Zhu R, Chen C, Kuang M
… +3 more, Tai Y, Qin Y, Wu C
Hypertension
· 2026 Mar · PMID 41498144
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BACKGROUND: The health benefits of different moderate-to-vigorous physical activity (MVPA) patterns, including weekend warrior and regularly distributed activity, in individuals with hypertension remain unclear. This stu...BACKGROUND: The health benefits of different moderate-to-vigorous physical activity (MVPA) patterns, including weekend warrior and regularly distributed activity, in individuals with hypertension remain unclear. This study investigated associations between MVPA patterns and mortality and stroke outcomes in patients with hypertension. METHODS: A total of 52 838 participants from the UK Biobank with accelerometer data following hypertension were included. Participants were classified by weekly MVPA amounts and distribution: active weekend warrior, active regular, and inactive. Cox proportional hazards models examined associations between MVPA patterns and all-cause mortality, with secondary outcomes including stroke mortality, stroke, and ischemic stroke. RESULTS: During a median follow-up of 7.5 years, 2636 all-cause mortality, 161 stroke mortality, 875 stroke, and 716 ischemic stroke events occurred. Compared with the inactive group, both active weekend warriors (hazard ratio [HR], 0.70 [95% CI, 0.64-0.77]; <0.0001) and active regular (HR, 0.73 [95% CI, 0.65-0.82];<0.0001) demonstrated ≈30% lower risk of all-cause mortality. Both active groups showed risk reduction trends for stroke mortality (active weekend warrior: HR, 0.85 [95% CI, 0.59-1.22]; active regular: HR, 0.87 [95% CI, 0.55-1.38]), stroke (HR, 0.86 [95% CI, 0.73-1.00] versus HR, 0.91 [95% CI, 0.75-1.10]), and ischemic stroke (HR, 0.83 [95% CI, 0.70-0.99] versus HR, 0.87 [95% CI, 0.70-1.08]), though these were not statistically significant. CONCLUSIONS: Our findings underscore the health benefits of actively engaging in guideline-recommended MVPA for patients with hypertension, demonstrating a 30% mortality risk reduction whether they distribute MVPA throughout the week or concentrate MVPA within 1 to 2 days compared with physical inactivity.
Ikeda S, Shinohara K, Ono Y
… +13 more, Nakashima H, Miyamoto R, Hara A, Kashihara S, Matsumoto S, Yoshida D, Nakashima R, Nishihara M, Matsushima S, Hashimoto T, Katsuki S, Tsutsui H, Abe K
Hypertension
· 2026 Mar · PMID 41498140
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BACKGROUND: Sympathetic activation plays a role in heart failure (HF) development. Afferent renal nerve input may induce sympathoexcitation via the hypothalamic paraventricular nucleus (PVN), which projects to the rostra...BACKGROUND: Sympathetic activation plays a role in heart failure (HF) development. Afferent renal nerve input may induce sympathoexcitation via the hypothalamic paraventricular nucleus (PVN), which projects to the rostral ventrolateral medulla, a center for sympathetic regulation. Central dendritic release of vasopressin from PVN neurons reportedly stimulates neighboring presympathetic neurons, causing sympathoexcitation. This study investigated whether afferent renal nerves contribute to hypertensive cardiac dysfunction and whether the afferent renal nerve-PVN axis mediates sympathoexcitation via central vasopressin using salt-loaded Dahl salt-sensitive rats, a model of hypertensive HF. METHODS: Salt loading began at 6 weeks of age, with selective afferent renal denervation and total renal denervation performed at 9 weeks in Dahl salt-sensitive rats. HF phenotypes were examined at 16 weeks, while sympathomodulation by afferent renal denervation was assessed at 12 weeks, the pre-HF phase. RESULTS: At 16 weeks, afferent renal denervation and total renal denervation similarly improved left ventricular systolic dysfunction, reduced myocardial fibrosis and related mRNA levels, and lowered plasma norepinephrine levels without reducing blood pressure in hypertensive rats. At 12 weeks, afferent renal denervation attenuated the increase in plasma norepinephrine and presympathetic neuron activity in the PVN and rostral ventrolateral medulla in hypertensive rats, while decreasing vasopressin-producing PVN neuron activity. In acute experiments, afferent renal nerve stimulation increased sympathetic outflow, but vasopressin V1a and V1b receptor blockade in the PVN suppressed this sympathoexcitation in hypertensive rats. CONCLUSIONS: Afferent renal nerve input activates the sympathetic nervous system before left ventricular systolic dysfunction and contributes to hypertensive HF, with PVN vasopressin driving this sympathoexcitation.
