OBJECTIVE:Metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexists with hypertension, yet comparative data on antihypertensive medication classes remain limited. We examined associations between antihypertensive medication class and liver fibrosis and mortality in US adults with MASLD. METHODS:We conducted a prevalent-user analysis using National Health and Nutrition Examination Survey (NHANES) 1999-2018 data linked to mortality through 2019. Antihypertensive exposure was defined at baseline based on self-reported medication use, consistent with a prevalent-user design. Steatosis was defined by the US Fatty Liver Index (US-FLI). Fibrosis was assessed using FIB-4 and APRI within a model-based framework derived from vibration-controlled transient elastography. Analyses comparing antihypertensive classes were restricted to monotherapy users. Logistic regression and Cox models with inverse probability of treatment weighting and survey weights were applied. RESULTS:Among participants with MASLD receiving antihypertensive monotherapy (n = 458; 86 deaths), ACEIs and ARBs were associated with lower all-cause mortality compared with calcium channel blockers (CCBs, reference group; n = 47; 15 deaths) (ACEIs: adjusted hazard ratio [aHR], 0.30; 95% CI, 0.11-0.82; ARBs: 0.25; 95% CI, 0.07-0.94). In cross-sectional analyses, antihypertensive medication use was associated with lower odds of liver fibrosis defined by FIB-4 and APRI within US-FLI-defined populations (MASLD: FIB-4 aOR 0.51 [0.29-0.91]; APRI aOR 0.49 [0.28-0.89]). Findings were broadly consistent across sensitivity analyses, including alternative model specifications and expanded covariate adjustment. CONCLUSIONS:Antihypertensive medication use, particularly ACEIs and ARBs, was associated with lower fibrosis prevalence and all-cause mortality in MASLD. These findings are hypothesis-generating and require confirmation in prospective studies.
Objective Stress-induced hypertension (SIH) is driven by sympathetic overactivity, with the rostral ventrolateral medulla (RVLM) serving as a key regulatory hub. Extracellular vesicles (EVs) mediate intercellular communication, but their role in RVLM-related SIH pathogenesis remains unclear.Methods A rat SIH model was established via 15 days of unpredictable stress. The EV secretion inhibitor GW4869 was microinjected into the RVLM of SIH rats to observe alterations in blood pressure and neuronal excitability. RVLM-EVs were isolated using iodixanol density gradient centrifugation and used to treat primary RVLM neurons in vitro; neuronal excitability was evaluated by c-FOS immunofluorescence staining. Bead-based flow cytometry was performed to detect the protein components of RVLM-EVs, and the TNF-α antagonist R7050 was administered for both in vitro and in vivo interventions to examine its regulatory effects on neuronal excitability and blood pressure.Results GW4869 reduced BP and neuronal excitability in SIH rats. SIH-RVLM-EVs, with larger particle size, were internalized by primary RVLM neurons, enhancing excitability and inducing hypertension in normotensive rats. TNF-α was enriched in SIH-RVLM-EVs; R7050 abrogated these pro-hypertensive effects in vitro and in vivo.Conclusion RVLM-derived EVs promote SIH by delivering TNF-α, which enhances RVLM pre-sympathetic neuronal excitability and sympathetic overactivity. TNF-α in RVLM-EVs is a promising therapeutic target for SIH.
