Including Angiotensin Converting Enzyme Inhibitors Research Articles

Investigating the potential association between hypertension and cancer: unveiling onco-hypertension as an innovative concept

Hypertension and cancer show a possible association, with hypertension being a result of cancer and its treatments and also serving as a potential risk factor for the development of cancer. The term "onco-hypertension" describes the presence of hypertension in individuals who have been diagnosed with cancer. Among individuals with cancer, hypertension is the most common coexisting medical condition, occurring in 38% of cases. Cancer-related hypertension involves various mechanisms, including tumor-related factors, coexisting conditions, renal dysfunction, hormonal abnormalities, and stress-related inflammation. Cancer treatments like chemotherapy-targeted therapies and immunotherapies have the potential to influence the regulation of blood pressure through the renin-angiotensin-aldosterone system (RAAS), sodium balance, and fluid retention. Epidemiological studies suggest a potential link between hypertension and specific types of cancer, although the exact reasons and underlying mechanisms remain uncertain. Antihypertensive medications have varying associations with cancer risk. Diuretics are linked to renal cell carcinoma (RCC), thiazide medications to squamous cell carcinoma (SCC), and angiotensin-converting enzyme (ACE) inhibitors to a potential increased risk of lung cancer. However, studies on angiotensin receptor blockers (ARBs) show inconclusive results. Managing onco-hypertension may require pharmacological interventions in addition to lifestyle modifications. Antihypertensive medications commonly used include ACE inhibitors, ARBs, diuretics, calcium channel blockers, and beta-blockers. Factors such as overall health, cancer stage, concomitant medications, treatment interactions, efficacy, tolerability, and side effects guide medication selection.

Feasibility, efficacy and safety of early and rapid initiation of evidence-based treatment for patients with HFrEF- a real world experience of the "four drugs in four weeks" strategy

Abstract Background Evidence-based treatment for heart failure with reduced ejection fraction (HFrEF) is associated with improved outcomes for patients. However, there is uncertainty as to how treatment with these foundational drugs should best be implemented. Objectives To evaluate whether early and rapid initiation of medications for patients with HFrEF using a 4 x 4 approach (4 pillars of HFrEF therapy in 4 weeks) is feasible, safe, and effective. Methods We recruited consecutive patients from April to July 2021 with a new diagnosis of HFrEF who were either assessed at our urgent HF clinic or had a recent HF hospitalisation. All patients had regular reviews (every 1-2 weeks, combination of telephone and face-to-face) at our hospital-based HF clinic by a HF consultant or senior HF specialist nurse for initiation and up-titration of guideline-recommended therapy including angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor neprilysin inhibitor (ARNI), beta blockers (BB), mineralocorticoid receptor antagonist (MRA) and sodium glucose co-transporter inhibitor (SGLT2i). Results Of 100 patients approached, 19 patients were considered unsuitable for the 4x4 pathway (79% due to severe frailty or significant comorbidities). 81 patients were enrolled (61% male, median (IQR) age: 73 (67-82) years, median (IQR) NT-proBNP: 3764 (1597-7487) ng/L); 39 (48%) patients achieved "4 drugs at 4 weeks". Of the 42 patients who did not, 33 (79%) had contraindication to one or more of the drug classes at the outset, including renal impairment (28%), bradycardia (18%) and hyperkalaemia (15%). Patients who did not achieve "4 drugs at 4 weeks" were older, more symptomatic, and had higher NTproBNP and worse renal function. During a median follow up of 554 days, 6 (7%) patients died and 31 (38%) experienced the combined outcome of all-cause death / hospitalisation. Patients who did not achieve "4 drugs at 4 weeks", compared to those who did, had a 2.5 fold increased risk of the combined outcome (Figure 1). They were also less likely to be up-titrated to targeted doses of HF medications (Figure 2). There was noticeable improvement in NTproBNP with no significant change in renal function or systolic BP in both groups. Compared to those who did not achieve "4 drugs at 4 weeks", those who did showed larger improvement in LVEF (8% vs 2%) at 6 months. 5 patients (6%) experienced significant side effects during medication up-titration: 4 had symptomatic hypotension and 1 had hyperkalaemia. Conclusion The 4x4 strategy is clinically feasible and safe when implemented in selected patients with HFrEF and may be associated with improved outcomes. Our results support larger studies to further investigate the generalisability and effectiveness of the 4x4 strategy.

ACE-Inhibitors in Hypertension: A Historical Perspective and Current Insights.

