Journal of Hypertension最新文献

Objective: Hypertension and diabetes frequently coexist and may interact to induce organ damage. Herein, we evaluated whether persons with prediabetes already have impaired retinal and glomerular autoregulatory responses to higher blood pressure.

Methods: We used cross-sectional, population-based data of 6594 participants [4206 with normal glucose metabolism (NGM), 1023 with prediabetes, and 1365 with type 2 diabetes (oversampled); mean age 59.8 ± 8.6 years; 50.2% men] of the Maastricht Study. Using multiple linear regression models, we tested if glucose metabolism status modified the associations of 24 h systolic and diastolic blood pressure (SBP/DBP) with retinal arteriolar and venular diameters (CRAE/CRVE) and urinary albumin excretion (uAE).

Results: The total modification for CRAE was significant for diabetes but not for prediabetes. The association of SBP with CRAE was attenuated by prediabetes ( Pinteraction = 0.098) and diabetes ( Pinteraction < 0.001) in females (but not males), with a beta of -0.21 SD per 10 mmHg (95% CI: -0.25; -0.16), -0.14 (-0.24; -0.05) and -0.04 (-0.14; 0.07) for NGM, prediabetes, and diabetes, respectively. The association of SBP with uAE was stronger in prediabetes ( Pinteraction = 0.002) and diabetes ( Pinteraction < 0.001) than in NGM, for the whole study population (no sex difference). The corresponding beta was 0.13 (0.11; 0.16), 0.20 (0.15; 0.26), and 0.24 (0.18; 0.29) for NGM, prediabetes and diabetes, respectively. No substantial changes were observed when replacing SBP by DBP.

Conclusions: Our findings suggest that retinal and glomerular autoregulatory responses to higher blood pressure are impaired in persons with prediabetes and with diabetes. This emphasizes the importance of both blood pressure and glycemic control already in those with prediabetes.

Background: Cold and hypoxic conditions often coexist in high-altitude environments and are associated with alterations in blood pressure during short-term exposure. Increasing evidence suggests that the microbiota-gut-brain axis may be involved in blood pressure regulation under environmental stress. However, evidence remains scarce, especially the related mechanisms.

Aims: This study aimed to investigate whether short-term combined exposure to cold and hypoxia is associated with blood pressure elevation and to explore the potential involvement of the microbiota-gut-brain axis in this process.

Methods: A rat model was established using combined exposure to cold (4°C) and hypoxia (61 kPa). Blood pressure, gut microbiota composition, intestinal and blood-brain barrier integrity, inflammatory responses, endothelial function, neuroinflammation, and sympathetic activity were assessed. The role of microbiota-gut-brain axis was also examined by γ-aminobutyric acid (GABA) supplementation.

Results: Short-term cold and hypoxia exposure was associated with elevated blood pressure, accompanied by gut microbiota dysbiosis, intestinal inflammation, and impaired intestinal barrier function. These changes coincided with increased circulating lipopolysaccharide (LPS) and pro-inflammatory cytokines, which were associated with vascular inflammation, oxidative stress, and endothelial dysfunction. Concurrently, impairment of the blood-brain barrier was detected, accompanied by increased accumulation of LPS and cytokines in the paraventricular nucleus, neuroinflammation, activation of microglia, and heightened sympathetic activity. Mechanistic analyses indicated the activation of the LPS-TLR4/MyD88/NF-κB signaling pathway in both the gut and brain. GABA supplementation lowered the blood pressure, restored the microbiota-gut-brain axis, and suppressed the LPS-TLR4/MyD88/NF-κB signaling pathway.

Conclusion: Short-term cold-hypoxia exposure may contribute to hypertension through disruption of the microbiota-gut-brain axis, suggesting it may act as a potential therapeutic target for hypertension prevention during short-term cold-hypoxia conditions.

