Use Of Converting Enzyme Inhibitors Research Articles

Impact of sociodemographic patient factors on prescriber adherence to antihypertensive prescription guidelines: a cross-sectional study using data from The Irish Longitudinal Study on Ageing

Abstract Introduction Uncontrolled hypertension causes significant morbidity and mortality worldwide. Several international prescribing guidelines have been created to address this. However, prescriber adherence to these guidelines may be influenced by sociodemographic patient factors such as socio-economic status, gender and age. Aim To examine the effects of gender and other patient factors, including age, geographical location, educational attainment, duration of disease, socio-economic status, smoking status, and previous history of cardiovascular diseases on prescriber adherence to hypertension prescription guidelines. Achievement of blood pressure goals (<140/90 mmHg) with adherence to prescription guidelines was also assessed. Methods This study is a secondary analysis of cross-sectional data from the first wave (2009-2011) of The Irish Longitudinal Study on Ageing (TILDA), which included 8,175 Irish adults ≥50 years of age. Participants were included in the present study if they reported a previous doctor diagnosis of hypertension. Antihypertensive medication regimens were compared and categorised according to the 2011 National Institute for Health and Clinical Excellence (NICE)[1] prescription guidelines, which included the use of angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, and thiazide diuretics in the treatment of hypertension. In this study, the antihypertensive medication regimens of participants were categorised based on age categories (<55, ≥55, and all age groups), and compared to the 2011 NICE Guidelines which differentiate treatment in those ≥55, and <55 years of age. The effects of patient sociodemographic factors on prescriber adherence to the guidelines, and the effects of guideline adherence on blood pressure control, (defined as blood pressure<140/90 mmHg), were determined using multinomial logistic regression models. The mlogit, RRR code in STATA 17 SE was used to report relative risks (RRs). Results A total of 2,992 participants were included, of whom 54.9% were women. The mean age of participants was 65.69 years (±9.23). Male gender, older age and lower socioeconomic status among participants were associated with increased prescriber guideline adherence. Prescribers were less likely to adhere to guidelines in female patients ≥55 years (RR 0.75 [0.62 to 0.91]), and female patients across all age groups (RR 0.80 [0.67 to 0.95]). Better blood pressure control was seen with medication regimens adherent to prescription guidelines with a mean of 140.38 (±18.98)/83.09 (±11.02) mmHg compared to a mean of 141.66 (±19.86)/84.77 (±11.71) mmHg in those non-adherent to guidelines. Conclusion This study highlights the effects of patient gender on prescriber adherence to antihypertensive prescription guidelines. A study strength is the use of a large, nationally representative cohort that used a standardised protocol of data collection within the Irish population. A potential limitation is the inclusion of self-reported data, including doctor diagnosis of hypertension. The results of this study may emphasise a larger issue of the systemic undertreatment of women within healthcare; however, these results should be interpreted in the context of 2011 guidelines, which have since been superseded by 2019 NICE guidelines. Further research may seek to determine possible reasons for such differences in hypertensive care. Reference 1. Linden B. NICE guidance on primary hypertension National Institute for Health and Clinical Excellence (2011) Hypertension: Clinical Management of Primary Hypertension in Adults. NICE Clinical Guideline 127. British journal of cardiac nursing. 2011;6:582-584.

ACE Inhibitor Use Does Not Significantly Affect Occurrence of Manipulation Under Anesthesia Following Total Knee Arthroplasty

Introduction Common medications may attenuate fibroblast proliferation and scar tissue formation. This study aims to evaluate the association between angiotensin converting enzyme inhibitor (ACEI) use and post-operative stiffness assessed by rate of manipulation under anesthesia (MUA) and change in range of motion (ROM) following total knee arthroplasty (TKA). Methods Patients undergoing primary TKA January 2014 - September 2019 were identified. Demographic information, use of ACEI medications, occurrence of MUA in the 6 months following surgery, and ROM was determined by chart review. MUA was indicated upon failure to achieve 90° ROM at 1-month follow-up. Demographics were analyzed using Student’s t-test and Chi-Squared tests. SPSS (version 24, IBM) multivariate regression calculated odds ratios for MUA controlling for age, BMI, American Society of Anesthesiologist’s class, and gender. Results 1590 primary TKA’s were identified. 274 patients (17.3%) were taking ACEI medications. 46 patients required MUA (2.9%). Five patients (1.8%) taking an ACEI required MUA, versus 41 of the 1316 control patients (3.1%). No significant difference in MUA rates between the ACEI and control cohorts (odds ratio 0.670, 95% CI: 0.259 – 1.735, p=0.410) was identified. Change in ROM was not significantly different between cohorts at 1 and 3 month intervals. At 1-year, improvement in ROM was significantly less in patients taking ACEIs (+6.54° vs. +9.90°, p=0.035) and significantly fewer ACEI cohort patients achieved 118° flexion (56.9% vs. 68.4%, p=0.013). Conclusions This study supplies evidence that ACEIs do not reduce post-operative stiffness following TKA. Additionally, patients taking ACEI medications have significantly less improvement in ROM 1 year post-operatively.

Retrospective study assessing the use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers to reduce toxicity from tyrosine kinase inhibitors in metastatic renal cell carcinoma.

