Journal of Clinical Hypertension最新文献

Hypertension is a multifactorial condition influenced by both genetic and environmental factors. Protein disulfide isomerase family A member 3 (PDIA3) is a key endoplasmic reticulum protein which may contribute to increased blood pressure. However, the relationship between PDIA3 polymorphisms and hypertension remain unclear. This study aims to explore the relationship between PDIA3 polymorphisms and hypertension. First, Mendelian randomization (MR) analyses were performed to assess the causal link between PDIA3 and hypertension. Second, key gene polymorphism on PDIA3 was identified using online databases and analyzed with Haploview software. Third, multivariate-adjusted logistic regression analyses were employed to evaluate the associations between PDIA3 rs2788 and hypertension. Finally, stratified analyses were conducted to further assess interactions between PDIA3 rs2788 and antihypertensive medications. MR analyses indicated a causal relationship between PDIA3 and hypertension. The rs2788 gene polymorphism locus on PDIA3 was identified using online databases and Haploview software. Multivariable-adjusted logistic regression analyses revealed that PDIA3 rs2788 was an independent risk for hypertension (OR: 4.603, 95% CI: 2.946-7.194; p < 0.001). Significant interactions were identified between PDIA3 and antihypertensive medications, particularly ACEI/ARB treatments (p = 0.013 for interaction). Similar findings were observed regarding the causal relationship between antihypertensive treatments and hypertension. PDIA3, particularly its rs2788 polymorphisms, may represent a novel biomarker for hypertension. These findings may contribute to the development of targeted screening strategies and personalized treatment approaches for hypertension management.

Limited research has investigated the impact of antihypertensive medications on type 2 diabetes mellitus (T2DM) and whether gut microbiome (GM) mediates this association. Thus, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the potential impact of various antihypertensive drug target genes on T2DM and its complications. Genetic instruments for the expression of antihypertensive drug target genes were identified with expression quantitative trait loci (eQTL) in blood, which should be associated with systolic blood pressure (SBP). Sensitivity analysis, including reverse causality detection, horizontal pleiotropy, phenotype scanning, and Bayesian colocalization, was used to validate our findings. We performed a two-step MR to detect the mediating role of GM. A 1-standard deviation (SD) decrease of KCNJ11 (acting on arteriolar smooth muscle, e.g., Pinacidil) gene expression was associated with lower SBP of 1.12 (95% confidence interval [CI], 0.93-1.31) mmHg, and a decreased risk of diabetic retinopathy (odds ratio [OR], 0.63; 95% CI, 0.52-0.76). Similarly, a 1-SD decrease of SLC12A2 (genetically a proxy for diuretics, for example, Torasemide) gene expression was correlated with a reduced risk of T2DM (OR, 0.88; 95% CI, 0.83-0.92). Interestingly, this causal effect was influenced by a decrease in the gut microbiota abundance of the genus Ruminococcus (effect proportion = 11.2%). Colocalization supports these results (KCNJ11: 98% for diabetic retinopathy; SLC12A2: 99% for T2DM). Findings provide novel targets for the treatment of T2DM and its complications, emphasize the importance of KCNJ11 and SLC12A2 in future drug development, and highlight the significant mediating role of the genus Ruminococcus.

Evidence suggests that approximately 63.0%-84.2% of stroke survivors have hypertension, yet there is currently no stroke prediction tool specifically designed for individuals with hypertension. Using data from 20 702 hypertensive patients from the China Stroke Primary Prevention Trial (CSPPT), we developed a 5-year stroke risk prediction model. This prospective study collected treated blood pressure every 3 months, resulting in 22 measurements over the study period. The model was internally validated using bootstrap resampling, and its predictive performance was assessed with the C-index and calibration curves. We also developed a random forest model to rank the variable importance. The 5-year stroke risk prediction model for hypertensive individuals includes 10 risk factors, ranked by importance as follows: average systolic blood pressure during treatment, age, average diastolic blood pressure during treatment, baseline systolic blood pressure, history of diabetes, baseline total cholesterol level, baseline folate level, self-reported stress, smoking, and folic acid supplementation or not. The C statistic of the equation was 0.74 and there were no significant differences by gender or treatment group. Calibration plots indicate good internal consistency between observed and predicted 5-year stroke risk. We also developed an online calculator to assist clinicians and patients (https://zhouziyi.shinyapps.io/CSPPT/). Our study indicates that for patients with hypertension, long-term posttreatment blood pressure is the primary predictor of stroke risk. Trial Registration: The CSPPT (clinicaltrials.gov Identifier: NCT00794885).

