Integrated network pharmacology and Chinmedomics reveal the molecular mechanisms of aqueous extract of Eleutherococcus senticosus fruit for treating essential hypertension.

To evaluate the efficacy and safety of sitokiren (SPH3127) tablet in patients with mild-to-moderate essential hypertension in comparison to valsartan capsule. This multicentre, randomised, double-blind, parallel Phase III trial was designed in 2 stages. In the 1st stage, eligible patients were randomised to receive 50 mg, 100 mg or 200 mg of SPH3127 tablet or 80 mg of valsartan capsule once daily (QD) for 12 consecutive weeks. In the 2nd stage, eligible patients were randomised to receive assigned dose of SPH3127 tablet based on the results from the 1st stage or valsartan 80 mg QD for 12 consecutive weeks. Primary outcome was the change from baseline in mean sitting diastolic blood pressure (msDBP) at Week 12. Safety outcome measures included any adverse events. Exploratory outcomes included plasma concentration of SPH3127, as well as the assessment of the correlation between SPH3127 exposure with the level of renin inhibition, clinical efficacy and occurrence of adverse events. The 1st stage enrolled 189 patients, of which 129 eligible patients were randomised. High plasma renin activity (PRA) inhibitory effect (83%) and the biggest reduction of msDBP at Week 12 from baseline (-8.17 ± 5.90 mmHg) was detected in SPH3127 group at the dosage of 100 mg, which was determined for the subsequent stage 2 of this trial. The 2nd stage screened 1260 patients, of which 828 eligible patients were randomised to receive SPH3127 tablet 100 mg (N = 413) and valsartan capsule 80 mg (N = 415), QD. Main analysis based on the treatment policy strategy indicated 5.97 (0.41) mmHg [least-square mean (LSM) and standard error (SE)] of the msDBP changes at Week 12 from baseline in the SPH3127 and 6.32 (0.41) in valsartan groups, with inter-group difference of -0.35 mmHg (95% CI: -1.48, 0.78, p = 0.005). Main analysis based on hypothetical strategy showed 5.95 (0.41) mmHg of the msDBP changes at Week 12 from baseline in the SPH3127 and 6.31 (0.42) mmHg in valsartan groups, with inter-group difference of -0.36 mmHg (95% CI: -1.51, 0.78, p = 0.006). During the 12-week treatment period, 250 (61.1%) patients in SPH3127 group and 231 (56.2%) patients in valsartan group reported treatment emergent adverse events (TEAEs). Adverse drug reaction (ADR) was reported by 34 (8.3%) and 41 (10.0%) patients in SPH3127 and valsartan group, respectively. The serious adverse events (SAEs) reported by 10 patients were considered not related to the investigational drugs. Death was reported in 1 patient in the valsartan group due to myocardial infarction, which was considered not related to the study drug. Oral SPH3127 tablet 100 mg QD is effective and safe for adult patients with mild-to-moderate essential hypertension. Clinicaltrials.gov Identifier number NCT05359068.

Arterial hypertension drives coronary vascular remodeling, yet disentangling the independent effects of physiological aging and chronic hemodynamic overload on the endothelium (CD31) and glycocalyx (CD138) in situ remains challenging. Most clinical studies evaluate soluble circulating markers, while direct morphological evidence of tissue-level spatial degradation is scarce. This observational post-mortem study evaluated coronary artery fragments from 30 deceased patients (10 controls, 20 with essential hypertension) using immunohistochemistry and digital pathology. To mitigate confounding bias caused by age discrepancies and acute pre-mortem systemic stressors in the control group (e.g., fatal trauma), multivariable linear regression modeling with robust standard errors was applied exclusively to the hypertensive cohort to isolate the independent impacts of chronological age and hypertension duration. Within the hypertensive cohort, chronological age emerged as a significant independent factor inversely associated with CD31 expression area (β = -0.74, 95% CI: -0.98 to -0.50, p = 0.016). The duration of hypertension was not independently associated with CD31 loss (p = 0.076). Furthermore, the multivariable model for CD138 did not reach overall statistical significance (for age: β = -0.17, 95% CI: -0.42 to 0.07, p = 0.200; for hypertension duration: β = 0.21, 95% CI: -0.06 to 0.48, p = 0.130). However, a robust positive correlation was observed between CD31 and CD138 tissue expression levels (R = 0.50, p = 0.025), indicating synchronized structural degradation. Chronological age, rather than the chronicity of hypertension, is significantly associated with reduced CD31 expression in the coronary arteries of hypertensive patients. The positive correlation between CD31 and CD138 expression highlights a synchronized spatial degradation of the endothelium and its protective glycocalyx. These findings highlight the critical necessity of isolating physiological senescence from pathological remodeling in vascular research.

