Telmisartan-Induced Myotoxicity in Patients with Essential Hypertension.

Drug-related muscular adverse effects are relatively common among certain groups of drugs, such as statins and steroids. However, these adverse effects are less well-known for angiotensin receptor blockers (ARBs). It is proposed that telmisartan and irbesartan may cause myotoxicity via increased Peroxisome Proliferator-Activated Receptor gamma (PPAR-gamma) activity. Herein, we present two hypertensive patients in whom telmisartan-induced myotoxicity was observed. Therefore, physicians should be aware that telmisartan, along with some other ARBs, can also cause myopathy. Possible drug-drug interactions should be considered in cases of concomitant prescription of these agents with other myopathic drugs.

Clinicopathological characteristics and gene mutations in 11 patients with lipoprotein glomerulopathy.

OBJECTIVE: Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E (APOE) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients. METHODS: Clinicopathological and follow-up data were obtained by extracting DNA, followed by APOE coding region sequencing analysis. This study analyzed clinical and pathological manifestations, gene mutations, treatment and prognosis. RESULTS: The mean age of the eleven patients was 33.82 years. Among them, five had a positive family history for LPG, ten presented with proteinuria, four exhibited nephrotic syndrome, and six presented with microscopic hematuria. Dyslipidemia was identified in ten patients. In all renal specimens, there was evident dilation of glomerular capillary lumens containing lipoprotein thrombi, and positive oil red O staining was observed in frozen sections of all samples. APOE gene testing revealed that one patient had no mutations, while the remaining ten patients exhibited mutations in the APOE gene, with three patients presenting with multiple mutations simultaneously. Following the confirmation of LPG diagnosis, treatment with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) was initiated, and the disease progressed slowly. CONCLUSION: LPG is histologically characterized by lamellated lipoprotein thrombi in glomeruli, and kidney biopsy is essential for diagnosis. Mutations in the APOE gene are the leading cause of LPG. This study revealed clinicopathological characteristics and APOE gene mutations in patients with LPG, which helps us better understand the disease.

Different Kynurenine Pathway Dysregulation in Systemic Sclerosis in Men and Women.

Systemic sclerosis (SSc), a predominantly female-affected systemic autoimmune disease, requires tailored treatment strategies contingent on organ involvement and symptom severity. Given SSc's inflammatory nature, the involvement of the kynurenine pathway (KP) in its pathophysiology is underexplored. Our study aimed to investigate sex-related differences in KP activation among SSc patients and assess the impact of angiotensin-converting enzyme (ACE) inhibitors and estimated glomerular filtration rate (eGFR) on KP metabolite concentrations. We enrolled 48 SSc patients and 53 healthy controls, quantifying KP metabolites (tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA)) in serum via high-performance liquid chromatography. Separate multivariate analyses of covariance (MANCOVAs) for women and men were performed to ascertain mean differences between patients and healthy controls while correcting for age. For our secondary objective, we conducted a MANCOVA to explore disparities in ACE inhibitor users and non-users among patients, with BMI correction. Our findings revealed decreased TRP concentrations but increased KYNA/TRP ratio and KYN/TRP ratio in both male and female SSc patients compared to their respective controls. Unlike women, SSc males exhibited higher KYN concentrations and decreased KYNA/KYN ratio relative to their controls. Additionally, SSc patients using ACE inhibitors had higher serum KYNA levels than non-users. Notably, we established a significant correlation between eGFR and KYNA in SSc patients. These results indicate differential KP activation in male and female SSc patients, with males demonstrating heightened KP activation. While ACE inhibitors may influence the KP in SSc patients, further research is necessary to comprehensively understand their impact on symptoms and prognosis in the context of these KP alterations.

Predicting Response to Immunotargeted Therapy in Endometrial Cancer via Tumor Immune Microenvironment: A Multicenter, Observational Study.

