BACKGROUND: Early-onset preeclampsia is characterized by maternal-fetal immune dysregulation and trophoblast dysfunction, commonly presenting with a reduction in regulatory T cells (Tregs) and impaired trophoblast invasi...BACKGROUND: Early-onset preeclampsia is characterized by maternal-fetal immune dysregulation and trophoblast dysfunction, commonly presenting with a reduction in regulatory T cells (Tregs) and impaired trophoblast invasion. However, the precise role of aberrant Treg-trophoblast communication in early-onset preeclampsia progression remains unclear. METHODS: A preeclampsia-like syndrome mouse model was established by administration of the nitric oxide inhibitor, NG-nitroarginine methyl ester hydrochloride. Mouse natural Tregs were adoptively transferred into the NG-nitroarginine methyl ester hydrochloride model via tail vein injection. Confirmatory experiments were conducted using an additional preeclampsia-like syndrome model generated by the administration of iMDK (MDK [midkine] and PI3K/Akt [the phosphatidylinositol 3-kinase/protein kinase B] inhibitor). An in vitro coculture model was established using a trophoblast cell line and human Tregs isolated from both umbilical cord/placental blood and maternal peripheral blood. RESULTS: Placentas from patients with early-onset preeclampsia had reduced numbers of Tregs compared with healthy controls. Adoptive Treg transfer activated the TβR1 (transforming growth factor β type I receptor)/Smad3 (Sma- and Mad-related protein 3) signaling pathway in trophoblasts, thereby enhancing their invasive and proliferative capacities and ultimately mitigating preeclampsia-like syndrome. Moreover, maternal peripheral blood MDK levels exhibited a significant inverse correlation with disease severity. MDK upregulates LAP (latency-associated peptide) expression on Tregs and acts synergistically with adoptive Treg transfer, resulting in a more pronounced therapeutic effect than Treg transfer alone. CONCLUSIONS: This study demonstrates that restoring Tregs ameliorates preeclampsia-like syndrome by enhancing trophoblast function. We further identify MDK as a key mediator enhancing this therapy, which upregulates LAP expression on Tregs and synergistically improves its overall efficacy against early-onset preeclampsia.
Semenikhina M, Jones AC, Pasham V
… +3 more, Budisavljevic MN, Palygin O, Ilatovskaya DV
Hypertension
· 2026 Jul · PMID 42100811
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Nicotine exposure is increasingly widespread due to the expansion of the use of noncombustible tobacco and nicotine-replacement products; yet nicotine is still being framed as an addictive but relatively benign compound....Nicotine exposure is increasingly widespread due to the expansion of the use of noncombustible tobacco and nicotine-replacement products; yet nicotine is still being framed as an addictive but relatively benign compound. This review synthesizes clinical and experimental evidence linking nicotine exposure to cardiorenal disease, emphasizing that risks persist after cessation. We discuss here a central novel concept that damage caused by nicotine in tissues is not determined solely by receptor signaling, as nicotine exists in chemical forms capable of strong receptor-independent membrane diffusion. Mechanistically, we highlight convergent pathways of nicotine-induced cellular injury, focusing on redox stress and underscoring major limitations in the field, such as the lack of studies in epithelial cells. We further emphasize the emerging paradigm that links nicotine and nitric oxide synthase (NOS) biology, in which reduced nitric oxide bioavailability, NOS uncoupling, and peroxynitrite-mediated protein nitration represent underappreciated drivers of persistent cardiorenal injury in response to nicotine. Finally, we outline gaps and research priorities needed to identify therapeutic strategies that specifically mitigate nicotine-driven oxidative and nitrosative injury in vulnerable populations with hypertension, diabetes, and chronic kidney disease.
BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a representative vascular remodeling disease with a poor prognosis. Previous findings from our study have implicated the NICD4 (Notch4 intracellular domain) in pulmonar...BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a representative vascular remodeling disease with a poor prognosis. Previous findings from our study have implicated the NICD4 (Notch4 intracellular domain) in pulmonary artery smooth muscle cells (PASMCs) in the pathogenesis of HPH. However, the underlying regulatory mechanisms remain unclear. In this study, we aimed to elucidate the potential regulatory mechanism of NICD4 in HPH. METHODS: Using coimmunoprecipitation combined with mass spectrometry, we identified USP8 (ubiquitin-specific peptidase 8) as a novel binding protein of NICD4 in PASMCs. The functional role of USP8 was investigated in vivo using smooth muscle cell-specific knockout (Usp8) mice and in vitro using primarily cultured PASMCs, alongside pharmacological inhibition with DUB-IN-2 (deubiquitinase-inhibitor-2). RESULTS: USP8 was significantly upregulated in lung tissues from patients with HPH due to interstitial lung disease or chronic obstructive pulmonary disease, HPH rodent models, as well as in hypoxic PASMCs. deficiency in Acta2-positive mice (Usp8) or pharmacological inhibition of USP8 by DUB-IN-2 markedly attenuated HPH development. In vitro, USP8 knockdown suppressed hypoxia-induced PASMC proliferation, migration, and apoptosis resistance by modulating the NICD4-MAPK pathway. Mechanistically, USP8 was bound directly to NICD4 to maintain its stability by removing the K48-linked ubiquitin chain on NICD4 at lysine 1760, thus preventing proteasomal degradation. Furthermore, can be transcriptionally upregulated by CSL/NICD4 under hypoxia, forming a NICD4/USP8-positive feedback loop. CONCLUSIONS: Our study unveils a critical NICD4/USP8-positive feedback loop that drives HPH pathogenesis, highlighting the importance of ubiquitination in pulmonary vascular remodeling. Targeted disruption of this loop represents a promising therapeutic strategy for HPH.
Preeclampsia is a pregnancy-specific hypertensive disorder, clinically defined by new-onset hypertension with proteinuria or other maternal organ dysfunction. It is a leading cause of maternal and perinatal mortality wor...Preeclampsia is a pregnancy-specific hypertensive disorder, clinically defined by new-onset hypertension with proteinuria or other maternal organ dysfunction. It is a leading cause of maternal and perinatal mortality worldwide and remains an incurable condition, with delivery as the only definitive treatment. Although heterogenous, the disorder originates in placental dysfunction, characterized by inadequate trophoblast invasion and impaired spiral uterine artery remodeling, resulting in syncytiotrophoblast stress and the release of placenta-derived factors. Increased placental secretion of antiangiogenic factors, including soluble fms-like tyrosine kinase-1 and soluble endoglin, promotes angiogenic imbalance and drives widespread maternal endothelial dysfunction. This narrative review synthesizes findings from human studies and experimental research models used to investigate angiogenic dysregulation in preeclampsia, with particular focus on in vitro and in vivo models, and emerging 3-dimensional placental platforms. In vitro models, such as trophoblast organoids, placenta-on-a-chip devices, and 3-dimensional bioprinted constructs, recapitulate key aspects of the placental microenvironment and enable detailed study of aberrant angiogenesis and how to target it, while reducing reliance on limited primary tissue and improving experimental control. Complementing in vitro models, in vivo models are essential for linking placenta-derived angiogenic imbalance to maternal disease phenotypes, therapeutic responses, and fetal outcomes. This review provides a comprehensive assessment of current literature on models that recapitulate angiogenic imbalance in preeclampsia. We emphasize the importance of integrating bioengineering, cell biology, and clinical insights to improve our understanding of preeclampsia pathogenesis and to develop predictive tools and therapeutic strategies to manage angiogenic dysregulation in preeclampsia.
