Lower Systolic Blood Pressure Research Articles

Genetic variation in CCDC93 is associated with elevated central systolic blood pressure, impaired arterial relaxation, and mitochondrial dysfunction.

Genetic studies of blood pressure (BP) traits to date have been performed on conventional measures by brachial cuff sphygmomanometer for systolic BP (SBP) and diastolic BP, integrating several physiologic occurrences. Genetic associations with central SBP (cSBP) have not been well-studied. Genetic discovery studies of BP have been most often performed in European-ancestry samples. Here, we investigated genetic associations with cSBP in a Chinese population and functionally validated the impact of a novel associated coiled-coil domain containing 93 (CCDC93) gene on BP regulation. An exome-wide association study (EWAS) was performed using a mixed linear model of non-invasive cSBP and peripheral BP traits in a Han Chinese population (N = 5,954) from Beijing, China genotyped with a customized Illumina ExomeChip array. We identified four SNP-trait associations with three SNPs, including two novel associations (rs2165468-SBP and rs33975708-cSBP). rs33975708 is a coding variant in the CCDC93 gene, c.535C>T, p.Arg179Cys (MAF = 0.15%), and was associated with increased cSBP (β = 29.3 mmHg, P = 1.23x10-7). CRISPR/Cas9 genome editing was used to model the effect of Ccdc93 loss in mice. Homozygous Ccdc93 deletion was lethal prior to day 10.5 of embryonic development. Ccdc93+/- heterozygous mice were viable and morphologically normal, with 1.3-fold lower aortic Ccdc93 protein expression (P = 0.0041) and elevated SBP as compared to littermate Ccdc93+/+ controls (110±8 mmHg vs 125±10 mmHg, P = 0.016). Wire myography of Ccdc93+/- aortae showed impaired acetylcholine-induced relaxation and enhanced phenylephrine-induced contraction. RNA-Seq transcriptome analysis of Ccdc93+/- mouse thoracic aortae identified significantly enriched pathways altered in fatty acid metabolism and mitochondrial metabolism. Plasma free fatty acid levels were elevated in Ccdc93+/- mice (96±7mM vs 124±13mM, P = 0.0031) and aortic mitochondrial dysfunction was observed through aberrant Parkin and Nix protein expression. Together, our genetic and functional studies support a novel role of CCDC93 in the regulation of BP through its effects on vascular mitochondrial function and endothelial function.

Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study.

Left ventricular hypertrophy (LVH) is frequently detected via echocardiography in individuals with Fabry disease (FD), sometimes leading to confusion with hypertrophic cardiomyopathy (HCM) of other aetiologies. Considering this diagnosis challenge, FD should be included in the list of differential diagnosis for patients presenting with LVH. To address this concern, we conducted a prospective screening study in China, using dried blood spot (DBS) testing, to evaluate patients with unexplained LVH. Our study was designed as a nationwide, multicentre prospective investigation. A total of 1015 patients from 55 different centres who were diagnosed with LVH by echocardiography were screened in the study from September 2022 to December 2023. Demographic information, biochemistry data, echocardiography parameters and clinical observations were meticulously collected from all participants. The DBS method was used to assess α-galactosidase A (α-Gal A) activity in males and both α-Gal A and globotriaosylsphingosine (lyso-Gb3) levels in females. The final screening population included 906 patients (589 males, 65%) with LVH, characterized by a mean maximal myocardial thickness of 14.8±4.6mm and an average age of 56.9±17.2years. In total, 43 patients (38 males, 5 females) exhibited low α-Gal A activity measurement (<2.2μmol/L), while 21 patients (10 males, 11 females) presented low α-Gal A activity or elevated lyso-Gb3 levels (>1.1ng/mL). Among these patients, eight individuals (7 males and 1 female) were genetically confirmed to harbour pathogenic GLA mutations, resulting in a total prevalence of 0.88%. Compared with patients without FD, patients with FD tended to have proteinuria (75% vs. 21.2%, P=0.001), family history of HCM (37.5% vs. 2.3%, P<0.01) and neuropathic pain (37.5% vs. 4.4%, P<0.01) but lower systolic blood pressure (118.5±12.5 vs. 143.3±29.3mmHg, P=0.017). Five mutations were previously recognized as associated with FD while the remaining two, p.Asp313Val (c.938A>T) and c.547+3A>G, were deemed potentially pathogenic. Subsequent familial validation post-diagnosis identified an additional 14 confirmed cases. This pioneering screening study for FD among Chinese patients with unexplained LVH using DBS measurement, revealed an FD detection rate of 0.88%. Our findings confirmed that the combined measurement of lyso-Gb3 and α-Gal A activity is beneficial for primary screening of FD in patients with LVH. Given the availability of efficacious therapies and the value of cascade screening in extended families, early detection of FD in LVH patients is clinically important.

