Angiotensin-converting Enzyme Inhibitors Research Articles

The Effect of Renin-Angiotensin-Aldosterone System Blocking Agents on the Long-term Disease Course of Patients With Crohn's Disease.

The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn's disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.

Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers After Transcatheter Aortic Valve Replacement: A Meta-Analysis

BackgroundPersistent left ventricular hypertrophy after transcatheter aortic valve replacement (TAVR) has been associated with poor outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), due to their favorable effects on ventricular remodeling, have been hypothesized to improve outcomes post-TAVR, yet there are no recommendations regarding their use. ObjectivesThis study aimed to compare the outcomes of patients receiving ACEIs/ARBs with those not receiving ACEIs/ARBs after TAVR. MethodsWe performed a literature search on PubMed and Cochrane Library until June 14, 2023, and included all studies comparing clinical outcomes between patients given ACEIs/ARBs and those not given ACEIs/ARBs after TAVR. All-cause mortality was the primary outcome. We used a random effects model with appropriate corrections to calculate relative risk (RR) and CIs, with all analyses carried out using R v4.0.3. ResultsWe included ten studies on the use of ACEIs/ARBs post-TAVR. Patients on ACEIs/ARBs had lower risk of all-cause mortality (RR: 0.74, 95% CI: 0.65-0.86, I2 = 62%, chi-square P < 0.01), cardiovascular mortality (RR: 0.70, 95% CI: 0.56-0.88, I2 = 0%, chi-square P = 0.54), and new-onset atrial fibrillation (RR: 0.71, 95% CI: 0.52-0.96, I2 = 0%, chi-square P = 0.59). Patients on ACEIs/ARBs had a similar risk of myocardial infarction, heart failure, stroke, new permanent pacemaker implantation, acute kidney injury, major bleeding, vascular complications, aortic regurgitation, and mitral regurgitation. ConclusionsWe found that patients receiving ACEIs/ARBs had a lower risk of all-cause mortality, cardiovascular mortality, and new-onset atrial fibrillation. Risk of other outcomes was similar to patients not receiving ACEIs/ARBs. Randomized clinical trials are needed to explore the benefits of ACEIs/ARBs post-TAVR, so that definitive guidelines can be developed.

Right Ventricle and Autoimmune Diseases.

Autoimmune diseases can express pathologies in specific organs (e.g. thyroid, pancreas, skin) or generate systemic pathologies (generalized lupus erythematosus, rheumatoid arthritis, systemic sclerosis), the latter usually present systemic inflammatory phenomena. Some studies have reported alterations in right ventricular contractility in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and juvenile idiopathic arthritis, which may contribute to the known outcome of increased cardiovascular risk. However, there is not much information available on the causes that generate these alterations, the most likely being small vessel damage and fibrosis due to subclinical inflammation.1-5 In this sense, the disease in which the alterations of the right ventricle have been more studied is systemic sclerosis, specifically at the changes induced due to pulmonary arterial hypertension, this being one of the main causes of death in this group of patients after the significant decrease in mortality associated with the sclerodermic renal crisis with the treatment of angiotensin-converting enzyme inhibitors. In this review, we will focus on explaining the structural and functional changes that occur in the right ventricle of patients with systemic sclerosis, from early alterations to late complications. In this context, it is necessary to distinguish between right heart alterations that occur in patients with systemic sclerosis and pulmonary arterial hypertension and those that occur without pulmonary arterial hypertension and that can be attributed to other causes such as microvascular damage or myocardial fibrosis.

Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient.

To assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19. We conducted a multiple population-based case-control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated. ACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69-0.89] and aOR = 0.80 [95%CI 0.72-0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52-0.98] and aOR = 0.69 [95%CI 0.52-0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82-0.94] and aOR = 0.92 [95%CI 0.86-0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61-0.85]), mortality (aOR = 0.59 [95%CI 0.38-0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79-0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60-0.95]), mortality (aOR = 0.36 [95%CI 0.17-0.75]) and disease progression (aOR = 0.73 [95%CI 0.56-0.95]). This large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes.

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.

Unplanned rehospitalisation due to medication harm following an Acute Myocardial Infarction.