Hao J, Fang G, Li X
… +8 more, Wang T, Peng K, Liu J, Yang D, Kang X, Wang Q, Yang Y, Lan C
Hypertension
· 2026 Mar · PMID 41498134
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BACKGROUND: Perivascular macrophages play a significant role in the pathogenesis of hypoxia-induced pulmonary hypertension via crosstalk to pulmonary artery smooth muscle cells (PASMCs) to stimulate their proliferation a...BACKGROUND: Perivascular macrophages play a significant role in the pathogenesis of hypoxia-induced pulmonary hypertension via crosstalk to pulmonary artery smooth muscle cells (PASMCs) to stimulate their proliferation and pulmonary vascular remodeling. However, whether hypoxia exposure of macrophages affects cellular crosstalk remains entirely unclear. This study aimed to decipher the effects of hypoxia on macrophages' crosstalk to PASMCs and elucidate the underlying molecular mechanisms. METHODS: Conditioned medium obtained from bone marrow-derived macrophages under normoxia or hypoxia was transferred for hypoxic culture of primary mouse PASMCs, followed by RNA sequencing analysis. Myeloid-specific SerpinB1-overexpressing mice were generated to explore SerpinB1's role in macrophage inflammatory phenotype, PASMC proliferation, and pulmonary vascular remodeling. RESULTS: Hypoxia-exposure of macrophages produced a conspicuous augmentation to the pro-proliferative effect of the conditioned medium on PASMCs. Hypoxia exposure aggravated macrophage inflammatory phenotype, as indicated by marked enrichment of multiple inflammatory pathways and elevated levels of inflammatory cytokines. SerpinB1 (serpin family B member 1) was identified as the key downstream mediator of hypoxia to regulate macrophage inflammatory phenotype because hypoxia induced its drastic downregulation and subsequent NLRP3 (NOD [nucleotide oligomerization domain]-, LRR [leucine-rich repeat]-, and PYD [pyrin domain]-containing protein 3)-independent inflammatory caspase-1 activation. Myeloid-specific overexpression of SerpinB1 largely blunted hypoxia-induced macrophage inflammatory phenotype and amplified the pro-proliferative effect on PASMCs. Myeloid SerpinB1-overexpressing mice exhibited lower right ventricular systolic pressure, milder right ventricular hypertrophy, and pulmonary vascular remodeling after chronic hypoxia exposure. CONCLUSIONS: Hypoxia exposure directly amplifies the pro-proliferative crosstalk of macrophages to PASMCs via downregulating SerpinB1 to induce caspase-1 activation and inflammatory phenotype. Targeting macrophage SerpinB1 may hold promise for treating pulmonary hypertension.