P099 EXERCISE TRAINING FURTHER ATTENUATES BLOOD PRESSURE VARIABILITY AND RENAL DAMAGE IN HYDROCHLOROTHIAZIDE TREATED-HYPERTENSIVE AND POSTMENOPAUSAL RATS

Background and Objective: Considering that blood pressure variability (BPV) has been associated with damage to target organs such as the kidney, this study aimed to investigate the effects of hydrochlorothiazide (HCTZ) combined with exercise training (CET) on BPV, as well as renal tissue morphology, function, inflammation, and oxidative stress. Methods: Female spontaneously hypertensive rats (SHR) were divided into 4 ovariectomized groups (n=5-6/group): sedentary (OS), sedentary + HCTZ (OSH), trained (OT), and trained + HCTZ (OTH). Both HCTZ (3 mg/kg) and CET (3 days/week) were administered for 8 weeks. Blood pressure was directly recorded for BPV analysis. Results: Renal function, morphology, inflammation and oxidative stress were assessed. The OSH, OT, and OTH groups had lower systolic BP (OSH: 189±13; OT: 179±5; OTH: 174±15 mmHg) compared to the OS group (208±15 mmHg). Only the combination of the drug with CET promoted a reduction in BPV variance. The HCTZ-treated groups showed lower plasma creatinine levels and increased creatinine clearance compared to the OS group. Treated groups showed a reduction in fields of 51–100% of interstitial tubule fibrosis when compared to the OS group; and the OTH group also showed reduction in fields in the range of 26–50% vs. other groups. The HCTZ-treated groups showed a reduction in protein oxidation. Renal catalase and IL10/TNF-alpha ratio were increased in the OTH group. Positive correlations were obtained between SBP variance and SBP (r=0.72), plasma creatinine (r=0.58), and levels of TNF-α (r=0.69), hydrogen peroxide (r=0.61), and protein oxidation (r=0.66) in renal tissue. Conclusions: Our results highlight the enhanced efficacy of the combination of HCTZ and CET compared to the use of either drug alone in the model studied. This combination effectively reduced BPV, resulting in beneficial changes in renal inflammatory and redox profiles, inducing morphological and functional benefits in hypertensive ovariectomized rats. Financial support: FAPESP (2022/04050-1), CNPq, CAPES-PROSUP, UNINOVE.

Lung ultrasonography underdiagnoses clinically significant pneumothorax

BackgroundUltrasonography for trauma is an integral part of the Advanced Trauma Life Support algorithm and supported extensively in the literature. The reliability of chest ultrasonography as a screening examination for pneumothorax during initial trauma evaluation is unclear. We performed a prospective study where we hypothesized that chest ultrasonography would have low sensitivity for detecting clinically significant pneumothorax. MethodsA prospective observational analysis of patients with blunt chest trauma at a level 1 trauma center was performed. Patients included had supine chest radiography and chest ultrasonography performed prior to intervention as well as confirmatory computed tomographic imaging. All chest ultrasonography was performed in the trauma bay by a registered sonographer. All imaging was evaluated by an attending trauma surgeon and radiologist in real time. ResultsOf 2,185 patients screened with a diagnosis of blunt thoracic trauma, 1,489 patients had chest radiography, chest ultrasonography, and confirmatory computed tomography and were included for analysis. Patients were 71% male, with median age of 42 years, and mean Injury Severity Score of 6. The sensitivity of chest ultrasonography to detect pneumothorax was low. Chest ultrasonography had a false negative rate of 72% (n = 58), with 22% (n = 13) undergoing tube thoracostomy. Patients with false negative examinations had lower initial O2 saturation and systolic blood pressure and were more likely to have rib fractures compared with true negative chest ultrasonography examinations. ConclusionChest ultrasonography performed on initial trauma evaluation has low sensitivity with a high rate of false negative examinations. Because many of these false negative results are clinically significant requiring thoracostomy, using chest ultrasonography alone to screen for pneumothorax should be done with caution.

