Clinical and Experimental Hypertension最新文献

Objectives: To evaluate the efficacy and safety of intensive blood pressure control in patients over 60 years.

Methods: Databases including PubMed, Embase and Cochrane library were searched from inception through February 1, 2024. Randomized controlled trials evaluating the efficacy or safety of intensive blood pressure control in patients over 60 years were included in the meta-analysis.

Results: Intensive blood pressure control in individuals with mild hypertension has been shown to reduce the risk of heart failure, stroke, myocardial infarction, major cardiovascular events, cardiovascular mortality, and all-cause mortality. The benefits of intensive blood pressure control in patients with moderate to severe hypertension are comparable to those observed in individuals with mild hypertension, with the exception of a reduced impact on all-cause mortality and cardiovascular mortality. Compared with maintaining systolic blood pressure (SBP) above 140 mmHg, SBP below 140 mmHg is associated with a decreased risk of major cardiovascular events in patients aged over 70, as well as a reduced risk of stroke in patients aged 60-69. Furthermore, compared to maintaining SBP above 130 mmHg, SBP below 130 mmHg is linked to a lower risk of major cardiovascular events, heart failure and myocardial infarction in patients over 60, a reduced risk of stroke and cardiovascular mortality in patients aged 60-69, and a decreased risk of all-cause mortality in patients over 70. However, a lower baseline blood pressure or more aggressive blood pressure control may be associated with an increased risk of hypotension.

Conclusions: Patients with hypertension aged over 60 years can derive benefits from intensive blood pressure management without experiencing significant adverse events, aside from hypotension.

Objectives: Sufficient attention has not been given to machine learning (ML) models using longitudinal data for investigating important predictors of new onset of hypertension. We investigated the predictive ability of several ML models for the development of hypertension.

Methods: A total of 15 965 Japanese participants (men/women: 9,466/6,499, mean age: 45 years) who received annual health examinations were randomly divided into a training group (70%, n = 11,175) and a test group (30%, n = 4,790). The predictive abilities of 58 candidates including fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, were investigated by statistics analogous to the area under the curve (AUC) in receiver operating characteristic curve analyses using ML models including logistic regression, random forest, naïve Bayes, extreme gradient boosting and artificial neural network.

Results: During a 10-year period (mean period: 6.1 years), 2,132 subjects (19.1%) in the training group and 917 subjects (19.1%) in the test group had new onset of hypertension. Among the 58 parameters, systolic blood pressure, age and FLI were identified as important candidates by random forest feature selection with 10-fold cross-validation. The AUCs of ML models were 0.765-0.825, and discriminatory capacity was significantly improved in the artificial neural network model compared to that in the logistic regression model.

Conclusions: The development of hypertension can be simply and accurately predicted by each ML model using systolic blood pressure, age and FLI as selected features. By building multiple ML models, more practical prediction might be possible.

This study investigated the impact of maternal high-fat diet on vascular function and endothelial homeostasis in offspring. We found that offspring exposed to maternal high-fat diet exhibited elevated blood pressure, impaired abdominal aortic vascular function, and endothelial homeostasis imbalance. These changes were accompanied by increased levels of reactive oxygen species (ROS) and upregulation of pro-inflammatory cytokines (including IL-1β, TNF-α, IL-6, and IL-10). Treatment with NLRP3 or IL-1β inhibitors prevented the deterioration in vascular function, reduced endothelial NO production, and inflammation induced by maternal high-fat diet exposure compared to the control group. The findings suggest that during pregnancy, mitigating the vascular impairments in offspring induced by maternal high-fat diet can be achieved by inhibiting the NLRP3/IL-1β pathway.

Objective: Contributing factors for the development of heart failure (HF) involve both apolipoprotein B (ApoB) and coronary microvascular dysfunction (CMD). Although ApoB has been linked to diverse cardiovascular risks, its association with CMD remains unclear.

Methods: A total of 145 patients undergoing cardiac single-photon emission computed tomography (SPECT) scan was enrolled into this retrospective study. Based on ApoB serum level, all subjects were classified into three groups (Group 1-3). Myocardial flow reserve (MFR) was calculated using myocardial blood flow (MBF) tested in different contexts.

Results: ApoB serum level was positively correlated to rest MBF but inversely associated with stress MBF and MFR. Following adjustment for covariates, a significant relationship was observed between increased ApoB and decreased MFR. The predictive value of ApoB was test by Receiver Operating Characteristic Curve (ROC) analysis, showing an area under curve (AUC) of 0.87.