Expanded screening with the aldosterone-renin ratio has improved detection of primary aldosteronism, the most common surgically curable cause of arterial hypertension. However, identification of surgically curable primar...Expanded screening with the aldosterone-renin ratio has improved detection of primary aldosteronism, the most common surgically curable cause of arterial hypertension. However, identification of surgically curable primary aldosteronism remains constrained by technical limitations of subtyping by adrenal vein sampling (AVS), as bilateral selectivity often fails. Although alternative biomarkers superior to cortisol may help reduce this rate, currently, the failure to achieve bilateral selectivity precludes calculation of the lateralization index and, thus, diverts patients toward lifelong medical therapy. Recent advances have established the relative aldosterone secretion index (RASI) as a physiologically grounded strategy to interpret partially successful AVS. By quantifying aldosterone secretion from each adrenal gland relative to peripheral values and incorporating contralateral suppression, RASI-based interpretation can rescue many AVS studies by enabling subtyping under unilateral selectivity with 80% concordance with the lateralization index, when available. Postoperative outcomes following RASI-guided adrenalectomy approximate those achieved after fully selective AVS, with biochemical cure rates of 85% to 90% and blood pressure improvement in 65% to 75%. Studies published over the past 3 years have clarified factors influencing RASI performance, including cosyntropin stimulation, variations in aldosterone secretion, and the limited utility of cross-sectional imaging alone for subtype classification. Collectively, the available data support the incorporation of RASI into contemporary AVS interpretation algorithms. As primary aldosteronism management enters a postdetection era, subtyping has emerged as the principal bottleneck to definitive cure. RASI provides a pragmatic, evidence-based means to overcome the imperative dependence on bilateral selectivity while preserving diagnostic accuracy, thereby improving access to adrenalectomy and associated cardiovascular benefits.
Ogyu A, Rouzier V, Sufra R
… +17 more, St Sauveur R, Celestin K, Forestal G, Préval F, Marcellin SE, Auguste S, Lee MH, Bennett C, Alexandre W, Huffman MD, Jamerson KA, Malebranche R, Théard M, Deschamps MM, Pape JW, Yan LD, McNairy ML
Hypertension
· 2026 Jul · PMID 42089122
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BACKGROUND: Elevated blood pressure (BP) is the leading cause of death globally, with the greatest burden in low-and-middle income countries. Longitudinal BP data are limited in settings of extreme poverty. We identified...BACKGROUND: Elevated blood pressure (BP) is the leading cause of death globally, with the greatest burden in low-and-middle income countries. Longitudinal BP data are limited in settings of extreme poverty. We identified longitudinal BP trajectories and associated risk factors in urban Haiti. METHODS: We analyzed data from 2073 adults (≥18 years) with ≥3 facility-based BP measurements between March 2019 and April 2025 in the population-based Haiti Cardiovascular Disease Cohort. Demographic, behavioral, and clinical data were collected annually. Participants received routine clinical care based on Ministry of Health guidelines. Latent class growth mixture modeling identified systolic BP trajectory groups. Enrollment characteristics associated with BP trajectory group membership were analyzed using multivariable generalized-logit models. RESULTS: At study enrollment, median age was 43 years (interquartile range, 30-56); 60% were female, 100% identified as Black Haitian, and 69% lived on <US$1/d. Over 13 446 facility visits (median follow-up, 3.9 years), we identified 4 systolic BP trajectories based on mean enrollment BP: normal, rising (107 mm Hg, 39.2%, mean change +0.7 mm Hg/y), moderate, rising (126 mm Hg, 34.7%, +1.3 mm Hg/y), high, reduction (151 mm Hg, 19.2%, -1.6 mm Hg/y), and very high, rebound (173 mm Hg, 6.9%, -0.8 mm Hg/y). Antihypertensive medication usage and BP control among participants with hypertension increased. Older age, lower education, and obesity were associated with high, reduction, or very high, rebound BP trajectory groups. CONCLUSIONS: In this cohort of young, Black adults in Haiti, we identify 4 BP trajectories, describe increases in antihypertensive medication usage and improvement in BP control, demonstrating BP care is feasible in a low-resourced setting.
