Wang H, Li S, Sun Y
… +21 more, Li Y, Bilige W, Qi F, Xie L, Wu G, Yan H, Yang Y, Zhai X, Luo X, Guo A, Niu W, Chen H, Ren Y, Zhang X, Huang C, Chen Z, Chen L, Zhang H, Li J, Liu J, Zheng X
Hypertens Res
· 2026 Jun · PMID 42014852
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We sought to investigate whether remnant cholesterol (RC) modified the effect of intensive blood pressure (BP) lowering treatment. This study was a post hoc analysis of ESPRIT. In this trial, hypertensive patients with h...We sought to investigate whether remnant cholesterol (RC) modified the effect of intensive blood pressure (BP) lowering treatment. This study was a post hoc analysis of ESPRIT. In this trial, hypertensive patients with high cardiovascular risk were randomly assigned to intensive (systolic BP < 120 mmHg) or standard (systolic BP < 140 mmHg) treatment. Cox regression analysis was used to examine heterogeneity of treatment effect on the primary composite outcome (myocardial infarction, heart failure, stroke, coronary or non-coronary revascularization, or death from cardiovascular causes), individual components, and death from any cause in participants grouped by RC tertiles or the cut-off value (0.8 mmol/L). A total of 11,221 participants with complete data of baseline RC were included for analysis (females 41.3%, mean age 64.6 years). During a median follow-up of 3.3 years, 1163 primary outcomes occurred, and hazard ratios (HR) for the primary outcome were 0.98 (95% CI 0.80-1.20), 0.90 (95% CI 0.74-1.11), and 0.77 (95% CI 0.64-0.94) in the lowest, middle, and highest RC tertiles, respectively (P for interaction: 0.11). Additionally, intensive treatment only reduced the risk of myocardial infarction in the highest RC tertile (HR 0.56, 95% CI 0.36-0.89, P for interaction: 0.01). When grouping by RC level of 0.8 mmol/L, significant interactions were also noted for the primary outcome, myocardial infarction, death from cardiovascular causes, and death from any cause (all P for interaction <0.05). These results showed that effects of intensive treatment were shown to be modified by baseline RC level, and further research is needed to confirm our findings.
Zhang W, Yan J, Zhang J
… +11 more, Ge Q, Lu XH, Xu WJ, Sun JC, Mu SM, Chen Y, Liu ZC, Wang Q, Zhou XN, Li Y, Wang JG
Hypertens Res
· 2026 Jun · PMID 42002633
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Hyperuricaemia is a known cardiovascular risk factor. Several angiotensin receptor blockers, such as losartan, can decrease serum uric acid level, but the effect on serum uric acid of angiotensin receptor neprilysin inhi...Hyperuricaemia is a known cardiovascular risk factor. Several angiotensin receptor blockers, such as losartan, can decrease serum uric acid level, but the effect on serum uric acid of angiotensin receptor neprilysin inhibitor remains unclear. This analysis aimed to investigate the effects of Sacubitril/Allisartan on serum uric acid level in Chinese patients with both hypertension and hyperuricaemia. We performed post-hoc analysis of data from a randomized controlled trial that compared the blood pressure-lowering effect at 12 weeks of treatment with Sacubitril/Allisartan (240 or 480 mg/d) and Olmesartan (20 mg/d). Hyperuricaemia was defined as a serum uric acid concentration exceeding the limit (420 μmol/L in male and 360 μmol/L in female) or patients already on antihyperuricemic drugs. The outcome measures included serum uric acid levels at 12, 24 and 52 weeks of treatment. Of the 1197 randomized patients, 401 (33.5%) patients with both hypertension and hyperuricaemia were included in this analysis. Mean serum uric acid levels at baseline were 441.4 ± 60.3 μmol/L, 430.5 ± 67.1 μmol/L, and 449.9 ± 78.6 μmol/L for the Sacubitril/Allisartan 240 mg, Sacubitril/Allisartan 480 mg, and Olmesartan groups, respectively (P = 0.41). Over the 12-week double-blind treatment period, serum uric acid levels decreased significantly from baseline in both Sacubitril/Allisartan groups compared to Olmesartan (-7.7 μmol/L), with a more pronounced reduction in the 240 mg (-37.7 μmol/L) and 480 mg groups (-43.3 μmol/L). Least square mean changes in serum uric acid reductions were greater with Sacubitril/Allisartan versus Olmesartan, with a difference of -30.0 μmol/L (P = 0.01) for Sacubitril/Allisartan 240 mg and -35.6 μmol/L (P = 0.002) for Sacubitril/Allisartan 480 mg. Treatment with Sacubitril/Allisartan decreased serum uric acid levels significantly more than Olmesartan in Chinese patients with both hypertension and hyperuricaemia, demonstrating a unique uricosuric effect of Sacubitril/Allisartan.
