Higher Incidence Of Cardiovascular Events Research Articles

Optimizing the care management pathway of patients with ischemia and non-obstructive coronary arteries

Ischemia with non-obstructive coronary arteries (INOCA) is defined by the coexistence of anginal symptoms and demonstrable ischemia, with no evidence of obstructive coronary arteries. The underlying mechanism of INOCA is coronary microvascular dysfunction with or without associated vasospasm. INOCA patients have recurrent symptoms, functional limitations, repeated access to the emergency department, impaired quality of life and a higher incidence of cardiovascular events than the general population. Although well described in chronic coronary syndrome guidelines, INOCA remains underdiagnosed in clinical practice because of insufficient awareness, lack of accurate diagnostic tools, and poorly standardized and consistent definitions to diagnose, both invasively and non-invasively, coronary microvascular dysfunction.To disseminate current scientific evidence on INOCA as a distinct clinical entity, during 2022 we conducted at 30 cardiology units all over the country a clinical practice improvement initiative, with the aim of developing uniform and shared management pathways for INOCA patients across different operational settings. The present document highlights the outcomes of this multidisciplinary initiative.

Coronary plaque phenotype associated with positive remodeling

BackgroundPositive remodeling is an integral part of the vascular adaptation process during the development of atherosclerosis, which can be detected by coronary computed tomography angiography (CTA). MethodsA total of 426 patients who underwent both coronary CTA and optical coherence tomography (OCT) were included. Four machine learning (ML) models, gradient boosting machine (GBM), random forest (RF), deep learning (DL), and support vector machine (SVM), were employed to detect specific plaque features. A total of 15 plaque features assessed by OCT were analyzed. The variable importance ranking was used to identify the features most closely associated with positive remodeling. ResultsIn the variable importance ranking, lipid index and maximal calcification arc were consistently ranked high across all four ML models. Lipid index and maximal calcification arc were correlated with positive remodeling, showing pronounced influence at the lower range and diminishing influence at the higher range. Patients with more plaques with positive remodeling throughout their entire coronary trees had higher low-density lipoprotein cholesterol levels and were associated with a higher incidence of cardiovascular events during 5-year follow-up (Hazard ratio 2.10 [1.26–3.48], P ​= ​0.004). ConclusionGreater lipid accumulation and less calcium burden were important features associated with positive remodeling in the coronary arteries. The number of coronary plaques with positive remodeling was associated with a higher incidence of cardiovascular events.

La hipertensión arterial intradiálisis, un diagnóstico por descubrir

IntroductionIntradialytic hypertension (IDH) is a poorly understood phenomenon with no consensus on its definition, etiology, or related factors, and there is limited evidence on its consequences. ObjectiveTo determine the prevalence of IDH according to different definitions in hemodialysis (HD) units, with different clinical practices and assessment of possible events after 18 months have passed. Materials and methodsA cross-sectional observational study was conducted in two HD units, including all prevalent patients from March 2021 to September 2022. We established three definitions of IDH: Def 1: Mean arterial pressure (MAP) difference pre- and pos-HD>15mmHg. Def 2: Systolic blood pressure (SBP) difference pre- and pos-HD>10mmHg. Def 3: SBP difference >0 and ultrafiltration rate (UFR)>5ml/kg/h.IDH was considered present if the criterion was met in more than 50% of the six consecutive sessions (2 weeks) of follow-up. Personal history, medications, dialysis characteristics, and pre- and post-HD biochemical data were collected. Residual renal function (RRF) was considered as urine output >250ml/24h. At 18 months, the possible events of the group were analyzed. ResultsWe included 169 patients (68% men) with a mean age of 67.9 (14.2) years and a median HD duration of 34.5 (IQR: 17.5-67.5) months. Of these, 94 come from one unit and 75 from the other. The prevalence of IDH was 8.3% according to Def 1, 27.2% according to Def 2, and 29.6% according to Def 3. Def 2 showed an association with a history of previous hypertension, use of renin-angiotensin system inhibitors (RASIs), and furosemide, as well as with patients with RRF. Def 3 showed an association only with coronary artery disease. There was an association with different prescriptions of dialysis fluids. Catecholaminergic hormones and aldosterone did not increase in patients with hypertension during the HD session. They did not present a higher incidence of cardiovascular events or mortality at 18 months. ConclusionsIDH has different prevalence rates depending on the definition used and the studied center. The future poses an important challenge: to determine which definition correlates with higher morbidity and mortality and the role of differences found in different HD units.