Only one-third of patients with advanced MSS/pMMR endometrial cancer exhibit a lasting response to the combination treatment of Pembrolizumab and Lenvatinib. The combined administration of these two drugs is based on Lenvatinib's ability to modulate the tumor microenvironment, enabling Pembrolizumab to exert its effect. These findings underscore the importance of exploring tumor microenvironment parameters to identify markers that can accurately select candidates for this type of therapy. An open non-randomized observational association study was conducted at six clinical centers, involving a total of 28 patients with advanced MSS/pMMR endometrial cancer who received Pembrolizumab and Lenvatinib therapy. Using TSA-associated multiplex immunofluorescence, we analyzed the proportion of CD8+ T lymphocytes, CD20+ B lymphocytes, FoxP3+ T regulatory lymphocytes, and CD163+ macrophages in tumor samples prior to immunotargeted therapy. The percentage of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio was significantly higher in patients who responded to treatment compared to non-responders (responders vs. non-responders: 0.24 (0.1-1.24)% vs. 0.08 (0.00-0.15)%, p = 0.0114; 1.44 (0.58-2.70) arb. unit vs. 19.00 (3.80-34.78) arb. unit, p = 0.0031). The sensitivity and specificity of these biomarkers were 85.71% and 70.59%, and 85.71% and 85.71%, respectively. The proportion of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio in the stroma of endometrial cancer serves as both a prognostic marker of response to immunotargeted therapy and a prognostic factor for progression-free survival in patients.

Renin-Angiotensin-Aldosterone System: From History to Practice of a Secular Topic.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are standard care in patients with hypertension, heart failure or chronic kidney disease (CKD). Although we have studied the RAAS for decades, there are still circumstances that remain unclear. In this review, we describe the evolution of the RAAS and pose the question of whether this survival trait is still necessary to humankind in the present age. We elucidate the benefits on cardiovascular health and kidney disease of RAAS inhibition and present promising novel medications. Furthermore, we address why more studies are needed to establish a new standard of care away from generally prescribing ACEi or ARB toward an improved approach to combine drugs tailored to the needs of individual patients.

Concurrent exercise training potentiates the effects of angiotensin-converting enzyme inhibitor on regulatory systems of blood pressure control in ovariectomized hypertensive rats.

OBJECTIVE: Enalapril has shown satisfactory potential in controlling increased and sustained blood pressure (BP). However, multiple dysregulated mechanisms that interact with each other and are involved in the pathophysiology of arterial hypertension may not be affected, contributing to the remaining cardiovascular risk. Using an exercise training protocol, we investigated whether adding both approaches to arterial hypertension management could promote higher modulation of regulatory mechanisms of BP in postmenopausal rats. METHODS: Spontaneously hypertensive rats were allocated into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with enalapril maleate (OSE) and trained treated with enalapril maleate (OTE). Both the pharmacological and exercise training protocols lasted for 8 weeks. The BP was directly recorded. Inflammation and oxidative stress were evaluated in the cardiac tissue. RESULTS: Although BP reduction was similar between OSE and OTE, trained group showed lower vasopressor systems outflow after sympathetic ganglion blocking by hexamethonium (mean BP) (OTE: -53.7 ±â€Š9.86 vs. OS: -75.7 ±â€Š19.2 mmHg). Bradycardic and tachycardic response were increased in OTE group (-1.4 ±â€Š0.4 and -2.6 ±â€Š0.4 vs. OS: -0.6 ±â€Š0.3 and -1.3 ±â€Š0.4 bpm/mmHg, respectively), as well as BP variability. In addition, the combination of approaches induced an increase in interleukin 10, antioxidant defense (catalase and glutathione peroxidase) and nitrite levels compared with the OS group. CONCLUSION: Despite similar BP, the inclusion of exercise training in antihypertensive drug treatment exacerbates the positive adaptations induced by enalapril alone on autonomic, inflammatory and oxidative stress profiles, probably affecting end-organ damage and remaining risk.

Angiotensin-converting enzyme inhibitors, statins and the polypill in cardiovascular diseases prevention: ignorance is bliss or not?

