionaha.125.25977","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25977","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"288 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044593","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}
Pub Date : 2026-01-26DOI: 10.1161/hypertensionaha.125.25159
Lauren Bandy,Ben Amies-Cull,Madison Luick,Linda J Cobiac,Susan A Jebb,Peter Scarborough
BACKGROUNDExcessive sodium intake is responsible for 3 million deaths a year globally. The UK is one of 64 countries to have a salt reduction program to help reduce the population's sodium intake. It is a voluntary scheme with 108 category-specific salt content targets for the grocery and out-of-home sectors. This study aimed to estimate the potential impact of the 2024 targets on cardiovascular outcomes and health care costs for UK adults.METHODSLong-term health modeling was based on the adult population in England. Changes in salt intake (g/d), whether the targets were met, were estimated using consumption data from the National Diet and Nutrition Survey 2018/19. Impact on ischemic heart disease and stroke, quality-adjusted life years, and health care costs were estimated using PRIMEtime, a proportional multistate life table model.RESULTSIf the salt reduction targets set for 2024 had been met, then salt intake would have reduced from 6.06 g/d (95% CI, 5.18-6.31) to 4.94 g/d (4.73-5.15), a reduction of 1.12 g/d (1.05-1.20). This would lead to 103 000 (UI, 41 000-161 000) fewer cases of ischemic heart disease and 25 000 (10 000-39 000) fewer cases of stroke over 20 years. A modeled 243 000 (94 000-383 000) quality-adjusted life years would be saved with a net saving of £1.00 billion (£0.35-1.73 billion) to the National Health Service over the remaining lifetime of the adult population.CONCLUSIONSReformulation of products to meet the targets could result in substantial reductions in cardiovascular disease without changes in dietary behaviors. Policymakers should consider options to strengthen salt reduction policies, including effective systems for monitoring and enforcement.
{"title":"Estimating the Potential Impact of the 2024 UK Salt Reduction Targets on Cardiovascular Health Outcomes and Health Care Costs in Adults: A Modeling Study.","authors":"Lauren Bandy,Ben Amies-Cull,Madison Luick,Linda J Cobiac,Susan A Jebb,Peter Scarborough","doi":"10.1161/hypertensionaha.125.25159","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25159","url":null,"abstract":"BACKGROUNDExcessive sodium intake is responsible for 3 million deaths a year globally. The UK is one of 64 countries to have a salt reduction program to help reduce the population's sodium intake. It is a voluntary scheme with 108 category-specific salt content targets for the grocery and out-of-home sectors. This study aimed to estimate the potential impact of the 2024 targets on cardiovascular outcomes and health care costs for UK adults.METHODSLong-term health modeling was based on the adult population in England. Changes in salt intake (g/d), whether the targets were met, were estimated using consumption data from the National Diet and Nutrition Survey 2018/19. Impact on ischemic heart disease and stroke, quality-adjusted life years, and health care costs were estimated using PRIMEtime, a proportional multistate life table model.RESULTSIf the salt reduction targets set for 2024 had been met, then salt intake would have reduced from 6.06 g/d (95% CI, 5.18-6.31) to 4.94 g/d (4.73-5.15), a reduction of 1.12 g/d (1.05-1.20). This would lead to 103 000 (UI, 41 000-161 000) fewer cases of ischemic heart disease and 25 000 (10 000-39 000) fewer cases of stroke over 20 years. A modeled 243 000 (94 000-383 000) quality-adjusted life years would be saved with a net saving of £1.00 billion (£0.35-1.73 billion) to the National Health Service over the remaining lifetime of the adult population.CONCLUSIONSReformulation of products to meet the targets could result in substantial reductions in cardiovascular disease without changes in dietary behaviors. Policymakers should consider options to strengthen salt reduction policies, including effective systems for monitoring and enforcement.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"40 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044591","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}
