American Journal of Hypertension最新文献

Background: This study investigates the causal associations between specific plasma lipids, immune cells, and aortic dissection (AD) pathogenesis, and explores immune cells as mediators in this relationship.

Methods: This study used two-sample Mendelian Randomization (MR) to examine causal links between plasma lipids, immune cells, and AD. SNPs served as instrumental variables, selected based on GWAS data with significance (P < 1e-5). AD outcomes were sourced from FinnGen, while data on 179 plasma lipids and 731 immune cells came from GWAS. IVW was the main analysis method, with sensitivity tests for heterogeneity and pleiotropy. Mediation MR assessed immune cells as mediators in the liposome-AD pathway, with mediation ratios calculated to quantify their effects. Analyses were conducted in R using the "Two Sample MR" package.

Results: MR analysis identified eight plasma lipids with significant causal associations with AD. Of these, three plasma lipids, including Phosphatidylinositol (16:0_18:1), increased AD risk (OR: 1.61 [1.22 to 2.12], P = 0.0007), while five others showed protective effects. Analysis revealed 38 immune cell types with causal links to AD, 22 as risk factors and 16 as protective factors. Transitional %B cells mediated 7.9% of the effect between Phosphatidylinositol (16:0_18:1) and AD.

Conclusions: This study used MR to identify plasma lipids linked to AD, with Phosphatidylinositol (16:0_18:1) showing the strongest effect. While some immune cells (e.g., Transitional %B cells) were associated with AD, their mediating role was limited and requires further validation. Future AD prevention should focus on lipid regulation while considering potential immune involvement.

Background: Thoracic aortic dissection (TAD) is a potentially fatal condition. It has been linked with hypertension, and guidelines recommend antihypertensives.

Methods: Electronic searches were conducted in MEDLINE and EMBASE with the following search strategy: (("thoracic aortic dissection"[Mesh]) AND ("antihypertensive agents"[Mesh] from database inception to August 2024.

Results: Hypertension is associated with a significant risk of TAD with a hazard ratio (HR) of 2.51 (95% CI: 1.75-3.60). Beta-blocker treatment produces a significant (P < 0.01) lower risk of an MACE HR of 0.55 (95% CI = 0.39-0.77). Angiotensin receptor blockers (ARBs) or ACE inhibitors also lower the risk of a major adverse cardiac event with a HR of 0.67 (95% CI = 0.58-0.78). Calcium channel blockers (CCB) significantly (P =0.0007) lowered MACE outcomes with a HR of 0.66 (95% CI = 0.53-0.84). A network meta-analysis was performed to evaluate the relative risk of aortic events associated with commonly prescribed antihypertensive agents, using beta-blockers (BB) as the reference comparator. Compared to BB, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB) were associated with a non-significant increase in risk (HR 1.28, 95% confidence interval (CI): 0.91-1.81). CCB also demonstrated a non-significant reduction in risk (HR 0.68, 95% CI: 0.33-1.40) to BBs.

Conclusions: Hypertension is strongly associated with a risk of TAD. Beta-blockers are associated with the greatest reduction in MACE and remain the most effective first-line therapy for patients at risk of TAD. ACE inhibitors and ARBs also demonstrate benefit.

Background: Evidence syntheses on the associations between blood pressure (BP) parameters and cognitive decline and/or dementia have taken different methodological approaches and targeted different BP parameters and outcomes. The aim of this umbrella review was to provide a high-level synthesis of published systematic reviews with meta-analyses on these associations.

Methods: PubMed, Embase, PsycINFO, and Cochrane were searched up to April 2025 for eligible reviews. Risk of bias was assessed using the AMSTAR-2 tool and overlap of constituent studies between reviews was explored.

Results: Among 31 included reviews, eight reported positive associations between higher BP and greater incidence of cognitive decline or dementia, five drew neutral conclusions, and one reported an inverse relationship. Greater mid-life BP was associated with greater risk of all-cause dementia, whereas late-life hypertension might have a mixed or overall neutral association. Three reviews reported associations between higher BP variability and all-cause dementia, and two for cognitive decline. Reviews also reported associations between higher pulse wave velocity and orthostatic hypotension and poorer outcomes. No reviews examined pulse pressure, mean-arterial pressure or cumulative BP load. Most reviews were of low quality, with considerable heterogeneity in BP parameter definitions and outcome criteria. Overlap of constituent studies for each BP parameter was low.

