Pub Date : 2024-09-01Epub Date: 2024-07-05DOI: 10.1161/HYPERTENSIONAHA.124.23001
Hiten D Mistry, Rahel Klossner, Paula J Scaife, Nicole Eisele, Lesia O Kurlak, Sampada Kallol, Christiane Albrecht, Carine Gennari-Moser, Louise V Briggs, Fiona Broughton Pipkin, Markus G Mohaupt
Background: Evidence suggests that increasing salt intake in pregnancy lowers blood pressure, protecting against preeclampsia. We hypothesized that sodium (Na+) evokes beneficial placental signals that are disrupted in preeclampsia.
Methods: Blood and urine were collected from nonpregnant women of reproductive age (n=26) and pregnant women with (n=50) and without (n=55) preeclampsia, along with placental biopsies. Human trophoblast cell lines and primary human trophoblasts were cultured with varying Na+ concentrations.
Results: Women with preeclampsia had reduced placental and urinary Na+ concentrations, yet increased urinary angiotensinogen and reduced active renin, aldosterone concentrations, and osmotic response signal TonEBP (tonicity-responsive enhancer binding protein) expression. In trophoblast cell cultures, TonEBP was consistently increased upon augmented Na+ exposure. Mechanistically, inhibiting Na+/K+-ATPase or adding mannitol evoked the TonEBP response, whereas inhibition of cytoskeletal signaling abolished it.
Conclusions: Enhanced Na+ availability induced osmotic gradient-dependent cytoskeletal signals in trophoblasts, resulting in proangiogenic responses. As placental salt availability is compromised in preeclampsia, adverse systemic responses are thus conceivable.
{"title":"Alterations of Placental Sodium in Preeclampsia: Trophoblast Responses.","authors":"Hiten D Mistry, Rahel Klossner, Paula J Scaife, Nicole Eisele, Lesia O Kurlak, Sampada Kallol, Christiane Albrecht, Carine Gennari-Moser, Louise V Briggs, Fiona Broughton Pipkin, Markus G Mohaupt","doi":"10.1161/HYPERTENSIONAHA.124.23001","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23001","url":null,"abstract":"<p><strong>Background: </strong>Evidence suggests that increasing salt intake in pregnancy lowers blood pressure, protecting against preeclampsia. We hypothesized that sodium (Na<sup>+</sup>) evokes beneficial placental signals that are disrupted in preeclampsia.</p><p><strong>Methods: </strong>Blood and urine were collected from nonpregnant women of reproductive age (n=26) and pregnant women with (n=50) and without (n=55) preeclampsia, along with placental biopsies. Human trophoblast cell lines and primary human trophoblasts were cultured with varying Na<sup>+</sup> concentrations.</p><p><strong>Results: </strong>Women with preeclampsia had reduced placental and urinary Na<sup>+</sup> concentrations, yet increased urinary angiotensinogen and reduced active renin, aldosterone concentrations, and osmotic response signal TonEBP (tonicity-responsive enhancer binding protein) expression. In trophoblast cell cultures, TonEBP was consistently increased upon augmented Na<sup>+</sup> exposure. Mechanistically, inhibiting Na<sup>+</sup>/K<sup>+</sup>-ATPase or adding mannitol evoked the TonEBP response, whereas inhibition of cytoskeletal signaling abolished it.</p><p><strong>Conclusions: </strong>Enhanced Na<sup>+</sup> availability induced osmotic gradient-dependent cytoskeletal signals in trophoblasts, resulting in proangiogenic responses. As placental salt availability is compromised in preeclampsia, adverse systemic responses are thus conceivable.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-15DOI: 10.1161/HYPERTENSIONAHA.124.22998
Paul Muntner, Byron C Jaeger, Kathryn Foti, Lama Ghazi, Joshua D Bundy, Ligong Chen, Monika M Safford
Background: The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends initiation of antihypertensive medication for adults with stage 1 hypertension (systolic blood pressure, 130-139 mm Hg, or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10% estimated by the pooled cohort equations (PCEs). In 2023, the American Heart Association published the predicting risk of cardiovascular disease events (PREVENT) equations to estimate ASCVD and total cardiovascular disease risk.
