Atherosclerotic Peripheral Disease Research Articles

A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients-A Review PART II-Pharmacological Approach for Management of Elderly Patients with Peripheral Atherosclerotic Lesions outside Coronary Territory.

Aging is a key risk factor for atherosclerosis progression that is associated with increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity, quality of life, and it is associated with reduced life expectancy. As most multicenter randomized trials exclude elderly and very elderly patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home, there is insufficient data on the management of older patients presenting with atherosclerotic lesions outside coronary territory. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment. In addition, due to a variety of severe comorbidities in the elderly, the average daily number of pills taken by octogenarians exceeds nine. Polypharmacy frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and non-adherence. Therefore, we have attempted to gather data on the medical treatment in patients with extra-cardiac atherosclerotic lesions indicating where there is some evidence of the management in elderly patients and where there are gaps in evidence-based medicine. Public PubMed databases were searched to review existing evidence on the effectiveness of lipid-lowering, antithrombotic, and new glucose-lowering medications in patients with extra-cardiac atherosclerotic occlusive disease.

Transcatheter Aortic Valve Implantation Access Sites: Same Goals, Distinct Aspects, Various Merits and Demerits.

Transcatheter aortic valve implantation (TAVI) has been established as a safe and efficacious treatment for patients with severe symptomatic aortic stenosis (AS). Despite being initially developed and indicated for high-surgical-risk patients, it is now offered to low-risk populations based on the results of large randomized controlled trials. The most common access sites in the vast majority of patients undergoing TAVI are the common femoral arteries; however, 10-20% of the patients treated with TAVI require an alternative access route, mainly due to peripheral atherosclerotic disease or complex anatomy. Hence, to achieve successful delivery and implantation of the valve, several arterial approaches have been studied, including transcarotid (TCr), axillary/subclavian (A/Sc), transapical (TAp), transaortic (TAo), suprasternal-brachiocephalic (S-B), and transcaval (TCv). This review aims to concisely summarize the most recent literature data and current guidelines as well as evaluate the various access routes for TAVI, focusing on the indications, the various special patient groups, and the advantages and disadvantages of each technique, as well as their adverse events.

Modifiable risk factors and inflammatory burden stratified by the presence and extent of atherosclerotic cardiovascular disease: insights from a population based cohort study

Abstract Background/Introduction Inflammation is recognized as a residual risk factor and mediator in patients with Atherosclerotic Cardiovascular Disease (ASCVD). High-sensitivity C-Reactive Protein (hsCRP), a marker of systemic inflammation, can be affected by modifiable risk factors (modRF). On the other hand, ASCVD and its extent might modify hsCRP levels. Data regarding the relationship between hsCRP, modRF and the extent of ASCVD remain scarce. Purpose We aimed to analyse the inflammatory burden in relation to the number of vascular beds affected by atherosclerosis and modRF in a contemporary large-scale population cohort. Methods After exclusion of individuals with inflammatory disorders, cancer, hsCRP concentrations >10 mg/L, missing hsCRP values and/or missing covariates 3,348 cases were left for analysis. Vascular beds affected were defined as coronary, peripheral and cerebrovascular atherosclerotic disease. ModRF were classified as follows: Lack of physical activity (PA) as <1.5 hours/week of exercise, a BMI ≥25 kg/m2 was considered as overweight, active smoking was defined as either current or quitted smoking within the last 6 months, and lastly poor adherence to a Mediterranean diet as a simple Mediterranean diet score (sMDS) of ≤2 points. Multivariable analyses were computed with hsCRP as dependent variable and modRF as covariates according to the number of vascular beds affected adjusting for age, sex, diabetes and intake of cholesterol-lowering drugs. Results Of the 3,348 participants at baseline 1,622 (48.1%) were female and mean age was 62 (1st, 3rd quartile: 54, 69) years. Concerning modRF 1,199 (39.5%) individuals showed low levels of PA, 1,877 (58.7%) were defined as overweight, poor adherence to MDS was determined in 1,421 (51.9%) participants and 694 (20.8%) were active smokers. Whilst no ASCVD was present in 1,612 (48.1%) participants, 1,134 (33.9%) and 602 (18.0%) individuals displayed atherosclerosis in 1 or ≥2 vascular beds, respectively. We found a stepwise increase of hsCRP levels with each incremental increase of modRF (median hsCRP for 0–4 modRF: 0.7, 0.9, 1.2, 1.5, 2.5 mg/L, respectively; p <0.05) and according to the number of vascular beds (median hsCRP for 0-≥2 vascular beds affected: 1.0, 1.1, 1.3 mg/L, respectively; p <0.05). The highest hsCRP concentration was found in individuals with atherosclerosis ≥2 beds and 4 modRF (Figure 1). In multivariable regression analyses, an independent association for increasing numbers of modRF with hsCRP levels across the extent of ASCVD was demonstrated (Table 1). Conclusion We demonstrate an increasing inflammatory burden according to the number of modRF and also with the presence and extent of ASCVD in a contemporary population-based cohort. These findings emphasize the important role of subclinical inflammation in the pathogenesis of ASCVD, and might be helpful for the definition of target populations for anti-inflammatory compounds across the extent of atherosclerotic disease.Figure 1Table 1