Onset Mechanisms and Prognosis of Neurally Mediated Syncope

Neurally mediated syncope (NMS) is associated with a sudden loss of consciousness. However, the diagnostic tools and measures for prognosis management are limited. To overcome these limitations, the differences in the binding energies of Giα-protein-coupled receptors to the Glu9 and Glu12 residues on the α2B-AR gene were elucidated through the analysis of α2B-AR gene polymorphism. The suppression of the activity of adenylate cyclase (AC), which is involved in vasoconstriction, may be related to the onset of NMS. The head-up tilt (HUT) test results indicated differences in systolic blood pressure (SBP) and AC activity between patients with vasodepressor (VT)-NMS and healthy volunteers. Patients with VT-NMS had increased AC activity and decreased SBP. Conversely, in healthy volunteers, no changes in AC activity or SBP were found. These findings suggest that a high SBP and elevated AC activity at rest are likely to cause syncope. A high incidence of cardiovascular events is found in patients with negative HUT test results, highlighting the importance of investigating the cause of syncope in cases where the HUT test results are negative. Overall, our results may provide a means of assessing the risk of NMS development within healthy populations and underscore the importance of subsequent treatments for NMS.

Association between Troponin Elevation and Decreased Myocardial Blood Flow Reserve in Patients without Obstructive Coronary Artery Disease

Introduction: To study the prognostic factors of patients with chest pain and without obstructive coronary artery disease is of great significance for the management of such patients. We assessed whether a high-sensitivity troponin I (hs-TnI) is associated with prognosis in patients with chest pain and without obstructive coronary artery disease. Methods: From 2011 to 2017, 489 consecutively hospitalized patients with chest pain and without significant coronary artery stenosis (<50%) were tested for hs-TnI and underwent stress myocardial contrast echocardiography (MCE). Myocardial blood flow reserve (MBFR) was measured by stress MCE. Patients were followed (median, 41 months) for composite endpoints, including cardiovascular death and non-fatal myocardial infarction. Cox proportional hazards models were performed to determine associations between hs-TnI and the composite endpoints. Results: Among 489 patients with chest pain and without significant coronary artery stenosis, 257 patients (52.6%) had elevated hs-TnI. Compared to patients with normal hs-TnI, patients with elevated hs-TnI were older (p = 0.013) and had a higher prevalence of atrial fibrillation (p = 0.003), higher left ventricular mass index (p = 0.002) and E/e’ septal (p < 0.001), and a lower MBFR (p < 0.001). After adjustment, there was still a significant association between hs-TnI and MBFR (odds ratio = 1.145; 95% confidence interval [CI], 1.079–1.214; p < 0.001). Compared with patients with normal hs-TnI, patients with elevated hs-TnI had a greater cumulative event rate (log-rank p = 0.002). Males (hazard ratio [HR], 4.770; 95% CI, 1.175–19.363; p = 0.029) and reduced MBFR (HR, 2.496; 95% CI, 1.446–4.311; p = 0.001) were risk factors associated with composite endpoints in patients with elevated hs-TnI. Conclusions: In patients with chest pain and without obstructive coronary artery disease, elevated hs-TnI is associated with decreased myocardial perfusion by contrast echocardiography as well as a higher incidence of cardiovascular events.

Abstract 17646: Maternal and Neonatal Outcomes in Pregnant Women With Congenital Heart Disease: The Magee Obstetric Maternal and Infant (MOMI) ACHD Substudy

Introduction: Adult patients with congenital heart disease (ACHD) have a life-long burden of cardiovascular morbidity that contributes to increased maternal and neonatal risk during pregnancy and the peripartum period. Hypothesis: Women with ACHD and their neonates have a higher risk of adverse pregnancy and peripartum outcomes as compared to women without ACHD. Methods: We matched 565 deliveries from women with ACHD and 1130 deliveries from women without cardiac disease (1:2 matching), for a delivery year, race and maternal age as a substudy of the Magee Obstetric Maternal and Infant (MOMI) study, of women who received perinatal care at the Magee-Womens Hospital at the University of Pittsburgh Medical Center between 1995-2020. We evaluated for in-hospital maternal and neonatal outcomes. Results: Of the 565 women with ACHD, 24.0% had aortic outflow and mitral valve abnormalities, 19.5% had pulmonary outflow and tricuspid valve abnormalities, 28.1% had isolated atrial or ventricular septal defects, 0.3% had single ventricle physiology, and 1.4% had outflow vessel abnormalities. Maternal and neonatal outcomes are summarized in Table 1. Women with ACHD had a higher rate of pregnancy loss (32.4% vs 26.2% p&lt;0.001), induction of labor, and cesarean section. Neonates from ACHD women were delivered at an earlier gestational age, with a lower birth weight, and had a higher incidence of respiratory distress syndrome. ACHD women had a higher incidence of cardiovascular events (predominantly arrhythmias and pulmonary edema) and required intensive care more frequently (10.5% vs 1.2%, p&lt;0.001) and for longer periods (2.1±1.8 vs. 1.1±0.3 days; P=0.027) after delivery. Conclusion: Women with ACHD are at higher risk for adverse clinical outcomes during pregnancy and delivery. Neonates of ACHD women are delivered slightly earlier by induction of labor and have consequent sequelae after birth.