This review describes the discovery and development of ACE inhibitors as antihypertensive agents, compares their efficacy, tolerability, and safety to ARBs, and highlights the contemporary issues surrounding ACE inhibitor use for HTN. Angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for the management of hypertension (HTN) and other chronic conditions including heart failure and chronic kidney disease. These agents inhibit ACE, the enzyme that is responsible for converting angiotensin (AT) I to AT II. Inhibiting the synthesis of AT II causes arterial and venous vasodilation, natriuresis, and a decrease in sympathetic activity, resulting in the reduction of blood pressure. ACE inhibitors are first-line therapy in HTN management along with thiazide diuretics, calcium channel blockers, and angiotensin receptor blockers (ARB). Along with inhibiting AT II synthesis, inhibition of ACE causes accumulation of bradykinin, increasing the risk of bradykinin-mediated side effects like angioedema and cough. Since ARBs do not work on ACE in the renin-angiotensin system, the risk of angioedema and cough are lower with ARBs. Recent evidence has also suggested ARBs may have neuroprotective effects compared to other antihypertensives, including ACE inhibitors; however, this warrants further study. Currently, ACE inhibitors and ARBs have an equal class of recommendation for first-line treatment for the management of HTN. Recent evidence has shown ARBs to be just as effective as ACE inhibitors for HTN but with improved tolerability.

Clinical outcomes of renin angiotensin system inhibitor-based dual antihypertensive regimens in chronic kidney disease: a network meta-analysis

This study comprehensively investigated clinical outcomes associated with renin angiotensin system inhibitor-based dual antihypertensive regimens in non-dialysis chronic kidney disease (CKD) patients. Keyword searches of databases were performed per PRISMA-NMA guidelines. Frequentist network meta-analysis were conducted with 16 head-to-head randomized controlled trials. The effect sizes of dichotomous and continuous variables were estimated with odds ratio (OR) and standard mean differences (SMD), respectively. The protocol is registered in PROSPERO (CRD42022365927). Dual antihypertensive regimens with combination of angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) demonstrated substantially reduced odd of major cardiovascular disease (CVD) events over other regimens including angiotensin converting enzyme inhibitor (ACEI) monotherapy (OR 3.19) and ARB monotherapy (OR 2.64). Most significant reductions in systolic (SBP) and diastolic blood pressure (DBP) were observed with ARB-based CCB dual regimen over ACEI monotherapy (SMD 17.60 SBP and 9.40 for DBP), ACEI-based CCB regimen (SMD 12.90 for SBP and 9.90 for DBP), and ARB monotherapy (SMD 13.20 for SBP and 5.00 for DBP). However, insignificant differences were noticed for the odds of hyperkalemia, end stage renal disease progression, and all-cause mortality. ARB-based CCB regimen has the greatest benefits on BP reduction as well as major CVD risks in non-dialysis CKD patients.

Efficacy and safety of sodium glucose cotransporter 2 inhibitors plus standard care in diabetic kidney disease: A systematic review and meta-analysis

IntroductionMany people with type 2 diabetes progress to end-stage diabetic kidney disease (DKD) despite blockade of the renin-angiotensin system, suggesting the need for innovative treatment options for DKD. To capture the findings of recent studies, we performed an updated systematic review and meta-analysis of the efficacy and safety of sodium glucose co-transporter 2 (SGLT2) inhibitors combined with standard care involving angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) on the development and progression of DKD in people with type 2 diabetes compared with standard care alone. MethodsThe Cochrane Library, MEDLINE, EMBASE, PubMed and clinical trials registers were systematically searched for randomized controlled trials published before 1 September 2022. Primary outcomes were urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Secondary outcomes were glycated hemoglobin (HbA1c) and systolic blood pressure (SBP). Relative risk was calculated for adverse events. ResultsEight studies enrolling 5512 participants were included. In the meta-analysis (n = 1327), SGLT2 inhibitors were associated with a statistically significant reduction in UACR (weighted mean difference [WMD] -105.61 mg/g, 95 % CI -197.25 to −13.98, I2 = 99 %, p = 0.02). There was no statistically significant difference in relation to eGFR (n = 1375; WMD -0.23 mL/min/1.73m2, 95 % CI -4.34 to 3.89, I2 = 94 %, p = 0.91). ConclusionsSGLT2 inhibitors in addition to standard care including ACE inhibitors and/or ARBs significantly reduced albuminuria, HbA1c and SBP when compared to standard care alone, supporting their routine use in people with type 2 diabetes.

Clinical outcomes following discontinuation of renin-angiotensin-system inhibitors in patients with type 2 diabetes and advanced chronic kidney disease: A prospective cohort study.