Abstract P440: Discovery of clinical candidate GSC002219, a highly selective oral CYP11B2 inhibitor for hypertension

Background: Aldosterone is an important mediator of hypertension and its aberration could contribute to heart and kidney diseases. Aldosterone synthase inhibitors (ASI) attenuate the production of aldosterone directly and have been proposed as an alternative to mineralocorticoid receptor antagonists (MRA) for treatment of resistant hypertension and chronic renal disease. GSC002219 is a potent inhibitor of aldosterone synthase (CYP11B2) with high selectivity over the closely related enzyme CYP11B1. The aim of the study was to evaluate the effect of GSC002219 on aldosterone and blood pressure. Methods: The inhibitory effect of GSC002219 against CYP11B2 and CYP11B1 proteins was assessed in human renal leiomyoblastoma cells expressing recombinant human / cynomolgus CYP11B1or CYP11B2 enzymes, respectively. GSC002219 was further evaluated in Synacthen (ACTH) challenged cynomolgus monkey model for its effects against various related key biomarkers including cortisol, aldosterone and precursors. The effects of GSC002219 on systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated in stroke-prone spontaneously hypertensive rat (SHRSP) model. Results: GSC002219 potently inhibits CYP11B2 with an IC 50 of 27nM, while maintains a &gt;150-fold selectivity over CYP11B1. In ACTH challenged cynomolgus monkey model, single oral doses of GSC002219 at 0.03 mg/kg and 0.1 mg/kg could suppress aldosterone production to 80% and 93%, respectively, comparing to vehicle-treated animals without any effect towards cortisol levels. In the rat SHRSP hypertension model, GSC002219 could effectively lower both SBP and DBP. GSC002219 has an excellent in vitro ADME and toxicology profile as well as a balanced physicochemical property. In 14-day rat and monkey toxicology studies, GSC002219 displayed good tolerance, excellent PK profile and a great safety window (&gt;100 fold). Conclusions: Taken together, GSC002219 is a safe and potent inhibitor of CYP11B2 and efficacious in various disease models of hypertension. GSC002219 is under IND-enabling study and may enter the clinical development early 2025.

Association of the ABCG2 rs2231142 variant with the Framingham Cardiovascular Disease Risk score in the Taiwanese population

BackgroundSerum uric acid (SUA) is an important predictor of cardiovascular events and mortality. The ABCG2 rs2231142 variant (TT genotype) is associated with hyperuricemia (HUA), but the relationship between ABCG2 gene polymorphisms and coronary artery disease (CAD) risk is poorly elucidated. We investigated the association between ABCG2 rs2231142 genetic variants and the Framingham Risk Score for Cardiovascular Disease (FRS-CVD) in a Taiwanese population. MethodsThis cross-sectional study enrolled 139,508 Taiwanese participants aged 30–70 years based on data from the Taiwan Biobank (TWB) database that was obtained from questionnaires, laboratory investigations, anthropometry, and Affymetrix TWB genome-wide single-nucleotide polymorphism (SNP) chip data analysis. The association between ABCG2 rs2231142 and FRS-CVD risk was evaluated using logistic regression analysis. ResultsCompared to those with the GG genotype, participants with the ABCG2 rs2231142 TT genotype had a significantly lower systolic blood pressure, smoking rate, body mass index, triglyceride level, waist circumference, waist–hip ratio, and body fat percentage, but had higher high-density lipoprotein cholesterol level. Despite the same FRS-CVD score, participants with TT genotypes had higher SUA. Even with the same SUA, TT carriers had a lower FRS-CVD than GT and GG carriers. Participants with the TT genotype had significantly lower CVD risk, particularly female participants with HUA and BMI <27 (OR: 0.760, 95 % CI: 0.587–0.985; p = 0.0381) group. ConclusionThe ABCG2 rs2231142 TT genotype is associated with a lower FRS-CVD, particularly in non-obese hyperuricemic female individuals. The complicated interplay among genetic variations, metabolic profile, and CVD risk provides insights for precision health.