The association of left ventricular fraction shortening with cardiovascular events in peritoneal dialysis patients

Background Peritoneal dialysis (PD) patients have a high incidence of cardiovascular events (CVEs). Left ventricular fraction shortening (LVFS), one of the echocardiographic parameters, is an independent risk factor for mortality in previous studies. The aim of this study was to evaluate associations between LVFS and CVEs in PD patients. Methods This was a single-center observational cohort study. Seven hundred and eighty-four PD patients were enrolled from 1 January 2012 to 1 June 2021 and followed until 1 June 2022. The primary outcome was the incidence of CVEs. PD patients were categorized into three groups according to the tertiles of LVFS levels (tertile 1-tertile 3). Kaplan-Meier method, Cox proportional hazard models and competing risk regression models were used for survival analysis. The areas under the curve (AUC) of receiver-operating characteristic analysis was used to determine the predictive values of LVFS for CVEs. A preplanned subgroup analysis was assessed according to age, gender, and the presence of hypertension and dyslipidemia, etc. Results During a median follow-up period of 42.3 months (interquartile range 24.0–79.0 months), 259 CVEs occurred. Compared to the other two groups respectively, patients in tertile 3 group had the lowest incidence of CVEs (24.5% vs 31.6% vs 43.0%, respectively, p < 0.05). After multiple adjustments, the tertile 3 group was associated with the 45.1% decrease in the CVEs hazard compared to that of the tertile1 group (SHR = 0.549, 95%CI: 0.395–0.762, p < 0.001). Subgroup analysis demonstrated that tertile 1 group as the reference, the association between LVFS and CVEs in tertile 3 group was robust among female patients (HR = 0.506, 95%CI: 0.309–0.829, p = 0.007), aged < 45 years (HR = 0.496, 95%CI: 0.331–0.744, p = 0.001), history of hypertension (HR = 0.586, 95%CI: 0.349–0.872, p = 0.008) and combined with dyslipidemia (HR = 0.464, 95%CI: 0.269–0.799, p = 0.006). Conclusions This study suggests that LVFS is independently associated with the increased risk of CVEs in PD patients, especially those with aged < 45 years, female, with hypertension and dyslipidemia.

Risk of cardiovascular disease associated with repeated proteinuria across annual kidney function screening among the middle-aged and older general population in Japan: a retrospective cohort study

ObjectivesWe aimed to investigate the association between repetitive proteinuria and cardiovascular events among the middle-aged and older general Japanese population.DesignRetrospective cohort study.SettingWe used repeated health screening results and medical claim...

Modifiability of Composite Cardiovascular Risk Associated With Chronic Kidney Disease in Type 2 Diabetes With Finerenone

It is currently unclear whether chronic kidney disease (CKD)-associated cardiovascular risk in type 2 diabetes (T2D) is modifiable. To examine whether cardiovascular risk can be modified with finerenone in patients with T2D and CKD. Incidence rates from Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis (FIDELITY), a pooled analysis of 2 phase 3 trials (including patients with CKD and T2D randomly assigned to receive finerenone or placebo) were combined with National Health and Nutrition Examination Survey data to simulate the number of composite cardiovascular events that may be prevented per year with finerenone at a population level. Data were analyzed over 4 years of consecutive National Health and Nutrition Examination Survey data cycles (2015-2016 and 2017-2018). Incidence rates of cardiovascular events (composite of cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, or hospitalization for heart failure) were estimated over a median of 3.0 years by estimated glomerular filtration rate (eGFR) and albuminuria categories. The outcome was analyzed using Cox proportional hazards models stratified by study, region, eGFR and albuminuria categories at screening, and cardiovascular disease history. This subanalysis included a total of 13 026 participants (mean [SD] age, 64.8 [9.5] years; 9088 male [69.8%]). Lower eGFR and higher albuminuria were associated with higher incidences of cardiovascular events. For recipients in the placebo group with an eGFR of 90 or greater, incidence rates per 100 patient-years were 2.38 (95% CI, 1.03-4.29) in those with a urine albumin to creatinine ratio (UACR) less than 300 mg/g and 3.78 (95% CI, 2.91-4.75) in those with UACR of 300 mg/g or greater. In those with eGFR less than 30, incidence rates increased to 6.54 (95% CI, 4.19-9.40) vs 8.74 (95% CI, 6.78-10.93), respectively. In both continuous and categorical models, finerenone was associated with a reduction in composite cardiovascular risk (hazard ratio, 0.86; 95% CI, 0.78-0.95; P = .002) irrespective of eGFR and UACR (P value for interaction = .66). In 6.4 million treatment-eligible individuals (95% CI, 5.4-7.4 million), 1 year of finerenone treatment was simulated to prevent 38 359 cardiovascular events (95% CI, 31 741-44 852), including approximately 14 000 hospitalizations for heart failure, with 66% (25 357 of 38 360) prevented in patients with eGFR of 60 or greater. Results of this subanalysis of the FIDELITY analysis suggest that CKD-associated composite cardiovascular risk may be modifiable with finerenone treatment in patients with T2D, those with eGFR of 25 or higher, and those with UACR of 30 mg/g or greater. UACR screening to identify patients with T2D and albuminuria with eGFR of 60 or greater may provide significant opportunities for population benefits.

