Hypertension最新文献

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Nationwide, Pragmatic, Direct-to-Patient Primary Aldosteronism Testing Program.
IF 6.9 1区 医学
Hypertension Pub Date : 2025-02-21 DOI: 10.1161/HYPERTENSIONAHA.125.24648
Jenifer M Brown, Laura C Tsai, Eva E Abel, Arnaldo Ferrebus, Anna E Moore, Yvonne M Niebuhr, Bassil Bacare, Brooke Honzel, Julia Milks, Kristen Foote, Andrew J Newman, Wasita W Parksook, Anand Vaidya
{"title":"Nationwide, Pragmatic, Direct-to-Patient Primary Aldosteronism Testing Program.","authors":"Jenifer M Brown, Laura C Tsai, Eva E Abel, Arnaldo Ferrebus, Anna E Moore, Yvonne M Niebuhr, Bassil Bacare, Brooke Honzel, Julia Milks, Kristen Foote, Andrew J Newman, Wasita W Parksook, Anand Vaidya","doi":"10.1161/HYPERTENSIONAHA.125.24648","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.24648","url":null,"abstract":"<p><strong>Background: </strong>Primary aldosteronism, an endocrinopathy present in ≥10% to 25% of patients with hypertension, confers excess cardiovascular risk that can be mitigated with aldosterone-directed therapy. However, only 2% of eligible patients undergo guideline-recommended screening. This study aimed to bypass clinical inertia and identify people with primary aldosteronism using pragmatic, direct-to-patient testing.</p><p><strong>Methods: </strong>Hypertensive adults were recruited via online platforms and underwent virtual consent and local phlebotomy. Using a standardized diagnostic algorithm, laboratory results with interpretations were communicated to patients and primary care providers. Follow-up was ascertained at 6 to 12 months. The primary outcome was the frequency of a positive test for primary aldosteronism. Secondary outcomes included follow-up primary aldosteronism testing and implementation of aldosterone-targeted therapies.</p><p><strong>Results: </strong>The study population (N=694) had a mean age of 63.3±11.3 years, was 52.2% female, and hailed from 41 US states. Overall, 25.4% had a positive test for primary aldosteronism. Sleep apnea, resistant hypertension, and hypokalemia were the most common testing indications, with 55.2% of participants having ≥2 indications. Over half of participants (57%) were already under endocrinology, cardiology, or nephrology care, yet had not been tested. In longitudinal follow-up of participants with a positive result, 25.5% had additional testing and 13.7% were started on aldosterone-targeted therapy (mineralocorticoid receptor antagonist or adrenalectomy).</p><p><strong>Conclusions: </strong>Pragmatic, direct-to-patient testing, and simplified results interpretation is a feasible, scalable method to increase primary aldosteronism diagnoses and implementation of aldosterone-targeted therapies. Given that new hypertension guidelines recommend primary aldosteronism screening in all hypertensive people, practical approaches to test, interpret, and implement results will be essential.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467878","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}
引用次数: 0
Persistence of a Proteomic Signature After a Hypertensive Disorder of Pregnancy. 妊娠高血压疾病后蛋白质组特征的持续性
IF 6.9 1区 医学
Hypertension Pub Date : 2025-02-21 DOI: 10.1161/HYPERTENSIONAHA.124.24490
Mark A Hlatky, Chi-Hung Shu, David K Stevenson, Gary M Shaw, Marcia L Stefanick, Heather A Boyd, Mads Melbye, Xi Du Plummer, Oshra Sedan, Ronald J Wong, Nima Aghaeepour, Virginia D Winn
{"title":"Persistence of a Proteomic Signature After a Hypertensive Disorder of Pregnancy.","authors":"Mark A Hlatky, Chi-Hung Shu, David K Stevenson, Gary M Shaw, Marcia L Stefanick, Heather A Boyd, Mads Melbye, Xi Du Plummer, Oshra Sedan, Ronald J Wong, Nima Aghaeepour, Virginia D Winn","doi":"10.1161/HYPERTENSIONAHA.124.24490","DOIUrl":"10.1161/HYPERTENSIONAHA.124.24490","url":null,"abstract":"<p><strong>Background: </strong>A hypertensive disorder of pregnancy is associated with a higher risk of cardiovascular disease later in life, but the potential mechanistic links are unknown.</p><p><strong>Methods: </strong>We recruited 2 groups of women, 1 during pregnancy and another at least 2 years after delivery. Cases had a hypertensive disorder of pregnancy, and controls had a normotensive pregnancy. The pregnancy cohort had study visits antepartum and postpartum; the mid-life group made a single study visit. We assayed 7228 plasma proteins, applied machine learning to identify proteomics signatures at each time point, and performed enrichment analyses to identify relevant biological pathways.