Conclusion: The findings indicated that a higher level of ApoB correlated with the severity of CMD.

Objective: To investigate the mechanism by which cinnamaldehyde (CA) alleviates pulmonary arterial hypertension (PAH) through the TLR4/NF-kB/HIF-1a pathway.

Methods: PAH was induced in rats via SU5416 injection and hypoxia. Hemodynamics (RVMP, RVSP, mPAP) were measured. Histological changes were assessed by HE staining, and protein expressions of α-SMA, Col I, TLR4, p-p65, p65, and HIF-1a were detected by western blot. In vitro, hypoxia-induced HPAECs were treated with CA and TLR4 activator RS09TFA. Cell function was assessed by CCK-8, colony formation, and scratch assays, with VE-Cadherin and α-SMA expression analyzed by western blot.

Results: PAH rats showed increased RVMP, RVSP, mPAP, and pulmonary artery thickening. CA significantly alleviated lung damage and reduced α-SMA and Col I expression. TLR4/NF-kB/HIF-1a activation with RS09TFA inhibited CA's effects. In vitro, CA mitigated hypoxia-induced HPAEC dysfunction, restoring VE-Cadherin and α-SMA expression, while RS09TFA blocked these effects.

Conclusion: CA alleviates PAH by inhibiting the TLR4/NF-kB/HIF-1a pathway and suppressing vascular remodeling, suggesting its potential as a therapeutic agent for PAH.

Aging-related diseases, which are associated with the senescence of endothelial progenitor cells (EPCs), are consistently accompanied by elevated levels of circulating trimethylamine-N-oxide (TMAO), a marker predictive of poor prognosis. Lycopene (Lyc) deficiency has been demonstrated to be linked to these age-related diseases. The AMPK/SIRT1 pathway plays a pivotal role in cellular senescence. In this study, we hypothesize that lycopene could mitigate TMAO-induced EPCs senescence, with involvement of the AMPK/SIRT1 pathway. EPCs were subjected to treatment with TMAO, Lyc, small interfering RNA targeting AMP-activated protein kinase (siAMPK), or sirtin-1 (siSIRT1). The biological functions of EPCs were evaluated through, CCK-8, transwell and tube formation assays, while their senescence was assessed via SA-β-gal activity assay and Western blotting. ROS generation was measured using dichlorodihydrofluorescein diacetate staining. TMAO-induced suppression of EPCs' functionality was alleviated by Lyc, but this effect was reversed by siAMPK and siSIRT1. TMAO increased SA-β-gal-positive cell number and ROS production, while reducing the expression of AMPK and SIRT1. These effects were attenuated by Lyc. However, the protective effects were diminished by siAMPK and siSIRT1. In conclusion, Lyc ameliorates TMAO-induced EPCs senescence through the AMPK/SIRT1 pathway.

This study investigated the safety and efficacy of the HyperQure™ extravascular renal denervation (RDN) system in a swine model of mild hypertension. Ten female pigs were fed a 3% salt diet to induce hypertension and underwent either extravascular RDN using the HyperQure™ RDN system (n = 7) or a sham procedure (n = 3). Blood pressure (BP) was continuously monitored using implanted transmitters, and safety assessments were conducted via computed tomography angiography (CTA) at 28 days post-procedure. The primary endpoint was the change in systolic blood pressure (SBP) at four weeks, while secondary endpoints included changes in diastolic BP (DBP), mean arterial pressure (MAP), and histological evaluation of renal nerve and artery integrity. At four weeks, SBP decreased by 11.8 ± 5.2 mmHg in the RDN group compared to an increase of 6.4 ± 4.2 mmHg in controls, resulting in a mean difference of 18.2 mmHg (p < .05). Similar improvements were observed in DBP and MAP, with mean differences of 15.4 and 16.2 mmHg, respectively (both p < .05). CTA revealed no significant renal artery or intraperitoneal organ injury. Histological analysis confirmed effective nerve ablation, as evidenced by reduced tyrosine hydroxylase staining, without intimal damage. No postoperative complications were observed during the 28-day study period. These findings demonstrate the safety and efficacy of the HyperQure™ extravascular RDN system in reducing BP, providing a promising alternative for patients with resistant hypertension or those ineligible for intravascular RDN. Further clinical trials are warranted to validate these results.