Introduction Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by disrupted hepatic lipid homeostasis and progressive liver injury, and frequently coexists with hypertension and systemic vascular remodeling, suggesting shared pathophysiological mechanisms. Although adipose tissue-derived microRNAs have emerged as important mediators of inter-organ communication, their roles in regulating hepatic cholesterol metabolism and vascular dysfunction during MASH remain incompletely understood.Objectives This study aimed to investigate whether microRNA-518a regulates hepatic cholesterol metabolism and MASH progression through the MST1-AMPK-SREBP2 signaling pathway and to explore its potential implications for vascular remodeling and hypertension.Methods Integrative bioinformatic analyses, including Mendelian randomization and transcriptomic network analysis, were performed to identify candidate regulatory pathways associated with MASH. Functional validation was conducted using human clinical samples, in vitro cell models, exosome-mediated microRNA delivery, and a dietary mouse model of MASH.Results MST1 was identified as a key regulatory target of microRNA-518a. Increased microRNA-518a expression suppressed MST1, resulting in reduced AMPK activation and enhanced SREBP2-mediated cholesterol biosynthesis. Functional experiments demonstrated that microRNA-518a promoted hepatic cholesterol accumulation, lipid deposition, inflammation, and fibrotic changes, whereas restoration of MST1 partially reversed these effects. Exosome-mediated delivery of microRNA-518a further supported its ability to modulate hepatic metabolic responses through intercellular communication.Conclusions MicroRNA-518a promotes hepatic cholesterol dysregulation and MASH progression by targeting the MST1-AMPK-SREBP2 signaling pathway. Notably, the convergence of this axis with vascular regulatory networks suggests broader implications for understanding the metabolic-vascular comorbidities frequently observed in MASH patients, including hypertension and arterial stiffness.
INTRODUCTION:PCOS is a common endocrine disorder with elevated cardiometabolic risk, yet the role of the renin-angiotensin system (RAS)-iron metabolism axis in this comorbidity remains unclear. We explored its underlying mechanisms and evaluated the therapeutic potential of gentiopicroside. METHODS:Integrated multi-omics analyses combining transcriptomics, single-cell RNA sequencing, Mendelian randomization, machine learning, molecular docking, and in vitro functional assays were performed to identify shared molecular pathways and therapeutic targets across PCOS, hypertension, NAFLD, and T2DM. RESULTS:SLC11A2 was consistently dysregulated in PCOS transcriptomic datasets, and associated with iron metabolism, inflammatory response and oxidative stress pathways. Genetic analyses validated RAS-related regulation in hypertension susceptibility and revealed shared genetic architecture between PCOS and cardiometabolic traits. Network and single-cell analyses characterized SLC11A2-associated molecular patterns in disease-relevant cell types; machine learning identified disease-classifying molecular signatures. Gentiopicroside alleviated inflammatory and oxidative stress phenotypes, including reduced IL-6 expression and reactive oxygen species accumulation. CONCLUSION:This study defines an RAS-SLC11A2 molecular framework linking iron metabolism dysregulation to PCOS-related cardiometabolic risk, elucidating the mechanisms connecting ovarian dysfunction, inflammation, oxidative stress and hypertension, and supports gentiopicroside as a promising therapeutic candidate.
This cross-sectional study aimed to analyze whether inter-ankle systolic blood pressure difference (sIAND) was associated with different stages of hypertensive renal damage. 1,658 and 831 nondiabetic hypertensive patients were included from two cohorts. The hypertensive renal damage was reflected by urinary albumin-to-creatinine ratio (UACR), Cystatin C, and estimated glomerular filtration rate. Logistic regression results showed that sIAND was only associated with subclinical hypertensive renal damage reflected by microalbuminuria (UACR > 30 mg/g) independently. Receiver operating characteristic curves indicated sIAND can identify microalbuminuria more effectively. sIAND can aid in identifying microalbuminuria to provide useful clues for risk stratification and clinical management.