</p><p><strong>Results: </strong>The pregnancy cohort (58 cases and 46 controls) had a mean age of 33.8 years, and the mid-life group (71 cases and 74 controls) had a mean age of 40.8 years. Protein levels differed significantly between cases and controls at each time point: 6233 antepartum, 189 postpartum, and 224 in mid-life. The postpartum protein signature discriminated well between cases and controls (c-index=0.78), and it also discriminated well in the independent mid-life samples (c-index=0.72). Pathway analyses identified differences in the complement and coagulation cascades that persisted across the antepartum, postpartum, and mid-life samples. The 28 proteins present in both the postpartum and mid-life signatures included 5 complement factors (3, B, H, H-related-1, and C1r-subcomponent-like) and coagulation factor IX.</p><p><strong>Conclusions: </strong>Differences in protein expression persist for years after a hypertensive disorder of pregnancy. The consistent differences in the complement and coagulation pathways may contribute to the increased risk of later life cardiovascular disease.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467879","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}
引用次数: 0
Aspirin Improves Uterine Artery Function in Hypercholesterolemic Preeclampsia.
IF 6.9 1区 医学
Hypertension Pub Date : 2025-02-12 DOI: 10.1161/HYPERTENSIONAHA.124.24435
Amanda A de Oliveira, Floor Spaans, Murilo E Graton, Angie Stokes, Raven Kirschenman, Anita Quon, Christy-Lynn M Cooke, Sandra T Davidge
{"title":"Aspirin Improves Uterine Artery Function in Hypercholesterolemic Preeclampsia.","authors":"Amanda A de Oliveira, Floor Spaans, Murilo E Graton, Angie Stokes, Raven Kirschenman, Anita Quon, Christy-Lynn M Cooke, Sandra T Davidge","doi":"10.1161/HYPERTENSIONAHA.124.24435","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.24435","url":null,"abstract":"<p><strong>Background: </strong>Excessive hypercholesterolemia in pregnancy increases the risk of preeclampsia, though the mechanisms remain unclear. We recently showed that uterine artery function is impaired in hypercholesterolemia-preeclampsia via activation of the TLR4 (toll-like receptor 4)/PGHS1 (prostaglandin H synthase 1) pathway. Low-dose aspirin lowers preeclampsia risk in high-risk pregnancies by inhibiting PGHS1, but its effects in hypercholesterolemia-preeclampsia pregnancies are not known. Moreover, oxidized low-density lipoprotein levels rise in hypercholesterolemia-preeclampsia, potentially activating TLR4 and LOX-1 (lectin-like oxLDL receptor-1; scavenger receptor linked to vascular dysfunction in preeclampsia). However, whether this occurs in hypercholesterolemia-preeclampsia is not known.</p><p><strong>Methods: </strong>Sprague Dawley rats received a control or high-cholesterol diet (to induce hypercholesterolemia-preeclampsia) from gestational day 6 to 20, with placebo or low-dose aspirin (1.5 mg/daily) given from gestational day 10 to 20. On gestational day 20, pregnancy outcomes and uterine artery function were assessed.</p><p><strong>Results: </strong>Uterine artery blood flow velocity and placental weights were higher in hypercholesterolemia-preeclampsia placebo-treated dams versus controls, but these were reduced by low-dose aspirin. Endothelium-dependent vasodilation was impaired in the uterine arteries of the hypercholesterolemia-preeclampsia placebo group versus controls and was corrected by low-dose aspirin. Ex vivo inhibition of TLR4, PGHS1, or LOX-1 also normalized endothelium-dependent vasodilation in the hypercholesterolemia-preeclampsia placebo-treated dams. Exposure to oxidized low-density lipoprotein in the bath (modeling a secondary hit) further impaired endothelium-dependent vasodilation in the uterine arteries of the hypercholesterolemia-preeclampsia placebo group, partially via TLR4 and LOX-1, which was prevented by low-dose aspirin.</p><p><strong>Conclusions: </strong>Low-dose aspirin improved uterine artery endothelial function in hypercholesterolemia-preeclampsia pregnancies; likely by suppressing the TLR4/LOX-1/PGHS1 pathway.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398881","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}
引用次数: 0
Epidemiology of Maternal Hypertensive Disorders.