Significance of Circulating Remnant Lipoprotein Cholesterol Levels Measured by Homogeneous Assay in Patients with Type 2 Diabetes

Remnant lipoproteins (RLs), which are typically present at high concentrations in patients with type 2 diabetes mellitus (T2DM), are associated with cardiovascular disease (CVD). Although an RL cholesterol homogeneous assay (RemL-C) is available for the measurement of RL concentrations, there have been no studies of the relationship between RemL-C and clinical parameters in T2DM. Therefore, we evaluated the relationships between RemL-C and CVD-related parameters in patients with T2DM. We performed a cross-sectional study of 169 patients with T2DM who were hospitalized at Kumamoto University Hospital. Compared with those with low RemL-C, those with higher RemL-C had higher fasting plasma glucose, homeostasis model assessment for insulin resistance (HOMA-R), total cholesterol, triglyceride, small dense low-density lipoprotein cholesterol (sdLDL-C), and urinary albumin-creatinine ratio; and lower high-density lipoprotein cholesterol, adiponectin, and ankle brachial pressure index (ABI). Multivariate logistic regression analysis showed that sdLDL-C and ABI were significantly and independently associated with high RemL-C. Although LDL-C was lower in participants with CVD, there was no difference in RemL-C between participants with or without CVD. Thus, RemL-C may represent a useful index of lipid and glucose metabolism, and that may be a marker of peripheral atherosclerotic disease (PAD) in male patients with T2DM.

Abstract 13841: Prevalence and Impact of Recreational Cannabis Use on Acute Ischemic Stroke and Related Mortality in Elderly (≥65 Yrs) Peripheral Vascular Disease Patients: A Population-Based Analysis in the US (2016-2019)

Background: Considering preliminary reports suggesting associations between peripheral atherosclerotic disease (cannabis arteritis) and acute ischemic stroke (AIS) with cannabis use disorder (CUD), we sought to study the burden and impact of CUD on AIS risk and outcomes in the elderly with PVD. Methods: The National Inpatient Sample (2016-2019) was used to identify geriatric PVD admissions with vs. without CUD . We compared the burden and risk of AIS admissions with vs. without CUD and subsequent in-hospital mortality using adjusted multivariable regression analyses. Results: Of 5,115,824 total geriatric admissions with PVD (50.6% males, 77.5% white), 21,405 had CUD. The prevalence of DM was lower in the CUD cohort (19.7% vs 33.7%) with comparable rates of HTN and smoking between groups [Table 1]. Concomitant drug use was higher in CUD vs non-CUD cohort. There was AIS period prevalence of 5.2% in CUD vs 4.0% in non-CUD cohorts (p<0.001). Among geriatric PVD patients, CUD was associated with higher odds of AIS hospitalizations aOR 1.34 (95%CI 1.18-1.52, p<0.001) without a statistically significant difference in subsequent all-cause in-hospital mortality (aOR 0.71, 95%CI 0.36-1.37, p=0.302). Elderly PVD patients with HTN (aOR 1 .73) predicted higher risk of AIS, however, interestingly, concomitant tobacco use disorder revealed a paradox protective effect while assessing the predictors of AIS in elderly PVD patients with CUD (aOR 0.58 95CI 0.42-0.79, p<0.001). Conclusions: There is a 34% risk of AIS in Geriatric PVD patients with CUD even after controlling for CVD risk factors and drug abuse. Future studies are warranted to explore and confirm the observed smoker’s paradox.