Methods: We analyzed US National Health and Nutrition Examination Survey data from 2013 to 2020 for 1703 adults aged 30 to 79 years without self-reported cardiovascular disease with stage 1 hypertension. We estimated 10-year ASCVD risk by the PCEs and 10-year ASCVD and total cardiovascular disease risk by the base PREVENT equations. Analyses were weighted to represent noninstitutionalized US adults with stage 1 hypertension.
Results: Mean 10-year ASCVD risk was 5.4% (95% CI, 5.0%-5.9%) and 2.9% (95% CI, 2.7%-3.1%) using the PCEs and PREVENT equations, respectively. The proportion with 10-year ASCVD risk of 10% to <15% and ≥15% was 8.1% and 7.8% estimated by the PCEs, respectively, and 3.0% and 0.3% estimated by the PREVENT equations, respectively. No participants had a 10-year ASCVD risk ≥10% on the PREVENT equations and <10% on the PCEs, while 12.5% had a 10-year ASCVD risk ≥10% on the PCEs and <10% on the PREVENT equations. The mean 10-year total cardiovascular disease risk estimated by the PREVENT equations was lower than the mean 10-year ASCVD risk on the PCEs.
Conclusions: Among US adults with stage 1 hypertension, the 10-year predicted ASCVD risk estimated by the PREVENT equations was approximately half the risk estimated by the PCEs.
{"title":"Predicted Cardiovascular Risk by the PREVENT Equations in US Adults With Stage 1 Hypertension.","authors":"Paul Muntner, Byron C Jaeger, Kathryn Foti, Lama Ghazi, Joshua D Bundy, Ligong Chen, Monika M Safford","doi":"10.1161/HYPERTENSIONAHA.124.22998","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22998","url":null,"abstract":"<p><strong>Background: </strong>The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends initiation of antihypertensive medication for adults with stage 1 hypertension (systolic blood pressure, 130-139 mm Hg, or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10% estimated by the pooled cohort equations (PCEs). In 2023, the American Heart Association published the predicting risk of cardiovascular disease events (PREVENT) equations to estimate ASCVD and total cardiovascular disease risk.</p><p><strong>Methods: </strong>We analyzed US National Health and Nutrition Examination Survey data from 2013 to 2020 for 1703 adults aged 30 to 79 years without self-reported cardiovascular disease with stage 1 hypertension. We estimated 10-year ASCVD risk by the PCEs and 10-year ASCVD and total cardiovascular disease risk by the base PREVENT equations. Analyses were weighted to represent noninstitutionalized US adults with stage 1 hypertension.</p><p><strong>Results: </strong>Mean 10-year ASCVD risk was 5.4% (95% CI, 5.0%-5.9%) and 2.9% (95% CI, 2.7%-3.1%) using the PCEs and PREVENT equations, respectively. The proportion with 10-year ASCVD risk of 10% to <15% and ≥15% was 8.1% and 7.8% estimated by the PCEs, respectively, and 3.0% and 0.3% estimated by the PREVENT equations, respectively. No participants had a 10-year ASCVD risk ≥10% on the PREVENT equations and <10% on the PCEs, while 12.5% had a 10-year ASCVD risk ≥10% on the PCEs and <10% on the PREVENT equations. The mean 10-year total cardiovascular disease risk estimated by the PREVENT equations was lower than the mean 10-year ASCVD risk on the PCEs.</p><p><strong>Conclusions: </strong>Among US adults with stage 1 hypertension, the 10-year predicted ASCVD risk estimated by the PREVENT equations was approximately half the risk estimated by the PCEs.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616192","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 : 2024-09-01Epub Date: 2024-08-14DOI: 10.1161/HYPERTENSIONAHA.124.23528
Rajiv Agarwal, Matthew R Weir