411 Background: The main toxicities associated with tyrosine-kinase inhibitors (TKIs) in the treatment of renal cell carcinoma (RCC) are proteinuria and hypertension. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have established reno-protective and anti-hypertensive effects and can help with toxicity in mRCC. We hypothesize that use of ACEIs/ARBs is an effective method to decrease the degree of proteinuria and hypertension in patients treated with TKIs for metastatic/advanced renal cell carcinoma (mRCC). Methods: Single Institution retrospective study; mRCC patients (pts) who received TKI and ACEIs/ARBs and had urine protein measurements available at baseline and at 4-6 wk follow up post ACEs/ARBs were included in the analysis. Primary endpoints included improvement in grade of proteinuria and BP in mRCC pts on TKI treatment at baseline and with addition of ACEIs/ARBs. Secondary endpoints included number of dose interruptions (DI), BUN and creatinine changes. Paired statistical tests were used to compare the selected outcome variables between baseline and post ACE/ARB measures: for example, nonparametric Wilcoxon Signed-rank test for paired quantitative data and McNemar test for paired binary data. Results: Out of 71 screened patients between 2020-2023, N of 22 mRCC (N=22, 72.7% male, 77.3% white; 9% Hispanic; N=14 for TKI+ immunotherapy; N=8 TKI alone) pts were selected. ACEIs/ARBs treatment was associated with significantly reduced levels of proteinuria at 4–6wk follow-up. At baseline vs. follow-up, pts were found to have significantly lower proteinuria overall after ACEI/ARBs (p=0.0147), and 45.4% of pts had clinically insignificant proteinuria vs. 22.7% at baseline. Additionally, DI rates for TKI were significantly lower for pts placed on ACEIs/ARBs, with an 81% chance that pts with prior DI would not experience similar event in the follow-up period (p=0.003). Reductions in BP, creatinine, and TKI dosing were seen but not statistically significant (p>0.05 for all measures). Conclusions: In our small study, degree of proteinuria was notably reduced with administration of ACEIs/ARBs. Further findings show fewer DI of TKIs with ACEIs/ARBs use. Our findings suggest a potential role for ACEIs/ARBs in managing toxicity in patients undergoing TKI based therapy for mRCC. Future studies are needed to evaluate the use of ACE/ARB from the time of initiation of TKI based therapy to reduce the toxicities and improve the adherence to mRCC treatment which may result in better outcomes.

Efficacy of the use of angiotensin converting enzyme inhibitors in the complex therapy of gastroduodenal erosions and ulcers in patients with unstable angina

Purpose of the study. To find out the effectiveness of the use of angiotensin-converting enzyme (ACE) inhibitors in the complex therapy of erosive and ulcer lesions of the stomach and duodenum in unstable angina pectoris (UA). Materials and methods. A survey of 109 patients with UA with gastroduodenal erosions and ulcers was carried out, taking into account their clinical signs, endoscopic features and the parameters of gastric secretion. The patients were divided into two groups depending on the nature of the treatment of erosions and ulcers. The first group included 40 patients treated with standard therapy, and the second one included 69 patients who additionally received ACE inhibitor lisinopril at an average dose of 7.27±0.16 mg a day. Results. The therapy by lisinopril resulted in decreasing of pain and dyspeptic syndrome, especially in patients with acute erosions, compared with conventional treatment group. According to endoscopic examination, in patients treated with lisinopril, an acceleration of repair processes in the tissues of the gastroduodenal zone was observed. The depth and size of damages, a reduction in the period of persistence of microbleeding signs and inflammatory changes in the periulcerous zone were also less pronounced in lisinopril patient’s group. In patients with acute erosions a decrease in the number and size of erosive defects of the mucous membrane was observed. The study of the parameters of gastric secretion showed that gastroduodenal erosions and ulcers in UA revealed the activation of the acid-peptic factor and a decreasing in the production of gastromucoproteins. Increased production of pepsinogen and a sharply reduced formation of protective mucus was observed in patients after conventional treatment, despite some positive dynamics. Normalization in pepsinogen secretion with some inhibition of the production of mucopolysaccharides was observed in Lisinopril treated patients at the end of therapy. Acid production in both groups was reduced, which was associated with could be provoked by an uptake of antisecretory agents. Conclusion. The use of ACE inhibitor lisinopril in the complex therapy in patients with UA with gastroduodenal erosions and ulcers is pathogenetically justified and clinically effective. This combination helps to reduce the duration of clinical signs, accelerate the healing of defects and normalize the parameters of gastric secretion.

A strategy to improve adherence to guideline-directed medical therapy (GDMT) and the role of the multidisciplinary team in a heart-failure programme.