Introduction The contribution of medication harm to rehospitalisation and adverse patient outcomes after an acute myocardial infarction (AMI) needs exploration. Rehospitalisation is costly to both patients and the healthcare facility. Following an AMI, patients are at risk of medication harm as they are often older, have multiple comorbidities and polypharmacy. This study aimed to quantify and evaluate medication harm causing unplanned rehospitalisation after an AMI. Methods This was a retrospective cohort study of patients discharged from a quaternary hospital post-AMI. All rehospitalisations within 18 months were identified using medical record review and coding data. The primary outcome measure was medication harm rehospitalisation. Preventability, causality and severity assessments of medication harm were conducted. Results A total of 1564 patients experienced an AMI and 415 (26.5%) were rehospitalised. Eighty-nine patients (5.7% of total population; 6.0% of those discharged) experienced a total of 101 medication harm events. Those with medication harm were older (p=0.007) and had higher rates of heart failure (p=0.005), chronic kidney disease (CKD) (p=0.046), chronic obstructive pulmonary disease (COPD) (p=0.037) and a prior history of ischaemic heart disease (p=0.005). Gastrointestinal (GI) bleeding, acute kidney injury (AKI) and hypotension were the most common medication harm events. Forty percent of events were avoidable and 84% were classed as 'serious'. Furosemide, antiplatelets and angiotensin-converting enzyme inhibitors (ACEi) were the most commonly implicated medications. The median time to medication harm rehospitalisation was 79 days (interquartile range [IQR]: 16-200 days). Conclusion Medication harm causes unplanned rehospitalisation in 5.7% of all AMI patients (1 in 17 patients; 6.0% of those discharged). The majority of harm was serious and occurred within the first 200 days of discharge. This study highlights that measures to attenuate the risk of medication harm rehospitalisation are essential, including post-discharge medication management.

Evaluating prescription of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in patients with diabetes and albuminuria.

Although guidelines recommend the use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) in patients with diabetes, hypertension, and albuminuria, their use remains suboptimal in several developed countries. Limited data are available on ACEi/ARB use in developing countries. Here, we assessed the use of ACEi/ARB and identified factors contributing to their underutilization at Hatyai Hospital, Thailand. This retrospective cross-sectional study was conducted using data from the Hatyai Hospital database. Adult patients with diabetes, hypertension, and albuminuria were included. Clinical data and laboratory results were extracted. Furthermore, this study recorded pre-specified conditions that influenced physicians' decisions regarding the prescription of ACEi/ARBs in patients who did not adhere to guidelines. Of 4,655 eligible patients, 500 patients were selected. The average age of the patients was 66.3 years, and 59.6% were female. The adherence rate was 72.4%. Multivariate logistic regression analysis found a significant association between non-adherence and chronic kidney disease (CKD) stage (OR = 1.29, 95% CI: 1.04-1.60, p = 0.019). The most common pre-specified condition contributing to non-adherence was "no condition identified" (69.8%). Among the cases of non-adherence, 21.7% were due to ACEi/ARB discontinuation after acute kidney injury, followed by hyperkalemia (5.1%) and a moderate increase in serum creatinine (4.3%). ACEi/ARB therapy was suboptimal in patients with diabetes, hypertension, and albuminuria. Non-adherence was associated with CKD stage, possibly because of concerns about adverse events and healthcare-related factors.

Sacubitril/valsartan compared to equivalent/sub-equivalent dose angiotensin receptor blocker or angiotensin-converting enzyme inhibitor in heart failure with reduced ejection fraction: a meta-analysis of randomized trials.

The objective of this meta-analysis is to determine how sacubitril/valsartan (SV) compares to equivalent and sub-equivalent angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEI) in patients with heart failure with reduced ejection fraction (HFrEF). The databases of PubMed and EMBASE were used to identify those randomized controlled trials which compared SV to ARB/ACEI in patients with HFrEF. Only those trials that reported outcomes regarding total mortality, cardiovascular mortality, and worsening heart failure were considered. Meta-analysis was performed separately in those patients receiving equivalent doses of ARB/ACEI and those receiving sub-equivalent doses. Equivalent doses were SV 97/103 = valsartan 160mg twice daily = enalapril 20mg twice daily = ramipril 5mg twice daily. Meta-analyses were performed using Review Manager 5.4. Twelve randomized trials were identified involving 17,484 patients: 11,291 in the sub-equivalent group (8 trials) and 6193 in the equivalent group (4 trials). Meta-analyses showed there were no statistical differences regarding the outcomes of total mortality, cardiovascular mortality, and worsening heart failure in the equivalent dosing group. However, SV reduced total mortality (risk ratio (RR) = 0.85, 95% confidence interval (CI) = 0.78-0.93, p < 0.001), cardiovascular mortality (RR = 0.81, 95% CI = 0.73-0.90, p ≤ 0.001) and worsening heart failure (RR = 0.77, 95% CI = 0.64-0.92, p = 0.005) in the sub-equivalent group. When compared to equivalent doses of ARB/ACEI, SV is not superior in reducing mortality and worsening heart failure. SV is superior when compared to sub-equivalent doses of ACEI.

