Clinical and Experimental Hypertension最新文献

Objective: To explore the mechanism by which glycyrrhetinic acid (GA) alleviates chronic heart failure (CHF), focusing on NR3C1-mediated regulation of Nrf2 and oxidative stress.

Methods: A CHF rat model was established via transverse aortic constriction and treated with GA or NR3C1 knockdown. Cardiac function, hypertrophy, fibrosis, and oxidative stress markers were evaluated. In vitro, H9c2 cells were treated with isoproterenol to mimic CHF and subjected to GA, Nrf2 inhibitor, or NR3C1 modulation. Gene/protein expression, ROS, GSH, MDA, and mitochondrial membrane potential were assessed. Regulatory interactions between NR3C1 and Nrf2 were examined using luciferase, ChIP-qPCR, and CHX assays.

Results: GA alleviated myocardial hypertrophy and fibrosis in CHF rat models. GA also suppressed oxidative stress in CHF cell models. GA upregulated Nrf2 and its downstream target HO-1 at the protein level. NR3C1 was identified as a key upstream regulator of Nrf2, promoting its protein stability. NR3C1 knockdown decreased Nrf2 and HO-1 protein expression, disrupted mitochondrial membrane potential, and weakened the protective effects of GA against oxidative stress and cardiac dysfunction both in vitro and in vivo.

Conclusion: GA alleviates CHF by enhancing NR3C1-mediated stabilization of Nrf2 and reducing oxidative stress.

Background: Using reliable, simple, and cost-effective tools to identify pre-hypertension (pre-HTN) early is crucial for reducing the risk of cardiovascular disease (CVD). This systematic review and meta-analysis aimed to assess the association between the risk of pre-HTN and non-insulin-based indices.

Methods: A comprehensive literature search was conducted across electronic databases, including PubMed, Web of Science, and Scopus, until January 2025. Cross-sectional studies investigating the relationship between pre-HTN and IR indices were included. Two investigators independently performed study screening, data extraction, and quality assessment. A random-effects model was used to pool effect sizes, with odds ratios (ORs) as the primary measure of effect.

Results: Overall, 15 studies met the inclusion criteria for this systematic review, and 14 were included in the meta-analysis. All were cross-sectional or employed a cross-sectional approach. The results of the random effects model showed that IR indices, including the fasting triglyceride and glucose index-to-body mass index (TyG-BMI), fasting triglyceride and glucose index-to-waist circumference (TyG-WC), triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), metabolic score for insulin resistance (METS-IR), and fasting triglyceride and glucose index (TyG), increased the odds of pre-HTN significantly (P < 0.05). The diagnostic odds ratios (DORs) were 2.67 (95% CI: 2.39-2.97) for TyG and 3.45 (95% CI: 2.73-4.35) for TyG-BMI.

Conclusions: This meta-analysis reveals that non-insulin-based IR indices are associated with a higher risk of pre-HTN. However, given the cross-sectional design of all included studies, a causal relationship cannot be inferred. As cost-effective and user-friendly tools, they could aid in the early detection and prevention of HTN, but further prospective and longitudinal research is needed to confirm these findings and establish causality.

Background: Abnormal circadian blood pressure variation, particularly a non-dipper pattern, is associated with increased cardiovascular risk. Naples Prognostic Score (NPS) is a laboratory-based score that reflects the immune-inflammatory and nutritional status. Nevertheless, data regarding the relationship between NPS, circadian blood pressure patterns, and arterial stiffness in patients with newly diagnosed hypertension are limited. This study aimed to evaluate the relationship between blood pressure dipping status, the NPS, and arterial stiffness assessed by pulse wave velocity (PWV).

Methods: This retrospective study included 297 newly diagnosed, untreated hypertensive patients who underwent 24-hour ambulatory blood pressure monitoring. Patients were classified as dipper (n = 145) or non-dipper (n = 152) according to nocturnal blood pressure decline. Laboratory parameters were recorded, NPS was calculated, and PWV was measured using a validated oscillometric device. Multivariate logistic regression analysis was performed to identify factors independently associated with non-dipper hypertension.

Results: Non-dipper patients had significantly higher median NPS values compared with dippers [2 (0-4) vs. 1 (0-4), p < 0.001] and a higher prevalence of high NPS (score 3-4: 42.8% vs. 13.8%, p < 0.001). Median PWV was also significantly higher in the non-dipper group [7.70m/s (4.70-12.90) vs. 7.00m/s (4.40-11.20), p = 0.005]. After adjustment for clinically relevant covariates, both NPS (OR 1.71, 95% CI 1.19-2.47; p = 0.004) and PWV (OR 1.37, 95% CI 1.12-1.68; p = 0.002) were independently associated with non-dipper hypertension.

Conclusion: In patients with newly diagnosed hypertension, a non-dipper blood pressure pattern is independently associated with higher systemic inflammatory burden and increased arterial stiffness. The NPS may serve as a simple and clinically applicable marker for early cardiovascular risk stratification in this population.

Background: Previous studies suggest links between sweet food consumption and metabolic conditions, but its role in preeclampsia (PE) remains unclear. This study combines a case‒control design with Mendelian randomization (MR) to explore the potential causal relationship between sweet food intake and PE.