Heart failure (HF) patients place a heavy burden on the healthcare system because of their frequent need for in-patient treatment, emergency room visits and subsequent hospital stays. To provide proper care and effective therapy, practitioners have streamlined delivery techniques such as clinical pathways, checklists and pocket manuals. However, a description of the establishment of a disease-management programme, including a multidisciplinary team of physicians, clinical pharmacists and nurse specialists is required. The aim of this study was to highlight the role of the multidisciplinary team in a heart-failure programme by assessing the improvement in adherence to guideline-directed medical therapy. A retrospective, observational research was undertaken on patients with HF at a cardiac centre in Riyadh, to observe the HF patients' management before (January to December 2014) and after (January to December 2015) the establishment of a programme. The use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers was 75.59% in 2014 at discharge and 81.17% in 2015 (p = 0.249). Beta-blockers use at release increased from 87.83% in 2014 to 94.53% in 2015 (p = 0.021). The flu vaccine was given to 48.24% of patients in 2014 and 75.13% of the patients in 2015 (p < 0.001). The pneumococcal vaccine was administered to 44.22% of patients in 2014 and 75.13% of patients in 2015 (p < 0.001). The ejection fraction improved from 30.21% in the first month to 39.56% in the 12th month (p = 0.001) in patients managed in 2015. The multidisciplinary heart-failure programme resulted in a positive effect, in the form of improved patient care after including the clinical pharmacist and nurse specialist.

Persistent Albuminuria and Chronic Kidney Disease in Adults with Sickle Cell Disease: Results from a Multicenter Natural History Study

Background: Patients with sickle cell disease (SCD) are at high risk for developing kidney disease. Albuminuria, an early marker of kidney injury, may be initially transient in patients with SCD. Existing guidelines propose confirming albuminuria at multiple timepoints before intervention. A recent study suggests a urinary albumin-creatinine ratio (UACR) ≥ 100 mg/g correlates highly with persistent albuminuria and subsequent decline in estimated glomerular filtration rate (eGFR). We examined a cohort of patients with SCD to assess those characteristics associated with persistent albuminuria and chronic kidney disease (CKD). Methods During routine clinical visits, we enrolled patients with HbSS or HbSß 0 thalassemia between 18 and 65 years at 4 centers into a prospective study to assess the natural history of kidney disease in SCD. We excluded patients if they had bone marrow transplantation, cancer, connective tissue disease, diabetic nephropathy, other glomerular diseases, hepatitis (B or C), HIV, or were on dialysis. Blood and urine were collected for routine clinical laboratory assessments. Serum cystatin C was measured by commercially available ELISA, and eGFR was calculated using the CKD-EPI-2012 cystatin C equation. We defined CKD as an eGFR &amp;lt; 60 mL/min/1.73m 2 or presence of albuminuria. Glomerular hyperfiltration was defined as an eGFR&amp;gt;130 in females and &amp;gt;140mL/min/1.73m 2 in males, respectively. Persistent albuminuria was considered present if 2 or 3 UACR values were ≥30 mg/g or if initial baseline value was ≥100 mg/g (PMID: 32289161). We utilized generalized linear models adjusting for age and sex to identify characteristics associated with persistent albuminuria and CKD. For multivariable selection, we fit binomial or multinomial LASSO regression models adjusted for age, sex, hemoglobin, %Hemoglobin F, hemoglobinuria, and hydroxyurea to identify those variables associated with outcomes of interest. Results Of 284 enrolled patients, 268 had complete data for UACR, cystatin C and serum creatinine at baseline; 104 (38.8%) of these had persistent albuminuria (Table 1). CKD was present in 40.7% of patients and 26.5% exhibited hyperfiltration. In analyses adjusted for age and sex, several factors were associated with the likelihood of persistent albuminuria. Higher hemoglobin, higher %Hemoglobin F, higher serum bicarbonate and use of NSAIDs were associated with decreased likelihood of persistent albuminuria. Higher systolic and diastolic blood pressure, elevated serum alkaline phosphatase, total bilirubin, and white blood cell count (WBC) were associated with an increased likelihood of persistent albuminuria as were presence of hemoglobinuria and use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). In multivariable selection, higher systolic and diastolic blood pressure, ACEi/ARB use, leg ulcers, higher WBC, higher aspartate transaminase (AST) remained associated with higher likelihood of persistent albuminuria. Presence of avascular necrosis, NSAID use, and higher serum bicarbonate were associated with lower likelihood of persistent albuminuria. When evaluating baseline UACR, individuals with UACR≥100 mg/g had similar probability of subsequent albuminuria as compared to those with severe albuminuria (UACR≥300 mg/g) [Table 2]. Conclusion Persistent albuminuria in this cohort was associated with multiple clinical features. Lower use of NSAIDs in this cohort likely represents counseling of patients to avoid these due to their kidney disease. The relationship with serum bicarbonate suggests a propensity for metabolic acidosis in these patients which could exacerbate the underlying SCD. These data confirm the predictive value of a single UACR value ≥100 mg/g for persistent albuminuria, suggesting this may be a sufficient trigger to warrant intervention. CKD, hyperfiltration and albuminuria were extraordinarily common, consistent with prior studies and validate use of this cohort for additional longitudinal assessment of kidney disease in SCD.