{"title":"George L. Bakris, MD (1952 to 2024).","authors":"Rajiv Agarwal, Matthew R Weir","doi":"10.1161/HYPERTENSIONAHA.124.23528","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.23528","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035679","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 : 2024-09-01Epub Date: 2024-08-14DOI: 10.1161/HYPERTENSIONAHA.124.23486
William B White
{"title":"Henry R. Black, MD (1942-2024).","authors":"William B White","doi":"10.1161/HYPERTENSIONAHA.124.23486","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.23486","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035680","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 : 2024-09-01Epub Date: 2024-07-24DOI: 10.1161/HYPERTENSIONAHA.124.22642
Gian Paolo Rossi, Federico Bernardo Rossi, Chiara Guarnieri, Giacomo Rossitto, Teresa M Seccia
Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events. Among these, atrial fibrillation is the most common, but left ventricular hypertrophy, stroke, chronic kidney disease, and myocardial infarction also occur more often than in patients with hypertension and no PA. Young patients, who have higher chances of being cured long term, and high-risk patients, such as those with stage III or resistant hypertension, are those who will benefit most from an early diagnosis of PA. Therefore, the implementation of strategies to detect PA by a simplified diagnostic algorithm is necessary. In the patients who seek for surgical cure, adrenal vein sampling is key for the identification of unilateral PA and the achievement of optimal outcomes. Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Adrenal Vein Sampling International Study-2), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available.
尽管原发性醛固酮增多症(PA)会增加心血管事件的风险,但它却是一种常被忽视的继发性动脉高血压。目前迫切需要提高对其高发病率的认识,并采取更广泛的筛查策略,以提高其检出率,实现早期诊断和有针对性的治疗。对于单侧 PA 患者,这些措施可纠正高醛固酮血症,确保治愈高血压(即使对药物治疗产生耐药性),从而预防不良心血管事件的发生。其中,心房颤动最为常见,但左心室肥厚、中风、慢性肾病和心肌梗死的发生率也高于无 PA 的高血压患者。年轻患者长期治愈的几率较高,而高危患者,如 III 期或抵抗性高血压患者,是早期诊断 PA 的最大受益者。因此,有必要实施通过简化诊断算法检测 PA 的策略。对于寻求手术治疗的患者来说,肾上腺静脉取样是识别单侧 PA 并获得最佳治疗效果的关键。遗憾的是,肾上腺静脉取样技术要求高且不易获得,是 PA 检查的瓶颈。考虑到过去 5 年中许多研究,特别是 AVIS-2 研究(使用赛乐星对高危患者进行动脉粥样硬化血栓干预)所产生的新知识,基于我们中心 40 年的经验和最新的指南,我们在此提供 PA 的最新治疗方法,并推荐药物治疗和避免肾上腺静脉取样的策略,只要肾上腺静脉取样不便或无法进行肾上腺静脉取样。
{"title":"Clinical Management of Primary Aldosteronism: An Update.","authors":"Gian Paolo Rossi, Federico Bernardo Rossi, Chiara Guarnieri, Giacomo Rossitto, Teresa M Seccia","doi":"10.1161/HYPERTENSIONAHA.124.22642","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22642","url":null,"abstract":"<p><p>Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events. Among these, atrial fibrillation is the most common, but left ventricular hypertrophy, stroke, chronic kidney disease, and myocardial infarction also occur more often than in patients with hypertension and no PA. Young patients, who have higher chances of being cured long term, and high-risk patients, such as those with stage III or resistant hypertension, are those who will benefit most from an early diagnosis of PA. Therefore, the implementation of strategies to detect PA by a simplified diagnostic algorithm is necessary. In the patients who seek for surgical cure, adrenal vein sampling is key for the identification of unilateral PA and the achievement of optimal outcomes. Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Adrenal Vein Sampling International Study-2), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751552","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}
Background: STIM1 (stromal interaction molecule 1) regulates store-operated calcium entry and is involved in pulmonary artery vasoconstriction and pulmonary artery smooth muscle cell proliferation, leading to pulmonary arterial hypertension (PAH).