Pub Date : 2026-01-26DOI: 10.1161/hypertensionaha.125.26008
Alexander A Leung,Raj S Padwal,Gregory L Hundemer,Erik Venos,David J T Campbell,Daniel T Holmes,Dennis J Orton,C Benny So,Stefan J Przybojewski,Cori E Caughlin,Janice L Pasieka,Doreen M Rabi,Gregory A Kline
BACKGROUNDConfirmatory testing to identify lateralizing primary aldosteronism (PA) is of uncertain benefit.METHODSBlinded clinical trial where patients with high-risk features for PA underwent the seated saline suppression test (SSST). All patients received adrenal vein sampling, where lateralization was defined by an aldosterone/cortisol ratio ≥3:1 comparing the dominant versus the nondominant sides. The primary outcome was the overall diagnostic accuracy of the SSST in identifying lateralizing PA using postinfusion aldosterone concentrations of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL) with immunoassay, and ≥162 pmol/L (5.8 ng/dL) with liquid chromatography/tandem mass spectrometry.RESULTSA total of 160 patients completed the trial. Lateralizing PA was diagnosed in 98 patients (61.3%). The overall diagnostic accuracy of the SSST using an aldosterone cutoff of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL) was 64.4% (95% CI, 56.4-71.8) and 67.5% (95% CI, 59.7-74.7), respectively. A positive result was equivocal at the lower cutoff of ≥140 pmol/L (5.0 ng/dL; positive likelihood ratio, 1.1 [95% CI, 1.0-1.3]) and minimally informative at the higher cutoff of ≥280 pmol/L (10.1 ng/dL; positive likelihood ratio, 1.9 [95% CI, 1.3-2.7]). Negative results modestly ruled against lateralization using cutoffs of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL; negative likelihood ratio, 0.3 [95% CI, 0.1-0.9]; and 0.5 [95% CI, 0.3-0.7], respectively). The SSST properties were similar with liquid chromatography/tandem mass spectrometry.CONCLUSIONSAldosterone suppression testing is unreliable for anticipating adrenal vein sampling outcomes. The SSST may misinform diagnostic-treatment decisions.REGISTRATIONURL: https://www.clinicaltrials.gov; Unique identifier: NCT04422756.
{"title":"Seated Saline Suppression Test for Lateralizing Primary Aldosteronism.","authors":"Alexander A Leung,Raj S Padwal,Gregory L Hundemer,Erik Venos,David J T Campbell,Daniel T Holmes,Dennis J Orton,C Benny So,Stefan J Przybojewski,Cori E Caughlin,Janice L Pasieka,Doreen M Rabi,Gregory A Kline","doi":"10.1161/hypertensionaha.125.26008","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.26008","url":null,"abstract":"BACKGROUNDConfirmatory testing to identify lateralizing primary aldosteronism (PA) is of uncertain benefit.METHODSBlinded clinical trial where patients with high-risk features for PA underwent the seated saline suppression test (SSST). All patients received adrenal vein sampling, where lateralization was defined by an aldosterone/cortisol ratio ≥3:1 comparing the dominant versus the nondominant sides. The primary outcome was the overall diagnostic accuracy of the SSST in identifying lateralizing PA using postinfusion aldosterone concentrations of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL) with immunoassay, and ≥162 pmol/L (5.8 ng/dL) with liquid chromatography/tandem mass spectrometry.RESULTSA total of 160 patients completed the trial. Lateralizing PA was diagnosed in 98 patients (61.3%). The overall diagnostic accuracy of the SSST using an aldosterone cutoff of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL) was 64.4% (95% CI, 56.4-71.8) and 67.5% (95% CI, 59.7-74.7), respectively. A positive result was equivocal at the lower cutoff of ≥140 