#4951 NON-ADHERENCE TO CARDIOMETABOLIC DRUGS AS ASSESSED BY LS-MS/MS IN URINE AND ITS ASSOCIATION WITH RENAL AND CARDIOVASCULAR OUTCOMES IN T2DM

Abstract Background and Aims Cardiovascular and renal complications have a detrimental impact on the prognosis and quality of life of patients with type 2 diabetes mellitus (T2DM). Guidelines recommend combination drug therapy to prevent or delay these complications[1]. However, non-adherence to medication is common and a barrier to successful disease management[2]. Most previous studies on adherence and outcome used indirect methods to assess adherence[3]. In this study we used liquid chromatography-tandem mass spectrometry (LC-MS/MS), a direct and objective adherence measure, to asses adherence to cardiometabolic drugs in a large real-world cohort of individuals with T2DM and analyzed non-adherence in the context of cardiovascular and renal outcomes. Method 1125 eligible PROVALID participants were included. PROVALID is a prospective observational cohort study of patients with T2DM followed annually at the primary health care level. Urine samples from the PROVALID biobank were screened for 79 cardiometabolic drugs and metabolites thereof by LC-MS/MS. An individual was classified as fully adherent when markers for all prescribed drugs were detected, partially non-adherent when at least a marker for one drug was detected and totally non-adherent when no marker for any prescribed drug was detectable. In order to assess outcome by adherence we defined a cardiovascular (myocardial infarction, stroke, and cardiovascular death) and a renal (ESKD, renal death, sustained 40% reduction in eGFR to &amp;lt; 60 ml/min per 1.73 m², sustained progression of albuminuria) composite endpoint. Results The mean age was 64.2 (±8.9) years and 46.1% were female. The mean duration of T2DM was 11.4 (±7.9) years. The mean HbA1c was 7.1 (±1.1)%, the mean eGFR was 77.6 (±23.6) ml/min/1.73 m2 and mean albuminuria 67.3 (±287.9) mg/g creatinine. Participants were prescribed 5.4 (±2.0) cardiometabolic drugs on average. Based on the results of LC-MS/MS measurements, 56.3% were totally adherent, 42.0% were partially adherent, and 1.7% were totally non-adherent to screened cardiometabolic drugs. Adherence was highest to antiplatelet and glucose lowering drugs and lowest to lipid lowering drugs (totally adherent individuals 90.1%, 89.2% and 70.7%, respectively). Non-adherent patients had a longer history of T2DM (12.3 ± 8.5 vs. 10.7 ± 7.5, p = 0.003) and a higher number of prescribed drugs (5.8 ± 2.1 vs. 5.1 ± 1.9, p &amp;lt; 0.001). Age per se had no influence on adherence, however the number of prescribed medications had more impact on adherence in younger patients (Fig. 1). Ex-smokers were more likely to be adherent than current or never-smokers (odds ratio 1.4, p-value = 0.014). Patients who were adherent to lipid lowering drugs had significantly lower LDL (82.4 ± 29.8 vs. 111.4 ± 39.7 mg/dl, p &amp;lt; 0.001). A trend for lower HbA1c with adherence to glucose-lowering drugs and lower systolic blood pressure with adherence to antihypertensive drugs could be observed, however these differences were not statistically significant. In the longitudinal analysis, worse cardiovascular prognosis was especially seen with non-adherence to antiplatelet drugs and worse renal outcome especially with non-adherence to antihypertensive drugs (Fig. 2). Conclusion Our analysis confirms that non-adherence, especially partial non-adherence, to cardiometabolic drugs is common in T2DM. A higher incidence of cardiovascular events was observed with non-adherence to antiplatelet drugs, whereas non-adherence to antihypertensive drugs was associated with a higher renal event rate.

Pulse Wave Amplitude Drops Index: A Biomarker of Cardiovascular Risk in Obstructive Sleep Apnea.

