Although young-onset type 2 diabetes is more prevalent than before, evidence on the management of hypertension in this population is limited. We aimed to evaluate the association between hypertension status and the risk...Although young-onset type 2 diabetes is more prevalent than before, evidence on the management of hypertension in this population is limited. We aimed to evaluate the association between hypertension status and the risk of cardiovascular disease. This retrospective cohort study included 173,483 patients (aged 20-39 years; median follow-up 7.1 years) with type 2 diabetes who were not on antihypertensive medication and underwent health examinations between January 2009 and December 2012. The participants were categorized according to their hypertension status as follows: normal blood pressure, elevated blood pressure, stage 1 isolated systolic hypertension (ISH), stage 1 isolated diastolic hypertension (IDH), stage 1 systolic and diastolic hypertension (SDH), stage 2 ISH, stage 2 IDH, and stage 2 SDH. Compared to those with normal blood pressure, patients with young-onset type 2 diabetes with stage 1 IDH (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.02-1.28), stage 1 SDH (HR 1.34, 95% CI 1.20-1.49), stage 2 ISH (HR 1.56, 95% CI 1.30-1.89), stage 2 IDH (HR 1.53, 95% CI 1.29-1.82), and stage 2 SDH (HR 1.94, 95% CI 1.71-2.19) showed increased risk of composite cardiovascular disease events. Among young adults with type 2 diabetes, the risks of myocardial infarction, ischemic stroke, heart failure, and CVD-specific mortality increased from stage 1 SDH and higher blood pressure categories. Our findings call attention to the early detection and strict management of hypertension in this population.
Hypertension phenotypes reflect the agreement or disagreement between office and out-of-office blood pressure (BP) measurements and are challenging to distinguish during a single office visit. Increased sympathetic nervo...Hypertension phenotypes reflect the agreement or disagreement between office and out-of-office blood pressure (BP) measurements and are challenging to distinguish during a single office visit. Increased sympathetic nervous system (SNS) activity is implicated in their pathophysiology. Aortic valve peak velocity, an echocardiographic parameter associated with SNS hyperactivity and high cardiac output states, may help differentiate hypertension phenotypes. This study examined the association between hypertension phenotypes and aortic valve peak velocity. Cross-sectional analysis of consecutive patients evaluated at a reference Hypertension Unit who underwent office (OBP), ambulatory BP (ABP) monitoring, and echocardiography. A total of 384 participants were included (mean age 58 years; 55% male; 60% treated systolic/diastolic OBP 136/84 mmHg, ABP 126/77 mmHg, aortic valve peak velocity 1.31 m/s, 34% normotension/controlled hypertension, 18% white-coat hypertension/white-coat uncontrolled hypertension (WCH/WCUH), 16% masked hypertension/masked uncontrolled hypertension, 32% sustained hypertension/uncontrolled hypertension]. Aortic valve peak velocity was significantly higher in the WCH/WCUH group (1.40 ± 0.26 m/s) compared with all other phenotypes (P < 0.01). This finding was consistent in analyses restricted to untreated patients and to those with a short ABP-echocardiography time interval, and remained significant in multivariable linear regression models. Among participants with office hypertension, a cut-off value of 1.32 m/s demonstrated moderate diagnostic accuracy for identifying WCH/WCUH (sensitivity 62%, specificity 66%). Aortic valve peak velocity is significantly elevated in WCH/WCUH and may serve as a supportive clinical tool to help identify or exclude this phenotype in patients presenting with office hypertension, particularly in untreated individuals undergoing baseline echocardiography.
