Park KY, Nam GE, Han K
… +6 more, Jung JH, Yoo JE, Lee CW, Kang SH, Kim CK, Shin DW
Hypertens Res
· 2026 Jun · PMID 42277407
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Prior research has established a positive correlation between blood pressure (BP) and ischemic stroke in the general population; however, this association has not been investigated in dementia patients. A population-base...Prior research has established a positive correlation between blood pressure (BP) and ischemic stroke in the general population; however, this association has not been investigated in dementia patients. A population-based cohort of 73,130 individuals with newly diagnosed dementia who underwent a Korean national health checkup after diagnosis was followed up until the end of 2019. Individuals were classified according to their systolic (SBP) and diastolic BP (DBP) during health checkups. Multivariable Cox proportional hazards regression was performed, calculating the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident ischemic stroke. During a mean follow-up of 3.6 years, 4446 (6.1%) patients developed ischemic stroke. In all-cause dementia patients, the risk of ischemic stroke increased after SBP/DBP exceeded 130/90 mmHg compared with SBP 120-129 mmHg and DBP 70-79 mmHg (reference) (both P for trend <0.001). Similar trends were observed in patients with Alzheimer's disease and vascular dementia. In particular, SBP/DBP ≥ 140/90 mmHg and SBP 100-109 mmHg were associated with incrementally higher risks of ischemic stroke and a decreased risk of Alzheimer's disease, respectively (both P for trend <0.001). The positive linear association of SBP and DBP with ischemic stroke in all-cause dementia remained after stratification by sex and antihypertensive medication use, and the association between SBP and ischemic stroke was greater among younger individuals (40-79 years old). In conclusion, both SBP and DBP showed positive linear relationships with the risk of incident ischemic stroke in dementia patients. Achievement of the target BP may be important for stroke prevention in individuals with dementia.
Bayaraa N, Yano Y, Kadota A
… +11 more, Azahar NM, Phap TNH, Hisamatsu T, Kondo K, Torii S, Fujiyoshi A, Ohkubo T, Shiino A, Nozaki K, Miura K, SESSA Research Group Members
Hypertens Res
· 2026 Jun · PMID 42270767
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Ushida T, Shimaya T, Inamura T
… +7 more, Katsuki S, Tano S, Matsuo S, Fuma K, Yoshida S, Yamashita M, Kajiyama H
Hypertens Res
· 2026 Jun · PMID 42270766
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In this study, we characterized the physiological blood pressure (BP) trajectories from an estimated pre-pregnancy period through pregnancy, labor, and postpartum among low-risk, normotensive women. This retrospective mu...In this study, we characterized the physiological blood pressure (BP) trajectories from an estimated pre-pregnancy period through pregnancy, labor, and postpartum among low-risk, normotensive women. This retrospective multicenter observational study was conducted at 12 primary obstetric care facilities in Japan and included 14,240 low-risk, normotensive women with term singleton deliveries between 2011 and 2018. Longitudinal outpatient BP trajectories during pregnancy and the postpartum period were modeled using linear mixed-effects models with restricted cubic splines. The pre-pregnancy BP was approximated using 1:1 matching with non-pregnant women undergoing routine health checkups. Changes in intrapartum BP were evaluated in women who underwent vaginal delivery (n = 11,836). The outpatient BP followed a classic gestational pattern, with a nadir at approximately 25 weeks of gestation, followed by a gradual increase toward term. The estimated pre-pregnancy BP was lower than the outpatient BP measured during early pregnancy. During the first stage of labor, systolic and diastolic BPs increased by up to 15.7 mmHg and 13.4 mmHg, respectively, compared with the final outpatient measurements, returning to near-outpatient levels within 2 h after delivery. During the postpartum period, the BP increased, peaked at days 5-7, and then gradually declined by approximately 5 weeks, converging toward non-pregnant levels. Low-risk normotensive women demonstrated elevated BP in early pregnancy relative to the estimated non-pregnant baseline during labor and in the first postpartum week. These data provide physiological reference patterns that may aid the interpretation of intrapartum and postpartum hypertension.