Pulmonary arterial hypertension (PAH) is a severe, progressive disease characterized by pulmonary vascular remodeling and increased resistance, ultimately leading to right heart failure and high mortality. The Hippo signaling pathway has emerged as a key regulator of PAH development by influencing cell proliferation, apoptosis, and phenotypic changes in pulmonary artery smooth muscle cells (PASMCs), endothelial cells, and adventitial fibroblasts. Disruption of this pathway - especially involving its effectors YAP1 and TAZ - contributes to excessive cell growth, migration, endothelial-to-mesenchymal transition (EndMT), metabolic reprogramming, and inflammatory responses, collectively driving pathological vascular remodeling. Recent studies have highlighted the complex interaction between the Hippo pathway and signaling axes such as Notch, Transforming growth factor (TGF-β), Akt/mTOR, and integrin-linked kinase, emphasizing its extensive influence on disease progression. Emerging therapies targeting Hippo components and new small molecules, including natural products such as luteolin and resveratrol, offer promising options for reversing remodeling and treating PAH. However, the potential for Hippo-focused therapies is limited by the pathway's diverse roles and context-dependent effects. This narrative review covers recent progress in understanding Hippo signaling in PAH vascular remodeling, molecular mechanisms, and therapeutic prospects, laying a foundation for future targeted treatments.

Introduction: Aortic stenosis significantly contributes to cardiovascular mortality. While hypertension often coexists with aortic stenosis, the long-term effects of transcatheter aortic valve implantation (TAVI) on blood pressure (BP), the predictors of BP changes, and their prognostic significance remain incompletely understood.

Methods: We conducted a retrospective cohort study of 1333 patients who underwent TAVI at Sheba Medical Centre between 2008 and 2023. Changes in SBP and DBP were divided into quintiles (lowest, intermediate, and highest) and assessed for associations with all-cause mortality using Kaplan-Meier survival curves and Cox proportional hazards models, adjusted for clinical and echocardiographic variables. Multinomial logistic regression identified predictors of BP changes.

Results: The mean age was 81 years; 50% were men, and 73% had preexisting hypertension. Mean baseline SBP and DBP were 135 and 69 mmHg, respectively. Post-TAVI, SBP increased in 53% of patients, and DBP in 47%. Over a median follow-up of 4.6 years, higher post-TAVI SBP and DBP were independently associated with improved survival, after adjustment for clinical and echocardiographic confounders. Lower baseline left ventricular ejection fraction (LVEF) predicted increased SBP (P < 0.001), and female sex predicted increased DBP (P < 0.001). Preexisting hypertension did not predict BP changes.

Conclusion: Post-TAVI BP elevation is linked to better long-term survival, especially among patients with reduced baseline LVEF, and may reflect a beneficial hemodynamic response rather than comorbidity. Lower baseline LVEF and female sex are independent predictors of this response. These findings support permissive management of BP changes post-TAVI to improve patient outcomes.

Introduction: Hypertension poses a significant threat to human health through its induction of cardiac damage. The calcium-sensing receptor (CaSR) has been implicated in cardiovascular diseases; however, its specific role in cardiomyocyte injury in spontaneously hypertensive rats (SHRs) remains unclear. This study therefore investigated the effects of Calhex231, a CaSR antagonist, on cardiac damage in SHRs.

Methods: Cardiac function and structure were evaluated by echocardiography, histological staining and transmission electron microscopy. To explore the underlying mechanisms, CaSR expression along with markers of mitophagy, autophagy and apoptosis were assessed in rat hearts tissues via Western blotting. Furthermore, mitochondrial membrane potential and intracellular calcium levels were measured in angiotensin II (Ang II)-treated cardiomyocytes at the cellular level.

Results: Relative to WKY rats, SHRs showed elevated blood pressure, cardiac injury (hypertrophy, fibrosis, apoptosis), and upregulated CaSR, mitophagy and autophagy. Calhex231 reversed these in-vivo pathologies and, in vitro, protected cardiomyocytes against Ang II-induced apoptosis. This protection was achieved by inhibiting mitophagy/autophagy, lowering [Ca2+]i, and preserving mitochondrial membrane potential. The pivotal role of CaSR was underscored by the fact that its knockdown reproduced the protective effects against Ang II.