In this study, we aimed to reveal the trends of self-measured blood pressure (SMBP) and SMBP-derived indices during pregnancy and the postpartum period. The Babies and Their Parents Longitudinal Observation in Suzuki Memorial Hospital in the Intrauterine Period (BOSHI) Study is a prospective cohort study in Japan. Participants were instructed to measure SMBP daily during pregnancy and for 1 month after delivery. Among 237 participants with normotensive blood pressure (BP) during pregnancy and the postpartum period who were analyzed using mixed-effects models for repeated measures, the SMBP was measured, on average, 14.3 times from the day before delivery to 28 days postpartum. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) on the day before delivery were 110.6 ± 1.0 and 68.1 ± 0.8 mmHg (estimate ± standard error). Postpartum BP increased from postpartum Days 3-8 in SBP and from Days 3-22 in DBP, compared to that on the day before delivery. The SBP and DBP were 4.9 and 4.7 mmHg higher on postpartum Days 8 and 7 than the day before pregnancy, respectively. During pregnancy, the pulse rate (PR) showed an inverted U-shaped trend and then sharply increased rapidly until the first postpartum day after delivery. The Shock Index showed a similar trend to that of the PR, decreased from labor until postpartum Day 8, and plateaued thereafter. The double product peaked during labor, remained higher than the prelabor levels for approximately 10 days, and then decreased in the postpartum period.

The objective of this study was to investigate the association between triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c), triglyceride-glucose index (TyG), and related parameters (TyG-BMI, TyG-WC) with prehypertension and hypertension over 45 years old. According to the blood pressure diagnosis, the enrolled individuals were divided into two groups, which were prehypertension and hypertension. In multivariate logistic regression analysis, after adjusting for confounders, the highest quartile groups of TG/HDL-c, TyG, and related parameters showed a significantly increased risk of hypertension compared to the lowest quartile groups, and there was associated with hypertension when comparing the highest TG/HDL-c to the lowest TG/HDL-c and corresponding ORs were 1.416 (1.234, 1.625) and 1.029 (0.893, 1.187), respectively. Furthermore, when comparing the fourth quartile to the first quartile of TG/HDL-c, TyG index, and related parameters, respectively, both corresponding ORs of hypertension were higher than prehypertension. Elevated TyG, TyG-BMI, TyG-WC index, and TG/HDL-c ratio levels were associated with hypertension in individuals over 45 years. Moreover, the receiver operating characteristic curve was used to compare the predictive ability of each parameter in identifying people with hypertension suggested that the TyG-WC index ([Area under the curve] AUC: 0.601 [CI: 0.588-0.615]), TyG-BMI, and TyG were more significant than TG/HDL-c in distinguishing hypertension. However, in the prehypertension population, the area under the ROC curve for TyG-BMI (0.543 [CI: 0.530-0.556]) was better than that of other parameters. They have the potential to become cost-effective monitors in the hierarchical management of hypertension.

The causal relationship between visceral adipose tissue (VAT) and hypertension remains unclear. We aimed to examine the potential association between them using observational and two-sample Mendelian randomization (MR) analyses. Data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were used, applying multivariable logistic regression analysis to investigate the association between VAT mass and hypertension risk. Independent genetic variants related to VAT mass were derived from genome-wide association studies (GWAS) in 325 153 UK Biobank participants. The primary analysis employed the random-effects inverse-variance weighted (IVW) method, with MR-Egger, weighted median, simple mode, and weighted mode as sensitivity analyses. A total of 7661 participants were included. After adjusting for confounding factors, increased VAT mass was associated with a higher risk of hypertension (quartile 4 vs. quartile 1: OR:1.85, 95% confidence intervals [CI]: 1.31-2.63). Furthermore, VAT mass exhibited greater accuracy than body mass index (BMI) in predicting hypertension (areas under the curve [AUC]: 0.701 vs. 0.676, p for comparison < 0.001). The MR analyses demonstrated a causal relationship between increased VAT mass and the risk of hypertension in primary analyses (odds ratio [OR]:1.768, 95% CI: 1.594-1.861). Consistent findings across various MR models substantiate the robustness and strength of this causal relationship. These analyses provide additional support for both the positive association and causal relationship between elevated VAT and the risk of developing hypertension, suggesting that targeted interventions for VAT may be beneficial in preventing hypertension.

Hypertension is the predominant cause of cardiovascular diseases (CVDs) globally, and essential hypertension (EH) represents a significant public health challenge due to its multifactorial etiology involving complex interactions between genetic and environmental factors. However, the pathogenesis of EH is still unclear. Hypertension is a dysregulation in the renin-angiotensin-aldosterone system and sympathetic nervous system, both regulating saline homeostasis and cardiovascular function. However, current therapeutic interventions targeting these systems have limited efficacy in approximately 40% of cases, suggesting the involvement of alternative mechanisms. Inflammation is associated with the occurrence and progression of hypertension, but the underlying mechanism remains elusive, while chronic inflammation leads to tissue damage, fibrosis, and irreversible organ dysfunction. The development and maintenance of EH are caused by endothelial dysfunction, oxidative stress, and chronic inflammation. Neutrophils are involved in both acute and chronic inflammation since they represent the primary line of defense against inflammatory insults once recruited to the inflamed site where they remove harmful impurities. The process involving the formation of neutrophil extracellular traps (NETs) is called NETosis are involved in the pathogenesis and progression of CVDs, including coronary artery disease, acute myocardial infarction, peripheral arterial disease, heart failure, and atrial fibrillation. Recent investigations demonstrated that NETs facilitate the development of hypertension; however, the precise role of NETs in hypertension remains largely elusive. Therefore, this review aims to provide an overview of the current understanding regarding the involvement of NETosis in hypertension and explore the potential therapies targeting NETs for future interventions.

