Prospective Comparison of Plasma Biomarker and Traditional Risk Factor Profiles for Incident Isolated Atherosclerotic Disease and Incident Isolated Abdominal Aortic Aneurysm

Background: Traditional risk factors for atherosclerotic disease (AD) are well-known, of which some are relevant also for abdominal aortic aneurysms (AAA). The present study compares the importance of plasma biomarkers and traditional risk factor profiles for incident AD without concomitant AAA (isolated AD) and AAA without concomitant AD (isolated AAA) during long-term follow-up.Methods: In the Malmö Diet and Cancer Study—cardiovascular cohort, 5,381 participants were free from atrial fibrillation or flutter, AD (coronary artery disease, atherothrombotic ischemic stroke, carotid artery disease, or peripheral artery disease), and AAA underwent blood sampling under standardized fasting conditions between 1991 and 1994. Cox proportional hazards regression analysis was used to calculate hazard ratios (HR) with 95% CIs.Results: During a median follow-up of 23.1 years, 1,152 participants developed isolated AD, and 44 developed isolated AAA. Adjusted HR for lipoprotein-associated phospholipase A2 (mass) (HR 1.53, 95% CI 1.14–2.04 vs. HR 1.05, 95% CI.99–1.12) was higher for incident isolated AAA compared to incident isolated AD, respectively. Mid-regional pro-adrenomedullin (MR-proADM) was associated with incident isolated AD (HR 1.17, 95% CI 1.1–1.25) and incident isolated AAA (HR 1.47, 95% CI 1.15–1.88). MR-proADM was correlated (r = 0.32; p < 0.001) to body mass index (BMI), and BMI was associated with increased risk of incident isolated AAA (HR 1.43, 95% CI 1.02–2). No participant with diabetes mellitus (DM) at baseline developed isolated AAA (0/44), whereas DM was associated with an increased risk of isolated AD (HR 2.57, 95% CI 2.08–3.18). Adjusted HR for male sex (HR 4.8, 95% CI 2.42–9.48, vs. HR 1.76, 95% CI 1.56–1.98) and current smoking (HR 4.79, 95% CI 2.42–9.47 vs. HR 1.97, 95% CI 1.73–2.23) were higher in the incident isolated AAA group compared to the incident isolated AD group, respectively.Conclusions: The data supports the view that components of vascular inflammation and cardiovascular stress drives AAA development, whereas glycated cross-links in abdominal aortic wall tissue may have a plausible role in reducing AAA risk in individuals with DM.

Contemporary (2019) prevalence of cardiovascular disease in adults with type 2 diabetes in Brazil: the cross-sectional CAPTURE study

Background Type 2 diabetes (T2D) is a known risk factor for cardiovascular disease (CVD), and CVD is a major cause of mortality in patients with T2D. The CAPTURE study investigated the contemporary (2019) prevalence of established CVD in adults with T2D around the world. We report the findings from Brazil. Methods The multinational, non-interventional, cross-sectional CAPTURE study was conducted across 13 countries from five continents. The current manuscript explores data for the CAPTURE study sample in Brazil. Standardized demographic and clinical data were collected from adults with T2D aged ≥ 18 years attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data were analyzed descriptively. Results Data from 912 adults with T2D were collected in the CAPTURE study in Brazil, with 822 patients from primary care and 90 patients from specialized care. Median (interquartile range [IQR]) patient characteristics were as follows: age 64 years (57; 71), diabetes duration 11 years (6; 19), glycated hemoglobin 7.7% (6.7; 9.1), and body mass index 29.5 kg/m2 (26.4; 33.5); 59% were female. The CVD prevalence and atherosclerotic CVD prevalence in the Brazil sample were 43.9% (95% confidence interval [CI] 40.9; 46.8) and 37.6% (95% CI 34.7; 40.5), respectively. The majority of patients with CVD had atherosclerotic CVD (85.8%). For the specific CVD subtypes, coronary heart disease prevalence was 27.9% (95% CI 25.2; 30.5), heart failure was 12.4% (95% CI 10.4; 14.4), cerebrovascular disease was 8.7% (95% CI 6.8; 10.5), and carotid artery disease was 3.4% (95% CI 2.3; 4.5). Glucagon-like peptide-1 receptor agonists and/or sodium-glucose co-transporter-2 inhibitors with proven cardiovascular benefit were prescribed to 15.5% of patients with CVD, compared with 18.4% of patients without CVD. Conclusions CAPTURE was the first multinational, standardized study to provide contemporary data on CVD prevalence in adults with T2D in Brazil, and it demonstrated that almost one in two adults with T2D had established CVD. Except for carotid artery disease, the prevalence of all CVD subtypes in adults with T2D in Brazil appeared higher than the global CAPTURE prevalence. Trial registration NCT03786406, NCT03811288

