Kim M, Tavolinejad H, Sarmiento Bustamante M
… +6 more, Segers P, Neirynck RE, De Meyer T, De Buyzere ML, Rietzschel E, Chirinos JA
Hypertension
· 2026 Apr · PMID 41717706
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BACKGROUND: Proteomic signatures may enhance the prediction of cardiometabolic diseases for targeted prevention. We evaluated whether a proteomic risk score (ProtRS) improves the prediction of incident hypertension. METH...BACKGROUND: Proteomic signatures may enhance the prediction of cardiometabolic diseases for targeted prevention. We evaluated whether a proteomic risk score (ProtRS) improves the prediction of incident hypertension. METHODS: Within the UK Biobank Proteomics data set, participants at risk for incident hypertension were randomly split into derivation (n=25 158) and test (n=10 781) sets. A ProtRS was trained in the derivation cohort using least absolute shrinkage and selection operator penalized Cox regression and evaluated in the test set with sequential adjustment for demographics, clinical risk factors, and a polygenic risk score (PRS). External replication was performed in the Asklepios study (n=793). RESULTS: In UK Biobank Proteomics (2312 events), each 1-SD higher ProtRS was associated with incident hypertension after covariate adjustment (hazard ratio, 1.68 [95% CI, 1.59-1.78]; <0.001). Adding the protein score to demographics, clinical variables, and PRS improved model fit (global χ from 1733 to 2048, <0.001), discrimination (C-index, 0.745-0.765), net reclassification improvement (19.0% [95% CI, 15.9-22.0]), and integrated discrimination improvement (2.9% [95% CI, 2.4-3.8]). In Asklepios (221 events), the ProtRS was associated with an increased risk of hypertension (hazard ratio, 1.32 [95% CI, 1.13-1.55]; <0.001) after covariate adjustment, and improved global χ (from 120.4 to 132.4; <0.001), C-index (from 0.723 to 0.736) and discrimination (net reclassification improvement, 13.1% [95% CI, 1.2%-24.1%]). Pathway analysis highlighted neutrophil degranulation, insulin-like growth factor, PI3K signaling, and extracellular matrix remodeling. CONCLUSIONS: A ProtRS improves prediction of incident hypertension beyond demographics, clinical, and genetic information in UK Biobank Proteomics, with supportive external replication. Proteomic information may enhance individualized hypertension risk stratification and provide biologic insights into disease development.
Bigalke JA, Tahsin CT, Ginty AT
… +3 more, Durocher JJ, Keller-Ross ML, Carter JR
Hypertension
· 2026 Apr · PMID 41717699
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BACKGROUND: Chronic anxiety increases the risk of incident hypertension, yet mechanisms remain equivocal. Recent evidence documents that trait anxiety is positively associated with muscle sympathetic nerve activity (MSNA...BACKGROUND: Chronic anxiety increases the risk of incident hypertension, yet mechanisms remain equivocal. Recent evidence documents that trait anxiety is positively associated with muscle sympathetic nerve activity (MSNA), a known contributor to hypertension risk. The purpose of this study was to address the hypothesis that the association between trait anxiety, MSNA, and elevated blood pressure would be moderated by cardiac vagal activity estimated via heart rate variability (HRV). METHODS: Resting blood pressure, MSNA (microneurography), and heart rate (ECG) were collected at rest in 130 adults (71 men, 59 women; age, 25±8 years; body mass index, 25±4 kg/m). Moderation analyses were used to investigate the moderating role of HRV on the association between trait anxiety, MSNA, and blood pressure. RESULTS: The association between trait anxiety and MSNA was significantly moderated by resting HRV such that the relationship between anxiety and MSNA was stronger (=0.322, =0.005) in those with lower HRV (-1 SD) compared with those with average (=0.146, =0.067) or higher (+1 SD) HRV (=-0.031, =0.785). Conversely, HRV did not moderate the positive association between trait anxiety and blood pressure. CONCLUSIONS: The present findings demonstrate that elevated trait anxiety is associated with elevated sympathetic neural activity and blood pressure. The association between trait anxiety and elevated sympathetic nerve activity is particularly prominent in those with low HRV, suggesting a potential utility of HRV as a cardiovascular risk biomarker in individuals with heightened anxiety.
