ADAM17 (A disintegrin and metalloproteinase 17) contributes to angiotensin-converting enzyme (ACE) 2 shedding in response to angiotensin II-AT1 receptor signaling, potentially shifting the renin-angiotensin system toward its pressor arm. We investigated whether ACE inhibitor (ACEI) or AT1 receptor blocker (ARB) therapy modulates ADAM17 expression. ADAM17 protein expression was evaluated by immunohistochemistry in alveolar type II pneumocytes of lung parenchymal samples from untreated control patients (n = 20) and patients treated with ACEI (n = 21) or ARB (n = 17; total ACEI/ARB-treated patients = 38). There were no significant differences in the proportion of ADAM17-expressing type II pneumocytes between patients without hypertension and ACEI/ARB-treated patients with hypertension (56.1 ± 4.3% vs 45.8 ± 3.1%, respectively). Similarly, no differences were observed according to smoking status (50.6 ± 4.1% in never smokers, 48.4 ± 4.0% in current smokers, and 50.8 ± 6.8% in former smokers) or sex (49.7 ± 4.2% in women vs. 49.1 ± 3.3% in men). In contrast, a significant age-related decline in the proportion of ADAM17-expressing type II pneumocytes was observed (56.2 ± 3.5% in patients <60 years vs. 43.0 ± 3.5% in patients ≥60 years; P = .005). These findings suggest that ACEI/ARB therapy, while targeting the pressor axis of the RAS, maintains ADAM17 expression at levels comparable to those in patients without hypertension. ACEI/ARB therapy may represent a potential strategy for the treatment of ADAM17-mediated cardiovascular, pulmonary, and inflammatory diseases.

Abstract Background Visit-to-visit blood pressure variability has been associated with cardiovascular outcomes; however, its role in predicting severe blood pressure (BP) elevation requiring emergency department care remains uncertain. We investigated whether long-term systolic blood pressure variability independently predicts severe BP elevation and evaluated externally validated prediction models. Methods We analyzed electronic health records from three tertiary hospitals. After excluding patients with cardiovascular events during a 2-year monitoring window, systolic blood pressure variability, quantified by standard deviation (SD), was assessed for incident severe BP elevation (systolic BP ≥ 180 mmHg or diastolic BP ≥ 120 mmHg at emergency department visits) during 5-year follow-up using landmark Cox models. Risk prediction models incorporating systolic blood pressure variability were developed and externally validated across institutions. Results Among 20,090 patients, 2,128 (10.6%) developed severe BP elevation. Each 1-SD increase in systolic blood pressure variability was independently associated with severe BP elevation (adjusted hazard ratio 1.21, 95% confidence interval 1.16-1.26; P &amp;lt; .001), irrespective of mean blood pressure and clinical covariates. The association was consistent across major subgroups. Prediction model incorporating blood pressure variability achieved good discrimination in external validation cohorts (area under the curve 0.763 [Guro] and 0.765 [Anam]). Conclusions Visit-to-visit blood pressure variability independently predicts severe hypertensive destabilization beyond mean blood pressure. These findings suggest that incorporating visit-to-visit blood pressure variability into clinical assessment may improve identification of patients at risk for severe hypertensive episodes.

Hypertension is a leading global cause of cardiovascular, renal, and cerebrovascular morbidity. Beyond classical genetic and environmental determinants, accumulating evidence highlights epigenetic regulation as a key contributor to blood pressure control and vascular pathology. Epigenetic mechanisms including DNA methylation, histone post-translational modifications, and non-coding RNAs govern gene expression without altering the underlying DNA sequence, thereby linking environmental and physiological stimuli to stable transcriptional changes. Aberrant epigenetic signatures have been identified in vascular, renal, and endocrine tissues integral to blood pressure regulation, influencing pathways that mediate vascular tone, sodium handling, oxidative stress, and inflammation. Among these, differential methylation and histone modification of renin angiotensin aldosterone system (RAAS) genes, including AGT, REN, ACE, and AT1R, have been shown to promote sustained activation of vasoconstrictive and sodium-retentive signaling cascades. Chronic exposure to a high-salt diet (HSD) represents a potent environmental modifier of this epigenetic landscape. Excess dietary sodium can alter CpG methylation patterns, histone acetylation states, and microRNA profiles across multiple tissues, leading to enhanced RAAS activity and vascular dysfunction. These HSD-induced alterations often persist despite subsequent sodium normalization, reflecting an enduring "epigenetic memory" of dietary stress that contributes to salt-sensitive hypertension. Understanding how HSD and other environmental factors reprogram RAAS-related gene networks through epigenetic mechanisms provides critical insight into the molecular basis of hypertension. Moreover, these findings open new avenues for therapeutic intervention utilizing DNA methyltransferase and histone deacetylase inhibitors, as well as RNA-based precision therapies aimed at reversing the maladaptive epigenetic imprint underlying chronic blood pressure elevation.