EP-474 An audit of cardiovascular risk modification in patients undergoing major limb amputation for the complications of peripheral atherosclerotic arterial disease and diabetes mellitus

Abstract Introduction The 5-year mortality for patients with peripheral atherosclerotic arterial disease is significant. Major adverse cardiovascular events are common – 16% of patients will have an event within 1-year of the diagnosis. Patients who present requiring major limb amputation represent a group where cardiovascular complications are significant – we have audited how risk is modified for this group at the point of discharge from hospital following treatment. Methods This was a retrospective review of patients admitted for major limb amputation. Specific variables of interest were the prescription of an antiplatelet agent (or oral anticoagulant) and a statin at the time of discharge from hospital. This was defined from immediate discharge letters. Results During the period of interest there were 282 major limb amputations performed and 235 patients were discharged from hospital. Most patients had peripheral atherosclerotic arterial disease (68%). A diagnosis of diabetes was mellitus was also common (52%). In this group of patients many had previous major adverse cardiovascular events – myocardial infarct 21%, angina 16% and previous stroke 18%. At the time of discharge on 80% of patients were prescribed an antiplatelet agent (or anticoagulant) and only 82% of patients had been prescribed a statin. Discussion Pharmacological management of cardiovascular risk in this high-risk group should be improved. At the point of admission a comprehensive assessment of cardiovascular risk should be made and modifiable risk factors addressed.

Macrophage Paired Immunoglobulin-Like Receptor B Deficiency Promotes Peripheral Atherosclerosis in Apolipoprotein E–Deficient Mice

Background: Peripheral atherosclerotic disease (PAD) is the narrowing or blockage of arteries that supply blood to the lower limbs. Given its complex nature, bioinformatics can help identify crucial genes involved in the progression of peripheral atherosclerosis. Materials and Methods: Raw human gene expression data for 462 PAD arterial plaque and 23 normal arterial samples were obtained from the GEO database. The data was analyzed using an integrated, multi-layer approach involving differentially-expressed gene analysis, KEGG pathway analysis, GO term enrichment analysis, weighted gene correlation network analysis, and protein-protein interaction analysis. The monocyte/macrophage-expressed leukocyte immunoglobulin-like receptor B2 (LILRB2) was strongly associated with the human PAD phenotype. To explore the role of the murine LILRB2 homologue PirB in vivo, we created a myeloid-specific PirB-knockout Apoe −/− murine model of PAD (PirB MΦKO) to analyze femoral atherosclerotic burden, plaque features of vulnerability, and monocyte recruitment to femoral atherosclerotic lesions. The phenotypes of PirB MΦKO macrophages under various stimuli were also investigated in vitro. Results: PirB MΦKO mice displayed increased femoral atherogenesis, a more vulnerable plaque phenotype, and enhanced monocyte recruitment into lesions. PirB MΦKO macrophages showed enhanced pro-inflammatory responses and a shift toward M1 over M2 polarization under interferon-γ and oxidized LDL exposure. PirB MΦKO macrophages also displayed enhanced efferocytosis and reduced lipid efflux under lipid exposure. Conclusion: Macrophage PirB reduces peripheral atherosclerotic burden, stabilizes peripheral plaque composition, and suppresses macrophage accumulation in peripheral lesions. Macrophage PirB inhibits pro-inflammatory activation, inhibits efferocytosis, and promotes lipid efflux, characteristics critical to suppressing peripheral atherogenesis.

Is the SMART risk prediction model ready for real-world implementation? A validation study in a routine care setting of approximately 380 000 individuals.

Reliably quantifying event rates in secondary prevention could aid clinical decision-making, including quantifying potential risk reductions of novel, and sometimes expensive, add-on therapies. We aimed to assess whether the SMART risk prediction model performs well in a real-world setting. We conducted a historical open cohort study using UK primary care data from the Clinical Practice Research Datalink (2000-2017) diagnosed with coronary, cerebrovascular, peripheral, and/or aortic atherosclerotic cardiovascular disease (ASCVD). Analyses were undertaken separately for cohorts with established (≥6 months) vs. newly diagnosed ASCVD. The outcome was first post-cohort entry occurrence of myocardial infarction, stroke, or cardiovascular death. Among the cohort with established ASCVD [n = 244 578, 62.1% male, median age 67.3 years, interquartile range (IQR) 59.2-74.0], the calibration and discrimination achieved by the SMART model was not dissimilar to performance at internal validation [Harrell's c-statistic = 0.639, 95% confidence interval (CI) 0.636-0.642, compared with 0.675, 0.642-0.708]. Decision curve analysis indicated that the model outperformed treat all and treat none strategies in the clinically relevant 20-60% predicted risk range. Consistent findings were observed in sensitivity analyses, including complete case analysis (n = 182 482; c = 0.624, 95% CI 0.620-0.627). Among the cohort with newly diagnosed ASCVD (n = 136 445; 61.0% male; median age 66.0 years, IQR 57.7-73.2), model performance was weaker with more exaggerated risk under-prediction and a c-statistic of 0.559, 95% CI 0.556-0.562. The performance of the SMART model in this validation cohort demonstrates its potential utility in routine healthcare settings in guiding both population and individual-level decision-making for secondary prevention patients.

