Concomitant Cardiovascular Risk Factors Research Articles

Epicardial adipose tissue volumes for long-term risk stratification in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement

Abstract Background Accurate risk stratification is important to improve patient selection and outcome of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). As epicardial adipose tissue (EAT) is discussed to be involved in cardiovascular disease, it could be useful as a marker of poor prognosis in patients with severe AS undergoing TAVR. Purpose We hypothesized that EAT impacts long-term outcome of patients with severe AS undergoing TAVR independently from subtype and other risk factors. Methods A total of 416 patients diagnosed with severe AS by transthoracic echocardiography were assigned for TAVR and enrolled for systematic assessment. Patients underwent clinical surveys and 5-year long-term follow-up, with all-cause mortality as the primary endpoint. EAT volume was quantified on pre-TAVR planning CTs. Patients were retrospectively dichotomized at the median of 74cm3 of EAT into groups with low-EAT and high-EAT volumes. Mortality rates were compared using Kaplan-Meyer plots and uni- and multivariable cox regression analyses. Results A total number of 341 of 416 patients (median age 80.9years, 45% female) was included in the final analysis. Patients with high-EAT volumes had similar short-term outcome (p=0.794) but significantly worse long-term prognosis (p=0.023) compared to patients with low-EAT volumes. Increased EAT volumes were associated with worse long-term outcome (HR1.59;p=0.031) independently from concomitant cardiovascular risk factors, general type of AS and functional echocardiography parameters of AS severity (HR1.69;p=0.013). Conclusion Increased EAT volume is an independent predictor of all-cause mortality in patients with severe AS undergoing TAVR. It can be easily obtained from pre-TAVR planning CTs and may thus qualify as a novel marker to improve prognostication and management of patient with severe AS.Graphical Abstract

Epicardial adipose tissue as an independent predictor of long-term outcome in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

Accurate risk stratification is important to improve patient selection and outcome of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). As epicardial adipose tissue (EAT) is discussed to be involved in cardiovascular disease, it could be useful as a marker of poor prognosis in patients with severe AS undergoing TAVR. A total of 416 patients diagnosed with severe AS by transthoracic echocardiography were assigned for TAVR and enrolled for systematic assessment. Patients underwent clinical surveys and 5-year long-term follow-up, with all-cause mortality as the primary endpoint. EAT volume was quantified on pre-TAVR planning CTs. Patients were retrospectively dichotomized at the median of 74 cm3 of EAT into groups with low EAT and high EAT volumes. Mortality rates were compared using Kaplan-Meyer plots and uni- and multivariable cox regression analyses. A total number of 341 of 416 patients (median age 80.9years, 45% female) were included in the final analysis. Patients with high EAT volumes had similar short-term outcome (p = 0.794) but significantly worse long-term prognosis (p = 0.023) compared to patients with low EAT volumes. Increased EAT volumes were associated with worse long-term outcome (HR1.59; p = 0.031) independently from concomitant cardiovascular risk factors, general type of AS, and functional echocardiography parameters of AS severity (HR1.69; p = 0.013). Increased EAT volume is an independent predictor of all-cause mortality in patients with severe AS undergoing TAVR. It can be easily obtained from pre-TAVR planning CTs and may thus qualify as a novel marker to improve prognostication and management of patient with severe AS. DRKS, DRKS00024479.

Coronary Artery Calcification: Current Concepts and Clinical Implications.

Coronary artery calcification (CAC) accompanies the development of advanced atherosclerosis. Its role in atherosclerosis holds great interest because the presence and burden of coronary calcification provide direct evidence of the presence and extent of coronary artery disease; furthermore, CAC predicts future events independently of concomitant conventional cardiovascular risk factors and to a greater extent than any other noninvasive biomarker of this disease. Nevertheless, the relationship between CAC and the susceptibility of a plaque to provoke a thrombotic event remains incompletely understood. This review summarizes the current understanding and literature on CAC. It outlines the pathophysiology of CAC and reviews laboratory, histopathological, and genetic studies, as well as imaging findings, to characterize different types of calcification and to elucidate their implications. Some patterns of calcification such as microcalcification portend increased risk of rupture and cardiovascular events and may improve prognosis assessment noninvasively. However, contemporary computed tomography cannot assess early microcalcification. Limited spatial resolution and blooming artifacts may hinder estimation of degree of coronary artery stenosis. Technical advances such as photon counting detectors and combination with nuclear approaches (eg, NaF imaging) promise to improve the performance of cardiac computed tomography. These innovations may speed achieving the ultimate goal of providing noninvasively specific and clinically actionable information.