Abstract OBJECTIVE To analyze the composition and characteristics of ocular surface microbiota in patients with essential hypertension based on high-throughput sequencing of 16S rDNA, and provide new ideas for the prevention and treatment of hypertension-related eye diseases. METHODS Sixty patients with essential hypertension who visited the outpatient department of Zigong First People’s Hospital from July 2022 to December 2022 were selected as the hypertension group (HTN group), and 30 healthy volunteers from the same period were selected as the control group (Ctrl group). High-throughput sequencing technology was used to detect the V3–V4 variable regions of the 16S rDNA gene in ocular surface bacteria, and the differences between the two groups were compared. RESULTS A total of 6,544,987 valid sequences and 3,748 operational taxonomic units (OTUs) were obtained through sequencing, including 1,296 OTUs unique to the HTN group and 476 OTUs unique to the Ctrl group. Diversity analysis showed that the abundance-based coverage estimator index [494.03 (356.68, 888.36) vs. 385.86 (333.99, 502.88), Z = −2.019, P = 0.043] and Chao1 index [387.50 (260.00, 558.10) vs. 343.15 (256.45, 413.55), Z = −2.009, P = 0.045] of the HTN group were higher than those of the Ctrl group, and β diversity analysis revealed distinct microbial community structures between the two groups (P &amp;lt; 0.05). The analysis of relative abundance of microbiota showed that the abundance of actinobacteria [0.203 (0.123, 0.319) vs. 0.117 (0.058, 0.181), Z = −2.441, P = 0.015] and corynebacterium [0.123 (0.051, 0.230) vs. 0.034 (0.017, 0.100), Z = −2.822, P = 0.004] in the HTN group was significantly higher than that in the Ctrl group. Characteristic bacterial linear discriminant analysis showed that compared with the Ctrl group, the abundance of actinobacteria, actinobacteria, corynebacteriales, and corynebacteriaceae in the HTN group increased. Functional analysis revealed that 14 pathways were enriched in the HTN group, including nicotinate and nicotinamide metabolism, arachidonic acid metabolism, and riboflavin metabolism. CONCLUSIONS The ocular surface microbiota of hypertensive patients has changed significantly in diversity, relative abundance and characteristic fungi compared with healthy individuals.

Over one-third of Canadians with hypertension do not achieve recommended blood pressure (BP) targets despite availability of effective treatments. Renal sympathetic nerve denervation (RDN) is a recently approved, minimally invasive treatment for hypertension being offered in multiple Canadian centers. How best to implement this procedure in contemporary Canadian clinical practice remains unclear. Herein, we provide a Canadian hypertension specialist viewpoint on use of RDN in Canada. We review the rationale for, and evidence supporting, the use of RDN and discuss, using two clinical cases, its potential therapeutic role. We note that RDN has effectively lowered BP in multiple, sham-controlled, randomized clinical trials and has a favourable safety profile. Economic modeling estimates that it is cost-effective in the Canadian context. Conversely, the BP lowering effect is relatively modest; no well-established method to pre-identify responders exists; cardiovascular endpoint data supporting use of RDN are lacking; and no clear funding model is currently in place in Canada. Accordingly, we suggest that use of RDN be reserved for willing patients with severely elevated BP despite the use of first-line conventional therapies who have had secondary causes excluded. Examples include patients with resistant hypertension or moderate or severe hypertension and multiple drug intolerance syndrome. In view of its recent approval and known operator-dependency, RDN should be offered solely through programmatic, multidisciplinary collaboration between hypertension specialists and experienced interventionalists using a shared decision-making approach with the patient. Funding deployment should target such programs and sites should carefully monitor their outcomes to confirm comparability to the published literature.