The polypill strategy, which combines several medicines that simultaneously control different risk factors/diseases in a single pill, is one of the approaches used in cardiovascular therapy. In different guidelines, this one-pill combination therapy is suggested as first-line step in disease management. Because the cardiovascular diseases (CVD) pandemia, prevention is essential. The approaches that could improve adherence are of great importance to achieve health, social and economical benefits. However, direct or indirect experience of adverse drug reaction is often the reason for discontinuation, with serious fatal and non-fatal consequences especially for a polypill. Angiotensin-converting enzyme inhibitors (ACEi) and statins are the most prescribed medications in CVD prevention. It is well known that both drugs may have adverse effects that induce discontinuation. Often, the personal awareness of these effects is a reason for self-discontinuation. In this study an analysis of the ACEi/statin awareness is reported. Is it potentially harmful for polypill?

Evaluation of antihypertensive medications use and survival in patients with ovarian cancer: a population-based retrospective cohort study.

BACKGROUND: Despite declining mortality in most countries and in Lithuania, ovarian cancer burden has remained high. Studies have indicated that antihypertensive medications use may help to improve ovarian cancer survival, however findings remain controversial. The aim of the study was to analyse the association between post-diagnosis antihypertensive medications intake and cancer-specific survival in ovarian cancer patients. METHODS: This retrospective cohort study included 588 ovarian cancer cases diagnosed between 2013 and 2015. Hazard ratios (HR) and corresponding 95% confidence intervals (95%CI) were estimated using multivariable Cox proportional hazards models to assess associations between antihypertensive medications and ovarian cancer-specific mortality. RESULTS: In total, 279 (47%) patients died during the follow-up; 242 (87%) of them died due to ovarian cancer. The risk of ovarian cancer death was reduced in angiotensin-converting enzyme inhibitors (ACE inhibitors) users vs. non-users (HR 0.55, 95% CI: 0.36-0.83). Subgroup analysis showed better ovarian cancer survival in higher dose ACE inhibitors users (HR 0.46, 95% CI: 0.28-0.77, p for trend 0.002); the effect was also stronger in age 51-65 years, stage I-III, surgery or chemotherapy treatment, pre-diagnosis ACE inhibitor users' and pre-diagnosis hypertension subgroups. The risk of cancer-specific death was slightly lower among calcium-channel blocker and angiotensin-receptor blocker users and higher among beta-blocker users as compared to non-users, however chance and confounding could not be ruled out. We found no association between the use of centrally and peripherally acting antiadrenergic agents and diuretics and risk of ovarian cancer-specific mortality. CONCLUSIONS: Our findings imply that post-diagnosis use of ACE inhibitors may be associated with reduced ovarian cancer-specific mortality; however, further research is needed for the comprehensive assessment.

Angiotensin I and II Stimulate Cell Invasion of SARS-CoV-2: Potential Mechanism via Inhibition of ACE2 Arm of RAS.

Angiotensin-converting enzyme 2 (ACE2), one of the key enzymes of the renin-angiotensin system (RAS), plays an important role in SARS-CoV-2 infection by functioning as a virus receptor. Angiotensin peptides Ang I and Ang II, the substrates of ACE2, can modulate the binding of SARS-CoV-2 Spike protein to the ACE2 receptor. In the present work, we found that co incubation of HEK-ACE2 and Vero E6 cells with the SARS-CoV-2 Spike pseudovirus (PVP) resulted in stimulation of the virus entry at low and high micromolar concentrations of Ang I and Ang II, respectively. The potency of Ang I and Ang II stimulation of virus entry corresponds to their binding affinity to ACE2 catalytic pocket with 10 times higher efficiency of Ang II. The Ang II induced mild increase of PVP infectivity at 20 microM; while at 100 microM the increase (129.74+/-3.99 %) was highly significant (p<0.001). Since the angiotensin peptides act in HEK ACE2 cells without the involvement of angiotensin type I receptors, we hypothesize that there is a steric interaction between the catalytic pocket of the ACE2 enzyme and the SARS-CoV-2 S1 binding domain. Oversaturation of the ACE2 with their angiotensin substrate might result in increased binding and entry of the SARS-CoV-2. In addition, the analysis of angiotensin peptides metabolism showed decreased ACE2 and increased ACE activity upon SARS-CoV-2 action. These effects should be taken into consideration in COVID-19 patients suffering from comorbidities such as the over-activated renin-angiotensin system as a mechanism potentially influencing the SARS-CoV-2 invasion into recipient cells.

