Severe Cardiovascular Disease Research Articles

Prevalence of primary aldosteronism and association with cardiovascular complications in patients with resistant and refractory hypertension.

To assess the prevalence of primary aldosteronism and its association with cardiometabolic complications in patients with resistant and refractory hypertension. One hundred and ten consecutive patients with true resistant hypertension [insufficient blood pressure control despite appropriate lifestyle measures and treatment with at least three classes of antihypertensive medication, including a diuretic] and without previous cardiovascular events were screened for secondary hypertension. Refractory hypertension was diagnosed in case of uncontrolled blood pressure despite the use of at least five antihypertensive drugs. Primary aldosteronism was diagnosed in 32 cases (29.1%). The multivariate analysis showed that primary aldosteronism is a strong factor positively associated with left ventricular hypertrophy [odds ratio (OR) = 12.98, 95% confidence interval (CI) 3.82-60.88; P < 0.001], microalbuminuria (OR = 3.67, 95% CI 1.44-9.78; P = 0.007), carotid intima-media thickness at least 0.9 mm (OR = 2.69, 95% CI 1.02-7.82; P = 0.037), aortic ectasia (OR = 4.08, 95% CI 1,18-15.04; P = 0.027) and atrial fibrillation (OR 8.80, 95% CI 1.53-73.98; P = 0.022). Moreover, primary aldosteronism was independently associated with the presence of at least one (OR = 8.60, 95% CI 1.73-69.88; P = 0.018) and at least two types of organ damage (OR = 3.08, 95% CI 1.19-8.24; P = 0.022). Thirteen patients (11.8%) were affected by refractory hypertension. This group was characterized by significantly higher values of carotid intima-media thickness, higher rate of aldosterone-producing adenoma and atrial fibrillation, compared with the other individuals with resistant hypertension. The current study indicates that primary aldosteronism is a frequent cause of secondary hypertension and cardiovascular complications among patients with resistant and refractory hypertension, suggesting a crucial role of aldosterone in the pathogenesis of severe hypertensive phenotypes and cardiovascular disease.

SUN-618 Decision Analysis for Glucagon-Like Peptide Receptor Agonists vs. Sodium-Glucose cotransporter2 Inhibitors in Type 2 Diabetes Mellitus

Background: Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD), and renal outcomes (RO). Objective. Evaluation of data to assist in the prescribing decision with regard to severity of illness and risk for adverse events. Study Design: Systemic review of the major CVOT and previous meta-analyses. Main Outcome Measures: Analysis of six trials on GLP-1 RA and 4 trials on SGLT2i, showed both drug classes reduced MACE and CVD compared to controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: (relative rate, rr MACE= 1.09, 95%CI;0.98,1.22, p= 0.129; rr, CVD =1.04, CI;0.87,1.24, p=0.657). Hospitalization for heart failure (HHF) improved with SGLT2i (rr=0.68, CI; 0.61,0.76, p<0.001) but not with GLP-1 RA, (rr = 0.94, CI; 0.86,1.03, p=0.17). Both GLP-1 RA and SGLT2i showed significant reduction in RO (GLP-1RA, rr=0.83, CI; 0.75,0.912, p=<0.001, SGLT2i, rr=0.0.67, CI; 0.57,0.79, p=0.001) without a preferential difference between the classes (GLP-1 RA vs SGLT2i, relative difference (rd) =0.005, CI;-0.011,0.021, p=0.532, number needed to treat (NNT)=200). Serious adverse events (SAE) for SGLT2i were predominantly mycotic genital infections in women (number needed to harm (NNH) =13 and diabetic ketoacidosis NNH=595. Gastrointestinal intolerance was the major SAE in the GLP1-RA class (NNH=35). Conclusion: Both GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and RO. SGLT2i have advantages over GLP-1 RA in reduction in HHF especially in those with more severe cardiovascular disease risk.

Long Noncoding RNA SOX2-OT Exacerbates Hypoxia-Induced Cardiomyocytes Injury by Regulating miR-27a-3p/TGFβR1 Axis.