pmol/L (5.0 ng/dL; positive likelihood ratio, 1.1 [95% CI, 1.0-1.3]) and minimally informative at the higher cutoff of ≥280 pmol/L (10.1 ng/dL; positive likelihood ratio, 1.9 [95% CI, 1.3-2.7]). Negative results modestly ruled against lateralization using cutoffs of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL; negative likelihood ratio, 0.3 [95% CI, 0.1-0.9]; and 0.5 [95% CI, 0.3-0.7], respectively). The SSST properties were similar with liquid chromatography/tandem mass spectrometry.CONCLUSIONSAldosterone suppression testing is unreliable for anticipating adrenal vein sampling outcomes. The SSST may misinform diagnostic-treatment decisions.REGISTRATIONURL: https://www.clinicaltrials.gov; Unique identifier: NCT04422756.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"217 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044595","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}
BACKGROUNDFinerenone is a novel nonsteroidal mineralocorticoid receptor antagonist. However, robust evidence about its efficacy and safety in primary aldosteronism is scarce.METHODSIn this prospective, multicenter, single-arm, and exploratory trial, we enrolled adults (aged ≤75 years) with primary aldosteronism, an office blood pressure (BP) ranging from 140 to 180/90 to 120 mm Hg, and an estimated glomerular filtration rate ≥60 mL/min per 1.73 m². Eligible patients received finerenone (20-40 mg/d) treatment for 12 weeks. The primary outcome was the change in daytime systolic BP at 12 weeks.RESULTSFifty-seven patients were ultimately treated. Per-protocol analysis revealed that finerenone treatment significantly reduced mean daytime systolic BP (-6.69±1.60 mm Hg; P<0.001) and diastolic BP (-4.55±1.06 mm Hg; P<0.001) according to ambulatory monitoring. Mean office BP decreased even more substantially (systolic BP, -15.58±1.69 mm Hg; diastolic BP, -8.61±1.02 mm Hg; both P<0.001). The mean increase in serum potassium concentration was 0.39±0.05 mmol/L, and 94.5% of patients exhibited a normal concentration after 12 weeks of treatment (versus baseline 61.8%; P<0.001). Plasma renin activity increased, and 32.7% of patients exhibited a plasma renin activity concentration ≥1 ng/mL per h. According to the Primary Aldosteronism Medical Treatment Outcome criteria, 29.1% and 20.0% of patients achieved complete biochemical and clinical responses, respectively. Treatment was well tolerated.CONCLUSIONSThis study demonstrated the efficacy and safety of finerenone in the treatment of primary aldosteronism, supporting its use as a potential alternative therapy for the condition. Nevertheless, further prospective and head-to-head randomized controlled trials are essential to establish finerenone as a viable substitute for spironolactone.REGISTRATIONURL: https://www.clinicaltrials.gov; Unique identifier: NCT06381323.
芬烯酮是一种新型的非甾体类矿物皮质激素受体拮抗剂。然而，关于其在原发性醛固酮增多症中的有效性和安全性的有力证据很少。方法在这项前瞻性、多中心、单臂、探索性试验中，我们招募了原发性醛固酮增多症的成年人（年龄≤75岁），血压（BP）范围为140 ~ 180/90 ~ 120 mm Hg，肾小球滤过率≥60 mL/min / 1.73 m²。符合条件的患者接受芬尼酮（20- 40mg /d）治疗，为期12周。主要终点是12周时白天收缩压的变化。结果57例患者最终得到治疗。按方案分析显示，根据动态监测，芬尼酮治疗可显著降低平均日间收缩压（-6.69±1.60 mm Hg， P<0.001）和舒张压（-4.55±1.06 mm Hg， P<0.001）。平均办公室血压下降幅度更大（收缩压，-15.58±1.69 mm Hg；舒张压，-8.61±1.02 mm Hg， P均<0.001）。血清钾浓度平均升高0.39±0.05 mmol/L，治疗12周后94.5%的患者血清钾浓度恢复正常（与基线61.8%相比，P<0.001）。血浆肾素活性升高，32.7%的患者血浆肾素活性浓度≥1 ng/mL / h。根据原发性醛固酮增多症医学治疗结局标准，29.1%和20.0%的患者分别获得完全的生化和临床反应。治疗耐受性良好。结论：本研究证实了芬烯酮治疗原发性醛固酮增多症的有效性和安全性，支持其作为原发性醛固酮增多症的潜在替代疗法。然而，进一步的前瞻性和头对头随机对照试验是必要的，以确定芬烯酮作为螺内酯的可行替代品。REGISTRATIONURL: https://www.clinicaltrials.gov;唯一标识符：NCT06381323。