Prior Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers and Clinical Outcomes of Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

Sepsis and septic shock are life-threatening conditions that are associated with high mortality and considerable health care costs. The association between prior angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) use and outcomes after sepsis is elusive. The aim of this study was to evaluate the role of the prior use of ACEi or ARBs and outcomes after sepsis and septic shock. A relevant literature review was performed in 4 databases from inception until July 2022. Independent reviewers first screened the title, abstract, and full text, and then, data extraction and analysis were performed. One post hoc analysis of a trial and 6 retrospective cohort studies were included in this review. There were 22% lower odds of in-hospital/30-day mortality among patients who have used ACEi/ARBs in the past [23.83% vs. 37.20%; odds ratio (OR), 0.78, 95% confidence interval (CI), 0.64-0.96], and reduced 90-day mortality (OR, 0.80, 95% CI, 0.69-0.92). ACEi/ARBs users were found to have 31% lesser odds of developing acute kidney injury as compared with nonusers (OR, 0.69, 95% CI, 0.63-0.76). There was no significant difference in the length of hospital stay (MD 1.26, 95% CI, ‒7.89 to 10.42), need for renal replacement therapy (OR, 0.71, 95% CI, 0.13-3.92), mechanical ventilation (OR, 1.10, 95% CI, 0.88-1.37) or use of vasopressors (OR, 1.21, 95% CI, 0.91-1.61). Based on this analysis, prior use of ACEi/ARBs lowers the risk of mortality and adverse renal events in patients with sepsis and septic shock.

Changes in left ventricular systolic function for 1 year in patients with acute heart failure &amp;lt;50 years of age

Abstract Funding Acknowledgements Type of funding sources: None. Background Though old age is an important risk factor for cardiovascular disease including heart failure (HF), HF can develop in young patients and can have a greater impact on a quality of life because they are active individuals. Purpose We evaluated the clinical characteristics and prognosis according to change of left ventricular (LV) function in younger patients with acute HF. Methods Study data were obtained from a multicenter cohort that included patients hospitalized for acute HF. Patients who were under 50 years of age and had available data regarding baseline and one-year follow-up left ventricular ejection fraction (LVEF) were included in this analysis. Patient were classified into two groups according changes in LVEF: the improved or stationary group whose LVEF improved or maintained at one-year follow-up; the aggravated LVEF group whose LVEF deteriorated at one-year follow-up. Results Among 437 patients, 14.6% of patients had experienced worsening of LVEF at the one-year follow-up. The patients in aggravated LVEF group had a worse clinical profile than patients with improved or stationary LVEF. During follow-up (median 1946 days), a total of 56 patients (12.8%) died. Among them, the aggravated LVEF group had higher incidence of all-cause death (32.8% vs. 9.4%, p &amp;lt; 0.001). The aggravated LVEF group showed significant lower cumulative all-cause death free survival rate than improved or stationary LVEF group (Figure). In addition, the aggravated LVEF group had significantly higher incidence of cardiac death (14.1% vs. 2.9%, p &amp;lt; 0.001), readmission (76.6% vs. 55.5%, p = 0.002), readmission due to cardiac cause (57.8% vs.30.8%, p &amp;lt; 0.001), and HF readmission (51.6% vs. 26.0%, p &amp;lt; 0.001). After adjusting for confounding factors, Cox regression analysis showed that use of angiotensin converting enzyme inhibitors at discharge was independently associated with 63% reduced risk of aggravated LVEF (Odds ratio 0.37, 95% confidence interval 0.168–0.791, p = 0.001). Conclusions Poor clinical prognosis is expected if LVEF worsens after 1 year in young patients with HF. Clinicians need to be aware of the deteriorating characteristics of young HF patients and provide delicate treatment.

Use of angiotensin converting enzyme inhibitors in chronic kidney disease - a review of the literature

Introduction: Chronic Kidney Disease (CKD) has become one of the most common chronic diseases of the XXI century and affects around 16% of the world's population. Despite the advancements of contemporary science and a range of therapeutic methods it considered a progressive and irreversible process. Nevertheless, use of ACEI halts the progression of the disease and postpones the necessity of renal replacement therapy and is the method of choice for this group of patients. &#x0D; Purpose of the work: The article reviews current literature and writing regarding Chronic Kidney Disease (CKD) and the impact of ACEI on the progression of this condition. &#x0D; Materials and methods: The sources available in the PubMed database have been analyzed using the keywords: “ACEI”, “angiotensin-converting-enzyme inhibitors”, ”chronic kidney disease”, “CKD”. Related publications to the topic of the work have been selected and utilized. &#x0D; Description of the state of knowledge: Pharmacological therapy using ACEI is the main method of treatment for patients with CKD and should primarily serve to reduce proteinuria and control blood pressure. It inhibits the progression of the disease and delays the development of end-stage renal failure. However, the treatment of CKD using ACEI is controversial in cases of advanced stages of the disease. &#x0D; Summary: ACEI inhibitors are one of the major advances in the treatment of patients dealing with CKD. Due to the increasing number of cases of the disease being observed, further research will be needed regarding the use of these drugs. Particularly ambiguous is the therapy for patients with advanced, just before end-stage renal failure, which will require a more in-depth analysis of these cases.