Biodirected Screening and Preparation of Larimichthys crocea Angiotensin-I-Converting Enzyme-Inhibitory Peptides by a Combined In Vitro and In Silico Approach.

Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However, there are some limitations of conventional methods for preparing ACE-inhibitory peptides. In this study, in silico hydrolysis, the quantitative structure-activity relationship (QSAR) model, LC-MS/MS, inhibition kinetics, and molecular docking were used to investigate the stability, hydrolyzability, in vitro activity, and inhibition mechanism of bioactive peptides during the actual hydrolysis process. Six novel ACE-inhibitory peptides were screened from the Larimichthys crocea protein (LCP) and had low IC50 values (from 0.63 ± 0.09 µM to 10.26 ± 0.21 µM), which were close to the results of the QSAR model. After in vitro gastrointestinal simulated digestion activity of IPYADFK, FYEPFM and NWPWMK were found to remain almost unchanged, whereas LYDHLGK, INEMLDTK, and IHFGTTGK were affected by gastrointestinal digestion. Meanwhile, the inhibition kinetics and molecular docking results were consistent in that ACE-inhibitory peptides of different inhibition forms could effectively bind to the active or non-central active centers of ACE through hydrogen bonding. Our proposed method has better reproducibility, accuracy, and higher directivity than previous methods. This study can provide new approaches for the deep processing, identification, and preparation of Larimichthys crocea.

[Contamination Characteristics，Detection Methods，and Control Methods of Antibiotic Resistance in Pharmaceutical Wastewater].

Pharmaceutical industry wastewater contains a large number of emerging pollutants such as antibiotics， antibiotic resistant bacteria （ARBs）， and antibiotic resistance genes （ARGs）. The present biological water treatment processes cannot effectively remove these pollutants. Eventually， they are discharged into various water bodies or penetrate into soil with the effluent， causing environmental pollution and affecting human health. Therefore， exploring the pollution characteristics of antibiotics， ARBs， and ARGs in pharmaceutical wastewater and knowing the methods to detect and control antibiotic resistance pollution in wastewater are crucial for reducing the contamination of antibiotics and ARGs and assessing the ecological risks of antibiotic resistance. Aiming at the problem of antibiotic resistance pollution in a pharmaceutical wastewater treatment plant （PWWTPs）， the pollution status of antibiotics， ARBs， and ARGs in pharmaceutical wastewater was discussed. Different assessment methods of antibiotic resistance in pharmaceutical wastewater were summarized. Finally， the wastewater treatment technologies commonly used to remove antibiotics and ARGs in PWWTPs were summarized in order to provide a theoretical basis for the ecological risk assessment and scientific control of antibiotics and ARGs in the environment.

Sacubitril/Valsartan in Patients Hospitalized With Decompensated Heart Failure.