Radiomics-Based Classification of Pathological Patterns in Common Carotid Artery Wall.

This study examines the prevalence and characteristics of obstructive sleep apnea (OSA) in the general population of a rural-provincial region of Denmark. Additionally, it assesses associations between OSA and various demographic, socioeconomic, and health-related factors. This cross-sectional study linked data from the Lolland-Falster Health Study (LOFUS) with nationwide Danish health registries. LOFUS provided data on age, sex, body mass index (BMI), cardiac autonomic neuropathy (CAN), socioeconomic status, smoking, alcohol consumption, snoring, and irregular breathing during sleep from participants recruited between 2016 and 2020. Data on OSA and related chronic comorbidities were obtained from The Danish National Patient Registry and Danish National Prescription Registry. Among 16,138 LOFUS participants, we observed a prevalence of OSA of 2.9%, compared to 2.5% in Lolland-Falster and 2.2% in Denmark. Male sex was associated with OSA (OR = 3.42), as was higher age peaking in the age group 60-79years old (OR = 6.54) compared to 18-39-year-olds. Age and sex-adjusted estimates showed higher BMI (OR = 2.60 for overweight; OR = 7.67 for obesity), unemployment due to long-term sickness or rehabilitation (OR = 2.70), early retirement due to invalidity (OR = 2.64), divorced/separated/widowed status (OR = 1.89 cohabiting; OR = 1.35 not cohabiting), and former smoking (OR = 1.33) to be significantly associated with OSA. The risk of having OSA was significantly increased if diagnosed with atrial fibrillation and flutter (OR = 2.40), diabetes mellitus (OR = 3.15), essential hypertension (OR = 2.66), or ischemic stroke (OR = 1.82). OSA disproportionately affects specific population groups, warranting increased awareness, particularly in patients with OSA-related chronic comorbidities.

This multicenter, randomized, double-blind, parallel-group, active-controlled study aimed to demonstrate a superior BP-lowering effect of sacubitril/valsartan (SacVal) and amlodipine (AML) combination therapy vs SacVal monotherapy in Japanese patients with grade Ⅰ/Ⅱ essential hypertension inadequately controlled with SacVal monotherapy. After 4 weeks of single-blind active run-in with SacVal 200 mg monotherapy, patients (n=717) with mean sitting systolic blood pressure (msSBP) of 140 to <180 mmHg were randomized and received SacVal 200 mg monotherapy or SacVal 200 mg in combination with AML (2.5, 5, or 10 mg) for 8 weeks. All SacVal/AML 200 mg/2.5 mg, 200 mg/5 mg, 200 mg/10 mg combinations achieved statistically significant, dose-dependent reductions in msSBP vs SacVal 200 mg monotherapy (treatment difference [mmHg] [95% CI]: -5.63 [ -8.01, -3.25], -12.94 [ -15.22, -10.67], -16.39 [ -19.01, -13.77], respectively; all p < 0.001). Treatment effects of all combinations were also statistically significant in 24-h ambulatory SBP (treatment difference [mmHg] [95% CI] vs SacVal: -6.48 [ - 8.79, -4.18], -14.18 [ -16.63, -11.73], -17.70 [ -20.24, -15.26], respectively; all p < 0.001) and BP control ( < 140/90 mmHg) rates (57.2, 72.5, 79.9%, respectively, vs 35.0% in SacVal with odds ratio [95% CI]: 2.16 [1.40, 3.33], 5.28 [3.31, 8.43], 7.23 [4.41, 11.86], respectively; all p < 0.001). Subgroup and waterfall plot analyses in msSBP demonstrated consistent BP-lowering effects across patient demographic and baseline characteristics. The safety profile of combination therapy was similar to that of SacVal with no new safety findings. These results demonstrated that combination therapy provided superior BP reduction with favorable safety and tolerability in Japanese patients inadequately controlled by SacVal 200 mg monotherapy. In this multicenter, randomized, double-blind, parallel group, active controlled trial, sacubitril/valsartan and amlodipine combination therapy showed dose-dependent reductions in office and 24-hour systolic blood pressure and a favourable safety profile in Japanese patients inadequately controlled on sacubitril/valsartan monotherapy, supporting its efficacy and safety as a treatment option.