Improvement of symptoms and quality of life in patients with coronary vasomotion disorders by endotype-based drug therapy

Abstract Introduction In patients with angina pectoris and/or signs of ischemia but no obstructive coronary artery disease (ANOCA) coronary vasomotion disorders are a frequent cause for their symptoms. However, the heterogeneous clinical presentation resulting from a wide spectrum of subtypes (so-called endotypes) poses a major therapeutic challenge. Many patients suffer from long-term refractory symptoms and severely reduced quality of life. Purpose The purpose of this study was to demonstrate that the quality of life of these patients can be improved by an endotype-based drug therapy. Methods A total of 50 patients (56% women, mean age 63±14 years) with a confirmed diagnosis of coronary vasomotion disorder were enrolled between April 2021 and February 2022. The endotypes were classified according to the diagnostically distinguishable subtypes (coronary spasm: n=30; vasodilatation disorder: n=3; combined vasomotion disorder: n=17). Based on the guideline recommendations of the European Society of Cardiology, an individual endotype-adapted medication was prescribed. The efficacy and tolerability of the medications were monitored over a period of 3 months. In addition, the quality of life was assessed quantitatively (score 0-100) using the Seattle Angina Questionnaire-7 (SAQ-7) at baseline and after 1, 2 and 3 months. The symptoms at home were documented weekly using a patient diary (PROM). Results Within the study population, arterial hypertension (74%) and dyslipidemia (80%) were among the most frequent concomitant cardiovascular risk factors. After 3 months of endotype-based antianginal therapy, a clinically relevant and significant improvement of 15 points on average in the SAQ7-score was achieved in 70% of the patients within the entire cohort (p<0.001), while no change (<5 points) was recorded in 14% of the study participants and 16% experienced an aggravation in the clinically relevant range (≥5 points). Accordingly, the PROM mood score (scale 1-5) also showed a significant improvement of 0.5 points (2.7±0.8 vs. 3.2±0.8; p<0.001) as well as a significant decrease in monthly number of chest pain attacks by 38% (11.7±13.6 vs. 7.3±15.4; p=0.041) and nitroglycerin intake by 67% (2.7±5.9 vs. 0.9±2.6; p=0.004). When comparing the initial and final medication, a significant increase (33%) in the intake of calcium channel antagonists (non-DHP) was recorded in patients with coronary spasm (p=0.004). Within the patient group with combined vasomotion disorders, statins, ezetimibe and ranolazine were taken significantly more often by 35% respectively at the end of the observation period (p=0.031). Conclusion Targeted endotype-based drug therapy can contribute decisively to a clinically relevant improvement of symptoms and quality of life in ANOCA patients.Outcome of the whole patient cohortSAQ improvement during follow-up

Embolic stroke due to atrial myxoma: about a case

Cardiac myxoma is recognized as the most common primary cardiac tumor, typically benign, slow-growing, with a predilection for the left atrium, presenting as a mobile mass attached to the inner surface of the heart by a peduncle. Although its presentation through cerebrovascular events is quite common, it remains an exceedingly rare cause, representing approximately 0.5% of all cerebrovascular events. In this clinical case, we describe a 54-year-old woman with no significant medical history who presented with embolization in both cerebral hemispheres without specific neurological deficits. A left atrial mass was identified on echocardiography. Given the risk of further systemic embolization, the patient underwent surgical excision of the left atrial mass, which histopathology confirmed to be a cardiac myxoma. Due to the high recurrence of systemic embolic events, particularly in the form of cerebral ischemic embolisms, the diagnosis of cardiac myxoma should prompt immediate surgical intervention, as the tumor's friability is more closely related to the embolic risk than its size or the presence of concomitant cardiovascular risk factors. Surgical resection is generally curative and the recurrence of new cerebrovascular events is rare, with an excellent prognosis, although recurrence of tumor is possible in cases of inadequate resection. Treatment with antiplatelet agents or anticoagulants is not an alternative to surgery, as cerebrovascular events can occur even under such treatments.