Neovascular Glaucoma Associated with Chronic Rhegmatogenous Retinal Detachment

Background To demonstrate the clinical features and natural course of chronic retinal detachment associated neovascular glaucoma. Methods Ten patients, diagnosed with chronic retinal detachment-associated neovascular glaucoma during 2007-2016 were retrospectively investigated. Besides chronic retinal detachment, no patients had any neovascular glaucoma-predisposing conditions, such as carotid artery disease. Retinal perfusion status was evaluated from postoperative visual acuity, intraocular pressures, ocular examination findings, and fluorescein angiography images. Results The mean age of patients was 57.5 (range: 22-78) years. Complete retinal reattachment was achieved in 3 eyes, while partial or total chronic retinal detachment persisted in 7 eyes. Wide-angle fundus fluorescein angiography revealed peripheral retinal capillary obstruction and severe non-perfusion. Neovascular glaucoma developed 213.4 months (17-634 months) after retinal detachment. Three eyes received Ahmed valve implantation, while 5 eyes received intravitreal bevacizumab injection. Intraocular pressure was controlled in 10 eyes. Two eyes developed phthisis bulbi during follow-up. Conclusions In eyes with a chronic retinal detachment history, iris neovascularization and neovascular glaucoma can develop due to retinal capillary obstruction and chronic retinal ischemia, even after achieving retinal reattachment. We suggest routine follow-up examinations for patients with chronic retinal detachment, particularly for eyes with retinal non-perfusion, as detected on fundus fluorescein angiography.

Carotid Artery Disease in Subjects with Type 2 Diabetes: Risk Factors and Biomarkers

Carotid atherosclerosis (CA) and, especially, carotid artery stenosis (CAS), are associated with a high risk of cardiovascular events in subjects with type 2 diabetes (T2D). In this study, we aimed to identify risk factors and biomarkers of subclinical CA and CAS in T2D individuals. High-resolution ultrasonography of carotid arteries was performed in 389 patients. Ninety-five clinical parameters were evaluated, including diabetic complications and comorbidities; antihyperglycemic, hypolipidemic, and antihypertensive therapy; indices of glycemic control and glucose variability (GV); lipid panels; estimated glomerular filtration rate (eGFR); albuminuria; blood cell count; and coagulation. Additionally, serum levels of calponin-1, relaxin, L-citrulline, and matrix metalloproteinase-2 and -3 (MMP-2, -3) were measured by ELISA. In univariate analysis, older age, male sex, diabetes duration, GV, diabetic retinopathy, chronic kidney disease, coronary artery disease, peripheral artery disease, and MMP-3 were associated with subclinical CA. In addition to these factors, long-term arterial hypertension, high daily insulin doses, eGFR, and L-citrulline were associated with CAS. In multivariate logistic regression, age, male sex, BMI, GV, and eGFR predicted CA independently; male sex, BMI, diabetes duration, eGFR, and L-citrulline were predictors of CAS. These results can be used to develop screening and prevention programs for CA and CAS in T2D subjects.