Association of serum sodium minus chloride level at initiation of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and hyperkalemia in patients with CKD: a case control study

Abstract Background Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) exert a renoprotective effect on patients with chronic kidney disease (CKD). Despite their benefit, one of their side effects is hyperkalemia, and it is one of the most common reasons for discontinuation of these drugs. Hyperchloremic metabolic acidosis is a known risk factor for hyperkalemia in patients with CKD. However, whether it is a risk factor for hyperkalemia after initiating ACE-I or ARB remains unclear. Methods In a previous study, serum sodium minus chloride level ([Na+) − (Cl−]) was identified as useful for diagnosing metabolic acidosis. To estimate the baseline acid–base status, we determined for the cutoff value of [Na+] − [Cl−] that correlates with [HCO3−] below 24 mEq/L in patients with CKD. We then investigated whether this cutoff value was associated with hyperkalemia (serum potassium level ≥ 5.0 mEq/L) after initiating ACE-I or ARB in patients with CKD. Results In the investigation of the cutoff value of [Na+] − [Cl−], 612 patients were examined, and [Na+] − [Cl−] showed a good correlation with [HCO3−] (r = 0.67, p &lt; 0.001). Based on receiver operating curve analysis, we derived a cut-off value of [Na+] − [Cl−] below 33.5 mEq/L. Using this cut off value, the sensitivity and specificity of [Na+] − [Cl−] for metabolic acidosis were 75.2% and 75.0%, respectively. To explore whether metabolic acidosis is associated with hyperkalemia after initiating ACE-I or ARB, we examined 1143 patients with CKD. Among this cohort, 403 (35.3%) patients had [Na+] − [Cl−] &lt; 33.5 mEq/L at baseline, and the incidence of hyperkalemia was significantly higher in univariate analysis (9.2% versus 4.2%, p = 0.03). However, in multivariate analysis, [Na+] − [Cl−] &lt; 33.5 mEq/L was not associated with hyperkalemia (odds ratio 1.13; 95% confidence interval 0.65–1.95). Conclusions Hyperchloremic metabolic acidosis was not associated with hyperkalemia after initiation of ACE-I or ARB in patients with CKD.

A new nomogram to predict in-hospital mortality in patients with acute decompensated chronic heart failure and diabetes after 48 Hours of Intensive Care Unit

BackgroundThe study set out to develop an accurate and clinically valuable prognostic nomogram to assess the risk of in-hospital death in patients with acute decompensated chronic heart failure (ADCHF) and diabetes.MethodsWe extracted clinical data of patients diagnosed with ADCHF and diabetes from the Medical Information Mart for Intensive Care III database. Risk variables were selected utilizing least absolute shrinkage and selection operator regression analysis, and were included in multivariate logistic regression and presented in nomogram. bootstrap was used for internal validation. The discriminative power and predictive accuracy of the nomogram were estimated using the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis (DCA).ResultsAmong 867 patients with ADCHF and diabetes, In-hospital death occurred in 81 (9.3%) patients. Age, heart rate, systolic blood pressure, red blood cell distribution width, shock, β-blockers, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, assisted ventilation, and blood urea nitrogen were brought into the nomogram model. The calibration curves suggested that the nomogram was well calibrated. The AUC of the nomogram was 0.873 (95% CI: 0.834–0.911), which was higher that of the Simplified Acute Physiology Score II [0.761 (95% CI: 0.711–0.810)] and sequential organ failure assessment score [0.699 (95% CI: 0.642–0.756)], and Guidelines-Heart Failure score [0.782 (95% CI: 0.731–0.835)], indicating that the nomogram had better ability to predict in-hospital mortality. In addition, the internally validated C-index was 0.857 (95% CI: 0.825–0.891), which again verified the validity of this model.ConclusionsThis study constructed a simple and accurate nomogram for predicting in-hospital mortality in patients with ADCHF and diabetes, especially in those who admitted to the intensive care unit for more than 48 hours, which contributed clinicians to assess the risk and individualize the treatment of patients, thereby reducing in-hospital mortality.