{"title":"Efficacy and Safety of Finerenone in Patients With Primary Aldosteronism: A Multicenter Prospective Study.","authors":"Ping Li,Fan Yang,Yuxing Lou,Ziwei Zhang,Yunfeng Du,Jie Zhang,Yan Ren,Anli Tong,Zuoling Xie,Bimin Shi,Jianping Liu,Libin Liu,Dalong Zhu","doi":"10.1161/hypertensionaha.125.26048","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.26048","url":null,"abstract":"BACKGROUNDFinerenone is a novel nonsteroidal mineralocorticoid receptor antagonist. However, robust evidence about its efficacy and safety in primary aldosteronism is scarce.METHODSIn this prospective, multicenter, single-arm, and exploratory trial, we enrolled adults (aged ≤75 years) with primary aldosteronism, an office blood pressure (BP) ranging from 140 to 180/90 to 120 mm Hg, and an estimated glomerular filtration rate ≥60 mL/min per 1.73 m². Eligible patients received finerenone (20-40 mg/d) treatment for 12 weeks. The primary outcome was the change in daytime systolic BP at 12 weeks.RESULTSFifty-seven patients were ultimately treated. Per-protocol analysis revealed that finerenone treatment significantly reduced mean daytime systolic BP (-6.69±1.60 mm Hg; P<0.001) and diastolic BP (-4.55±1.06 mm Hg; P<0.001) according to ambulatory monitoring. Mean office BP decreased even more substantially (systolic BP, -15.58±1.69 mm Hg; diastolic BP, -8.61±1.02 mm Hg; both P<0.001). The mean increase in serum potassium concentration was 0.39±0.05 mmol/L, and 94.5% of patients exhibited a normal concentration after 12 weeks of treatment (versus baseline 61.8%; P<0.001). Plasma renin activity increased, and 32.7% of patients exhibited a plasma renin activity concentration ≥1 ng/mL per h. According to the Primary Aldosteronism Medical Treatment Outcome criteria, 29.1% and 20.0% of patients achieved complete biochemical and clinical responses, respectively. Treatment was well tolerated.CONCLUSIONSThis study demonstrated the efficacy and safety of finerenone in the treatment of primary aldosteronism, supporting its use as a potential alternative therapy for the condition. Nevertheless, further prospective and head-to-head randomized controlled trials are essential to establish finerenone as a viable substitute for spironolactone.REGISTRATIONURL: https://www.clinicaltrials.gov; Unique identifier: NCT06381323.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"151 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015006","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}
Pub Date : 2026-01-22DOI: 10.1161/hypertensionaha.125.25199
Takeshi Fujiwara,Satoshi Hoshide,Kazuomi Kario
BACKGROUNDNocturnal blood pressure (BP) is a better predictor of health outcomes than office or daytime BP. However, the clinical significance of nocturnal hypertension in patients of very advanced age remains unexplored. We aimed to assess the association between nocturnal hypertension and composite cardiovascular outcomes in this population.METHODSThis was a prospective observational study including Japanese elderly outpatients aged ≥80 years. All patients underwent 24-hour ambulatory BP monitoring at baseline. Nocturnal hypertension was defined as nocturnal systolic BP ≥120 mm Hg and diastolic BP≥70 mm Hg. Daytime hypertension was defined as daytime systolic BP ≥135 mm Hg and diastolic BP ≥85 mm Hg. The association between those BP phenotypes and composite cardiovascular outcomes (including fatal and nonfatal cardiovascular disease and all-cause mortality) was examined using Cox regression analysis.RESULTSA total of 485 patients were followed for a median of 3.9 years (1734 person-years), during which 72 (14.8%) composite cardiovascular outcomes occurred. The median age (interquartile range) was 82 (81-85) years; 44.7% were male; and 89.3% took antihypertensive medications. Nocturnal hypertension and daytime hypertension were present in 54.2% and 33.6% of patients, respectively. Relative to nocturnal normotension (nocturnal systolic BP <120 mm Hg and diastolic BP <70 mm Hg), nocturnal hypertension was associated with an increased risk of composite cardiovascular outcomes, even after adjustment for daytime BP values (adjusted hazard ratio, 2.15 [95% CI, 1.18-3.93]). Daytime hypertension showed no such association.CONCLUSIONSScreening for nocturnal hypertension identifies a high-risk group for composite cardiovascular outcomes among patients of very advanced age.