Renin-angiotensin-system inhibitors (RASi), that include angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) reduce proteinuria, delay chronic kidney disease (CKD) progression, protect against cardiovascular events and heart failure hospitalizations. We examined the associations of discontinuation of ACEi/ARBs with risk of clinical outcomes in Chinese patients with type 2 diabetes (T2D) and advanced-CKD (estimated-glomerular filtration rate [eGFR] <30ml/min/1.73m2). We conducted a prospective, population-based cohort study including 10,400 patients with T2D in Hong Kong stratified by continuation of ACEi/ARBs within 6 months after reaching eGFR <30ml/min/1.73m2 from January 01, 2002 to December 31, 2018 and observed until December 31, 2019. The primary outcomes were death, major-adverse cardiovascular events (MACE), heart failure, end-stage kidney disease (ESKD), and all-cause mortality. Cox-model with time-dependent exposure and covariates was used to estimate the hazard ratio (HR) of outcomes in a propensity-score overlap-weighted cohort. The risk of occurrence of hyperkalemia (plasma potassium >5.5mmol/L) in discontinued-ACEi/ARBs versus continued-ACEi/ARBs users was assessed in a register-based cohort. In the population-based cohort of 10,400 ACEi/ARBs users with new-onset eGFR<30ml/min/1.73m2, 1766 (17.0%) discontinued ACEi/ARBs and 8634 (83.0%) persisted with treatment. During a median follow-up of 3.6 (interquartile range, IQR: 2.11-5.8) years (41,623 person-years), 13.5%, 12.9%, and 27.6% had incident MACE, heart failure and ESKD respectively, and 35.8% died. Discontinued-ACEi/ARBs use was associated with higher risk of MACE (HR=1.27, 95% CI: 1.08-1.49), heart failure (HR=1.85, 95% CI: 1.53-2.25) and ESKD (HR=1.30, 95% CI: 1.17-1.43), and neutral risk of all-cause mortality (HR=0.93, 95% CI: 0.86-1.01) compared to counterparts with continued use. In the register-based cohort (583 discontinued-ACEi/ARBs users and 3817 continued-ACEi/ARBs users), discontinued-ACEi/ARBs had neutral risk of hyperkalemia (HR=0.95, 95% CI: 0.84-1.08). Discontinuation of ACEi/ARBs was associated with increased risk of cardiovascular-renal events supporting their continued use in patients with T2D and advanced-CKD. CUHK Impact Research Fellowship Scheme.

Renin-angiotensin system in the central nervous system: focus on Huntington's disease.

Renin-angiotensin system in the central nervous system: focus on Huntington's disease.

Abstract 9861: Geographic Variation in Prescription of Heart Failure Guideline Directed Medical Therapies for United States Veterans is Prevalent Nationwide

Introduction: In patients with heart failure with reduced ejection fraction (HFrEF), use of guideline directed medical therapies (GDMT) reduces mortality. Whether there is geographic variation in GDMT prescribing is not well-characterized. Hypothesis: We assessed the hypothesis that there is wide geographic variation nationally within the Veterans Affairs (VA) healthcare system for the receipt of GDMT. Methods: We linked the primary residence address of a cohort of Veterans with HFrEF receiving care at VA facilities (n=178,856) to hospital referral regions (HRRs). Using VA and non-VA pharmacy data between July 1, 2020 and July 1, 2021, we defined receipt of GDMT. For each HRR, we calculated the percentage of eligible Veterans that were prescribed each class of GDMT and a composite GDMT z-score. Lastly, we constructed national choropleth maps to depict HRR geographic variation in composite z-scores and prescription of each class of GDMT. Results: There was significant variation in individual GDMT class prescription and composite score across HRRs as shown in choropleth maps ( Figure) . Within HRRs, beta-blocker prescription was highest, with a median 80% of Veterans (interquartile range [IQR] 77.3% to 82.2%), afterload-reducing agents including angiotensin converting enzyme inhibitor / angiotensin receptor blocker / angiotensin receptor-neprilysin inhibitors (ARNI) 69.3% (IQR 66.4% to 72.1%), mineralocorticoid receptor antagonists (MRA) 29.2% (IQR 25.8% to 33.9%), sodium-glucose cotransporter 2 inhibitors (SGLT2I) 10.3% (IQR 7.7% to 12.8%), and ARNI 12.2% (IQR 8.6% to 15.3%). HRRs with the highest and lowest composite scores were often found in the same U.S. Census Regions. Conclusions: In conclusion, wide geographic disparities are present for GDMT prescribing to Veterans across HRRs. Veteran receipt of ARNI, SGLT2I, and MRA is low nationwide. Targeted approaches may be necessary to improve GDMT prescription for Veterans in lower performing HRRs.