BACKGROUND:Preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity. Women of advanced maternal age (AMA, ≥ 35 years) constitute a rapidly expanding high-risk subpopulation in China. Existing first-trimester prediction models were derived in general obstetric populations and often rely on specialized biophysical or proprietary biomarker assays, with limited validation in AMA women. METHODS:This multicenter retrospective study enrolled 2,582 AMA pregnant women from three tertiary centers in southern China, partitioned into a training cohort (n = 1,327), an internal validation cohort (n = 569), and two external validation cohorts (n = 399 and 287). Predictors were selected using LASSO and multivariable logistic regression and assembled into a nomogram. Performance was evaluated by area under the receiver operating characteristic curve (AUC), calibration, Brier scores, decision curve analysis, and clinical impact curves. RESULTS:Seven independent predictors were retained: pre-pregnancy BMI, parity, mode of conception, uric acid, white blood cell count, red blood cell count, and hemoglobin. The nomogram achieved AUCs of 0.819, 0.795, 0.787, and 0.756 across the four cohorts, with close calibration and favorable net benefit. Performance was preserved when women with chronic hypertension were included and across early-onset and late-onset PE subgroups. Notably, maternal age itself was not discriminative within the AMA stratum (P = 0.626). CONCLUSIONS:This nomogram relying exclusively on routine clinical and laboratory parameters provides an accessible tool for individualized early-pregnancy PE risk assessment and risk-stratified antenatal management in AMA women.
Objective Aortic dissection (AD) is a fatal cardiovascular emergency that is predominantly induced by long-term uncontrolled hypertension.Materials and methods The mouse AD model was established by combining β-aminopropionitrile with angiotensin II. The incidence rate, rupture rate, and survival status of the mice were evaluated. The structural damage of the aorta was observed using tissue staining technology, the extracellular matrix status, and macrophage pyroptosis were evaluated by immunofluorescence staining, the infiltration of inflammatory cells was detected by immunohistochemistry, the expression of pyroptosis-related molecules, and inflammatory factors was analyzed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Cell proliferation was detected by EdU staining, and cell apoptosis was detected by flow cytometry.Results In the aortic tissues of AD model mice, the expression of APN, and the content of APN in the serum were significantly decreased. APN intervention can alleviate the thickening of the aortic media, rupture of elastic fibers, and degradation of the extracellular matrix. APN inhibits the proliferation, apoptosis, and phenotypic transformation of vascular smooth muscle cells (VSMCs). At the same time, it can inhibit the infiltration of neutrophils and macrophages and the inflammatory response. Underlying mechanism, it was found that APN inhibited NLRP3-mediated pyroptosis by reducing the release of inflammatory factors; this effect was dependent on the phosphorylation activation of AMPKα and APN receptor.Conclusion APN plays a protective role in AD. Its underlying mechanism is related to the activation of the AMPK pathway, which in turn inhibits macrophage pyroptosis and vascular inflammation. This study offers a new perspective for the pathological mechanism of AD.
OBJECTIVE:Hyponatremia is one of the most common electrolyte disorders in clinical practice and is frequently observed following thiazide use. Advanced age and female gender are implicated in the etiology of hydrochlorothiazide (HCTZ)-associated hyponatremia. There has also recently been mention of a genetic disposition. This study evaluated the genetic component, and particularly the clinical significance, of variants in the SLC12A3 gene in the development of hyponatremia in hypertensive patients using HCTZ-group diuretics. METHOD:Ninety-five patients presenting to the Tekirdağ Namık Kemal University nephrology clinic and receiving antihypertensive therapy including HCTZ for at least one month were examined. Peripheral blood specimens were collected from hyponatremic (n = 62) and non-hyponatremic (n = 33) individuals. Variants in the SLC12A3 gene were analyzed using next generation sequencing and were compared with the clinical data. RESULTS:A total of 947 variants were detected in the SLC12A3 gene, the majority of which were classified as of uncertain significance. Hyponatremia was determined at a higher rate in patients with c.506-276A>G (75.00%), c.282+492G>A (85.70%), c.282+499G>C (87.00%), c.282+495G>A (85.00%), and c.505+375G>A (92.30%) variants in particular. The risk of hyponatremia development increased 9.2-fold in the presence of the c.282+492G>A variant (OR = 9.243; 95% CI: 2.259-37.818; p = 0.002). CONCLUSION:In conclusion, we think that HCTZ-associated hyponatremia cannot be predicted by clinical and biochemical parameters alone, and that genetic factors should also be considered. Further multi-center prospective studies involving larger populations will clarify the clinical significance of variants in SLC12A3 and other genes and will make a significant contribution to individualized therapeutic approaches.