Torimoto K, Nakayama Y, Terada Y
… +10 more, Okuno K, Cicalese S, Mangano B, Akiyama T, Kimura Y, Utsunomiya H, Hashimoto T, O-Uchi J, Osei-Owusu P, Eguchi S
Hypertension
· 2026 Mar · PMID 41467343
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BACKGROUND: Chronic unfolded protein response due to endoplasmic reticulum stress has been proposed as a therapeutic target for hypertension. Here, we tested our hypothesis that inactivation of one of the central unfolde...BACKGROUND: Chronic unfolded protein response due to endoplasmic reticulum stress has been proposed as a therapeutic target for hypertension. Here, we tested our hypothesis that inactivation of one of the central unfolded protein response effectors, inositol-requiring enzyme 1α, mitigates hypertension and vascular remodeling in mice infused with angiotensin II. METHODS: C57BL6 mice were infused with angiotensin II for 2 weeks with or without an inositol-requiring enzyme 1α inhibitor KIRA6 treatment to evaluate blood pressure and cardiovascular remodeling. Mouse small mesenteric arteries were used to assess vascular reactivity. Rat vascular smooth muscle cells were used to assess inositol-requiring enzyme 1α activation, intracellular Ca concentration, and secretory phenotype via proteomics. RESULTS: KIRA6 treatment mitigated hypertension induced by angiotensin II infusion. KIRA6 treatment also prevented angiotensin II-induced vascular thickening and perivascular fibrosis. Immunohistochemical staining of aortas indicated that phosphorylated inositol-requiring enzyme 1α signal in vascular smooth muscle cells was elevated with angiotensin II infusion and attenuated with KIRA6 treatment. Vasoconstriction in small mesenteric arteries after incubation with angiotensin II was attenuated by KIRA6 coincubation. Angiotensin II-induced elevation in intracellular Ca concentration was partially reduced by KIRA6 pretreatment in vascular smooth muscle cells. Proteomic analysis demonstrated that angiotensin II induced a unique secretory phenotype in vascular smooth muscle cells, which was mitigated by KIRA6. CONCLUSIONS: Targeting inositol-requiring enzyme 1α is a potential therapy for hypertension and vascular remodeling by reducing vascular resistance, mitigating intracellular Ca elevation, and protecting against secretory phenotype in vascular smooth muscle cells.
Theken KN, Ghosh S, Skarke C
… +6 more, Fries S, Lahens NF, Sarantopoulou D, Grant GR, FitzGerald GA, Grosser T
Hypertension
· 2026 Feb · PMID 41459594
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BACKGROUND: Large clinical trials compared distinct nonsteroidal anti-inflammatory drugs in terms of their risk of adverse cardiovascular events. However, whether pharmacologically equipotent doses were used, that is, wh...BACKGROUND: Large clinical trials compared distinct nonsteroidal anti-inflammatory drugs in terms of their risk of adverse cardiovascular events. However, whether pharmacologically equipotent doses were used, that is, whether a similar degree of COX (cyclooxygenase)-2 inhibition was achieved, was not considered. We compared drug target inhibition and blood pressure (BP) response to celecoxib and naproxen. METHODS: Sixteen healthy participants were treated with celecoxib (200 mg/d), naproxen (500 mg/d), or placebo for 7 days in a double-blind, crossover design. The degree of COX inhibition was assessed ex vivo using established whole blood assays and in vivo by quantifying urinary metabolites of thromboxane A (COX-1) and prostacyclin (COX-2). Ambulatory BP was measured throughout the final dosing interval. RESULTS: Both nonsteroidal anti-inflammatory drugs inhibited COX-2 activity relative to placebo, but naproxen inhibited COX-2 activity to a greater degree (62.9±21.7%) than celecoxib (35.7±25.2%; <0.05). Similarly, naproxen treatment inhibited prostacyclin formation in vivo (48.0±24.9%) to a greater degree than celecoxib (26.7±24.6%; <0.05). Naproxen significantly increased BP compared with celecoxib (mean arterial pressure, +2.5 [95% CI, 1.5-3.5] mm Hg; systolic BP, +4.0 [95% CI, 2.9-5.1] mm Hg; and diastolic BP, +1.8 [95% CI, 0.8-2.8] mm Hg; <0.05 for all). The difference in systolic BP relative to placebo was associated with the degree of COX-2 inhibition (<0.05). CONCLUSIONS: Future studies should consider pharmacokinetic and pharmacodynamic properties, as well as patient-specific factors that may modulate the cardiovascular risk of nonsteroidal anti-inflammatory drug use. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02502006.