Santalahti A, Ojanen A, Palosaari T
… +5 more, Jääskeläinen T, Kaartinen NE, Sääksjärvi K, Laatikainen T, Lundqvist A
Hypertension
· 2026 Jul · PMID 42063398
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BACKGROUND: We examined 50-year time trends in hypertension prevalence and salt intake in Finland to evaluate the impact of public health interventions and inform future strategies for salt reduction and hypertension pre...BACKGROUND: We examined 50-year time trends in hypertension prevalence and salt intake in Finland to evaluate the impact of public health interventions and inform future strategies for salt reduction and hypertension prevention. METHODS: Twelve cross-sectional health examination surveys conducted in Finland between 1972 and 2023 included 77 418 randomly selected adults aged 25 to 64 years, with blood pressure measured in all participants and 24-hour urine samples collected from a subsample of 5035 individuals. Year-to-year changes in the prevalence of hypertension and mean salt intake were assessed using age-adjusted logistic regression, with the previous adjacent survey year as the reference for each year. RESULTS: Hypertension prevalence (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg or current use of antihypertensive medication) declined in men from 1972 to 2002 and in women until 1997, after which reductions slowed, with 2023 rates remaining high (42.6% in men, 31.8% in women). Mean salt intake decreased until the early 2000s (men: from 13.9-9.7 g/d; women: from 11.1-7.6 g/d) but plateaued thereafter, remaining above recommended levels in 2023 (men: 10.3 g/d; women: 7.6 g/d). CONCLUSIONS: The previously declining trend in hypertension prevalence in Finland has plateaued over the last 2 decades, coinciding with persistently high salt intake remaining largely unchanged throughout the 21st century. Actions aimed at enhancing hypertension prevention and reducing population salt intake should therefore be reintroduced into Finland's public health discourse.
BACKGROUND: Atrial and brain natriuretic peptides activate GC-A/NPRA (guanylyl cyclase-A/natriuretic peptide receptor-A) and regulate blood pressure and electrolyte homeostasis. Renal tubule (RT) dysfunction results in d...BACKGROUND: Atrial and brain natriuretic peptides activate GC-A/NPRA (guanylyl cyclase-A/natriuretic peptide receptor-A) and regulate blood pressure and electrolyte homeostasis. Renal tubule (RT) dysfunction results in decreased kidney function and increased blood pressure. We determined the sex-specific consequences of RT cell-specific deletion of (encoding NPRA) on blood pressure and renal hemodynamics. METHODS: Mice were generated with inducible RT knockout by breeding lox-flanked (flox/flox: ) exons 1 to 2 in with mice expressing the Pax8-rtTA-LC-1- transgene. Doxycycline-treated RT cell-specific knockout (-), heterozygous (HT; ), and wild-type () male and female mice were used. Proximal tubule, distal tubule, and cortical collecting duct were isolated from RT- knockout mice and did not express mRNA or protein. RESULTS: RT cell-specific male knockout and HT mice showed significantly lower glomerular filtration rate, creatinine clearance, and urinary sodium excretion than female mice, compared with wild-type mice. The effect of deletion was more severe on high-salt diets than their normal-diet counterparts. Loss of in RT segments significantly increased systolic blood pressure and mean arterial pressure in a sex-specific manner. Mutant male mice showed higher total urinary protein and albumin-creatinine ratios than female mice. On a high-salt diet, male knockout and HT mice showed greater salt sensitivity than female mice. CONCLUSIONS: Loss of along the nephron tubules leads to arterial hypertension and abnormal renal functional hemodynamic changes that are more pronounced in male mice compared with female mice.