Ahn JC, Lee CW, Ahn JH
… +22 more, Lim KH, Sohn IS, Sung KC, Kim KH, Bae JH, Hong SP, Jang WY, Jo SH, Han SH, Kim JB, Lee CJ, Lee JH, Kim N, Cho EJ, Sung JH, Ahn HS, Kim SY, Shin J, Seo SM, Hong SJ, Kim W, Park CG
Hypertension
· 2026 Apr · PMID 41717679
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BACKGROUND: Although low-dose triple single-pill combination therapies show promising efficacy and safety, studies comparing them to standard-dose monotherapies remain limited. This phase III, randomized, double-blind tr...BACKGROUND: Although low-dose triple single-pill combination therapies show promising efficacy and safety, studies comparing them to standard-dose monotherapies remain limited. This phase III, randomized, double-blind trial evaluated the efficacy and safety of a low-dose single-pill combination of telmisartan, amlodipine, and chlorthalidone versus standard-dose telmisartan monotherapy in patients with essential hypertension. METHODS: After a 4-week placebo run-in period, 314 eligible subjects were randomized to either receive telmisartan/amlodipine/chlorthalidone 20/2.5/6.25 mg or telmisartan 40 mg for 8 weeks. The primary efficacy end point was the change in mean sitting systolic blood pressure from baseline to week 8, with noninferiority assessed in the per-protocol set (PPS), followed by superiority testing in the full analysis set using a gatekeeping approach to control for type I error. RESULTS: At week 8, the combination group demonstrated significant mean sitting systolic blood pressure reduction compared with monotherapy in the per-protocol set analysis (least squares mean difference, -3.8 mm Hg [95% CI: -6.7 to -0.9]; =0.01), establishing its noninferiority. Furthermore, the superiority of the combination therapy was confirmed in the full analysis set (LS mean difference, -4.0 mm Hg [95% CI, -6.8 to -1.3]; <0.01). Mean sitting diastolic BP, BP normalization rates, and response rates also favored the combination group at weeks 4 and 8 (all <0.01). Subgroup analyses showed consistent efficacy across clinical strata, including age and prior antihypertensive treatment. The incidence of adverse events was comparable between groups, with no serious drug-related events reported. CONCLUSIONS: Low-dose triple single-pill combination of telmisartan/amlodipine/chlorthalidone demonstrated superior BP-lowering efficacy with well-tolerated and comparable safety to standard-dose telmisartan monotherapy. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06348576.
Lakshminarayan K, Murray TA, Lunos S
… +11 more, McCarthy T, Everson-Rose SA, Overton V, Drawz PE, Streib C, Sakboonyarat B, Hatch H, Hibbard JH, Luepker RV, Connett J, Westberg SM
Hypertension
· 2026 Apr · PMID 41717677
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BACKGROUND: The mGlide RCT (randomized controlled trial) evaluated whether a pharmacist-led, mobile health technology facilitated care model improves hypertension control in diverse populations. METHODS: We recruited adu...BACKGROUND: The mGlide RCT (randomized controlled trial) evaluated whether a pharmacist-led, mobile health technology facilitated care model improves hypertension control in diverse populations. METHODS: We recruited adult English, Spanish, or Hmong-speaking patients with uncontrolled hypertension from a large health care system and smaller community clinics serving low-income patients. Participants were randomized 1:1 to mGlide or usual care. The 6-month intervention included daily blood pressure (BP) self-monitoring using a smartphone and wireless monitor, automated app-based data sharing, and responsive medication adjustment by a pharmacist-led provider-team. Comparison participants received a digital monitor. Outcomes included mean 6-month systolic BP (SBP), 12-month sustained BP control, 24-hour ambulatory BP and patient activation. RESULTS: A total of 395 participants (mean age, 66.9 years; 46.6% women; mean [SD] SBP, 143.4 [16.5] mm Hg) were randomized to mGlide (n=198) or usual care (n=197). Mean (SD) 6-month SBP (mm Hg) was lower in the mGlide arm (128.1 [13.9] versus 134.0 [16.0]). The adjusted mean difference between groups for the primary outcome of 6-month SBP favored mGlide: -5.8 mm Hg (95% CI, -8.6 to -3.0), sustained at 12 months (-5.7 mm Hg [-8.7 to -2.6]). The mGlide arm also had a 4.8 mm Hg (=0.014) lower 24-hour average ambulatory SBP. The 6-month intervention effect varied significantly by activation level, with a difference of -12.6 mm Hg (-20.5 to -4.8) SBP among the lowest versus -2.5 mm Hg (-6.5 to 1.6) among the highest activation level participants. CONCLUSIONS: A mobile health-facilitated care model with pharmacist-led medication adjustment was effective in lowering BP in diverse populations. Patients with low activation benefited more from the intervention; activation levels may inform efficient intervention selection. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03612271.