Prognostic value of humoral markers in patients with anthracycline-related cardiac dysfunction

Aim. To carry out a 12-month study on the prognostic role of humoral markers responsible for the main mechanisms of initiation of cardiotoxic myocardial damage (endothelin-1, soluble Fas-L, N-terminal pro-brain natriuretic peptide (NT-proBNP), tumor necrosis factor-α, interleukin (IL)-1β, matrix metalloproteinase (MMP)-2 and MMP9, soluble form of the ST2 protein (sST2), a tissue inhibitor of metalloproteinase-1, and tetranectin) in assessing the risk of progression of anthracycline-related left ventricular dysfunction.Materials and methods. The study included a total of 114 women aged 48.0 (46.0; 52.0) years without concomitant cardiovascular diseases and risk factors who received chemotherapy with anthracyclines in the past. The levels of serum biomarkers were determined using the enzyme immunoassay. Transthoracic echocardiography was performed at baseline and at 12 months of follow-up.Results. After 12 months of follow-up, all patients were retrospectively divided into 2 groups: group 1 (n = 54) included patients with an unfavorable course of anthracycline-related cardiac dysfunction (ARCD), group 2 (n = 60) encompassed patients with a favorable course of the disease. According to the ROC analysis, MMP-2 ≥ ≥ 338.8 pg / ml (sensitivity 57%, specificity 78%; AUC = 0.629; p = 0.025), MMP-9 ≥ 22.18 pg / ml (sensitivity 89%, specificity 87%; AUC = 0.886; p < 0.001), sST2 ≥ 32.4 ng / ml (sensitivity 64%, specificity 70.5%; AUC = 0.691; p = 0.002), and tetranectin ≤ 15.4 pg / ml (sensitivity 69%, specificity 72%; AUC = 0.764; p < 0.001) were identified as predictors of an adverse course of ARCD. When comparing ROC curves, it was found that the concentration of MMP-9 (p = 0.002) was the most significant predictor of the progression of ARCD.Conclusion. MMP-2 and -9, soluble ST2, and tetranectin can be considered as non-invasive markers for assessing the risk of ARCD progression. At the same time, an increased level of MMP-9 is the most significant predictor of ARCD progression.

Dual Antiplatelet Therapy and Cancer; Balancing between Ischemic and Bleeding Risk: A Narrative Review.

Cardiovascular (CV) events in patients with cancer can be caused by concomitant CV risk factors, cancer itself, and anticancer therapy. Since malignancy can dysregulate the hemostatic system, predisposing cancer patients to both thrombosis and hemorrhage, the administration of dual antiplatelet therapy (DAPT) to patients with cancer who suffer from acute coronary syndrome (ACS) or undergo percutaneous coronary intervention (PCI) is a clinical challenge to cardiologists. Apart from PCI and ACS, other structural interventions, such as TAVR, PFO-ASD closure, and LAA occlusion, and non-cardiac diseases, such as PAD and CVAs, may require DAPT. The aim of the present review is to review the current literature on the optimal antiplatelet therapy and duration of DAPT for oncologic patients, in order to reduce both the ischemic and bleeding risk in this high-risk population.

Review on Toxicity of Antihypertensive Drugs

Adverse drug reactions are common and pose a serious health problem, limiting treatment options, causing compliance issues, and even leading to therapy discontinuation. Hypertension is a chronic disease that is regarded as a major risk factor for cardiovascular disease. To achieve a target blood pressure in an individual patient, a wide range of anti-hypertensive agents are available as single or combination therapy, whereas combination therapy increases the risk of developing Adverse Drug Reaction. Hypertensive patients frequently have coexisting disease conditions such as hyperlipidemia, impaired glucose metabolism, and renal impairment, which increase the risk of Cardio Vascular morbidity and mortality. When treating hypertensive patients, comprehensive management of both hypertension and concomitant Cardio Vascular Disease risk factors is essential. Some of the rare and serious Adverse Drug Reactions that occurred in patients treated with these drugs included beta-blockers causing psoriasis, calcium channel blockers causing gingival hyperplasia, peripheral oedema, Angiotensin Converting Enzyme inhibitors causing ankle oedema, and thiazide diuretics causing hyponatremia and hyperglycemia. Asymptomatic hypertension is more common and necessitates lifelong treatment with antihypertensive agents, predisposing to Adverse Drug Events.In order to improve treatment outcomes and reduce morbidity and mortality associated with adverse drug reactions, healthcare professionals must monitor adverse drug reactions in patients taking antihypertensive drugs. Keywords: Adverse drug reactions, Hypertension, hyperlipidemia, glucose metabolism

Blood-glucose control status in type 2 diabetes patients with high cardiovascular risk