Triglyceride-Rich Lipoproteins and Their Remnants as Silent Promoters of Atherosclerotic Cardiovascular Disease and Other Metabolic Disorders: A Review.

While targeting elevated serum levels of low-density lipoprotein cholesterol has been the mainstay of atherosclerosis prevention and treatment for decades, the evidence regarding the atherogenic role of hypertriglyceridemia is still controversial. Various epidemiological population-based studies on statin-treated subjects nominated triglycerides, triglyceride-rich lipoproteins (namely, chylomicrons and very-low-density lipoprotein particles), and their remnants as major determinants of the substantial residual cardiovascular risk. With the triglyceride-glucose index and triglyceride to high-density lipoprotein ratio emerging as surrogate indicators of peripheral artery disease and atherosclerotic cerebrovascular disease, one can conclude that further research addressing the intricate relationship between triglycerides and atherosclerosis is warranted. Therefore, this review aims to provide insight into the current clinical and epidemiological state of knowledge on the relationship between triglycerides and atherosclerotic cardiovascular disease. It also intends to highlight the connection between triglycerides and other metabolic disorders, including diabetes mellitus, and the potential benefits of triglyceride-lowering agents on cardiovascular outcomes and all-cause mortality.

Identification of Predictors of Abnormal Calcium, Magnesium and Phosphorus Blood Levels in the Emergency Department: A Retrospective Cohort Study

PurposeWith rising healthcare costs limiting access to care, the judicious use of diagnostic tests has become a critical issue for many jurisdictions. Calcium, magnesium and phosphorus serum levels are regularly performed tests in the emergency department, but their clinical relevance have come into question. Authors sought to determine risk factors that could predict abnormal calcium, magnesium and phosphorus serum levels, as well as identify patients who may need corrective interventions.MethodsA retrospective cohort study was conducted in two academic hospitals in Québec City. Demographic and clinical characteristics of 1008 patients who had serum calcium and/or magnesium and/or phosphorus levels drawn by an emergency physician were collected. Multivariate logistic regression models were fitted to obtain adjusted odds ratios for each risk factor for abnormal calcium or magnesium or phosphorus blood levels, and for a required intervention.ResultsAmong patients for whom calcium, magnesium and phosphorus were tested in the Emergency Department, the most significant risk factors (OR>2) for electrolytic abnormality were as follows: hypocalcemia – respiratory distress, diuretics (excluding loop and thiazide), anti-neoplastic medication, long QTc, chronic kidney disease (CKD); hypercalcemia – bone pain, vitamin D, hallucinations; hypomagnesemia – diabetes, corticosteroids; hypermagnesemia – poor extremity perfusion, CKD, furosemide; hypophosphatemia – seizure; hyperphosphatemia – phosphate-binders, CKD, peripheral vascular atherosclerotic disease. Of all patients tested, 3.4% received a corrective intervention initiated by the emergency physician. Predictors of intervention on an electrolyte abnormality include poor peripheral perfusion, nausea and chronic obstructive pulmonary disease (COPD).ConclusionEmergency physicians can potentially reduce the unnecessary testing of calcium, magnesium and phosphorus blood levels by targeting patients with high-acuity conditions or chronic comorbidities such as CKD, diabetes and COPD.

Potential of nicergoline in polymorbidity and cognitive impairment (clinical case)

In real clinical practice, the problem of polymorbidity and, in particular, its cardiometabolic phenotype, is now widespread. One of the its variants is a combination of arterial hypertension with diabetes mellitus, overweight, cognitive impairment, and peripheral atherosclerotic arterial disease. The clinical significance of such polymorbidity portrait, on the one hand, lies in its frequent occurrence, and, on the other hand, in the cardiovascular risk amplification in the settings of simultaneous coexistence of diseases initially characterized by an extremely unfavorable prognosis for the patient. The article presents a clinical case of a patient with a such polymorbidity variant and considers the nicergoline potential in the complex correction of mutually associated comorbidities. The nicergoline ability to improve cognitive functioning, to have a beneficial effect on peripheral circulation, which is reflected in an increase in the distance of painless walking, and also to realize some antihypertensive effect has been demonstrated. No less important is the fact that the high therapeutic efficacy of nicergoline was combined with an optimal safety profile, which consists in good tolerability of therapy and the absence of adverse drug reactions.