Effect of haemodynamics on the risk of ischaemic stroke in patients with severe vertebral artery stenosis

ObjectivesEndovascular treatment strategies to optimise individualised care for patients with vertebral artery (VA) stenosis need to be revisited. This study aimed to investigate the relationship between net VA flow volume (NVAFV) and the risk of posterior circulation infarction (PCI) in a high-risk patient population.MethodsWe screened 1239 patients with extracranial VA stenosis, of whom 321 patients with severe VA V1 segment stenosis (≥70%) were enrolled in our study. We restratified the patients based on NVAFV and contralateral VA stenosis grades to analyse the proportion of each PCI mechanism—large artery atherosclerosis and branch artery occlusive disease. Furthermore, we estimated the incidence of recurrent ischaemic stroke between groups with different NVAFV over a follow-up period of 2 years.ResultsNVAFV was lower in the PCI group. Multiple logistic regression analysis showed that NVAFV is an independent risk factor for PCI and that the OR for PCI for the lowest NVAFV (<112.8 mL/min) was 4.19 (1.76 to 9.95, p=0.001). In patients with severe carotid artery disease, the OR for the lowest NVAFV was 14.03 (3.18 to 61.92, p<0.001). The lower NVAFV group had a higher incidence of recurrent ischaemic stroke events than the higher NVAFV group (HR 2.978, 95% CIs 1.414 to 6.272).ConclusionOur study demonstrated that NVAFV, as estimated by colour duplex ultrasonography, was associated with the incidence of PCI and subsequent ischaemic events and that a high-risk population could be identified for further posterior circulation revascularisation.

338 Autonomic function and hyper-adrenergic tone despite beta-blockers in chronic coronary syndrome with preserved ejection fraction: prevalence and related factors

Aims Autonomic dysfunction is a prevalent and independent risk factor for adverse cardiovascular events and mortality in chronic coronary syndrome (CCS). Beta-blockers (BB), directly inhibiting adrenergic receptors, have been associated with a significant reduction in mortality and/or cardiovascular events in patients with recent acute coronary syndrome (ACS) or in those with heart failure (HF) with reduced left ventricular ejection fraction (LV-EF); on the other hand, the protective benefit in CCS patients without prior ACS or HF is less well established and lacks placebo-controlled trials. The aim of the study was to investigate the prevalence of hyper-adrenergic tone in CCS with preserved LV-EF in patients with or without BB as well as to assess related factors of hyper-adrenergic tone despite BB. Methods A total of 165 consecutive CCS patients have been enrolled. Inclusion criteria were documented coronary artery disease and preserved left-ventricular ejection fraction (&gt;50%). Exclusion criteria were: recent ACS (&lt;6 months), HF symptoms (NYHA &gt;1) and atrial fibrillation. According to Heart rate variability (HRV) guidelines, 5 min beat-to-beat analysis was performed in order to assess sympatho-vagal balance (without BB wash-out). Patients were then divided into in two groups: hyper adrenergic tone (LF/HF &gt; 2.01) and normal adrenergic tone (LF/HF &lt; 2.01). Moreover, patients with hyper-adrenergic tone despite BB were classified as ‘BB non-responders’ while patients with normal adrenergic tone as ‘BB responders’. Results Mean age was 64 ± 12 years and male gender was prevalent (75%). Patients treated with BB were 56% and the majority (96%) were treated with high selective. Overall hyper adrenergic tone (isolated or associated with blunted vagal tone) was found in 47% of CCS patients and no difference was found in the percentage of hyper-adrenergic tone between patients with or without beta-blockers (45% vs. 55% P = 0.716). Within the BB groups, 89% had heart rate at target (&lt;70 b.p.m.), while only 11% showed heart rate not at target (&gt;70 b.p.m.). Among the heart rate not at target 80% had hyper-adrenergic tone despite beta-blockers (non-responders); on the other hand, among the heart rate not at target hyper-adrenergic tone despite beta-blockers was found in 43%. No differences in types of BB (metoprolol vs. bisoprolol) between BB responders and non-responders was found (P = 0.714). Higher left atrial volume index (36 ± 8 vs. 42 ± 14; P = 0.029) and E/e’ ratio (an echocardiographic marker of high left ventricular filling pressure) (9.4 ± 2.1 vs. 7.4 ± 2.1; P = 0.038) were found in patients with hyper-adrenergic tone despite beta-blockers (non-responder). Moreover, a trend toward significance of higher Lown’s arrhythmic risk was found in non-responders (19% vs. 8%; P = 0.066) (Figure). Finally, Beta-blockers patients with bradycardia and hyper-adrenergic tone (non-responders) had higher prevalence of carotid artery disease (64% vs. 44%; P = 0.047), where baroreceptors are located. Conclusion The prevalence of hyper-adrenergic tone is high in CCS patients with preserved ejection fraction; about half of patients treated with beta-blockers had residual hyper-adrenergic tone (non-responders). Hyper-adrenergic tone in BB patients is higher in those with 24-h heart rate not at target (&gt;70 b.p.m.), thereby suitable of BB titration, as well as in those with diastolic dysfunction or with carotid artery disease, where baroceptors are located.