Background Myocardial infarction (MI) was a severe cardiovascular disease resulted from acute, persistent hypoxia, or ischemia condition. Additionally, MI generally led to heart failure, even sudden death. A multitude of research studies proposed that long noncoding RNAs (lncRNAs) frequently participated in the regulation of heart diseases. The specific function and molecular mechanism of SOX2-OT in MI remained unclear. Aim of the Study. The current research was aimed to explore the role of SOX2-OT in MI. Methods Bioinformatics analysis (DIANA tools and Targetscan) and a wide range of experiments (CCK-8, flow cytometry, RT-qPCR, luciferase reporter, RIP, caspase-3 activity, trans-well, and western blot assays) were adopted to investigate the function and mechanism of SOX2-OT. Results We discovered that hypoxia treatment decreased cell viability but increased cell apoptosis. Besides, lncRNA SOX2-OT expression was upregulated in hypoxic HCMs. Hereafter, we confirmed that SOX2-OT could negatively regulate miR-27a-3p levels by directly binding with miR-27a-3p, and miR-27a-3p also could negatively regulate SOX2-OT levels. Furthermore, knockdown of SOX2-OT promoted cell proliferation, migration, and invasion, but limited cell apoptosis. However, these effects were reversed by anti-miR-27a-5p. Besides, we verified that miR-27a-3p binding with the 3′UTR of TGFBR1 and SOX2-OT regulated TGFβR1 level by collaborating with miR-27a-3p in HCMs. Eventually, rescue assays validated that the influence of SOX2-OT silence or miR-27a-3p overexpression on cellular processes in cardiomyocytes injury was counteracted by TGFBR1 overexpression. Conclusions Long noncoding RNA SOX2-OT exacerbated hypoxia-induced cardiomyocytes injury by regulating miR-27a-3p/TGFβR1 axis, which may provide a novel insight for heart failure treatment.

Homozygous familial hypercholesterolemia with severe involvement of the aortic valve-A sibling-controlled case study on the efficacy of lipoprotein apheresis.

Homozygous familial hypercholesterolemia (hoFH) can cause severe atherosclerotic cardiovascular disease (ASCVD) in early infancy. Diagnosis and initiation of effective lipid-lowering therapy (LLT) are recommended as early as possible to prevent ASCVD-related morbidity and mortality. The clinical courses of a pair of siblings with an identical hoFH genotype, who exhibited major similarities of their clinical phenotype were analyzed in a case-control fashion including the family. The older sibling was diagnosed with hoFH at the age of 4. Untreated LDL-cholesterol (LDL-C) was 17 mmol/L (660 mg/dL). LLT including lipoprotein apheresis (LA) was initiated and has been successful for 8 years now. A reduction of estimated cholesterol burden by 74% was achieved by LA and combined drug therapy including statins and ezetimibe. The efficacy of escalation of drug therapy was limited because the underlying LDL receptor (LDLR) mutation in the family resulted in substantially reduced receptor function. Treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9)-antibodies failed. His younger brother died at the age of 2 years shortly after the hoFH diagnosis of the elder sibling. Postmortem examination revealed advanced aortic root atheroma and aortic valve stenosis. In the older sibling, aortic valve stenosis and insufficiency were treated at the age of 9 years with mechanical aortic valve replacement. LLT including LA should be initiated as early as possible following the diagnosis of hoFH with very high LDL-C levels. With the same genotype, the phenotype of hoFH can exhibit similar patterns but outcome is substantially related to treatment.

Diabetes and atherothrombosis: The circadian rhythm and role of melatonin in vascular protection.