Breakthrough: a first-in-class virtual simulator for dose optimization of ACE inhibitors in translational cardiovascular medicine

The renin–angiotensin–aldosterone-systems (RAAS) play a central role in the pathophysiology of congestive heart failure (CHF), justifying the use of angiotensin converting enzyme inhibitors (ACEi) in dogs and humans with cardiac diseases. Seminal studies in canine CHF had suggested that the pharmacological action of benazepril was relatively independent of doses greater than 0.25 mg/kg P.O, thereby providing a rationale for the European labeled dose of benazepril in dogs with CHF. However, most of these earlier studies relied on measures of ACE activity, a sub-optimal endpoint to characterize the effect of ACEi on the RAAS. The objectives of this study were (i) to expand on previous mathematical modeling efforts of the dose-exposure–response relationship of benazepril on biomarkers of the RAAS which are relevant to CHF pathophysiology and disease prognosis; and (ii) to develop a software implementation capable of simulating clinical trials in benazepril in dogs bedside dose optimization. Our results suggest that 0.5 mg/kg PO q12h of benazepril produces the most robust reduction in angiotensin II and upregulation of RAAS alternative pathway biomarkers. This model will eventually be expanded to include relevant clinical endpoints, which will be evaluated in an upcoming prospective trial in canine patients with CHF.

Medication related problems among ambulatory patients with chronic kidney disease at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.

Medication related problem (MRP) is an event occurring, as a result, the medication therapy that actually or potentially interferes with desired health outcomes. Evidences reported that the prevalence of MRPs may result in a high burden of morbidity and decrease patients' quality of life. The problem is more significant among patients with chronic kidney disease (CKD) as a decline in kidney function and increase number of medications required to treat kidney disease and its complications. Thus, this study aimed to assess MRPs and its associated factors among patients with chronic kidney disease. Hospital-based cross-sectional study was conducted among 248 adult ambulatory patients with CKD (stage 1-4) at St. Paul's Hospital Millennium Medical College. Data were collected through patient interview and medical chart review from 1st of June to 30th of August 2019. MRPs were identified based on the standard treatment guidelines. Cipolle MRPs classification was used to classify the MRPs and Micromedex® was used as drug interaction checker. Binary logistic regression was utilized to identify the associated factors and p value <0.05 was considered as statistically significant. A total of 325 MRPs were identified from 204 (82.3%) study participants giving 1.6 MRPs per participant. One MRP was identified among 114 (55.9%) patients while two MRPs were identified among 64 (31.4%). The most common class of MRPs were need additional drugs 114 (35.1%) followed by non-compliance 54 (16.6%), unnecessary drug therapy 46 (14.2%) and dose too low 46 (14.2%). The two most common reasons for non-compliance were unaffordability of drugs 26(48.1%) and the lack of patient understanding about drug taking instruction 10 (18.5%). The study showed that only occupation (AOR = 5.2, 95% CI: 1.292-21.288, P = 0.020) and angiotensin converting enzyme inhibitor use (AOR = 6.6, 95% CI: 2.202-19.634, P = 0.001) had an association with the occurrence of MRPs. The prevalence of MRPs among ambulatory patients with CKD was high and need of additional drug therapy was the commonest MRPs.

Cognitive impairment and low health literacy are associated with poor health outcomes in patients with heart failure

Abstract Background Cognitive impairment and low health literacy are prevalent in patients with heart failure (HF). Low health literacy is associated with poor health outcomes, such as frequent re-hospitalizations and increased mortality. Little is known about the relationships among cognitive impairment, health literacy, and health outcomes (HF rehospitalization and cardiac death). Objective To explore the associations among cognitive impairment, health literacy, and cardiac event-free survival in patients with HF. Methods This was a longitudinal study of 614 rural patients with HF (male 59%, age 66±13 NYHA class III/IV: 35%). Cognitive function was measured using the Mini-Cog test. Health literacy was measured by the Short Test of Functional Health Literacy in Adults. HF hospitalizations and cardiac mortality were followed at least 2 years and obtained by patient interview, medical record review, and death certificate review. Chi-squares, t-tests, ANOVA, Kaplan-Meier with log rank tests, logistic and Cox regressions were used for data analysis. Results Two hundred and seven patients (34%) had cognitive impairment. Compared to those without cognitive impairment, patients with cognitive impairment were 2.77 times more likely to have low health literacy (P&amp;lt;0.001). Patients were divided into 4 groups based on cognitive impairment or not and adequate/low health literacy: (1) No cognitive impairment with adequate health literacy; (2) cognitive impairment with adequate health literacy; (3) no cognitive impairment with low health literacy; and (4) cognitive impairment with low health literacy. Both cognitive impairment and health literacy independently predicted cardiac event-free survival. Cardiac event-free survival was worst in those with both cognitive impairment and low health literacy compared to patients in any of the other three groups. Patients with cognitive impairment and low health literacy had 3.5 times higher risk of a cardiac event compared to those without cognitive impairment or low health literacy (P&amp;lt;0.001, Figure). Age, income, angiotensin converting enzyme inhibitor use, beta-blocker use, New York Heart Association functional class, left ventricular ejection fraction, BNP level were significantly different among the four cognitive and literacy groups. Conclusion Patients with cognitive impairment with low health literacy were at high risk of experiencing a cardiac event. Interventions need to be developed to target high risk patients with cognitive impairment and low health literacy, such as older, low-income patients, to alleviate poor outcomes in patients with HF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIH/NHLBI

S1563 ACE Inhibitor Use Is Associated With Angioectasias on Video Capsule Endoscopy (VCE) in Patients With Iron Deficiency Anemia