Conclusions: In addition to high BP, incorporating variability, pulse wave velocity and orthostatic hypertension into risk assessments of cognitive decline or dementia and adopting standardized definitions for BP parameters and cognitive outcomes may improve comparability across future studies and strengthen clinical guidance.

Background: Salt-sensitive hypertension (SSHT) is associated with reduced expression of SIRT3 and promotes endothelial-mesenchymal transition (EndMT). Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin (DAPA), have been shown to ameliorate high-salt-induced hypertension. We hypothesized that DAPA attenuate SSHT-induced EndMT and reduce myocardial fibrosis by upregulating SIRT3 expression. This study aims to provide new insights into the mechanisms underlying the cardioprotective effects of SGLT2 inhibitors in hypertension.

Methods: Seven-week-old male Dahl salt-sensitive rats were fed either a high-salt diet (8% NaCl; HSD group), a normal-salt diet (0.3% NaCl; NSD group), or an HSD supplemented with DAPA (2 mg/kg/day administered via drinking water). Systolic blood pressure (SBP) was measured, and left atrial tissue was examined for fibrosis and the expression of SIRT3 and EndMT-related markers, including CD31, Snail, FSP1, Twist, VE-cadherin, and α-SMA.

Results: Compared with the NSD group, the HSD group exhibited increased SBP, left atrial end-systolic volume index (LAESVI), incidence and duration of atrial fibrillation (AF), and atrial fibrosis. Expression of α-SMA, Snail, FSP1, and Twist was elevated, while SIRT3, CD31, and VE-cadherin expression were decreased, along with reduced left atrial ejection fraction (LAEF) and left atrial function index (LAFI). DAPA treatment reversed these changes.

Conclusions: Our findings indicate that a high-salt diet decreases SIRT3 expression, induces EndMT, and promotes myocardial fibrosis in SSHT rats. DAPA mitigates high-salt-induced EndMT and fibrosis-related AF by upregulating SIRT3, suggesting a potential mechanism for the cardioprotective effects of SGLT2 inhibitors in SSHT.

Background: Out-of-office blood pressure (BP) monitoring is recommended for hypertension management. Home BP monitoring (HBPM), which involves patients measuring their BP and transmitting readings to their provider, remains underutilized. We sought to understand how HBPM is utilized in routine clinical care and factors associated with enrollment in a national HBPM program.

Methods: We conducted a retrospective study of Veterans with uncontrolled BP (systolic BP > 140mmHg) in the Veterans Health Administration (VHA) from 2013-2019. We identified patient-, provider- and systems-level factors associated with enrollment in the HBPM program and with duration of monitoring and number of BPs transmitted.

Results: Among 1,759,851 Veterans meeting eligibility criteria, 63,361 (3.6%) were enrolled in HBPM. Black race, Hispanic ethnicity, and higher systolic BP at the eligible primary care visit were associated with higher likelihood of enrollment. Older age and living in an area with lower socioeconomic status were associated with lower likelihood of enrollment. Non-physician providers, providers with higher percent of patients with controlled BP, and providers at VA medical center main campuses were more likely to enroll patients in the HBPM program. The average number of BPs transmitted in the first four weeks of monitoring was 25.0; the median duration of HBPM was 192 days. Older age was associated with transmission of more BP measurements and longer duration of HBPM.