Methods: Bioinformatics analysis and a 2-stage matched case-control study were conducted to screen for noncoding variants that may potentially affect STIM1 transcriptional regulation in 242 patients with idiopathic PAH and 414 healthy controls. Luciferase reporter assay, real-time quantitative polymerase chain reaction, western blot, 5-ethynyl-2'-deoxyuridine (EdU) assay, and intracellular Ca2+ measurement were performed to study the mechanistic roles of those STIM1 noncoding variants in PAH.
Results: Five noncoding variants (rs3794050, rs7934581, rs3750996, rs1561876, and rs3750994) were identified and genotyped using Sanger sequencing. Rs3794050, rs7934581, and rs1561876 were associated with idiopathic PAH (recessive model, all P<0.05). Bioinformatics analysis showed that these 3 noncoding variants possibly affect the enhancer function of STIM1 or the microRNA (miRNA) binding to STIM1. Functional validation performed in HEK293 and pulmonary artery smooth muscle cells demonstrated that the noncoding variant rs1561876-G (STIM1 mutant) had significantly stronger transcriptional activity than the wild-type counterpart, rs1561876-A, by affecting the transcriptional regulatory function of both hsa-miRNA-3140-5p and hsa-miRNA-4766-5p. rs1561876-G enhanced intracellular Ca2+ signaling in human pulmonary artery smooth muscle cells secondary to calcium-sensing receptor activation and promoted proliferation of pulmonary artery smooth muscle cells under both normoxia and hypoxia conditions, suggesting a possible contribution to PAH development.
Conclusions: The potential clinical implications of the 3 noncoding variants of STIM1, rs3794050, rs7934581, and rs1561876, are 2-fold, as they may help predict the risk and prognosis of idiopathic PAH and guide investigations on novel therapeutic pathway(s).
{"title":"Identification of Noncoding Functional Regulatory Variants of <i>STIM1</i> Gene in Idiopathic Pulmonary Arterial Hypertension.","authors":"Bingxun Liu, Cen-Jin Wen, Guangyuan Zhou, Yun-Peng Wei, Zeang Wu, Ting Zhang, Yudan Zhou, Shuyi Qiu, Tao Wang, Matthieu Ruiz, Jocelyn Dupuis, Ping Yuan, Jinming Liu, Liping Zhu, Zhi-Cheng Jing, Qinghua Hu","doi":"10.1161/HYPERTENSIONAHA.124.22766","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22766","url":null,"abstract":"<p><strong>Background: </strong>STIM1 (stromal interaction molecule 1) regulates store-operated calcium entry and is involved in pulmonary artery vasoconstriction and pulmonary artery smooth muscle cell proliferation, leading to pulmonary arterial hypertension (PAH).</p><p><strong>Methods: </strong>Bioinformatics analysis and a 2-stage matched case-control study were conducted to screen for noncoding variants that may potentially affect <i>STIM1</i> transcriptional regulation in 242 patients with idiopathic PAH and 414 healthy controls. Luciferase reporter assay, real-time quantitative polymerase chain reaction, western blot, 5-ethynyl-2'-deoxyuridine (EdU) assay, and intracellular Ca<sup>2+</sup> measurement were performed to study the mechanistic roles of those <i>STIM1</i> noncoding variants in PAH.