BACKGROUND AND PURPOSE:Intracranial atherosclerotic stenosis (ICAS) is common in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA), but its relationship with long-term cognitive impairment remains unclear. This study examined whether ICAS was associated with 1-year cognitive impairment after AIS/TIA independently of cerebral small vessel disease (CSVD) and extracranial carotid artery stenosis (ECAS). METHODS:Data were obtained from the impairment of cognition and sleep after AIS or TIA in Chinese patients (ICONS), a subgroup of the China National Stroke Registry III. Patients with AIS or TIA within 7 days of onset who had baseline vascular imaging and 12-month cognitive assessment were included. ICAS was defined as intracranial arterial stenosis ≥50%. The primary outcome was cognitive impairment at 12 months, defined as a Montreal Cognitive Assessment (MoCA) score <23. Multivariable logistic regression and domain-specific linear regression analyses were performed after adjustment for demographic characteristics, vascular risk factors, CSVD markers, ECAS, stroke severity, and baseline cognitive status. RESULTS:A total of 1261 patients were included. Patients with ICAS had a significantly higher rate of cognitive impairment at 1 year than those without ICAS. After full adjustment, ICAS remained independently associated with 1-year cognitive impairment (odds ratio 1.524, 95% confidence interval 1.068-2.176; p = 0.020). ICAS was also significantly associated with poorer recall performance (β = -0.182, 95% confidence interval -0.293 to -0.071; p = 0.001), but not with other cognitive domains. CONCLUSIONS:ICAS was independently associated with an increased risk of 1-year cognitive impairment after AIS/TIA, particularly in memory performance.
Background Essential hypertension (EH) remains a leading modifiable risk factor for cardiovascular morbidity and mortality worldwide. Electroacupuncture (EA), combining traditional acupuncture with pulsed electrical stimulation at specific acupoints, has attracted growing attention as a potential adjunctive strategy.Methods A structured narrative literature search was conducted across PubMed, Web of Science, and CNKI databases up to January 2026. Search terms combined electroacupuncture-related terms with hypertension-, mechanism-, clinical trial-, and neuroimaging-related terms. Eligible studies included preclinical hypertension models, selected mechanistic studies from related cardiovascular models, completed clinical studies, published clinical trial protocols, and neuroimaging investigations relevant to EA and blood pressure regulation. Evidence sources were categorized as direct EH-specific evidence, indirect mechanistic evidence, adjunctive clinical evidence, or protocol-based evidence. No formal systematic review methodology was applied; this review should be interpreted as an integrative narrative synthesis.Results Current evidence suggests that EA may influence blood pressure regulation through multiple preclinically supported mechanisms, including modulation of central sympathetic outflow, autonomic rebalancing, anti-inflammatory signaling, endothelial protection, and attenuation of myocardial remodeling. However, direct human evidence for EA in EH remains sparse. The current clinical literature consists mainly of one stage 1 hypertension study, adjunctive-therapy evidence, and published protocols with pending results, rather than completed, definitive EA-specific randomized trials that establish clinical efficacy.Conclusion EA remains a biologically plausible but clinically unconfirmed adjunctive approach for EH. Its clinical efficacy, optimal parameters, and target populations require confirmation in completed, adequately powered, sham-controlled multicenter randomized trials.