Obesity-related euglycaemic insulin resistance clusters with cardiometabolic risk factors, contributing to the development of both type 2 diabetes and cardiovascular disease. An increased thrombotic tendency in diabetes stems from platelet hyperactivity, enhanced activity of prothrombotic coagulation factors and impaired fibrinolysis. Furthermore, a low-grade inflammatory response and increased oxidative stress accelerate the atherosclerotic process and, together with an enhanced thrombotic environment, result in premature and more severe cardiovascular disease. The disruption of circadian cycles in man secondary to chronic obesity and loss of circadian cues is implicated in the increased risk of developing diabetes and cardiovascular disease. Levels of melatonin, the endogenous synchronizer of circadian rhythm, are reduced in individuals with vascular disease and those with deranged glucose metabolism. The anti-inflammatory, antihypertensive, antioxidative and antithrombotic activities of melatonin make it a potential therapeutic agent to reduce the risk of vascular occlusive disease in diabetes. The mechanisms behind melatonin-associated reduction in procoagulant response are not fully known. Current evidence suggests that melatonin inhibits platelet aggregation and might affect the coagulation cascade, altering fibrin clot structure and/or resistance to fibrinolysis. Large-scale clinical trials are warranted to investigate the effects of modulating the circadian clock on insulin resistance, glycaemia and cardiovascular outcome.

Increasing Individual Target Glucose Levels to Prevent Hypoglycemia in Patients with Diabetes.

Hypoglycemia is one of the severe complications of diabetes. To prevent hypoglycemia, an emphasis is placed on maintaining an appropriate balance between nutrition, activity, and treatment, which can be achieved by the repetition of self-trials based on self-monitoring. Clinicians routinely focus on patients’ contribution, including timely intake of an adequate amount of carbohydrates, physical activity, antidiabetic medication, and abstinence from alcohol. Recently, many guidelines have highlighted the importance of clinicians’ factors and recommend individualized treatments according to lifestyle patterns and specific needs following the de-intensification of treatment. The optimal value of hemoglobin A1c (HbA1c) levels for blood glucose level regulation remains controversial among countries, but it generally does not exceed 8.0%. In populations that are at a risk of hypoglycemia, such as the older adults, it is advisable to adjust the target blood glucose level to less than 8.0%. Meanwhile, a blood glucose level of 7.0%–7.5% is generally recommended for healthy older adults. If the expected lifetime is shorter than 10 years or in patients with chronic kidney disease and severe cardiovascular disease, the HbA1c level target can be increased to 7.5%–8.0%. For even shorter lifetime expectancy, the target can be adjusted up to 8.0%–9.0%. To prevent hypoglycemia, the target blood glucose level needs to be adjusted, particularly in older adult patients. Ultimately, it is important to identify the maximum blood glucose levels that do not cause hypoglycemia and the minimum blood glucose levels that do not cause hyperglycemia-associated complications.

Hypothyroidism in a physician’s practice: difficulties of diagnostics and treatment

Hypothyroidism is the most common endocrine disease after diabetes mellitus. Its frequency depends on age, sex and iodine intake. The highest prevalence of hypothyroidism is observed in older women. Chronic autoimmune thyroiditis is the most common cause of this condition. The peculiarity of hypothyroidism is an erased clinical picture, diversity and nonspecific symptoms. This makes it difficult to diagnose the disease, leads to an erroneous diagnosis and later detection of thyroid insufficiency. This article discusses the various «masks» of hypothyroidism and peculiarities of clinical manifestations. The main «masks» are: cardiological, dermatological, urological, gastroenterological, endocrine and reproductive system disorders, neurological, psychiatric, hematological, rheumatological. Free thyroxine and thyroid-stimulating hormone are used to diagnose hypothyroidism, as well as antibody titer to thyroid peroxidase and thyroglobulin to detect chronic autoimmune thyroiditis. Levothyroxine preparations are used as a substitution therapy. The dose of the drug depends on the age of the patient and the presence of cardiovascular disease. Patients under 50 years of age without a severe concomitant cardiovascular disease are given 1.6 µg of levothyroxine per kg of body weight. In persons over 50 years of age with cardiovascular diseases, the drug dose is prescribed at the rate of 0.9 µg per kg of body weight. The therapy starts with small doses, slowly increasing it under the control of electrocardiography. At occurrence or strengthening of symptoms of angina a dose of levothyroxine is reduced to the previous one and the cardiovascular therapy is corrected. Evaluation of the effectiveness of the treatment is carried out on the level of thyroid hormone.