背景：夜间血压（BP）比办公室或白天血压更能预测健康状况。然而，夜间高血压在高龄患者中的临床意义尚不清楚。我们的目的是评估该人群夜间高血压与复合心血管结局之间的关系。方法本研究为前瞻性观察性研究，纳入年龄≥80岁的日本老年门诊患者。所有患者均在基线时进行24小时动态血压监测。夜间高血压定义为夜间收缩压≥120 mm Hg和舒张压≥70 mm Hg。白天高血压定义为白天收缩压≥135 mm Hg和舒张压≥85 mm Hg。这些BP表型与复合心血管结局（包括致死性和非致死性心血管疾病以及全因死亡率）之间的关联使用Cox回归分析进行检验。结果485例患者随访时间中位数为3.9年（1734人年），其中72例（14.8%）发生心血管复合结局。年龄中位数（四分位数间距）为82（81-85）岁；44.7%为男性；89.3%的人服用抗高血压药物。夜间高血压和日间高血压分别占54.2%和33.6%。相对于夜间血压正常（夜间收缩压<120 mm Hg和舒张压<70 mm Hg），夜间高血压与复合心血管结局的风险增加相关，即使在调整了白天血压值之后也是如此（调整后的危险比为2.15 [95% CI, 1.18-3.93]）。日间高血压则没有这种关联。结论：夜间高血压筛查确定了高龄患者复合心血管结局的高危人群。
{"title":"Nocturnal Hypertension and Prognosis in Patients of Very Advanced Age.","authors":"Takeshi Fujiwara,Satoshi Hoshide,Kazuomi Kario","doi":"10.1161/hypertensionaha.125.25199","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25199","url":null,"abstract":"BACKGROUNDNocturnal blood pressure (BP) is a better predictor of health outcomes than office or daytime BP. However, the clinical significance of nocturnal hypertension in patients of very advanced age remains unexplored. We aimed to assess the association between nocturnal hypertension and composite cardiovascular outcomes in this population.METHODSThis was a prospective observational study including Japanese elderly outpatients aged ≥80 years. All patients underwent 24-hour ambulatory BP monitoring at baseline. Nocturnal hypertension was defined as nocturnal systolic BP ≥120 mm Hg and diastolic BP≥70 mm Hg. Daytime hypertension was defined as daytime systolic BP ≥135 mm Hg and diastolic BP ≥85 mm Hg. The association between those BP phenotypes and composite cardiovascular outcomes (including fatal and nonfatal cardiovascular disease and all-cause mortality) was examined using Cox regression analysis.RESULTSA total of 485 patients were followed for a median of 3.9 years (1734 person-years), during which 72 (14.8%) composite cardiovascular outcomes occurred. The median age (interquartile range) was 82 (81-85) years; 44.7% were male; and 89.3% took antihypertensive medications. Nocturnal hypertension and daytime hypertension were present in 54.2% and 33.6% of patients, respectively. Relative to nocturnal normotension (nocturnal systolic BP <120 mm Hg and diastolic BP <70 mm Hg), nocturnal hypertension was associated with an increased risk of composite cardiovascular outcomes, even after adjustment for daytime BP values (adjusted hazard ratio, 2.15 [95% CI, 1.18-3.93]). Daytime hypertension showed no such association.CONCLUSIONSScreening for nocturnal hypertension identifies a high-risk group for composite cardiovascular outcomes among patients of very advanced age.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"85 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015008","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}
BACKGROUNDChronic thromboembolic pulmonary hypertension is characterized by proximal pulmonary artery obstruction and distal microvasculopathy. However, the mechanisms driving this dual-compartment pulmonary vascular remodeling remain unclear.METHODSMale Sprague-Dawley rats were injected with gelatin sponge combined with SU5416 as a secondary insult. Hemodynamics, echocardiography, and pulmonary vascular remodeling were evaluated to investigate the development of chronic thromboembolic pulmonary hypertension. Single-cell RNA sequencing of rat lung tissue was conducted to elucidate the molecular mechanisms underlying pulmonary vascular remodeling. The results were validated by immunofluorescence and cell-based experiments.RESULTSThe optimal size range of gelatin sponge for large pulmonary artery obstruction was 710 to 1000 µm, which synergized with a low dose of SU5416 (10 mg/kg) to induce significant increases in right ventricular systolic pressure and right ventricular hypertrophy at 5 weeks. The model exhibited persistent elastic pulmonary artery obstruction and remodeling, along with significant wall thickening and muscularization of pulmonary microvessels. Single-cell transcriptomic analysis revealed a significant reduction in microvascular endothelial cells and an increase in smooth muscle cells in the chronic thromboembolic pulmonary hypertension rats. STAT3, EGR1, and HIF1A were identified as key genes driving aberrant smooth muscle cell proliferation. The Sell-Podxl ligand-receptor pair was found specifically in diseased rats and mediated immune cell-endothelial cell interactions. L-selectin promoted neutrophil adhesion and dysfunction in pulmonary arterial and microvascular endothelial cells, both of which were reversed by PODXL knockdown.CONCLUSIONSOur new model recapitulates human chronic thromboembolic pulmonary hypertension pathophysiology and is useful for understanding pulmonary microvasculopathy. Sell-Podxl is a previously unrecognized link between inflammation and vascular remodeling, offering a potential therapeutic target.