Vernail VL, Mehay DL, Kimbark KD
… +4 more, Tanner JA, Bingaman SS, Silberman Y, Arnold AC
Hypertension
· 2026 Jun · PMID 41705339
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BACKGROUND: Angiotensin-(1-7) lowers blood pressure and improves metabolic outcomes in animal models of obesity and hypertension. Whether central mechanisms are involved in these protective cardiometabolic effects is poo...BACKGROUND: Angiotensin-(1-7) lowers blood pressure and improves metabolic outcomes in animal models of obesity and hypertension. Whether central mechanisms are involved in these protective cardiometabolic effects is poorly understood. In this study, we hypothesized that angiotensin-(1-7) engages central neurocircuits originating in the arcuate nucleus of the hypothalamus under normal conditions and in diet-induced obesity. METHODS: Male mice were placed on a control diet or 60% high-fat diet for 12 weeks. Immunohistochemistry, in situ hybridization, electrophysiology, and physiological approaches were employed to determine whether angiotensin-(1-7) activates arcuate neurocircuits, to characterize the molecular identity of activated arcuate cells, and to assess the functional importance of this neurocircuit in blood pressure regulation. RESULTS: Under control diet conditions, systemic angiotensin-(1-7) administration (2 mg/kg, SC) increased the number of c-fos positive cells in the arcuate nucleus. Angiotensin-(1-7) receptors were highly localized to proopiomelanocortin neurons containing markers of gamma-aminobutyric acid transmission in the arcuate, with angiotensin-(1-7) increasing the firing activity of proopiomelanocortin neurons in a receptor-dependent manner. Acute intra-arcuate angiotensin-(1-7) administration lowered blood pressure. This effect was prevented by gamma-aminobutyric acid receptor antagonism in the downstream hypothalamic paraventricular nucleus, suggesting that angiotensin-(1-7) engages inhibitory arcuate-paraventricular circuits to lower blood pressure. Acute angiotensin-(1-7) could not activate proopiomelanocortin neurons or engage this arcuate-paraventricular neurocircuit in obese mice. CONCLUSIONS: These findings suggest that angiotensin-(1-7) activates arcuate proopiomelanocortin neurons and engages arcuate-paraventricular inhibitory neurocircuits to lower blood pressure under normal conditions. In obesity, this circuit appears disrupted, which could contribute to the elevated blood pressure in this model.