</p><p><strong>Results: </strong>Five noncoding variants (rs3794050, rs7934581, rs3750996, rs1561876, and rs3750994) were identified and genotyped using Sanger sequencing. Rs3794050, rs7934581, and rs1561876 were associated with idiopathic PAH (recessive model, all <i>P</i><0.05). Bioinformatics analysis showed that these 3 noncoding variants possibly affect the enhancer function of <i>STIM1</i> or the microRNA (miRNA) binding to <i>STIM1</i>. Functional validation performed in HEK293 and pulmonary artery smooth muscle cells demonstrated that the noncoding variant rs1561876-G (<i>STIM1</i> mutant) had significantly stronger transcriptional activity than the wild-type counterpart, rs1561876-A, by affecting the transcriptional regulatory function of both hsa-miRNA-3140-5p and hsa-miRNA-4766-5p. rs1561876-G enhanced intracellular Ca<sup>2+</sup> signaling in human pulmonary artery smooth muscle cells secondary to calcium-sensing receptor activation and promoted proliferation of pulmonary artery smooth muscle cells under both normoxia and hypoxia conditions, suggesting a possible contribution to PAH development.</p><p><strong>Conclusions: </strong>The potential clinical implications of the 3 noncoding variants of <i>STIM1</i>, rs3794050, rs7934581, and rs1561876, are 2-fold, as they may help predict the risk and prognosis of idiopathic PAH and guide investigations on novel therapeutic pathway(s).</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579476","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 : 2024-09-01Epub Date: 2024-07-17DOI: 10.1161/HYPERTENSIONAHA.124.22820
Bianca R Fato, Natasha de Alwis, Sally Beard, Natalie K Binder, Natasha Pritchard, Tu'uhevaha J Kaitu'u-Lino, Kristen J Bubb, Natalie J Hannan
Background: Preeclampsia is a serious condition of pregnancy, complicated by aberrant maternal vascular dysfunction. CNP (C-type natriuretic peptide) contributes to vascular homeostasis, acting through NPR-B (natriuretic peptide receptor-B) and NPR-C (natriuretic peptide receptor-C). CNP mitigates vascular dysfunction of arteries in nonpregnant cohorts; this study investigates whether CNP can dilate maternal arteries in ex vivo preeclampsia models.
Methods: Human omental arteries were dissected from fat biopsies collected during cesarean section. CNP, NPR-B, and NPR-C mRNA expression was assessed in arteries collected from pregnancies complicated by preeclampsia (n=6) and normotensive controls (n=11). Using wire myography, we investigated the effects of CNP on dilation of arteries from normotensive pregnancies. Arteries were preconstricted with either serum from patients with preeclampsia (n=6) or recombinant ET-1 (endothelin-1; vasoconstrictor elevated in preeclampsia; n=6) to model vasoconstriction associated with preeclampsia. Preconstricted arteries were treated with recombinant CNP (0.001-100 µmol/L) or vehicle and vascular relaxation assessed. In further studies, arteries were preincubated with NPR-B (5 µmol/L) and NPR-C (10 µmol/L) antagonists before serum-induced constriction (n=4-5) to explore mechanistic signaling.
Results: CNP, NPR-B, and NPR-C mRNAs were not differentially expressed in omental arteries from preeclamptic pregnancies. CNP potently stimulated maternal artery vasorelaxation in our model of preeclampsia (using preeclamptic serum). Its vasodilatory actions were driven through the activation of NPR-B predominantly; antagonism of this receptor alone dampened CNP vasorelaxation. Interestingly, CNP did not reduce ET-1-driven omental artery constriction.
Conclusions: Collectively, these data suggest that enhancing CNP signaling through NPR-B offers a potential therapeutic strategy to reduce systemic vascular constriction in preeclampsia.