The risk of cardiovascular injury and death in type 2 diabetes patients is 2 to 4 times higher than in the general population. Patients with type 2 diabetes at high cardiovascular risk were defined as having 10 years of diabetes without end-organ damage and/or any additional risk factors such as hypertension, dyslipidemia, smoking, or obesity.
 Aims: To investigate blood-glucose control status and some related factors in patients with type 2 diabetes with high cardiovascular risk.
 Methods: A cross-sectional, prospective study of 85 diabetes patients with high cardiovascular risk who visited the Outpatient Department, Bach Mai Hospital from November 2021 to August 2022.
 Results: The average age is 55.9 years old, with 60.0% of the population being female. When follow-up began, the ratio of HbA1C < 7 was 51.8%; and the mean HbA1c was 7.79 ± 2.1% and the mean fasting plasma glucose was 8.78 ± 3.05 mmol/L. After the follow-up period, HbA1C < 7 was 50.8%, mean HbA1c was 7.21 ± 1.13%, and the rate of noncompliance with treatment was 20%.
 High cardiovascular risk factors in patients with type 2 diabetes include: dyslipidemia (91.8%) and hypertension (44.7%), smoking (16.5%), obesity (24.7%), and family history of early cardiovascular disease (3.5%). 80% of patients had 1-2 concomitant cardiovascular risk factors.
 Conclusion: Blood glucose control is associated to exercise regimen, medication compliance, number of hypoglycemic drug classes, and years of diabetes. The majority of patients with type 2 diabetes who are at high cardiovascular risk do not achieve multi-risk factor control goals, which is mainly correlated to medication compliance.

Therapeutic effects of exercise interventions for patients with chronic kidney disease: an umbrella review of systematic reviews and meta-analyses

ObjectiveTo conduct an overview of meta-analyses evaluating the impact of exercise interventions on improving health outcomes in patients with chronic kidney disease (CKD).DesignAn umbrella review of systematic review and meta-analyses...

Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke.

Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age- and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics.

Treatment of high- and very high-risk patients for the prevention of cardiovascular events in Europe: baseline demographics from the multinational observational SANTORINI study

Abstract Background The ESC/EAS 2019 guidelines recommend ambitious lower goals for low-density lipoprotein cholesterol (LDL-C), especially for patients with high and very high cardiovascular (CV) risk which could necessitate more intensive lipid-lowering therapy (LLT) regimens. Multiple real-world studies in Europe have demonstrated suboptimal achievement of older 2016 LDL-C goals, with combination therapy with ezetimibe or proprotein convertase subtilisin kexin 9 inhibitors (PCSK9i) used in 9% and 1% of patients, respectively. SANTORINI is the first European observational study since the 2019 guidelines to assess whether management of high- and very high-risk patients has improved. Purpose To describe patient characteristics and treatment patterns of LLT in real-world practice for the management of LDL-C levels in high- and very high-risk patients. Methods Baseline data were assessed from SANTORINI, which recruited patients aged ≥18 years with high and very high CV risk requiring LLT. Risk was defined as per a commonly available assessment system, e.g. the Systematic Coronary Risk Estimation (SCORE) system, for which ESC/EAS guidelines classify high-risk and very high-risk as a calculated 10-year risk of fatal CV disease of ≥5–<10% and ≥10%, respectively. Patients were recruited from 14 European countries across primary and secondary care settings, with patient characteristics, medical history, current LLT and other co-medications documented at baseline. Results Of 9606 patients recruited from March 2020 to February 2021 (55.0% from secondary care), cleaned data on 4308 were available through to February 2021. In this interim report, mean (standard deviation [SD]) age was 64.8 (10.8) years and 27.8% were female. Mean (SD) LDL-C was 2.45 (1.21) mmol/L. The majority of patients were classified as very high risk (69.3%), with 30.6% high risk. ESC/EAS guidelines were the most common basis for risk classification (51.3%), then clinical experience (33.5%) and national guidelines (10.4%). Concomitant CV risk factors included being a current or former smoker (16.5% and 41.8%, respectively), hypertension (70.9%), diabetes (35.4%) and familial hypercholesterolemia (10.1%). At baseline, 18.6% of patients were not receiving any LLT. 54.1% of patients were receiving LLT monotherapy, including 51.1% on statins, 1.4% ezetimibe, 1.2% a PCSK9i, and 0.5% other oral LLT. Combination therapy was used in 27.3% of patients, including 17.1% receiving statin plus ezetimibe, 4.1% PCSK9i plus oral LLT, and 6.1% any other oral combination therapy. Conclusions This large study in patients at high and very high CV risk from 14 European countries suggests that, although the ESC/EAS guidelines are the most frequently used basis for risk classification, LDL-C levels remain substantially higher than recommended goals, with combination therapies underutilised. An expanded data cut from SANTORINI will be reported in 2021. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH, Munich, Germany

Secondary Stroke Prevention in Polish Adults: Results from the LIPIDOGRAM2015 Study.