Kario K, Rakugi H, Ito C
… +4 more, Sayyed S, Kitamura T, Tanaka Y, Malhotra A
Hypertens Res
· 2026 Jun · PMID 42373836
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This multicenter, randomized, double-blind, parallel-group, active-controlled study aimed to demonstrate a superior BP-lowering effect of sacubitril/valsartan (SacVal) and amlodipine (AML) combination therapy vs SacVal m...This multicenter, randomized, double-blind, parallel-group, active-controlled study aimed to demonstrate a superior BP-lowering effect of sacubitril/valsartan (SacVal) and amlodipine (AML) combination therapy vs SacVal monotherapy in Japanese patients with grade Ⅰ/Ⅱ essential hypertension inadequately controlled with SacVal monotherapy. After 4 weeks of single-blind active run-in with SacVal 200 mg monotherapy, patients (n=717) with mean sitting systolic blood pressure (msSBP) of 140 to <180 mmHg were randomized and received SacVal 200 mg monotherapy or SacVal 200 mg in combination with AML (2.5, 5, or 10 mg) for 8 weeks. All SacVal/AML 200 mg/2.5 mg, 200 mg/5 mg, 200 mg/10 mg combinations achieved statistically significant, dose-dependent reductions in msSBP vs SacVal 200 mg monotherapy (treatment difference [mmHg] [95% CI]: -5.63 [ -8.01, -3.25], -12.94 [ -15.22, -10.67], -16.39 [ -19.01, -13.77], respectively; all p < 0.001). Treatment effects of all combinations were also statistically significant in 24-h ambulatory SBP (treatment difference [mmHg] [95% CI] vs SacVal: -6.48 [ - 8.79, -4.18], -14.18 [ -16.63, -11.73], -17.70 [ -20.24, -15.26], respectively; all p < 0.001) and BP control ( < 140/90 mmHg) rates (57.2, 72.5, 79.9%, respectively, vs 35.0% in SacVal with odds ratio [95% CI]: 2.16 [1.40, 3.33], 5.28 [3.31, 8.43], 7.23 [4.41, 11.86], respectively; all p < 0.001). Subgroup and waterfall plot analyses in msSBP demonstrated consistent BP-lowering effects across patient demographic and baseline characteristics. The safety profile of combination therapy was similar to that of SacVal with no new safety findings. These results demonstrated that combination therapy provided superior BP reduction with favorable safety and tolerability in Japanese patients inadequately controlled by SacVal 200 mg monotherapy. In this multicenter, randomized, double-blind, parallel group, active controlled trial, sacubitril/valsartan and amlodipine combination therapy showed dose-dependent reductions in office and 24-hour systolic blood pressure and a favourable safety profile in Japanese patients inadequately controlled on sacubitril/valsartan monotherapy, supporting its efficacy and safety as a treatment option.
Vakka A, Kyriakoulis KG, Tatakis F
… +7 more, Iliakis P, Kalliakouda E, Papadomarkaki K, Damianaki A, Dimitriadis K, Konstantinidis D, Tsioufis K
Hypertens Res
· 2026 Jun · PMID 42362815
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Overactivation of sympathetic nervous system (SNS) has a key role in the pathophysiology of hypertension, as well as in chronic kidney disease, heart failure, atrial fibrillation, type 2 diabetes mellitus, obstructive sl...Overactivation of sympathetic nervous system (SNS) has a key role in the pathophysiology of hypertension, as well as in chronic kidney disease, heart failure, atrial fibrillation, type 2 diabetes mellitus, obstructive sleep apnea, and anxiety disorders. Renal denervation (RDN) has been proven to lower blood pressure (BP) in hypertensive patients by reducing SNS activity. Beyond hypertension, data from a limited number of preclinical studies and clinical trials suggest that RDN may also be nephroprotective, have beneficial hemodynamic and clinical effects in patients with heart failure, reduce the burden of atrial fibrillation, have a moderate beneficial effect on glucose metabolism, and decrease the severity of obstructive sleep apnea. This study reviews the potential pleiotropic effects of RDN in these diseases that are characterized by SNS overactivation, and highlights the need for further well-designed, large-scale clinical trials to define the extent of these effects, clarify their clinical significance, and determine how they relate to RDN-induced changes in blood pressure.
Nishikawa M, Suzuki Y, Kaneko H
… +16 more, Okada A, Takeda N, Morita H, Fujiu K, Azegami T, Hayashi K, Kitaoka K, Miura K, Mizuno A, Nomura A, Kario K, Node K, Yasunaga H, Nangaku M, Arima H, Takeda N
Hypertens Res
· 2026 Jun · PMID 42332085
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Chen C, Zhang X, Wang Y
… +10 more, Yu Z, Chen Z, Xu T, Huang J, He X, Zhao J, He J, Dong Y, Liu C, Wei FF
Hypertens Res
· 2026 Jun · PMID 42332084
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Impaired ventricular-arterial coupling (VAC) is associated with adverse health outcomes. However, the predictive values of VAC calculated by different non-invasive methods remain uncertain. We aimed to assess prognostic...Impaired ventricular-arterial coupling (VAC) is associated with adverse health outcomes. However, the predictive values of VAC calculated by different non-invasive methods remain uncertain. We aimed to assess prognostic values of VAC calculated as the ratio between arterial elastance (Ea) and left ventricular end-systolic elastance (Ees) and between carotid-femoral pulse wave velocity (PWV) and global longitudinal strain (GLS). In 3634 Atherosclerosis Risk In Communities study participants (57.4% women; mean age, 75.1 years), Cox proportional hazard models were constructed to determine associations of VAC metrics with heart failure (HF) and all-cause mortality. Risk prediction models were employed to examine prediction improvement of VAC beyond established risk factors. Over approximately 6.3 years (median), 316 participants experienced HF, and 482 died. The hazard ratios of HF related to 1-SD increment in VAC metrics were 1.28 (95% CI, 1.18-1.38; P < 0.001) for Ea/Ees and 1.40 (1.27-1.54; P < 0.001) for PWV/GLS with adjustments applied for potential confounders. PWV/GLS was the only VAC parameter associated with mortality (adjusted HR, 1.18; 1.08-1.28; P < 0.001). PWV/GLS was observed to have stronger associations with all outcomes in individuals aged ≤74 years than those aged >74 years (P for interaction ≤0.034). The addition of VAC maker to the conventional risk factors improved risk prediction for incident HF (P ≤ 0.010) assessed by C statistics, net reclassification improvement, and integrated discrimination improvement for Ea/Ees (0.702, 22.4%, and 1.40%) and for PWV/GLS (0.701, 22.1%, and 1.46%). In the general population, impaired VAC was associated with a higher risk of incident HF and total mortality.
Miyashita Y, Kimoto N, Onoue K
… +6 more, Yata Y, Aketa T, Yabumoto M, Washio T, Takashima S, Kitakaze M
Hypertens Res
· 2026 Jun · PMID 42332083
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We previously established an interpretable combinatorial data-mining framework to identify combinations of clinical factors predictive of heart failure. Because hypertension (HT) is a major contributor to heart failure,...We previously established an interpretable combinatorial data-mining framework to identify combinations of clinical factors predictive of heart failure. Because hypertension (HT) is a major contributor to heart failure, accurate prediction of new-onset HT is critically important for prevention. To identify combinations of clinical factors predictive of HT onset using a novel limitless-arity multiple-testing procedure (LAMP) and to estimate the probability of developing HT. We analyzed 2,610,286 individuals without HT who underwent annual health check-ups starting in 2005-2015 and were followed for 5 consecutive years without missing data. Using the LAMP method, we systematically identified statistically significant combinations of fewer than four clinical factors associated with HT onset. Among 28,618 subjects used for rule discovery, 4802 combinations predictive of HT onset were identified. The remaining 2,581,668 individuals were classified into one group with no predictive combinations (G0) and 20 groups (G1-G20) according to increasing numbers of predictive combinations. The incidence of HT increased stepwise with the number of predictive combinations, as confirmed by Kaplan-Meier analyses (p < 0.001). Receiver-operating characteristic analysis demonstrated a moderate discriminative performance (area under the curve = 0.69). We identified combinations of routine clinical parameters that predict new-onset HT in the general population. A greater number of matching predictive combinations was associated with a proportionally higher probability of developing HT. This interpretable combinatorial data-mining framework may enable risk stratification for HT and support early preventive strategies.
Hypertens Res
· 2026 Jun · PMID 42321350
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The Guidelines for the Management of Elevated Blood Pressure and Hypertension 2025 (JSH2025) were published last year. Additionally, the Prevention of Cognitive Impairment by Hypertension Management (PCIHM) working group...The Guidelines for the Management of Elevated Blood Pressure and Hypertension 2025 (JSH2025) were published last year. Additionally, the Prevention of Cognitive Impairment by Hypertension Management (PCIHM) working group of the Japanese Society of Hypertension's Academic Committee released a statement summarizing the latest basic research and clinical and epidemiological findings on "hypertensive dementia". Numerous research papers on hypertension-related dementia were published over the past year, and evidence is accumulating. Reports indicate that blood pressure variability, rather than absolute blood pressure levels, is gaining attention as a factor inducing dementia; furthermore, blood pressure targets are being set lower, and even strict blood pressure control in the elderly does not lead to cognitive decline. On the other hand, it goes without saying that we must avoid a one-size-fits-all approach for the elderly; instead, we must determine blood pressure targets on an individual basis, for example, by avoiding excessive blood pressure reduction in elderly patients who already have cerebral small-vessel disease. As a "beyond guidelines" initiative, we here summarize reports related to "hypertensive dementia" published since the guidelines were released and explore the trends. Recent reports on "hypertensive dementia" are on the rise. The number of PubMed articles found by searching for "high blood pressure" and "dementia" reached nearly 800 last year and has already exceeded 220 this year (as of the end of March). While the JSH2025 guidelines were published in August 2025, I would like to review some of the interesting basic and clinical research papers published over the past year or so, consider recent trends and future developments regarding hypertension and dementia.
Kwon AG, He J, Hamm LL
… +12 more, Alper A, Geng S, Lanza P, Qin H, He H, Erol HK, Oygen S, Bundy JD, Lederer E, Toto R, Chen J, CRIC Study Investigators
Hypertens Res
· 2026 Jun · PMID 42310367
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Abnormal phosphate homeostasis is associated with inflammation, vascular calcification, and endothelial dysfunction in chronic kidney disease (CKD). Apparent treatment-resistant hypertension (ATRH) is common in CKD and i...Abnormal phosphate homeostasis is associated with inflammation, vascular calcification, and endothelial dysfunction in chronic kidney disease (CKD). Apparent treatment-resistant hypertension (ATRH) is common in CKD and is associated with increased cardiovascular mortality. We examined the associations between phosphate homeostasis-related biomarkers and ATRH in patients with CKD. The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled 3939 participants with CKD in the United States between 2003 and 2008. After excluding those with missing ATRH data, 3752 were analyzed. ATRH was defined as blood pressure (BP) ≥ 140/90 mm Hg while taking ≥3 antihypertensive medications, or BP < 140/90 mm Hg while taking ≥4 medications. In addition to phosphate homeostasis-related biomarkers, we calculated the phosphate burden index as the combined effect of phosphate retention on circulation and bone metabolism: index = serum phosphate × parathyroid hormone. Elastic Net and multivariable regression models assessed associations between phosphate biomarkers and ATRH. Participants with ATRH were older and more often male and Black. The adjusted odds ratios (95% confidence intervals) for the highest quartiles compared with the lowest quartile were 1.42 (1.09-1.86) for serum phosphate, 1.48 (1.15-1.91) for the urine phosphate-to-creatinine ratio, and 2.30 (1.72-3.08) for phosphate burden index. These associations were also significant in linear regression models for the urine phosphate-to-creatinine ratio and the phosphate burden index. We conclude that higher levels of phosphate-related biomarkers are independently associated with ATRH. Future studies should investigate whether targeting abnormal phosphate homeostasis can reduce ATRH risk in patients with CKD.
Kim S, You SC, Il Kim S
… +3 more, Bae JH, Choi JI, Park S
Hypertens Res
· 2026 Jun · PMID 42310366
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Direct oral anticoagulants (DOACs) are frequently co-prescribed with angiotensin II receptor blockers (ARBs) in atrial fibrillation (AF). Because ARBs differ in P-glycoprotein (P-gp) inhibition, bleeding risk may vary. W...Direct oral anticoagulants (DOACs) are frequently co-prescribed with angiotensin II receptor blockers (ARBs) in atrial fibrillation (AF). Because ARBs differ in P-glycoprotein (P-gp) inhibition, bleeding risk may vary. We compared major bleeding when DOACs were combined with telmisartan (high P-gp inhibition) versus olmesartan (low P-gp inhibition). We conducted a nationwide cohort study from 2016-2023 in Korea. We identified AF patients who started a DOAC with telmisartan or olmesartan. The primary outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding. Secondary outcomes included each component of the primary outcome and ischemic stroke. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Among DOAC-treated patients with AF, 27,851 and 20,010 patients were included in the telmisartan and olmesartan groups, respectively. The incidence rates of the primary outcome were 9.13 per 1000 person-years in the telmisartan group and 6.69 in the olmesartan group (HR 1.35, 95% CI 1.11-1.65). Concomitant use of telmisartan was associated with a higher risk of gastrointestinal bleeding (1.49, 1.17-1.89), but not with intracranial hemorrhage (1.06, 0.74-1.54) or ischemic stroke (0.94, 0.78-1.14). Among patients with AF using DOACs, concomitant use of ARBs with high P-gp inhibitory activity was associated with a significantly higher risk of major bleeding and gastrointestinal bleeding compared-ARBs with low P-gp inhibitory activity. These findings suggest that differences in P-gp inhibitory activity among ARBs may influence bleeding risk in clinical practice when co-administered with DOACs.
Yamaguchi M, Morinaga J, Sagara A
… +3 more, Yamanouchi Y, Miyashita A, Kondoh E
Hypertens Res
· 2026 Jun · PMID 42304127
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Management of chronic hypertension in pregnancy remains uncertain, and current guidelines do not address whether the prognostic significance of blood pressure (BP) varies across gestation. To evaluate gestational age-spe...Management of chronic hypertension in pregnancy remains uncertain, and current guidelines do not address whether the prognostic significance of blood pressure (BP) varies across gestation. To evaluate gestational age-specific associations between maternal BP in the first half of pregnancy and adverse maternal and neonatal outcomes. We conducted a multicenter registry-based cohort study from April 2022 to March 2023 at 65 tertiary referral centers in Japan. A total of 273 women with chronic hypertension and singleton pregnancies were enrolled before 14 weeks' gestation (median age, 37 years; IQR, 34-40). Systolic and diastolic BP were assessed at three gestational windows (8-9, 10-13, and 14-18 weeks). Aspirin exposure was treated as time-dependent. The primary outcome was a composite of adverse maternal and neonatal events. Cox proportional hazards models and restricted cubic spline analyses were used. Adverse outcomes occurred in 32.6% (89/273). BP-risk associations differed by timing. No association was observed at 8-9 weeks. At 10-13 weeks, risk increased progressively with higher systolic BP, including excess risk in the moderate range (120-134 mmHg) and the highest risk at ≥135 mmHg (HR, 4.11; 95% CI, 1.14-14.82). At 14-18 weeks, a threshold pattern emerged, with increased risk above 140 mmHg (HR, 2.19; 95% CI, 1.40-3.43). Associations were weaker among women who initiated aspirin before 10 weeks, although interaction was not statistically significant. In chronic hypertension, maternal BP during 10-13 weeks of gestation carries heightened prognostic relevance. These findings support gestational age-specific risk assessment and motivate evaluation of early preventive strategies.
Hypertens Res
· 2026 Jun · PMID 42304126
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To evaluate the association between gestational age at delivery beyond 37 weeks and perinatal outcomes in women initially diagnosed with gestational hypertension(GH). This retrospective cohort study was conducted involvi...To evaluate the association between gestational age at delivery beyond 37 weeks and perinatal outcomes in women initially diagnosed with gestational hypertension(GH). This retrospective cohort study was conducted involving 661 singleton pregnancies admitted with a diagnosis of gestational hypertension who delivered at or beyond 37 weeks of gestation. Participants were grouped according to the gestational week of delivery (37-37, 38-38, 39-39+6, and ≥ 40 weeks). Composite maternal and neonatal outcomes were evaluated using multivariable logistic regression. After adjusting for confounders, delivery at 39-39 weeks was associated with a lower risk of composite neonatal outcomes (aOR = 0.53, 95%CI: 0.29-0.98) without increasing the risk of composite adverse maternal outcomes (aOR = 1.36, 95%CI: 0.78-2.35). This association remained consistent in a sensitivity analysis excluding women who progressed to preeclampsia (aOR 0.49, 95% CI 0.26-0.95). In contrast, the 37-37 weeks group demonstrated the highest risk of adverse composite neonatal outcomes (26.53%) and some adverse maternal outcome (preeclampsia:23.47%, placental abruption:2.04%). Delivery at ≥40 weeks was associated with an increased risk of intrapartum cesarean section (aOR = 2.78, 95% CI: 1.28-6.05). Among women initially diagnosed with gestational hypertension who remained clinically stable beyond 37 weeks, delivery at 39-39⁺⁶ weeks was associated with more favorable neonatal outcomes without an apparent increase in maternal morbidity. However, given the observational design and potential confounding by clinical indication, these findings should be interpreted as associative rather than causal, and individualized management remains essential.
Jhee JH, Joo YS, Seo J
… +5 more, Lee CJ, Ko YE, Park SH, Yoo TH, Park S
Hypertens Res
· 2026 Jun · PMID 42304125
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Blood pressure (BP) control in chronic kidney disease (CKD) remains suboptimal despite renin-angiotensin system (RAS) blockade, contributing to disease progression. This study examined associations of relative aldosteron...Blood pressure (BP) control in chronic kidney disease (CKD) remains suboptimal despite renin-angiotensin system (RAS) blockade, contributing to disease progression. This study examined associations of relative aldosterone excess (RAE) with BP control and kidney outcomes in CKD. 745 patients with CKD from the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (2013-2024) Study were analyzed. BP control status was defined by ambulatory BP: uncontrolled BP (UBP, ≥125/75 mmHg with <3 AHAs or <4 AHAs without diuretics), apparent treatment-resistant hypertension (aTRH, ≥125/75 mmHg with ≥3 AHAs including diuretics or ≥4 AHAs), and controlled BP (CBP, <125/75 mmHg with <4 AHAs). RAE was defined as baseline serum aldosterone ≥ 10 ng/dL with aldosterone to renin ratio ≥30 despite RAS inhibition. The primary kidney outcome was a composite of ≥40% decline in eGFR, new onset eGFR <60 mL/min/1.73 m, or ESKD. The mean age was 61.5 years, and 53.6% were men. RAE was independently associated with higher odds of uncontrolled hypertension (ABPM ≥ 125/75 mmHg), whereas CBP was associated with lower odds of RAE. Over a median follow-up of 6.9 years, 244 kidney outcomes occurred. In multivariable Cox models, CBP was associated with a reduced risk of kidney outcomes compared to UBP (HR, 0.67; 95% CI, 0.46-0.97), while aTRH was not (HR, 0.88; 95% CI, 0.57-1.37). However, in the interaction model, aTRH with RAE showed a significantly elevated risk of kidney outcomes (HR, 3.04; 95% CI, 1.12-8.24), while the protective effect of CBP was not modified by RAE. Stratified analyses further showed that RAE was associated with the highest risk of kidney outcomes in the aTRH group (HR 2.67, 95% CI 1.2-5.93). Monitoring RAE may help identify high-risk hypertensive CKD patients who could particularly benefit from mineralocorticoid receptor antagonist therapy.