{"title":"Development and Characterization of a Novel Chronic Thromboembolic Pulmonary Hypertension Rat Model: Identifying Sell-Podxl as Potential Regulators.","authors":"Jixiang Liu,Lin Hou,Jie Yang,Zifeng Xu,Hong Zhang,Ximei Niu,Ran Miao,Yufei Hu,Wenyi Pang,Min Liu,Ziyi Chang,Han Tian,Xincheng Li,Lu Sun,Zhu Zhang,Shuai Zhang,Yunxia Zhang,Yu Zhang,Qian Gao,Dingyi Wang,Wanmu Xie,Qiang Huang,Wanlu Song,Peiran Yang,Zhenguo Zhai","doi":"10.1161/hypertensionaha.125.25589","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25589","url":null,"abstract":"BACKGROUNDChronic thromboembolic pulmonary hypertension is characterized by proximal pulmonary artery obstruction and distal microvasculopathy. However, the mechanisms driving this dual-compartment pulmonary vascular remodeling remain unclear.METHODSMale Sprague-Dawley rats were injected with gelatin sponge combined with SU5416 as a secondary insult. Hemodynamics, echocardiography, and pulmonary vascular remodeling were evaluated to investigate the development of chronic thromboembolic pulmonary hypertension. Single-cell RNA sequencing of rat lung tissue was conducted to elucidate the molecular mechanisms underlying pulmonary vascular remodeling. The results were validated by immunofluorescence and cell-based experiments.RESULTSThe optimal size range of gelatin sponge for large pulmonary artery obstruction was 710 to 1000 µm, which synergized with a low dose of SU5416 (10 mg/kg) to induce significant increases in right ventricular systolic pressure and right ventricular hypertrophy at 5 weeks. The model exhibited persistent elastic pulmonary artery obstruction and remodeling, along with significant wall thickening and muscularization of pulmonary microvessels. Single-cell transcriptomic analysis revealed a significant reduction in microvascular endothelial cells and an increase in smooth muscle cells in the chronic thromboembolic pulmonary hypertension rats. STAT3, EGR1, and HIF1A were identified as key genes driving aberrant smooth muscle cell proliferation. The Sell-Podxl ligand-receptor pair was found specifically in diseased rats and mediated immune cell-endothelial cell interactions. L-selectin promoted neutrophil adhesion and dysfunction in pulmonary arterial and microvascular endothelial cells, both of which were reversed by PODXL knockdown.CONCLUSIONSOur new model recapitulates human chronic thromboembolic pulmonary hypertension pathophysiology and is useful for understanding pulmonary microvasculopathy. Sell-Podxl is a previously unrecognized link between inflammation and vascular remodeling, offering a potential therapeutic target.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"62 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015007","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}
Pub Date : 2026-01-22DOI: 10.1161/hypertensionaha.125.25783
Daichi Shimbo,C Barrett Bowling,Kimberly Cannavale,Chloe Fang,Teresa N Harrison,Lei Qian,Paul Muntner,Joseph E Schwartz,John J Sim,Rong Wei,Kristi Reynolds
BACKGROUNDA barrier to intensification of antihypertensive medication among older adults with hypertension is the perceived risk of falls. Blood pressure (BP) measured in the clinic setting is primarily used to decide whether antihypertensive medication should be intensified. Scarce data exist on whether a lower out-of-clinic BP relative to in-clinic BP is associated with an increased risk of falls among older adults with hypertension.METHODSThe sample included 630 participants, enrolled from May 2019 to November 2022 from Kaiser Permanente Southern California, who were aged ≥65 years, had hypertension, were taking antihypertensive medication, and had not experienced a serious fall injury since their last clinic visit. The primary exposure was quartiles (Qs) of the difference between clinic systolic BP from the electronic health record and awake systolic BP