Guo T, Yang L, Yang Y
… +17 more, Xie J, Ren J, He M, Chu C, Liu Z, Li C, Yan Y, Sun Y, Wang D, Hu G, Du M, Jia H, Yan Y, Zhao M, Magnussen CG, Xi B, Mu J
BACKGROUND: Blood pressure (BP) is a dynamic trait associated with cardiovascular disease. We aimed to estimate age-specific BP levels and rates of change from childhood to mid-adulthood and to examine their associations...BACKGROUND: Blood pressure (BP) is a dynamic trait associated with cardiovascular disease. We aimed to estimate age-specific BP levels and rates of change from childhood to mid-adulthood and to examine their associations with subsequent subclinical target organ damage. METHODS: We included 2508 participants from the Hanzhong Adolescent Hypertension Study with BP measured ≥4× from 1987 to 2023. Surrogate markers of target organ damage were assessed, including arterial stiffness, left ventricular hypertrophy, and albuminuria. Growth models were used to construct BP trajectories and estimate age-specific BP levels and rates of change (slopes). RESULTS: Rates of change in BP at each age point from childhood to mid-adulthood were positively associated with arterial stiffness and albuminuria in mid-adulthood, independent of corresponding BP levels. The magnitude of the associations rose from childhood, peaked in adolescence, and declined thereafter. For example, odds ratios (95% CIs) per 1 SD increase in systolic BP change rates for arterial stiffness increased from 1.94 (1.69-2.24) at age 6 to 2.11 (1.82-2.44) at age 13, then declined to 1.13 (1.01-1.28) by age 52. Faster BP increases were more strongly associated with arterial stiffness and albuminuria than concurrent BP levels during childhood and adolescence, whereas the opposite trend was observed in young and mid-adulthood. Similar age-dependent trends were identified for left ventricular hypertrophy, with minor variations in the ages at which associations reached statistical significance. CONCLUSIONS: Accelerated BP increases during childhood and adolescence show a stronger association with mid-adult subclinical target organ damage than increases occurring in adulthood.
BACKGROUND: Peri-arterial neural tissue surrounding the renal artery contributes to sympathetic overactivity in hypertension. During adrenal surgery, surgical peri-arterial neural dissection may interrupt these fibers an...BACKGROUND: Peri-arterial neural tissue surrounding the renal artery contributes to sympathetic overactivity in hypertension. During adrenal surgery, surgical peri-arterial neural dissection may interrupt these fibers and exert a renal denervation-like effect. Whether this maneuver improves postoperative blood pressure control remains unclear. METHODS: We retrospectively reviewed 127 hypertensive patients who underwent adrenal surgery between January 2022 and March 2025. According to intraoperative findings, patients were classified into a surgical peri-arterial neural dissection group or a nondissection group. After 1:2 manual matching by age, sex, and hypertension duration, 54 patients were included. Postoperative hypertension remission and changes in antihypertensive medication use, quantified by the defined daily dose, were assessed. Multivariable logistic regression was used to explore factors associated with postoperative nonremission. Renal and adrenal function markers were compared between groups. RESULTS: The surgical peri-arterial neural dissection group had a higher remission rate than the nondissection group (50.0% versus 16.1%; =0.008). Surgical peri-arterial neural dissection was independently associated with lower odds of postoperative nonremission (odds ratio, 0.150 [95% CI, 0.030-0.744]; =0.020), supporting its potential role in improving postoperative blood pressure control. Patients in the dissection group showed greater reductions in antihypertensive medication use (median change in defined daily dose, -1.0 versus 0.0; =0.006). Creatinine, blood urea nitrogen, cortisol, and adrenocorticotropic hormone levels were similar between groups. CONCLUSIONS: Surgical peri-arterial neural dissection performed during adrenal surgery was associated with improved postoperative blood pressure control and reduced medication burden without evidence of impaired renal or adrenal function.
BACKGROUND: Whether central systolic blood pressure (cSBP) compared with brachial systolic blood pressure (bSBP) improves risk stratification remains debated. This study investigated whether cSBP is more closely associat...BACKGROUND: Whether central systolic blood pressure (cSBP) compared with brachial systolic blood pressure (bSBP) improves risk stratification remains debated. This study investigated whether cSBP is more closely associated with total and cardiovascular mortality than bSBP when recorded by 24-hour ambulatory BP monitoring with an arm cuff-based oscillometric monitor. METHODS: Consecutive patients referred for ambulatory BP monitoring and enrolled in the Shanghai Ruijin Ambulatory BP Monitoring Registry (2017-2023) were analyzed. bSBP and cSBP were recorded over 24 hours. cSBP was calibrated on brachial systolic and diastolic BP (cSBPc1) or on mean arterial pressure and brachial diastolic BP (cSBPc2). Total and cardiovascular mortality up to December 31, 2024, was assessed by record linkage with , coded death certificates. Linear and nonlinear Cox proportional hazard regression was applied with age as the underlying time-scale and adjusted for established cardiovascular risk factors. RESULTS: Over 4.0 years of follow-up, 505 of 36 594 participants (52.8% women; median age, 53.4 years) died, 174 from cardiovascular disease. With multivariable adjustment applied, the nonlinear compared with linear Cox models provided a better model fit for both end points (<0.001), irrespective of the period of the day and the calibration method of cSBP. Adding any 24-hour SBP to the base model increased the C statistics for total and cardiovascular mortality (0.003≤≤0.06). Adding cSBPc1 or cSBPc2 to the base model extended by bSBP also increased the C statistics, but not by a statistically significant amount (0.054≤≤0.22). CONCLUSIONS: cSBP compared with bSBP did not improve the associations with mortality. Measurement of the ambulatory bSBP is adequate for BP-based risk stratification.