Angiotensin II Is Involved in MLKL Activation During the Development of Heart Failure Following Myocardial Infarction in Rats.

Several reports assume that myocardial necroptotic cell death is induced during the development of chronic heart failure. Although it is well accepted that angiotensin II induces apoptotic cell death of cardiac myocytes, the involvement of angiotensin II in the induction of myocardial necroptosis during the development of heart failure is still unknown. Therefore, we examined the role of angiotensin II in myocardial necroptosis using rat failing hearts following myocardial infarction and cultured cardiomyocytes. We found that administration of azilsartan, an angiotensin II AT1 receptor blocker, or trandolapril, an angiotensin-converting enzyme inhibitor, to rats from the 2nd to the 8th week after myocardial infarction resulted in preservation of cardiac function and attenuation of mixed lineage kinase domain-like (MLKL) activation. Furthermore, the ratio of necroptotic cell death was increased in neonatal rat ventricular cardiomyocytes cultured with conditioned medium from rat cardiac fibroblasts in the presence of angiotensin II. This increase in necroptotic cells was attenuated by pretreatment with azilsartan. Furthermore, activated MLKL was increased in cardiomyocytes cultured in conditioned medium. Pretreatment with azilsartan also prevented the conditioned medium-induced increase in activated MLKL. These results suggest that angiotensin II contributes to the induction of myocardial necroptosis during the development of heart failure.

Mineralocorticoid receptor antagonists in kidney transplantation.

The fundamental role of the renin-angiotensin-aldosterone system in the pathophysiology of chronic kidney disease, congestive heart failure, hypertension and proteinuria is well established in pre-clinical and clinical studies. Mineralocorticoid receptor antagonists are among the primary options for renin-angiotensin-aldosterone system blockage, along with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. In this narrative review, we aim to evaluate the efficiency and safety of mineralocorticoid receptor antagonists in kidney transplant recipients, including the potential underlying pathophysiology. The efficiency and safety of mineralocorticoid receptor antagonists in managing chronic kidney disease and proteinuria, either non-nephrotic or nephrotic range, have been demonstrated among nontransplanted patients, though studies investigating the role of mineralocorticoid receptor antagonists among kidney transplant recipients are scarce. Nevertheless, promising results have been reported in pre-clinical and clinical studies among kidney transplant recipients regarding the role of mineralocorticoid receptor antagonists in terms of ischaemia-reperfusion injury, proteinuria, or calcineurin inhibitor-mediated nephrotoxicity without considerable adverse events such as hypotension, hyperkalaemia or worsening renal functions. Even though initial results regarding the role of mineralocorticoid receptor antagonist therapy for kidney transplant recipients are promising, there is clear need for large-scale randomized clinical trials with long-term follow-up data.

Evaluation of Alacepril Administration in Canine Patent Ductus Arteriosus According to Plasma Chymase Activity.

Chymase in the renin-angiotensin system (RAS) actively contributes to cardiac disease progression. Chymase is activated to produce angiotensin II during tissue injury and is involved in hemodynamics. A recent study demonstrated that plasma chymase activity reflects hemodynamic changes and aids in understanding patent ductus arteriosus (PDA) pathophysiology. The present study examined the relationship between plasma chymase activity and the administration of angiotensin-converting enzyme (ACE) inhibitor. Alacepril was administered to 13 puppies with PDA. Conventional echocardiographic parameters and non-invasive blood pressure were measured before and after medication. Plasma chymase activity was calculated using the colorimetric absorbance method. Plasma chymase activity significantly increased, but blood pressure significantly decreased. We detected an increase in plasma chymase activity due to ACE inhibition in PDA cases treated with alacepril. Plasma chymase activity was affected and altered by alacepril. In veterinary medicine, plasma chymase activity may be a novel method for assessing the pathology of and therapy for cardiac diseases.

The Potential Role of Angiotensin-Converting Enzyme Inhibitors and Beta-Blockers in Reducing Pneumonia Severity in Older Adults

The Potential Role of Angiotensin-Converting Enzyme Inhibitors and Beta-Blockers in Reducing Pneumonia Severity in Older Adults

Repurposing of Angiotensin-converting-enzyme Inhibitor on Prevention of Post-surgical Tendon Adhesion.