Hypertens Res
· 2026 Jun · PMID 42270765
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Primary aldosteronism (PA) is the most common endocrine cause of hypertension, yet emerging longitudinal data indicate that its injurious effects extend to the brain. A nationwide Korean cohort study demonstrated that pa...Primary aldosteronism (PA) is the most common endocrine cause of hypertension, yet emerging longitudinal data indicate that its injurious effects extend to the brain. A nationwide Korean cohort study demonstrated that patients with PA exhibit a significantly higher incidence of all-cause dementia than matched individuals with essential hypertension, independent of blood pressure. However, this association was attenuated for Alzheimer's disease after multivariable adjustment, whereas vascular dementia remained significantly associated with PA. Aldosterone activates mineralocorticoid receptors (MRs) in the brain, triggering oxidative stress, blood-brain-barrier leakage and neuro-inflammation that damage hippocampal and prefrontal networks, leading to deficits in executive function, language and attention. Notably, these effects are amplified by dietary salt intake, and experimental evidence suggests that aldosterone-induced end-organ damage requires a high-salt milieu. In animal models, chronic aldosterone exposure reproduces these cognitive impairments, whereas MR blockade or adrenalectomy reverses learning and memory deficits. However, current PA guidelines omit recommendations for cognitive screening or intervention, rendering this potentially reversible aetiology largely overlooked. Here we systematically synthesize the pleiotropic mechanisms of aldosterone signalling in neurons, glia and cerebral vessels; integrate cross-sectional, prospective and interventional clinical evidence to quantify the strength of the PA-dementia association; and compare the differential cognitive outcomes of surgery versus pharmacotherapy. We also discuss emerging aldosterone synthase inhibitors as a novel therapeutic strategy that eliminates ligand production rather than merely blocking receptor signalling. Finally, we propose a risk-prediction framework that incorporates neuroimaging and fluid biomarkers, and call for a transdisciplinary clinical pathway to enable early recognition and precision intervention.
Shichida S, Takahashi Y, Shiraki A
… +2 more, Nakagami H, Node K
Hypertens Res
· 2026 Jun · PMID 42265329
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We developed a soluble epoxide hydrolase (sEH) vaccine as a novel therapeutic strategy against hypertension. A placebo-controlled study was conducted to investigate its efficacy. Fifty-five wild-type mice were randomly d...We developed a soluble epoxide hydrolase (sEH) vaccine as a novel therapeutic strategy against hypertension. A placebo-controlled study was conducted to investigate its efficacy. Fifty-five wild-type mice were randomly divided into three groups: control (n = 5), angiotensin Ⅱ (Ang II) induced hypertension with vaccine (n = 23) and without vaccine (n = 24). Hypertension was induced by subcutaneous Ang II infusion via an osmotic mini pump, whereas controls received saline. Vaccinations were administered at 8, 10, 12, and 14 weeks of age. Ang II significantly increased systolic and diastolic blood pressure both in hypertension groups; however, vaccination significantly mitigated this rise. Mean reductions were - 8 ± 2 mmHg (systolic) and - 5 ± 2 mmHg (diastolic). Vaccinated mice also exhibited reduce myocardial hypertrophy and smaller aortic diameters. These findings indicate that anti-sEH vaccination suppresses hypertension and associated cardiovascular remodeling, indicating its potential as a long-acting therapeutic option. The proposed mechanism of anti-sEH vaccination. Anti-sEH vaccination induces sEH antibody production, thereby inhibiting sEH activity, leading to increased EETs and reduced DHETs. The vaccination attenuates Angiotensin II-induced cardiac hypertrophy and aortic dilatation. CYP450 cytochrome P450, EETs epoxyeicosatrienoic acids, sEH soluble epoxide hydrolase, DHETs dihydroxyeicosatrienoic acids.
Matsushita T, Wada Y, Saburi M
… +11 more, Kobayashi K, Tsukamoto S, Kawanami D, Suzuki D, Tsuriya D, Wakui H, Kanasaki K, Muta Y, Tamura K, Takeuchi Y, Toyoda M
Hypertens Res
· 2026 Jun · PMID 42243292
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Combination therapy with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) is increasingly used to prevent cardiovascular events. Our previous study demonstrated t...Combination therapy with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) is increasingly used to prevent cardiovascular events. Our previous study demonstrated the renal benefits of this combination therapy. Both drug classes exert pleiotropic effects on metabolic factors, such as obesity and hypertension; however, the impact of this combination therapy on blood pressure (BP) has not been fully evaluated. This post hoc analysis aimed to assess the effects of SGLT2i-GLP-1RA combination therapy on BP control in patients with type 2 diabetes (T2D). Among the 643 T2D patients enrolled in the RECAP study, 431 with baseline hypertension were analyzed (GLP-1RA-preceding group, n = 207; SGLT2i-preceding group, n = 224). The achievement rate of the target office BP ( < 130/80 mmHg) after the initiation of combination therapy was evaluated using multiple imputations. Changes in office and home BP were analyzed using generalized linear mixed models. The influence of preceding treatment was assessed using propensity score-based inverse probability weighting (PS-IPW). The achievement rate of the target BP increased from 25.4% after treatment to 33.3% after combination therapy (p = 0.003). Office BP decreased from 141.8/82.4 mmHg at baseline to 135.2/78.5 mmHg after treatment addition and 131.7/79.4 mmHg after combination therapy (all p < 0.001). The home systolic BP also significantly decreased (p = 0.03). PS-IPW analysis showed no significant differences in BP outcomes or target achievement rates according to the preceding treatment. Collectively, SGLT2i-GLP-1RA combination therapy significantly improved BP control, independent of the order in which the agents were initiated.