Robberechts T, Stoenoiu MS, Soliveri L
… +10 more, Kiernan A, Canning C, Latosinska A, Smajda S, Hammer F, Pascarella R, Caroli A, Mischak H, Zedde M, Persu A
The First International Consensus on the diagnosis and management of fibromuscular dysplasia is a landmark document. Since its publication in 2019, important research has been ongoing in the field. In this review, we add...The First International Consensus on the diagnosis and management of fibromuscular dysplasia is a landmark document. Since its publication in 2019, important research has been ongoing in the field. In this review, we address current clinical challenges and discuss novel research approaches designed to overcome them. First, beyond the current distinction between multifocal and focal fibromuscular dysplasia (FMD), we propose a novel, more detailed and comprehensive classification of FMD and related diseases, which may be instrumental both as a research tool and as a common language between clinicians. Second, we discuss new information concerning phenotypes related to this condition. Third, we discuss the potential of emerging imaging and proteomic biomarkers to improve detection, diagnosis, and classification of FMD, as well as to predict prognosis and response to drugs or interventions. Finally, we describe promising novel approaches based on quantitative imaging, including computational fluid dynamics (enhanced or not by artificial intelligence), to assess the hemodynamic significance of FMD lesions. Along with further understanding of the genetics of FMD and animal models, these elements may allow for a more definite and personalized approach to this condition.
Ogunwole SM, Bertrand KA, Palmer JR
… +7 more, Bennett WL, Zeng Y, Jennings JM, Amoah AA, Boyer T, Cozier YC, Thorpe RJ
Hypertension
· 2026 Jul · PMID 42052660
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BACKGROUND: Black women in the United States experience higher rates of preeclampsia incidence, severity, and case fatality than White women, which contributes to cardiovascular disease disparities. Differences in cardio...BACKGROUND: Black women in the United States experience higher rates of preeclampsia incidence, severity, and case fatality than White women, which contributes to cardiovascular disease disparities. Differences in cardiometabolic risk factors do not fully explain this disparity, and there is growing consensus that racism may be a root cause. Few studies have evaluated associations between racism and preeclampsia among cohorts of exclusively Black women. METHODS: We analyzed data from the Black Women's Health Study, a follow-up study of ≈59 000 Black women in the United States established in 1995. We included women who were nulliparous at the time of enrollment and had their first birth from 1995 through 2009. Racism was measured as a total daily racism score (reported as daily exposure to interpersonal racism) and an institutional racism summary score (reported as ever being treated unfairly due to race with respect to police, housing, or on the job). We used logistic regression models adjusted for demographic, reproductive, and health factors to estimate odds ratios and 95% CIs. RESULTS: Women in the highest quartile of daily racism had a 50% higher odds of preeclampsia compared with those in the lowest quartile (adjusted odds ratio, 1.50 [95% CI, 1.13-1.99]). Women reporting institutional racism in 2 domains had 47% higher odds compared with those reporting none (adjusted odds ratio, 1.47 [95% CI, 1.14-1.91]). CONCLUSIONS: Greater experiences of daily and institutional racism were associated with an increased risk of preeclampsia, suggesting that racism contributes to the disproportionate burden of preeclampsia among Black women in the United States.