The Hiroshima Registry for Evaluation and Treatment of Nocturnal and Early Morning Hypertension (Hiroshima NOCTURNE) was a prospective, multicenter study designed to determine whether elevated nighttime blood pressure (BP), assessed using a home BP monitoring (HBPM) device, can be normalized through active antihypertensive therapy in patients already receiving antihypertensive medication. In this subanalysis, we aimed to identify factors associated with failure to normalize nocturnal hypertension. Patients with nocturnal hypertension at baseline who underwent a 6-month intervention based on nighttime BP were included. Nocturnal hypertension was defined as a mean nighttime systolic BP of ≥120 mmHg. Treatment decisions were left to the discretion of the attending physicians. Among the 90 patients with baseline nocturnal hypertension, 42 (46.7%) failed to achieve normalization (<120 mmHg) after the intervention. In the multivariable analysis, higher baseline nighttime systolic BP (OR 1.07, 95% CI, 1.001-1.15, P = .046) and baseline diuretic use (OR 3.99, 95% CI, 1.17-13.6, P = .03) were significantly associated with failure to normalize nocturnal hypertension. Diabetes mellitus tended to be associated with the failure to normalize nocturnal hypertension (OR 3.01, 95% CI, 0.93-9.72, P = .06). Participants using diuretics at baseline and those with diabetes mellitus were already receiving multiple antihypertensive medications, and additional drug classes were not often prescribed during the intervention. In patients already receiving antihypertensive medication, failure to normalize nocturnal hypertension despite treatment guided by nighttime BP measurements was associated with elevated baseline nighttime BP, diuretic use, and possibly diabetes mellitus. These findings highlight the need for more individualized therapeutic approaches, particularly in patients receiving diuretics or those with diabetes mellitus. University Hospital Medical Information Network Clinical Trials Registry (UMIN000019173).

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

Abstract OBJECTIVE To analyze the distribution characteristics of genotypes and alleles of the sodium channel epithelial 1 subunit gamma (SCNN1G) gene in patients with essential hypertension, and to investigate the relationship between these polymorphisms and 24-hour urinary sodium (24h-UNa) excretion and blood pressure. METHODS A total of 511 patients diagnosed with essential hypertension at Yan’an Hospital Affiliated to Kunming Medical University between May 2018 and August 2021 were selected. Twenty-four-hour urinary electrolytes were collected from the patients, and the SCNN1G gene was tested. Linear regression analysis was used to examine the relationship between the SCNN1G gene and blood pressure/24h-UNa. The generalized multifactor dimensionality reduction (GMDR) method was used to analyze gene–environment interactions involving the SCNN1G gene. RESULTS Compared with individuals with the WM genotype of the SCNN1G gene rs4299163 locus, individuals with the MM genotype had a lower 24h-UNa excretion ([160.69 ± 82.11] vs. [189.46 ± 91.36] mmol, P &amp;lt; 0.05). Compared with individuals with the WM genotype of the SCNN1G gene rs4499238 locus, individuals with the MM genotype had a lower 24h-UNa excretion ([160.16 ± 81.35] vs. [191.05 ± 93.06] mmol, P &amp;lt; 0.05). Compared to individuals with the WW or WM genotype at the SCNN1G gene rs5735 locus, those with the MM genotype had significantly higher 24h-UNa excretion ([208.53 ± 79.75] vs. [164.74 ± 89.58], [164.55 ± 68.43] mmol, respectively; both P &amp;lt; 0.05). Statistically significant differences were observed in 24-hour systolic blood pressure (SBP), daytime SBP, and daytime diastolic blood pressure (DBP) among patients with different genotypes at the SCNN1G gene loci (P&amp;lt; 0.05). However, no statistically significant difference was found in nighttime DBP (P &amp;gt; 0.05). Multiple linear regression analysis revealed that gender (B = −24.556, P = 0.001), body mass index (B = 2.639, P = 0.013), 24-hour urinary potassium excretion (B = 0.589, P&amp;lt;0.001), and the SCNN1G gene rs5735 locus (B = 40.649, P = 0.039) were influencing factors for 24h-UNa excretion. Furthermore, gender, age, and 24h-UNa excretion were influencing factors for both 24-hour SBP and 24-hour DBP (P &amp;lt; 0.05). GMDR analysis identified that the interaction models constructed from rs40739309, rs7404408, rs4299163, rs5735, and environmental factors (age, gender, body mass index), and constructed from rs40739309, rs7404408, rs4299163, rs4073291, rs5735, and environmental factors (age, gender, body mass index) were the optimal models, demonstrating the best training accuracy, testing accuracy, and cross-validation consistency. CONCLUSIONS Different genotypes at the SCNN1G rs4299163, rs5735, and rs4499238 loci are associated with 24h-UNa excretion. Interactions exist between various SCNN1G loci and environmental factors, which synergistically contribute to elevated blood pressure.