ABSTRACT Background Lipoprotein(a) [Lp(a)] is an established cardiovascular risk factor associated with inflammation, endothelial dysfunction, oxidative stress, and arterial stiffness. Although elevated Lp(a) levels have been linked to cardiovascular disease, their relationship with left ventricular (LV) geometric remodeling in hypertension remains insufficiently characterized. This study aimed to investigate the association between serum Lp(a) levels and LV geometry in non-diabetic patients with essential hypertension. Methods This cross-sectional observational study included 110 non-diabetic patients with essential hypertension. Patients were categorized into low Lp(a) (<50 mg/dL, n = 70) and elevated Lp(a) (≥50 mg/dL, n = 40) groups. Comprehensive transthoracic echocardiography was performed to evaluate LV mass index (LVMI), relative wall thickness, and LV geometric patterns. Correlation, multivariate linear regression, and multinomial logistic regression analyses were used to determine independent associations between Lp(a) levels and LV remodeling parameters. Results Patients with elevated Lp(a) levels had significantly greater LVMI values compared with those with lower Lp(a) levels (139.6 ± 28.5 vs. 117.6 ± 24.2 g/m2, p < 0.001). Concentric LV hypertrophy was substantially more prevalent in the elevated Lp(a) group (55.0% vs. 20.0%, p = 0.001), whereas normal LV geometry was more frequently observed in patients with lower Lp(a) concentrations. Serum Lp(a) levels demonstrated a moderate positive correlation with LVMI (r = 0.357, p < 0.001). In multivariate linear regression analysis, Lp(a) remained independently associated with LVMI after adjustment for major clinical confounders (standardized β = 0.363, p < 0.001). Multinomial logistic regression analysis demonstrated that elevated Lp(a) levels were independently associated with markedly greater odds of concentric LV hypertrophy. Conclusions Elevated serum Lp(a) levels were independently associated with adverse LV geometric remodeling and concentric hypertrophy in non-diabetic patients with essential hypertension. Assessment of Lp(a) levels may provide additional value for cardiovascular risk stratification and identification of hypertensive patients at increased risk for hypertensive target organ damage.

Hypertension remains a prevalent, modifiable risk factor for cardiovascular disease, with many patients failing to achieve optimal blood pressure (BP) control despite existing therapies. Pharmacometabolomics offers promise by identifying metabolic biomarkers linked to drug response and holds potential for individualizing antihypertensive treatment. We conducted a systematic review of studies from 2013 to 2023, screening 2577 articles and including five that investigated metabolomics-based biomarkers for antihypertensive drug response in cases of primary hypertension. In total, 46 metabolites were significantly associated with BP responses to diuretics, beta-blockers, and ACE inhibitors or angiotensin receptor blockers. Key predictive metabolites included arachidonic acid, sphingosine-1-phosphate, 2-oxoglutarate, and arachidonoyl-carnitine, affecting responses across fatty acid metabolism, sphingolipid metabolism, the TCA cycle, and amino acid metabolism. This review highlights the potential of pharmacometabolomics to uncover metabolites and pathways associated with individual BP response to antihypertensive drugs. Further validation in diverse populations, drug classes, and combination treatments is needed.