{"title":"Exploring the Therapeutic Potential of C-Type Natriuretic Peptide for Preeclampsia.","authors":"Bianca R Fato, Natasha de Alwis, Sally Beard, Natalie K Binder, Natasha Pritchard, Tu'uhevaha J Kaitu'u-Lino, Kristen J Bubb, Natalie J Hannan","doi":"10.1161/HYPERTENSIONAHA.124.22820","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22820","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a serious condition of pregnancy, complicated by aberrant maternal vascular dysfunction. CNP (C-type natriuretic peptide) contributes to vascular homeostasis, acting through NPR-B (natriuretic peptide receptor-B) and NPR-C (natriuretic peptide receptor-C). CNP mitigates vascular dysfunction of arteries in nonpregnant cohorts; this study investigates whether CNP can dilate maternal arteries in ex vivo preeclampsia models.</p><p><strong>Methods: </strong>Human omental arteries were dissected from fat biopsies collected during cesarean section. CNP, NPR-B, and NPR-C mRNA expression was assessed in arteries collected from pregnancies complicated by preeclampsia (n=6) and normotensive controls (n=11). Using wire myography, we investigated the effects of CNP on dilation of arteries from normotensive pregnancies. Arteries were preconstricted with either serum from patients with preeclampsia (n=6) or recombinant ET-1 (endothelin-1; vasoconstrictor elevated in preeclampsia; n=6) to model vasoconstriction associated with preeclampsia. Preconstricted arteries were treated with recombinant CNP (0.001-100 µmol/L) or vehicle and vascular relaxation assessed. In further studies, arteries were preincubated with NPR-B (5 µmol/L) and NPR-C (10 µmol/L) antagonists before serum-induced constriction (n=4-5) to explore mechanistic signaling.</p><p><strong>Results: </strong>CNP, NPR-B, and NPR-C mRNAs were not differentially expressed in omental arteries from preeclamptic pregnancies. CNP potently stimulated maternal artery vasorelaxation in our model of preeclampsia (using preeclamptic serum). Its vasodilatory actions were driven through the activation of NPR-B predominantly; antagonism of this receptor alone dampened CNP vasorelaxation. Interestingly, CNP did not reduce ET-1-driven omental artery constriction.</p><p><strong>Conclusions: </strong>Collectively, these data suggest that enhancing CNP signaling through NPR-B offers a potential therapeutic strategy to reduce systemic vascular constriction in preeclampsia.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626612","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 : 2024-09-01Epub Date: 2024-06-27DOI: 10.1161/HYPERTENSIONAHA.124.22729
Smriti Badhwar, Louise Marais, Hakim Khettab, Federica Poli, Yanlu Li, Patrick Segers, Soren Aasmul, Mirko de Melis, Roel Baets, Steve Greenwald, Rosa Maria Bruno, Pierre Boutouyrie
Background: Carotid-femoral pulse wave velocity (cfPWV) is the gold standard for noninvasive arterial stiffness assessment, an independent predictor of cardiovascular disease, and a potential parameter to guide therapy. However, cfPWV is not routinely measured in clinical practice due to the unavailability of a low-cost, operator-friendly, and independent device. The current study validated a novel laser Doppler vibrometry (LDV)-based measurement of cfPWV against the reference technique.
Methods: In 100 (50 men) hypertensive patients, cfPWV was measured using applanation tonometry (Sphygmocor) and the novel LDV device. This device has 2 handpieces with 6 laser beams each that simultaneously measure vibrations from the skin surface at carotid and femoral sites. Pulse wave velocity is calculated using ECG for the identification of cardiac cycles. An ECG-independent method was also devised. Cardiovascular risk score was calculated for patients between 40 and 75 years old using the WHO risk scoring chart.
Results: LDV-based cfPWV correlated significantly with tonometry (r=0.86, P<0.0001 ECG-dependent [cfPWVLDV_ECG] and r=0.80, P<0.001 ECG-independent [cfPWVLDV_w/oECG] methods). Bland-Altman analysis showed nonsignificant bias (0.65 m/s) and acceptable SD (1.27 m/s) between methods. Intraobserver coefficient of variance for LDV was 4.7% (95% CI, 3.0%-5.5%), and interobserver coefficient of variance was 5.87%. CfPWV correlated significantly with CVD risk (r=0.64, P<0.001; r=0.41, P=0.003; and r=0.37, P=0.006 for tonometry, LDV-with, and LDV-without ECG, respectively).
Conclusions: The study demonstrates clinical validity of the LDV device. The LDV provides a simple, noninvasive, operator-independent method to measure cfPWV for assessing arterial stiffness, comparable to the standard existing techniques.