BACKGROUND:Existing evidence on the interrelationship among hyperuricemia, physical frailty, and stroke remains limited and unclear. This study aimed to examine the associations of hyperuricemia and frailty with the incidence of stroke, and to evaluate the potential mediating role of frailty. METHODS:We include Chinese adults aged 45 years and above from the China Health and Retirement Longitudinal Study (CHARLS). Serum urate concentrations were measured using an enzymatic colorimetric method, and hyperuricemia was defined as serum urate ≥420 μmol/L. The frailty index (FI) was constructed based on 28 baseline items. Stroke was ascertained based on self-reported, physician-diagnosed events. Multivariable logistic regression and mediation analyses were conducted to examine the associations among hyperuricemia, physical frailty, and stroke. RESULTS:A total of 7462 eligible participants were included in the analysis. Hyperuricemia was positively associated with frailty status (OR = 1.54, 95% CI: 1.02-5.84) and with the incidence of stroke (OR = 4.07, 95% CI: 1.25-13.19). Pri-frail and frail participants exhibited a substantially higher risk of incident stroke (OR = 1.55, 95% CI: 1.11-2.92 and OR = 2.87, 95% CI: 1.29-6.37, respectively). Mediation analysis further indicated that the FI partially mediated the relationship between hyperuricemia and incident stroke, accounting for 10.82% (95% CI: 6.51%-21.65%) of the total effect. CONCLUSIONS:Hyperuricemia is associated with an increased risk of stroke, and frailty may partially mediate this association. Early identification and management of frailty in individuals with hyperuricemia may represent a novel, integrative strategy to reduce stroke risk and promote healthy aging.
BACKGROUND:Left ventricular hypertrophy (LVH) is a serious complication of hypertension. However, the association between the nondipper heart rate (NDHR) and the risk of LVH remains unclear. METHODS:A cross-sectional analysis was conducted involving 991 patients with essential hypertension. NDHR was defined as a <10% reduction in nocturnal heart rate assessed by 24-h ambulatory blood pressure monitoring. Propensity score matching (PSM) was used to balance baseline characteristics. The independent association was assessed using multivariable logistic regression, and interactions were evaluated on multiplicative and additive scales. RESULTS:After exclusions, 991 eligible hypertensive patients were included, with 234 PSM pairs of nondipper and dipper participants achieving balanced baseline characteristics. The NDHR was independently associated with LVH after multivariable adjustment (OR = 1.588 [95%CI: 1.062-2.373]; P = 0.024). A significant synergistic interaction was observed between NDHR and nondipper blood pressure, with the dual nondipper phenotype conferring the highest odds of LVH (OR = 2.52 [95%CI: 1.68-3.78]). Additive interaction measures confirmed biological synergy (RERI = 0.98; AP, 0.39). A nomogram incorporating NDHR demonstrated acceptable discrimination for LVH (AUC = 0.66 [95%CI: 0.61-0.71]) and provided superior net benefit across a wide threshold probability range (20%-80%). Subgroup analyses indicated stronger associations in younger patients and those not using ACEI/ARBs. CONCLUSION:NDHR is an independent risk factor for LVH and exhibits significant synergy with NDBP. Assessment of nocturnal heart rate decline, despite its behavioral confounders, may enhance cardiovascular risk stratification in hypertension.
White-coat Uncontrolled Hypertension (WUH) is characterized by elevated office blood pressure but normal out-of-office levels, and it has shifted from a phenomenological concept to a precision diagnosis model centered on ambulatory and home monitoring. This study provides a comprehensive review of the evolution of definitions, epidemiology, pathophysiology, and risk evidence, and compares the diagnostic value of Office Blood Pressure Monitoring (OBPM), Ambulatory Blood Pressure Monitoring (ABPM), and Home Blood Pressure Monitoring (HBPM). Within this analytical framework, the investigation examines cardiovascular and metabolic risks, interventions in special populations, and ongoing controversies in treatment. These findings are significant for integrating both Chinese and international guidelines with emerging digital monitoring trends. The study further proposes an integrated "home-clinic-cloud platform" model to support individualized hypertension management. This framework offers a more nuanced understanding of evolving paradigms in hypertension diagnosis and treatment. Based on current guideline-supported evidence, we emphasize ABPM/HBPM-based confirmation, risk stratification, and long-term surveillance to avoid misclassification and overtreatment. Emerging directions-including psycho-physiological modeling, multi-scenario monitoring, and digital-twin-enabled simulation-should be regarded as conceptual or research-oriented frameworks that require prospective validation and outcome data before clinical implementation.