Background: The purpose of the study was to evaluate secondary stroke prevention in Poland and its association with sociodemographic factors, place of residence, and concomitant cardiovascular risk factors. Material and methods: From all patients in LIPIDOGRAM2015 Study (n = 13,724), 268 subjects had a history of ischaemic stroke and were included. Results: 165 subjects (61.6%) used at least one preventive medication. Oral antiplatelet and anticoagulation agents were used by 116 (43.3%) and 70 (26.1%) patients, respectively. Only 157 (58.6%) participants used lipid-lowering drugs, and 205 (76.5%) were treated with antihypertensive drugs. Coronary heart disease (CHD) and dyslipidaemia were associated with antiplatelet treatment (p = 0.047 and p = 0.012, respectively). A history of atrial fibrillation, CHD, and previous myocardial infarction correlated with anticoagulant treatment (p = 0.001, p = 0.011, and p < 0.0001, respectively). Age, gender, time from stroke onset, place of residence, and level of education were not associated with antiplatelet or anticoagulant treatment. Only 31.7% of patients were engaged in regular physical activity, 62% used appropriate diet, and 13.6% were current smokers. Conclusions: In Poland drugs and lifestyle modification for secondary stroke prevention are not commonly adhered to. Educational programmes for physicians and patients should be developed to improve application of effective secondary prevention of stroke.

Агрегационная способность тромбоцитов у пациентов с гипертонической болезнью в сочетании с неалкогольной жировой болезнью печени на фоне ожирения

Актуальность. Активация тромбоцитов и их агрегации являются важнейшими процессами в патофизиологии ишемической болезни сердца. Зависимость смертности от сердечно-сосудистой заболеваемости может усугубляться присутствием других сопутствующих сердечно-сосудистых факторов риска, в том числе гипертонической болезнью (ГБ), ожирением, неалкогольной жировой болезнью печени (НАЖБП). Цель работы: изучить наличие тромбофилических изменений крови у пациентов с гипертонической болезнью и сопутствующим ожирением и неалкогольной жировой болезнью печени путем определения агрегационной способности тромбоцитов. Материалы и методы. Обследован 91 пациент. Средний возраст — (57,9 ± 9,4) года. Выделено три группы пациентов: I — 36 больных ГБ II стадии с сопутствующей НАЖБП, II — 28 пациентов с НАЖБП без ГБ, III группа — 27 пациентов с ГБ II стадии без сопутствующей НАЖБП. Результаты. Выявлено достоверное увеличение степени спонтанной агрегации у пациентов во всех группах по сравнению с группой контроля: у пациентов с ГБ II ст. — в 3 раза (p &lt; 0,05), у пациентов с НАЖБП — в 4,2 раза (p &lt; 0,001), у пациентов с НАЖБП + ГБ II ст. — в 7 раз (p &lt; 0,01). Степень АДФ-индуцированной агрегации тромбоцитов достоверно возрастала во всех группах пациентов: в группе ГБ II ст. увеличивалась на 116 % (p &lt; 0,05), в группе НАЖБП + ГБ II ст. — на 93 % (р &lt; 0,001), при самостоятельной НАЖБП — на 71,7 % (p &lt; 0,05). Степень агрегации, индуцированной арахидоновой кислотой, достоверно снижалась на 8,3 % (p &lt; 0,05) в группе пациентов с НАЖБП + ГБ II ст. Выводы. При гипертонической болезни наблюдалось увеличение функциональной активности тромбоцитов, выраженность которой значительно возрастала при присоединении НАЖБП. У пациентов с изолированной НАЖБП также наблюдалось статистически значимое усиление спонтанной агрегации тромбоцитов, что позволяет рассматривать НАЖБП как один из факторов риска тромбофилических изменений первичного звена гемостаза.