Methods: This retrospective cohort study included 1146 pregnant women from Fujian Provincial Maternity and Children's Hospital (60 with PE, 1086 controls). Dietary habits, specifically sweet food consumption (≥3 times/week), were recorded pre-delivery. Logistic regression assessed the association between sweet food intake and PE, adjusting for confounders like age, prenatal weight, blood glucose, and anemia. MR analysis used genetic variants from UK Biobank and FinnGen databases, analyzed via the inverse variance weighted (IVW) method, with sensitivity tests (MR-Egger, weighted median).

Results: Frequent sweet food consumption was associated with increased PE risk in the cohort study (OR = 2.51, 95% CI: 1.46-4.44, P = 0.001) after adjustments. However, MR analysis found no causal link between sweet food intake and PE. Instead, a causal association between higher BMI and PE was identified (OR = 1.56, 95% CI: 1.40-1.74, P = 6.51 × 10^-16).

Conclusion: While the case-control study linked frequent sweet food consumption to higher PE risk, MR analysis did not confirm causality. Elevated BMI, driven by excessive energy intake, emerged as a significant PE risk factor. Further research is needed to clarify dietary influences on PE and the interplay of diet, weight, and metabolic health in pregnancy.

Background: The carotid body (CB) is a key regulator of sympathetic tone, and its overactivity is implicated in the pathogenesis of neurogenic hypertension. While structural enlargement of the CB may reflect chronic autonomic dysregulation, its association with early markers of hypertension-mediated organ damage (HMOD) remains insufficiently characterized.

Objective: This exploratory study investigated whether carotid body size is associated with subclinical cardiac remodeling and peripheral vascular resistance in hypertensive patients.

Methods: We analyzed 49 patients with hypertension who underwent carotid computed tomography angiography (CTA) and comprehensive cardiovascular phenotyping. CB diameter was measured via CTA, and patients were categorized into Group 1 (CB < 2.5 mm, n = 22) and Group 2 (CB ≥ 2.5 mm, n = 27). Cardiac mechanics were assessed using two-dimensional speckle-tracking echocardiography (2DSTE), and hemodynamic parameters were evaluated via oscillometric pulse wave analysis.

Results: Despite similar peripheral systolic and central blood pressure levels, Group 2 demonstrated significantly impaired left atrial (LA) mechanics and higher vascular resistance. Specifically, Group 2 had lower LA global peak atrial longitudinal strain (PALS) (23.88 ± 7.70% vs. 30.84 ± 11.40%, p = 0.014) and higher total vascular resistance (TVR) (1.56 ± 0.49 vs. 1.22 ± 0.18 s⋅mmHg/mL, p < 0.001) compared to Group 1. Augmentation index normalized to 75 bpm (AIx@75) was also elevated in the CB enlargement group (31.11 ± 7.91% vs. 24.36 ± 11.77%, p = 0.021). In multivariate linear regression analysis, LA diameter, TVR, and urinary microalbumin-to-creatinine ratio were independent determinants of CB size (Adjusted R² = 0.429, p = 0.022).

Conclusion: Carotid body enlargement is associated with impaired left atrial strain parameters and increased peripheral vascular load in patients with hypertension. These findings suggest that CB morphology may serve as a potential marker for early subclinical cardiovascular and renal alterations, reflecting a distinct neurovascular phenotype in hypertension.

As a gastrointestinal hormone, gastrin stimulates gastric acid secretion and intestinal mucosal nutrition. Evidence links it closely to coronary heart disease, ischemia‒reperfusion injury and hypertension. The relevant literature was systematically retrieved from PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and other scientific databases, as well as other sources. Gastrin is a polypeptide hormone that is synthesized mainly by G cells in the antrum and proximal small intestine. Its secretion is controlled by neural regulation and humoral regulation. Gastrin is significantly associated with coronary heart disease, cardiac ischemia-reperfusion injury, hypertension and other cardiovascular diseases. The risk of coronary heart disease in patients with high serum gastrin levels is greater than that in the general population, and the serum gastrin level is higher in patients with myocardial infarction, which further suggests that hypergastrinemia may be an important risk factor for CHD. Myocardial cells express CCKBR, and intracoronary gastrin administration improves myocardial contractility through CCKBR. Several studies have shown that gastrin can also protect the myocardium against ischemia-reperfusion injury through the STAT3 signaling pathway. Gastrin may regulate blood pressure through the central nervous system or directly dilate blood vessels. Gastrin can promote the secretion of gastric acid and nutrition of intestinal mucosa. Gastrin exerts cardioprotective effects and regulates the occurrence of hypertension.

Objective: This study seeks to unravel the effects of trimetazidine (TMZ) on hypertensive nephropathy (HN) in mice and its underlying mechanisms.