Essential hypertension is influenced by conventional risk factors and genetic susceptibility. We tested the prespecified hypothesis that the combined AGT M235T-ACE I/D TT/DD genotype is associated with essential hypertension in Vietnamese adults. We conducted a hospital-based case-control study among 471 Vietnamese Kinh adults at the University Medical Center, Ho Chi Minh City, Vietnam, including 238 cardiology-clinic participants with essential hypertension and 233 health-screening participants without hypertension. Hypertension was defined according to Vietnamese guideline thresholds as office systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or current antihypertensive treatment; controls had no history of hypertension, were not receiving antihypertensive medication, and had office blood pressure < 140/90 mmHg. The primary exposure was TT/DD versus non-TT/DD. Multivariable logistic regression adjusted for age, sex, overweight or obesity, diabetes mellitus, salt-rich diet, smoking, alcohol misuse, physical inactivity, and family history of hypertension. TT/DD was observed in 37 of 238 cases (15.55%) and 15 of 233 controls (6.44%). TT/DD was associated with hypertension in crude analysis (OR 2.67, 95% CI 1.38-5.40; p = 0.002) and remained associated after adjustment (adjusted OR 3.26, 95% CI 1.53-6.92; p = 0.002). In an exploratory six-category model using (MM + MT)/II as the reference, TT/DD was the only genotype category significantly associated with hypertension, although the estimate was imprecise (adjusted OR 3.46, 95% CI 1.24-9.70; p = 0.018). The combined AGT M235T-ACE I/D TT/DD genotype was associated with essential hypertension in this hospital-based Vietnamese sample. Because of the case-control design, hospital-based recruitment, covariate imbalance, and absence of external replication, the finding should be interpreted as associative and hypothesis-generating.

To evaluate the efficacy and safety of sepetaprost, a novel dual FP/EP3 receptor agonist, in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). ANGEL-J1 (NCT05495061) was a phase 3, randomised, investigator-masked, active-controlled, parallel-group, non-inferiority study across 49 sites in Japan. Adults with POAG or OHT were randomised 1:1 to topical sepetaprost 0.002% or latanoprost 0.005%, once daily for 3 months. The primary endpoint was change in mean diurnal intraocular pressure (IOP) from baseline at week 4 (non-inferiority margin, 1.5 mmHg); a key secondary endpoint was mean change in IOP from baseline over 3months. Safety outcomes included the incidence of adverse drug reactions (ADRs). In total, 325 patients were randomised to sepetaprost (n=162) or latanoprost (n=163). In mixed model for repeated measures analyses, ANGEL-J1 met its primary endpoint; the least-squares mean (± standard error) change in mean diurnal IOP from baseline at week 4 was -5.77±0.16 mmHg in the sepetaprost group, which was non-inferior to -6.10±0.16 mmHg in the latanoprost group (least-squares mean difference, 0.32mmHg [95% confidence interval, -0.12, 0.77]). Non-inferiority for the key secondary endpoint was also established, with comparable mean reductions in IOP between groups maintained over 3 months. ADRs occurred in 59 patients (36.4%) receiving sepetaprost and 33 (20.2%) receiving latanoprost; the most common ADR was conjunctival hyperaemia (29.6% and 8.6%, respectively; mostly mild in severity). In patients with POAG or OHT, sepetaprost demonstrated IOP-lowering efficacy that was non-inferior to latanoprost, and an acceptable safety profile.