Evidence on subtype-specific risks of adverse outcomes associated with hypertensive disorders of pregnancy (HDP) remains limited. This study aimed to analyze temporal trends in HDP prevalence and investigate subtype-spec...Evidence on subtype-specific risks of adverse outcomes associated with hypertensive disorders of pregnancy (HDP) remains limited. This study aimed to analyze temporal trends in HDP prevalence and investigate subtype-specific associations with maternal and fetal complications. A retrospective cohort study was conducted using data from 1508 maternity hospitals across mainland China from 2016 to 2019, involving 18,916,671 pregnant individuals aged 15-49 years. Poisson regression models were used to estimate adjusted relative risks (aRRs) for outcomes including maternal morbidity, in-hospital mortality, and fetal complications. The prevalence of HDP increased from 4.92 to 6.48% (P < 0.001). The incidence of superimposed preeclampsia almost tripled, rising from 0.11 to 0.32%. In-hospital maternal mortality associated with HDP decreased from 40.26/100,000 to 16.26/100,000, while HDP-related organ dysfunction, such as heart failure and renal failure, increased from 0.78 to 1.02% and from 0.17 to 0.25%, respectively. Examining subtype-specific outcomes, women with preeclampsia with severe features faced the highest risk for heart failure (aRR 3.01; 95% CI, 2.91-3.10), whereas those with superimposed preeclampsia were more susceptible to renal failure (aRR 28.85; 95% CI, 24.70-33.70). Regarding fetal outcomes, superimposed preeclampsia was associated with the highest risks of preterm birth (aRR 4.85; 95% CI, 4.76-4.94) and stillbirth (aRR 5.09; 95% CI, 4.84-5.35). The prevalence of HDP and its related organ dysfunction increased during the study period. The findings underscore the critical need to address HDP-associated organ injury and to develop tailored management strategies for different HDP subtypes.
Bayaraa N, Yano Y, Kadota A
… +11 more, Azahar NM, Phap TNH, Hisamatsu T, Kondo K, Torii S, Fujiyoshi A, Ohkubo T, Shiino A, Nozaki K, Miura K, SESSA Research Group Members
Hypertens Res
· 2026 May · PMID 42191819
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AIM: Hypertension is a leading contributor to the global disease burden and mortality. Although various risk factors have been identified, the roles of psychosocial stress and stress-coping strategies in the development...AIM: Hypertension is a leading contributor to the global disease burden and mortality. Although various risk factors have been identified, the roles of psychosocial stress and stress-coping strategies in the development of hypertension remain unclear. This study examined the longitudinal association between having a stress-coping strategy and the incidence of hypertension in Japanese communities. METHODS: A prospective cohort study, a part of the Circulatory Risk in Communities Study, included 3668 participants (1359 men and 2309 women), aged 40-74 years, from three rural areas in Japan. Stress levels, the presence of a stress-coping strategy, and hypertension status were assessed annually from 2010 to 2018. Generalized linear mixed models were used to examine longitudinal associations of stress levels and stress-coping strategies with the incidence of hypertension, adjusting for potential confounding factors. Separate models were fitted to explore sex-specific associations. RESULTS: The presence of a stress-coping strategy was significantly associated with a lower incidence of hypertension at baseline in both women (OR = 0.21 and 95% confidence interval (CI): 0.11 to 0.38, p < 0.001) and men (OR = 0.33, 95% CI: 0.18 to 0.60, p < 0.001). This association persisted throughout the follow-up period for both sexes, although the association was not significant in men with high stress. CONCLUSIONS: Having a stress-coping strategy was associated with a lower incidence of hypertension in both sexes. These findings highlight the potential role of coping strategies in hypertension prevention.