BACKGROUND: The efficacy and safety of sacubitril/valsartan in patients hospitalized with heart failure (HF) across the spectrum of left ventricular ejection fraction (EF) has not been described. OBJECTIVES: Data from randomized trials of sacubitril/valsartan in HF patients with EF ≤40% (PIONEER-HF [Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode] trial) and >40% (PARAGLIDE-HF [Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF] trial) following recent worsening heart failure (WHF) were pooled to examine treatment effect across the EF spectrum. METHODS: The PIONEER-HF and PARAGLIDE-HF trials were double-blind, randomized trials of sacubitril/valsartan vs control therapy (enalapril or valsartan, respectively). All participants in the PIONEER-HF trial and 69.5% in the PARAGLIDE-HF trial were enrolled during hospitalization for HF after stabilization. The remainder in the PARAGLIDE-HF trial were enrolled ≤30 days after a WHF event. The primary endpoint of both trials was time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8. Adjudicated clinical endpoints were analyzed through the end of follow-up, adjusting for trial. RESULTS: The pooled analysis included 1,347 patients (881 from PIONEER-HF, 466 from PARAGLIDE-HF). Baseline characteristics included median age 66 years, 36% women, 31% Black, 34% de novo HF, and median EF 30%. The reduction in NT-proBNP was 24% greater with sacubitril/valsartan vs control therapy (n = 1,130; ratio of change = 0.76; 95% CI: 0.69-0.83; P < 0.0001). Cardiovascular death or hospitalization for HF was reduced by 30% with sacubitril/valsartan vs control therapy (HR: 0.70; 95% CI: 0.54-0.91; P = 0.0077). This effect was consistent across the spectrum of EF ≤60%. Sacubitril/valsartan increased symptomatic hypotension (risk ratio: 1.35; 95% CI: 1.05-1.72). CONCLUSIONS: In patients stabilized after WHF, sacubitril/valsartan led to a greater reduction in plasma NT-proBNP and improved clinical outcome compared with control therapy, in particular across the spectrum of EF ≤60%. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890; Changes in NT-proBNP, Safety, and Tolerability in HFpEF Patients With a WHF Event [HFpEF Decompensation] Who Have Been Stabilized and Initiated at the Time of or Within 30 Days Post-decompensation [PARAGLIDE-HF]; NCT03988634).

Investigating the use of finerenone in children with chronic kidney disease and proteinuria: design of the FIONA and open-label extension studies.

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria. OBJECTIVE: FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria. DESIGN: FIONA (NCT05196035; Eudra-CT: 2021-002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months' duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m2 if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021-002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints. CONCLUSION: FIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05196035. Registered on 19 January 2022.

Effect of angiotensin-converting enzyme inhibitors versus that of angiotensin receptor blockers on survival in patients undergoing hemodialysis: a nationwide observational cohort study.

BACKGROUND: This study aimed to evaluate the patient survival rates based on the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in a large cohort of patients undergoing maintenance hemodialysis (HD). METHODS: Data from a national HD quality assessment program were used in this retrospective study. The patients were classified into four groups based on the use of renin-angiotensin system blockers (RASBs) as follows: No group, patients without a prescription of any anti-hypertensive drugs including RASBs; Other group, patients with a prescription of anti-hypertensive drugs excluding RASBs; ACEI group, patients with a prescription of an ACEI; and ARB group, patients with a prescription of an ARB. RESULTS: The 5-year survival rates in the no, other, ACEI, and ARB groups were 68.6%, 67.8%, 70.6%, and 69.2%, respectively. The ACEI group had the best patient survival trend among the four groups. In multivariable Cox regression analyses, no differences were observed between the ACEI and ARB groups. Among young patients and patients without diabetes or heart disease, the ACEI group had the best patient survival among the four groups. However, among patients with DM or heart disease, the ARB group had the best patient survival. CONCLUSIONS: Our study found that patients receiving ACEI and ARB had comparable survival. However, patients receiving ARB had better survival in the subgroups of patients with DM or heart disease, and patients receiving ACEI had better survival in the subgroup of young patients or patients without diabetes or heart disease.

Pressure control and treatment interact in the deterioration of incidental visuospatial memory in hypertensive patients.

BACKGROUND: Systemic hypertension (SH) is the main risk factor to cognitive deterioration, whereas visuospatial memory is more vulnerable to ageing. Some antihypertensive agents have a neuroprotector effect, however, such effects could be masked by comorbidities and/or the lack of effective control on the arterial pressure of patients. OBJECTIVE: To assess this, the evaluation of incidental visuospatial memory of SH patients and the relation to the treatment received and the effective control of pressure were made. METHOD: 80 patients (46 woman) were included grouped by the received medication: angiotensin 2 receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI). A multiple correlation analysis between visuospatial scores and clinical variables was made; also, a mixed model analysis (fixed factors: treatment, pressure control, diabetes comorbidity; aleatory factors: age, schooling, months from SH diagnoses). RESULTS: Half of the patients had a controlled pressure, from them the higher proportion received ARB, and a minor number of patients received ACEI. The normotensive patients receiving ACEI were inefficient whereas the hypertensive patients were more efficient. The systolic pressure was negatively related with the visuospatial scores in spite of no correlations occurred with MoCA and Raven tests. CONCLUSIONS: The visuospatial incidental/intentional scores were negatively correlated with systolic pressure. The efficiency in the visuospatial ability depends on the interaction of treatment and effective control of blood pressure. The interaction between treatment and effective pressure control must be taken in count when cognitive deterioration is studied.