Soulié M, Sánchez-Bayuela T, Lima-Posada I
… +9 more, Stephan Y, Nicol L, Lamiral Z, Lagrange J, Voors A, Lopez-Andres N, Girerd N, Mulder P, Jaisser F
Hypertension
· 2026 Jun · PMID 41700406
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BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular complications. We have shown that Ngal (neutrophil gelatinase-associated lipocalin)/lcn2 is involved in aldosterone-induced cardia...BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular complications. We have shown that Ngal (neutrophil gelatinase-associated lipocalin)/lcn2 is involved in aldosterone-induced cardiac remodeling and inflammation. Here, we investigated the role of Ngal in the progression of cardiorenal syndrome. METHODS: CKD was induced in rats via 5/6 nephrectomy in wild-type and Ngal knockout rats. Cardiorenal functions were assessed 3 months after subtotal nephrectomy or sham operation. Cardiac fibroblasts were isolated from wild-type rats and incubated with or without rNgal (recombinant Ngal) and Gal-3 (galectin-3). RESULTS: Cardiac perfusion was less impaired in CKD Ngal knockout than in CKD wild type. Left ventricle interstitial fibrosis was more severe in CKD wild type than in sham but was blunted in CKD Ngal knockout rats. Levels of Gal-3, Col1 (collagen 1), Ccl2 (C-C motif chemokine ligand 2), and IL-6 (interleukin-6) were high in cardiac fibroblasts incubated with rNgal. A similar pattern was observed in cells treated with recombinant Gal-3. Both Ngal and Gal-3 induced activation of the Tlr4 (toll-like receptor 4)-Myd88 (myeloid differentiation primary response 88) pathway. The effects of rNgal were blunted by concomitant treatment with Gal-3 or Tlr4 inhibitors, suggesting that Gal-3 contributes to Ngal-induced cardiac fibrosis and inflammation by activating the Tlr4-Myd88 pathway. In both MEDIA-DHF (Metabolic Road to Diastolic Heart Failure) and BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) cohorts, elevated levels of Ngal and Gal-3 were associated with advanced diastolic dysfunction and adverse clinical outcomes, particularly among patients with impaired renal function. CONCLUSIONS: In CKD rats, Ngal was involved in cardiac remodeling via a Gal-3/Tlr4-dependent pathway, increasing inflammation and fibrosis, and correlated to cardiac outcomes in the MEDIA-DHF and BIOSTAT-CHF cohorts.
Yin Y, Xu Q, Liao L
… +6 more, Zhang Y, Yuan L, Li Y, Wang Y, Zheng X, Zhou R
Hypertension
· 2026 Jun · PMID 41700395
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BACKGROUND: Preeclampsia is a pregnancy-specific disorder characterized by placental hypoxia and superficial invasion of trophoblast cells. However, the precise mechanisms by which hypoxia induces lactate and lactylation...BACKGROUND: Preeclampsia is a pregnancy-specific disorder characterized by placental hypoxia and superficial invasion of trophoblast cells. However, the precise mechanisms by which hypoxia induces lactate and lactylation remain unclear. METHODS: Pan lysine lactylation levels were analyzed in the placentae of 36 patients with severe preeclampsia (sPE) and 36 normotensive pregnancies. A global lactylome analysis was performed, and branched-chain amino acid transaminase 2-lysine 377 (BCAT2-K377) was selected for further investigation. The BCAT2 mutant with lysine 377 mutated to arginine (BCAT2-377R) was constructed to evaluate the effect on trophoblast migration, invasion, tube formation, and oxidative stress. The impact of the BCAT2-377R mutant on BCAT2 ubiquitination and degradation was further examined using MG132 and cycloheximide supplementation. Co-immunoprecipitation and double-immunofluorescence staining were conducted to identify the lactyltransferase of BCAT2. The specialized antibody was developed to validate branched-chain amino acid transaminase 2-lysine 377 lactylation (BCAT2-K377la) abundance in tissues and treated cells. A preeclampsia-like rat model was constructed to further verify whether the results were consistent with the clinical findings. RESULTS: Lactylation levels were elevated in the placentae of sPE. High lactate concentration enhanced Pan lysine lactylation and reduced BCAT2 protein levels while inhibiting cell migration, invasion, and tube formation. BCAT2-K377la impaired cell biological behaviors, increased oxidative stress, and promoted BCAT2 ubiquitination. The EP300 lysine acetyltransferase (p300) acted as a lysine lactylation writer of BCAT2. BCAT2-K377la abundance was upregulated in sPE placentae and cells treated with hypoxia and lactate. In the rat model, elevated placental Pan lysine lactylation and BCAT2-K377la levels mirrored findings in clinical samples. CONCLUSIONS: Our findings emphasized the role of nonhistone lactylation in sPE pathogenesis. Targeting BCAT2-K377la may serve as a potential intervention strategy for sPE.
Hypertension
· 2026 May · PMID 41685462
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Medical therapy for primary aldosteronism has been stagnant for decades, relying on mineralocorticoid receptor antagonists, which block downstream signaling of aldosterone rather than aldosterone production. This approac...Medical therapy for primary aldosteronism has been stagnant for decades, relying on mineralocorticoid receptor antagonists, which block downstream signaling of aldosterone rather than aldosterone production. This approach typically leads to reactive elevation of aldosterone production, and possible implications of its nongenomic effects. In addition, steroidal mineralocorticoid receptor antagonist use is limited by cross-reactivity with other nuclear receptors and concern for hyperkalemia, particularly in kidney insufficiency. These limitations have propelled a rising interest in therapies that suppress aldosterone production. Aldosterone synthase inhibitors directly target aldosterone synthase overexpression and aldosterone excess. This review presents the evolving landscape of primary aldosteronism therapies, including emerging aldosterone synthase inhibitors and nonsteroidal mineralocorticoid receptor antagonists, and it presents a perspective on expected benefits and limitations of these emerging classes.
Hypertension
· 2026 May · PMID 41685446
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Atrial fibrillation represents the most prevalent cardiac arrhythmia and is associated with substantial morbidity, including an increased risk for stroke and heart failure. The pathophysiology of atrial fibrillation invo...Atrial fibrillation represents the most prevalent cardiac arrhythmia and is associated with substantial morbidity, including an increased risk for stroke and heart failure. The pathophysiology of atrial fibrillation involves electrical and structural remodeling of the atria, often referred to as atrial myopathy, that together increase the risk for arrhythmias. However, a specific approach to target the proarrhythmic substrate of atrial fibrillation is still lacking. Aldosterone and the mineralocorticoid receptor are well-known drivers of cardiac remodeling, and recent clinical and experimental studies indicate that they play a critical role in the pathogenesis of atrial fibrillation. Elevated aldosterone levels, for example, in primary aldosteronism, are associated with a higher risk for atrial fibrillation. Mineralocorticoid receptor antagonists reduce the onset of atrial fibrillation across various patient populations, including patients with hypertension, heart failure, chronic kidney disease, or undergoing cardiac surgery. In patients with preexisting atrial fibrillation, mineralocorticoid receptor antagonists may decrease atrial fibrillation recurrence when added to antiarrhythmic therapies. Experimental studies provide a direct link between aldosterone and atrial remodeling and arrhythmia. Mineralocorticoid receptor activation modulates several key cellular processes involved in atrial inflammation, fibrosis, and arrhythmogenesis, including fibroblast activation, cardiomyocyte dysfunction, and ion channel activity. Here, we review what is currently known about the role of aldosterone and the mineralocorticoid receptor in atrial fibrillation, summarize the mechanistic basis as supported by experimental studies, and discuss the potential of mineralocorticoid receptor antagonists in the prevention and treatment of atrial fibrillation.
Liu M, Liu X, Zhan P
… +9 more, Jin H, Wu J, Han H, Gao C, Wang Z, Wang X, Tang W, Zuo F, Yi F
Hypertension
· 2026 Jun · PMID 41685428
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BACKGROUND: Endothelial dysfunction is recognized as a crucial initiating factor for hypertension and associated cardiovascular/renal injury. Although MYDGF (myeloid-derived growth factor) is mainly derived from bone mar...BACKGROUND: Endothelial dysfunction is recognized as a crucial initiating factor for hypertension and associated cardiovascular/renal injury. Although MYDGF (myeloid-derived growth factor) is mainly derived from bone marrow cells, recent studies have also found the expression of MYDGF in different parenchymal cells. However, the expression pattern and the role of endothelial MYDGF in hypertension remain unclear. METHODS: Endothelial-specific knockout of mice and recombinant MYDGF were used to examine the role of MYDGF in hypertension and associated cardiovascular/renal injury. RESULTS: Endothelial MYDGF was significantly downregulated in hypertensive mice. deficiency in the endothelium aggravated endothelial dysfunction and cardiovascular/renal injury in hypertensive mice, which was attenuated by the overexpression of MYDGF or recombinant MYDGF. Functionally, MYDGF maintained endothelial homeostasis via pleiotropic protective effects, including anti-inflammation, antiapoptosis, inhibiting aberrant endothelial permeability and senescence, and inducing NO generation. Mechanistically, MYDGF promoted the activation of HMOX1 (heme oxygenase-1) transcription by mediating STAT3 (signal transducer and activator of transcription 3) phosphorylation, thereby reestablishing endothelial homeostasis. CONCLUSIONS: MYDGF governs endothelial homeostasis in hypertension through regulating HMOX1 expression. Targeting MYDGF may offer an innovative approach for treating hypertension and its cardiovascular complications.
BACKGROUND: This study aims to develop a prediction model to identify individuals at risk of hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, by integrating epigenetic biom...BACKGROUND: This study aims to develop a prediction model to identify individuals at risk of hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, by integrating epigenetic biomarkers and clinical factors in the first trimester of pregnancy. METHODS: A 2-stage nested case-control study, matched by age and body mass index, was conducted with 618 pregnant women in China, with peripheral blood samples collected in the first trimester to evaluate the average methylation levels of differentially methylated regions (DMRs) between controls and HDP cases. In stage 1 (discovery set), 24 controls and 27 cases were used to identify the differential DMRs. In stage 2, 294 controls and 273 cases were used to validate the previously identified DMRs. DMRs selected from the intersectional results of lasso regression, XGBoost, random forest, and Shapley Additive Explanations models were further combined with women's clinical risk factors to construct prediction models using logistic regression. RESULTS: In stage 1, 52 differential DMRs were identified with a false-positive rate <0.05. In stage 2, 12 differential DMRs were consistently observed, and 3 DMRs located in the , , and genes were selected to construct a prediction model for HDPs. After combining the selected DMRs with clinical factors, the model achieved an area under the curve of 0.863 (95% CI, 0.826-0.901) in the training set and 0.757 (95% CI, 0.686-0.828) in the test set. CONCLUSION: Findings of this study offer potential opportunities to identify high-risk patients with HDP in early pregnancy through DMRs identified in peripheral blood and provide new insights into the epigenetic cause of HDP.
Fang Y, Wang Z, Li Y
… +18 more, Shang X, Xu D, Zhao L, Niu Y, Zou J, Zhao D, Ouyang G, Xiao H, Li N, Yu Y, Liu Y, Liu C, Wang Y, Qin Y, Zhang H, Legro RS, Wei D, Chen ZJ
Hypertension
· 2026 Apr · PMID 41669843
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BACKGROUND: The latest updated 2025 and 2017 American College of Cardiology and the American Heart Association guidelines lowered the diagnostic threshold for hypertension to 130/80 mm Hg. Whether the new classification...BACKGROUND: The latest updated 2025 and 2017 American College of Cardiology and the American Heart Association guidelines lowered the diagnostic threshold for hypertension to 130/80 mm Hg. Whether the new classification for hypertension has implications for reproductive outcomes remains uncertain. METHODS: This retrospective cohort study was conducted at the Reproductive Medicine Center of Shandong University in China. Women who underwent the initial embryo transfer of their first in vitro fertilization cycle were categorized into the normal blood pressure (BP), elevated BP, stage 1 hypertension, and stage 2 hypertension groups based on BP levels measured just before in vitro fertilization treatment. We examined associations of prepregnancy BP and reproductive outcomes. RESULTS: This study included 43 629 women who received in vitro fertilization treatment. The rate of live birth was lower in women with stage 1 and stage 2 hypertensions (46.1% and 41.4%, respectively) compared with women with normal BP (49.2%), with the adjusted relative ratios of 0.97 (95% CI, 0.937-0.996; =0.027) and 0.91 (95% CI, 0.85-0.98; =0.009), respectively. Compared with normal BP, both stage 1 and stage 2 hypertension were associated with higher risks of pregnancy loss, preeclampsia, and preterm delivery. Elevated BP was associated with a higher risk of gestational hypertension. Optimal BP cutoffs for adverse reproductive outcomes were consistent with the diagnostic threshold for stage 1 hypertension. CONCLUSIONS: Compared with normal BP, prepregnancy stage 1 and stage 2 hypertension were associated with a lower rate of live birth after in vitro fertilization treatment and increased risks of pregnancy complications.