Introduction: Small bowel bleeding poses a clinical challenge in patients with vascular lesions. Bleeding recurrence after endoscopic therapy is high and medical therapies have limited efficacy. In those with left ventricular assist devices (LVADs), the use of angiotensin converting enzyme inhibitors (ACEi) has been associated with a reduced rate of gastrointestinal bleeding. Conversely, the antiplatelet effects of ACEi have been described thought due to their effects in decreasing platelet aggregation. Our aim was to determine whether ACEi or angiotensin receptor blocker (ARB) therapy had an impact on the rate of positive VCE small bowel findings in those with iron deficiency anemia (IDA). Methods: Data was collected from consecutive inpatient and outpatient VCE examinations performed between January 1, 2009 to March 1, 2018 at a single U.S. tertiary medical center performed for IDA. VCE studies were excluded in those with incomplete small bowel examinations (9) or technical failure (1). Patient demographics, laboratory values, medication use and endoscopic findings were recorded. VCE findings were based on the P0-P2 grading system. The primary outcome of interest was a positive (P2) VCE. Data were analyzed using Wilcoxon rank-sum test for continuous variables and Fischer’s exact test for dichotomous variables. Bivariate logistic regression was performed to identify independent factors predictive of positive VCE. Results: Eighty-two VCE were included in the final analysis. Median age was 67.6 (IQR: 57.1-75.5) years and 38 (46.3%) patients were male. Thirty-seven (45.1%) VCE examinations were positive with the most common finding of angiectasia in 21 (55.3%). Risk factors for positive VCE are listed in Table 1. In univariate analysis, ACEi therapy associated with both positive VCE (P=0.014) and the presence of angiectasia (P=0.021), whereas ARB therapy did not associate with positive VCE. ACEi findings remained significant in bivariate analysis after controlling for cardiac and pulmonary comorbidities. Conclusion: In this single center study the presence of ACEi use was associated with small bowel and/or stomach angiectasias on VCE in univariate analysis and when controlled for cardiac and pulmonary risk factors. Further studies are required to determine the mechanistic impact of ACEi on gastrointestinal bleeding risk such as the reduction in von Willebrand factor or factors that affect platelet aggregation. Table 1. - Univariate predictors of positive video capsule endoscopy in iron deficiency anemia Negative VCE (n = 45) Positive VCE (n =37) P-value Age, years, mean (SD) 63.6 (15.8) 68.6 (9.3) 0.303 Male sex, n (%) 21 (46.7) 17 (46) 1 White race, n (%) 22 (48.9) 20 (54.1) 0.223 Active smoking, n (%) 6 (14) 11 (29.7) 0.105 Outpatient location, n (%) 31 (68.9) 21 (56.8) 0.357 Chronic kidney disease, n (%) 10 (22.2) 13 (35.1) 0.224 Chronic liver disease, n (%) 3 (6.7) 4 (10.8) 0.696 Congestive heart failure, n (%) 10 (22.2) 13 (35.1) 0.224 Diabetes mellitus, n (%) 15 (33.3) 15 (40.5) 0.645 Cardiac valvular disease, n (%) 7 (15.6) 6 (16.2) 1 Coronary artery disease, n (%) 14 (31.1) 14 (37.8) 0.641 Cardiac arrhythmia, n (%) 10 (22.2) 18 (48.7) 0.019 Chronic lung disease, n (%) 10 (22.2) 13 (35.1) 0.224 Left ventricular assist device, n (%) 2 (4.4) 2 (5.4) 1 Blood transfusion in the preceding 4 weeks, n (%) 17 (37.8) 16 (43.2) 0.656 Aspirin, n (%) 20 (44.4) 14 (37.8) 0.654 Thienopyridine, n (%) 3 (6.7) 2 (5.4) 1 Coumadin, n (%) 1 (2.2) 5 (13.5) 0.086 SSRI/SNRI, n (%) 7 (15.6) 9 (24.3) 0.404 ACEi 7 (15.6) 15 (40.5) 0.014 ARB 9 (20) 7 (18.9) 1 Hemoglobin, g/dL1 9.9 (1.7) 9.2 (2.3) 0.216 Platelets, 109/L1 225.4 (67.5) 208.6 (84.9) 0.202 BUN, mg/dL1 21.9 (13.1) 26.7 (22) 0.869 Creatinine, mg/dL1 1.3 (0.5) 1.9 (1.5) 0.197 Ferritin, ng/mL,1 128 (259) 39.6 (28.7) 0.966 Percent saturation, %1 14.8 (15.1) 13.7 (15.4) 0.76

An overview of the effects of combination therapy with a renin-angiotensin system blocker plus a calcium channel blocker on glucose homeostasis in non-diabetic hypertensive patients

Arterial hypertension (AH) is a major cardiovascular risk factor and often coexists with insulin resistance. Insulin resistance impairs glucose homeostasis and has been associated with the development of new-onset type 2 diabetes mellitus (T2D). Overactivity of renin-angiotensin system (RAS) mediated by angiotensin II adversely affects glucose homeostasis. The blockade of RAS with the use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) has been associated with beneficial effects on glucose metabolism. On the other hand, calcium channel blockers (CCBs) have been reported to exert a metabolic neutral effect. By contrast, the use of diuretics and beta-blockers has been shown to have an overall negative effect on glucose metabolism. Current ESH/ESC treatment guidelines recommend the use of fixed single-pill combinations of RAS blockers with either CCBs or thiazide/thiazide-like diuretics in hypertensive patients with grade 1 AH and high cardiovascular risk, or greater. Nonetheless, considering the patient’s medical history and comorbidities, antihypertensive treatment should be carefully tailored. To this, hypertensive patients at risk of developing new-onset T2D, with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), should be preferentially treated with either monotherapy or combined treatment using agents which do not affect or worsen glucose homeostasis.