ANTECEDENTES: La hipertensión arterial sistémica (HAS) es el principal factor de riesgo para el deterioro cognitivo; por otro lado, la memoria visuoespacial es más vulnerable al envejecimiento. Algunos fármacos antihipertensivos tienen un efecto neuroprotector, pero tal efecto puede enmascararse o bien no manifestarse por comorbilidad o por falta de control efectivo de la presión arterial. OBJETIVO: Evaluar las alteraciones en la memoria visuoespacial incidental de pacientes con HAS en relación con su tratamiento antihipertensivo y su control de la presión. MÉTODO: Se incluyeron 80 pacientes con HAS (46 mujeres), agrupados por su medicación en bloqueadores de los receptores de la angiotensina II (BRA) o inhibidores de la enzima convertidora de angiotensina (IECA). Se realizó un análisis de correlaciones múltiples para los puntajes obtenidos en la prueba de memoria visuoespacial incidental/intencional y un análisis de modelos mixtos (factores fijos: tratamiento, control de la presión y comorbilidad con diabetes; factores aleatorios: edad, escolaridad, meses desde el diagnóstico de HAS y coeficiente intelectual). RESULTADOS: De los pacientes controlados, la mayoría de los que recibían BRA fueron eficientes y los que recibían IECA fueron deficientes. De los que recibían IECA, los descontrolados hipertensos fueron más eficientes que los normotensos. La memoria visuoespacial se correlacionó negativamente con la presión sistólica a pesar de no haber diferencias en MoCA y Raven. CONCLUSIONES: La eficiencia en la memoria visuoespacial dependió de la interacción del tratamiento y el control de la presión. Ambos factores, tratamiento y control efectivo de la presión, deben considerarse en la evaluación del deterioro cognitivo asociado a la HAS.

A simple tandem bioassay-guided SCX-RP SPE fractionation for efficient active peptide screening from Inca nut cake protein hydrolysate.

Typically, bioactive peptides were uncovered from complex hydrolysates using sequential bioassay-guided fractionation. To increase the efficiency of bioactive peptide screening, a simple and convenient tandem bioassay-guided fractionation based on solid-phase extraction (SPE) was conducted to screen the angiotensin-I-converting enzyme (ACE) inhibitory peptides from the hydrolysate of Inca nut cake protein (INCP). The so-called SCX-RP SPE system was constructed by assembling SCX (strong cation exchange) and RP (reversed phase) SPE cartridges. Using this tandem SCX-RP SPE, the INCP digested with combined gastrointestinal protease (INCP GP) was fractionated into 30 fractions. The fraction F11 exhibited the highest ACE inhibitory activity among 30 fractions. The ACE IC50 of fraction F11 was calculated to be 6.6 ± 0.5 µg/mL. The ACEI activity of fraction F11 was stronger than the INCP GP hydrolysate (ACE IC50 of 12.7 ± 0.4 µg/mL). The tandem SCX-RP SPE fractionation reduced the number of ACE inhibitory (ACEI) peptide candidates from 127 peptides in the INCP GP hydrolysate to only ten peptides in fraction F11. Subsequently, WALPTQSW (WW-8) and WLPTKSW (WW-7) from fraction F11 were synthesized, and their ACE IC50 was determined to be 4.7 ± 0.1 and 7.9 ± 0.1 µM, respectively. The dipeptidyl peptidase-4 (DPP4) inhibitory and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activities of WALPTQSW (WW-8) were also explored to give IC50 values of 131.7 ± 5.2 and 191.8 ± 7.0 µM, respectively. The molecular docking and inhibition mechanism studies indicated that WW-8 inhibited ACE and DPP4 as competitive and non-competitive inhibitors, respectively. The pre-incubation experiment of WW-8 toward ACE and DPP4 demonstrated that WW-8 was a true-inhibitor type. Additionally, the amount of WW-8 was quantified to be 5.8 ± 0.2 and 35 ± 0.4 µg per milligram hydrolysate and fraction F11, respectively. This study demonstrated tandem bioassay-guided SCX-RP SPE fractionation efficiently screened ACEI peptide derived from INCP GP hydrolysate, adding more value to Inca nut cake (a leftover of the oil industry) as a bioactive peptide precursor.