on ambulatory BP monitoring. The primary outcome was time to the first fall, determined using monthly falls calendars over 12 months of follow-up.RESULTSThe mean age (SD) was 74.6 (6.2) years with 56.5% female. During follow-up, 240 (38.1%) of the 630 participants fell. After adjusting for demographics, clinical characteristics, and geriatric measures, participants in Q4 (7.2-47.7 mm Hg) versus Q1-Q3 (-56.7 to <7.2 mm Hg) of clinic systolic BP from the electronic health record and awake systolic BP did not have an increased fall risk: adjusted hazard ratio, 0.79 (95% CI, 0.57-1.09).CONCLUSIONSThere was no evidence of an association of a lower awake systolic BP on ambulatory BP monitoring relative to clinic systolic BP with an increased risk of falls.
{"title":"Association of Clinic Blood Pressure and Out-of-Clinic Blood Pressure Difference With Falls Among Older Adults With Hypertension.","authors":"Daichi Shimbo,C Barrett Bowling,Kimberly Cannavale,Chloe Fang,Teresa N Harrison,Lei Qian,Paul Muntner,Joseph E Schwartz,John J Sim,Rong Wei,Kristi Reynolds","doi":"10.1161/hypertensionaha.125.25783","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25783","url":null,"abstract":"BACKGROUNDA barrier to intensification of antihypertensive medication among older adults with hypertension is the perceived risk of falls. Blood pressure (BP) measured in the clinic setting is primarily used to decide whether antihypertensive medication should be intensified. Scarce data exist on whether a lower out-of-clinic BP relative to in-clinic BP is associated with an increased risk of falls among older adults with hypertension.METHODSThe sample included 630 participants, enrolled from May 2019 to November 2022 from Kaiser Permanente Southern California, who were aged ≥65 years, had hypertension, were taking antihypertensive medication, and had not experienced a serious fall injury since their last clinic visit. The primary exposure was quartiles (Qs) of the difference between clinic systolic BP from the electronic health record and awake systolic BP on ambulatory BP monitoring. The primary outcome was time to the first fall, determined using monthly falls calendars over 12 months of follow-up.RESULTSThe mean age (SD) was 74.6 (6.2) years with 56.5% female. During follow-up, 240 (38.1%) of the 630 participants fell. After adjusting for demographics, clinical characteristics, and geriatric measures, participants in Q4 (7.2-47.7 mm Hg) versus Q1-Q3 (-56.7 to <7.2 mm Hg) of clinic systolic BP from the electronic health record and awake systolic BP did not have an increased fall risk: adjusted hazard ratio, 0.79 (95% CI, 0.57-1.09).CONCLUSIONSThere was no evidence of an association of a lower awake systolic BP on ambulatory BP monitoring relative to clinic systolic BP with an increased risk of falls.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"29 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015117","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}
Pub Date : 2026-01-22DOI: 10.1161/hypertensionaha.125.25739
Tsukasa Iwakura,Kengo Kidokoro,Rie Tatsugawa,Akira Hirano,Eriko Kajimoto,Masanobu Takasu,Masafumi Wada,Yoshihisa Wada,Hiroyuki Kadoya,Seiji Kishi,Hajime Nagasu,David Z I Cherney,Tamaki Sasaki,Naoki Kashihara
BACKGROUNDRecent studies have confirmed the protective effects of nonsteroidal MR (mineralocorticoid receptor) antagonists in diabetic kidney disease. However, the physiological mechanisms underlying their albuminuria-reducing effects remain incompletely defined. We hypothesized that inhibition of the MR could protect podocytes by limiting excessive calcium influx via TRPC (transient receptor potential canonical) 5, thereby reducing albuminuria.METHODSWe evaluated the effects of the nonsteroidal MR antagonist finerenone on albuminuria, podocyte morphology, and glomerular function in diabetic mice. Reactive oxygen species