Hypertension and subclinical atherosclerosis are major contributors to cardiovascular morbidity. Asprosin, a fasting-induced adipokine involved in glucose homeostasis and inflammation, has been proposed as a novel metabolic biomarker. This study investigated the relationship between serum asprosin levels and subclinical atherosclerosis in patients with primary hypertension. A total of 114 patients with primary hypertension and 62 age- and sex-matched healthy controls were enrolled between July 2022 and June 2023. Coronary artery calcium (Agatston) score was used to assess subclinical atherosclerosis. Serum asprosin concentrations were measured using the ELISA method. Correlation, regression, and ROC analyses were performed to identify determinants and discriminatory performance. Serum asprosin levels were significantly higher in hypertensive patients than in controls (3.0 ± 0.9 ng/mL vs. 2.6 ± 0.8 ng/mL, p = 0.012). In hypertensive individuals, increasing age, blood pressure, and ASCVD risk score were independently associated with higher atherosclerotic burden, whereas the neutrophil-to-lymphocyte ratio (NLR) was inversely related (p < 0.05). ROC analysis showed that serum asprosin could discriminate hypertensive patients with subclinical atherosclerosis (AUC = 0.710 [95% CI: 0.62-0.80, p = 0.001]) at a cut-off > 3.05 ng/mL, with 69% sensitivity and 72% specificity. Serum asprosin levels were elevated in patients with primary hypertension and may reflect metabolic-inflammatory alterations rather than directly indicate subclinical atherosclerosis. Given its modest discriminatory performance, serum asprosin should be considered an exploratory and complementary biomarker, not a standalone clinical tool. Larger longitudinal studies are required to validate its clinical relevance.Clinical trial numberNot applicable.

Primary aldosteronism (PA) carries excess cardiovascular risk not fully explained by hemodynamic load. While aldosterone promotes fibroblast activation experimentally, in vivo evidence linking adrenocortical activity with myocardial remodeling remains limited. This study integrated CXCR4 (C-X-C chemokine receptor type 4)-targeted 68Ga-Pentixafor positron emission tomography (PET)/magnetic resonance and FAP (fibroblast activation protein)-targeted 68Ga-FAPI-04 PET/cardiac magnetic resonance to evaluate the adrenal-cardiac axis in PA. Eighty-two participants (40 with PA [21 aldosterone-producing adenoma (APA), 19 idiopathic hyperaldosteronism], 21 with essential hypertension, and 21 normotensive controls) underwent 68Ga-FAPI-04 PET/cardiac magnetic resonance; 48 concurrently underwent 68Ga-Pentixafor PET/magnetic resonance. Adrenal CXCR4 and myocardial FAPI uptake, as well as integrated volumetric-uptake burdens, were quantified and correlated with clinical and cardiac magnetic resonance indices. Eight patients with APA underwent follow-up imaging postadrenalectomy. Adrenal volume-adjusted CXCR4 signal served as a reliable marker of in vivo aldosterone burden and was significantly associated with adverse left ventricular remodeling, independent of blood pressure levels or hypertension duration. Myocardial 68Ga-FAPI-04 uptake was detected in 55% of patients with PA (APA 71.4%, idiopathic hyperaldosteronism 36.8%), compared with 19% of patients with essential hypertension and 0% of controls (P<0.001), localizing predominantly to the basal septum. Importantly, total adrenal volume-adjusted CXCR4 signal correlated with myocardial FAPI activity (r=0.38-0.64; all P<0.05) and cardiac magnetic resonance markers of remodeling, both of which were positively associated with aldosterone levels. At 5.2±1.2 months post-adrenalectomy, myocardial FAPI uptake in 8 patients with APA declined significantly (P<0.01), whereas late gadolinium enhancement and global cardiac function showed no significant change. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06756737. Dual-tracer PET/magnetic resonance provided in vivo molecular evidence of a CXCR4-FAP-mediated adrenal-cardiac axis in PA, revealing cross-talk between adrenocortical function, aldosterone secretion, and myocardial fibroblast activation beyond blood pressure effects. FAPI PET demonstrated more severe myocardial activation in APA, with partial postadrenalectomy reversibility, underscoring the value of early diagnosis and timely surgical intervention.