Conclusion: These findings suggests that Calhex231 protects against cardiomyocyte apoptosis by inhibiting both the PINK1/Parkin-mediated mitophagy pathway and general autophagy. Therefore, targeting the CaSR represents a promising therapeutic strategy to prevent cardiac damage induced by hypertension.

Background: The long-term reproducibility of the nighttime blood pressure (BP) phenotypes, namely, dipping (D) and nondipping (ND) has never been described in population-based studies. We investigated this issue in the participants to the third survey of PAMELA study in which clinical, laboratory, ambulatory BP monitoring (ABPM) and target organ damage data were prospectively collected over a 25-year period.

Methods: A total of 541 participants who attended the initial survey and two subsequent ones, 10 and 25 years later, were included in the analysis. ND pattern was defined as a night-time reduction in systolic BP lower than 10% compared to day-time values.

Results: During the 25 years of follow-up, 201 of the 541 participants (37.15%) with D pattern at entry maintained the same circadian BP profile in the two subsequent visits 10 and 25 years later (i.e. persistent D pattern). The corresponding rate of participants with ND pattern at the initial observation and confirmed at both subsequent data collection was about six times lower (i.e. 5.7%). No difference was found in cardiac and vascular end-organ damage markers among participants with prevalent (2 of 3) and persistent ND phenotype compared with their counterparts with occasional ND (1 of 3) and persistent D, after adjustment for conventional risk factors.

Conclusions: Our results suggest that nocturnal BP phenotypes are poorly reproducible. In particular the detection of fully reproducible ND pattern over the course of a quarter of a century involves just a minute fraction of the entire cohort. We failed to find an association of persistent vs. occasional nighttime BP phenotypes with target organ damage and this important issue requires to be further investigated in larger studies.

MicroRNAs have been suggested as essential hypertension biomarkers, but evidence remains inconclusive due to limited high-throughput studies in population cohorts. We analyzed data from the Young Finns Study (YFS) from 2011 and 2018-2020 to assess cross-sectional and prospective associations between circulatory microRNAs, blood pressure (BP), and hypertension. Hypertension risk prediction potential was assessed using nested logistic and Weibull survival models; model performance was evaluated with likelihood ratio (LR) test and c-statistic. All models were adjusted with relevant risk factors. In 2011, whole blood microRNAs were profiled for 871 individuals (83 with hypertension); in 2018-2020, 760 were re-examined, with 67 newly diagnosed. Cross-sectionally, 16 miRNAs correlated with BP (Spearman, PFDR < 0.05); miR-122-5p (fold change = 1.33) and miR-144-5p (fold change = -1.10) differentiated hypertensive individuals (U test, PFDR < 0.05). Associations persisted in adjusted regression models and some replicated in LURIC (n = 999) and YFS serum data (n = 126). Prospectively, miR-19a-3p [odds ratio (OR) = 1.51, 95% confidence interval (95% CI): 1.14-2.18], miR-19b-3p (OR = 1.50, 95% CI:1.11-2.04), and miR-329-3p (OR = 0.58, 95% CI: 0.39-0.74) levels prognosed hypertension incident. miR-329-3p improved model fit (LR test, P = 2.85×10-4) and discrimination (c-statistic = 0.849, Δ = 0.026). miR-19b-3p predicted time to onset (hazard ratio = 2.13, 95% CI: 1.38-4.45), improving model fit (LR test, P = 0.0012) and time-dependent discrimination at 7 and 8-year horizons. Our findings highlight both novel and previously reported miRNAs associating with BP and hypertension and suggest that miR-329-3p, miR-19a-3p, and miR-19b-3p as promising candidates for further investigation in hypertension risk prediction.

Background: Although there is a well established link between blood pressure (BP) levels and the severity of hypertension-mediated organ damage (HMOD), some patients with hypertension exhibit a disproportionate degree of HMOD relative to their BP.

Objective: This study aims to define disproportionate degrees, relative to blood pressure, of left ventricular hypertrophy (LVH) measured by Sokolow-Lyon (SL) index and of arterial stiffness measured by carotid-femoral pulse wave velocity (PWV), and to assess the sex differences and characteristics of individuals with such disproportional SL index and PWV.