Fermín-Martínez CA, Núñez-Luna A, Guerra EC
… +9 more, Ramírez-García D, Perezalonso-Espinosa J, Zarco-Morales KP, León-Álvarez M, Ponce-Acosta C, De la Maza-Bustindui NS, Vargas-Vázquez A, Antonio-Villa NE, Bello-Chavolla OY
BACKGROUND: Systemic arterial hypertension is a public health concern, and timely diagnosis and management are critical to mitigate long-term effects. Here, we evaluated prevalence trends and determinants of hypertension...BACKGROUND: Systemic arterial hypertension is a public health concern, and timely diagnosis and management are critical to mitigate long-term effects. Here, we evaluated prevalence trends and determinants of hypertension phenotypes in the Mexican population over 2 decades. METHODS: We analyzed cross-sectional Mexican Health and Nutrition Surveys (2000-2024), including 146 904 adults aged ≥20 years. Hypertension was defined as self-reported diagnosis or blood pressure ≥140/90 mm Hg; undiagnosed hypertension (UDH) as blood pressure ≥140/90 mm Hg without prior diagnosis; and untreated hypertension as a prior diagnosis without treatment. UDH was classified as isolated systolic, isolated diastolic, or systolic-diastolic hypertension. We assessed trends with Poisson models and determinants of UDH and untreated hypertension with logistic models. RESULTS: We observed an overall decrease in hypertension prevalence from 33.1% in 2000 to 26.0% in 2024, concurrently with increases in diagnosed (12.3%-19.3%) and decreases in undiagnosed (20.7%-6.7%) hypertension. Isolated diastolic hypertension and systolic-diastolic hypertension declined over time, while isolated systolic hypertension increased, particularly among older adults. Among diagnosed cases, treatment percentage increased (69%-80%) and blood pressure control improved (40.5%-81.1%). Despite these trends, by 2024, ≈5 million Mexican adults still had UDH (25.9% of all hypertension cases), 2.9 million remained untreated, and 2.7 million were uncontrolled. Lack of diagnosis and treatment were more likely among men, individuals with unhealthy lifestyles, and those with social disadvantage. CONCLUSIONS: Results highlight evolving trends in hypertension diagnosis, treatment, and control in Mexico, with persistent challenges in UDH and untreated hypertension. Strengthening screening, treatment access, and equity is crucial to reduce hypertension-related cardiovascular risk.
Large language models have emerged as potential tools to support hypertension care, including diagnosis, treatment decision-making, and patient education. However, evidence regarding their validity, performance, and clin...Large language models have emerged as potential tools to support hypertension care, including diagnosis, treatment decision-making, and patient education. However, evidence regarding their validity, performance, and clinical applicability remains limited. The objective is to map current applications of large language models in hypertension care, with emphasis on model optimization strategies, evaluation approaches, and reported limitations. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews-compliant scoping review of primary studies published between 2023 and 2025 evaluating large language models in hypertension. Thirty-three studies were included. Data were charted on clinical use cases, model optimization techniques, evaluation metrics, data sets, and limitations. Applications were categorized into clinical decision support systems, patient education, medical education, research support, and administrative functions. GPT-based models predominated (82%). Model optimization was limited: 89% relied exclusively on prompt engineering. Most applications focused on patient education (52%) and clinical decision support systems (24%). In clinical decision support systems, reported accuracy ranged from 65% to 100%, reaching 87% to 91% for ambulatory blood pressure monitoring interpretation. Patient education applications showed accuracy between 80% and 90%, but frequent issues included excessive language complexity and occasional unsafe outputs. Across domains, evaluation methods were heterogeneous, reproducibility was inconsistently assessed, and safety concerns, including hallucinations and outdated knowledge, were commonly reported. Current evidence suggests that large language models may support selected tasks in hypertension care; however, their clinical reliability remains uncertain. The limited methodological rigor, minimal use of advanced optimization techniques, and narrow scope of evaluated applications preclude conclusions regarding routine clinical use. Further rigorously designed studies are required before broader implementation can be considered.