Primary aldosteronism (PA) is the most common endocrine cause of hypertension, yet emerging longitudinal data indicate that its injurious effects extend to the brain. A nationwide Korean cohort study demonstrated that patients with PA exhibit a significantly higher incidence of all-cause dementia than matched individuals with essential hypertension, independent of blood pressure. However, this association was attenuated for Alzheimer's disease after multivariable adjustment, whereas vascular dementia remained significantly associated with PA. Aldosterone activates mineralocorticoid receptors (MRs) in the brain, triggering oxidative stress, blood-brain-barrier leakage and neuro-inflammation that damage hippocampal and prefrontal networks, leading to deficits in executive function, language and attention. Notably, these effects are amplified by dietary salt intake, and experimental evidence suggests that aldosterone-induced end-organ damage requires a high-salt milieu. In animal models, chronic aldosterone exposure reproduces these cognitive impairments, whereas MR blockade or adrenalectomy reverses learning and memory deficits. However, current PA guidelines omit recommendations for cognitive screening or intervention, rendering this potentially reversible aetiology largely overlooked. Here we systematically synthesize the pleiotropic mechanisms of aldosterone signalling in neurons, glia and cerebral vessels; integrate cross-sectional, prospective and interventional clinical evidence to quantify the strength of the PA-dementia association; and compare the differential cognitive outcomes of surgery versus pharmacotherapy. We also discuss emerging aldosterone synthase inhibitors as a novel therapeutic strategy that eliminates ligand production rather than merely blocking receptor signalling. Finally, we propose a risk-prediction framework that incorporates neuroimaging and fluid biomarkers, and call for a transdisciplinary clinical pathway to enable early recognition and precision intervention.

With the intensification of aging in China, limited medication access and financial burden hinder effective blood pressure management in older adults. In July 2021, Quzhou introduced a policy providing free antihypertensive medications to individuals aged ≥ 65 years. This study aimed to evaluate its impact on long-term blood pressure outcomes. An interrupted time series analysis was performed using 28 quarters of longitudinal blood pressure data from 1,310 older patients with primary hypertension (aged ≥ 65 years) in Quzhou. A segmented regression model embedded with quarterly seasonal dummy variables was constructed to adjust for long-term physiological trends and seasonal blood pressure fluctuations. Autocorrelation was diagnosed by Durbin-Watson and Breusch-Godfrey tests, and counterfactual prediction was applied to quantify the net policy effect. Prior to the policy, DBP showed a slow declining trend (-0.048 mmHg per quarter) while SBP exhibited a significant upward trend (0.275 mmHg per quarter). The policy produced no immediate level change but significantly altered long-term trajectories. Following implementation, the rate of DBP decline accelerated by an additional - 0.062 mmHg per quarter (P = 0.029), whereas SBP trend reversed from an increase to a decrease, resulting in a net change of -0.310 mmHg per quarter (P < 0.001). By the fourth quarter of 2024, actual SBP was 4.4 mmHg lower than the counterfactual scenario without the policy, and DBP was 0.8 mmHg lower. The cumulative policy effects over the entire follow-up period were 6.6 (95%CI: -1.2, 14.3) mmHg for DBP and 32.2 (95%CI: 13.6, 50.8) mmHg for SBP. The free antihypertensive medication policy in Quzhou is not only a social welfare initiative but also an effective public health intervention with significant clinical benefits. It significantly altered the long-term trajectory of blood pressure among elderly patients by accelerating the decline in diastolic blood pressure and reversing the upward trend in systolic blood pressure.