THE STATE OF PLATELET HEMOSTASIS IN PATIENTS WITH HYPERTENSIVE DISEASE COMBINED WITH NON-ALCOHOLIC FAT LIVER DISEASE

Relevance. Platelet activation and platelet aggregation are central processes in the pathophysiology of coronary heart disease and thrombosis. The relationship between cardiovascular morbidity and mortality varies with the presence of other concomitant cardiovascular risk factors.&#x0D; Objective. To determine the state of platelet hemostasis in patients with essential hypertension (HT), with concomitant non-alcoholic fatty liver disease (NAFLD).&#x0D; Materials and methods. 152 patients were examined: 72 men and 80 women. Three groups were identified: I - 46 patients with stage II HT without concomitant NAFLD, II - 54 patients with NAFLD without HT, group III - 52 patients with HT and concomitant NAFLD. A study of total platelet count, mean platelet volume (MPV), platelet distribution width (PDW), platelet count (PCT) and spontaneous platelet aggregation was performed.&#x0D; Results. The level of mean platelet volume (MPV) in both groups of patients with hepatic steatosis exceeded control values equally - by 6%, both in patients with NAFLD (p&lt;0.001) and in NAFLD with concomitant hypertension (p&lt;0.01). In patients of the NAFLD group and hypertension, the relative width of the platelet distribution by volume (PDW) had high values - 2% (p&lt;0.05) higher than in the control cohort, and 2.4% (p&lt;0.05) than in patients with isolated HT. An increase in the degree of spontaneous aggregation in patients of all surveyed groups compared to controls. So in patients with HT II stage. spontaneous aggregation increased 2.2 times (p&lt;0.001), while in both groups of patients with hepatic steatosis, the increase in spontaneous platelet activity was twice as high: in patients with NAFLD - 4.3 times (p&lt;0.001), in patients with HT II stage. and concomitant NAFLD - 4.1 times (p&lt;0.001).&#x0D; Conclusion. NAFLD is accompanied by an increased in MPV, the size of which correlates with their functional activity. In patients with isolated NAFLD, a statistically significant increase in spontaneous platelet aggregation is also observed, which allows considering NAFLD as one of the risk factors for thrombophilic changes in the primary hemostasis.

Atrial Fibrillation (AF) and Ibrutinib, a Monocentric Experience: Should Cardiological Evaluation be a Guide in Clinical Practice?

IntroductionReported prevalence of AF in patients with chronic lymphocytic leukemia (CLL) on ibrutinib is approximately 5-10%. Management of AF in ibrutinib treated patients represents a multidisciplinary and challenging clinical need. Despite therapeutic advances, substantial morbidity and mortality still remain, and preventive or therapeutic strategies need to be implemented. Older age, male gender, arterial hypertension (AH) and valvular heart disease have recently been recognized as strong predictors of AF on ibrutinib. A clear relationship exists between an enlarged left atrium (LA), assessed by transthoracic echocardiography (TTE), and incidence of AF. LA dysfunction at ibrutinib start has been suggested as a predictor of AF: it helps identifying a selected cohort of patients who may benefit from strict follow-up and preventive strategies to reduce incidence of AF and associated complications. To date no prospective clinical trials have been conducted.AimTo analyse cardiovascular predictors and incidence of AF in a monocentric population of CLL patients on ibrutinib and in regular cardio-oncologic follow-up.MethodsFrom June 2014 to June 2017 we prospectively evaluated CLL patients requiring ibrutinib treatment at our Institution. Before starting therapy a full cardiovascular evaluation including accurate history, clinical examination and assessment of concomitant cardiovascular risk factors and cardioactive therapy were performed by an expert cardio-oncologist. All patients underwent non-invasive instrumental investigations performed by the same clinician: baseline electrocardiography (ECG) was used for rhythm documentation and TTE was focused on studying LA size and function. In a selected group of patients a 24 hours ECG monitoring was performed.ResultsFourty-three patients on ibrutinib were evaluated for a median of 12 months (range 1-37). Male/female ratio was 2.07 (M/F 29/14) and median age was 71 years (range 54-86). AF occurred in 7 patients (16.3%) after a median period of 6 months from the beginning of ibrutinib. Before starting therapy 30 patients (69.8%) had at least one cardiovascular risk factor, with 23 (53.5%) suffering from AH and 27 (62.8%) having more than one cardiovascular comorbidity. Twenty-three patients (53.5%) were regularly taking at least one cardioactive drug. We observed male gender and AH (p=0.009) to be significantly related to incidence of AF (p=0.04). One or more pre-existent cardiovascular comorbidity was found to be a strong predictive factor for AF (p=0.03). Concomitant cardioactive therapy and incidence of AF failed to show a significant correlation. Analysing TTE data, a strong predictive value of increased LA linear dimensions (p 0.02) and area (p 0.03) clearly emerged. Sixteen patients (37.2%) were evaluated through prolonged ECG-monitoring. We observed a trend to significance (p=0.07) of a higher maximal heart rate (HR) (109,5±0,7) reached in AF patients compared to those in stable sinus rhythm (73,35±30,6): higher HR, uncovering an increased sympathetic tone, is known to be a risk factor for AF. No significant correlation emerged between occurrence of AF and atrial conduction abnormalities recorded by baseline ECG.ConclusionsDue to the widespread use of ibrutinib in CLL population prompt recognition of AF high risk patients represents an emerging issue.As reported in literature, male sex and AH significantly correlate with AF development. LA enlargement represents a strong predictive factor for AF and TTE can reliably be used as a non-invasive exam to detect early signs of atrial dysfunction. In our cohort AF has occurred in a slightly higher percentage of patients treated with Ibrutinib than in literature. This finding, especially if validated in a larger CLL cohort, can suggest that silent, undetected AF is a common and a often underdiagnosed event in older patients with multiple risk factors. These initial results support a systematic cardiologic monitoring and AF screening program. Proper cardiological evaluation aims to identify patients at higher risk of AF. Educating patients to early recognize adverse events and behave accordingly to clinician's instructions allow to avoid unnecessary drug suspension. Comorbidity control and implementation of cardioactive therapy by an expert cardio-oncologist, preventing LA dilation and dysfunction, could be pursued as a means of reducing AF on ibrutinib. DisclosuresNo relevant conflicts of interest to declare.