Chronic Kidney Disease Related to Cognitive Disorders in the Elderly: A Narrative Literature Review

Chronic kidney disease (CKD) is characterized by progressive and irreversible kidney damage, leading to the inability of the kidneys to perform their functions. Chronic kidney disease causes hypertension, anemia, vascular dysfunction, uremia, proteinuria, systemic inflammation, and oxidative stress associated with cognitive impairment. Age is a population group aged 60 years or more at risk of experiencing health problems and the consequences associated with CKD. One of the common comorbidities experienced by elderly patients with CKD is cognitive impairment. Current treatment options for CKD with cognitive impairment aimed at common risk factors, including angiotensin converting enzyme inhibitors (ACEI) and, angiotensin receptor blockers (ARBs), SGLT-2 inhibitors., GLP-1 RA, and DPP-4 inhibitors. Other interventions, such as erythropoietin (EPO) compensation and reduction of inflammation and oxidative stress, can help improve patients' clinical symptoms. This literature review aims to describe the relationship between chronic kidney disease and cognitive disorders that occur in the elderly.

High throughput screen of small molecules as potential countermeasures to galactic cosmic radiation induced cellular dysfunction

Space travel increases galactic cosmic ray exposure to flight crews and this is significantly elevated once travel moves beyond low Earth orbit. This includes combinations of high energy protons and heavy ions such as 56Fe or 16O. There are distinct differences in the biological response to low-energy transfer (x-rays) or high-energy transfer (High-LET). However, given the relatively low fluence rate of exposure during flight operations, it might be possible to manage these deleterious effects using small molecules currently available. Virtually all reports to date examining small molecule management of radiation exposure are based on low-LET challenges. To that end an FDA approved drug library (725 drugs) was used to perform a high throughput screen of cultured cells following exposure to galactic cosmic radiation. The H9c2 myoblasts, ES-D3 pluripotent cells, and Hy926 endothelial cell lines were exposed to a single exposure (75 cGy) using the 5-ion GCRsim protocol developed at the NASA Space Radiation Laboratory (NSRL). Following GCR exposure cells were maintained for up to two weeks. For each drug (@10µM), a hierarchical cumulative score was developed incorporating measures of mitochondrial and cellular function, oxidant stress and cell senescence. The top 160 scores were retested following a similar protocol using 1µM of each drug. Within the 160 drugs, 33 are considered to have an anti-inflammatory capacity, while others also indirectly suppressed pro-inflammatory pathways or had noted antioxidant capacity. Lead candidates came from different drug classes that included angiotensin converting enzyme inhibitors or AT1 antagonists, COX2 inhibitors, as well as drugs mediated by histamine receptors. Surprisingly, different classes of anti-diabetic medications were observed to be useful including sulfonylureas and metformin. Using a hierarchical decision structure, we have identified several lead candidates. That no one drug or even drug class was completely successful across all parameters tested suggests the complexity of managing the consequences of galactic cosmic radiation exposure.

An umbrella review and meta-analysis of the use of renin-angiotensin system drugs and COVID-19 outcomes: what do we know so far?