Hypertension and organ damage caused by an inappropriate balance between aldosterone and salt are deeply involved in pathologies such as chronic heart failure, chronic kidney disease, and vascular disorders. Mineralocort...Hypertension and organ damage caused by an inappropriate balance between aldosterone and salt are deeply involved in pathologies such as chronic heart failure, chronic kidney disease, and vascular disorders. Mineralocorticoid receptor antagonists are effective not only as antihypertensives, but also as organ-protective drugs, blocking direct aldosterone-induced organ damage independent of blood pressure. In recent years, research into selective aldosterone synthase inhibitors has progressed, resulting in the development of drugs such as baxdrostat, lorundrostat, and vicadrostat. These drugs are highly selective for aldosterone synthase with little inhibition of 11β-hydroxylase, making them promising antihypertensive and organ-protecting drugs. This article summarizes the basic and clinical research on aldosterone synthase inhibitors to date and reviews their characteristics. Aldosterone synthase inhibitors are drugs with the unprecedented characteristic of reducing blood aldosterone levels. Many studies have shown that low serum aldosterone levels are associated with a reduced risk of cardiovascular events. In fact, clinical trials of aldosterone synthase inhibitors have shown that lowering serum aldosterone levels by 50-70% results in lower blood pressure and organ protection. Even a small reduction in serum or local aldosterone levels is highly likely to improve hypertension and organ damage. Clinically, lowering blood aldosterone levels is very important. Compared to the clinical evidence for mineralocorticoid receptor antagonists, clinical evidence for aldosterone synthase inhibitors remains insufficient. How these two drug types should be used given their differences thus remains unresolved. Discussing the differences in clinical effects in the future is thus important. The site of action of aldosterone synthase inhibitors (ASIs), and differences in mineralocorticoid receptors (MR)-mediated actions in epithelial and non-epithelial tissues. Although the MR in epithelial and non-epithelial tissues are genetically identical, their physiological functions differ significantly. In epithelial tissues, aldosterone is the physiological ligand because cortisol is inactivated to cortisone by the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). In contrast, in non-epithelial tissues, this enzyme is absent or present at low levels, making cortisol, which has approximately 100-fold higher free circulating levels, the physiological ligand. The actions of aldosterone and cortisol are mediated by intracellular classical MR, but the existence of a putative membrane MR with high affinity exclusively for aldosterone is also thought to exist. Upon binding to the ligand, MR translocates to the nucleus, and acts through transcriptional activity. On the other hand, membrane MR is thought to mediate rapid, non-genomic effects that do not involve transcriptional activity. ASIs may attenuate aldosterone actions without significantly affecting cortisol actions in epithelial tissues. In non-epithelial tissues, aldosterone actions are not major, and ASIs do not affect the physiological actions of cortisol via MR. Further investigation is needed to determine the pharmacological effects of this mechanism, and how it differs from MR antagonists (The recruitment of co-activators and co-repressors in transcriptional activity is omitted).
The renin-angiotensin-aldosterone system regulates blood pressure and is influenced by antihypertensive therapy. We examined plasma aldosterone concentration (PAC), plasma renin activity (PRA), and clinical characteristi...The renin-angiotensin-aldosterone system regulates blood pressure and is influenced by antihypertensive therapy. We examined plasma aldosterone concentration (PAC), plasma renin activity (PRA), and clinical characteristics in untreated hypertensive patients without primary aldosteronism, followed for 3 years. Among 456 newly diagnosed patients, 397 (219 males, 178 females) were analyzed after excluding those with low blood pressure, suspected primary aldosteronism, or renovascular hypertension. PAC and PRA were measured at baseline, and clinic blood pressure was monitored at 3 months, 1 year, and 3 years. A high PAC/PRA ratio (>200) was found in 19.6% of patients and was significantly associated with female sex (p < 0.0001) and higher serum sodium (p = 0.0004). PAC did not differ between groups, but PRA was markedly lower in the high PAC/PRA group (p < 0.0001). Multivariate analysis identified female sex as the only independent predictor (p < 0.0001), with prevalence rates of 29.8% in females and 11.4% in males. In females, PAC/PRA correlated positively with sodium, while PRA correlated negatively, relationships not observed in males. Mineralocorticoid receptor antagonists (MRAs) were used as first-line therapy in patients with high PAC/PRA. Their blood pressure declined from 159/95 mmHg at baseline to 137/80, 135/78, and 133/77 mmHg at 3 months, 1 year, and 3 years, respectively. In the normal group, values were 159/96, 142/81, 138/77, and 136/77 mmHg, with greater systolic reduction at 3 months in the high PAC/PRA group (p = 0.03). We identified gender differences in the renin-aldosterone-sodium system. MRAs effectively reduced blood pressure in patients with relatively low PRA levels.