The Rationale for Using Fixed-Dose Combination Therapy in the Management of Hypertension in Colombia: A Narrative Review.

Hypertension is a major risk factor for cardiovascular disease and the leading cause of death in Colombia. While the rate of hypertension awareness in Colombia is generally high, rates of treatment initiation, adherence, and blood pressure (BP) control are suboptimal. Major international hypertension guidelines recommend starting treatment with a combination of antihypertensive agents, and the use of a single-pill combination (SPC) to maximize adherence. In contrast, Colombian hypertension guidelines recommend starting treatment with diuretic monotherapy in most patients, and only initiating combination therapy in those with BP > 160/100 mmHg. Therefore, the aim of the current narrative review is to examine the rationale for using SPCs to treat hypertension in Colombia, in the context of the major issues for BP control there. There is evidence of widespread therapeutic inertia in hypertension management, particularly in primary care, in Colombia. Moreover, combination therapy, angiotensin-converting enzyme inhibitors, and long-acting calcium channel blockers, which are internationally recommended as first-line drug therapies, are underutilized there. Adherence to antihypertensive therapy is low in Colombia and may be enhanced by use of SPCs as well as better patient education and follow-up. While there are promising national initiatives to improve BP management, more needs to be done by individual physicians. Antihypertensive SPCs are available on the national essential medicines list and may help to overcome some of the problems with suboptimal adherence, therapeutic inertia, and low rates of BP control that contribute to the high cardiovascular death rate in Colombia.

Development and validation of a prognostic model for predicting post-discharge mortality risk in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).

BACKGROUND: Accurately predicting post-discharge mortality risk in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) remains a complex and critical challenge. The primary objective of this study was to develop and validate a robust risk prediction model to assess the 12-month and 24-month mortality risk in STEMI patients after hospital discharge. METHODS: A retrospective study was conducted on 664 STEMI patients who underwent PPCI at Xiangtan Central Hospital Chest Pain Center between 2020 and 2022. The dataset was randomly divided into a training cohort (n = 464) and a validation cohort (n = 200) using a 7:3 ratio. The primary outcome was all-cause mortality following hospital discharge. The least absolute shrinkage and selection operator (LASSO) regression model was employed to identify the optimal predictive variables. Based on these variables, a regression model was constructed to determine the significant predictors of mortality. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). RESULTS: The prognostic model was developed based on the LASSO regression results and further validated using the independent validation cohort. LASSO regression identified five important predictors: age, Killip classification, B-type natriuretic peptide precursor (NTpro-BNP), left ventricular ejection fraction (LVEF), and the usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ACEI/ARB/ARNI). The Harrell's concordance index (C-index) for the training and validation cohorts were 0.863 (95% CI: 0.792-0.934) and 0.888 (95% CI: 0.821-0.955), respectively. The area under the curve (AUC) for the training cohort at 12 months and 24 months was 0.785 (95% CI: 0.771-0.948) and 0.812 (95% CI: 0.772-0.940), respectively, while the corresponding values for the validation cohort were 0.864 (95% CI: 0.604-0.965) and 0.845 (95% CI: 0.705-0.951). These results confirm the stability and predictive accuracy of our model, demonstrating its reliable discriminative ability for post-discharge all-cause mortality risk. DCA analysis exhibited favorable net benefit of the nomogram. CONCLUSION: The developed nomogram shows potential as a tool for predicting post-discharge mortality in STEMI patients undergoing PPCI. However, its full utility awaits confirmation through broader external and temporal validation.