Фактори смертності хворих на серцево-судинну патологiю з коронавірусною інфекцією

Due to the COVID-19 outbreak, management of patients with severe cardiovascular disease has become much more complicated. The paper describes first-hand experience of managing a COVID-19 patient with chronic heart failure secondary to myocardial infarction who died from sudden cardiac death. Mortality risk factors in COVID-19-associated cardiac patients are discussed. The authors describe a case of a female patient B., 67 years old, who was taken to the hospital by ambulance with a preliminary diagnosis of community-acquired right lower lobe pneumonia, respiratory failure (RF) II (SpO294%). Coronary heart disease (CHD). Athero-sclerotic and postinfarction (2019) cardiosclerosis. Permanent atrial fibrillation. Hypertension, stage III, grade 3, risk 4 (stroke, 2019). Heart failure (HF) II-A (NYHA class II). Rapid tests for the diagnosis of influenza A and B and detection of COVID-19 antibodies IgG and IgM were negative. From the patient’s history it was found out that over the last 2 months she was in a private medical rehabilitation center. Nine days before her hospitalization, her relatives took her home. According to them, the patient developed fever (37.5–38.4 °C) 4 days before hospitalization, she took paracetamol in her discretion. On admission, her body temperature was 37.5 °C. The patient was hospitalized to the triage department; on the day of hospitalization, her nasopharyngeal lavage was taken for real-time PCR (polymerase chain reaction) for COVID-19. During the hospital stay the patient’s condition stabilized. The next day after hospitalization, the maximum body temperature was within 37.0 °C, shortness of breath decreased, heart rate slowed, RF disappeared, room-air SpO2increased up to 96%. According to the results of echocardiography, the left ventricle (LV) pump function remained preserved (LV ejection fraction was 50%), LV cavities were slightly enlarged, and valvular pathology was characterized by moderate mitral and tricuspid insufficiency. The area of hypokinesia due to myocardial infarction was determined only in the apical segment of the lateral wall and was compensated due to moderate left ventricular hypertensive hypertrophy (left ventricular mass index 129 g/L2). R wave amplitude on the electrocardiography was preserved, which indicated relative compensation of the central hemodynamics of the patient B. On day 2 of hospitalization, the patient’s condition remained stable. The body temperature normalized, leg swelling disappeared, cough and shortness of breath decreased, physical activity significantly improved. The patient was examined by an infectious disease specialist. After receiving the COVID-19 test result (positive PCR test), it was agreed to transfer the patient to a coronavirus hospital for further treatment in the infectious department. However, the patient died suddenly. Final diagnosis: coronavirus disease. COVID-19. Community-acquired bilateral lower lobe pneumonia (viral). Respiratory failure (RF) – 0. CHD. Atherosclerotic and postinfarction (2019) cardiosclerosis. Permanent atrial fibrillation. Hypertension, stage III, grade 3, risk 4 (stroke, 2019). HF II-B. Since dissection was not performed, the exact cause of death is unknown. The article describes important aspects of diagnosis and treatment that can prevent mortality. The authors emphasize that prevention and control of infectious diseases should be prioritized at any time. Individual measures of diagnosis and treatment should be taken considering specific local epidemic situations.

Subjective Quality of Life, Religiousness, and Spiritual Experience in Greek Orthodox Christians: Data from Healthy Aging and Patients with Cardiovascular Disease.

The goal of this study is to examine subjective quality of life-life satisfaction, religiousness, and spiritual experience in healthy younger and older adults, as well as in older patients suffering from severe cardiovascular disease, while examining the role of marital status, employment and socioeconomic status, existence of social network, urbanicity, education, depression, and personal opinion about the country's current socioeconomic situation. Results revealed that there are no age differences and that the role of demographic variables as predictors of religiousness, spiritual experience, and quality of life-life satisfaction don't seem to be very strong. Marital status, employment, and religiousness moderately predict quality of life-life satisfaction. Quality of life-life satisfaction, religiousness, and spirituality are not strongly interconnected in this Greek Orthodox Christian sample. Future cross-cultural research should further investigate the role of other psychological and social parameters that may have a stronger predictive role in quality of life of older adults.