Arterial hypertension leads to urological complications by impairing urinary bladder function. Physical exercise, particularly high-intensity interval training (HIIT), is a non-pharmacological strategy for blood pressure...Arterial hypertension leads to urological complications by impairing urinary bladder function. Physical exercise, particularly high-intensity interval training (HIIT), is a non-pharmacological strategy for blood pressure control. HIIT improves oxygen consumption, body composition, and cardiovascular health, but its effects on the urinary bladder remain unclear. This study evaluated the effects of HIIT on structural and molecular markers of urinary bladder remodeling in spontaneously hypertensive rats (SHR), with emphasis on fibrosis, neurotrophic and angiogenic signaling, hypoxia-related pathways, and the balance between the ACE/Ang II/AT1R and ACE2/Ang-(1-7)/MasR axes. We also assessed its effects on blood pressure, metabolism, and redox biomarkers in blood circulation. HIIT significantly reduced serum glucose and lipid levels while improving redox balance with increased antioxidants. In the bladder, HIIT downregulated VEGF and NGF, reduced collagen deposition, and decreased TGF-β and SMAD2 expression. Additionally, HIIT modulated the angiotensin receptor axis (AT1/MAS ratio) and upregulated VEGF, promoting angiogenesis. Publicly available microarray data from ischemic and aging models support our findings, highlighting the role of TGF-β pathways in bladder fibrosis. This study reveals key intracellular mechanisms linking HIIT to redox balance, fibrosis, hypoxia, vascular remodeling, and angiotensin receptor modulation. Together, our findings suggest HIIT as a potential therapeutic approach for vascular and structural remodeling in the hypertensive urinary bladder. Impact of hypertension and HIIT on bladder physiology in SHR rats. The illustration depicts changes in bladder structure and protein modulation in spontaneously hypertensive rats (SHR) compared to normal controls, and the effects of an 8-week high-intensity interval training (HIIT) regimen. In normal bladder tissue, muscle structure and contractility are intact, with normal compliance. Following the onset of hypertension (SHR bladder), markers such as HIF-1α, AT1, detrusor collagen, NGF, and TGF-β1/SMAD2/3 are upregulated, leading to increased fibrosis, reduced contractility, and decreased bladder capacity, while VEGF, MAS receptor (MASr), and antioxidants are decreased. After HIIT (SHR + HIIT bladder), the bladder shows reduced fibrosis, improved contractility and increased capacity, accompanied by decreased expression of HIF-1α, AT1, detrusor collagen, NGF and TGF-β1/SMAD2/3, while VEGF, MASr and antioxidants are upregulated.
Pulmonary arterial hypertension (PAH) often leads to right heart failure and death. While pharmacological therapies offer symptomatic relief and functional improvement, many patients remain refractory or progress despite...Pulmonary arterial hypertension (PAH) often leads to right heart failure and death. While pharmacological therapies offer symptomatic relief and functional improvement, many patients remain refractory or progress despite optimal treatment. This review explores emerging interventional strategies besides pharmacotherapy. Techniques such as pulmonary artery denervation (PADN), balloon atrial septostomy (BAS), renal denervation, transcatheter Potts shunt, right ventricular assist devices, catheter-based cell therapies and implantable hemodynamic monitoring devices are evaluated based on safety, efficacy, and long-term outcomes. Notably, PADN has demonstrated encouraging results across multiple trials, with improvements in exercise capacity, hemodynamic parameters, and clinical status. BAS remains a palliative bridge to transplantation in severe cases, with newer modifications aiming to overcome spontaneous closure. Renal denervation and transcatheter Potts shunts show promise but require further validation. Catheter-based cell therapies show promising results and could perhaps be used as an alternative in the future. Moreover, mechanical support devices like ECMO and pressure monitors such as CardioMEMS offer adjunctive benefits in advanced disease. Right ventricular assist devices could in circumstances be used as bridge to transplant or bridge to recovery. This review illustrates the need for robust randomized controlled trials in PAH.