Rationale: It is currently unclear which patients with obstructive sleep apnea (OSA) are at increased cardiovascular risk. Objective: To investigate the value of pulse wave amplitude drops (PWADs), reflecting sympathetic activations and vasoreactivity, as a biomarker of cardiovascular risk in OSA. Methods: PWADs were derived from pulse oximetry-based photoplethysmography signals in three prospective cohorts: HypnoLaus (N = 1,941), the Pays-de-la-Loire Sleep Cohort (PLSC; N = 6,367), and "Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome. Effect of intervention with CPAP" (ISAACC) (N = 692). The PWAD index was the number of PWADs (>30%) per hour during sleep. All participants were divided into subgroups according to the presence or absence of OSA (defined as ⩾15 or more events per hour or <15/h, respectively, on the apnea-hypopnea index) and the median PWAD index. Primary outcome was the incidence of composite cardiovascular events. Measurements and Main Results: Using Cox models adjusted for cardiovascular risk factors (hazard ratio; HR [95% confidence interval]), patients with a low PWAD index and OSA had a higher incidence of cardiovascular events compared with the high-PWAD and OSA group and those without OSA in the HypnoLaus cohort (HR, 2.16 [1.07-4.34], P = 0.031; and 2.35 [1.12-4.93], P = 0.024) and in the PLSC (1.36 [1.13-1.63], P = 0.001; and 1.44 [1.06-1.94], P = 0.019), respectively. In the ISAACC cohort, the low-PWAD and OSA untreated group had a higher cardiovascular event recurrence rate than that of the no-OSA group (2.03 [1.08-3.81], P = 0.028). In the PLSC and HypnoLaus cohorts, every increase of 10 events per hour in the continuous PWAD index was negatively associated with incident cardiovascular events exclusively in patients with OSA (HR, 0.85 [0.73-0.99], P = 0.031; and HR, 0.91 [0.86-0.96], P < 0.001, respectively). This association was not significant in the no-OSA group and the ISAACC cohort. Conclusions: In patients with OSA, a low PWAD index reflecting poor autonomic and vascular reactivity was independently associated with a higher cardiovascular risk.

Clinical characteristics and frequency of anticoagulation in patients with atrial fibrillation and heart failure: results of a retrospective big data analysis

Aim. To evaluate the clinical characteristics and frequency of prescribed anticoagulant therapy for patients with atrial fibrillation (AF) and heart failure (HF) in subjects of the Russian Federation based on a retrospective big data analysis using artificial intelligence technologies.Material and methods. For retrospective analysis, information was obtained from the Webiomed predictive analytics platform, which includes depersonalized data from electronic health records of outand/ or inpatients in 6 subjects of the Russian Federation, extracted using artificial intelligence technologies. From the database of patients with AF (n=144431), a group of individuals (n=20970) with an established diagnosis of HF and information on left ventricular ejection fraction (LVEF) was selected.Results. Patients with AF and HF (men, 43,7%; age 72,1±13,2 years; LVEF, 58,9±11,0%) had a history of smoking in 36,6% of cases, hypertension — in 86,7%, type 2 diabetes — in 26,6%, gout — in 2,7%, stage III and IV-V chronic kidney disease — in 50,9 and 15,6%, lower limb peripheral arterial disease — in 15,8%. The incidence of ischemic stroke, LV myocardial infarction and pulmonary embolism was 8,8, 14,7 and 2,4%, respectively. Anticoagulants, including direct oral ones, were administered to patients with AF and HF in 62,5% and 32,0% of cases, respectively. The frequency of their appointment did not significantly differ depending on LVEF.Conclusion. Patients with AF and HF are characterized by significant comorbidity, a higher incidence of cardiovascular events compared with the group of individuals with AF without HF, and an unsatisfactory percentage of anticoagulant therapy.

Cardiac Incidental Findings on Abdominopelvic Computed Tomography: Prevalence and Association with Subsequent Cardiovascular Events

The aim of this study was to assess the prevalence of reportable cardiac findings detected on abdominopelvic CTs and the association with subsequent cardiovascular events. We performed a retrospective search of electronic medical record of patients who underwent abdominopelvic CT between November 2006 and November 2011 with a clinical history of upper abdominal pain. A radiologist blinded to the original CT report reviewed all 222 cases for the presence of pertinent reportable cardiac findings. The original CT report was also evaluated for documentation of pertinent reportable cardiac findings. The following findings were recorded on all CTs: presence of coronary calcification, fatty metaplasia, ventricle wall thinning and thickening, valve calcification or prosthesis, heart/chamber enlargement, aneurysm, mass, thrombus, device, air within ventricles, abnormal pericardium, prior sternotomy, and adhesions if prior sternotomy. Medical records were reviewed to identify cardiovascular events on follow-up in patients with the presence or absence of cardiac findings. We compared the distribution findings in patients with and without cardiac events using the Wilcoxon test (for continuous variables) and the Pearson's chi-squared test (for categorical variables). Eighty-five of 222 (38.3%) patients (52.7% females, median age 52.5 years) had at least one pertinent reportable cardiac finding on the abdominopelvic CT, with a total of 140 findings in this group. From the total 140 findings, 100 (71.4%) were not reported. The most common findings seen on abdominal CTs were: coronary artery calcification (66 patients), heart or chamber enlargement (25), valve abnormality (19), sternotomy and surgery signs (9), LV wall thickening (7), device (5), LV wall thinning (2), pericardial effusion (5), and others (3). After a mean follow-up of 43.9 months, 19 cardiovascular events were found in the cohort (transient ischemic attack, cerebrovascular accident, myocardial infarction, cardiac arrest, acute arrhythmia, palpitation, syncope and acute chest pain). Only 1 event occurred in the group of patients with no incidental pertinent reportable cardiac findings (1/137=0.73%). All other 18 events occurred in patients with incidental pertinent reportable cardiac findings (18/85=21.2%), which was significantly different (p < 0.0001). One out of the total 19 events in the overall group (5.24%) occurred in a patient with no incidental pertinent reportable cardiac findings while 18 of 19 total events (94.74%) occurred with patients with incidental pertinent reportable cardiac findings, which was also significantly different (p < 0.001). Fifteen of the total events (79%) occurred in patients in whom the incidental pertinent reportable cardiac findings were not reported, which was significantly different (p < 0.001) from the four events that occurred in patients in whom the incidental pertinent reportable cardiac findings were reported or had no findings. Incidental pertinent reportable cardiac findings are common on abdominal CTs and are frequently not reported by radiologists. These findings are of clinical relevance since patients with pertinent reportable cardiac findings have a significantly higher incidence of cardiovascular events on follow-up.