Hypertension
· 2026 Feb · PMID 41457982
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BACKGROUND: Although epigenetic modification of histone in embryonic development is well documented, its mechanistic role in the pathogenesis of hypertension is poorly understood. The purpose of this study is to investig...BACKGROUND: Although epigenetic modification of histone in embryonic development is well documented, its mechanistic role in the pathogenesis of hypertension is poorly understood. The purpose of this study is to investigate how histone 3 modification (H3K27me3 [trimethylation of histone 3 lysine 27]) in renal tubule cells regulates sodium excretion and blood pressure. METHODS: A mouse model of inducible renal tubule cell-specific deletion of KDM6A cKO (histone 3 lysine 27 demethylase 6A gene) was generated. RESULTS: Here, we uncovered the potential role of FBLN2 (fibulin 2) in the pathogenesis of epigenetic hypertension due to KDM6A cKO. KDM6A is a specific demethylase for H3K27me3. ChIP-seq analysis revealed that the H3K27me3 mark was increased in the promoter region of the gene, resulting in downregulation of FBLN2 protein expression in the kidney of KDM6A cKO mice. Treatment with rFBLN2 (recombinant FBLN2) largely attenuated blood pressure elevation, rescued impairment in sodium excretion, and prevented high salt-induced salt-sensitive hypertension in KDM6A cKO mice. Mechanistically, treatment with rFBLN2 rescued upregulation of NCC (Na-Cl cotransporter) and AQP2 (aquaporin 2) expression and decreased NKCC2 expression in renal tubular cells in the KDM6A cKO hypertensive mice. Intriguingly, FBLN2 may regulate NCC trafficking via forming an FBLN2/NCC complex, which decreases the cell membrane abundance of NCC by translocating NCC to the total membrane in distal convoluted tubule cells. CONCLUSIONS: These findings highlight a critical role of FBLN2 in the regulation of renal sodium excretion and blood pressure and suggest that FBLN2 deficiency may drive KDM6A deficiency-induced epigenetic hypertension. FBLN2 treatment may provide a new preventive and therapeutic strategy for salt-sensitive hypertension.
Yu Y, Xia T, Wang Y
… +10 more, Qin K, Gao L, Zhao B, Zha J, Zhou J, Cui Y, Lu C, Tang T, Xiao Z, Ju S
Hypertension
· 2026 Feb · PMID 41457966
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BACKGROUND: White matter hyperintensities (WMH), a hallmark imaging feature of small vessel disease, are strongly associated with neurodegenerative and cardiovascular conditions. METHODS: We performed bidirectional and m...BACKGROUND: White matter hyperintensities (WMH), a hallmark imaging feature of small vessel disease, are strongly associated with neurodegenerative and cardiovascular conditions. METHODS: We performed bidirectional and mediation Mendelian randomization analyses using summary statistics from GWAS (genome-wide association studies) of 9 large cohorts of plasma proteins (n=997-35 559), blood pressure (n=1 028 980), and WMH (n=21 381). The inverse-variance-weighted method or Wald ratio was applied as the primary Mendelian randomization approach, with false discovery rate correction and independent replication. We further integrated Mendelian randomization with PheWAS (phenome-wide association studies) to prioritize WMH risk factors and assess mediation via systolic blood pressure and diastolic blood pressure. RESULTS: Eighteen plasma proteins were genetically associated with WMH, 13 of which were replicated. Thirteen antihypertensive target genes were also linked to WMH burden, including , (amine oxidase copper containing 1), (sex hormone binding globulin), and (potassium voltage-gated channel subfamily H member 2), which influenced both systolic blood pressure and diastolic blood pressure. Mendelian randomization-PheWAS highlighted systolic blood pressure and diastolic blood pressure as the top-ranked WMH risk factors among 21 976 traits. Antihypertensive drug targets, including angiotensin II receptor blockers, β-blockers, calcium channel blockers, and diuretics, were significantly associated with WMH burden. Mediation analysis showed that systolic blood pressure partially mediated TFPI's effect (3.04%), and diastolic blood pressure mediated the effects of ACP1 (acid phosphatase 1) (2.74%) and LAMC1 (laminin subunit gamma 1; 4.94%). CONCLUSIONS: The findings outline protein- and blood pressure-centered mechanisms in small vessel disease, highlighting proteins and antihypertensive targets as biomarkers and therapeutic entry points for precision intervention.