Early neurological deterioration (END) following endovascular treatment (EVT) in acute ischemic stroke (AIS) patients is associated with poor long-term outcomes. Although unstable systolic blood pressure (SBP) after EVT is recognized as a risk factor for END, it remains unclear whether this association persists after excluding identifiable causes of END. In this prospective, observational cohort study, AIS patients who underwent EVT within 24 h of stroke onset were included. Invasive arterial blood pressure (BP) monitoring recorded hourly BP readings during the first 24 h post-EVT. Unexplained END was defined as an increase of ≥4 points in the National Institutes of Health Stroke Scale score 24 h after EVT without any identifiable cause. Two distinct SBP trajectories-high and low-were identified within 24 h post-EVT. The high-trajectory group, characterized by elevated mean SBP and increased SBP variability (SBPV), exhibited a significantly higher incidence of unexplained END (odds ratio [OR] = 3.28, p < 0.01). SBPV alone was an independent risk factor for unexplained END (OR = 1.11, p < 0.05). Moreover, patients with both higher mean SBP and increased SBPV had a markedly greater risk of unexplained END (OR = 13.79, p < 0.05). Notably, the harmful threshold for SBPV was lower during nighttime compared to daytime. These findings suggest that increased SBPV, particularly when combined with elevated mean SBP, significantly heightens the risk of unexplained END post-EVT. Therefore, comprehensive post-EVT blood pressure management should address both absolute BP levels and BPV, with particular emphasis on nighttime monitoring, to optimize early neurological recovery.

This first-in-man (FIM) study evaluated the feasibility and safety of a new peripheral plaque atherectomy system in patients with symptomatic lower extremity artery disease (LEAD). Ten patients with symptomatic LEAD (Rutherford class 2-5) were enrolled in a prospective, single-center study from March to April 2024. Patients aged 18-85 years with target lesions showing ≥70% stenosis and reference vessel diameters ≥1.8 mm underwent treatment using a novel atherectomy device with a "shaving" mechanism to excise calcified plaques. Outcomes included post-procedural stenosis improvement, 6-month primary patency rate, and safety endpoints such as thrombosis, vasospasm, acute occlusion, and distal embolization. Statistical analysis used SPSS 23.0. Ten male patients (mean age: 61.4 ± 9.2 years) were treated. Most had diabetes (80%), hypertension (70%), and hyperlipidemia (80%). Pre-procedural ankle-brachial index (ABI) averaged 0.50 ± 0.14. Angiographic analysis showed 60% of lesions in the femoral artery and 40% as chronic total occlusions. No major adverse events occurred, with 100% technical success. Post-procedural ABI improved to 0.92 ± 0.12 (p < 0.05). At 6 months, the primary patency rate was 100%, with no clinically-driven revascularization or adverse cardiovascular events. Mortality was 0%. All patients reported significant improvement in symptoms and walking distance, as well as enhanced quality of life and reduced pain during physical activity. The novel atherectomy device showed promising safety and efficacy for treating calcified LEAD. Larger-scale trials are needed to confirm these outcomes.

Angiotensin II receptor blockers (ARBs) and calcium channel blockers (CCBs) are commonly prescribed as first- and second-line treatments for older Japanese patients with hypertension. However, due to age-related decline in renin activity, the effectiveness of ARBs may decrease. This highlights the need for other antihypertensive agents to be used in combination with CCBs to replace ARBs for more effective blood pressure (BP) control. The ESCORT-HT study is a multicenter, randomized, controlled, open-label, parallel-group study with a 4-week run-in period and 12-week treatment period. This study aims to evaluate the efficacy of esaxerenone as a second-line treatment for hypertension and to determine whether its BP-lowering effect is noninferior to that of ARBs in older patients with uncontrolled hypertension on CCB monotherapy. The safety profiles of esaxerenone and ARBs will also be evaluated. Patients will be randomly assigned in a 1:1 ratio to receive either esaxerenone or an ARB. The primary efficacy endpoint will be the change from baseline in morning home systolic BP at the end of the treatment period. The BP-lowering effect of esaxerenone will be considered noninferior to that of ARBs if the upper limit of the two-sided 95% confidence interval (CI) for the difference in systolic BP change between esaxerenone and ARB is <3.8 mmHg, and will be considered superior if the upper limit of the two-sided 95% CI is <0. The findings may elucidate the possible benefits of earlier use of mineralocorticoid receptor blockers in combination with CCBs in older patients with essential hypertension.