Atrial fibrillation and ischaemic heart disease: should we use acetylsalicylic acid beside anticoagulants?

Coexistence of atrial fibrillation and ischaemic heart disease is very common and patients affected by these conditions are exposed to both a high ischaemic and haemorrhagic risk. The choice of an appropriate combination of anticoagulant therapy with single or dual antiplatelet treatment is indeed one of the most relevant and contemporary challenges in clinical practice. Several studies and meta-analyses pointed out that 1 year after an acute coronary syndrome or percutaneous revascularization, the use of the sole anticoagulant therapy is not associated with increased risk of major cardiovascular events, whereas there is a substantial reduction of clinical significant bleeding events, as compared to patients treated also with antiplatelet medications. However, there are no clear-cut data regarding the possibility to implement this strategy in each patient, regardless the cardiovascular risk class. Furthermore, for patients requiring a combined anticoagulant and antiplatelet treatment, the available data seem to favour an association of direct anticoagulant and inhibitors of P2Y12, rather than regimens including aspirin. These data are derived mainly from observational studies, with all their limitations. The use of aspirin could be beneficial in patients with significant comorbidities, such as diabetes mellitus, or with severe peripheral atherosclerotic disease, involving the carotids and other large arteries.

CT Angiography in Patients with Peripheral Arterial Disease

Background: Peripheral arterial disease is one of the most important causes of morbidity. Non-invasive characterization of peripheral arterial disease is possible by using CT angiography. The aim of this research is to evaluate CT angiographic findings in patients with peripheral arterial disease, to characterize lesion, risk factors and site of lesion.
 Methods: This hospital based prospective study was conducted in 40 consecutive patients with lower limb peripheral arterial disease who underwent CT angiography in the Department of Radiodiagnosis College of Medical Sciences-Teaching Hospital from January 2018 to Jan 2019.
 Results: Atherosclerotic peripheral disease was most common in elderly male patient with history of smoking, hypertension, diabetes or dyslipidemia and usually presents in the late stages with single or multiple arterial segmental involvement including the abdominal aorta. However, non- atherosclerosis peripheral arterial disease was seen in younger patients and presents with vascular thrombosis.
 Conclusions: CT angiography is a reliable non-invasive imaging modality for evaluating patients with peripheral arterial disease and lesion characterization.
 Keywords: CTA; Peripheral arterial disease.

Methods for Creating Medium and Large Animal Models of Peripheral Atherosclerosis

Atherosclerosis (AS) is the main pathological basis for the occurrence of many vascular diseases and has a strong association with metabolic syndrome. Peripheral arterial diseases caused by AS have high morbidities and mortalities but lack still effective treatment. AS animal models are highly valuable for research on peripheral arteriosclerotic diseases. While small and medium AS animal models based on high-fat feeding and balloon injuries have been successfully established,few literatures have described the creation of large animal models for AS treatment. This article elucidates the current methods for creating medium and large animal models of peripheral atherosclerotic disease,with an attempt to further promote the clinical translation of AS treatment research.

Changes and significance of T helper-9 cells and interleukin-9 in patients with atherosclerotic chronic lower limb ischemia: Effect on IL-17 release.