Methods: SL index was analysed in 6487 participants of The Maastricht Study [50.9% men; 23.7% type 2 diabetes mellitus (T2DM)]. PWV was analysed in 6239 participants (51.3% men; 23.5% T2DM). The residuals of linear regression models for the relationship between SL index or PWV and 24 h mean arterial pressure (MAP) was used to define participants with disproportional SL index and PWV, respectively. Individuals with higher-than-expected (>90th percentile of the residuals) and lower-than-expected (<10th percentile) of SL index or PWV were defined as subclinical HMOD. A multinomial regression analysis was conducted to identify the clinical characteristics associated with subclinical HMOD.

Results: Males and females with higher SL index than expected based on their 24 h MAP, were older, had a higher BMI and were more often living with type 2 diabetes in comparison to those in the as-expected and lower-than-expected groups. In line, men who are living with diabetes are 34% less likely to be in the group with lower-than-expected SL index while women living with prediabetes and type 2 diabetes are 40% more likely to be in the group with higher-than-expected SL index. Likewise, males and females with higher-than-expected PWV were older and more often living with type 2 diabetes than those in the as-expected and lower-than-expected groups.

Conclusions: Persons who are older, or living with obesity and/or T2D are more likely to have subclinical HMOD, than would be expected based on their prevailing level of BP. Therefore, these clinical determinants would result in higher-than-expected HMOD. Treating those with overweight and obesity with prediabetes and diabetes more aggressively will likely reduce subclinical HMOD.

Objective: Uncontrolled hypertension presents a substantial challenge to healthcare systems. This study was designed to investigate whether pharmacogenomics-guided personalized medication regimens could enhance blood pressure control and medication optimization in patients with hypertension compared to conventional management approaches.

Methods: In this multicenter, single-blind, prospective, randomized controlled trial, 776 hypertensive outpatients were enrolled and allocated to either a personalized medication group or a control group across eight participating hospitals. All patients received 4 weeks of standardized hypertension management, followed by a first follow-up. Subsequently, the personalized medication group adjusted antihypertensive therapy according to seven predefined pharmacogenetic polymorphisms, while the control group continued standard treatment. After an additional 4 weeks, a second follow-up was performed to reassess blood pressure, medication utilization, and adverse events.

Results: The personalized medication group achieved a notably higher blood pressure control rate compared to the control group, with female patients demonstrating particularly pronounced benefits. Additionally, the personalized medication group required fewer antihypertensive medications. The incidence of adverse events, including reactions to angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, β-blockers, calcium channel blockers, and diuretics, did not differ significantly between groups. Multifactorial analysis indicated that personalized medication significantly lowered the risk of uncontrolled blood pressure. Furthermore, the CYP2C9*3 gene variant was associated with uncontrolled blood pressure after standardized treatment.

Conclusion: Pharmacogenomics-guided personalized medication regimens significantly improved blood pressure control and optimized medication usage without increasing adverse events. These findings highlight the potential of pharmacogenomics to guide precision therapy in hypertension management.

Trial registration: Chinese Clinical Trial Registry (ChiCTR2200057507). Registered 14 March 2022.

Hypertension remains a major public health concern. Diet is a well established modifiable risk factor for hypertension and may interact with antihypertensive drugs. This scoping review aimed to identify dietary factors that modify the blood pressure (BP) lowering effects of antihypertensive drugs. The review protocol was preregistered on Zenodo and was guided by PRISMA-ScR. Studies were included when participants were treated with a specified antihypertensive drug class and a dietary intervention. Of 7346 screened reports, 43 met inclusion criteria and investigated 16 dietary factors across five antihypertensive drug classes. Evidence for effect modification was available for eight dietary factors in ten drug-diet combinations. Of these, seven combinations suggested modification of the BP lowering effect of antihypertensive drugs, either a trend toward enhancement or attenuation. In addition, sodium restriction, potassium and magnesium supplementation showed consistent BP-lowering effects when added to drug therapy. These findings support the potential of integrating dietary considerations into antihypertensive treatment strategies to improve BP control.