generation and single-nephron glomerular filtration rate were analyzed using in vivo imaging. Cultured podocytes were used to assess MR-TRPC5 signaling through measurements of Sgk1 (serum- and glucocorticoid-regulated kinase 1) and TRPC5 expression, intracellular calcium, and actin cytoskeletal organization.RESULTSFinerenone significantly reduced albuminuria, ameliorated podocyte morphological abnormalities, and decreased glomerular reactive oxygen species production in diabetic mice. In cultured podocytes, aldosterone increased Sgk1 and TRPC5 expression, elevated intracellular calcium, and induced actin reorganization; these changes were attenuated by finerenone and by the AC1903 (TRPC5 inhibitor). Activation of MR-TRPC signaling was associated with increased calcium influx and features of podocyte injury. In vivo imaging further indicated that finerenone was associated with lower single-nephron glomerular filtration rate, consistent with an attenuation of glomerular hyperfiltration.CONCLUSIONSFinerenone is associated with reductions in albuminuria in diabetic kidney disease, together with improvements in podocyte injury indices and glomerular hemodynamics. These benefits may be mediated in part through MR-TRPC5 signaling although additional pathways are likely to contribute.
{"title":"Finerenone Improves Albuminuria via MR-TRPC Signaling in Diabetic Kidney Disease.","authors":"Tsukasa Iwakura,Kengo Kidokoro,Rie Tatsugawa,Akira Hirano,Eriko Kajimoto,Masanobu Takasu,Masafumi Wada,Yoshihisa Wada,Hiroyuki Kadoya,Seiji Kishi,Hajime Nagasu,David Z I Cherney,Tamaki Sasaki,Naoki Kashihara","doi":"10.1161/hypertensionaha.125.25739","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25739","url":null,"abstract":"BACKGROUNDRecent studies have confirmed the protective effects of nonsteroidal MR (mineralocorticoid receptor) antagonists in diabetic kidney disease. However, the physiological mechanisms underlying their albuminuria-reducing effects remain incompletely defined. We hypothesized that inhibition of the MR could protect podocytes by limiting excessive calcium influx via TRPC (transient receptor potential canonical) 5, thereby reducing albuminuria.METHODSWe evaluated the effects of the nonsteroidal MR antagonist finerenone on albuminuria, podocyte morphology, and glomerular function in diabetic mice. Reactive oxygen species generation and single-nephron glomerular filtration rate were analyzed using in vivo imaging. Cultured podocytes were used to assess MR-TRPC5 signaling through measurements of Sgk1 (serum- and glucocorticoid-regulated kinase 1) and TRPC5 expression, intracellular calcium, and actin cytoskeletal organization.RESULTSFinerenone significantly reduced albuminuria, ameliorated podocyte morphological abnormalities, and decreased glomerular reactive oxygen species production in diabetic mice. In cultured podocytes, aldosterone increased Sgk1 and TRPC5 expression, elevated intracellular calcium, and induced actin reorganization; these changes were attenuated by finerenone and by the AC1903 (TRPC5 inhibitor). Activation of MR-TRPC signaling was associated with increased calcium influx and features of podocyte injury. In vivo imaging further indicated that finerenone was associated with lower single-nephron glomerular filtration rate, consistent with an attenuation of glomerular hyperfiltration.CONCLUSIONSFinerenone is associated with reductions in albuminuria in diabetic kidney disease, together with improvements in podocyte injury indices and glomerular hemodynamics. These benefits may be mediated in part through MR-TRPC5 signaling although additional pathways are likely to contribute.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"37 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015100","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}
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