Characterization of patients with adrenal insufficiency and frequent adrenal crises.

ObjectiveThis study aimed to characterize the clinical and biochemical features of patients with primary (PAI) and secondary (SAI) adrenal insufficiency who developed adrenal crises (ACs) and estimate the incidence of ACs in these patients.DesignRetrospective case-control analysis of the European Adrenal Insufficiency Registry (EU-AIR; NCT01661387).MethodsTwo thousand six hundred and ninety-four patients with AI (1054 PAI; 1640 SAI) enrolled in EU-AIR. Patients who developed ≥ 1 AC were matchd 1:3 with patients without ACs for age, sex and AI type. Data were collected at baseline and follow-up (mean ± s.d.: PAI 3.2 ± 1.7 years; SAI 2.9 ± 1.7 years).ResultsOne hundred and forty-eight out of 2694 patients (5.5%; n = 84 PAI; n = 64 SAI) had an AC during the study: 6.53 (PAI) and 3.17 (SAI) ACs/100 patient-years. Of patients who experienced an AC, 16% (PAI) and 9.4% (SAI) experienced ≥ 1 AC/year. The incidence of adverse events, infectious intercurrent illnesses and infectious serious adverse events were higher in patients with ACs than without ACs. No differences were observed in BMI, HbA1c, blood pressure and frequencies of diabetes mellitus or hypertension between subgroups (PAI and SAI, with and without ACs). At baseline, PAI patients with AC had higher serum potassium (4.3 ± 0.5 vs 4.2 ± 0.4 mmol/L; P = 0.03) and lower sodium (138.5 ± 3.4 vs 139.7 ± 2.9 mmol/L; P = 0.004) than patients without AC. At last observation, SAI patients with AC had higher hydrocortisone doses than patients without AC (11.9 ± 5.1 vs 10.1 ± 2.9 mg/m2; P < 0.001).ConclusionsThese results demonstrate that concomitant diseases and cardiovascular risk factors do not feature in the risk profile of AC; however, patients with AC had a higher incidence of infectious events.

Emicizumab prophylaxis in haemophilia patients older than 50 years with cardiovascular risk factors: Real-world data.

Emicizumab (Hemlibra™) is approved for prophylaxis of Haemophilia A (HA) patients with and without inhibitors. However, real-world data on emicizumab use in the elderly HA patients with concomitant cardiovascular risk factors are lacking. To evaluate the safety and efficacy of emicizumab in a real-world cohort of elderly HA patients. A prospective longitudinal observational study on HA patients over 50years old treated, followed and monitored during emicizumab prophylaxis was conducted. We documented any bleeding or adverse events and collected plasma samples for emicizumab levels, aPTT and thrombin generation (TG). Seventeen HA patients (2 with inhibitor), whose median age was 62.4years (range: 51.5-77.1) composed the cohort, including 9/17 with multiple cardiovascular risk factors (high risk group). Seven patients had chronic HIV infection. The median follow-up of our cohort was 400days (range 89-805, IQR 211-479days). The median annualized bleeding rate (ABR) significantly decreased for all patients. Among patients who displayed significant bleeding tendencies, emicizumab steady state levels as well as TG were lower as compared with the group. The ABR of four patients concomitantly treated by antiplatelet agents was significantly higher compared with the rest of the cohort. Neither thrombosis nor thrombotic microangiopathy (TMA) was encountered. Emicizumab prophylaxis for HA patients older than 50years including those with cardiovascular risk factors was well tolerated. As lower emicizumab and TG levels were observed among bleeding patients, we suggest that monitoring laboratory assays could be of value within this age group.

Pre-Existing Cardiovascular Conditions as Clinical Predictors of Myocarditis Reporting with Immune Checkpoint Inhibitors: A VigiBase Study.