IF 6.9 1区 医学
Hypertension Pub Date : 2025-02-12 DOI: 10.1161/HYPERTENSIONAHA.124.23765
Yan Zhao, Yue Wang, Fei Tong, Qianqian Gao, Baoxuan Li
{"title":"Epidemiology of Maternal Hypertensive Disorders.","authors":"Yan Zhao, Yue Wang, Fei Tong, Qianqian Gao, Baoxuan Li","doi":"10.1161/HYPERTENSIONAHA.124.23765","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.23765","url":null,"abstract":"<p><strong>Background: </strong>Maternal hypertensive disorders during pregnancy are a worldwide health problem, particularly in the countries/regions with low sociodemographic levels. This study aimed to reveal and predict the hypertensive disorders during pregnancy-related epidemiological trends.</p><p><strong>Methods: </strong>Using data from the Global Burden of Disease 2019 study, we constructed an age-period-cohort model to assess the net drift (annual percentage changes), associated age, period, and cohort effects across global and different sociodemographic index (SDI) regions. Moreover, we analyzed attributable risk factors and future trends based on the autoregressive integrated moving average model.</p><p><strong>Results: </strong>The numbers of hypertensive disorders during pregnancy worldwide increased by 10.9% (95% uncertainty interval, 6.1-15.3) from 1990 to 2019 and only increased in the low-SDI countries. The age-standardized incidence rate declined by 23.6% (20.6, 26.9), with a global net drift of -0.8%, whereas some higher-SDI countries showed a positive net drift. After controlling for period and cohort factors, the highest incidence was observed in the 20- to 29-year age group. The period and cohort effects showed decreasing trends, whereas unfavorable period effects occurred after 2010 in high-SDI and middle-high-SDI countries. High-income North America and western sub-Saharan Africa have shown increased numbers of disability-adjusted life years due to malnutrition. The autoregressive integrated moving average model revealed downward trends in the global incidence and age-standardized incidence rate by 2030.</p><p><strong>Conclusions: </strong>Our study highlights significant regional and national variations and age differences in the burden of hypertensive disorders during pregnancy associated with SDI stratification, which will facilitate the targeting of cost-effective health policy planning, resource allocation, and women's health management by policymakers.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399052","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}
引用次数: 0
Prenatal Psychosocial Stressors and Blood Pressure Across 4 Years Postpartum.