Abstract P166: Genetic Ablation of the Bile Acid Receptor- Takeda G-protein Coupled Receptor 5 (TGR5) Promotes Weight Gain but Lowers Hypertension

Introduction: TGR5 belongs to G-protein coupled receptor family, that mediates bile acid signaling. Activation of TGR5 by bile acids triggers intestinal glucagon-like peptide-1 secretion, whereby pharmacological activation of TGR5 constitutes a promising incretin-based strategy for the treatment of metabolic disorders. Hypertension is one of the hallmark features of metabolic disorders. We previously reported that hypertension is associated with lower conjugated bile acids, which are ligands for TGR5. Therefore, we hypothesized that lack of activation of TGR5-mediated bile acid signaling promotes not only body weight gain, but also hypertension. Methods: CRISPR/Cas9 technology was used to generate Tgr5 -/- rats from hypertensive Dahl Salt-sensitive (S) rats. Twenty-four-hour blood pressure (BP) readings of 8-weeks-old control female Tgr5 +/+ S rats and age-matched female Tgr5 -/- S rats (n=7/group) were monitored by radiotelemetry for 4 weeks. Body weight, food intake, and water intake were recorded every week. At the end of the study, vascular function was examined using wire myography of dorsal and mesenteric resistance arteries, cardiac function was assessed by echocardiography, and microbiota profiling was conducted via fecal 16S rRNA gene sequencing using Miseq. Results: In support of our hypothesis, despite no difference in food and water intake, at 4 weeks, the body weights of Tgr5 -/- S rats were significantly higher compared to Tgr5 +/+ S rats (236.3gm vs. 225.4gm; p&lt;0.01). Surprisingly, in contrast to our hypothesis, at 4 weeks, Tgr5 -/- S rats had significantly lower systolic BP (151.8mmHg vs. 156.9mmHg, p&lt;0.0001), diastolic BP (107.9mmHg vs. 115.5mmHg, p&lt;0.0001), and mean arterial BP (128.8mmHg vs. 134.9mmHg, p&lt;0.0001) compared to Tgr5 +/+ S rats. However, no significant differences were observed either in vascular reactivity or cardiac function between the groups. Interestingly, fecal microbiota analysis revealed that Tgr5 -/- S rats presented with significant remodeling of gut microbiota with lower α-diversity (observed features; p=0.05), b-diversity (Bray-Curtis; p&lt;0.05, Jaccard; p&lt;0.01), and higher relative abundance of the BP-lowering genera Akkermansia . Conclusion: Our study revealed that deletion of TGR5 resulted in weight gain but lowered BP. It implies that activation of TGR5 may be a risk factor for raising BP. The mechanism by which TGR5 regulates BP seem independent of changes in vascular or cardiac function but is likely mediated by gut microbiota.

Indian Consensus on the Role and Position of Angiotensin Receptor-neprilysin Inhibitors in the Management of Heart Failure.

The incidence of heart failure (HF) in India is estimated to be 0.5-1.7 cases per 1,000 people per year, and approximately 4,92,000-1.8 million new cases are detected every year. Despite the high rate of mortality associated with HF, most patients do not receive maximal guideline-directed medical therapy (GDMT). Current guidelines advocate early multidrug combination therapy with four classes of drugs, namely, beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium-glucose transport protein 2 inhibitors (SGLT-2is), particularly in patients with heart failure with reduced ejection fraction (HFrEF). ARNIs reduce cardiac morbidity and mortality in patients with HFrEF. However, recent data indicated that only 4.8% of patients with HFrEF receive ARNI in India. Hence, at a national consensus on HF meeting, cardiology experts from India formulated a national consensus on the use of ARNI in HF based on current evidence and guidelines. The consensus states that ARNI should be used early in HF, particularly in de novo patients with HFrEF, and those with acute decompensated heart failure (ADHF), irrespective of the presence of low systolic blood pressure (SBP) or diabetes. Moreover, those with HFrEF on renin-angiotensin-aldosterone system (RAAS) inhibitors should be switched to ARNI to reduce the risk of repeated hospitalization for HF, worsening HF, and cardiac death, and to improve the quality of life (QoL). Starting ARNI during the first hospitalization is preferable, and it is safe and effective across all doses. ARNIs can also be used for secondary benefits in patients with preserved ejection fraction [heart failure with preserved ejection fraction (HFpEF)] and HF with mildly reduced EF [heart failure with mildly reduced ejection fraction (HFmrEF)].

