Hypertension最新文献

{"title":"Youth Blood Pressure and Target Organ Injury Markers: The SHIP AHOY Study.","authors":"Gilad Hamdani, Elaine M Urbina, Stephen R Daniels, Bonita E Falkner, Michael A Ferguson, Joseph T Flynn, Coral D Hanevold, Julie R Ingelfinger, Philip R Khoury, Marc B Lande, Kevin E Meyers, Joshua Samuels, Mark Mitsnefes","doi":"10.1161/HYPERTENSIONAHA.124.23018","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23018","url":null,"abstract":"<p><strong>Background: </strong>Hypertension in adolescence is associated with subclinical target organ injury. We aimed to determine whether different blood pressure thresholds were associated with an increasing number of target organ injury markers in healthy adolescents.</p><p><strong>Methods: </strong>A total of 244 participants (mean age 15.5±1.8 years, 60.1% male) were studied. Participants were divided based on systolic clinic and systolic awake ambulatory blood pressure into low- (<75th percentile), mid- (75th-90th percentile), and high-risk (>90th percentile) groups. The ambulatory blood pressure phenotype was classified as normotensive, white-coat, masked, or sustained hypertension. Target organ injury assessments included left ventricular mass, systolic and diastolic function, and vascular stiffness. A multivariable general linear model was constructed to evaluate the association of different participant characteristics with higher numbers of target organ injury markers.</p><p><strong>Results: </strong>A total of 31.2% of participants had 1, 11.9% 2, 3.7% 3, and 0.8% 4 target organ injury markers. The number of target organ injury markers increased according to the risk groups: the percentage of participants with >1 marker in the low-, mid-, and high-risk groups was 6.7%, 19.1%, and 21.8% (<i>P</i>=0.02) and 9.6%, 15.8%, and 32.2% (<i>P</i><0.001), based on clinic and ambulatory blood pressure, respectively. Participants with white-coat (23%), masked (35%), and sustained hypertension (32%) had significantly higher >1 target organ injury marker than normotensives (8%, <i>P</i><0.001). The results were unchanged in multivariate analysis.</p><p><strong>Conclusions: </strong>High clinic and ambulatory blood pressure values, as well as ambulatory blood pressure phenotypes (white-coat, masked, and sustained hypertension), were independently associated with an increasing number of subclinical cardiovascular injury markers in adolescents.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515380","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":"Hypertension Prevention and Healthy Life Expectancy in Black Adults: The Jackson Heart Study.","authors":"Kathryn Foti, Yiyi Zhang, Susan E Hennessy, Lisandro D Colantonio, Lama Ghazi, Shakia T Hardy, Milla Arabadjian, Rushelle Byfield, Valy Fontil, Cora E Lewis, Daichi Shimbo, Paul Muntner, Brandon K Bellows","doi":"10.1161/HYPERTENSIONAHA.124.23702","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.23702","url":null,"abstract":"<p><strong>Background: </strong>The impact of preventing hypertension and maintaining normal blood pressure (BP) on life expectancy and healthy life expectancy (HLE) among Black adults, who are disproportionately affected by hypertension, has not been quantified.</p><p><strong>Methods: </strong>We used a discrete event simulation to estimate life expectancy and HLE among a cohort of Black adults from the Jackson Heart Study (n=4933) from age 20 to 100 years or until death. We modeled preventing hypertension as having BP <130/80 mm Hg and maintaining normal BP as having BP <120/80 mm Hg across the lifespan. In the primary analysis, we assumed that lowering BP decreased the risk of cardiovascular disease events, resulting in life expectancy and HLE gains. In a secondary analysis, we assumed that preventing hypertension and maintaining normal BP directly reduced both cardiovascular disease and mortality risk.</p><p><strong>Results: </strong>At age 20 years, the projected average life expectancy was age 80.8 (95% uncertainty interval [UI], 80.6-81.1) years, and HLE was 70.5 (95% UI, 70.3-70.7) healthy life years. In the primary analysis, preventing hypertension and maintaining normal BP added 0.9 (95% UI, 0.8-1.1) and 1.1 (95% UI, 0.9-1.3) years to life expectancy, respectively, and 2.7 (95% UI, 2.6-2.9) and 2.9 (95% UI, 2.7-3.1) healthy life years to HLE, respectively. In the secondary analysis, preventing hypertension and maintaining normal BP added 4.5 (95% UI, 4.3-4.6) and 4.6 (95% UI, 4.4-4.8) years to life expectancy, respectively, and 5.7 (95% UI, 5.6-5.8) and 5.9 (95% UI, 5.7-6.0) healthy life years to HLE, respectively.</p><p><strong>Conclusions: </strong>Preventing hypertension and maintaining normal BP were projected to increase life expectancy and HLE among Black adults.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500324","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":"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}