IF 6.9 1区 医学
Hypertension Pub Date : 2025-02-10 DOI: 10.1161/HYPERTENSIONAHA.124.23979
Noelle Pardo, Sandrah P Eckel, Zhongzheng Niu, Rima Habre, Tingyu Yang, Xinci Chen, Mario Vigil, Brendan Grubbs, Laila Al-Marayati, Nathana Lurvey, Claudia Toledo-Corral, Jill Johnston, Genevieve Dunton, Carrie Breton, Theresa M Bastain, Shohreh F Farzan
{"title":"Prenatal Psychosocial Stressors and Blood Pressure Across 4 Years Postpartum.","authors":"Noelle Pardo, Sandrah P Eckel, Zhongzheng Niu, Rima Habre, Tingyu Yang, Xinci Chen, Mario Vigil, Brendan Grubbs, Laila Al-Marayati, Nathana Lurvey, Claudia Toledo-Corral, Jill Johnston, Genevieve Dunton, Carrie Breton, Theresa M Bastain, Shohreh F Farzan","doi":"10.1161/HYPERTENSIONAHA.124.23979","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23979","url":null,"abstract":"<p><strong>Background: </strong>Psychosocial stress is a cardiovascular risk factor; however, little is known about whether prenatal psychosocial stressors influence postpartum cardiovascular health. We aimed to examine the associations of multiple measures of prenatal psychosocial stress on maternal blood pressure (BP) in the first 4 years after birth.</p><p><strong>Methods: </strong>Among 225 MADRES cohort (Maternal and Developmental Risks From Environmental and Social Stressors) participants, we examined associations of average prenatal Perceived Stress Scale (PSS), Center for Epidemiological Studies Depression (CES-D) scores, and second-trimester neighborhood social cohesion scores on systolic and diastolic BP collected at annual postpartum study visits (1-4 years) using linear mixed-effects models, adjusted for covariates.</p><p><strong>Results: </strong>Higher prenatal PSS and CES-D scores were associated with greater diastolic BP at 1 year postpartum (0.24 [95% CI, 0.01-0.46] and 0.24 [95% CI, 0.08-0.40] mm Hg per 1-unit higher PSS and CES-D, respectively) and greater systolic BP (0.25 [95% CI, 0.02-0.48] mm Hg per 1-unit higher CES-D). Overall associations of PSS and CES-D with BP were attenuated over the 4-year postpartum period (<i>P</i><0.05). Stratified analyses suggested larger associations of PSS and CES-D among US-born participants and participants with normotensive pregnancies. While neighborhood social cohesion was not associated with postpartum BP overall, higher neighborhood social cohesion scores were associated with lower BP at 1 year postpartum among participants with normotensive pregnancies and lower systolic BP among foreign-born Hispanic participants.</p><p><strong>Conclusions: </strong>Higher prenatal perceived stress and depressive symptoms were associated with greater 1-year postpartum BP, whereas neighborhood cohesion was associated with lower 1-year postpartum BP. These results suggest prenatal psychosocial factors may impact cardiovascular health within the first year after birth.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382010","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}
引用次数: 0
Cross-Sex Hormone Therapy Is Associated With Loss of Circadian Rhythm in the Male Rat. 异性激素治疗与雄性大鼠昼夜节律丧失有关。
IF 6.9 1区 医学
Hypertension Pub Date : 2025-02-01 Epub Date: 2024-12-05 DOI: 10.1161/HYPERTENSIONAHA.124.23901
Jordan H Mallette, Breland F Crudup, Adrian Oudomrath Speyrer, Adam Z Rawls, Kathy Cockrell, Alex T Willis, Kacey Davenport, Licy L Yanes Cardozo, Noha M Shawky, Barbara T Alexander
{"title":"Cross-Sex Hormone Therapy Is Associated With Loss of Circadian Rhythm in the Male Rat.","authors":"Jordan H Mallette, Breland F Crudup, Adrian Oudomrath Speyrer, Adam Z Rawls, Kathy Cockrell, Alex T Willis, Kacey Davenport, Licy L Yanes Cardozo, Noha M Shawky, Barbara T Alexander","doi":"10.1161/HYPERTENSIONAHA.124.23901","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23901","url":null,"abstract":"<p><strong>Background: </strong>Transgender women are individuals born male but identify as female. Many transgender women undergo gender-affirming hormone therapy to alleviate the distress that can occur due to gender incongruence. For transgender women, gender-affirming hormone therapy includes 17β-estradiol (E2) combined with an antiandrogen therapy (AA) or surgical intervention. Numerous studies suggest that the risk of cardiovascular disease is elevated in transgender women; yet, the biological effects of gender-affirming hormone therapy on cardiovascular health are unknown. We hypothesize that a shift in the hormonal milieu versus natal sex in the male rat is associated with an increase in blood pressure at baseline and an enhanced responsiveness to a hypertensive challenge.