Kario K, Kai H, Rakugi H
… +12 more, Hoshide S, Node K, Katsurada K, Shinohara K, Maekawa Y, Sakata Y, Matsue Y, Yamaki M, Fujihara M, Kobayashi Y, Kozuma K, Aoki J
Hypertens Res
· 2026 Jun · PMID 42002632
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This document presents the Guidelines for the Appropriate Use of Renal Denervation (RDN) Systems in Japan, jointly endorsed by the Japanese Society of Hypertension (JSH), the Japanese Association of Cardiovascular Interv...This document presents the Guidelines for the Appropriate Use of Renal Denervation (RDN) Systems in Japan, jointly endorsed by the Japanese Society of Hypertension (JSH), the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT), and the Japanese Circulation Society (JCS). Based on the final consensus statement of the Joint Committee on RDN, these guidelines identify resistant hypertension as the principal indication for RDN treatment in Japan. Indicated resistant hypertension is strictly defined as uncontrolled blood pressure, confirmed by both office and out-of-office measurements (ambulatory blood pressure monitoring or home blood pressure monitoring), despite lifestyle modification and appropriate antihypertensive therapy with three or more drug classes, including a diuretic. RDN procedures should be performed by a multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, composed of JSH-, CVIT-, and JCS-certified specialists, nurses, pharmacists, and registered dietitians, within accredited centers providing accessible outpatient care. Using standardized checklists and procedural manuals, the HRT team thoroughly evaluates lifestyle factors, pharmacological therapy, and patient background, and determines the indication for RDN based on a shared decision-making process with each patient. The Japanese Society of Hypertension Guidelines for the Management of Elevated Blood Pressure and Hypertension 2025 (JSH2025) explicitly state that RDN may serve as a novel adjunctive treatment option for resistant hypertension (recommendation strength: 2, evidence strength: B, consensus rate: 100%). This recognition represents a pivotal step toward integrating RDN into clinical practice in Japan. Moving forward, the Joint RDN Committee will revise and update indications and implementation guidance as appropriate, informed by real-world clinical evidence.
Ono Y, Shinohara K, Nakashima H
… +13 more, Miyamoto R, Hara A, Ikeda S, Matsumoto S, Yoshida D, Nakashima R, Matsushima S, Hashimoto T, Katsuki S, Yoshida K, Kinugawa S, Tsutsui H, Abe K
Hypertens Res
· 2026 Jun · PMID 41992025
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Tirzepatide, a dual agonist for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has shown robust efficacy in treating diabetes and obesity, and in obese patients with hea...Tirzepatide, a dual agonist for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has shown robust efficacy in treating diabetes and obesity, and in obese patients with heart failure with preserved ejection fraction (HFpEF), it reduced weight, lowered blood pressure, and improved outcomes. However, its cardiovascular effects in non-obese, non-diabetic hypertension remain unclear. We investigated the impact of tirzepatide on blood pressure, cardiac function, and sympathetic nervous system activity in stroke-prone spontaneously hypertensive rats. Starting at 8 weeks of age, rats received tirzepatide (TZP, 25 nmol/kg, every two days), vehicle (VEH), or pair-fed vehicle (VEH-PF) to control for differences in food intake for 4 weeks. Tirzepatide significantly reduced food intake and body weight. Contrary to prior clinical observations, tirzepatide elevated mean blood pressure (197.4 ± 16.6 vs. 153.7 ± 5.4 mmHg at Day 28; TZP vs. VEH-PF, n = 9 vs. 8; p < 0.05) and increased heart rate, accompanied by left ventricular hypertrophy, myocardial fibrosis, and impaired diastolic function. Sympathetic activation was evident, with higher plasma norepinephrine levels and increased ΔFosB expression-a marker of sustained neuronal excitation-in the parvocellular paraventricular nucleus and the rostral ventrolateral medulla. Moreover, ΔFosB expression was increased in anorexigenic proopiomelanocortin neurons within the hypothalamic arcuate nucleus, which reduce feeding and have been implicated in promoting sympathetic excitation. These findings point to a central mechanism underlying increased sympathetic outflow. In conclusion, tirzepatide increased blood pressure and sympathetic activity in hypertensive rats without cardiac protection, highlighting context-dependent cardiovascular actions. Tirzepatide increased blood pressure, impaired LV diastolic function, and induced cardiac hypertrophy and fibrosis, as well as sympathetic overactivation in SHRSP.