Atherosclerosis is considered as a chronic inflammatory disorder where the central role of T cells in its pathogenesis is well known. T helper-9 cells have a distinctive effect upon the inflammatory processes. They stimulate macrophages via secretion of their cytokine interleukin-9. Based on its known involvement with other inflammatory disorders, we hypothesized that interleukin-9 might be associated with the inflammatory limb of peripheral atherosclerotic disease. We tested this hypothesis on peripheral blood mononuclear cells (PBMCs) and freshly resected arterial tissues from 84 patients with peripheral arterial occlusive disease (PAOD) and 50 non-atherosclerotic subjects. A number of experimental methods were used including flow cytometry analysis of T helper-9 cells using anti-CD3, anti-CD4, and anti-interleukin-9monoclonal antibodies as well as real-time polymerase chain reaction for the assessment of gene expression of interleukin-9. In addition, circulating serum levels of interleukin-9 were measured using enzyme linked immunosorbent assay. We also evaluated the ability of recombinant interleukin-9 to modulate IL-17 release in cultured isolated CD3+ T cells with relation to atherosclerotic disorder in vitro. Here we report increased percentages of T helper-9 cells and interleukin-9 levels in patients with chronic lower limb atherosclerotic ischemia, compared to healthy controls. Through investigation of different atherosclerotic patient populations with different disease stages, we found elevated interleukin-9 level both systemically and within the lesion and increased expression of cells in severe disease stages. The current study also revealed enhanced expression of mRNA levels of interleukin-9 within the atherosclerotic lesion when compared with non-atherosclerotic vessels. Levels of released IL-17 in CD3+ T cell culture supernatants supplemented with interleukin-9 were significantly positively correlated in the enrolled patients. The results suggest a role for T helper-9 cells and IL-9 in atherosclerotic process, potentially involving IL-17-mediated mechanisms. Indeed, we found that interleukin-9 promoted IL-17 release in PBMCs, with a particularly marked response in severe disease.

Low-density lipoprotein cholesterol goal attainment rates in high-risk patients with cardiovascular diseases and diabetes mellitus in Korea: a retrospective cohort study

BackgroundReal-world evidence of low-density lipoprotein cholesterol (LDL-C) goal attainment rates for Asian patients is deficient. The objective of this study was to assess the status of dyslipidemia management, especially in high-risk patients with cardiovascular disease (CVD) including stroke and acute coronary syndrome (ACS).MethodsThis was a retrospective cohort study of 514,866 subjects from the National Health Insurance Service-National Health Screening Cohort database in Korea. Participants were followed up from 2002 to 2015. Subjects with a high-risk of CVD prior to LDL-C measurement and subjects who were newly-diagnosed for high-risk of CVD following LDL-C measurement were defined as known high-risk patients (n = 224,837) and newly defined high-risk patients (n = 127,559), respectively. Data were analyzed by disease status: stroke, ACS, coronary heart disease (CHD), peripheral artery disease (PAD), diabetes mellitus (DM) and atherosclerotic artery disease (AAD).ResultsOverall, less than 50% of patients in each disease category achieved LDL-C goals (LDL-C < 70 mg/dL in patients with stroke, ACS, CHD and PAD; and LDL-C < 100 mg/dL in patients with DM and AAD). Statin use was observed in relatively low proportions of subjects (21.5% [known high-risk], 34.4% [newly defined high-risk]). LDL-C goal attainment from 2009 to 2015 steadily increased but the goal-achiever proportion of newly defined high-risk patients with ACS remained reasonably constant (38.7% in 2009; 38.1% in 2015).ConclusionsLDL-C goal attainment rates in high-risk patients with CVD and DM in Korea demonstrate unmet medical needs. Proactive management is necessary to bridge the gap between the recommendations of clinical guidelines and actual clinical practice.

A Multinational Real-World Study on the Clinical Characteristics of Patients with Type2 Diabetes Initiating Dapagliflozin in Southern Europe.

IntroductionA real-world study was performed to describe the clinical characteristics of patients who received dapagliflozin to better understand differences when initiating dapagliflozin in various countries and different prescribing settings.MethodsWe assessed pooled data from observational studies carried out in Italy (n = 2484), Spain (n = 564) and Greece (n = 87). The primary objective was to compare the clinical profile of patients initiating dapagliflozin in the three countries. We also evaluated the percentage of patients who received dapagliflozin in clinical practice who satisfied DECLARE-TIMI 58 enrolment criteria.ResultsIn Italy and Spain, around 90% of patients were receiving metformin vs. 66% in Greece (p < 0.0001). Patients in Greece had lower levels of estimated glomerular filtration rate and lower prevalence rates of retinopathy, prior stroke, acute myocardial infarction, peripheral arterial disease and atherosclerotic cardiovascular disease. Grouping the cohorts by prescribing setting (primary vs. specialist care), baseline HbA1c was lower in primary care (8.4 ± 1.7 vs. 8.7 ± 1.5, respectively; p < 0.0001). Significantly more patients were receiving other medications for concomitant conditions in specialist care. A total of 1416 patients (48%) did not meet DECLARE inclusion criteria, while 1561 (52%) patients met the criteria (Greece 41.05%, Italy 53.19%, Spain 51.35%).ConclusionsSignificant differences were seen among patients initiating dapagliflozin in southern Europe. Our results suggest that dapagliflozin was being initiated at different stages of the disease according to the country and prescribing settings. Such geographic heterogeneity may have an impact upon effectiveness of dapagliflozin on glucose lowering, as well as cardiovascular and renal outcomes.Electronic supplementary materialThe online version of this article (10.1007/s13300-019-00744-6) contains supplementary material, which is available to authorized users.