Effects of Spironolactone on Arrhythmias in Hemodialysis Patients: Secondary Results of the SPin-D Randomized Controlled Trial.

Background Patients receiving maintenance hemodialysis (HD) have a high incidence of cardiovascular events, including arrhythmia and sudden death. Spironolactone reduces the risk of cardiovascular events and sudden death in patients with heart failure, but the effects of spironolactone on arrhythmic events in patients treated with maintenance HD are unclear. Methods The Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent ESRD (SPin-D) trial, was a 36-week randomized, placebo-controlled, double-blind trial comparing 3 different doses of spironolactone with placebo in maintenance HD patients. We performed a post-hoc analysis in a subset (n=57) who underwent extended electrocardiographic monitoring using a wearable device at baseline and follow-up. Generalized estimating equations models were fit to determine the associations of spironolactone (individual doses and combined) versus placebo on the incidence rate of predefined categories of arrhythmic events. Results The average age of participants was 55 ±12 years; 61% were male; and 77% were Black. The overall proportion of patients with at least one arrhythmia event was 43% (15/35) at baseline and 81% (43/53) at the end of follow-up. At the end of follow-up, the rate of bradycardic events or conduction blocks was higher in the combined spironolactone group, compared with placebo, (82.4 versus 38.7 events/100 patient days; P<0.001). Similar findings were noted in adjusted models, but did not meet statistical significance (adjusted rate ratio of 2.04; 95%CI 0.83 - 5.05). Conclusions In a 36-week trial of patients receiving maintenance hemodialysis, a higher frequency of bradycardia and conduction blocks was observed among those treated with spironolactone treatment compared with placebo. Larger studies are required to investigate the longer-term effects of spironolactone on cardiac conduction in patients receiving hemodialysis.

Clonal hematopoiesis onset in chronic myeloid leukemia patients developing an adverse cardiovascular event

Life expectation of chronic myeloid leukemia patients in the tyrosine kinase inhibitors era is almost equal to that of healthy subjects. On the other hand, their long-term management must take into account a higher risk of adverse events, at least partly related to the treatment. Various studies reported a higher incidence of cardiovascular events in these patients. Clonal hematopoiesis is broadly considered a major independent risk factor for cardiovascular events. Of note, the underlying physiopathological mechanisms connect clonal hematopoiesis with a global proinflammatory status, triggering a vicious circle in which the somatic mutations and inflammation feed each other. All this considered, we investigated the occurrence of clonal hematopoiesis in chronic myeloid leukemia patients developing a cardiovascular event under tyrosine kinase inhibitor therapy.

Outcomes in patients with cardiometabolic disease who develop hyperkalemia while treated with a renin-angiotensin-aldosterone system inhibitor

Many patients with indications for renin-angiotensin-aldosterone system inhibitor (RAASi) therapy are not receiving these medications. Concern about hyperkalemia is thought to contribute to this lack of evidence-based therapy. A retrospective cohort study included adult patients in primary care practices affiliated with an integrated health care delivery system treated with RAASi between 2000 and 2019 for any of the following indications: (a) coronary artery disease (CAD); (b) heart failure (HF) with a left ventricle ejection fraction ≤ 40%; (c) diabetes mellitus (DM) with proteinuria; or (d) chronic kidney disease (CKD) with proteinuria. Relationship between hyperkalemia (K > 5.0 mEg/L) over the first 12 months of follow-up and a composite end point of cardiovascular events, renal dysfunction, and all-cause mortality was evaluated. Among 82,732 study patients, 7,727 (9.34%) developed hyperkalemia. Patients with hyperkalemia were older (69.0 vs 64.6) and more likely to have CAD (57.8 vs 53.7%), CKD (57.3 vs 51.1%), HF (19.3 vs 9.7%), and DM (45.3 vs 33.3%) (P < .001 for all). Five-year cumulative risk of the primary outcome was higher in patients who did (63.9%; 95% CI: 62.8%-65.1%) versus did not (37.2%; 95% CI: 36.8%-37.6%) develop hyperkalemia. Five-year cumulative risk of ED visit or hospitalization for hyperkalemia was 15.6% (14.7%-16.6%) for patients with versus 2.7% (95% CI: 2.6-2.9) for patients without hyperkalemia, rising to 25.9% (95% CI: 22.4-29.9) for patients with severe (K > 6.0 mEq/dL) hyperkalemia. Patients who experienced hyperkalemia were more likely (34.4%) than patients who did not (29.2%) to deintensify RAASi therapy (P < .001). Five-year cumulative risk of the primary outcome was higher in patients who lowered RAASi dose (50.4%; 95% CI: 48.5%-52.4%) or stopped RAASi therapy completely (49.3%; 95% CI: 48.5%-50.1%), compared to patients who continued RAASi therapy (36.1%; 95% CI: 25.7-36.5). Similar findings were observed in multivariable analyses and for individual components of the primary outcome. Hyperkalemia is a common complication of RAASi therapy and is associated with an increased risk of multiple adverse outcomes. Patients who have their RAASi medications deintensified after a hyperkalemic event have higher incidence of cardiovascular events, renal dysfunction and death.