Chronic Administration of Red Yeast Rice Mitigates Endothelial Dysfunction in Spontaneously Hypertensive Rats by Inhibiting Oxidative Stress and Endothelial Nitric Oxide Synthase Uncoupling.

Hypertension is associated with endothelial dysfunction. An imbalance in the production of Nitric Oxide (NO) and Reactive Oxygen Species (ROS), leading to impaired NO-cyclic Guanosine Monophosphate (cGMP) pathway, contributes to this disorder. Red Yeast Rice (RYR), produced from the fermentation of rice with Monascus purpureus, is a traditional functional food originating from China. Although recognized for its anti-dyslipidemia properties, there has been growing evidence regarding the anti-hypertensive effects of RYR. However, these studies only focused on its direct and short-term effects. This study aims to investigate the vasoprotective effects of chronic oral RYR administration using Spontaneously Hypertensive Rats (SHR). SHR were randomly divided into 3 groups: SHR - Control; SHR - RYR extract (100 mg/kg/day); SHR - lovastatin (10 mg/kg/day). Wistar-Kyoto Rats (WKY) were used as normotensive controls. All animals were treated for 12 weeks by oral gavage. Systolic Blood Pressure (SBP) was measured weekly (tail-cuff method). Vascular reactivity was determined using isolated rat aortic rings in an organ bath. Aortic ROS, NO, tetrahydrobiopterin (BH4), and cGMP levels were evaluated. Administration of RYR attenuated SBP elevation and enhanced endothelium-dependent vasodilation in aortic rings. In addition, RYR decreased ROS production and significantly improved the level of vascular NO, BH4, and cGMP. In an SHR model, treatment with RYR for 12 weeks exerts an SBP lowering effect that can be attributed to improved vascular function via reduction of oxidative stress, decreased endothelial NO Synthase (eNOS) uncoupling and enhanced NO-cGMP pathway.

Comparative effects of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors on heart failure with preserved ejection fraction in diabetic patients: a meta-analysis

BackgroundHeart failure with preserved ejection fraction (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients.MethodsWe conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors’ impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP). ResultsTwelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001).ConclusionsGLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects.

The Buddy System: African American Women with Self-Reported Hypertension and Their Experiences in a Peer (Dyadic) Support Intervention

INTRODUCTION: Hypertension is the leading modifiable risk factor for cardiovascular disease, and it disproportionately affects African American women, who face increased risks of heart disease, kidney disease, and stroke. The Dietary Approaches to Stop Hypertension (DASH) diet effectively reduces blood pressure, but African American women often face challenges with adhering to it. Peer support, a proven mechanism for improving health behaviors through social connections and community resources, may help these women better manage their diet and hypertension. This qualitative study explored the experiences of African American women participating in an eight-week peer (dyadic) support intervention to improve DASH diet adherence and lowering systolic blood pressure, with an emphasis on understanding the dyadic relationship. METHODS: A purposive sample of 40 African American women (20 dyads) was recruited for five focus groups that were conducted both online and in person. Content analysis was used to identify themes related to the nature and quality of peer interactions and relationships from the perspectives of the 34 women who completed the intervention (Mean age = 71.38 years; SD = 8.38). RESULTS: Four subthemes emerged: emotional support, shared experiences, informational/inspirational support, and accountability. The participants reported forming strong, supportive relationships that were crucial in improving diet and blood pressure management. CONCLUSION: This study underscores the benefits of peer support in managing hypertension among older African American women, suggesting the need for future randomized controlled trials to examine the effectiveness of the DASH diet with and without peer support.