BACKGROUND: Hypertension is a major modifiable risk factor for chronic kidney disease (CKD), yet predicting which hypertensive individuals will progress to CKD remains challenging. We aimed to develop and validate a plas...BACKGROUND: Hypertension is a major modifiable risk factor for chronic kidney disease (CKD), yet predicting which hypertensive individuals will progress to CKD remains challenging. We aimed to develop and validate a plasma protein-based risk score for incident CKD in hypertension and to identify causal proteins and potential therapeutic targets. METHODS: Using data from the UK Biobank Pharma Proteomics Project, we included 22 258 hypertensive participants without baseline CKD. A protein risk score was developed in a training set (n=11 671) and validated in internal testing (n=7778) and external validation (Scotland/Wales, n=2809) cohorts. Hypothesis-generating Mendelian randomization using - protein quantitative trait loci was performed to prioritize proteins for functional follow-up. RESULTS: A 13-protein risk score (C-index ≈0.78) was developed, with a simplified 3-protein panel (RNASE1 [pancreatic ribonuclease], IGFBP4 [insulin-like growth factor-binding protein 4], GDF15 [growth differentiation factor 15]) capturing most of its predictive power. Adding the 13-protein score to the clinical model significantly improved the C-index by 0.019 (95% CI, 0.011-0.026) in internal testing and 0.047 (95% CI, 0.013-0.090) in external validation cohorts, with significant net reclassification improvement and integrated discrimination improvement, while an estimated glomerular filtration rate-based polygenic risk score provided no meaningful improvement. Mendelian randomization analysis identified 7 proteins (BMPER [BMP-binding endothelial regulator protein], GFRA1 [GDNF family receptor alpha-1], CST3 [cystatin-C], CXCL16 [C-X-C motif chemokine 16], FOLR1 [folate receptor alpha], AMBP [protein AMBP], and STC1 [stanniocalcin-1]) with nominally significant associations with hypertensive CKD, all with higher levels increasing risk. Enrichment analyses highlighted protease inhibition and folate metabolism pathways. FOLR1 and STC1 emerged as druggable targets. CONCLUSIONS: This study establishes a robust plasma protein signature for predicting hypertensive CKD and provides genetic evidence supporting several proteins as prioritized candidates, revealing novel pathways and nominating FOLR1 and STC1 as potential therapeutic targets for further investigation.
Hypertension
· 2026 Jun · PMID 42017239
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Obesity has been shown to correlate directly with circulating aldosterone levels and urinary aldosterone excretion in normotensive and hypertensive individuals without primary aldosteronism (PA). This relationship may be...Obesity has been shown to correlate directly with circulating aldosterone levels and urinary aldosterone excretion in normotensive and hypertensive individuals without primary aldosteronism (PA). This relationship may be bi-directional, though it is probably not symmetrical. Activation of the mineralocorticoid receptor in adipocytes may cause expansion of visceral fat mass. Conversely, adipocytes have been shown to augment the adrenal production of aldosterone by their release of aldosterone secretagogues-leptin, C1q/TNF-related proteins 1, and resistin-into the circulation. Patients with PA are more obese (idiopathic hyperaldosteronism>aldosterone-producing adenoma) than those with essential or no hypertension (women>men). The stronger association of obesity with idiopathic hyperaldosteronism than with the more metabolically severe unilateral PA, and the reductions in aldosterone levels after weight loss, suggest a substantive role for adipocytes in circulating aldosterone levels. A 2-sample Mendelian randomization analysis suggested that peri-renal adipose tissue, a form of visceral adipose tissue encompassing the adrenal glands, was causally linked to idiopathic hyperaldosteronism but not to other forms of hypertension. These observations support the speculation that at least a portion of idiopathic hyperaldosteronism cases represent adipocyte-driven hyperaldosteronism that might be effectively treated by weight loss. This review will provide the trans-disciplinary rationale for the hypothesis supporting a causal relationship between obesity and idiopathic hyperaldosteronism. This unproven hypothesis is eminently testable given the powerful pharmacological and surgical weight loss strategies currently available.