Background: Recent studies indicate that tenapanor, an inhibitor of sodium/proton exchanger-3 (NHE3), diminishes intestinal phosphorus (Pi) absorption. Given NHE3's pivotal role in sodium (Na+) metabolism, there is a suspected functional link between Na+ and Pi metabolism. High-salt diets (HSD) have been demonstrated to disrupt calcium (Ca2+) metabolism. Since Ca2+ and Pi share analogous metabolic pathways, it is yet to be determined whether HSD also impacts Pi metabolism.

Methods: Male C57 mice were randomly assigned to three groups: a standard diet group, HSD groups for 1 week (HSD-1w) and 4 weeks (HSD-4w). Throughout the study, dietary intake and water consumption were monitored using metabolic cages, and urine and feces were collected. Blood pressure was measured using a noninvasive tail vein sphygmomanometer. Upon completion of the intervention, mice were euthanized under anesthesia for blood collection, and intestinal and renal tissues were harvested for molecular analysis.

Results: Although plasma Pi levels were comparable between HSD groups and the control group, HSD groups exhibited increased urinary Pi excretion and decreased fecal Pi excretion. The HSD-4w group displayed elevated parathyroid hormone levels, reduced fibroblast growth factor 23 levels, and higher renal Cyp27b1 mRNA expression. The expression of sodium-dependent phosphate transporter 2b (Npt2b) and NHE3 was elevated in the intestine of HSD mice.

Conclusion: HSD disrupts Pi metabolism by enhancing urinary Pi excretion and altering hormonal levels. The decrease in fecal Pi excretion, coupled with the upregulation of intestinal Pi transporter expression, suggests that HSD promotes intestinal Pi absorption in mice.

Objectives: We aimed to: (1) explore the effect of oral potassium supplementation on urinary potassium excretion, and (2) evaluate the value of urinary potassium-related indicators in distinguishing primary aldosteronism (PA) from non-PA patients.

Design and methods: A prospective study of 20 patients with hypertension and hypokalemia caused by renal potassium loss between November 2023 and April 2024 was conducted. Demographic features, 24-hour urine collection before and after potassium supplementation were all collected.

Results: The patients had a mean age of 49.38 years and 70% were male. Following a median potassium supplement dose of 8.50 g, serum potassium increased from 3.25 to 3.90 mmol/L (p < .001), and 24-hour urinary potassium (24 h UK) rose from 41.40 to 59.75 mmol/24 h (p = .004). After supplementation, 20% of patients had decreased 24 h UK, while 25%, 25%, and 40% showed increases of 0-10, 10-20, and > 20 mmol/24 h. Urinary-to-serum potassium ratio (USR) decreased in 40% of patients, while it increased by 0-5, 5-10, and > 10 L/24 h in 25%, 25%, and 10% of patients, respectively. Both 24 h UK and USR after repletion predicted PA with moderate-to-high accuracy (AUC = 0.808 for both). The optimal cutoff of 24 h UK and USR after supplementation were 51 mmol/24 h and 17.43 L/24 h. The AUC for 24 h USR and 24 h UK before repletion in predicting PA were 0.788 and 0.652, respectively.

Conclusions: Urinary potassium does not increase proportionally with serum potassium levels or the oral potassium dose, showing individual variability. Post-supplementation urinary potassium has greater diagnostic value for distinguishing PA than pre-supplementation indicators.

Purpose: This study aimed to examine the impact of CA on DN and elucidate its underlying molecular mechanisms of inflammation.

Methods: We fed C57BL/6 mice injected with streptozotocin to induce diabetes. In addition, we stimulated NRK-52E cells with 20 mmol/L d-glucose to mimic the diabetic condition.

Results: Our findings demonstrated that CA effectively reduced blood glucose levels, and improved DN in mice models. Additionally, CA reduced kidney injury and inflammation in both mice models and in vitro models. CA decreased high glucose-induced ferroptosis of NRK-52E cells by inducing GSH/GPX4 axis. Conversely, the ferroptosis activator or the PI3K inhibitor reversed positive effects of CA on DN in both mice and in vitro models. CA suppressed PAQR3 expression in DN models to promote PI3K/AKT activity. The PAQR3 activator reduced the positive effects of CA on DN in vitro models. Moreover, CA directly targeted the PAQR3 protein to enhance the ubiquitination of the PAQR3 protein.

Conclusion: Overall, our study has uncovered that CA promotes the ubiquitination of PAQR3, leading to the attenuation of ferroptosis in DN. This effect is achieved through the activation of the PI3K/AKT signaling pathways by disrupting the interaction between PAQR3 and the P110α pathway. These findings highlight the potential of CA as a viable therapeutic option for the prevention of DN and other forms of diabetes.