{"title":"Clinical Validation of Carotid-Femoral Pulse Wave Velocity Measurement Using a Multi-Beam Laser Vibrometer: The CARDIS Study.","authors":"Smriti Badhwar, Louise Marais, Hakim Khettab, Federica Poli, Yanlu Li, Patrick Segers, Soren Aasmul, Mirko de Melis, Roel Baets, Steve Greenwald, Rosa Maria Bruno, Pierre Boutouyrie","doi":"10.1161/HYPERTENSIONAHA.124.22729","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22729","url":null,"abstract":"<p><strong>Background: </strong>Carotid-femoral pulse wave velocity (cfPWV) is the gold standard for noninvasive arterial stiffness assessment, an independent predictor of cardiovascular disease, and a potential parameter to guide therapy. However, cfPWV is not routinely measured in clinical practice due to the unavailability of a low-cost, operator-friendly, and independent device. The current study validated a novel laser Doppler vibrometry (LDV)-based measurement of cfPWV against the reference technique.</p><p><strong>Methods: </strong>In 100 (50 men) hypertensive patients, cfPWV was measured using applanation tonometry (Sphygmocor) and the novel LDV device. This device has 2 handpieces with 6 laser beams each that simultaneously measure vibrations from the skin surface at carotid and femoral sites. Pulse wave velocity is calculated using ECG for the identification of cardiac cycles. An ECG-independent method was also devised. Cardiovascular risk score was calculated for patients between 40 and 75 years old using the WHO risk scoring chart.</p><p><strong>Results: </strong>LDV-based cfPWV correlated significantly with tonometry (r=0.86, <i>P</i><0.0001 ECG-dependent [cfPWV<sub>LDV_ECG</sub>] and r=0.80, <i>P</i><0.001 ECG-independent [cfPWV<sub>LDV_w/oECG</sub>] methods). Bland-Altman analysis showed nonsignificant bias (0.65 m/s) and acceptable SD (1.27 m/s) between methods. Intraobserver coefficient of variance for LDV was 4.7% (95% CI, 3.0%-5.5%), and interobserver coefficient of variance was 5.87%. CfPWV correlated significantly with CVD risk (r=0.64, <i>P</i><0.001; r=0.41, <i>P</i>=0.003; and r=0.37, <i>P</i>=0.006 for tonometry, LDV-with, and LDV-without ECG, respectively).</p><p><strong>Conclusions: </strong>The study demonstrates clinical validity of the LDV device. The LDV provides a simple, noninvasive, operator-independent method to measure cfPWV for assessing arterial stiffness, comparable to the standard existing techniques.</p><p><strong>Registration: </strong>URL: https://clinicaltrials.gov/study/NCT03446430; Unique identifier: NCT03446430.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-03DOI: 10.1161/HYPERTENSIONAHA.124.22876
Devin Haney, Yuan Ma, Djhenne Dalmacy, Nicholas M Pajewski, Ihab Hajjar, James A de Lemos, Wenxin Zhang, Elsayed Z Soliman, Christie M Ballantyne, Vijay Nambi, Naveed Sattar, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Jarett D Berry, Simon B Ascher
Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.
Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.
Results: Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; Pinteraction=0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively.
Conclusions: In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar.
{"title":"High-Sensitivity Troponin T, NT-proBNP, and Cognitive Outcomes in SPRINT.","authors":"Devin Haney, Yuan Ma, Djhenne Dalmacy, Nicholas M Pajewski, Ihab Hajjar, James A de Lemos, Wenxin Zhang, Elsayed Z Soliman, Christie M Ballantyne, Vijay Nambi, Naveed Sattar, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Jarett D Berry, Simon B Ascher","doi":"10.1161/HYPERTENSIONAHA.124.22876","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22876","url":null,"abstract":"<p><strong>Background: </strong>Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.</p><p><strong>Methods: </strong>In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.</p><p><strong>Results: </strong>Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; <i>P</i><sub>interaction</sub>=0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively.</p><p><strong>Conclusions: </strong>In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491678","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 : 2024-09-01Epub Date: 2024-07-17DOI: 10.1161/HYPERTENSIONAHA.124.23439
Qianhui Ling, Xilan Dong, Jingjing Bai, Yue Deng, Qirui Song, Jun Cai
Background: The optimal timing for initiating intensive systolic blood pressure (SBP) treatment remains unclear. While longer hypertension duration is positively associated with increased cardiovascular disease risk, it is unknown whether patients with prolonged hypertension can derive similar benefits from intensive SBP treatment.