The role of microRNA in primary hypertension remains unclear. This study examined the expression of microRNA-16, -21, -27a, -27b, -133a, and -145 in untreated hypertensive children, their response to aerobic exercise, and correlations with blood pressure and related parameters. A pre-post study, observational, hypothesis generating study included 56 hypertensive (SG - study group) and 59 healthy children (CG - control group). Plasma microRNA levels and clinical, biochemical, blood pressure, vascular, and hypertension-mediated organ damage (HMOD) parameters were assessed before and after one session of standardized aerobic exercise. The baseline relative microRNA-27b (p < 0.001) and microRNA-133a (p = 0.018) expressions were significantly lower in the SG; similarly, after an exercise bout. After an exercise bout, the expression of microRNA-27b, -133a, and -145 increased in CG, whereas only the expression of microRNA-145 increased in SG. In SG, microRNA-16, -21, -27a, and -145 correlated positively with pre-exercise blood pressure. There were no correlations between the analyzed microRNA particles and parameters of HMOD. ROC analysis identified the best prognostic profile for relative microRNA-27b expression as a potential biomarker of the absence of primary hypertension. Multivariate analysis revealed the relative microRNA-16 expression as the only significant predictor of elevated diastolic blood pressure. MicroRNA-27b, as well as microRNA-133a, are underexpressed in children with PH. These particles may represent potential markers of hypertension in children and may also be associated with a lower burden of hypertension-related alterations. MicroRNA-16 may serve as a marker of diastolic hypertension.

Efficacy and Safety Profile of a Triple Single-Pill Combination of Valsartan/Amlodipine/Chlorthalidone in Patients with Uncontrolled Hypertension.

Renal artery stenosis is usually considered as a contraindication for renal denervation. Whether renal denervation can be safe and effective in the presence of a renal artery stenosis once secondary renovascular hypertension has been ruled-out has never been investigated to date. We report our experience with radiofrequency-based renal denervation in patients with moderate-to-severe renal artery stenosis. Patients with uncontrolled hypertension eligible for renal denervation referred to our Center were evaluated for this study. Renal artery stenosis >50% as evaluated by quantitative angiography analysis underwent physiological evaluation (ratio of the distal pressure to aortic pressure: Pd/Pa). Those with Pd/Pa ≥ 0.90 underwent renal denervation, as did patients with normal kidney arteries. Patients with Pd/Pa < 0.90 were treated with renal artery stenting. Office systolic and diastolic blood pressure (BP) and estimated glomerular filtration rate (eGFR) were assessed and compared among patients with normal renal arteries (Group 1), those with non-hemodynamically significant renal artery stenosis (Group 2), and patients undergoing renal artery stenting (Group 3). All patients with at least one-year of follow-up were included (n = 139). Similar systolic BP reduction was reported in Groups 1 (n = 114) and 2 (n = 25) : -5.76 ± 3.50, -5.86 ± 3.74, -14.46 ± 3.6, -22.79 ± 27.12 mmHg and -14.93 ± 26.53, -11.29 ± 27.32, -17.38 ± 22.72 and -19.21 ± 23.70 mmHg at 3, 6, 12, and 24 months, respectively. Kidney function remained stable. The patients in group 3 (n = 9) showed significant BP lowering after renal artery stenting. Physiologic assessment of renal artery stenosis distinguished hemodynamically relevant lesions, responsible for renovascular hypertension and suitable to undergo revascularization, from lesions without significant hemodynamic impact, which may be encountered in patients with essential hypertension. An accurate algorithm for stenosis assessment allows the selection of the most appropriate treatment (ie, renal artery stenting or renal denervation).

This study aimed to evaluate the association between intraocular pressure (IOP) and circadian blood pressure (BP) patterns-specifically dipper and nondipper status-in patients with newly diagnosed essential hypertension. A total of 180 participants were enrolled and equally divided into individuals with normal blood pressure (n=90) and individuals with hypertension (n=90). Individuals with hypertension were further classified into dipper and nondipper subgroups based on 24-hour ambulatory BP monitoring. IOP was assessed using a noncontact tonometer during morning hours (9:00 a.m.-12:00 p.m.). Individuals with hypertension demonstrated significantly higher right and left eye IOP values compared to individuals with normal blood pressure (16.86 ± 3.84 mmHg vs. 14.56 ± 2.79 mmHg and 16.69 ± 4.02 mmHg vs. 14.43 ± 3.08 mmHg, respectively; both p<0.001). Among hypertensives, nondippers had significantly higher IOP than dippers (right eye: 17.91 ± 3.93 vs. 15.85±3.52 mmHg, p=0.010; left eye: 17.88±3.98 vs. 15.55±3.76 mmHg, p=0.005). Linear regression analysis identified 24-hour systolic BP (β=0.902, 95% CI: 0.220-0.395, p<0.001) and nondipper status (β=-0.608, 95% CI: -7.294 to -3.218, p<0.001) as independent predictors of mean IOP in individuals with newly diagnosed and untreated hypertension. ROC analysis revealed that, in individuals with newly diagnosed and untreated hypertension, a mean IOP ≥16.85 mmHg predicted nondipping status with 59.1% sensitivity and 63% specificity (AUC=0.666, p=0.007). These findings suggest that a nondipping circadian BP profile is independently associated with elevated IOP in individuals with newly diagnosed and untreated hypertension, emphasizing the potential value of ocular pressure monitoring in this population, particularly those without nocturnal BP decline.