OBJECTIVE:This study aimed to compare the metabolic and inflammatory profiles of dipper and non-dipper hypertensive patients versus healthy controls, specifically evaluating the Triglyceride-glucose (TyG) index's association with nocturnal blood pressure patterns. METHODS:This retrospective, cross-sectional study included 325 participants (110 normotensive controls, 106 dipper hypertensive, and 109 non-dipper hypertensive). Circadian blood pressure phenotypes were defined using 24-hour ABPM according to the 2024 ESC Hypertension Guidelines. Inflammatory indices (NLR, LMR, and HALP score) and the TyG index were calculated from fasting blood samples. RESULTS:Hypertensive groups had higher BMI and waist circumference than controls (p < 0.001). HALP, NLR, and LMR did not differ between the cohorts (p > 0.05). The TyG index showed the greatest intergroup variation and was strongly associated with the non-dipper phenotype (OR = 3.6, p = 0.004). TyG was positively correlated with nocturnal SBP/DBP and negatively correlated with nocturnal SBP decline. It showed significant diagnostic performance for hypertension and non-dipper status (AUC 0.667-0.696, p < 0.001), but limited accuracy for classifying hypertensive subgroups (AUC = 0.573, p = 0.064). CONCLUSION:The TyG index serves as a significant independently associated with the non-dipper hypertension phenotype, reflecting predominant metabolic and cardio-renal stress rather than cellular inflammation. These findings suggest that clinical management should extend beyond blood pressure control to include early optimization of insulin resistance and atherogenic lipid imbalance. Ultimately, the TyG offers a practical and cost-effective clinical tool for multidimensional cardiometabolic and cardio-renal risk assessment.
Coronary artery disease (CAD) remains a major cause of global mortality. While established risk factors are targets of effective preventive interventions, a substantial proportion of CAD patients exhibit no conventional risk factors. To investigate potential metabolomic biomarkers of residual risk in such individuals, we conducted untargeted metabolomic profiling of serum from CAD patients lacking traditional risk factors using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Comparative analysis with non-CAD controls revealed significant alterations in metabolite levels, with 43 metabolites elevated and 46 reduced in CAD patients. Notably, we observed a marked upregulation of circulating unsaturated fatty acids (UFAs) which reflects dysregulated unsaturated fatty acid biosynthesis. Pathway analysis further indicated enrichment in biosynthetic pathways of unsaturated fatty acids, implicating a potential role of dysregulated UFA metabolism in CAD pathogenesis. These altered fatty acids may act as potential biomarkers and residual risk factors for predicting CAD in individuals without conventional risk factors. Collectively, our study identifies elevated circulating UFAs as a novel metabolic signature in this patient subgroup, which may serve as a potential predictive indicator for noninvasive risk stratification and targeted prevention. To our knowledge, this is one of the initial metabolomic studies to identify UFA dysregulation in CAD patients without conventional risk factors, and the clinical utility requires further validation in larger multi-center cohorts.