Methods: From the STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients), 8442 participants with complete hypertension duration data were categorized by hypertension duration ≤5 years, 5 to 10 years, 10 to 15 years, and >15 years. The primary outcome was a composite of cardiovascular events. Hazard ratios were calculated using the Fine-Gray subdistribution hazard model.
Results: The incidences of the primary outcome increased significantly in patients with hypertension over 15 years than those <5 years in the standard SBP treatment group (adjusted hazard ratios, 1.68 [95% CI, 1.11-2.56]) but not in the intensive treatment group. Each 1-year increase in hypertension duration continuously increased the adjusted risk of major cardiovascular events by 4% (95% CI, 1.01-1.08) up to 20 years, plateauing at an adjusted hazard ratio of 2.27 (95% CI, 1.28-4.04). After intensive SBP treatment, the incidences of major cardiovascular events were similar across different hypertension duration groups, which were 2.22%, 1.69%, 3.02%, and 2.52%, respectively (P>0.05). Subgroup analyses indicated a potential sex difference in this relationship between hypertension duration and the primary outcome in the standard SBP treatment group (Pinteraction=0.05).
Conclusions: Initiating intensive SBP treatment at any stage of hypertension duration could reduce cardiovascular disease risk to a comparable level.
{"title":"Impact of Hypertension Duration on the Cardiovascular Benefit of Intensive Blood Pressure Control.","authors":"Qianhui Ling, Xilan Dong, Jingjing Bai, Yue Deng, Qirui Song, Jun Cai","doi":"10.1161/HYPERTENSIONAHA.124.23439","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23439","url":null,"abstract":"<p><strong>Background: </strong>The optimal timing for initiating intensive systolic blood pressure (SBP) treatment remains unclear. While longer hypertension duration is positively associated with increased cardiovascular disease risk, it is unknown whether patients with prolonged hypertension can derive similar benefits from intensive SBP treatment.</p><p><strong>Methods: </strong>From the STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients), 8442 participants with complete hypertension duration data were categorized by hypertension duration ≤5 years, 5 to 10 years, 10 to 15 years, and >15 years. The primary outcome was a composite of cardiovascular events. Hazard ratios were calculated using the Fine-Gray subdistribution hazard model.</p><p><strong>Results: </strong>The incidences of the primary outcome increased significantly in patients with hypertension over 15 years than those <5 years in the standard SBP treatment group (adjusted hazard ratios, 1.68 [95% CI, 1.11-2.56]) but not in the intensive treatment group. Each 1-year increase in hypertension duration continuously increased the adjusted risk of major cardiovascular events by 4% (95% CI, 1.01-1.08) up to 20 years, plateauing at an adjusted hazard ratio of 2.27 (95% CI, 1.28-4.04). After intensive SBP treatment, the incidences of major cardiovascular events were similar across different hypertension duration groups, which were 2.22%, 1.69%, 3.02%, and 2.52%, respectively (<i>P</i>>0.05). Subgroup analyses indicated a potential sex difference in this relationship between hypertension duration and the primary outcome in the standard SBP treatment group (<i>P</i><sub>interaction</sub>=0.05).</p><p><strong>Conclusions: </strong>Initiating intensive SBP treatment at any stage of hypertension duration could reduce cardiovascular disease risk to a comparable level.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626613","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}