IntroductionCoronavirus disease 2019 (COVID-19) is caused by the “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), and commonly presents with fever, loss of smell/taste, and a persistent cough; in severe cases, patients require hospitalisation and external ventilation. Advanced age and pre-existing conditions such as cardiovascular diseases and diabetes have been associated with an increased risk of COVID-19 related mortality.Based on their mechanisms of action and widespread use among patients at high risk of poor disease outcomes, the impact of renin-angiotensin-aldosterone system (RAAS) inhibitors – including angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) – on COVID-19 related outcomes has become a topic of interest, resulting in rapid dissemination of a large number of predominantly retrospective, observational studies since early 2020. Since many of these studies were limited in scope and results were inconclusive, systematic reviews and meta-analyses of published and unpublished findings swiftly followed.AimTo assess the effect of ACEIs and ARBs on COVID-19 related outcomes by summarising the currently available evidence.MethodsUmbrella review of systematic reviews and subsequent meta-analysis. Eligible for inclusion were systematic reviews with meta-analysis focusing on patients with or without COVID-19 exposed to ACEIs and/or ARBs compared to patients not exposed to the medication. Outcomes of interest included risk of infection; hospitalisation; severity; and death. Reviews were identified through a literature search in Medline, EMBASE, Scopus, the Cochrane database of systematic reviews, and medRxiv, from 2019 until 1st of February 2021. Data was extracted using a standardised extraction sheet; the AMSTAR 2 Critical Appraisal Tool for systematic reviews was used for quality assessment. Heterogeneity between studies was evaluated using I2 statistics, and findings of included meta-analyses were summarised using random-effects models. The protocol was registered with PROSPERO (CRD42021233398).ResultsOut of an initial 157 publications, 66 systematic reviews underwent full text screening; after further exclusions based on pre-specified criteria, 47 studies were identified to be relevant. The number of included studies as well as the outcomes of interest varied widely between reviews, with death being the most common.Odds ratio for risk of COVID-19 infection among patients treated with ACEIs/ARBs versus patients not on treatment was 0.99 (95% Confidence Interval (CI) 0.97 – 1.02; 19 studies, I2 = 24.7%); and for hospitalisation among COVID-19 patients treated with ACEIs/ARBs versus not on treatment, 1.23 (95% CI 1.04 – 1.46; 11 studies, I2 = 76.4%); severe disease 0.86 (95% CI 0.78 – 0.95; 28 studies, I2 = 68%); and death, 0.80 (95% CI 0.75 – 0.86; 47 studies, I2 = 51.9%).ConclusionWhile treatment with ACEIs or ARBs does not appear to impact the risk of COVID-19 infection, it appears that patients on treatment have lower risks of severe disease and mortality compared to patients not on ACEIs/ARBS treatment. Findings should be interpreted cautiously as the systematic reviews/meta-analyses included in this study were of variable quality, and there was high heterogeneity among studies for most outcomes. Findings will inform evidenced-based guidelines on the appropriate measures for patients at risk of COVID-19 infection and prescribed RAAS inhibitors.

Management of heart failure in older people

AbstractHeart failure contributes substantially to morbidity and mortality in older people. It is a chronic and progressive disease, with prevalence set to increase with the ageing population as incidence is strongly associated with age. There are many pharmacotherapies available for the treatment of heart failure which reduce morbidity and mortality. These include angiotensin converting enzyme inhibitors, beta‐blockers, mineralocorticoid receptor antagonists and more recently angiotensin receptor‐neprilysin inhibitor and sodium glucose co‐transporter type 2 inhibitors. Older people are under‐represented in large randomised clinical trials and therefore data supporting efficacy and safety of heart failure treatments for older people is not as strong as it is for younger people. Additionally, older people with heart failure have higher rates of polypharmacy, comorbidity, cognitive impairment and frailty. This article summarises the principles of heart failure therapy based on evidence‐based guidelines as well as the challenges of appropriate management in older people.

Cardiovascular Medication Use and Risk of Acute Exacerbation in Patients With Asthma-COPD Overlap (CVACO Study).

PurposeCurrent clinical guidelines are unclear regarding the association of cardiovascular medication with the risk of acute exacerbation (AE) in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO).MethodsWe conducted a retrospective cohort study by interrogating the claims database of Taipei Veterans General Hospital. Patients with coexistent fixed airflow limitation and asthma were enrolled as an ACO cohort between 2009 and 2017. Exposure to cardiovascular medications, including angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), non-selective beta-blockers, cardioselective beta-blockers, dihydropyridine (DHP) calcium channel blockers (CCBs), and non-DHP CCBs, in 3-month period each served as time-dependent covariates. Patients receiving a cardiovascular medication ≥ 28 cumulative daily doses were defined as respective cardiovascular medication users. Patients were followed up until December 31, 2018. The primary endpoint was severe AE, defined as hospitalization or emergency department visit for either asthma, COPD, or respiratory failure. The secondary outcome was moderate AE.ResultsThe final study cohort consisted of 582 ACO subjects, with a mean follow-up period of 2.98 years. After adjustment, ARB (hazard ratio [HR], 0.64, 95% confidence interval [CI], 0.44–0.93, P = 0.019), cardioselective beta-blocker (HR, 0.29, 95% CI, 0.11–0.72, P = 0.008) and DHP CCB (HR, 0.66, 95% CI, 0.45–0.97, P = 0.035) therapies were associated with lower risks of severe AE. ARB (HR, 0.42, 95% CI, 0.30–0.62, P < 0.001) and DHP CCB (HR, 0.55, 95% CI, 0.38–0.80, P = 0.002) therapies were associated with lower risks of moderate AE. Cardioselective beta-blockers, ARBs, and DHP CCBs were associated with lower risks of severe AE in frequent exacerbators. ACEI, non-selective beta-blocker, or non-DHP CCB use did not change the risk of severe AE.ConclusionsARB, cardioselective beta-blocker, and DHP CCB therapies may lower the risk of AE in patients with ACO.