Monocyte/Lymphocyte Ratio and MCHC as Predictors of Collateral Carotid Artery Disease—Preliminary Report

Background: Carotid artery disease accounts for 30% of ischemic strokes in the general population. Numerous biomarkers have been investigated for predicting either the progression or the severity of the disease. The aim of this retrospective study was to compare hematologic indices among patients referred for surgical interventions due to severe carotid disease. Methods: In total, 135 patients (87 (64.4%) men and 48 (35.6%) women) with a mean age of 70 ± 8 years who underwent surgical carotid intervention were enrolled into the study. Results: A Mann–Whitney test for independent samples revealed significant differences in monocyte to lymphocyte ratio (MLR) and mean corpuscular hemoglobin concentration (MCHC) between patients with one and two (collateral) carotid diseases. The cut-off value for MLR was 0.3 (AUC = 0.654, p = 0.048, 70.0% sensitivity and 74.6% specificity) and for MHCH was 21.6. (AUC = 0.730, p < 0.001, 70.0% sensitivity and 77.2% specificity). A multivariable model of logistic regression revealed two significant parameters for collateral carotid stenosis disease including MLR > 0.3 (OR 6.19 with 95% CI 2.02–19.01, p = 0.001) and MCHC > 21.6 (OR 7.76, 95% CI 2.54–23.72, p < 0.001). Conclusions: MLR above 0.3 and MCHC above 21.6 have predictive values for colleterial carotid stenosis and may be used as easily accessible indicators for atherosclerosis severity.

ABCA1 and ABCG1 DNA methylation in epicardial adipose tissue of patients with coronary artery disease

Background Recent studies have focused on the potential role of epicardial adipose tissue (EAT) in the development of coronary artery disease (CAD). ABCA1 and ABCG1 transporters regulate cell cholesterol content and reverse cholesterol transport. We aimed to determine whether DNA methylation and mRNA levels of the ABCA1 and ABCG1 genes in EAT and subcutaneous adipose tissue (SAT) were associated with CAD. Methods Paired EAT and SAT samples were collected from 82 patients undergoing elective cardiac surgery either for coronary artery bypass grafting (CAD group, N = 66) or valve surgery (NCAD group, N = 16). ABCA1 and ABCG1 mRNA levels in EAT and SAT samples were analyzed using real time polymerase chain reaction, ABCA1 protein levels in EAT samples were assessed by western blotting. ABCA1 and ABCG1 DNA methylation analysis was performed in 24 samples from the CAD group and 9 samples from the NCAD group via pyrosequencing. Results DNA methylation levels in the ABCA1 promoter and ABCG1 cg27243685 and cg06500161 CpG sites were higher in EAT samples from patients with CAD compared with NCAD (21.92% vs 10.81%, p = 0.003; 71.51% vs 68.42%, p = 0.024; 46.11% vs 37.79%, p = 0.016, respectively). In patients with CAD, ABCA1 and ABCG1 DNA methylation levels were higher in EAT than in SAT samples (p < 0.05). ABCA1 mRNA levels in EAT samples were reduced in the subgroup of patients with CAD and concomitant carotid artery disease or peripheral artery disease compared with the NCAD group (p = 0.024). ABCA1 protein levels in EAT samples tended to be lower in CAD patients than in the NCAD group (p = 0.053). DNA methylation levels at the ABCG1 cg27243685 site positively correlated with plasma triglyceride concentration (r = 0.510, p = 0.008), body mass index (r = 0.556, p = 0.013) and waist-to-hip ratio (r = 0.504, p = 0.012) in SAT samples. Conclusion CAD is associated with ABCA1 and ABCG1 DNA hypermethylation in EAT. CAD with concomitant carotid artery disease or peripheral artery disease is accompanied by decreased ABCA1 gene expression in EAT. DNA methylation levels at the ABCG1 cg27243685 locus in SAT are associated with hypertriglyceridemia and obesity.