Kawahara M, Tsukinoki R, Miyamatsu N
… +10 more, Kuwabara K, Kubo S, Kubota Y, Higashiyama A, Hirata A, Hirata T, Miyazaki J, Sugiyama D, Miyamoto Y, Okamura T
Hypertens Res
· 2026 Jun · PMID 41975133
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Little is known about the associations between changes in the urinary sodium-to-potassium (Na/K) ratio and blood pressure (BP) in healthy individuals. Using survey data, urinary data, and BP data from the KOBE Study, thi...Little is known about the associations between changes in the urinary sodium-to-potassium (Na/K) ratio and blood pressure (BP) in healthy individuals. Using survey data, urinary data, and BP data from the KOBE Study, this longitudinal study aimed to assess the associations between changes in the urinary Na/K ratio and BP in a healthy Japanese population over an 8-year follow-up period. We analyzed 567 participants aged 40-74 years who did not initiate antihypertensive or cardiovascular disease treatment during follow-up. Changes in the spot urinary Na/K ratio and BP were calculated by subtracting the baseline values from the follow-up measurements, and their associations were examined using a multivariable linear regression analysis that adjusted for sex, age, body mass index, baseline Na/K ratio and BP, low-density lipoprotein, hemoglobin A1c, ethanol intake, smoking status, salt taste sensitivity, years of education, employment status, baseline survey season, and 8-year follow-up survey season. The study cohort had a mean spot urinary Na/K ratio of 2.1 at baseline. While BP increased significantly over the 8-year follow-up period, the urinary Na/K ratio remained unchanged. However, urinary Na/K ratio changes were positively associated with changes in systolic BP (β = 1.48, p = 0.001) and diastolic BP (β = 0.76, p = 0.004). In conclusion, increases in spot urinary Na/K ratios were predictive of long-term BP elevation in a healthy, normotensive population with near-optimal urinary Na/K ratios at baseline. These findings indicate that maintaining a low urinary Na/K ratio is important for BP control, even among healthy individuals.
Koyanagi Y, Iigaya K, Ikeda K
… +2 more, Onimaru H, Izumizaki M
Hypertens Res
· 2026 Jun · PMID 41963534
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Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used to manage type 2 diabetes mellitus. However, there are reports indicating that patients administered GLP-1 receptor agonists often experience an increased...Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used to manage type 2 diabetes mellitus. However, there are reports indicating that patients administered GLP-1 receptor agonists often experience an increased heart rate. Although activation of the sympathetic nervous system may be involved in this response, the detailed mechanisms of action of GLP-1 receptor agonists are still not well understood. We hypothesized that GLP-1 receptor agonists could excite sympathetic nerve activity through direct effects on sympathetic-related neurons in the spinal cord and the medulla oblongata. Therefore, we examined the effects of a major GLP-1 receptor agonist, exendin-4, on sympathetic nerve activity at three different levels using in vitro preparations: (1) sympathetic nerve activity from the sympathetic nerve trunk, (2) preganglionic neurons in the intermediolateral cell column at the Th2-4 level of the spinal cord and (3) neurons in the rostral ventrolateral medulla corresponding to the C1 pressor area. Brainstem-spinal cord preparations were isolated from newborn rats (P0-P4) under deep isoflurane anesthesia and superfused with artificial cerebrospinal fluid, bubbled with 95% O and 5% CO at 25-26 °C. We found that 20-100 nM exendin-4 induced an increase in sympathetic nerve activity and the effect was blocked by the application of a GLP-1 antagonist. The application of 100 nM exendin-4 also induced membrane depolarization of the intermediolateral cell column and rostral ventrolateral medulla neurons. These results suggested that exendin-4 could induce increased sympathetic nerve activity via excitation of sympathetic-related neurons in the medulla and spinal cord.
Hypertens Res
· 2026 Jun · PMID 41946896
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Hypertension and non-alcoholic fatty liver disease (NAFLD) frequently coexist and share metabolic pathways that elevate cardiovascular and all-cause mortality risk. Although physical activity (PA) is known to reduce card...Hypertension and non-alcoholic fatty liver disease (NAFLD) frequently coexist and share metabolic pathways that elevate cardiovascular and all-cause mortality risk. Although physical activity (PA) is known to reduce cardiovascular risk, its impact among individuals with both hypertension and NAFLD remains unclear. This nationwide cohort study examined the independent and joint associations of PA and fatty liver burden with mortality in adults with hypertension. We analyzed 139,015 individuals aged ≥ 20 years who participated in the Korean National Health Insurance Service health screening program between 2009 and 2012 and were followed through 2021. Fatty liver burden was assessed using the Fatty Liver Index (FLI) and categorized as < 30, 30-59, or ≥ 60. PA levels were self-reported and classified as < 500, 500-999, and ≥ 1000 MET-min/week. Over a median follow-up of 9.1 years, 12,281 deaths occurred, including 2013 from cardiovascular causes. Higher FLI (≥ 60) was associated with significantly increased all-cause (HR 1.35, 95% CI 1.26-1.44) and cardiovascular mortality (HR 1.32, 95% CI 1.12-1.56). In contrast, higher PA (≥ 1000 MET-min/week) was consistently associated with lower mortality across all FLI categories, with the strongest benefit among those with FLI < 30 (HR 0.51 for all-cause mortality and 0.49 for CVD mortality). Importantly, high PA levels remained protective even in individuals with severe fatty liver burden. These findings suggest that regular PA substantially reduces mortality risk in adults with hypertension, regardless of underlying fatty liver severity. PA promotion should be considered an essential strategy in managing hypertension and related metabolic dysfunction.
Dawuti W, Du J, Tian X
… +6 more, Li M, Li B, Zhang Y, Gao W, Li Z, Huang T
Hypertens Res
· 2026 Jun · PMID 41946895
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This study investigated the associations between dynamic blood pressure (BP) trajectories during pregnancy and adverse birth outcomes using data from the China-US Collaborative Project on Neural Tube Defect Prevention. A...This study investigated the associations between dynamic blood pressure (BP) trajectories during pregnancy and adverse birth outcomes using data from the China-US Collaborative Project on Neural Tube Defect Prevention. Among 281,224 pregnant women (mean age 25.07 ± 3.57 years), group-based trajectory modeling (GBTM) identified three distinct systolic (SBP) and diastolic (DBP) BP patterns: "Low-stable", "Fast-increasing", and "High-stable". Compared to the Low-stable SBP group, women with Fast-increasing or High-stable SBP trajectories had significantly elevated risks of adverse outcomes, including an 16% higher risk of preterm birth (adjusted OR = 1.16, 95% CI:1.09-1.23) and 37% increased risk of low birth weight (LBW) (aOR=1.37,1.27-1.49) in the High-stable group. For DBP, the Fast-increasing trajectory showed the strongest associations, with a 19% higher preterm birth risk (aOR=1.19,1.11-1.26) and 63% increased LBW risk (aOR=1.63,1.51-1.76). Each 10 mmHg rise in SBP and DBP from mid-to-late pregnancy was independently linked to higher risks of preterm birth (SBP: aOR=1.10,1.06-1.12; DBP: aOR=1.16,1.13-1.20) and low birth weight (SBP: aOR=1.12,1.09-1.14; DBP: aOR=1.22,1.18-1.26). These findings highlight that dynamic BP changes during pregnancy are robust predictors of adverse birth outcomes, underscoring the importance of continuous BP monitoring for early risk identification and intervention.
Ishida S, Kawazoe M, Fujii T
… +22 more, Inoue Y, Yamamoto K, Sakima A, Inoue T, Komori T, Ninomiya T, Nozato Y, Kubozono T, Akasaka H, Nohara Y, Yamamoto E, Nagai M, Ihara M, Takami Y, Takeda S, Yamashita T, Shibata S, Node K, Kario K, Mogi M, Arima H, Working Group for the Prevention of Cognitive Impairment by Hypertension Management (PCIHM) of the Japanese Society of Hypertension
Hypertens Res
· 2026 Jun · PMID 41942738
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As Japan faces rapid population aging, understanding modifiable risk factors for dementia is critical. This review explores the impact of hypertension and blood pressure (BP) management on dementia onset. Midlife hyperte...As Japan faces rapid population aging, understanding modifiable risk factors for dementia is critical. This review explores the impact of hypertension and blood pressure (BP) management on dementia onset. Midlife hypertension emerges as a key risk factor, especially for vascular dementia, while late-life BP effects are variable. Observational studies suggest a critical window for intervention between ages 55-74. Moreover, BP variability independently predicts cognitive decline. Though randomized controlled trials show mixed outcomes, meta-analyses suggest that intensive BP lowering may reduce dementia risk, particularly in settings where BP reductions are substantial. These results suggest that systolic BP of <130 mmHg is desirable and support lower and stable BP control from early age as a public health strategy to delay the onset of dementia. The Japanese Society of Hypertension emphasizes three fundamental principles of BP management-early initiation, lower BP in midlife, and stable control-for preventing dementia/cognitive impairment.
Chanthavong P, Kobayashi K, Akagi Y
… +22 more, Yoshida H, Kido M, Godai K, Fukata Y, Tachibana Y, Terada S, Shi L, Anzai C, Maeyama Y, Kikuchi H, Yokoyama Y, Wada A, Higashi M, Kikuchi T, Matsuno F, Nagayoshi S, Asayama K, Ohkubo T, Rakugi H, Tabara Y, Kabayama M, Kamide K
Hypertens Res
· 2026 Jun · PMID 41942737
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The Japanese Society of Hypertension Guidelines (JSH 2019) introduce stricter blood pressure (BP) targets, but BP status (hypertension prevalence and treatment) and control rates under these criteria, particularly by hom...The Japanese Society of Hypertension Guidelines (JSH 2019) introduce stricter blood pressure (BP) targets, but BP status (hypertension prevalence and treatment) and control rates under these criteria, particularly by home BP monitoring, remain limited. This study investigated BP status, guideline-based BP control rates, and associated factors in a community-dwelling population. We analyzed baseline data (2020-2021) from 623 participants (mean age 67.6 years; 37.4% men) in the NOSE Study. BP status and control were defined using JSH 2019 criteria, with thresholds modified by age and comorbidities and 5 mmHg lower for home BP. Office BP and 30-day mean morning and evening home BP values (≥14 days) were assessed. Multivariable regression analysis was used to identify factors associated with hypertension prevalence, treatment status, and poor BP control. Hypertension prevalence was 66.8% and was associated with older age and higher body mass index. Approximately half of adults with hypertension were untreated, despite having higher BP levels, and tended to be younger with fewer comorbidities. Among treated participants, BP control rates were 22.9% based on office BP and 7.3% based on morning home BP. Masked hypertension was frequent (24.8%). Monotherapy was common (59.2%), while diuretics (10.1%) and beta-blockers (4.1%) were underutilized. A higher number of anti-hypertensive medications was associated with better BP control. Community-dwelling adults showed high hypertension prevalence, substantial untreated BP, and very low control rates under guideline targets. Home BP monitoring is essential for detecting uncontrolled morning and masked hypertension, and current treatment patterns appear insufficient to meet JSH recommendations.
Lee J, Lee A, Song M
… +6 more, Han J, Ha KH, Lee HH, You SC, Kim HC, Lee H
Hypertens Res
· 2026 May · PMID 41912672
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The COVID-19 pandemic has broadly disrupted healthcare utilization, potentially affecting the diagnosis and treatment of hypertension. While most reports focus on countries with strict lockdowns, the impact on care in co...The COVID-19 pandemic has broadly disrupted healthcare utilization, potentially affecting the diagnosis and treatment of hypertension. While most reports focus on countries with strict lockdowns, the impact on care in countries like South Korea that did not impose lockdowns remains unclear. This study aimed to investigate the changes in trends of new diagnosis and treatment initiation of hypertension in Korea during the pandemic. Using Korean nationwide claims data from 2015 to 2020, we identified new diagnosis and treatment initiation of hypertension. New diagnosis was defined as a claim for essential hypertension (International Classification of Diseases-10 code: I10), and treatment initiation was defined as a hypertension claim with antihypertensive prescription. Age-standardized rates were calculated using the 2020 insured population. Monthly trends in 2020 were compared with 2019 and with projected rates estimated using autoregressive integrated moving average (ARIMA) models based on pre-pandemic trends from 2015 to 2019. Analyses were conducted at the national and subnational levels. From 2015 to 2019, the rates of new diagnosis and treatment initiation of hypertension increased steadily, but both decreased in 2020. The most pronounced monthly decrease occurred in March 2020, with the largest regional declines observed in Daegu and Gyeongbuk. In the ARIMA model analysis, the observed rates in March 2020 were approximately 21% lower than expected rates for new diagnosis and 18% lower for treatment initiation. A substantial decline in new diagnosis and treatment initiation of hypertension was observed during the early phase of the COVID-19 pandemic in Korea.