Abstract 10069: Effect of Renin-Angiotensin-Aldosterone System Inhibitors on Left Ventricular Structure and Function in Duchenne Muscular Dystrophy Carriers

Introduction: Duchenne muscular dystrophy (DMD) is a rare X-linked neuromuscular disorder affecting 1:5,000 males that results in terminal injury to the skeletal muscle and the heart. Recent evidence suggests that DMD female carriers are also at increased risk of developing cardiomyopathy. Renin-angiotensin-aldosterone system (RAAS) antagonists reduce morbidity and mortality and inhibit adverse left ventricular remodeling in patients with heart failure with reduced ejection fraction. The benefit of RAAS inhibition in DMD carriers has not been studied to date. Hypothesis: We hypothesize that RAAS inhibition will improve left ventricular function and induce favorable left ventricular structural changes in DMD carriers over time. Methods: A retrospective, single-center cohort study was undertaken to compare cardiac magnetic resonance imaging (cMRI) parameters in DMD carriers at the time of RAAS inhibitor initiation and after treatment with RAAS inhibitors for at least 12 months. RAAS inhibitors included angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor neprilysin inhibitors. Through EMR review, demographic data and cMRI parameters were collected retrospectively on 20 consecutive DMD carriers. Results: The average time elapsed between cMRIs was 39 months. Overall, left ventricular ejection fraction (LVEF) increased in DMD carriers over time, though the improvement in LVEF did not reach significance (57% + 8 vs 59% + 6, p=0.2). However, subgroup analysis of 16 DMD carriers with reduced LVEF (defined as LVEF &lt;62%) demonstrated significant improvement in LVEF following RAAS inhibition (54% + 6 vs 58% + 7; p= 0.004). DMD carriers with reduced LVEF additionally demonstrated a significant decrease in left ventricular end systolic volume index (LVESVi) after RAAS inhibition (38 + 10 vs 32 + 10 ml/m2; p= 0.013). Conclusions: DMD carriers with reduced LVEF showed significant improvement in LVEF and LVESVi following RAAS inhibition. Collectively, the data suggest that RAAS inhibition significantly improves left ventricular systolic function and significantly reduces maladaptive left ventricular remodeling and dilation in this population.

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

The influence of patient expectations on adherence to treatment regimen after myocardial infarction

ObjectiveIn-hospital patient education is one of the elements affecting patient adherence to treatment regimen after myocardial infarction (MI). Its effectiveness is determined by educator and patient-dependent factors. Previous studies did not identify patient expectations as an independent determinant of successful education. The aim of this study was to assess whether patient knowledge and expectations affect adherence to treatment regimen in a 1-year follow-up. MethodsThis was a single-center, cohort study with a 1-year follow-up. Patient knowledge and expectations were evaluated using the Readiness for Hospital Discharge after Myocardial Infarction Scale (RHD-MIS scale). Medication adherence (including angiotensin converting enzyme inhibitors (ACEI), P2Y12 receptor inhibitors and statins) was verified based on prescription refill data extracted from The National Health Fund database. ResultsThe study included 225 patients aged 30–91 years (mean age 62.9 ± 11.9 years). In the 4th quarter of follow-up, patients with the highest expectations had lower adherence regarding ACEI (p = 0.01), P2Y12 receptor inhibitors (p = 0.03) and the combination of all three analysed medications (p = 0.003). ConclusionsThe initial results suggest presence of a relationship between patient expectations and long-term adherence to treatment. Practice ImplicationsPost-MI patient education directed at fulfilling or modification of patient expectations could possibly improve execution of treatment regimen.

Current Therapies in Nephrotic Syndrome: HDAC inhibitors, an Emerging Therapy for Kidney Diseases