BACKGROUND:The cardiometabolic index (CMI) integrates central adiposity with atherogenic dyslipidaemia and may identify individuals at elevated cardiometabolic risk. However, evidence linking CMI to advanced cardiovascular-kidney-metabolic (CKM) syndrome across diverse populations remains limited. METHODS:We conducted cross-sectional analyses on adults aged ≥ 45 years using data from NHANES (2001-2018) and CHARLS (2011/2015). CMI was calculated as (triglycerides/HDL-cholesterol) × (waist/height). The primary outcome was advanced CKM (stages 3-4). Multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines and two-piecewise regression assessed non-linearity and thresholds. RESULTS:The analytic sample included 10,198 participants from NHANES and 17,285 from CHARLS. Higher CMI was independently associated with advanced CKM (NHANES: OR 1.35, 95% CI 1.15-1.57; CHARLS: OR 1.86, 95% CI 1.70-2.04). In quartile analyses, the highest CMI quartile demonstrated the strongest associations compared to the lowest (NHANES: OR 1.72, 95% CI 1.30-2.26; CHARLS: OR 3.33, 95% CI 2.85-3.89). While the relationship was linear in NHANES, it was non-linear in CHARLS (P < 0.001), with a threshold effect at CMI = 0.509. Below this threshold, risk increased sharply (OR 3.879, 95% CI 2.137-7.040), whereas above it, the association was attenuated but remained significant (OR 1.528, 95% CI 1.360-1.717). CONCLUSIONS:CMI was associated with an increased risk of advanced CKM in two large, nationally representative cohorts. These findings support the potential utility of CMI in risk stratification. Future prospective studies are needed to confirm its predictive value and define clinically relevant thresholds.
OBJECTIVE:The aim of this study was to evaluate serum endothelin-1 (ET-1) and endothelin-2 (ET-2) levels in patients with dipper and non-dipper hypertension compared to normotensive controls and to investigate the potential diagnostic value of these biomarkers in distinguishing circadian blood pressure phenotypes. METHODS:This prospective case-control study included 163 participants classified into three groups based on 24-hour ambulatory blood pressure monitoring (ABPM): normotensive controls (n = 60), dipper hypertensive (n = 61), and non-dipper hypertensive (n = 42) patients. Dipper status was defined as a 10% nocturnal reduction in both systolic and diastolic blood pressure. Individuals with diabetes, established cardiovascular disease, or secondary hypertension were excluded. Serum endothelin-1 (ET-1) ET-1 and endothelin-2 (ET-2) ET-2 levels were analyzed using double-antibody sandwich ELISA kits. RESULTS:ET-1 levels were significantly lower in dipper hypertensive patients (p < 0.001) compared to other groups. Conversely, ET-2 levels did not significantly differ between hypertensive phenotypes. ET-1 proved to be a strong diagnostic marker for distinguishing non-dipper hypertension (AUC = 0.830, sensitivity 83.3%, specificity 75.4%). While advanced age independently predicted the non-dipper pattern (OR = 1.101, p = 0.002), BMI and D-dimer were associated with the dipper phenotype. CONCLUSION:This study identifies serum endothelin-1 is a strong, independent marker of the non-dipper hypertensive phenotype, which is associated with increased cardiovascular risk. The preservation of low endothelin-1 levels in dipper hypertension patients reflects intact endothelial and circadian regulation, whereas the absence of this response in non-dipper patients indicates impaired vascular adaptation. The inverse association of endothelin-2 with non-dipper status further suggests a protective buffering role that may be attenuated by increasing metabolic burden.
Objective This study examined differences in aldosterone responsiveness to adrenocorticotropic hormone (ACTH) between the unilateral aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (IHA) subtypes of primary aldosteronism (PA) and the impacts on vascular function and treatment outcomes.Methods This retrospective study enrolled 97 patients with PA (63 with APA and 34 with IHA) who underwent adrenal venous sampling (AVS) with ACTH stimulation. During AVS, baseline and ACTH-stimulated plasma aldosterone concentration (PAC) and cortisol levels were also assessed. Vascular function was assessed by measuring flow-mediated dilation (FMD). APA tissues were analyzed for KCNJ5 mutations.Results Among 97 patients with PA, those with APA showed higher baseline and ACTH-stimulated plasma aldosterone concentration levels, which correlated inversely with FMD. In patients with IHA, the logarithmic difference between PAC measurements before and after ACTH stimulation correlated positively with the blood pressure-normalization effect after mineralocorticoid receptor antagonist (MRA) therapy, with a cutoff value of 2.140 for predicting treatment response.Conclusion These findings suggest that ACTH-stimulated aldosterone may offer a useful marker for personalized management of PA, particularly in assessing vascular health and guiding MRA treatment.