ABSTRACTHypertension is a major modifiable risk factor for chronic kidney disease (CKD), accelerating renal injury by promoting arterial stiffness. Estimated pulse wave velocity (ePWV), an indicator of arterial stiffness, is associated with CKD progression, but its relationship with urinary albumin‐to‐creatinine ratio (UACR) in non‐diabetic hypertensive patients remains unclear. This retrospective study included 509 non‐diabetic adults with essential hypertension. Participants were classified as having early renal impairment (UACR ≥30 mg/g, n = 167) or not (UACR <30 mg/g, n = 342). ePWV was calculated from age and mean blood pressure (MBP). The impairment group showed significantly higher ePWV (P < 0.001). Restricted cubic splines revealed a positive linear correlation between ePWV and UACR (P for nonlinear = 0.938). Multivariable logistic regression identified that ePWV was an independent risk factor for early renal impairment. Each 1 m/s increase in ePWV was associated with a 43.9% elevated risk of early renal impairment (OR = 1.439, 95% CI: 1.176–1.761), with the highest ePWV quartile (>9.70 m/s) showing an OR of 4.894 (95% CI: 2.019–11.86). ROC analysis showed that ePWV had the highest AUC at 0.710, higher than age (0.585) and MBP (0.693), and it provided greater incremental value for identifying early renal impairment than age and MBP when incorporated into the base model. Subgroup analyses by sex, age, BMI, and eGFR consistently supported these associations. In conclusion, ePWV is an independent risk marker for early renal impairment in non‐diabetic hypertensive patients, supporting its potential use in early risk stratification.

This study investigates genetic evidence for a causal association between alcohol intake and 1174 diseases, and various biomarkers. A phenome-wide Mendelian randomization (MR) study was conducted using data from 337,463 UK Biobank participants. Five MR methods and sensitivity analyses tested linear associations, while non-linear MR assessed intake-dependent effects. Alcohol consumption was associated with 22 distinct diseases across ten categories. Beyond the strong association between genetically indexed alcohol intake with 'alcohol-related disorders' (OR per log-unit/week: 7.02, 95% CI: 5.26-9.37), MR analyses suggested robust evidence for increased risks of 'cerebrovascular diseases' (1.63, 1.20-2.21), 'essential hypertension' (1.34, 1.07-1.67), 'electrolyte imbalance' (1.82, 1.34-2.48), 'magnesium metabolism disorder' (4.39, 2.06-9.39), 'open wounds of head, neck, and trunk' (2.15, 1.39-3.33), and 'symptoms involving nervous and musculoskeletal systems' (2.16, 1.60-2.91). Suggestive evidence indicated higher risks for 12 diseases, mostly mental and digestive disorders, and lower risks for 'benign neoplasms of connective and other soft tissue', 'urinary calculus', and migraines. Seven diseases exhibited non-linear yet monotonic trends (all Pnon-linearity ≤ 0.05). Alcohol intake was robustly associated with biomarkers including bilirubin, urine sodium, urea, and blood pressure. This comprehensive analysis supports alcohol's causal role in multiple diseases and biomarkers, highlighting significant risks with minimal benefits.