• Nephrotic syndrome (NS) is one among the chronic kidney conditions occurring in children as well as in adult population. • Conventional therapies for NS include treatment with steroids, ACE inhibitors and monoclonal antibodies, with no universal treatment for the condition as yet. • HDAC inhibitors have been greatly explored in the recent past for their anti-fibrotic, anti-inflammatory and immunosuppressive effects in several tissues and organs. • Increasing evidence suggests that treatment with HDAC inhibitors can attenuate renal sclerosis, fibrosis and proteinuria associated with chronic kidney diseases. • HDAC inhibitors can be considered as an emerging therapy for treating NS however; further preclinical and clinical investigations are indispensable. Nephrotic syndrome (NS) is one amongst the foremost chronic kidney conditions occurring in children as well as in adults with a characteristic feature of podocyte injury. Currently, there is no refined treatment available for this condition and in most of the cases, the treatment is essentially experiential. Therapies for NS presently include angiotensin converting enzyme inhibitors, angiotensin receptor blockers, monoclonal antibodies, steroids, and immunosuppresants. Steroids continue to be the initial treatment approach for NS patients and are considered as the foundation of the therapy. However, it is observed that about 50% of the patients with NS are steroid sensitive and therefore portray some response to steroids while the remainder are considered to be steroid-resistant and patients advance to end stage renal disease. As a result, the freight of morbidity becomes prodigious to patients and health services, specifically in the management of dialysis and transplantation. Although numerous studies have been done in the area of renal disorders, treatment of NS remains a critical challenge till date. This is due to the fact that the underlying mechanisms and causes are still not clearly understood. Therapies are now being refined and directed specifically to target the podocyte. In the recent past, histone deacetylase inhibitors (HDACi) have been greatly explored to treat chronic kidney diseases because of the anti-fibrotic, anti-inflammatory, and immunosuppressive effects that they exhibit. Histone deacetylases (HDACs) are the class of enzymes that remove the acetyl groups from the lysine amino acid on histone and thereby promote chromatin condensation and repression of transcription. HDACi are the chemical compounds that inhibit HDAC and alter gene transcription by inducing changes in the structure of proteins in transcription factor complexes. An irregular expression of HDACs has been noted that subsequently play a role in renal fibrosis and glomerulosclerosis associated with chronic renal conditions. Therefore, targeting HDACs can be a favourable therapeutic strategy to treat NS. In the present review, we outline the potential use of HDACi as therapeutic alternatives in treating NS. The promise of HDACi in NS is pragmatically put forth in this review.

Epidemiology of potassium derangements among chronic cardiovascular, metabolic and renal conditions: a population-based analysis data from more than 375,000 individuals

Abstract Introduction In patients with chronic cardiovascular, metabolic and renal disorders, potassium (K)+ homeostasis is often delicate, especially in the presence of renin-angiotensin-aldosterone system inhibition (RAASI) and/or diuretic therapies. In this context, current clinical practical guidelines for the management of these patients recommend close monitoring of renal function and K+ levels, particularly in the presence of drug titration. Nevertheless, very limited epidemiological data on their importance at a population level is available. Purpose The objectives of the present analysis are to estimate the prevalence of potassium (K+) derangements in five key chronic cardiovascular, metabolic and renal conditions at the population level, its use of RAASI medication and describe potassium derangements among RAASI users. Methods We used data from more than 375,000 individuals 55 years of age or older included in the population-based healthcare database of a public Institute of Health between 2015 and 2017. The conditions of interest were chronic heart failure (CHF), chronic kidney disease (CKD), diabetes mellitus (DM), ischemic heart disease (IHD), and hypertension (HTN). RAASI medications included angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists (MRAs), and rennin inhibitors. Hyperkalemia was defined as K+ levels &amp;gt;5.0 mEq/L and hypokalemia as K+ &amp;lt;3.5 mEq /L Results The prevalence of chronic cardiovascular, metabolic and renal conditions was high, particularly of HTN (48.2–48.9%). The prevalence of hyperkalemia was ranging between 10% and 25% depending of the condition, more frequent in CKD and less frequent in HTN patients. In figure, we display the prevalence of hyperkalemia among individuals with each of the relevant chronic conditions, January 1st, 2016 and January 1st, 2017. Use of at least one RAASI medication was very prevalent in HTN patients (75.2–77.3%). Among RAASI users, the frequency of K+ derangements and mainly of hyperkalemia was very noticeable (12% overall), especially in patients with CKD, CHF, elderly individuals, and users of MRAs. Hypokalemia was less frequent (1%). Conclusion The high prevalence of K+ derangements and predominantly hyperkalemia among RAASI users highlights the real-world relevance of K+ derangements and the importance of close monitoring and management of K+ levels in routine clinical practice. This is likely to benefit a large number of patients, particularly those at higher risk. Figure 1. Prevalence of hyperkalemia Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Josep Comin-Colet and Miguel Cainzos-Achirica have participated in other research projects funded by unrestricted grants from Vifor Pharma

Central aortic pressure and long-term outcome in hypertensive patients undergoing percutaneous coronary intervention