</p><p><strong>Methods: </strong>We developed clinically relevant models that mimic gender-affirming hormone therapy combination therapies utilized for the endocrine treatment of gender dysphoria in transgender women.</p><p><strong>Results: </strong>Chronic E2 plus castration or the E2+antiandrogen spironolactone was associated with a significant reduction in lean mass and testosterone. At baseline, 24-hour mean arterial pressure did not differ in E2+castration or E2+antiandrogen therapy versus control, but circadian rhythm was disrupted. In response to chronic Ang II (angiotensin II; 200 ng/kg per minute), the Ang II-induced increase in blood pressure was attenuated in E2+castration compared with control, but the blood pressure response to Ang II was similar in E2+antiandrogen therapy versus control.</p><p><strong>Conclusions: </strong>Thus, these data indicate that the type of combination therapy utilized may exert differential effects on blood pressure and that disruption of circadian rhythm may be a contributory factor to the increased risk of adverse cardiovascular outcomes in transgender women exposed to high 17β-estradiol coupled to androgen suppression.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"241-254"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780176","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}
引用次数: 0
Cost-Effectiveness of Intensive Blood Pressure Control in Youth With Chronic Kidney Disease. 青少年慢性肾病患者强化血压控制的成本-效果
IF 6.9 1区 医学
Hypertension Pub Date : 2025-02-01 Epub Date: 2024-12-05 DOI: 10.1161/HYPERTENSIONAHA.124.23437
Carol L Vincent, Katherine A Poehling, Joseph Rigdon, Christopher L Schaich, Andrew M South, Stephen M Downs
{"title":"Cost-Effectiveness of Intensive Blood Pressure Control in Youth With Chronic Kidney Disease.","authors":"Carol L Vincent, Katherine A Poehling, Joseph Rigdon, Christopher L Schaich, Andrew M South, Stephen M Downs","doi":"10.1161/HYPERTENSIONAHA.124.23437","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23437","url":null,"abstract":"<p><strong>Background: </strong>Intensive blood pressure (BP) control in youth with chronic kidney disease (CKD) slows progression, delaying the need for kidney replacement therapy (KRT). Most youth with CKD have hypertension and BP control is difficult to achieve outside of controlled experimental settings. Implementing effective BP control strategies in this population may be cost-saving despite requiring additional resources. Our objective was to determine the economic and clinical impact of intensive versus usual care for BP management in youth with CKD in a microeconomic model.</p><p><strong>Methods: </strong>We developed a decision tree from the US payer perspective to estimate the total costs and clinical effect of an intensified BP intervention over 5 years, modeled after the ESCAPE trial (Effect of Strict Blood Pressure Control and Angiotensin-Converting Enzyme [ACE] Inhibition on Progression of Chronic Renal Failure in Pediatric Patients) protocol. We compared this intervention to usual care in a hypothetical population of youth with mild-to-moderate CKD. Probabilities were informed by published literature; cost estimates were informed by publicly available data. Our outcomes were the net discounted cost of an intensive BP intervention, number needed to treat with the intervention to prevent 1 KRT episode, and incremental cost per KRT episode avoided.</p><p><strong>Results: </strong>An intensive BP intervention, with a goal of an average 24-hour mean arterial pressure <50th percentile, improved outcomes with net cost savings of $9440 per participant over 5 years compared with usual care. To prevent 1 episode of KRT over 5 years, 13 participants need to receive intensive BP intervention.</p><p><strong>Conclusions: </strong>Routine use of the ESCAPE protocol for intensive BP control in youth with CKD could save overall costs for the payer and improve clinical outcomes.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"393-401"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780203","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}
引用次数: 0
ACE2, From the Kidney to SARS-CoV-2: Donald Seldin Award Lecture 2023. ACE2,从肾脏到SARS-CoV-2:唐纳德·塞尔丁奖演讲2023。