Trends in Antihypertensive Medicine Utilization in the Republic of Srpska, Bosnia and Herzegovina: An Eleven-Year Follow-Up.

Background: In last 2 decades, there have been substantial changes in the utilization patterns of antihypertensive medicines following new clinical trials and the introduction of new treatment guidelines. The aim of this study was to analyze utilization and prescribing patterns regarding antihypertensive medicines in the Republic of Srpska, Bosnia and Herzegovina during an 11-years follow-up according to national and European treatment guidelines. Methods: In this retrospective, observational study, medicine utilization data were analyzed between 2009–2019 period using the ATC/DDD methodology and expressed as the number of DDD/1,000 inhabitants/day (DID/TID). The medicine utilization 90% (DU90%) method was used for determine the quality of prescribing. Results: During the observed period, the use of antihypertensive medicines increased more than 3-times (125.97 DDD/TID in 2009 vs 414.95 DDD/TID in 2019), corresponding to a rise in the prevalence of hypertensive patients from 91.7/1,000 to 186.3/1,000 in the same period. This was mainly driven by increased use of angiotensin converting enzyme inhibitors with 241.69%, beta blockers with 146.87%, calcium channel blockers with 251.55%, and diuretics with 178.95%. Angiotensin receptor blockers were the fastest growing group of antihypertensive medicines in this period and their utilization increased nearly 40 times. Conclusions: The overall antihypertensive medicines utilization was largely influenced by national and ESH/ESC guidelines and strongly corresponded to the positive medicine list of the national health insurance fund. Antihypertensive medicines utilization is comparable with medicine utilization trends in other countries.

Factors associated with coronary heart disease in COPD patients and controls.

COPD and coronary heart disease (CHD) frequently co-occur, yet which COPD phenotypes are most prone to CHD is poorly understood. The aim of this study was to see whether COPD patients did have a true higher risk for CHD than subjects without COPD, and to examine a range of potential factors associated with CHD in COPD patients and controls. 347 COPD patients and 428 non-COPD controls, were invited for coronary computed tomography angiography (CCTA) and pulmonary CT. Arterial blood gas, bioelectrical impedance and lung function was measured, and a detailed medical history taken. The CCTA was evaluated for significant coronary stenosis and calcium score (CaSc), and emphysema defined as >10% of total area <-950 Hounsfield units. 12.6% of the COPD patients and 5.7% of the controls had coronary stenosis (p<0.01), whereas 55.9% of the COPD patients had a CaSc>100 compared to 31.6% of the controls (p<0.01). In a multivariable model adjusting for sex, age, body composition, pack-years, CRP, cholesterol/blood pressure lowering medication use and diabetes mellitus, the OR (95% CI) for having significant stenosis was 1.80 (0.86-3.78) in COPD patients compared with controls. In a similar model, the OR (95% CI) for having CaSc>100 was 1.68 (1.12-2.53) in COPD patients compared with controls. Examining the risk of significant stenosis and CaSc>100 among COPD patients, no variable was associated with significant stenosis, whereas male sex [OR 2.85 (1.56-5.21)], age [OR 3.74 (2.42-5.77)], statin use [OR 2.23 (1.23-4.50)] were associated with CaSc>100, after adjusting for body composition, pack-years, C-reactive protein, use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), diabetes, emphysema score, GOLD category, exacerbation frequency, eosinophilia, and hypoxemia. COPD patients were more likely to have CHD, but neither emphysema score, lung function, exacerbation frequency, nor hypoxemia predicted presence of either coronary stenosis or CaSc>100.

Why not change the therapy of hypertension in patients with COVID-19. Dual role of angiotensin-converting enzyme 2

Despite many organizational and medical efforts, the COVID-19 epidemic continues and is taking a lethal toll. Preliminary reports have already reported that the mortality associated with this disease is much higher in people with comorbidities, including hypertension. SARS-CoV-2 virus enters the body through the receptor which is the angiotensin converting enzyme 2 (ACE2). The administration of angiotensin converting enzyme inhibitors or sartans increases the activity of this enzyme. Therefore, there was a suspicion that patients treated with these preparations become more easily infected, and the infection itself is more severe and is associated with greater mortality. On the other hand, the ACE2 enzyme is known to reduce the risk of lung damage. The paper presents current reports describing the frequency of SARS-CoV-2 virus infection in patients with hypertension, the course of infection and the effect of administration of ACE inhibitors and sartans on the mortality of these patients. The presented data indicate that the use of angiotensin converting enzyme inhibitors and sartans in patients with COVID-19 does not worsen the course of the disease, and according to some authors this treatment even reduces the mortality of this infection.

