Clinical and Experimental Hypertension最新文献

Background: Hyperuricemia and hypertension are prevalent chronic diseases that often co-occur. While numerous observational studies suggest an association between serum uric acid (SUA) levels and hypertension, the causal nature of this relationship remains unresolved due to confounding and reverse causation. This study systematically investigates the causal association between SUA levels and hypertension risk using Mendelian randomization (MR) methodologies.

Methods: We utilized single nucleotide polymorphisms (SNPs) identified in large-scale genome-wide association studies (GWAS) of European populations as genetic instruments for SUA levels. MR, a genetic epidemiology technique, uses genetic variations as proxies to mimic a randomized controlled trial and minimizing biases from confounding and reverse causation. Systolic and diastolic blood pressure (SBP and DBP) were the primary outcomes of interest. A two-sample MR analysis was conducted to assess the causal relationships, complemented by sensitivity analyses (weighted median, weighted mode, MR-Egger) to ensure result robustness. Findings are expressed as odds ratios (ORs) with 95% confidence intervals (Cis) per one standard deviation (SD) increase in SUA levels.

Results: Our MR analysis identified a significant causal effect of SUA levels on hypertension risk. Specifically, genetically predicted SUA levels were positively associated with SBP (β = 0.136 [0.035-0.238], p < .05) and DBP (β = 0.108 [0.007-0.209], p < .05).Conversely, reverse MR analysis revealed no significant causal effect of SBP (b = 0.058 [ - 9.52E-05-0.116],p = .0504] or DBP (β = 0.016 [ - 0.028-0.059], p > .05] on SUA levels, confirming the unidirectional nature of this association.

Conclusion: This study provides compelling evidence from MR supporting a unidirectional causal link between SUA levels and increased hypertension risk. Unlike prior observational studies, our genetic approach effectively mitigates confounding and reverse causation, offering novel insights into the etiology of hypertension. These findings highlight the clinical importance of managing SUA levels to mitigate hypertension risk. Further research, including randomized controlled trials, is needed to confirm these findings and explore potential therapeutic interventions targeting SUA.

Purpose: Obstructive Sleep Apnea Syndrome (OSAS) is a heterogeneous syndrome and shows different phenotypic, clinical and physiopathological features. The aim of this study was to examine the relationships between OSAS phenotypes and comorbidities and anthropometric measurements and to identify OSAS phenotypes that should be referred for early diagnosis and treatment.

Materials and methods: We retrospectively reviewed 600 patients who underwent polysomnography (PSG) in our sleep center. Seven phenotypes were defined as Simple Snoring (SS)-Control, Mild, Moderate and Severe OSAS, Rem Dependent OSAS (RDO), Position Dependent OSAS (PDO) and Rem+Position dependent OSAS (R+PDO). Demographic data, anthropometric measurements and comorbid diseases of the patients were obtained retrospectively from their files. OSAS phenotypes were compared with comorbidities and anthropometric measurements.

Results: Severe OSAS was the most common phenotype. Oxygen desaturation index (ODI) and anthropometric measurements showed significant differences between phenotypes (p < .001). Hypertension (HT) (43.7%) and ischemic heart disease (CHD) (14.2%) were the most common comorbidities and were most commonly associated with severe OSAS. In logistic regression analysis, neck circumference (NC) and body mass index (BMI) were the anthropometric measures that predicted OSAS phenotypes. NC and BMI predicted severe OSAS, NC predicted PDO and R+PDO, and BMI predicted RDO.

Conclusion: This study revealed that OSAS phenotypes exhibit different clinical and anthropometric characteristics and differ in comorbidity risks. HT was found to be higher in severe OSAS, moderate OSAS and R+PDO, and CHD was higher in severe OSAS and RDO. Our study emphasized the importance of phenotypic characteristics as well as AHI in the management of comorbidities in OSAS.

Objective: Based on Mendelian randomization (MR) methods, this study aims to explore causal associations of uric acid (UA) levels with aortic aneurysms (AAs).