IF 6.9 1区 医学
Hypertension Pub Date : 2025-02-01 Epub Date: 2024-12-03 DOI: 10.1161/HYPERTENSIONAHA.124.22064
Daniel Batlle, Luise Hassler, Jan Wysocki
{"title":"ACE2, From the Kidney to SARS-CoV-2: Donald Seldin Award Lecture 2023.","authors":"Daniel Batlle, Luise Hassler, Jan Wysocki","doi":"10.1161/HYPERTENSIONAHA.124.22064","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22064","url":null,"abstract":"<p><p>ACE2 (angiotensin-converting enzyme 2) is a monocarboxypeptidase that cleaves Ang II (angiotensin II) among other substrates. ACE2 is present in the cell membrane of many organs, most abundantly in epithelial cells of kidney proximal tubules and the small intestine, and also exists in soluble forms in plasma and body fluids. Membrane-bound ACE2 exerts a renoprotective action by metabolizing Ang II and therefore attenuating the undesirable actions of excess Ang II. Therefore, soluble ACE2, by downregulating this peptide, may exert a therapeutic action. Our laboratory has designed ACE2 truncates that pass the glomerular filtration barrier to target the kidney renin-angiotensin system directly and, therefore, compensate for loss of kidney membrane-bound ACE2. Membrane-bound ACE2 is also the essential receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble ACE2 proteins have been studied as a way to intercept SARS-CoV-2 from binding to membrane-bound ACE2 and prevent cell entry of SARS-CoV-2 altogether. We bioengineered a soluble ACE2 protein, termed ACE2 618-DDC-ABD, with increased binding affinity for SARS-CoV-2 and prolonged duration of action, which, when administered intranasally, provides near-complete protection from lethality in k18hACE2 mice infected with different SARS-CoV-2 variants. The main advantage of soluble ACE2 proteins for the neutralization of SARS-CoV-2 is their immediate onset of action and universality for current and future emerging SARS-CoV-2 variants. It is notable that ACE2 is critically involved in 2 dissimilar functions: as a receptor for cell entry of many coronaviruses and as an enzyme in the metabolism of Ang II, and yet in both cases, it is a therapeutic target.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"166-180"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768559","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}
引用次数: 0
Burden of Cardio-Cerebrovascular and Renal Diseases Attributable to Systolic Hypertension in France in 2021. 2021年法国收缩期高血压导致的心脑血管和肾脏疾病负担
IF 6.9 1区 医学
Hypertension Pub Date : 2025-02-01 Epub Date: 2024-12-09 DOI: 10.1161/HYPERTENSIONAHA.124.23760
Clémence Grave, Christophe Bonaldi, Laure Carcaillon-Bentata, Amélie Gabet, Jean-Michel Halimi, Christophe Tzourio, Yannick Béjot, Marion J Torres, Philippe Gabriel Steg, Isabelle Durand Zaleski, Jacques Blacher, Valérie Olié
{"title":"Burden of Cardio-Cerebrovascular and Renal Diseases Attributable to Systolic Hypertension in France in 2021.","authors":"Clémence Grave, Christophe Bonaldi, Laure Carcaillon-Bentata, Amélie Gabet, Jean-Michel Halimi, Christophe Tzourio, Yannick Béjot, Marion J Torres, Philippe Gabriel Steg, Isabelle Durand Zaleski, Jacques Blacher, Valérie Olié","doi":"10.1161/HYPERTENSIONAHA.124.23760","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23760","url":null,"abstract":"<p><strong>Background: </strong>Hypertension is the most common chronic disease and a major modifiable risk factor for cardio-cerebrovascular and renal diseases. This study estimated the national burden of hypertension, defined as systolic blood pressure ≥140 mm Hg, on morbidity and mortality in 2021 in France.</p><p><strong>Methods: </strong>For all diseases causally associated with hypertension (cardiovascular diseases, chronic kidney diseases, and dementia), the number and proportion of cases attributable to hypertension in adults aged ≥35 years were estimated using population attributable fractions. Age- and sex-specific population attributable fractions were computed using the distribution of hypertension in the French population. These population attributable fractions were applied to nationwide statistics for mortality, hospitalizations, disease prevalence, years of life lost, years of life lived with disability, and disability-adjusted years of life.