A Novel Index for Survival in Acute Heart Failure: Diuretic Efficiency Score

Aims: Acute heart failure (AHF) is the leading cause of hospital admissions among adults ≥65. Loop diuretics are the mainstay of treatment of congestion in AHF. Response to loop diuretics is closely related to morbidity and mortality. In this study, we aimed to investigate (1) the clinical determinants of diuretic efficiency (DE) by using three separate indicators for assessing DE and (2) the prognostic effect of diuretic efficiency in acutely decompensated heart failure patients. Methods: 42 consecutive patients admitted to the hospital for acutely decompensated heart failure were included. Early diuretic response, spot urine sodium excretion (UNa), and hemoconcentration were evaluated individually to predict loop diuretic efficiency. Results: Good early diuretic response (EDR) was associated with higher diastolic blood pressure on admission and eGFR, atrial fibrillation, and bolus dosing of intravenous furosemide. Hypertension and low systolic blood pressure on admission were inversely related to hemoconcentration. Conclusion: Diuretic efficiency is strongly influenced by the heart rhythm, renal function, blood pressure, prevalence of hypertension, and schedule of furosemide administration. We developed a novel, 3-variable index called DES (diuretic efficiency score) that predicts mortality in AHF patients. Future research in larger cohorts is needed to validate DES as a predictor of mortality in heart failure.

Chemical composition, anti-hypertensive properties, and sensory attributes of salt extracted from ash of Hygrophilia schulli.

The traditional usage of salt taken from vegetables for the treatment of blood pressure and diabetes is seen in several regions of Ethiopia, particularly in Gambella. The aim of the study was to investigate the mineral content, anti-hypertensive properties, and sensory attributes of salt obtained from the Hygrophilia schulli. The salt was extracted from the ashing of stems of Hygrophilia schulli. Optical Emission Spectroscopy with Inductively Coupled Plasma was used to identify macro-minerals, micro-minerals, and some toxic metals. Flame Atomic Absorption Spectroscopy was used to assess the levels of arsenic and mercury. The anti-hypertensive property of the salt was determined invivo using the Wistar rats. The extracted salt was rich in potassium and was deficient in sodium from the analyzed macro-minerals. It was free from mercury, cadmium, chromium, and arsenic. Lead and nickel were below the Tolerable Weekly Intake Provisional specified by the European Union. Among carbonate and sulfate, chloride was the main anion in this salt. The salt was discovered to have a low taste characteristic compared to common salt. However, the taste attribute of the combination of vegetable and common salt in different proportions was better than common salt. Rats fed with salt from Hygrophilia schulli showed a statistically significant lower systolic, diastolic, and mean blood pressure compared to normal-fed and common salt-fed rat groups. Generally, this study suggests that Hygrophilia schulli salt has the potential to be a viable alternative to common salt, particularly for those suffering from hypertension and other related chronic conditions.

Clinical effectiveness of amlodipine/indapamide/perindopril fixed-dose combination in patients with metabolic disorders: results of post hoc analyzes of the TRICOLOR study

Aim. To describe antihypertensive effectiveness of triple fixed-dose combination of am lo dipine/indapamide/perindopril and assess predictors of its clinical effectiveness in pati ents depending on body mass index (BMI) and presence of type 2 diabetes (T2D).Material and methods. This observational prospective study TRICOLOR (NCT03722524) (n=1247) demonstrated high antihypertensive effectiveness and good tolerability of amlodipine/indapamide/perindopril fixed-dose combination. Subgroup analyzes based on BMI included data from 1144 patients. In a second subgroup analysis, 1128 patients were stratified according to concomitant T2D.Results. In patients with overweight/obesity and diabetes, good antihypertensive effectiveness of amlodipine/indapamide/perindopril was observed, comparable in blood pressure (BP) reduction with the comparison groups (patients with normal BMI and patients without diabetes). At the same time, patients with normal BMI, compared with patients with overweight and obesity, had significantly lower systolic BP (SBP) (after 4 and 12 weeks) and diastolic BP (DBP) (after 2 and 12 weeks). In the subgroups, depending on the diabetes status, there were no significant differences in the decrease in SBP and DBP levels at all follow-up points. By the 12th week, BP decrease in the group of patients with normal BMI was 32,9 (10,5)/15,3 (8,6) mm Hg, in the group with overweight — 33,2 (11,3)/14,2 (8,5) mm Hg, in the obesity group — 33,9 (12,3)/14,1 (8,8) mm Hg (p&gt;0,05 for intergroup comparison). Target BP &lt;140/90 mm Hg already after 2 weeks of therapy achieved a higher number of patients with a normal BMI compared to overweight group (50,8% vs 37,2%, p=0,009). By the 12th week, the vast majority of patients, regardless of BMI and diabetes status, achieved a target BP &lt;140/90 mm Hg, which demonstrates a good and rapid response to triple fixed-dose therapy.Conclusion. Thus, additional analyzes of the TRICOLOR study demonstrate the high antihypertensive effectiveness of amlodipine/indapamide/perindopril in hypertensive patients, regardless of the presence of diabetes, overweight or obesity.