PS-C36-6: REAL-WORLD ANALYSIS OF ADHERENCE, OUTCOMES AND HEALTHCARE COSTS OF THE QUADRUPLE COMBINATION PERINDOPRIL, INDAPAMIDE, AMLODIPINE AND BISOPROLOL IN ITALY

Objective: this real-world analysis aimed to evaluate drug utilization, outcomes and direct healthcare costs in hypertensive patients treated with the combination of perindopril, indapamide, amlodipine and bisoprolol (PER/IND/AML/BIS) in Italy. Design and method: a retrospective analysis was performed using administrative databases covering approximately 7 million health-assisted Italian subjects. Adults prescribed with PER/IND/AML/BIS in free combination during 2018 were included. Index date corresponded to first prescription date of the four drugs (prescribed within 30 days). Follow-up was 1 year after index date; patients who died during this period were excluded. Drug utilization was evaluated as adherence (proportion of days covered (PDC): PDC &lt; 40% non-adherence; PDC = 40–79% partial adherence; PDC&gt; = 80% adherence); persistence/interruption (presence/absence of PER/IND/AML/BIS in last trimester of follow-up); add-on (new antihypertensive agent added to PER/IND/AML/BIS), switch (change of at least 1 among PER/IND/AML/BIS). Outcomes [i.e. incidence rate per 1,000-person/year of death and cardiovascular (CV) events] and mean annual direct healthcare costs (related to all-cause drugs, hospitalizations and outpatient services) covered by National Health Service, were evaluated. Results: A total of 5,677 patients (50.6% male, mean age 70 years) had a prescription of the antihypertensive drugs PER/IND/AML/BIS. 98.5% had a history of cardiovascular diseases and 35.2% had diabetes. During first year of follow-up, 44% of patients were adherent to PER/IND/AML/BIS, 24% partially adherent, 32% non-adherent. A higher proportion of adherent patients was found among those receiving PER/IND/AML/BIS in 2 pills compared to 3 pills (45.4% and 30.2%, p &lt; 0.001). Among all patients, 682 (12%) received additional antihypertensive treatment to PER/IND/AML/BIS, while 761 (13%) had at least one switch. Switch of therapy was around 5-times more frequent among non-adherent patients (25.3% vs 5.1%, p &lt; 0.001). 53% of patients were persistent to PER/IND/AML/BIS while 47% had an interruption. In adherent patients, a significant reduction of the incidence rate of death and CV events was found (62.7/1,000-person/year) compared to non-adherent and partially-adherent (88.1 and 76.8/1,000-person/year, respectively, p &lt; 0.001). Mean total individual annual direct cost was higher for non-adherent (euro 2,456) compared to adherent (euro 2,071), with hospitalization costs almost 2-fold higher in non-adherent patients (euro 918 vs euro 456, p &lt; 0.001). Conclusions: This analysis provides real-world evidence on sub-optimal adherence and persistence in patients treated concomitantly with four antihypertensive drugs in Italy. In non-adherent patients, higher incidence of CV events and higher healthcare costs were reported. Better adherence was observed when fewer pills were taken. Further strategies to improve treatment adherence, especially in poly-medicated patients, are needed.

OVERVIEW ON ROLE OF PRIMARY CARE IN MANAGEMENT OF CHRONIC KIDNEY DISEASE

Chronic kidney disease (CKD) is characterised by the presence of kidney damage or an estimated glomerular filtration rate (eGFR). Patients with more advanced stage 3 or stage 4 CKD experience a higher incidence of cardiovascular events and mortality. Because chronic kidney disease is a growing health concern, family physicians must be equipped to care for this unique patient population. Practice recommendations encourage proactive care of cardiovascular risk, the side effects of metabolic bone disease, and anaemia in these individuals as well as surveillance for increasing kidney disease. Primary care physicians (PCPs) are on the front lines of identifying and treating CKD as early as possible. However, the majority of PCPs frequently miss the existence of CKD. Additionally, the majority of patients with stages 3 and 4 CKD are not co-managed by nephrologists, despite the fact that increasing nephrologists' engagement in the care of these patients has been associated with improved dialysis-free survival. Early detection and treatment of these issues can stop the onset of subsequent sequelae, thus they shouldn't wait till nephrology is involved. This patient population also need appropriate counselling and health maintenance, both of which should be provided by the family doctor overseeing the patient's care.