Formation of adhesion bands is a frequent clinical complication after tendon injury or surgery with limited treatment options. This study investigates the repurposing of Angiotensin-Converting-Enzyme Inhibitor (ACEI) in attenuating post-operative tendon-sheath adhesion bands in an Achilles tendon rat model. Structural, mechanical, histological, and biochemical characteristics of the Achilles tendons were compared in the presence and absence of oral ACEI (enalapril) using the Achilles tendon adhesion (TA) model in rats. Inflammation and total fibrosis of tendon tissues were compared between groups using molecular investigations along with macroscopic and histological scoring methods. ACEI significantly alleviated the severity, length, and density of Achilles TAs. Moreover, histopathological changes, recruitment of inflammatory cells, and inflammation were significantly decreased in post-operative tissue samples as quantified with the Moran scoring model. We showed that ACEI treatment elicits a potent anti-fibrotic effect on tendon tissue samples, as illustrated by decreasing the severity and extent of the formed fibrotic tissue and collagen accumulation at the site of surgery when scored either by Tang or Ishiyama grading systems. The H&E staining showed no histopathological changes or damage to the principal organs. Our results showed that ACEI is a safe and effective therapeutic candidate with potent immunomodulatory and anti-fibrotic features to alleviate surgery-induced development of fibrotic adhesive tissue. However, its efficacy needs to be further validated in clinical studies.

Prescribing Trends of Renin-Angiotensin System Inhibitors and Mortality among Acute Coronary Syndrome Patients: Insights from the Malaysian National Cardiovascular Disease Registry

Abstract Background: Despite guideline recommendations, suboptimal prescription rates of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been observed in patients with acute coronary syndrome. Objective: This study aimed to examine the temporal trends, variations, and mortality outcomes among acute coronary syndrome patients prescribed ACEIs/ARBs in the multi-ethnic population of Malaysia. Methodology: This retrospective study utilized data from the Malaysian National Cardiovascular Disease–Acute Coronary Syndrome registry, encompassing consecutive patient records from 2008 to 2017 (N = 60,854). Ten-year temporal trends of on-discharge ACEIs/ARBs prescription were examined. Demographics, clinical characteristics and 1-year all-cause mortality outcomes were compared between patients prescribed and not prescribed ACEIs/ARBs. Results: The 10-year prescription rate of on-discharge ACEIs/ARBs was 52.8% (n = 32,140), with a significant decline over the years [linear trend test, P = 0.008; SD = 0.03; SE = 0.001; 95% CI = 0.55-0.64]. Patients aged ≥65 years (aOR = 0.79; 95% CI = 0.73–0.86) were less likely to be prescribed ACEIs/ARBs than those aged &lt;65 years. In addition, patients with comorbid diabetes mellitus (DM) (aOR = 0.85; 95% CI = 0.79–0.92) and chronic kidney disease (CKD) (aOR = 0.34; 95% CI = 0.30–0.40) were significantly less likely to receive ACEIs/ARBs. IPW-adjusted survival analysis revealed a 38% lower 1-year all-cause mortality rate in patients prescribed on-discharge ACEIs/ARBs (HR = 0.62; 95% CI = 0.56–0.69; P &lt; 0.001). Conclusion: Acute coronary syndrome patients with concomitant DM and CKD were less likely to receive on-discharge ACEIs/ARBs in Malaysia. Suboptimal prescription rates of ACEIs/ARBs persisted over the 10-year period, despite improved 1-year survival in ACS patients prescribed ACEIs/ARBs.

Are Guideline Concordant Processes of Care Consistent Across the Rural-Urban Continuum? A Retrospective Cohort Study of Adults Newly Treated for Type 2 Diabetes.