P651Prevalence of hypertriglyceridemia in statin treated high risk patients who might benefit from treatment with icosapent ethyl for secondary prevention in clinical practice - Results of DYSIS

Abstract Background Patients with elevated triglyceride (TG) levels are at increased risk for ischemic events. In the recently published REDUCE-IT-Study among patients with elevated triglyceride levels who were receiving statin therapy, the risk of major ischemic events, including cardiovascular death, was significantly lower with 2 g of icosapent ethyl twice daily than with placebo. Little is known about how many patients in clinical practice might benefit from this additional treatment. Methods The cross sectional, observational Dyslipidemia International Study (DYSIS) examined lipid goal attainment among statin-treated very high cardiovascular risk patients (defined as per 2011 EAS/ESC guidelines, including patients suffering from coronary heart disease, diabetes, chronic kidney disease or peripheral atherosclerotic disease) in Canada, Europe, Middle East countries and China. Data were collected under real life conditions in physicians' offices and hospital outpatient wards between 2008–2012. We examined the prevalence of mixed dyslipidemia with TG &gt;135 mg/dl in high statin treated high risk patients in clinical practice. Results Of a total of 44,593 patients on very high cardiovascular risk, all on chronic statin treatment, 21,312 (47.8%) had mixed dyslipidemia with TG values &gt;135mg/dl. Patients with elevated TG also had higher levels of total and LDL-cholesterol. The overall use of additional fibrates on top of statins was low (4.0%), but more frequent in patients with TG &gt;135 mg/dl. CVD patients with TG&gt;135 mg/dl Pts with TG &gt;135 mg/dl Pts with TG ≤135 mg/dl p-value OR (95% CI) n=21,312 (47.8%) n=23,281 (52.2%) Age (years) 65.4±10.1, 68.1±10.2 &lt;0.0001 Females 42.2% 38.6% &lt;0.0001 1.16 (1.12–1.21) Sedentary lifestyle 43.0% 37.6% &lt;0.0001 1.25 (1.20–1.30) Risk factors/CV-disease Hypertension 79.0% 74.9% &lt;0.0001 1.26 (1.21–1.32) Diabetes mellitus 56.3% 45.3% &lt;0.0001 1.55 (1.50–1.61) Ischemic heart disease 50.6% 54.4% &lt;0.0001 0.86 (0.83–0.89) Cerebrovascular disease 16.1% 17.7% &lt;0.0001 0.90 (0.85–0.94) Peripheral artery disease 8.1% 6.9% &lt;0.0001 1.18 (1.10–1.27) Lipid lowering therapy Rosuvastatin 11.3% 11.8% 0.13 0.95 (0.90–1.01) Atorvastatin 38.2% 40.9% &lt;0.0001 0.89 (0.86–0.93) Simvastatin 41.9% 38.9% &lt;0.0001 1.13 (1.09–1.18) Other statins 8.6% 8.4% 0.12 0.96 (0.88–1.05) Fibrates 5.5% 1.5% &lt;0.0001 3.86 (3.40–4.37) Lipid Profile Total Cholesterol (mg/dl) 185.6 159.0 &lt;0.0001 LDL-Cholesterol (mg/dl) 102.1 88.9 &lt;0.0001 Triglyderides (mg/dl) 189.5 95.7 &lt;0.0001 Conclusion Almost half of consecutive patients with cardiovascular disease treated with statins for secondary prevention in clinical practice suffer from TG levels &gt;135 mg/dl and might benefit from additional treatment with icosapent ethyl with further reduction in subsequent major ischemic events, including cardiovascular death. Acknowledgement/Funding MSD

The reasons of poor lipid target attainment for secondary prevention in real life practice: Results from EPHESUS.