Comparison of cardiorenal safety of nonsteroidal anti-inflammatory drugs in the treatment of arthritis: a network meta-analysis.

Arthritis includes osteoarthritis (OA), rheumatoid arthritis (RA), and other arthritis-related disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used drugs for the treatment of arthritis. However, there remains a concern that some currently used NSAIDs may increase the risk of cardiorenal adverse events in patients with arthritis. Although it has been established that some NSAIDs are associated with a higher risk of cardiovascular and renal events, their safety varies widely. To provide insight into drug use, this study systematically assessed and compared the incidence of cardiovascular and renal events in different NSAIDs by using Bayesian meta-analysis. The PubMed, Cochrane Library, and Embase databases were searched for randomized controlled trials (RCTs) on NSAIDs. Databases were searched from the inception to April 25, 2022. Two investigators independently screened articles according to the Population, Intervention, Comparator, Outcomes, Study design (PICOS) principle, extracted data, and assessed the quality of articles using Cochrane Risk of Bias assessing tools. R software (version 4.1.3) was used for network meta-analysis (NMA). The analysis ultimately included 20 articles with a total of 144,957 patients and 13 interventions. The risk of bias in the included articles was generally moderate. Ibuprofen was associated with the highest incidence of hypertension outcomes [comparing with placebo OR (95% CI): 3.24 (1.71, 5.82)], rofecoxib with the highest incidence of renal events [comparing with placebo OR (95% CI): 4.46 (1.49, 14.73)], ibuprofen with the highest incidence of cardiovascular events [comparing with placebo OR (95% CI): 2.39 (0.82, 8.06), and naproxen with the highest incidence of edema [comparing with placebo OR (95% CI): 2.31 (1.16, 4.47)]. The NMA results showed that amtolmetin guacil was relatively safer, but it needs further investigation. Rofecoxib was associated with a higher incidence of cardiorenal adverse events, ibuprofen with a higher incidence of cardiovascular events and hypertension, and naproxen with a higher incidence of renal events and edema. Clinicians should weigh the efficacy of NSAIDs against renal and cardiovascular toxicity when prescribing NSAIDs for the treatment of arthritis.

Abstract 10065: Higher Cholesterol Absorption Marker at Baseline Predicts Less Cardiovascular Events in Elderly Patients With Hypercholesterolemia Treatment: Kyushu Elderly Ezetimibe Phytosterol (KEEP) Study

Introduction: Serum cholesterol levels depend on both cholesterol synthesis in the liver and absorption in the intestine. The higher absorption of cholesterol is reported to be related to a higher incidence of cardiovascular events (CVEs). Hypothesis: When treated with a cholesterol absorption inhibitor, higher cholesterol absorption marker could be associated with less CVEs. Methods: The participants in the Kyushu Elderly Ezetimibe Phytosterol (KEEP) study were the intension-to-treat (ITT) population of the EWTOPIA75 study which has proved the beneficial effect of ezetimibe on the prevention of CVEs in the elderly older than 75 years old (Ouchi Y, et al: Circulation 140:992-1003, 2019). A total of 1,131 participants were randomly assigned to a group receiving diet therapy only (diet group) and a group receiving ezetimibe (10 mg/day) in addition to diet therapy (ezetimibe group), and were followed up for 4 years. Blood sampling was performed at baseline and at 24 weeks of follow-up to measure serum lipids and related compounds including cholesterol absorption and synthesis markers. Serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) were also measured. The data of 1,061 participants (501 in the ezetimibe group and 560 in the diet group) were analyzed. Results: The mean age of participants analyzed was 80.5+/-4.8, and the female to male ratio was 3.2. The number of CVEs was 64. Both higher levels of campesterol (cholesterol absorption marker) and campesterol/lathosterol (cholesterol synthesis marker) ratio at baseline were significantly associated with lower risk of CVEs by ezetimibe (p=0.01 and p=0.04, respectively). No interaction of either lathosterol or campesterol with ezetimibe treatment on CVEs was found. NT-pro BNP was significantly associated with the risk of CVEs (p=0.004), but not hs-CRP. Conclusions: The KEEP Study has revealed that CVEs were significantly reduced in hypercholesterolemic participants with higher levels of campesterol, suggesting a rationale to treat patients with higher level of cholesterol absorption marker by ezetimibe which has been proved to be effective for the prevention of CVEs.