{"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}

{"title":"Environmental Hypertensionology and the Mosaic Theory of Hypertension.","authors":"Sanjay Rajagopalan, Robert D Brook, Thomas Münzel","doi":"10.1161/HYPERTENSIONAHA.124.18733","DOIUrl":"10.1161/HYPERTENSIONAHA.124.18733","url":null,"abstract":"<p><p>Hypertension is a multifactorial condition influenced by the intricate interplay of biological and genetic determinants. The growing field of Environmental Hypertensionology endorses the outsized role of environmental factors in the pathogenesis and exacerbation of hypertension. It provides a clinical approach to address these factors at the individual and societal levels. Environmental stressors contributing to blood pressure levels can be viewed within the mosaic model of hypertension, which offers a comprehensive framework for understanding blood pressure regulation through its connection with multiple other nodes causally related to the pathogenesis of hypertension. This review synthesizes growing evidence supporting the impact of several factors in the physical environment and adverse stressors embedded in key provisioning systems, including air, noise, and chemical pollution, along with aspects of the built environment, green spaces, food systems, on the global burden of hypertension. Although many factors may not be directly in the causal cascade of hypertension, the web of connections between many behooves an understanding of the important nodes for intervention. Public health strategies emphasizing the redesign of environments present an unprecedented opportunity to enhance global hypertension control rates. Future research should thus focus on integrating environmental risk assessment and interventions into clinical practice, optimizing urban planning, and public policy to achieve meaningful reductions in the global burden of hypertension. By understanding hypertension as a mosaic of interconnected causes, healthcare professionals are better equipped to individualize treatment, combining lifestyle interventions and multiple drug classes to target environmental and genetic factors driving high blood pressure.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448949","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":"Modulation of Calcium Signaling on Demand to Decipher the Molecular Mechanisms of Primary Aldosteronism.","authors":"Bakhta Fedlaoui, Teresa Cosentino, Zeina R Al Sayed, Rita Alexandre Coelho, Isabelle Giscos-Douriez, Nicolo Faedda, May Fayad, Jean-Sebastien Hulot, Chris Magnus, Scott M Sternson, Simon Travers-Allard, Stephanie Baron, David Penton, Fabio L Fernandes-Rosa, Maria-Christina Zennaro, Sheerazed Boulkroun","doi":"10.1161/HYPERTENSIONAHA.124.23295","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.23295","url":null,"abstract":"<p><strong>Background: </strong>Primary aldosteronism is the most common form of secondary hypertension. The most frequent genetic cause of aldosterone-producing adenomas is somatic mutations in the potassium channel KCNJ5. They affect the ion selectivity of the channel, with sodium influx leading to cell membrane depolarization and activation of calcium signaling, the major trigger for aldosterone biosynthesis.</p><p><strong>Methods: </strong>To investigate how <i>KCNJ5</i> mutations lead to the development of aldosterone-producing adenomas, we established an adrenocortical cell model in which sodium entry into the cells can be modulated on demand using chemogenetic tools (H295R-S2 α7-5HT3-R [α7-5HT3 receptor] cells). We investigated their functional and molecular characteristics with regard to aldosterone biosynthesis and cell proliferation.</p><p><strong>Results: </strong>A clonal cell line with stable expression of the chimeric α7-5HT3-R in H295R-S2 cells was obtained. Increased sodium entry through α7-5HT3-R upon stimulation with uPSEM-817 led to cell membrane depolarization, opening of voltage-gated Ca²⁺ channels, and increased intracellular Ca²⁺ concentrations, resulting in the stimulation of <i>CYP11B2</i> expression and increased aldosterone biosynthesis. Increased intracellular sodium influx did not increase proliferation but rather induced apoptosis. RNA sequencing and steroidome analyses revealed unique profiles associated with Na⁺ entry, with only partial overlap with Ang II (angiotensin II) or potassium-induced changes.</p><p><strong>Conclusions: </strong>H295R-S2 α7-5HT3-R cells are a new model reproducing the major features of cells harboring <i>KCNJ5</i> mutations. Increased expression of <i>CYP11B2</i> and stimulation of the mineralocorticoid biosynthesis pathway are associated with a decrease of cell proliferation and an increase of apoptosis, indicating that additional events may be required for the development of aldosterone-producing adenomas.</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":"143399104","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":"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}