Methods: Sixty male 129 mice (8-10 weeks old) were randomly categorized into six groups (n = 10 per group): control, model, TMZ, TMZ + small interfering RNA targeting prolyl hydroxylase domain protein 2 (si-PHD2), TMZ + zinc protoporphyrin [ZnPP, a heme oxygenase-1 (HO-1) inhibitor], and TMZ + KC7F2 [a hypoxia-inducible factor-1 alpha (HIF-1α) inhibitor]. All groups except the control group received angiotensin II to induce HN models. TMZ was administered by gavage for 28 days, while the other TMZ-based groups received additional si-PHD2, ZnPP, or KC7F2. Blood pressure, renal function, proinflammatory cytokines, and kidney pathology were measured. Protein/mRNA levels of PHD2, HO-1, HIF-1α, and Collagen I were analyzed via reverse transcription quantitative polymerase chain reaction/Western blot.

Results: The model group showed increased blood pressure, renal injury, fibrosis, and elevated levels of PHD2, HIF-1α, HO-1, Collagen I, and inflammatory markers compared to the control group (P < 0.05). TMZ treatment alleviated renal damage and downregulated PHD2, while upregulating HIF-1α and HO-1. These effects were further enhanced by PHD2 knockdown (TMZ + si-PHD2), but reversed by the inhibition of HO-1 or HIF-1α (TMZ + ZnPP, TMZ + KC7F2).

Conclusion: TMZ improves HN in mice by modulating the PHD2/HIF-1α/HO-1 pathway.

Background: Hypertension is a major contributor to the global burden of disease and increased mortality in the general population. Currently, the etiology and pathogenesis of hypertension are not fully understood. Emerging evidence suggests an association between aspartate aminotransferase (AST) and hypertension, but whether this relationship is causal remains unclear.

Methods: A two-sample MR analysis was conducted using GWAS summary data. Five MR methods - MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode - were applied, with IVW as the primary approach. Sensitivity analyses, including heterogeneity and pleiotropy assessments, as well as leave-one-out (LOO) analysis, were performed. Functional annotation of non-coding SNPs was conducted using the 3DSNP database, while GeneMania and enrichment analysis explored gene interactions and biological pathways.

Results: Forward MR analysis using the IVW method indicated a significant causal effect of AST on hypertension (β = 0.0003, Standard Error (SE) = 6.93E-05, P = 0.0002). However, reverse MR analysis found no significant causal relationship between hypertension and AST (β = 15.7148, SE = 12.7551 P = 0.2179). The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. These findings were robust across several reliability analyses. Finally, network and functional enrichment analyses showed that, under the influence of IVs, the SNP-hosted genes and AST promote disease progression through involvement in aspartic acid family metabolism and hexose biosynthesis.

Conclusion: The present study reports the potential role of AST in the development of hypertension. The link between AST and hypertension may be due to regulation of substance and energy metabolism. These findings offer new insights into the pathophysiology of hypertension and suggest that AST could serve as a potential biomarker or therapeutic target for hypertension management.

Hypertensive target organ damage (TOD) is a pivotal driver of cardiovascular events and mortality. Despite widespread control of traditional blood pressure (BP) averages, TOD progression persists in some patients, underscoring the independent and significant role of blood pressure variability (BPV). Accumulating evidence has established BPV not only as an independent predictor of TOD risk but also as an active contributor to its pathogenesis by propelling the vicious cycle of "hypertension-arteriosclerosis." This article systematically reviews the epidemiological evidence supporting BPV as an independent risk factor, elucidates its mediating pathways through mechanisms such as endothelial dysfunction, inflammatory activation, and arterial stiffness, and discusses recent advances and future directions in precision management strategies focused on attenuating BPV. This review aims to provide a novel theoretical basis and practical guidance for risk assessment and individualized treatment in hypertension. We advocate shifting the clinical paradigm from solely targeting mean BP to integrating BPV control into a comprehensive management strategy. This integrated approach is critical for disrupting the vicious cycle of TOD and achieving effective prevention of cardiovascular events.

Hypertension and Alzheimer's disease (AD) are common comorbidities that seriously damage the health of the elderly. This review lays out the complex bidirectional association between hypertension and AD. From a pathological perspective, hypertension can not only indirectly increase the risk of AD through inducing cerebrovascular lesions such as atherosclerosis and stroke but also directly accelerate the core pathological progression of AD, including promoting the accumulation of amyloid-β (Aβ) proteins and the hyperphosphorylation of tau protein. Additionally, various shared modifiable risk factors, such as obesity, sleep disturbances, diet patterns, psychosocial factors etc., are summarized in detail, and their shared pathophysiological pathways, including chronic inflammation, oxidative stress and intestinal dysbiosis, are revealed. This article focuses on exploring the potential of synergistic management: on the one hand, some antihypertensive drugs, such as angiotensin II receptor blockers (ARBs), exhibit neuroprotective effects beyond blood pressure reduction. On the other hand, DASH, Mediterranean and MIND dietary patterns, along with regular physical exercise and positive psychological interventions, have all been proven to reduce the incidence risk of both diseases simultaneously. Digital health technology, such as the LETHE App provides a new paradigm for realizing dynamic monitoring and personalized management of risk factors. This review emphasizes that integrating hypertension prevention and control into the primary prevention strategy for AD and adopting a synergistic management plan that combines lifestyle interventions, medications, and digital technologies is crucial for achieving healthy aging.