</p><p><strong>Results: </strong>The largest population attributable fractions were for ischemic heart disease and hemorrhagic stroke, with over 40% of cases attributable to hypertension. Overall, more than 385 000 patients were hospitalized due to hypertension, with 3.7 million hospitalizations and 6.2 million hospital days (all hospitalizations, including 3.4 million for chronic kidney disease) and including 390 000 overnight hospitalization. In 2021, more than 1.15 million individuals lived with ischemic heart disease attributable to hypertension, 1.26 million with chronic kidney diseases, and 358 033 with heart failure. Among 184 059 annual deaths from cardiovascular diseases, dementia, and chronic kidney diseases, 30% (55 280 deaths) were attributable to hypertension. Hypertension accounted for 8.5% of all deaths and 498 052 years of life lost.</p><p><strong>Conclusions: </strong>In France, despite near-universal health coverage and free health care access, the burden attributable to hypertension remains high.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"357-369"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794476","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}
引用次数: 0
Definitive Evidence for the Identification and Function of Renin-Expressing Cholinergic Neurons in the Nucleus Ambiguus. 模棱两可核中肾素表达胆碱能神经元的鉴定和功能的明确证据。
IF 6.9 1区 医学
Hypertension Pub Date : 2025-02-01 Epub Date: 2024-12-02 DOI: 10.1161/HYPERTENSIONAHA.124.23740
Éva M Fekete, Javier Gomez, Mina Ghobrial, Kathren Kaminski, Patricia C Muskus, Carie R Boychuk, Ana Hantke Guixa, Ibrahim Vazirabad, Michelle Xie, Azeez Ganiyu, Daria Golosova, Natalia M Mathieu, Yoko B Wang, Ko-Ting Lu, Kelsey K Wackman, Daniel T Brozoski, Gary C Mouradian, Matthew R Hodges, Jeffrey L Segar, Justin L Grobe, Curt D Sigmund, Pablo Nakagawa
{"title":"Definitive Evidence for the Identification and Function of Renin-Expressing Cholinergic Neurons in the Nucleus Ambiguus.","authors":"Éva M Fekete, Javier Gomez, Mina Ghobrial, Kathren Kaminski, Patricia C Muskus, Carie R Boychuk, Ana Hantke Guixa, Ibrahim Vazirabad, Michelle Xie, Azeez Ganiyu, Daria Golosova, Natalia M Mathieu, Yoko B Wang, Ko-Ting Lu, Kelsey K Wackman, Daniel T Brozoski, Gary C Mouradian, Matthew R Hodges, Jeffrey L Segar, Justin L Grobe, Curt D Sigmund, Pablo Nakagawa","doi":"10.1161/HYPERTENSIONAHA.124.23740","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23740","url":null,"abstract":"<p><strong>Background: </strong>The importance of the brain renin-angiotensin system in cardiovascular function is well accepted. However, not knowing the precise source of renin in the brain has been a limitation toward a complete understanding of how the brain renin-angiotensin system operates.</p><p><strong>Methods: </strong>Highly sensitive in situ hybridization techniques and conditional knockout mice were used to address the location and function of renin in the brainstem.</p><p><strong>Results: </strong>We identified novel renin-expressing cholinergic neurons in the nucleus ambiguus (NuAm), a major vagal cardioinhibitory center in the brainstem. The expression of renin-angiotensin system genes was relatively abundant in the NuAm, implying that angiotensin II might mediate an important regulatory role in this nucleus and other regions with neural connectivity to the NuAm. Then, we generated conditional knockout mice lacking the classical renin isoform (Ren-a<sup>ChAT-KO</sup>), specifically in cholinergic neurons. Ablation of Ren-a in cholinergic neurons abrogated renin expression in the NuAm. Moreover, studies using radiotelemetry, heart rate variability analyses, and pharmacological approaches revealed that the parasympathetic nervous system is depressed in Ren-a<sup>ChAT-KO</sup> males while augmented in the Ren-a<sup>ChAT-KO</sup> females. Subsequently, transcriptomic approaches were used to infer putative genes and signaling pathways regulated by renin within the NuAm.</p><p><strong>Conclusions: </strong>This study revealed that renin in cholinergic neurons plays a fundamental role in preserving autonomic balance and cardiovascular homeostasis in a sex-dependent manner. These findings define the NuAm as an endogenous, local source of renin with biological function and serve as conclusive evidence for the presence and functionality of the brain renin-angiotensin system.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"282-292"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768564","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}
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