There are lack of studies considering the suboptimal management of dyslipidemia especially in cardiology outpatient clinics. This study was conducted to assess the patient adherence to cholesterol treatment recommendations and attainment of low-density-lipoprotein cholesterol (LDL-C) goals. EPHESUS (NCT02608645) is a national, observational and multicenter registry which has been designed as a cross-sectional study to allow inclusion of all consecutive patients with hypercholesterolemia in cardiology outpatient clinics. The present subgroup analyses of the EPHESUS trial included patients with known peripheral artery disease or atherosclerotic cerebrovascular disease, and coronary heart disease namely secondary prevention. The present analysis of the EPHESUS study included 1482 patients (62.79±10.4years, 38.2% female) with secondary prevention from 40 sites in Turkey. Regarding recommended lipid targets for LDL-C, only 267 patients (18%) were below the target of 70mg/dL. Females were significantly more off-target when compared with male patients (396, 85.5% vs 67, 14.5%; P=0.017). Moreover, the achievement of LDL-C goal was significantly decreased with illiteracy (233, 19.2% vs 35, 13.1%; P=0.02). Patients who think that the cholesterol treatment should be terminated when the cholesterol level of a patient has normalised were higher in the off-target group (34.0% vs 24.7%, P<0.001). Besides, physician perceptions about LDL-C goal for secondary prevention were significantly related with LDL-C target attainment. EPHESUS is an important study with large population in terms of representing real-life practice of the adherence to dyslipidemia guidelines in secondary prevention patients in Turkey. Perceptions, knowledge, and compliance with the guidelines for secondary prevention have increased, but it is far below from the desired levels even in cardiology outpatient clinics. There is a need for patients' and physicians' education regarding the treatment of hyperlipidemia.

Invited commentary

Sharma and colleagues from the Brigham have shown that aortobilateral femoral bypass remains an important reconstruction in select patients with advanced aortoiliofemoral artery disease, despite the preferential use of endovascular therapy in these patients. Several important findings are evident from this analysis, some of which corroborate prior publications on this topic, and others that are new. First, experienced aortic surgeons can perform the operation with low mortality, less than 1% in the historic and contemporary cohorts. The mortality rate in this series is less than one-half that reported in broader practice assessments, such as the National Surgical Quality Improvement Program. Second, patency was lower in the contemporary cohort, driven by more extensive atherosclerotic disease, particularly in young patients; differences in prior aortic surgery; and a greater number of patients having aortobilateral femoral bypass for chronic limb ischemia. There is no doubt that common and deep femoral endarterectomy as an adjunct to aortobilateral femoral bypass is necessary more now than what it was two decades ago. The deep femoral artery remains the most important outflow vessel associated with long-term durability in most series. Although not mentioned by the authors, I wonder if patients whose distal anastomoses were to the superficial femoral artery had lower patency. Third, durability and limb salvage rates with this operation remain excellent. Moreover, the 10-year survival was better in the contemporary cohort, even though peripheral atherosclerotic disease burden was high. This difference likely is due to less coronary artery disease and significantly greater number of patients on statin, beta-blocker, and antiplatelet agents, as the authors note. Clearly, aggressive risk factor modification is beneficial. The study lacks in some detail, such as a comparison with matched patients treated by endovascular techniques, the extent of iliac (most had TransAtlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease class C and D disease) and infrainguinal disease, which impacts patency, surgeon choice for treatment, and specific technical details. Interestingly, more than one-half of the patients in the contemporary group had end-to-side aortic anastomoses for reasons that are unclear. Our preference has been for end-to-end aortic anastomoses except the rare circumstances in which there is a large inferior mesenteric artery, multiple renal arteries, or external iliac artery occlusions in which pelvic blood flow needs to be maintained. Configuration and length of the body of a graft sewn end-to-side is important to avoid buckling and kinking of the graft limbs, which impacts patency. No mention is made about aortoiliac occlusion versus diffuse disease, either of which may affect operative approach and choice of clamp position. Nonetheless, the clinical outcomes in this study are exemplary. The Brigham group rightly raises questions as to whether such results can be broadly applied to practices at large, and if there will be experienced open aortic surgeons to perform such operations in the future. There is no doubt that aortofemoral reconstruction is still necessary. The authors stress the importance of maintaining open aortic surgical skills, a challenge today in many training programs. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Thirty-year trends in aortofemoral bypass for aortoiliac occlusive diseaseJournal of Vascular SurgeryVol. 68Issue 6PreviewEndovascular intervention has supplanted open bypass as the most frequently used approach in patients with aortoiliac segment atherosclerosis. We sought to determine whether this trend together with changing demographic and clinical characteristics of patients undergoing aortobifemoral bypass (ABFB) for aortoiliac occlusive disease (AOD) have an association with postoperative outcomes. Full-Text PDF Open Archive