Methods: In this MR study, data on UA levels and gout were extracted from genome-wide association study (GWAS) meta-analysis conducted by UK Biobank (UKB) for European population and the Biobank Japan Project (BBJ) for Asian population. Summary statistics of AAs were obtained from different databases. Inverse variance weighted (IVW), weighted-mode, weighted median, MR-Egger, and MR-PRESSO methods were used to examine the potential causal association of UA with AAs.

Results: The IVW estimates indicated that elevated UA level was associated with higher AAA risk among the European population (OR = 1.315, 95%CI: 1.024-1.689). In the Asian population, the UA level was positively linked to the odds of AA (OR = 1.393, 95%CI: 1.061-1.829). In addition, sensitivity analyses through MR leave-one-out and single SNP effect methods showed that these results were relatively robust.

Conclusions: UA may be a potential risk factor for AAs, indicating that clinicians should focus on serum UA levels among populations with high-risk of AAs. Studies to reveal the true relationship between them and clarify the underlying mechanism are still needed in the future.

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.

Objective: This study aimed to evaluate the diagnostic performance, risk assessment, and treatment-guiding value of coronary computed tomographic angiography (CCTA) in patients with coronary heart disease (CHD).

Methods: The diagnostic value of CCTA for CHD was assessed by analyzing key parameters including sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Additionally, the diagnostic relevance of specific CCTA-derived metrics was explored. Patients with confirmed CHD underwent percutaneous coronary intervention (PCI), and the occurrence of major adverse cardiovascular events (MACE) within one year after PCI were recorded. Differences in CCTA parameters between patients with and without MACE were compared. Multivariate logistic regression was conducted to identify independent risk factors for post-PCI MACE.

Results: CCTA demonstrated high diagnostic value for CHD. Compared to the control group, patients with CHD exhibited significantly greater plaque length, total plaque volume, calcified plaque volume, lipid plaque volume, plaque burden, and coronary diameter stenosis, along with a smaller minimum lumen area. These imaging features were predictive of CHD. Relative to the non-MACE group (n = 69), the MACE group (n = 56) had higher plaque length, total plaque volume, plaque burden, and coronary diameter stenosis rate, and smaller minimum lumen area. Multivariate logistic regression analysis identified plaque burden, coronary diameter stenosis, and hypertension serve as independent predictors for adverse cardiovascular events following PCI in CHD patients.

Conclusion: CCTA is a valuable noninvasive modality for the diagnosis of CHD, risk assessment, and optimization of treatment strategies, particularly in predicting adverse outcomes following PCI.

Background: Mitochondrial dysfunction of pulmonary vascular endothelial cells is one of the important pathogenesis of pulmonary arterial hypertension (PAH). Anthocyanin can protect mitochondrial function, but whether anthocyanin can prevent PAH and its related mechanism has not been reported.

Methods: Using rodent PAH models induced by chronic hypoxia for 21 days, we investigated the changes of hemodynamics, histopathology and vascular endothelial function after anthocyanin treatment for 21 days.

Results: We found that anthocyanin treatment improved pulmonary endothelial function, vascular remodeling and associated right heart failure. Mechanistically, we found that anthocyanin treatment promoted the nucleus translocation of Nrf2 and improved the impaired mitochondrial function. The beneficial effects of anthocyanin on regulation of mitochondrial function were abolished by inhibition of Nrf2. Finally, in Nrf2 deficient mice, the protective effects of anthocyanin on PAH were largely vanished.

Conclusions: Collectively, we showed that anthocyanin attenuated PAH and associated right heart failure via improving mitochondrial function through Nrf2-dependent mechanism, suggesting that anthocyanin may represent a novel therapeutic potential for PAH.

Background: Pyroptosis is a novel kind of programmed cell death and Caspase-1 plays key roles in driving pyroptosis. The current study aims to elucidate the molecular mechanism affecting cardiomyocyte pyroptosis in myocardial ischemia/reperfusion (I/R) injury, both in vivo and in vitro.

Methods: A murine model of myocardial I/R injury was established and then treated with lentivirus-mediated shRNA targeting Caspase-1 to evaluate the effect of Caspase-1 on myocardial I/R injury. Further, Caspase-1 was silenced in the cardiomyocytes following hypoxia-reoxygenation (H/R) to detect the function of Caspase-1 in mitochondrial homeostasis and cardiomyocyte pyroptosis.