{"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}

{"title":"Role of Inflammatory Biomarkers in Mediating Causal Effect of Life Course Body Composition on Hypertension.","authors":"Liwan Fu, Yan Li, Hong Cheng, Jingfan Xiong, Pei Xiao, Hongbo Dong, Xinying Shan, Yanyan Li, Jie Mi","doi":"10.1161/HYPERTENSIONAHA.124.24542","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.24542","url":null,"abstract":"<p><strong>Background: </strong>The mediating role of inflammatory biomarkers in the causal relationship between body composition and hypertension remains unclear and requires further investigation.</p><p><strong>Methods: </strong>This study used a combination of retrospective observational analysis and Mendelian randomization approaches. Observational data were derived from 4717 Chinese children and adolescents aged 6 to 18 years who underwent dual-energy X-ray absorptiometry to assess body composition. Mendelian randomization analyses utilized summary statistics from large-scale data sets, including UK Biobank, deCODE2021, International Consortium of Blood Pressure, FinnGen, and other consortia. The inflammatory biomarkers included leptin, insulin, adiponectin, osteocalcin, FGF23 (fibroblast growth factor 23), and PTH (parathyroid hormone).</p><p><strong>Results: </strong>The observational analysis revealed that increased fat mass positively influenced diastolic blood pressure through osteocalcin, while fat-free mass had an inverse effect. Insulin mediated the association between fat mass and systolic blood pressure, diastolic blood pressure, and hypertension, with additional indirect effects observed for PTH (all <i>P</i><0.05). The Mendelian randomization analyses demonstrated a causal relationship between childhood body mass index and hypertension mediated by insulin (indirect effect: odds ratio, 0.87 [95% CI, 0.78-0.97]) and adiponectin (odds ratio, 1.13 [95% CI, 1.04-1.23]). Adiponectin mediated the effects of fat-free mass (odds ratio, 0.81 [95% CI, 0.71-0.93]) and fat mass (odds ratio, 1.30 [95% CI, 1.11-1.51]) on hypertension. Leptin, adiponectin, and insulin also mediated the causal effects of body composition on systolic blood pressure, diastolic blood pressure, and hypertension.</p><p><strong>Conclusions: </strong>These findings indicate that body composition influences blood pressure through distinct inflammatory biomarkers. Targeting inflammatory biomarkers may provide tailored strategies for managing body composition and hypertension.</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":"143399107","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":"GWAS for Defining the Etiology of Hypertension: Have They Delivered?","authors":"Matthew R Alexander, Todd L Edwards, David G Harrison","doi":"10.1161/HYPERTENSIONAHA.124.23451","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.23451","url":null,"abstract":"<p><p>Genome-wide association studies have identified >3500 associated single nucleotide polymorphisms and over 1000 independent loci associated with hypertension. These individually have small effect sizes, and few associated loci have been experimentally tested for causal roles in hypertension using animal models or in humans. Thus, methods to prioritize and maximize the relevance of identified single nucleotide polymorphisms and associated loci are critical to determine their importance in hypertension. We propose several approaches to aid in these efforts, including: (1) integration of genome-wide association study data with multiomic data sets, including proteomics, transcriptomics, and epigenomics, (2) utilizing linked clinical and genetic data sets to determine genetic contributions to hypertension subphenotypes with distinct drivers, and (3) performing whole exome/genome sequencing on cohorts of individuals with severe hypertension to enrich for rare variants with larger effect sizes. Rather than creating longer lists of hypertension-associated single nucleotide polymorphisms, these approaches are needed to identify key mediators of hypertension pathophysiology.</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":"143399100","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}