Simple SummaryUp to 50% of myocarditis events developed in cancer patients upon treatment with immune checkpoint inhibitors (ICIs) are fatal. Therefore, identification of clinical risk factors predicting myocarditis onset during treatment with ICIs is important for the purpose of cardiac surveillance of high-risk patients. The aim of this retrospective matched case-control study was to assess whether pre-existing cardiovascular conditions were associated with the reporting of myocarditis with ICIs in VigiBase, the World Health Organization global database of suspected adverse drug reactions. Taking drugs labelled for the treatment of cardiovascular conditions as a proxy for concomitant cardiovascular risk factors and/or cardiovascular diseases, we found an association of moderate size between pre-existing cardiovascular conditions and the reporting of myocarditis with ICIs. Future prospective pharmacoepidemiological studies should assess the causal relationship between pre-existing cardiovascular conditions and myocarditis onset in a cohort of cancer patients followed during treatment with ICIs.Although rare, immune checkpoint inhibitor (ICI)-related myocarditis can be life-threatening, even fatal. In view of increased ICI prescription, identification of clinical risk factors for ICI-related myocarditis is of primary importance. This study aimed to assess whether pre-existing cardiovascular (CV) patient conditions are associated with the reporting of ICI-related myocarditis in VigiBase, the WHO global database of suspected adverse drug reactions (ADRs). In a (retrospective) matched case-control study, 108 cases of ICI-related myocarditis and 108 controls of ICI-related ADRs other than myocarditis were selected from VigiBase. Drugs labeled as treatment for CV conditions (used as a proxy for concomitant CV risk factors and/or CV diseases) were found to be associated more strongly with the reporting of ICI-related myocarditis than with other ICI-related ADRs (McNemar’s chi-square test of marginal homogeneity: p = 0.026, Cramer’s coefficient of effect size: Φ = 0.214). No significant association was found between pre-existing diabetes and ICI-related myocarditis reporting (McNemar’s test of marginal homogeneity: p = 0.752). These findings offer an invitation for future prospective pharmacoepidemiological studies to assess the causal relationship between pre-existing CV conditions and myocarditis onset in a cohort of cancer patients followed during ICI treatment.

Do European patients with peripeheral arterial disease receive optimal lipid lowering therapy and achieve LDL-C goals? Results from the DA VINCI study

Abstract Background 2016 and 2019 EAS/ESC dyslipidemia guidelines recommend lipid lowering therapy (LLT) to reduce LDL-C in patients with peripheral arterial disease (PAD) with or without established cardiovascular (CV) disease, and recommend target LDL-C goals based on individual CV risk. Data regarding the implementation of these guidelines in clinical practice across Europe is currently lacking. Purpose Describe LLT and achievement of the target LDL-C goals recommended in EAS/ESC dyslipidemia guidelines in patients with PAD. Methods The cross-sectional Da Vinci study enrolled consenting adults who had received LLT in the 12 months prior to the study visit and had at least one LDL-C measurement in the 14 months prior to the study visit, seen in a primary or secondary care setting across 18 European countries. Patients with coronary, peripheral and cerebral disease were enrolled at a ratio of 1:2:2. FH patients with prior CV events were excluded. Data were collected from medical records at a single visit between Jun '17–Nov '18, including LLT and most recent LDL-C. Primary outcome was LDL-C goal attainment ≥28 days after starting most recent LLT (treatment-stabilised LLT). Results Of 5888 patients enrolled, 2794 met our definition of atherosclerotic cardiovascular disease (ASCVD). Of these ASCVD patients, 1036 (37%) had PAD. 31% (323/1036) of PAD patients were female and mean (SD) age was 69 (9.4) years. Concomitant CV risk factors included diabetes mellitus (473/1036 patients [46%]), hypertension (809/1036 [78%]) and smoking (794/1036 [77%]). 26% (271/1036) of patients with PAD also had coronary vascular disease and 12% (122/1036) also had cerebrovascular disease. At the visit date, approximately half (497/1036 [48%]) of all PAD patients were receiving moderate intensity statins and 41% (421/1036) were receiving high intensity statins. 818 (73%) of the PAD patients had a treatment-stabilised LDL-C measurement (median, 2.20 mmol/L), of whom 40% (326/818) achieved the 2016 EAS/ESC LDL-C goal of 1.8 mmol/L and only 19% (159/818) achieved the 2019 goal of 1.4mmol/L. Conclusions European patients with PAD are not treated as per EAS/ESC recommendations, with a large proportion receiving suboptimal LLT and fewer than half achieving target LDL-C levels. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen