Hypertension [JOURNAL]
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200 papers
Human 3D Cardiac Microtissue Model to Investigate Aldosterone-Induced Fibrosis and Electrical Dysfunction.
Burrello J, Senesi G, Altomare C … +6 more , Buffolo F, D'Ascenzo F, Barile L, Mulatero P, Balbi C, Monticone S
Hypertension · 2026 May · PMID 41834728 · Publisher ↗
BACKGROUND: Aldosterone induces cardiac fibrotic remodeling and arrhythmogenic alterations. The lack of suitable preclinical models has hampered an in-depth investigation of the molecular mechanisms involved in aldostero...
BACKGROUND: Aldosterone induces cardiac fibrotic remodeling and arrhythmogenic alterations. The lack of suitable preclinical models has hampered an in-depth investigation of the molecular mechanisms involved in aldosterone-induced cardiac damage. Our aim was to evaluate the effects of aldosterone on 3D human microtissue (hMT) cardiac organoids. METHODS: hMT were generated by coculturing human cardiac fibroblasts, aortic endothelial cells and induced pluripotent stem cell-derived cardiomyocytes. hMT were treated with aldosterone, the mineralocorticoid receptor antagonist eplerenone, and serum from patients with primary aldosteronism or matched subjects with essential hypertension. Immunofluorescence, histology, and Western blot analyses were used to assess fibrosis; a multielectrode array was used to record extracellular field potentials of spontaneously beating human cardiomyocytes. RESULTS: Levels of profibrotic markers increased after incubation with serum from primary aldosteronism patients, compared with untreated organoids and hMT incubated with essential hypertension patient-derived serum. Aldosterone treatment reproduced the same profibrotic effect in a dose-dependent manner, and coadministration of eplerenone blunted these effects. Aldosterone treatment increased corrected field potential duration (an estimate of the QT interval) and downregulated the expression levels of and , responsible for the slow delayed rectifier potassium current and for calcium handling in the sarcoplasmic reticulum. Eplerenone cotreatment reverted these electrical alterations. CONCLUSIONS: 3D hMT organoids offer a relevant in vitro model to study aldosterone-mediated cardiac effects. Aldosterone directly induces fibrosis and prolongation of the QT interval in this model, which may partially explain the increase of cardiovascular risk in patients with primary aldosteronism and underscores the benefit of mineralocorticoid receptor antagonist therapy.
Enhanced Mitochondrial Mrs2-Mg Signaling Drives Mitochondrial Dysfunction in Pulmonary Arterial Hypertension Rats.
Chen RN, Weng XQ, Yan Y … +8 more , Chen QY, Lin YC, Liu L, Zhuang XL, Gui LX, Sham JSK, Lin MJ, Lin DC
Hypertension · 2026 Jun · PMID 41834713 · Publisher ↗
BACKGROUND: Pulmonary arterial hypertension (PAH) involves ionic homeostasis and vascular remodeling. While cytosolic magnesium ([Mg]ᵢ) depletion is a hallmark of PAH, the role of mitochondrial Mg (Mg) remains elusive. m...
BACKGROUND: Pulmonary arterial hypertension (PAH) involves ionic homeostasis and vascular remodeling. While cytosolic magnesium ([Mg]ᵢ) depletion is a hallmark of PAH, the role of mitochondrial Mg (Mg) remains elusive. mitochondrial RNA splicing 2 (Mrs2), the primary Mg influx transporter, is hypothesized to drive PAH by orchestrating mitochondrial ionic imbalance and dysfunction. METHODS: Primary pulmonary arterial smooth muscle cells isolated from monocrotaline-induced PAH rats were used for mechanistic investigation, with key metabolic and mitochondrial alterations validated in the Su5416 (semaxanib)/hypoxia model. In vivo, adeno-associated virus-mediated Mrs2 knockdown was used to evaluate therapeutic potential. RESULTS: In PAH-pulmonary arterial smooth muscle cells, Mrs2 upregulation and Slc41a3 (solute carrier family 41 member 3) downregulation caused Mg overload and [Mg]ᵢ depletion. Excess Mg promoted pyruvate dehydrogenase phosphorylation, driving glycolysis and lactate production in association with Hif-1α (hypoxia-inducible factor-1α) activation and a Pkm2 (pyruvate kinase M2)-linked glycolytic shift. Proinflammatory cytokines further amplified lactate accumulation, which exacerbated Mg and cytosolic calcium ([Ca]ᵢ) overload, establishing a maladaptive Mg-lactate feedback loop. This ionic-metabolic stress triggered Ca-dependent mitochondrial fission, redox imbalance, and pulmonary arterial smooth muscle cell hyperproliferation. Moreover, Mrs2 was associated with enhanced Trpc3 (transient receptor potential channel 3)-dependent mitochondrial Ca uptake. Crucially, Mrs2 knockdown restored mitochondrial bioenergetics and morphology, attenuated vascular remodeling, and improved hemodynamics in monocrotaline-PAH rats. CONCLUSIONS: Aberrant Mrs2-mediated Mg signaling disrupts global ionic and metabolic homeostasis, driving mitochondrial dysfunction and pathogenic remodeling in PAH. Targeting the Mrs2-centered ionic-metabolic-dynamic axis may represent a potential therapeutic approach that warrants further investigation to interrupt PAH progression.
-Negative Primary Aldosteronism: Histopathology and Surgical Outcomes.
Wu CH, Peng KY, Yang YW … +6 more , Chen PY, Chen YL, Chang CC, Lin YH, Wu VC, TAIPAI Study Group
Hypertension · 2026 May · PMID 41822958 · Publisher ↗
BACKGROUND: Unilateral primary aldosteronism (uPA) is the most common surgically curable secondary hypertension. mutations are frequent in aldosterone-producing adenomas, but the clinical significance of -negative uPA r...
BACKGROUND: Unilateral primary aldosteronism (uPA) is the most common surgically curable secondary hypertension. mutations are frequent in aldosterone-producing adenomas, but the clinical significance of -negative uPA remains unclear. We investigated whether histopathologic subtypes defined by the HISTALDO (Histopathology of Primary Aldosteronism) consensus are associated with postoperative outcomes in -negative uPA. METHODS: We analyzed 171 -negative uPA patients from the Taiwan Primary Aldosteronism Investigation registry who underwent adrenalectomy. Somatic mutations were identified by Sanger sequencing and targeted next-generation sequencing. Adrenal histopathology was classified as classical (solitary adenoma or dominant nodule) or nonclassical (multiple nodules, micronodules, or diffuse hyperplasia) per the HISTALDO criteria. Postsurgical outcomes at 12 months were assessed using the Primary Aldosteronism Surgical Outcome consensus criteria. RESULTS: The cohort (mean age, 55.0±11.3 years; 53.8% women) comprised 90 (52.6%) patients with classical histopathology and 81 (47.4%) with nonclassical features. Complete clinical success was achieved in 40.9% of patients at 12 months. Patients with classical histopathology had significantly higher complete clinical success (50%) than those with nonclassical histopathology (30.9%; =0.01). On multivariate analysis, nonclassical histopathology (odds ratio, 0.33 [95% CI, 0.16-0.68]; =0.003), higher preoperative serum creatinine (odds ratio, 0.24; =0.022), and higher diastolic blood pressure (odds ratio, 0.97; =0.017) independently predicted failure to achieve complete clinical success. CONCLUSIONS: Nearly half of -negative uPA cases exhibit nonclassical adrenal histopathology, which is associated with significantly lower complete clinical success rates. These findings underscore the prognostic value of histopathologic classification in -negative uPA and support integrating histology and genetics to improve patient management.
Treatment of Primary Aldosteronism.
Parisien-La Salle S, Hundemer GL, Nehs MA … +2 more , Barletta JA, Vaidya A
Hypertension · 2026 May · PMID 41808633 · Publisher ↗
Primary aldosteronism (PA) is a common cause of hypertension, characterized by renin-independent aldosterone production that drives inappropriate mineralocorticoid receptor activation, sodium retention, volume expansion,...
Primary aldosteronism (PA) is a common cause of hypertension, characterized by renin-independent aldosterone production that drives inappropriate mineralocorticoid receptor activation, sodium retention, volume expansion, and potassium wasting, ultimately resulting in hypertension and adverse cardiorenal outcomes. Management of PA involves therapies that target these pathophysiologic mechanisms to restore homeostasis and reduce risk, which is usually tailored based on patient preference and whether PA is lateralizing or nonlateralizing. For patients with lateralizing PA, surgical adrenalectomy, and to a lesser extent, minimally invasive adrenal or adrenal artery ablation, is highly effective at improving blood pressure control and risk for incident cardiovascular outcomes. However, the vast majority of patients with PA will be treated with medical therapy using steroidal mineralocorticoid receptor antagonists as the cornerstone of therapy, and epithelial sodium channel inhibitors serving as infrequent alternatives. Dietary sodium restriction in PA should be strongly encouraged because it reduces the substrate that fuels PA pathophysiology; dietary sodium restriction can facilitate substantial reductions in blood pressure, especially when combined with mineralocorticoid receptor antagonist therapy. Once initiated, medical therapy should be intensified to achieve 3 objectives in the following order of importance: normalization of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium when applicable, and increases in renin from baseline as a biomarker of adequate aldosterone blockade.
Ultrasound-Targeted Ablation of the Aortorenal Ganglion in Canine Model for Hypertension Treatment.
Li Q, Lou Y, Xu T … +8 more , Liu Y, Zhang Z, Wu Y, Li C, Fang Q, Du Y, Li X, Huang J
Hypertension · 2026 Jun · PMID 41808618 · Publisher ↗
BACKGROUND: Precisely map and ablate the aortorenal ganglion (ARG) using noninvasive ultrasound technology to evaluate therapeutic effects and mechanisms in hypertension and related organ involvement. METHODS: A noninvas...
BACKGROUND: Precisely map and ablate the aortorenal ganglion (ARG) using noninvasive ultrasound technology to evaluate therapeutic effects and mechanisms in hypertension and related organ involvement. METHODS: A noninvasive dual-frequency ultrasound with a 3-dimensional targeting system was utilized to precisely map and ablate the ARG in a hypertensive canine model (2-kidney, 1-clip). Blood pressure changes from ultrasound stimulation served as a real-time evaluation metric, leading to an ultrasound stimulation-ablation-re-stimulation-supplementary ablation protocol for comprehensive ablation. Follow-up assessments at 1, 3, and 6 months post-ablation included evaluations of blood pressure, ventricular fibrosis and hypertrophy, cardiac function, and both local and systemic sympathetic nerve activity. RESULTS: One month postultrasound-targeted ARG ablation, there was a significant reduction in systolic blood pressure (∆ = -8.67±2.07 mm Hg; <0.05), with further decreases at 3 months (∆ = -14.17±3.49 mm Hg; <0.001) and 6 months (∆ = -24.83±4.49 mm Hg; <0.001). Histological and echocardiographic assessments indicated improvements in ventricular fibrosis and hypertrophy, along with an enhanced left ventricular ejection fraction. Moreover, a reduction in sympathetic nerve activity was observed in the body, heart, and kidneys. In addition, aortic and adrenal tissue integrity, as well as normal liver and kidney functions, with no significant differences between the hypertension model and ARG ablation groups were observed. CONCLUSIONS: Ultrasound-targeted ablation of the ARG significantly reduces blood pressure, suppresses sympathetic nerve activity in the systemic, cardiac, and renal regions, and alleviates hypertension-induced ventricular remodeling, offering a promising therapeutic strategy for hypertension and related cardiovascular diseases.
Stress Trajectory and Hypertension 2 to 7 Years After Delivery: A nuMoM2b-HHS Study.
Nuckols VR, Barone Gibbs B, Brewer BC … +11 more , Gaffey AE, Greaney JL, Patterson F, Greenland P, Saade GR, Grobman WA, Yee LM, Bairey Merz CN, Chung JH, Theilen LH, Wenner MM
Hypertension · 2026 Apr · PMID 41797710 · Full text
BACKGROUND: Adverse pregnancy outcomes (APOs) are associated with a higher risk of developing chronic hypertension. The objectives of this study were to determine whether patterns of perceived stress during and after pre...
BACKGROUND: Adverse pregnancy outcomes (APOs) are associated with a higher risk of developing chronic hypertension. The objectives of this study were to determine whether patterns of perceived stress during and after pregnancy were associated with blood pressure and incident hypertension 2 to 7 years after delivery, and whether having an APO modified this association. METHODS: Analyses utilized data from the prospective nuMoM2b-HHS cohort (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study). Perceived stress was assessed using the Perceived Stress Scale in the first and third trimester and 2 to 7 years after delivery. Latent class trajectory analysis characterized subgroups with similar patterns of perceived stress over time. APOs were abstracted from medical charts and included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age, and stillbirth. Multivariable regression models evaluated the independent effects of perceived stress on systolic and diastolic blood pressure and incident hypertension and 2 to 7 years after delivery. RESULTS: Three distinct stress trajectory groups emerged, delineated by persistently low, moderate, and high stress levels. No associations between stress trajectory group and blood pressure or incident hypertension were observed after adjustment for covariates. However, there was a significant interaction between stress trajectory group and APO on blood pressure ( for interaction=0.04). Stress trajectory group was associated with higher blood pressure only among those with APO (=1.991±0.819 mm Hg; =0.02) but not without APO (=0.040±0.471 mm Hg, =0.93). CONCLUSIONS: These findings suggest that elevated perceived stress may contribute to higher blood pressure, specifically among women who had an APO.
BRISC Deficiency Drives Heart Failure by Regulating β-Catenin K63 Ubiquitination.
Liu L, Ren GM, Chen C … +10 more , Liu GY, Niu WH, Yang XM, Wang MX, Xie YP, Jia LX, Cui W, Du J, Yin RH, Wang L
Hypertension · 2026 Jun · PMID 41789465 · Publisher ↗
BACKGROUND: Adverse cardiac remodeling and dysfunction are hallmarks of hypertensive heart failure, yet molecular mechanisms remain incompletely understood. K63-linked deubiquitination has emerged as a critical posttrans...
BACKGROUND: Adverse cardiac remodeling and dysfunction are hallmarks of hypertensive heart failure, yet molecular mechanisms remain incompletely understood. K63-linked deubiquitination has emerged as a critical posttranslational regulatory process in cardiac remodeling. This study investigated the role of BRISC (BRCC3 [BRCA1/BRCA2-containing complex subunit 3] isopeptidase complex), a K63-specific deubiquitinase, in hypertensive cardiac remodeling. METHODS: Expression of BRISC subunits was analyzed in hypertrophic human and murine hearts. Cardiac phenotypes were assessed in global and cardiomyocyte-specific (Abraxas 2, BRISC complex subunit) knockout, cardiomyocyte-specific overexpression, or knockout mice under baseline and Ang II (angiotensin II)-infused conditions. Ubiquitinome profiling, coimmunoprecipitation, immunoprecipitation-mass spectrometry, cleavage under targets and tagmentation analysis, ubiquitination site mutation, and rescue experiments were performed to identify BRISC substrates and mechanisms. RESULTS: The BRISC scaffolding subunit ABRO1 was markedly downregulated in cardiomyocytes from hypertrophic hearts. Global or cardiomyocyte-specific deletion led to spontaneous cardiac hypertrophy and contractile dysfunction, which were further aggravated by Ang II stimulation. Conversely, cardiomyocyte-specific overexpression alleviated Ang II-induced cardiac remodeling and dysfunction. Knockout of , the catalytic subunit of BRISC, phenocopied the cardiac abnormalities observed in -deficient mice. Mechanistically, ABRO1 directly interacted with β-catenin and cleaved K63-linked polyubiquitination chains at lysine 508, thereby restraining β-catenin nuclear accumulation and transcriptional activation. Pharmacological inhibition of β-catenin with ICG-001 (inhibitor of β-catenin/transcription factor mediated transcription) effectively rescued hypertensive cardiac remodeling and dysfunction caused by deficiency. CONCLUSIONS: BRISC acts as a critical K63-specific deubiquitinase that preserves cardiac homeostasis by restraining β-catenin overactivation. Targeting the BRISC-β-catenin axis may represent a novel therapeutic strategy for hypertensive heart failure.
Reliable Detection of SGLT2 Protein by Knockout-Based Antibody Characterization.
Hirose T, Ito H, Endo A … +14 more , Sato S, Takahashi C, Kaburaki T, Yano K, Ishikawa R, Kamada A, Oba-Yabana I, Satoh M, Morozumi K, Kaiho Y, Nakamura Y, Kamijo K, Yumura W, Mori T
Hypertension · 2026 Jun · PMID 41789460 · Publisher ↗
BACKGROUND: SGLT2 (sodium-glucose cotransporter 2) mediates renal glucose reabsorption, and its pharmacological inhibition exerts cardio- and renoprotective benefits. Despite widespread clinical interest, reliable detect...
BACKGROUND: SGLT2 (sodium-glucose cotransporter 2) mediates renal glucose reabsorption, and its pharmacological inhibition exerts cardio- and renoprotective benefits. Despite widespread clinical interest, reliable detection of SGLT2 protein remains challenging due to concerns regarding antibody specificity. METHODS: Eight commercially available anti-SGLT2 antibodies were evaluated by immunohistochemistry and Western blotting using kidneys and hearts from genetically engineered -deficient mice and rats. Human kidney tissues, including renal cell carcinoma samples, were also examined. RESULTS: Among the antibodies tested, ab306558 and HPA041603 showed specific immunostaining in rodent kidneys, with minimal background in wild-type tissues and complete absence of staining in -deficient samples. However, ab306558 was unsuitable for human samples because of nonspecific staining. In renal cell carcinoma, HPA041603 detected SGLT2 immunostaining in proximal tubules of nontumor regions but not in tumor areas. Subcellular analyses revealed that SGLT2 was enriched within proximal tubular microvilli, partially overlapping with PDZK1IP1 (MAP17), but not with LRP2 (megalin) or NHE3. Western blotting identified an SGLT2-specific band at ≈55 kDa in rodent kidney lysates using ab306558, 20802, 24654-1-AP, and HPA041603 under optimized conditions, whereas no SGLT2-specific signals were detected in heart lysates. In contrast, ab85626 detected a weak ≈55 kDa band even in -deficient kidneys. N-linked glycan removal shifted the SGLT2-specific band from ≈55 kDa to ≈45 kDa. CONCLUSIONS: HPA041603 consistently detected SGLT2 in rodent and human kidney tissues, whereas other antibodies showed limited specificity. Knockout-based antibody validation and optimized experimental conditions are essential for accurate interpretation of SGLT2 protein expression in experimental and translational studies.
Frailty Index Offers Greater Discrimination Than Age for Optimal Blood Pressure Targets: A Pooled Analysis of Two Randomized Trials.
Lyu Y, Bian W, Liu Y … +6 more , Liu Y, Zhang J, Song Z, Liu Y, Chen T, Li C
Hypertension · 2026 Jun · PMID 41789453 · Publisher ↗
BACKGROUND: Contemporary hypertension guidelines emphasize individualized blood pressure (BP) management, often incorporating age; yet chronological age alone may be insufficient to guide optimal treatment. The frailty i...
BACKGROUND: Contemporary hypertension guidelines emphasize individualized blood pressure (BP) management, often incorporating age; yet chronological age alone may be insufficient to guide optimal treatment. The frailty index offers a multidimensional measure of biological aging and may better guide BP management. METHODS: We pooled participant-level data from SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD (Action to Control Cardiovascular Risk in Diabetes). The frailty index was calculated using a 31-item Rockwood cumulative-deficit model, with frailty defined as a frailty index >0.21. Participants were also categorized by age (<65 versus ≥65 years). Systolic BP (SBP) time in target range (TTR) was calculated using linear interpolation across 10 mm Hg intervals. Restricted cubic splines and stratified Cox models were used to assess the association between TTR within predefined SBP targets and major adverse cardiovascular events. RESULTS: A total of 19 230 participants were included in the analysis (mean age, 65.2 years; 49.0% women; 68.2% classified as frail). Restricted cubic spline analyses showed a J-shaped relationship between average SBP and major adverse cardiovascular events, with clearer separation by frailty than by age. Among frail individuals, greater time spent within SBP intervals between 110 and 140 mm Hg was associated with lower major adverse cardiovascular event risk (hazard ratios per 10% increase in TTR, 0.92-0.94), whereas among nonfrail individuals, greater time spent below 130 mm Hg was associated with lower risk (hazard ratios per 10% increase in TTR, 0.89-0.98). Age demonstrated limited discrimination. Findings were consistent in separate analyses of SPRINT and ACCORD. CONCLUSIONS: The frailty index, rather than chronological age, more accurately discriminates optimal SBP targets in hypertensive patients, whereas chronological age may remain a more practical tool in resource-limited settings.
Randomized Study of Antithrombin in Early-Onset Preeclampsia: KOUNO-TORI Study.
Takeda J, Tachibana D, Itakura A … +15 more , Takagi K, Nakami S, Mano H, Kobayashi T, Kanayama N, Sameshima H, Morikawa M, Sago H, Adachi T, Ohkuchi A, Takeda S, Masuyama H, Seki H, Saito S, KOUNO-TORI Study Group
Hypertension · 2026 Jun · PMID 41789451 · Full text
BACKGROUND: In preeclampsia, prolonging pregnancy decreases the risks of fetal morbidity and death. This study aimed to evaluate the efficacy and safety of antithrombin in prolonging pregnancy early-onset severe preeclam...
BACKGROUND: In preeclampsia, prolonging pregnancy decreases the risks of fetal morbidity and death. This study aimed to evaluate the efficacy and safety of antithrombin in prolonging pregnancy early-onset severe preeclampsia. METHODS: This was a randomized, double-blind, placebo-controlled study involving women with early-onset preeclampsia from 61 institutions. Participants developed early-onset severe preeclampsia from 24+0 to 31+6 weeks' gestation and had ≤100% antithrombin activity. Two groups were created, with random and blinded assignment of the participants 1:1 to a placebo (saline) group (n=92) or a recombinant human antithrombin-gamma (rhAT-gamma) group (n=90). The number of days from treatment initiation to delivery was recorded in each group, as the primary end point. RESULTS: Pregnancy was prolonged by 13 days (95% CI, 10.4-15.6) in the placebo group and 16.9 days (95% CI, 13.8-20.0) in the rhAT-gamma group (=0.07). Compared with the placebo group, hemorrhage-related adverse events occurred at a 19.0% higher rate in the rhAT-gamma group (mean difference [95% CI, 4.3%-32.7%]), and anemia occurred at a 16.8% higher rate (mean difference [95% CI, 2.0%-30.6%]). CONCLUSIONS: No significant difference in pregnancy prolongation was found between the placebo and rhAT-gamma participants with early-onset severe preeclampsia. However, compared with the placebo group, the rhAT-gamma group appeared to have higher rates of hemorrhage-related adverse events and anemia. REGISTRATION: URL: https://jrct.niph.go.jp/en-top; Unique identifier: jRCT2080224912. URL: https://clinicaltrials.gov/; Unique identifier: NCT04182373.
Interplay of Age and Sex With Clinic and Ambulatory Blood Pressure and Mortality.
Böhm M, de la Sierra A, Schwantke I … +12 more , Haring B, Vinyoles E, Gorostidi M, Segura J, Williams B, Staplin N, Tokcan M, Mahfoud F, Lauder L, Fleig S, Schneider CV, Ruilope LM
Hypertension · 2026 Jun · PMID 41778327 · Publisher ↗
BACKGROUND: To explore associations of clinic and 24-hour ambulatory blood pressure (BP) monitoring (ABPM) with cardiovascular death (CVD), parameters were modeled for age and sex in this large cohort in primary care. ME...
BACKGROUND: To explore associations of clinic and 24-hour ambulatory blood pressure (BP) monitoring (ABPM) with cardiovascular death (CVD), parameters were modeled for age and sex in this large cohort in primary care. METHODS: In the Spanish ABPM Registry, 59.124 patients had complete data on mortality, age, sex, and all ABPM. Office, mean, 24-hour, daytime, and nighttime systolic BP (SBP), diastolic BP, and pulse pressure (PP) were related to CVD according to age and sex and were modelled with restricted cubic splines to get trajectories. During a median of 9.7 years, 2361 patients had CVD (1229 males, 1132 females). RESULTS: Nonlinear relationships for office, 24-hour mean, daytime, and nighttime SBP, diastolic BP, and PP (<0.0001 for all) for both sexes were observed. Until 75 years, SBP was higher in males than females, but differences were minimized after ≈60 to 70 years ( for interaction <0.0001). High SBP and PP are associated with CVD without heterogeneity between sexes and across aging. The increase of SBP and PP was higher at a higher age for females than males ( for interaction <0.0001). CVD was age-dependent, and ABPM, in particular nighttime BP did more closely associated with risk than office BP in younger than in older individuals. CONCLUSIONS: Twenty-four-hour mean, nighttime BP, and PP were closely associated with risk being higher in elderly females than males after 75 years, corresponding to a rise in BP in older females. Guidelines should continue to mandate the evaluation of 24-hour ABPM data for risk prediction.
Cold-Induced Hypertension as Life-Environment Disease in Winter: Focus on Data From Japan.
Kario K
Hypertension · 2026 Jun · PMID 41778326 · Full text
An increase in the rate of cardiovascular events (eg, myocardial infarction, stroke, heart failure) during the winter season has been reported worldwide, including Japan. As 1 contributor to the increase in cardiovascula...
An increase in the rate of cardiovascular events (eg, myocardial infarction, stroke, heart failure) during the winter season has been reported worldwide, including Japan. As 1 contributor to the increase in cardiovascular risk during the colder months, winter hypertension likely reflects an interaction between environmental factors and human physiological responses. In particular, the prognostically important morning blood pressure (BP) surge is accentuated in winter versus other seasons, as is BP variability. Some individuals may exhibit more marked changes in BP in response to cold exposure, referred to as thermosensitive hypertension. During winter mornings, sympathetic activation due to cold stress and the arousal response overlap, producing a synergistic effect that raises baseline BP, amplifies BP variability, and augments the morning BP surge simultaneously. These mechanisms help explain why cardiovascular event risk peaks during the early morning hours in winter. Approaches to optimizing the living environment and lifestyle during winter to help reduce cold-induced increases in BP are discussed, with a focus on Japan. Incorporation of home BP monitoring and newer approaches, such as digital therapeutics are also important. Overall, winter BP management should consider BP variability, time of day (chronobiology), and the environment, rather than focusing solely on absolute BP levels. The period immediately after awakening represents the most dangerous time window, during which cold exposure, low indoor temperature, awakening-related sympathetic activation, and initiation of physical activity converge. Effective management for individual cardiovascular risk reduction requires a comprehensive approach that optimizes living conditions, lifestyle factors, BP monitoring, and hypertension pharmacotherapy.
Contemporary Prevalence and Treatment Patterns Among US Adults With Apparent Treatment-Resistant Hypertension.
Earle WB, Watson NW, Juraschek SP … +3 more , Cluett JL, Krawisz AK, Secemsky EA
Hypertension · 2026 Jun · PMID 41778325 · Publisher ↗
BACKGROUND: Resistant hypertension is associated with adverse cardiovascular outcomes and mortality. In the past decade, management guidelines have shifted to target lower blood pressures (BP). Current prevalence and pre...
BACKGROUND: Resistant hypertension is associated with adverse cardiovascular outcomes and mortality. In the past decade, management guidelines have shifted to target lower blood pressures (BP). Current prevalence and prescribing patterns among adults with resistant hypertension are not well characterized. METHODS: We used data from the National Health and Nutrition Examination Survey from 2003 to 2020. Apparent treatment-resistant hypertension (aTRH) was defined as patients on a diuretic, either with a systolic BP ≥130 or diastolic BP ≥80 mm Hg while on 3 medications or those on ≥4 medications regardless of BP. Medications were identified through pill bottle review. RESULTS: Of 24 579 adults with hypertension , 1939 had aTRH (42.4% male, 19.9% Black), corresponding to a weighted total of 6 989 821 US patients. Among hypertensive adults, the prevalence of aTRH was 6.41% (95% CI, 5.97%-6.88%) and remained stable over time. Over the study duration, aTRH prevalence among adults on treatment decreased from 17.7% to 12.6%. The overall prevalence of hypertension rose from 50.1% to 54.0%, while the prevalence of uncontrolled BP decreased from 75.0% to 68.7%. Over time, use of 3 drug regimens for aTRH decreased (57.8%-42.9%), while 4 drug regimens increased (34.0%-51.8%). aTRH was most strongly associated with older patients, those of Black race, higher body mass index, and more advanced cardiovascular comorbidities. CONCLUSION: The prevalence of aTRH has remained stable over the past 2 decades despite the rising incidence of hypertension . Use of multidrug treatment regimens has increased, aligning with national guidelines. However, uncontrolled hypertension remains high.
Big Data Approach to Assessment of an Aldosterone-Renin Ratio for Detection of Potential Surgical Cases of Primary Aldosteronism.
Leung AA, Burkart JJ, Low JC … +16 more , Hu L, Mellor K, Austin K, Przybowjewski SJ, Caughlin CE, Wright C, Chin A, Orton DJ, Venos E, Harvey A, Yeo C, Hundemer GL, Pasieka JL, So CB, King J, Kline GA
Hypertension · 2026 May · PMID 41778324 · Publisher ↗
BACKGROUND: Prior retrospective studies of aldosterone-renin ratio (ARR) measures were confounded by selection bias. METHODS: To define ARR sensitivity independent of case definition, administrative health and diagnostic...
BACKGROUND: Prior retrospective studies of aldosterone-renin ratio (ARR) measures were confounded by selection bias. METHODS: To define ARR sensitivity independent of case definition, administrative health and diagnostic imaging repositories in Alberta, Canada, were used to construct a 5-component definition for primary aldosteronism (PA) for the most easily recognizable cases. Components included hypertension, hypokalemia, adrenal mass, suppressed renin, and nonsuppressed aldosterone. ARR was omitted from the definition, permitting independent evaluation of the ARR using receiver operating characteristic curve analysis. The definition was validated by adrenal vein sampling and surgical outcomes. RESULTS: Of 931 adrenal vein sampling patients, 19.2% met the 5-component PA case definition; of these, 86.8% had unilateral disease, and of the 76.8% who underwent surgery, 91.2% achieved complete biochemical response. Between 2012 and 2019, 6717 patients with hypertension had ARR measured; 60.9% had computed tomography or magnetic resonance imaging performed for any reason. The prevalence of the 5-component PA cases was 4.8% by direct renin concentration and 6.6% by plasma renin activity. The area under the receiver operating characteristic curve for the ARR was 0.84 (0.81-0.86) and 0.82 (0.78-0.85) when direct renin concentration and plasma renin activity were used. The 90% sensitivity ARR threshold for the 5-component PA case definition was 26 pmol/mIU (direct renin) and 350 pmol/ng per mL/h (renin activity), with specificities of 60% and 56%. At 5% prevalence rates, positive predictive values were 11% and 10%. Commonly recommended ARR screening thresholds of 70 pmol/mIU or 550 pmol/ng per mL/h had sensitivities of 68% and 82%, respectively, for a surgically relevant PA phenotype. CONCLUSIONS: Current ARR thresholds have low-to-moderate sensitivity for cases of PA where adrenal vein sampling and surgery are strong considerations.
Association Between 24-Hour Systolic Blood Pressure Time in Target Range and Mortality.
Lauder L, Schwantke I, de la Sierra A … +8 more , Vinyoles E, Gorostidi M, Segura J, Williams B, Staplin N, Ruilope LM, Böhm M, Mahfoud F
Hypertension · 2026 Jun · PMID 41757387 · Publisher ↗
BACKGROUND: Time in target range (TTR) reflects the proportion of time blood pressure (BP) remains within a defined range, integrating BP variability and control. We examined associations of systolic BP (SBP) TTR during...
BACKGROUND: Time in target range (TTR) reflects the proportion of time blood pressure (BP) remains within a defined range, integrating BP variability and control. We examined associations of systolic BP (SBP) TTR during ambulatory BP monitoring with cardiovascular and all-cause mortalities. METHODS: Patients from the Spanish Ambulatory BP Monitoring Registry who were receiving antihypertensive medications or who had sustained or masked hypertension without treatment, defined by office BP ≥140/90 mmHg and 24-hour BP ≥130/80 mmHg, were included. TTR was estimated by linear interpolation between consecutive SBP recordings obtained from ambulatory BP monitoring and expressed as the proportion of time SBP remained within 120 to 134 mm Hg during daytime and 110 to 119 mm Hg during nighttime, from which 24-hour TTR was derived. Associations with mortality were assessed by Cox regression adjusted for demographic and clinical variables. RESULTS: A total of 48 687 patients (46% women) were analyzed. Over a median follow-up of 9.7 years, 6502 deaths occurred, including 2185 cardiovascular deaths. Higher 24-hour TTR was associated with lower all-cause mortality (hazard ratio, 0.83 per 1-SD increment [95% CI, 0.80-0.85]). Similarly, higher 24-hour TTR was associated with lower cardiovascular mortality (hazard ratio, 0.80 per 1-SD increment [95% CI, 0.76-0.84]). Both associations remained significant after adjusting for the mean 24-hour SBP and SBP variability. CONCLUSIONS: Higher 24-hour SBP TTR derived from ambulatory BP monitoring was independently associated with lower all-cause and cardiovascular mortalities.
Predicting Nocturnal Hypertension in CKD Through Table-Value Diffusion Model.
Cai X, Li R, Liu Z … +9 more , Liu S, Zhang X, Jiang X, Ge S, Zhang J, Li M, Peng H, Lu Y, Wang C
Hypertension · 2026 Apr · PMID 41744090 · Publisher ↗
BACKGROUND: Ambulatory blood pressure monitoring is indispensable for diagnosing nocturnal hypertension (NH) among patients with chronic kidney disease, but it is costly and time-consuming. Screening tools for predicting...
BACKGROUND: Ambulatory blood pressure monitoring is indispensable for diagnosing nocturnal hypertension (NH) among patients with chronic kidney disease, but it is costly and time-consuming. Screening tools for predicting high-risk NH are urgently needed. METHODS: A large cohort of 5769 patients with nondialysis chronic kidney disease were enrolled (hospital A: 4565; hospital B: 1204). Patients from hospital A were split 8:2 into training/internal test sets; hospital B served as the external test set. A total of 1006 patients with at least 2 valid ambulatory blood pressure monitoring recordings were used for secondary validation. We proposed a table-value diffusion model by incorporating generative modeling concepts to map distributions between clinical variables and predict NH. The predicted probabilities for NH were stratified and validated according to patients' true adverse renal/cardiovascular prognoses. RESULTS: Through a rigorous selection process combining univariate ranking and clinical expertise, we selected 7 core predictors: age, body mass index, clinic systolic/diastolic blood pressure, estimated glomerular filtration rate, hypertension history, and use of non-renin-angiotensin-aldosterone system antihypertensive agents. In the test sets, the 7-variable diffusion model achieved a significantly higher area under the curve than the 7-variable logistic model (internal: 0.870 versus 0.807, <0.001; external: 0.854 versus 0.792, <0.001). Secondary validation confirmed the 7-variable diffusion model's stability (area under the curve=0.869, Cohen kappa index=0.560). Risk stratification was established (high-risk >0.692, intermediate-risk 0.692-0.515, and low-risk <0.515). Patients in the high-risk group had a higher incidence of adverse renal/cardiovascular events than those in the low-risk group. CONCLUSIONS: We developed a concise 7-variable diffusion model for NH using a table-value diffusion model, supporting targeted ambulatory blood pressure monitoring screening in patients with chronic kidney disease.
Intensive BP Control and Cognitive Function: A Randomized Clinical Trial.
Wang B, Sun Y, Li Y … +16 more , Wu L, Peng Y, Li S, Ge J, Zhang L, Zhao L, Liu J, Su S, Zhang B, Liu Y, Ma X, Zuo Z, Zhang H, Wang Y, Liu J, Li J
Hypertension · 2026 Apr · PMID 41744069 · Full text
BACKGROUND: The impact of intensive blood pressure (BP) control on cognitive function in East Asian populations remains uncertain. We aimed to assess the effect of a lower systolic BP target on global cognitive function...
BACKGROUND: The impact of intensive blood pressure (BP) control on cognitive function in East Asian populations remains uncertain. We aimed to assess the effect of a lower systolic BP target on global cognitive function in Chinese hypertensive adults. METHODS: This secondary analysis of a randomized trial involved hypertensive patients with high cardiovascular risk across 116 sites in China. Participants were assigned to receive intensive treatment (systolic BP target <120 mm Hg) or standard treatment (systolic BP target <140 mm Hg) for a median of 3.4 years. Cognitive function was assessed via MMSE (Mini-Mental State Examination) at baseline and the end of the study. Prespecified outcomes were a change in MMSE score and investigator-reported probable dementia. RESULTS: Among 11 255 randomized participants, all completed cognitive assessment at baseline and 10 440 (92.8%) at the end of the study. The mean change in MMSE score was not significantly different between arms (difference, 0.05 [95% CI, -0.07 to 0.17]), with a mean change of -0.54 (95% CI, -0.63 to -0.46) in the intensive arm and -0.60 (95% CI, -0.68 to -0.51) in the standard arm. Results were robust across sensitivity analyses and consistent across most subgroups. Exceptions included subgroups of coronary heart disease or antiplatelet treatment. The incidence of probable dementia was too low for meaningful interpretation. CONCLUSIONS: Intensive systolic BP lowering to a target of <120 mm Hg for 3 years did not adversely affect global cognitive function in Chinese hypertensive adults, irrespective of age, sex, BP level, and comorbidities, affirming the cognitive safety of this treatment strategy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04030234.
Outcome-Based Cardiovascular Risk Framework is Required After Spinal Cord Injury.
Khavandegar A, Sachdeva R, Krassioukov A
Hypertension · 2026 Apr · PMID 41732873 · Publisher ↗
Blood pressure (BP) instability is a hallmark of disrupted autonomic cardiovascular control after spinal cord injury (SCI). Individuals frequently experience hypertensive surges during autonomic dysreflexia and hypotensi...
Blood pressure (BP) instability is a hallmark of disrupted autonomic cardiovascular control after spinal cord injury (SCI). Individuals frequently experience hypertensive surges during autonomic dysreflexia and hypotensive drops during orthostatic hypotension, yet the commonly used thresholds for defining these events are derived from expert consensus rather than outcome-based evidence. Similarly, arterial stiffness, typically assessed by pulse wave velocity, is consistently elevated in SCI, but no validated cut points exist to guide clinical intervention. This lack of outcome-anchored thresholds limits risk stratification and leaves clinicians without tools to evaluate the cumulative cardiovascular burden imposed by chronic hemodynamic instability. Accumulating data indicate that individuals with SCI demonstrate profound BP variability, particularly those with cervical or high thoracic injuries, and exhibit higher rates of ischemic heart disease, stroke, and sudden cardiac death compared with the general population. Pulse wave velocity values are also markedly increased across multiple cohorts, indicating the presence of accelerated vascular aging. However, the long-term consequences of BP instability and increased pulse wave velocity remain unquantified. A comprehensive, multicenter prospective framework is urgently needed to link BP fluctuations and pulse wave velocity changes to hard cardiovascular end points. Advances in registry-based longitudinal cohorts now make this achievable. Establishing outcome-validated thresholds, whether based on absolute BP levels, frequency of BP excursions, or degree of arterial stiffness, would enable the development of SCI-specific cardiovascular risk calculators and shift clinical practice from reactive management to proactive prevention. Closing this evidence gap is essential to reducing the disproportionate cardiovascular burden faced by individuals living with SCI.
Association of Perinatal HIV Exposure and HIV Disease Severity With BP in Youth.
Brady TM, Yu W, Jacobson DL … +9 more , Brummel SS, Lipshultz SE, Colan SD, Williams PL, Jao J, Yao TJ, Van Dyke R, Urbina EM, Pediatric HIV/AIDS Cohort Study (PHACS)
Hypertension · 2026 Apr · PMID 41732863 · Full text
BACKGROUND: HIV infection is associated with cardiovascular events in adults. We compared mean blood pressure (BP) obtained at study visits between youth with/without perinatally acquired HIV infection and evaluated whet...
BACKGROUND: HIV infection is associated with cardiovascular events in adults. We compared mean blood pressure (BP) obtained at study visits between youth with/without perinatally acquired HIV infection and evaluated whether HIV disease severity was associated with BP. METHODS: BP was compared between participants with/without HIV in the Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study. Marginal repeated measures analyses using generalized estimating equations evaluated the association of HIV disease severity with BP index (mean BP/95th percentile BP) and abnormal BP. RESULTS: 447 youth with HIV and 226 youth without HIV were included. Youth with HIV were more often Black non-Hispanic (66% versus 54%), had greater household income (54% versus 35%), and lower measures of adiposity than those without. Systolic BP was similar between groups, but mean diastolic BP was lower for preadolescents (63.3 mm Hg [95% CI, 59.0-67.0] versus 65.0 [61.5-68.7]) with HIV. Although youth with HIV had lower diastolic BP index (-0.011 [95% CI, -0.021 to -0.001]) and lower prevalence of abnormal BP (odds ratio, 0.78 [95% CI, 0.62-0.97]) at study visits in initial adjusted models, these associations were attenuated after adjustment for body mass index (-0.007 [95% CI, -0.017 to 0.003], odds ratio, 0.94 [95% CI, 0.76, 1.17], respectively). HIV disease severity was not associated with systolic or diastolic BP. CONCLUSIONS: Youth with HIV had lower adiposity and BP than youth without HIV during study visits. Although youth with HIV had a lower risk of abnormal BP, this association did not persist after adjustment for adiposity. Prevention and treatment of other traditional cardiovascular disease risk factors remain important among youth living with HIV.
Renal Denervation Improves Hepatic Steatosis in Hypertensive Patients With Metabolic Syndrome.
Tokcan M, Hohl M, Schneider CV … +9 more , Schneider KM, Markwirth P, Bernhard B, Haring B, Lauder L, Schattenberg J, Mahfoud F, Kulenthiran S, Böhm M
Hypertension · 2026 Apr · PMID 41732855 · Full text
BACKGROUND: Sympathetic overactivity is associated with hepatic steatosis. Renal denervation (RDN) is an approved treatment for uncontrolled hypertension through sympathetic modulation; however, its hepatic effects are u...
BACKGROUND: Sympathetic overactivity is associated with hepatic steatosis. Renal denervation (RDN) is an approved treatment for uncontrolled hypertension through sympathetic modulation; however, its hepatic effects are unknown. This study aimed to assess the effects of RDN on noninvasive tests for hepatic steatosis. METHODS: This single-center study included patients with uncontrolled hypertension and cardiometabolic comorbidities undergoing RDN (n=32) or a sham procedure (n=10). Noninvasive tests for hepatic steatosis, including the hepatic steatosis index (HSI) and fatty liver index (FLI), were calculated at baseline and follow-up visits. An external cohort from the UK Biobank was used to validate the correlation between proton density fat fraction magnetic resonance imaging scans of the liver and these surrogates. RESULTS: Compared with the control group, RDN significantly reduced HSI at 3 months (0.4±0.5 versus -1.3±0.3; =0.009), 6 months (0.0±0.9 versus -2.6±0.5; =0.027), and 12 months (0.0±0.6 versus -2.1±0.5; =0.013), as well as FLI at 3 months (2.6±2.2 versus -3.8±1.2; =0.021), 6 months (4.1±2.4 versus -5.7±1.2; =0.002), and 12 months (2.0±2.7 versus -6.2±1.3; =0.018). No significant differences were found in HSI (-1.9±0.7 versus -2.2±0.7; =0.77) and FLI (-7.1±1.8 versus -5.3±1.7; =0.49) between subjects in the intervention group whose office blood pressure decreased above or below the median of 19.5 mm Hg after 12 months. In the UK Biobank, correlation analysis showed a significant relationship between proton density fat fraction magnetic resonance imaging and HSI (=0.40; <0.0001) and FLI (=0.27; <0.0001). CONCLUSIONS: RDN significantly reduced HSI and FLI in patients with uncontrolled hypertension and cardiometabolic comorbidities, suggesting a potential role of sympathetic modulation in metabolic disorders.
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