To explore the association between place of residence (metropolitan, urban, rural) and guideline concordant processes of care in the first year of type 2 diabetes management. We conducted a retrospective cohort study of new metformin users between April 2015 and March 2020 in Alberta. Outcomes were identified as guideline concordant processes of care through the review of clinical practice guidelines and published literature. Using multivariable logistic regression, the following outcomes were examined by place of residence: dispensation of a statin, angiotensin-converting-enzyme-inhibitor (ACEi) or angiotensin-II-receptor-blocker (ARB), eye examination, and glycated hemoglobin A1C, cholesterol, and kidney function testing. Of 60,222 new metformin users, 67% resided in a metropolitan area, 10% in urban, and 23% in rural. After confounder adjustment, rural residents were less likely to have a statin dispensed (aOR0.83; 95%CI:0.79-0.87) or undergo cholesterol testing (aOR0.86; 95%CI:0.83-0.90), compared to metropolitan residents. In contrast, rural residents were more likely to receive A1C and kidney function testing (aOR1.14; 95%CI:1.08-1.21 and aOR1.17; 95%CI:1.11-1.24, respectively). ACEi/ARB use and eye examinations were similar across place of residence. Processes of care varied by place of residence. Limited cholesterol management in rural areas is concerning because this may lead to increased cardiovascular outcomes.

Optimization of Extraction Process and Activity of Angiotensin-Converting Enzyme (ACE) Inhibitory Peptide from Walnut Meal.

In order to further realize the resource reuse of walnut meal after oil extraction, walnut meal was used as raw material to prepare polypeptide, and its angiotensin-converting enzyme (ACE) inhibitory activity was investigated. The ACE inhibitory peptides were prepared from walnut meal protein by alkaline solution and acid precipitation. The hydrolysis degree and ACE inhibition rate were used as indexes to optimize the preparation process by single-factor experiment and response surface method. The components with the highest ACE activity were screened by ultrafiltration, and their antioxidant activities were evaluated in vitro. The effect of gastrointestinal digestion on the stability of walnut peptide was analyzed by measuring molecular weight and ACE inhibition rate. The results showed that the optimal extraction conditions were pH 9.10, hydrolysis temperature 54.50 °C, and hydrolysis time 136 min. The ACE inhibition rate of walnut meal hydrolysate (WMH) prepared under these conditions was 63.93% ± 0.43%. Under the above conditions, the fraction less than 3 kDa showed the highest ACE inhibitory activity among the ACE inhibitory peptides separated by ultrafiltration. The IC50 value of scavenging ·OH free radical was 1.156 mg/mL, the IC50 value of scavenging DPPH free radical was 0.25 mg/mL, and the IC50 value of scavenging O2- was 3.026 mg/mL, showing a strong total reducing ability. After simulated gastrointestinal digestion in vitro, the ACE inhibitory rate of walnut peptide decreased significantly, but it still maintained over 90% ACE inhibitory activity. This study provides a reference for the application of low-molecular-weight walnut peptide as a potential antioxidant and ACE inhibitor.

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.

OUTPATIENT FOLLOW-UP OF PATIENTS WITH ATHEROSCLEROSIS OF LOWER EXTREMITIES: PROMISING WAYS TO IMPROVE RESULTS

HighlightsThe article shows the positive impact of 3-year cardiology follow-up in patients with atherosclerosis of lower extremities. Aim. To study the impact of outpatient cardiology follow-up in patients with peripheral artery disease on the prognosis and the frequency and outcomes of surgical interventions.Methods. The study included 585 patients with peripheral artery disease who underwent outpatient follow-up - by a surgeon (n = 131) and a cardiologist (n = 454). The groups were compared according to the main clinical and anamnestic data and type of drug therapy. After 3 years, the incidence of adverse outcomes (nonfatal myocardial infarction, nonfatal stroke, new amputations and deaths) and factors associated with adverse outcomes in the selected cohort were evaluated.Results. The group of patients who were followed by cardiologist received optimal drug therapy more often compared with patients followed by surgeon: β-blockers (80.4% vs. 32.8%; p &lt; 0.001), angiotensin converting enzyme inhibitors (61.0% vs. 38.2%; p &lt; 0.001), statins (87.0% vs. 63.4%; p &lt; 0.001). Within three years, fatal outcome was more common in the group of patients followed by surgeon (13.0% vs. 6.8%, p = 0.023). The factors that positively affected the prognosis of patients were cardiology follow-up (OR 0.34; 95% CI 0.17–0.7; p &lt; 0.001), taking aspirin (OR 0.12; 95% CI 0.06–0.22, p &lt; 0.001) and statins (OR 0.11; 95% CI 0.05–0.21; p &lt; 0.001).Conclusion. The results of this study confirm the need for more effective cardiology follow-up of patients with peripheral artery disease. This will improve the results of treatment and reduce the number of complications. Further research in this area can help determine the optimal strategies for follow-up and improve the quality of life of patients with peripheral artery disease.