Incidence, associated factors, and effect on renal function of amoxicillin crystalluria in patients receiving high doses of intravenous amoxicillin (The CRISTAMOX Study): A cohort study.

SummaryBackgroundAmoxicillin crystalluria (AC), potentially responsible for acute kidney injury (AKI), is reported more and more frequently in patients treated with high doses of intravenous amoxicillin (HDIVA). The main objective of this study was to evaluate AC incidence in these patients. The secondary objectives were to identify factors associated with AC and to evaluate its impact on the risk of AKI.MethodsThis multicentre, observational, cohort study was conducted between Mar 18, 2014 and Aug 16, 2019 in Dijon, Nancy, and Reims University Hospitals as well as Châlon-sur-Saône, Charleville-Mézières, and Troyes general hospitals in France. Adult patients (≥18 years) treated with HDIVA and having been tested for AC at least once during treatment were included. Clinical, biological, and therapeutic characteristics of the patients were collected. A univariable mixed logistic regression model assessed the factors associated with AC. A multivariable Cox model with AC as a time-dependent variable assessed the prognostic factors for AKI. ClinicalTrials.gov number: NCT02853292.FindingsOf the 112 included patients, 27 (24.1%, 95% CI [16.2-32.0]) developed at least one episode of AC within a mean of 5.1 days. The factors associated with its occurrence were the concomitant use of angiotensin converting enzyme (ACE) inhibitors (OR=4.6, 95% CI [2.2-9.3], p<0.0001) and the decrease of urinary pH (OR=2.1 for one pH point decrease, 95% CI [1.2-3.7], p=0.009). 20 patients (17.9%) presented with AKI, within a mean time of 10.9 days. The main factor associated with the occurrence of AKI was the occurrence of AC (aHR=7.4, 95% CI [2.5-22.2], p=0.0003).InterpretationAC occurred in a quarter of patients treated with HDIVA and was highly prognostic of AKI.FundingNone.

Genetic risk of hyperuricemia in hypertensive patients associated with antihypertensive drug therapy: A longitudinal study.

Elevated serum uric acid (UA) level has been shown to be influenced by multiple genetic variants, but it remains uncertain how UA‐associated variants differ in their influence on hyperuricemia risk in people taking antihypertensive drugs. We examined a total of 43 UA‐related variants at 29 genes in 1840 patients with hypertension from a community‐based longitudinal cohort during a median 2.25‐year follow‐up (including 1031 participants with normal UA, 440 prevalent hyperuricemia at baseline, and 369 new‐onset hyperuricemia). Compared with the wild‐type genotypes, patients carrying the SLC2A9 rs3775948G allele or the rs13129697G allele had decreased risk of hyperuricemia, while patients carrying the SLC2A9 rs11722228T allele had increased risk of hyperuricemia, after adjustment for cardiovascular risk factors and correction for multiple comparisons; moreover, these associations were modified by the use of diuretics, β‐blockers, or angiotensin converting enzyme inhibitors. The rs10821905A allele of A1CF gene was associated with increased risk of hyperuricemia, and this risk was enhanced by diuretics use. The studied variants were not observed to confer risk for incident cardiovascular events during the follow‐up. In conclusion, the genes SLC2A9 and A1CF may serve as potential genetic markers for hyperuricemia risk in relation to antihypertensive drugs therapy in Chinese hypertensive patients.

Use of angiotensin converting enzyme inhibitors is associated with reduced risk of late bladder toxicity following radiotherapy for prostate cancer

Background and purposeGenome-wide association studies (GWAS) of late hematuria following prostate cancer radiotherapy identified single nucleotide polymorphisms (SNPs) near AGT, encoding angiotensinogen. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEi) have a reduced risk of late hematuria. We additionally tested genetically-defined hypertension. Materials and methodsProstate cancer patients undergoing potentially-curative radiotherapy were enrolled onto two multi-center observational studies, URWCI (N = 256) and REQUITE (N = 1,437). Patients were assessed pre-radiotherapy and followed prospectively for development of toxicity for up to four years. The cumulative probability of hematuria was estimated by the Kaplan-Meier method. Multivariable grouped relative risk models assessed the effect of ACEi on time to hematuria adjusting for clinical factors and stratified by enrollment site. A polygenic risk score (PRS) for blood pressure was tested for association with hematuria in REQUITE and our Radiogenomics Consortium GWAS. ResultsPatients taking ACEi during radiotherapy had a reduced risk of hematuria (HR 0.51, 95%CI 0.28 to 0.94, p = 0.030) after adjusting for prior transurethral prostate and/or bladder resection, heart disease, pelvic node radiotherapy, and bladder volume receiving 70 Gy, which are associated with hematuria. A blood pressure PRS was associated with hypertension (odds ratio per standard deviation 1.38, 95%CI 1.31 to 1.46, n = 5,288, p < 0.001) but not hematuria (HR per standard deviation 0.96, 95%CI 0.87 to 1.06, n = 5,126, p = 0.41). ConclusionsOur study is the first to show a radioprotective effect of ACEi on bladder in an international, multi-site study of patients receiving pelvic radiotherapy. Mechanistic studies are needed to understand how targeting the angiotensin pathway protects the bladder.