Larbi Kwapong F, Grobman B, Col H
… +18 more, Khan MM, Patil D, Aidoo EL, Zhang M, Turkson-Ocran RN, Ngo L, Cluett JL, Mukamal K, Selvin E, Lutsey PL, Windham BG, Mosley TH, Wagenknecht LE, Hughes T, Coresh J, Ring K, Valint A, Juraschek SP
Hypertension
· 2026 Apr · PMID 41669826
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BACKGROUND: Home blood pressure (BP) monitoring (HBPM) is increasingly used as an alternative to office BP. However, factors influencing agreement between office and home BP among very old adults remain unclear. METHODS:...BACKGROUND: Home blood pressure (BP) monitoring (HBPM) is increasingly used as an alternative to office BP. However, factors influencing agreement between office and home BP among very old adults remain unclear. METHODS: During ARIC (Atherosclerosis Risk in Communities) visit 10, participants underwent 3 automated office BP (AOBP) measurements using an Omron HEM-907XL and performed HBPM twice daily for 8 days using an Omron BP7450. Discordance was defined as a systolic BP difference of ±10 mm Hg between mean AOBP and HBPM. Multivariable regression models evaluated demographic, anthropometric, and clinical factors associated with discordance. RESULTS: Among 792 participants (58% female; mean age, 84±3.7 years), mean systolic BP was 130.6 mm Hg (AOBP) and 129.6 mm Hg (HBPM). Despite a minimal average difference (1.0±15.7 mm Hg), 49% had ≥10 mm Hg systolic BP discordance. Higher AOBP was associated with greater discordance. Compared with females, males had lower AOBP relative to HBPM (-4.69 mm Hg [95% CI, -6.86 to -2.51]). Smaller arm circumference was associated with higher discordance (β=14.4 mm Hg [95% CI, 4.78-24.04]). Frail adults had lower AOBP relative to HBPM (β, -5.1 mm Hg [95% CI, -11.0 to 0.9]). Baseline AOBP systolic BP ≥140 mm Hg strongly predicted discordance ≥+10 mm Hg (odds ratio, 8.27 [95% CI, 5.52-12.40]). Participants aged 91 to 100 years had lower AOBP than those aged 78 to 80 years (β, -5.0 mm Hg [95% CI, -10.06 to 0.001]). CONCLUSIONS: Among very old adults, substantial BP discordance between AOBP and HBPM was common and influenced by higher BP, age, male sex, arm circumference, and frailty.
Hypertension
· 2026 May · PMID 41645899
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Fewer than 2% of eligible patients are screened for primary aldosteronism, despite evidence that early detection and targeted therapy are associated with lower cardiovascular and kidney morbidity. Recent updates to major...Fewer than 2% of eligible patients are screened for primary aldosteronism, despite evidence that early detection and targeted therapy are associated with lower cardiovascular and kidney morbidity. Recent updates to major hypertension and endocrine guidelines reflect growing recognition that primary aldosteronism is far more prevalent than previously understood and that broader, more practical screening approaches are needed. These recommendations increasingly extend screening beyond resistant hypertension to adults with stage 2 hypertension and even to all individuals with hypertension. They also aim to lower barriers to testing through more flexible guidance on antihypertensive medication management, reaffirm the aldosterone-to-renin ratio as the preferred initial test, and provide more standardized criteria for interpretation. Supporting evidence includes epidemiological data demonstrating a continuum of renin-independent aldosterone production across blood pressure categories, strong associations between untreated primary aldosteronism and adverse cardiovascular and kidney outcomes independent of blood pressure, and favorable cost-effectiveness of screening even in lower-risk groups. Implementation remains the principal challenge, with obstacles spanning patient, clinician, and health system levels. Emerging electronic health record strategies, including electronic phenotyping and integrated clinical decision support, have shown early promise in increasing screening uptake and streamlining diagnostic pathways. Collectively, contemporary guideline updates and implementation innovations represent a shift toward earlier and broader detection of primary aldosteronism, with the potential to reduce preventable cardiorenal disease across the hypertensive population.
Liu Z, Zhang X, Wang C
… +6 more, Luo S, Liu H, Yu Y, Pei J, Tang Y, Gu W
Hypertension
· 2026 Jun · PMID 41645896
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BACKGROUND: Preeclampsia is a severe hypertensive disorder of pregnancy associated with low (sirtuin 1) levels in trophoblasts. Single-cell sequencing showed abnormal activation of trophoblast (retinoic acid receptor r...BACKGROUND: Preeclampsia is a severe hypertensive disorder of pregnancy associated with low (sirtuin 1) levels in trophoblasts. Single-cell sequencing showed abnormal activation of trophoblast (retinoic acid receptor responder 2) and macrophage (chemokine-like receptor 1) at the maternal-fetal interface in systemic heterozygous knockout mice. This study investigated how low SIRT1 in trophoblasts increases RARRES2 expression, affecting macrophage polarization and preeclampsia pathogenesis. METHODS: We conducted coculture experiments to analyze trophoblast RARRES2 and macrophage CMKLR1 interactions, performed luciferase and chromatin immunoprecipitation assays to validate transcription factors for RARRES2 in trophoblasts, and utilized mass spectrometry and immunoprecipitation to identify transcriptional coregulators. cKO (trophoblast-specific knockout) mice were generated and treated with knockout or progesterone supplementation to validate the role of the SIRT1/RARRES2 axis in preeclampsia pathogenesis and prevention by progesterone. Finally, we measured RARRES2 and SIRT1 levels in the plasma of patients with preeclampsia. RESULTS: Low-SIRT1 expression in trophoblasts promoted M1-type macrophage polarization and inhibited trophoblast invasion, mediated by the RARRES2-CMKLR1 interaction. SIRT1 regulated RARRES2 expression in trophoblasts by recruiting NCOR2 (nuclear receptor corepressor 2). cKO mice showed preeclampsia-like symptoms and RARRES2-CMKLR1 activation at the maternal-fetal interface, which were reversed by knockout or progesterone supplementation. Notably, RARRES2 levels were higher and were a risk factor, whereas SIRT1 levels were lower and were a protective factor for preeclampsia in early pregnancy. CONCLUSIONS: This study highlights SIRT1's potential role in regulating abnormal trophoblast-macrophage interactions at the maternal-fetal interface in preeclampsia and offers a new strategy for its early prediction and prevention.
Li SS, Guo M, Zhao Y
… +4 more, Huang S, You Y, Cai Y, Jin X
Hypertension
· 2026 Jun · PMID 41641542
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BACKGROUND: Circular RNAs have emerged as key regulators of vascular remodeling and promising therapeutic targets, yet their specific contributions to pulmonary hypertension (PH) remain largely unknown. METHODS: We ident...BACKGROUND: Circular RNAs have emerged as key regulators of vascular remodeling and promising therapeutic targets, yet their specific contributions to pulmonary hypertension (PH) remain largely unknown. METHODS: We identified a PH-related circular RNA, circMFN2, generated from the MFN2 (mitofusin-2) locus, which was significantly downregulated in the peripheral blood of patients with PH and in pulmonary arteries of Sugen/hypoxia-induced PH mice. Functional studies were performed in human pulmonary artery smooth muscle cells under hypoxic conditions and in Sugen/hypoxia mice treated intranasally with R8-circMFN2 (R8-peptide-modified liposomal circMFN2). Transcriptomic profiling, RNA-protein interaction assays, and mitochondrial function analyses were used to define the downstream mechanisms. RESULTS: circMFN2 overexpression significantly attenuated hypoxia-induced human pulmonary artery smooth muscle cell proliferation, migration, and mitochondrial dysfunction. RNA sequencing after circMFN2 knockdown revealed activation of gene networks associated with respiratory system diseases. Mechanistically, circMFN2 directly bound the RNA-binding protein IGF2BP3 (insulin-like growth factor 2 mRNA-binding protein 3), thereby blocking its stabilization of PDK4 (pyruvate dehydrogenase kinase 4) mRNA. This circMFN2-IGF2BP3-PDK4 regulatory axis limited PDK4-mediated metabolic reprogramming, restored mitochondrial fusion, reduced reactive oxygen species, and normalized oxidative phosphorylation. In Sugen/hypoxia mice, therapeutic intranasal delivery of R8-circMFN2 significantly improved pulmonary hemodynamics, reduced vascular remodeling, and downregulated PDK4 expression. CONCLUSIONS: circMFN2 functions as a hypoxia-responsive regulator that preserves mitochondrial homeostasis by restraining the IGF2BP3-PDK4 axis. Intranasal delivery of R8-circMFN2 establishes a translational potential for noninvasive circular RNA-based therapy to reverse pulmonary vascular remodeling and hemodynamic impairment in PH.