Conclusion: HBPM is underutilized in eligible VHA patients. Older age was associated with lower likelihood of enrollment but greater number of transmitted BPs. Interventions to improve HBPM utilization could focus on provider and facility factors.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for the treatment of type 2 diabetes and, more recently, for weight management among individuals without diabetes. Beyond their metabolic effects, growing evidence suggests that GLP-1 RAs produce modest reductions in blood pressure (BP), typically 2 to 5 mmHg systolic, across diverse populations with diabetes, obesity, or at high cardiovascular risk. These reductions appear to be driven primarily by weight loss, with additional contributions from potential weight-independent mechanisms such as natriuresis, improved endothelial function, and attenuation of vascular inflammation. Although smaller in magnitude than those achieved with traditional antihypertensive drugs, the BP-lowering effects of GLP-1 RAs can translate into meaningful cardiovascular risk reduction at the population level and provide additive BP benefit when used alongside conventional therapies. Among individuals with hypertension, GLP-1 RAs are generally well tolerated, although small increases in heart rate and potential interactions with volume-regulating medications may warrant clinical attention. This review the synthesizes current evidence on the mechanisms by which GLP-1 RAs affect BP, their clinical effects across populations, and the implications for patient care. We discuss subpopulations who may benefit from their BP-lowering effects, identify limitations in the existing evidence, and explore future directions for research. As newer GLP-based therapies continue to emerge, a clearer understanding of their effects on BP may inform more integrated approaches to cardiometabolic care.

Background: Sex differences in blood pressure (BP) regulation may modify associations between BP variability (BPV) and hypertension-mediated organ damage (HMOD), but organ-specific effects remain unclear.

Methods: We studied 398 hypertensive patients from a multicenter home BP monitoring registry. The office-home BP difference (ΔBP = office-home) was analyzed as a single continuous exposure variable, with positive values indicating the white-coat effect and negative values indicating the masked effect. Multivariable regression examined sex-specific associations of BPV patterns with HMOD, including electrocardiographic left ventricular hypertrophy (ECG-LVH) and microalbuminuria/proteinuria.

Results: Women demonstrated higher home systolic BPV than men despite similar mean BP levels (p < 0.01). Office BP was the primary determinant of white-coat phenotypes (office SBP: adjusted odds ratio [aOR] 1.29 [95% CI: 1.22-1.37]; office DBP: aOR 1.27 [1.19-1.37], both P < 0.01), while home BP predicted masked phenotype (home SBP: aOR 1.23 [1.12-1.39]; home DBP: aOR 1.34 [1.23-1.48], both P < 0.01). White-coat effects showed protective associations with total HMOD (systolic aOR 0.97 [0.94-1.00], P < 0.05), while office BPV demonstrated consistent positive associations (systolic aOR 1.10 [1.05-1.16]; diastolic aOR 1.12 [1.05-1.20], both P < 0.01). Critically, significantly sex interaction emerged for ECG-LVH, while microalbuminuria/proteinuria showed consistent associations across sexes.

Conclusions: Sex fundamentally modifies BP patterns-HMOD relationships in an organ-specific manner. Cardiac target organ damage requires sex-attentive monitoring approaches, while renal damage shows universal associations with office BPV. These findings support precision medicine approaches to hypertension management incorporating sex-specific BP assessment strategies.

Background and objective: Hypertensive disorders of pregnancy (HDP) substantially increase maternal and fetal morbidity and mortality. Although reduced circulating bioavailable testosterone (BT) has been observed in women with HDP, the causal relationship and underlying mechanisms remain unresolved. Based on previous clinical and experimental evidence, we hypothesized a potential causal relationship between BT levels and HDP, with subsequent analyses designed to explore the possible metabolic and anti-inflammatory pathways involved.

Methods: Summary statistics for BT and HDP were obtained from the IEU OpenGWAS database. A two-sample Mendelian randomization (MR) framework was implemented to evaluate causality, complemented by extensive sensitivity analyses to strengthen robustness. To explore potential mechanisms, expression quantitative trait loci (eQTL) integration, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network analyses were performed.

Results: MR analyses provided evidence of a protective causal effect of BT on HDP (IVW OR = 0.81, 95% CI: 0.68-0.97, P = 0.023), with no indication of reverse causality. Sensitivity tests consistently confirmed the reliability of these findings. Genes associated with BT-related SNPs were enriched in metabolic and immune pathways, notably the NOD-like receptor and IL-17 signaling pathways. Within the PPI network, NFKBIA emerged as a pivotal regulator of NF-κB signaling, thereby supporting a role for testosterone-mediated modulation of inflammation in HDP protection.

Conclusion: From a genetic standpoint, BT appears to act as a protective factor against HDP, potentially safeguarding cardiovascular function through interconnected metabolic and anti-inflammatory mechanisms.