Vibhatavata P, Mermejo LM, Zhao L
… +2 more, Shields JJ, Turcu AF
Hypertension
· 2026 May · PMID 41410035
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BACKGROUND: Adrenal vein (AV) sampling (AVS) is used to guide therapy in primary aldosteronism (PA). When a single AV is successfully cannulated, the relative aldosterone secretion index (RASI), which compares the aldost...BACKGROUND: Adrenal vein (AV) sampling (AVS) is used to guide therapy in primary aldosteronism (PA). When a single AV is successfully cannulated, the relative aldosterone secretion index (RASI), which compares the aldosterone/cortisol ratio in that AV versus the periphery, has been proposed as sufficient for PA subtyping, particularly when <1. Data on RASI reliability have, however, been inconsistent. METHODS: This retrospective cohort study included patients with PA who underwent AVS before and after cosyntropin stimulation at a referral center between January 2015 and December 2024. To simulate partially successful AVS, RASI was calculated in patients with successful bilateral AV cannulation and compared across PA subtypes and postoperative outcomes, with assessment of distributional overlap. RESULTS: Of 460 patients (mean age 53±12 years; 58% men), bilateral AVS was successful in 437 patients at baseline and in all patients after cosyntropin stimulation. Without cosyntropin, 98% of dominant AV and 97% of nondominant AV RASI from lateralized PA overlapped with bilateral PA RASI. Similar patterns were observed postcosyntropin. In adrenalectomized patients, RASI did not distinguish between those with and without PA cure. Previously proposed RASI thresholds misclassified up to 74% of lateralized PA and 64% of bilateral PA. When corroborated with cross-sectional imaging, the prediction of correct lateralization improved, particularly when using RASI from cosyntropin-stimulated AVS. CONCLUSIONS: Considering the substantial overlap of RASI across PA subtypes, partially successful AVS has limited utility and is unreliable in guiding adrenalectomy for PA.
Hsiao TW, Fede L, Gocke C
… +3 more, Waller LA, Ali MK, Varghese JS
Hypertension
· 2026 Feb · PMID 41410032
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BACKGROUND: As the leading modifiable risk factor for death in the United States, hypertension requires timely and locally detailed surveillance. Current estimates of the high blood pressure (BP) care continuum are laggi...BACKGROUND: As the leading modifiable risk factor for death in the United States, hypertension requires timely and locally detailed surveillance. Current estimates of the high blood pressure (BP) care continuum are lagging national averages from sample surveys with low participation and unknown subnational variation. This study explores the use of self-service health kiosks in retail stores as an alternative source for subnational estimates of prevalence, awareness, and control. METHODS: We analyzed data from adult kiosk users (n=1270 485) across 1892 counties in 49 States (except Massachusetts) and the District of Columbia in a serial cross-sectional analysis from November 2017 to September 2024. High BP was defined as self-reported diagnosed (aware) or elevated BP (systolic ≥140 mm Hg or diastolic ≥90 mm Hg). Among those aware, control was defined as BP <140/90 mm Hg. Small area estimates for counties were calculated using multilevel regression and poststratification based on individual and areal socio-demographic covariates. We compared the prevalence of diagnosed hypertension with the Behavioral Risk Factor Surveillance System 2021. RESULTS: The analytic sample had a mean age of 42.0 years (SD=15.6). Prevalence of high BP was 51.9% in 2017 to 2018 and 50.4% in 2023 to 2024. In 2023 to 2024, awareness and control were 73.7% and 61.8% and county-level prevalence ranged from 39.5% to 63.1%. Similar hotspots in the Southeast were identified in both the kiosk and Behavioral Risk Factor Surveillance System (Spearman ρ=0.52). CONCLUSIONS: Health kiosk data reveal substantial spatial and socio-demographic variation in high BP. Near real-time subnational surveillance of health kiosk users can provide insights to guide interventions and track progress.
Ebinger JE, Kauko A, Vaura F
… +6 more, Hage P, Sundström J, FinnGen, Joung SY, Cheng S, Niiranen TJ
Hypertension
· 2026 Feb · PMID 41404655
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BACKGROUND: Resistant hypertension (RH), in which blood pressure remains elevated on ≥3 medications or controlled on ≥4 medications, increases the risk of adverse cardiovascular events nearly 50% more than primary hypert...BACKGROUND: Resistant hypertension (RH), in which blood pressure remains elevated on ≥3 medications or controlled on ≥4 medications, increases the risk of adverse cardiovascular events nearly 50% more than primary hypertension. We sought to identify genetic drivers of RH in a reliable and generalizable manner. METHODS: We utilized FinnGen (discovery) and UKBB (UK Biobank, replication) data sets to identify potential genetic drivers of RH. Using standard RH definitions, we developed cohorts in each data set and performed genome-wide (genome-wide association studies) and transcriptome-wide association studies, as well as Mendelian randomization analysis to evaluate potential causal associations. RESULTS: We replicated 5 genetic loci in , and near the locus for RH. Of these, and are strongly associated with aldosterone homeostasis, while and are associated with pathways mediating vasodilation. are involved in mesendodermal lineage differentiation during gastrulation. Gene- and pathway-based analyses identified associations with vascular and cardiac developmental pathways in addition to aldosterone synthesis and secretion pathways. Transcriptome-wide association study analyses identified 37 genes, of which the genetically regulated expression is associated with RH, with particularly strong tissue-specific associations with . Finally, Mendelian randomization identified possible causal association for 4 vascular risk factors (CRP [C-reactive protein]), triglycerides, waist circumference, and body mass index) with RH, with strong associations with identified lead variants. CONCLUSIONS: We identified distinct genetic variants associated with RH, including those implicating the role of hyperaldosteronism, highlighting distinct pathways and targets for more effectively treating RH.
Trifan G, Daviglus ML, Gonzalez HM
… +15 more, Tarraf W, Gorelick PB, Elkind MSV, Gallo LC, Wassertheil-Smoller S, Perreira KM, Stickel A, Anita N, Márquez F, Pirzada A, Lamar M, Llabre MM, Elfassy T, Zhou H, Testai FD
Hypertension
· 2026 Feb · PMID 41392895
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BACKGROUND: Studies showed that hypertension predicts cognitive performance. It remains uncertain whether a bidirectional relationship exists. We investigated whether cognitive function predicts incident hypertension. ME...BACKGROUND: Studies showed that hypertension predicts cognitive performance. It remains uncertain whether a bidirectional relationship exists. We investigated whether cognitive function predicts incident hypertension. METHODS: Data from the Hispanic Community Health Study/Study of Latinos were analyzed. Global cognitive score (GC) of nonhypertensive participants at baseline was derived by averaging z scores across 4 neurocognitive tests (brief Spanish-English verbal learning test sum and recall, word fluency, and digit symbol substitution test). Incident hypertension was investigated, on average, 6 years later. Sociodemographic characteristics and unhealthy behaviors (obesity, physical activity not at goal, low diet quality, smoking) were ascertained at baseline. Association of GC at baseline with incident hypertension (defined as blood pressure ≥130/80 mm Hg or on treatment) was investigated using logistic regression analyses adjusted for sociodemographic characteristics and time between visits. Multimodal analyses assessed whether unhealthy behaviors were pathway variables between GC and incident hypertension. RESULTS: A total of 6755 participants (mean [interquartile range] age, 53[48-59] years; 62% female) were included. At follow-up, 57% of individuals developed hypertension. In our final model, higher GC was associated with lower odds of incident hypertension (odds ratio, 0.85 [95% CI, 0.74-0.98]). In pathway analysis, indirect effects through unhealthy behaviors were small. Obesity was the only significant mediator (indirect odds ratio, 0.95 [95% CI, 0.90-0.99]). Smoking and physical activity not at goal were in the pathway of GC and obesity, but did not mediate GC-incident hypertension. CONCLUSIONS: Higher GC was associated with a lower incidence of hypertension 6 years later. Unhealthy behaviors may influence the association of cognitive function and incident hypertension.
King JB, An J, Bellows BK
… +6 more, Cohen JB, Commodore-Mensah Y, Ghazi L, Langford AT, Brook RD, American Heart Association Council on Hypertension; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology
Hypertension
· 2026 Mar · PMID 41392889
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The growing global burden of hypertension and inadequate blood pressure control necessitate effective therapeutic strategies to improve blood pressure management and reduce the risks of cardiovascular diseases attributab...The growing global burden of hypertension and inadequate blood pressure control necessitate effective therapeutic strategies to improve blood pressure management and reduce the risks of cardiovascular diseases attributable to hypertension. Single-pill combination medications for hypertension combine ≥2 antihypertensive agents in a single tablet. Single-pill combination medications offer a promising opportunity to achieve faster and more sustained blood pressure control compared with stepped care (ie, prescribing antihypertensive monotherapy, titrating the dose, and later adding more antihypertensive agents). Single-pill combination medications combine complementary mechanisms of action of antihypertensive agents to more effectively lower blood pressure while reducing adverse effects. This approach simplifies treatment regimens by lowering pill burden, improves patient adherence, overcomes clinician inertia by simplifying prescribing, is cost-effective, and results in faster blood pressure control compared with using separate pills. Minor limitations of single-pill combination medications include constrained flexibility for dosing adjustments and lack of commercial availability of certain combinations of agents. By incorporating single-pill combination medications into routine practice for most patients with hypertension, health care professionals may improve long-term cardiovascular outcomes while reducing patient burden. This scientific statement provides an overview of the clinical evidence surrounding the use of single-pill combination medications for hypertension, strategies to implement single-pill combination medications into clinical practice, and knowledge gaps that merit further investigation.
Tarhriz V, Xia H, Patel A
… +7 more, Eivazi M, Scarborough A, Miao K, Mir H, Abkhooie L, Mauvais-Jarvis F, Lazartigues E
Hypertension
· 2026 Mar · PMID 41392884
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BACKGROUND: Hypertension is a multifactorial disease influenced by sex hormones, with notable sex-specific differences in its development and progression. Extracellular vesicles have emerged as important mediators in hyp...BACKGROUND: Hypertension is a multifactorial disease influenced by sex hormones, with notable sex-specific differences in its development and progression. Extracellular vesicles have emerged as important mediators in hypertension pathophysiology. This study aimed to investigate sex-specific extracellular vesicle-derived microRNA and protein profiles in deoxycorticosterone acetate-salt-induced hypertension. METHODS: Male and female C57BL/6J mice underwent deoxycorticosterone acetate-salt treatment, with blood pressure monitored via telemetry and cardiac function assessed using echocardiography and invasive hemodynamics. Extracellular vesicles from plasma and cerebrospinal fluid were isolated and analyzed for microRNA (high-throughput RNA sequencing) and protein (liquid chromatography-mass spectrometry) content. To determine the contribution of sex hormones, gonadectomy was performed before deoxycorticosterone acetate-salt exposure. Hypothalamic and plasma samples were then used to validate key molecular findings. RESULTS: Deoxycorticosterone acetate-salt treatment caused more severe hypertension, cardiac dysfunction, and mortality in males compared with females. Gonadectomy reduced hypertension and mortality in males but exacerbated them in females, confirming the protective effect of estrogens and the deleterious influence of androgens. Sex-specific extracellular vesicle-derived microRNA and protein expression profiles were identified, revealing 10 key regulatory microRNAs and highlighting potential regulatory axes such as miR (microRNA)-125b-5p/ACE (angiotensin-converting enzyme) 2, miR-1a-3p/G6PD (glucose-6-phosphate dehydrogenase), miR-410-3p/ATR (angiotensin II type 1 receptor), and miR-378a-5p/IRAP (insulin-regulated aminopeptidase). Gonadectomy altered expression patterns, supporting the hormone-dependent regulation of these microRNAs. Proteomic data showed renin-angiotensin system and diabetic cardiomyopathy pathway activation in hypertensive males. In silico and ex vivo analyses identified 25 microRNA-targeted genes, such as and , reinforcing the role of sex hormone-sensitive microRNA-protein interactions. CONCLUSIONS: This study highlights potential sex-specific microRNA networks in hypertension and proposes novel molecular targets for validation toward personalized, sex-tailored therapies.