Results: Knockdown of Caspase-1 inhibited the secretion of interleukin-1 beta (IL-1β), improved cardiac dysfunction and decreased pyroptosis in vivo. The cardio-protective effect was verified in the H/R-induced cardiomyocyte model. Recombinant IL-1β protein reversed the inhibitory effect of Caspase-1 knockdown on pyroptosis.

Conclusion: Overall, activating the Caspase-1/IL-1β axis by myocardial I/R injury causes mitochondrial homeostasis imbalance, pyroptosis, and the consequent cardiomyocyte injury.

Objective: This study aims to identify risk factors for adverse pregnancy outcomes in primipara with gestational diabetes mellitus (GDM) combined with pregnancy-induced hypertension syndrome (PIH) and to develop a predictive model for such outcomes.

Methods: A total of 120 primipara with GDM and PIH, admitted from January 2019 to May 2023, were divided into two groups: the adverse group (n = 57) and the good group (n = 63), based on pregnancy outcomes. Multivariate logistic regression analysis was used to identify independent risk factors for adverse outcomes. A nomogram was constructed based on these factors, and its efficacy was validated through internal evaluation.

Results: The adverse group had higher proportions of elderly parturients, higher pre-pregnancy BMI, and more weight gain during pregnancy. Additionally, the adverse group showed a higher incidence of family history of diabetes, and more severe types of PIH. Biochemical markers such as HbA1c and total cholesterol (TC) were higher in the adverse group, while high-density lipoprotein cholesterol (HDL-C) was lower (p < .01, p < .05). Multivariate logistic regression revealed that advanced maternal age, pre-pregnancy BMI, family history of diabetes, preeclampsia/chronic hypertension complicated by preeclampsia, and elevated HbA1c were independent risk factors for adverse pregnancy outcomes (p < .01). A nomogram prediction model was developed, with an AUC of 0.821. Bootstrap internal validation confirmed the model's robust discriminative ability.

Conclusion: Advanced maternal age, pre-pregnancy BMI, family history of diabetes, preeclampsia, and elevated HbA1c are significant risk factors for adverse pregnancy outcomes in GDM combined with PIH. The nomogram model provides an effective tool for predicting such outcomes.

Objective: This study explored miRNA-126 and HIF-1α levels in patients with OSAHS-related hypertension. To analyze the relationship between miRNA-126 and OSAHS-related hypertension and explore the pathogenic mechanisms of miRNA-126 and the HIF-1α pathway.

Materials and methods: The 120 participants were assigned to four groups based on their apnea-hypopnea index (AHI) and the presence of hypertension: healthy control group, hypertension group, non-hypertensive OSAHS group, and OSAHS-related hypertension group, with 30 objects in each group. All subjects underwent overnight sleep monitoring and 24-hour (h) ambulatory blood pressure. Their blood samples were analyzed for the following parameters: triglycerides (TG), fasting blood glucose (GLU), total cholesterol (TC), HDL, uric acid (UA), and LDL, hypoxia-inducible factor-1 alpha (HIF-1α), VEGF, C-reactive protein (CRP), IL-6 and tumor necrosis factor alpha (TNF-α). The relative expression levels of miRNA-126 were assessed by RT-qPCR and Western blotting, and dual-luciferase reporter assays were conducted to verify the association between miR-126-3p and HIF1-α.

Results: Results indicated that HIF-1α is a target gene of miRNA-126 and is negatively regulated by miRNA-126; Levels of miRNA-126 were significantly lower in OSAHS and hypertension patients relative to healthy controls, with the lowest levels observed in the OSAHS-related hypertension group(p < .05). miRNA-126 levels were negatively correlated with HIF-1α, VEGF, TNF-α, CRP, IL-6, TG, TC, LDL, GLU and UA levels (p < .01), while it showed positive correlation with HDL level (p < .01).

Conclusion: The level of miRNA-126 in patients with OSAHS-related hypertension is lower than that in patients with OSAHS alone and those with hypertension alone.