Antihypertensive and antioxidant effects of food-derived bioactive peptides in spontaneously hypertensive rats.

Hypertension significantly impacts the survival and quality of life of animals, often leading to chronic kidney failure. Current clinical drugs used to manage hypertension carry the risk of causing adverse reactions. In contrast, certain natural peptides have demonstrated the ability to safely reduce blood pressure by inhibiting the production of angiotensin. We administered four biologically active peptide solutions to spontaneously hypertensive rats: derived from corn, wheat, egg white, and soybean. The efficacy of these peptides in reducing blood pressure was assessed through regular measurements of systolic pressure. Additionally, we analyzed levels of angiotensin-converting enzyme and angiotensin 2 using immunohistochemistry and ELISA invivo. The indicators of oxidative stress and inflammation in hypertensive rats were evaluated using qRT-PCR and ELISA, respectively. Both wheat (from 182.5 ± 12.26 mmHg at day 0 to 168.86 ± 5.86 mmHg at day 20, p = .0435) and soybean (from 189 ± 2.19 mmHg at day 0 to 178.25 ± 5.14 mmHg at day 20, p = .0017) notably lowered systolic blood pressure compared to their starting systolic blood pressures in spontaneously hypertensive rats. Both wheat and soybean peptides significantly reduced plasma ANG II levels, akin to captopril's effect. Wheat peptides additionally exhibited antioxidant properties. Only the corn peptide showed a significant increase in transcript levels of the proinflammatory factors IL-6 and TNF-α. At the protein level, all four kinds of peptides significantly elevated IL-6 levels while inhibiting TNF-α secretion. This study demonstrates that wheat peptides and soybean peptides administered as dietary supplements exhibit significant hypotensive and antioxidant effects.

Magnitude of systolic blood pressure reduction following endovascular treatment and clinical outcomes in acute large artery occlusion stroke

BackgroundThe impact of lowering systolic blood pressure (SBP) following endovascular treatment (EVT) in acute large vessel occlusion stroke (LVOS) patients remains unclear. We aimed to explore the effect of the...

Bayesian analysis of the effects of some identified risk factors of systolic pressure among pregnant women in Ogbomoso, Oyo State

Unhealthy condition during pregnancy is a function of abnormal Systolic Blood Pressure (SBP). Therefore, this becomes a threat to women and health policy makers on how to reduce the consequence of high SBP. To overcome this challenge, appropriate model must be specified to capture some identified clinical-genetic factors for SBP in pregnant women when the informative prior to these factors is not sufficiently available. The aim of the study is to develop a Bayesian Logit (BLM) to calculate probabilities of different SBP outcomes among pregnant women in LAUTECH Teaching Hospital, Oyo State. The results shows that age, packed cell volume and genotype increase the likelihood of having High Systolic Blood Pressure (HSBP), while blood group and occupation increase the likelihood of having low Systolic Blood Pressure (LSBP) among pregnant women. Also, the probabilities of increase in height and weight cause a systematic change in the SBP among pregnant women. The study concludes that the identified clinical and genetic risk factors contribute to the likelihood of having HSBP and LSBP among pregnant women in Ogbomoso, Oyo State.