Elevated central pulse pressure (CPP) had a negative influence on long-term outcome in patients with hypertension (HT). However, little is known about the impact of central pulse pressure on long-term outcomes in hypertensive patients undergoing PCI. A total number of 1184 hypertensive patients who received PCI procedure were prospectively collected. They were divided into two groups according to the median of central pulse pressure. Baseline characteristics, risk factors, hemodynamic data including central systolic pressure (CSP), central diastolic pressure (CDP) and CPP were measured. Invasive strategies were also analyzed to compare the long term outcome between patients with reference CPP and patients with high CPP. We further analyzed the predictors for myocardial infarction (MI), mortality, repeated PCI procedure in hypertensive patients undergoing PCI. We found patients in the reference CPP group had a lower CSP and higher CDP compared with high CPP group (Both P < 0.001) and male preponderance (P < 0.001). Patients with diabetes and chronic kidney disease (CKD) tend to have a high CPP (both P < 0.001). Drugs including Angiotensin Converting Enzyme inhibitors (ACEI) and statin were used more frequently in patients with reference CPP group (P = 0.035 and P = 0.001, respectively). Freedom from all-cause mortality and cardiovascular(CV) mortality was lower in the patients with high CPP group (P = 0.001, P = 0.01, respectively).Logistic regression revealed that CPP is a major predictor for all-cause mortality and repeated PCI procedure [hazard ratio (HR): 2.46 and 1.41, respectively]. In hypertensive patients receiving PCI, elevated CPP had a negative impact on long-term mortality; CPP also strongly predicts all-cause mortality and repeated PCI procedures in hypertensive patients undergoing PCI.

Peri-Implantitis Risk in Patients Taking Statins and Antihypertensives

Managing modifiable risk factors, such as cholesterol and blood pressure, is the conventional strategy to combat heart disease, the number 1 cause of death in the United States. Medications for lowering cholesterol and blood pressure have also been shown to play a role in bone metabolism. As such, these medications are of potential interest to the osseointegration and health of dental implants. Given the widespread use of these medications, it is imperative to understand their role in enhancing or deteriorating the health of dental implants. The most common class of cholesterol-lowering medications (known as statins) lower serum cholesterol by inhibiting the rate-limiting enzyme in the hepatic cholesterol biosynthesis pathway. Animal studies have shown statins to increase osteogenesis around dental implants, which has been explained by increased expression of bone morphogenic protein-2 and osteoblast differentiation. The applicability of these results to dental implant health in humans, however, remains unclear.1 Many pharmacologic mechanisms exist for lowering blood pressure, and as such, antihypertensives can affect bone physiology in different ways. For example, thiazide diuretics increase renal calcium absorption, beta adrenergic blockers inhibit osteoclasts, and drugs targeting the renin-angiotensin-aldosterone system block the bone resorptive activity of angiotensin II. These mechanisms have been used to explain an association between decreased implant failure and antihypertensive medications.2 This study aims to elucidate how cholesterol-lowering and antihypertensive medications affect long-term peri-implant health. A retrospective cohort study was performed to evaluate implants placed between 2006 and 2013. Medical and dental encounter notes were used to determine which medications a patient had been prescribed. Peri-implantitis was defined as radiographic evidence of bone loss of osseointegrated implants in conjunction with inflammatory signs, such as bleeding on probing, peri-implant probing depth of 5 or more millimeters, with or without suppuration. A minimum follow-up period of 5 years after placement was necessary to be included in the analysis. Of the 1362 implants placed in 398 patients, 881 implants in 284 unique patients met the inclusion criteria. Descriptive statistics were computed using the SAS system (SAS Institute Version 9.4, 2002-2012, Cary, NC). The predictive variables were prescriptions for cholesterol-lowering and antihypertensive medications. The primary outcome variable was peri-implantitis, with P < .05 used to define statistical significance. Of the implants that met the inclusion criteria, 456 (52%) were placed in patients’ prescribed statins. Risk of developing peri-implantitis was 77% higher in patients’ prescribed statins (OR: 1.772; 95% CL 1.285-2.445) compared to non-users (P = .0005). Peri-implantitis risk was not associated with overall antihypertensive medications or specific classes of antihypertensives, including angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta adrenergic blockers, calcium channel blockers, diuretics, or clonidine. Peri-implantitis risk was also not associated with other cholesterol-lowering medications, fibrates, or ezetimibe. The results from this retrospective cohort study reveal an increased risk of peri-implantitis in patients taking statins. This finding is clinically significant because there is substantial overlap between patients in need of dental implants and patients taking statins for cardiovascular protection, as evidenced by the numbers in our study. Further studies are needed to expound this association and establish recommendations for increasing long-term implant success in patients taking statins.