A preliminary investigation of worry, cortical amyloid burden, and stressor-evoked brain and cardiovascular reactivity in older adults

Worry is a transdiagnostic symptom common to many neurocognitive disorders of aging, including early stages of Alzheimer's disease and related dementias (ADRD). Severe worry is associated with amyloid burden in cognitively intact older adults, yet the mechanisms underlying this association are not well understood. We hypothesize that this relationship involves altered brain and cardiovascular reactivity to acute stressors, a brain-body phenotype that also increases risk for cardiovascular disease. Twenty cognitively normal older adults (age 60 to 80) with varying levels of worry severity underwent positron emission tomography using Pittsburgh Compound-B and functional magnetic resonance imaging. We examined associations of worry severity and amyloid burden with cardiovascular reactivity, brain activation, and brain connectivity using a cognitive stressor task. Worry severity was not associated with global amyloid burden, but was associated with greater resting levels of cardiovascular physiology and lower systolic blood pressure reactivity. Worry severity also was associated with altered stressor-evoked activation and effective connectivity in brain circuits implicated in stress processing, emotion perception, and physiological regulation. These associations showed small to medium effect sizes. These preliminary findings introduce key components of a model that may link severe worry to ADRD risk via stressor-evoked brain-body interactions.

Ropivacaine combined with dexmedetomidine in ultrasound-guided axillary brachial plexus block in children, a randomized controlled trial

ObjectiveIn this study, we evaluated the efficacy and safety of 1 μg/kg dexmedetomidine as an adjuvant treatment to ropivacaine in children undergoing upper limb surgeries under ultrasound-guided axillary brachial plexus blocks and general anesthesia.MethodsWe enrolled 90 children (aged 1–8 years; ASA I-II) undergoing closed reduction and internal fixation for upper extremity fractures at the Xiamen Children's Hospital and randomly assigned them to one of two groups: L (injection with 0.25% ropivacaine) or D (injection with 0.25% ropivacaine containing 1 μg/kg dexmedetomidine) using the random number table method. The main outcome indicators recorded were the facial expression, leg activity, position, crying, and Face, Legs, Activity, Cry, and Consolability (FLACC) scale scores of children after surgery and the duration of block and analgesia maintenance. The secondary outcome indicators were vital sign data at the time of ultrasound probe placement (T1), at the time of block completion (T2), prior to the beginning of surgery (T3), 5 min after the beginning of surgery (T4), and at the end of surgery (T5), as well as the time of postoperative recovery, the number of cases of remedial analgesia, and complications.ResultsThere was no statistical difference between the two groups in terms of general data, block completion time, postoperative recovery time, and complications (P > 0.05). Compared to the L group, the D group had significantly lower FLACC scores at 6 h after surgery, as well as significantly lower systolic blood pressure, diastolic blood pressure, and heart rate values at T4 and T5, and significantly longer duration of postoperative analgesia maintenance (all P < 0.05).ConclusionDexmedetomidine (1 μg/kg) as a local anesthetic adjuvant to ropivacaine can alleviate pain at 6 h postoperatively, prolong analgesia maintenance, and reduce intraoperative blood pressure and heart rate in pediatric patients undergoing closed reduction and internal fixation for upper extremity fractures, with no obvious complications or delayed recovery.Clinical registry numberRegistration website: www.chictr.org.cn, Registration number: ChiCTR2200065163, Registration date: October, 30, 2022.

The VExUS score and mortality in patients with Acute Kidney Injury: findings from a multidisciplinary prospective study.

The utility of the venous excess ultrasound (VExUS) score in predicting mortality remains uncertain in acute kidneyinjury (AKI) patients. This was a post-hoc study involving 246 AKI patients presenting to a tertiarycare emergency department. Venous ultrasound assessments were conducted to determine the VExUS score. Cox regressionanalysis was used to identify predictors of 6-month mortality. The study found no significant association between theVExUS score and 6-month mortality in AKI patients in the regression analyses. However, in the subgroup analyses, VExUSgrades 2-3 were associated with lower survival rates in the cardiorenal subgroup (HR: 3.98 [95% CI: 1.33-11.93]), and in AKIgrade 1 (HR: 4.07 [95% CI: 1.74-9.49]). This association was not present in other AKI subgroups. The predictors of mortalityincluded higher age (OR: 1.024; 95% CI 1.005-1.043), malignancy (OR: 2.186; 95% CI 1.408-3.392), lower systolic bloodpressure (OR: 0.990; 95% CI 0.982-0.998), elevated pulse (OR: 1.013; 95% CI 1.005-1.022), and higher lactate levels (OR:1.210; 95% CI 1.097-1.334). The VExUS score did not predict 6-month mortality in the general cohort of AKIpatients in the emergency department. However, VExUS grades 2-3 were associated with lower survival rates in the cardiorenalsubgroup and patients with AKI grade 1.