P204 Automated detection of atrial fibrillation based on stationary wavelet transform and artificial neural network targeted for embedded system-on-chip technology

Abstract Stroke is one of the most severe cardiovascular disease which can potentially cause permanent disability. Atrial Fibrillation (AF) is one of the major risk factors of stroke that can be detected from electrocardiogram (ECG) monitoring. Objective This study proposed an AF detection algorithm based on stationary wavelet transform (SWT) and artificial neural network (ANN) for screening purpose. The algorithm is aimed for embedded System-on-Chip (SoC) technology deployment as a standalone AF classifier for community in rural area where the internet infrastructure may not well established. Methods After standard ECG signal pre-processing, SWT is applied to filtered ECG and produces 12 sets of primary features in time-frequency domain. The power spectral density (PSD) and log energy entropy (LogEn) were calculated from these 12 sets of primary features, to measure atrial activity fall in frequency range of 4 to 9 Hz, and the randomness of an ECG signal caused by AF, respectively. Finally, the ANN classifier recognizes the pattern of AF based on high atrial activity and randomness of ECG signal. Algorithm exploration is carried out to determine the optimum parameter value which can yield the best classification and suitable to be implemented in embedded SoC technology for real-time computation performance. ECG training and testing datasets of the proposed AF detection algorithm were extracted from MIT-BIH Atrial Fibrillation Database which consists of 23 ECG record with each record contains a 10 hours ECG data. Results AF detection accuracy is 95.3% which was able to classify an ECG signal into categories of AF, sinus rhythm, and other arrhythmia. Conclusion The proposed AF detection algorithm based on combination of SWT and ANN can achieve high accuracy and is suitable to be implemented as a standalone AF classifier based on embedded SoC technology targeted for early detection of AF in the community.

Poor Renal and Cardiovascular Outcomes in Patients with Biopsy-Proven Diabetic Nephropathy

Background: Despite the high mortality of cardiovascular disease (CVD) in diabetic patients with renal injury, few studies have compared cardiovascular characteristics and outcomes between patients with diabetic nephropathy (DN) and non-diabetic renal disease (NDRD). Methods: A total of 326 type 2 diabetes mellitus patients with renal biopsy were assigned to DN and NDRD groups. Echocardiography and Doppler ultrasound were performed to evaluate left ventricular hypertrophy (LVH) and peripheral atherosclerosis disease (PAD). Renal and cardiovascular survival rates were compared between the DN and NDRD groups by Kaplan-Meier analysis. Risk factors for renal and cardiovascular events in DN patients were identified by a Cox proportional hazards model. Results: In total, 179 patients entered the DN group (54.9%) and 147 made up the NDRD group (45.1%). The presence of diabetic retinopathy, family history of diabetes, and dependence on insulin therapy were associated with the presence of DN. DN patients had more CVD with more severe LVH and PAD. Poorer renal (log-rank χ² = 26.534, p < 0.001) and cardiovascular (log-rank χ² = 16.257, p < 0.001) prognoses were seen in the DN group. DR (HR 1.539, 95% CI 1.332–1.842), eGFR (HR 0.943, 95% CI 0.919–0.961), and 24-h proteinuria (HR 1.211, 95% CI 1.132–1.387) were identified as risk factors for renal endpoints. Age (HR 1.672, 95% CI 1.487–1.821), HbA1C (HR 1.398, 95% CI 1.197–1.876), and 24-h proteinuria (HR 1.453, 95% CI 1.289–1.672) were associated with cardiovascular endpoints. Conclusion: Patients with DN had more severe CVD along with poorer renal and cardiovascular prognoses than those with NDRD.

Independent Impact of Gynoid Fat Distribution and Free Testosterone on Circulating Levels of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) in Humans.

Background: Natriuretic peptides (NPs), including brain natriuretic peptide (BNP), are neurohormones involved in the regulation of water-sodium balance and the maintenance of cardiovascular homeostasis. A higher concentration of NPs is observed in females, but the mechanism behind this difference has not been fully elucidated. Methods: Randomly chosen 255 volunteers from the general population were examined. Overall, 196 people without severe cardiovascular disease were included (mean age 48 years, 35.7% male). A comprehensive assessment was performed, including anthropometric measurements, N-terminal pro-brain natriuretic peptide (NT-proBNP), total testosterone (TT) and sex hormone-binding globulin (SHBG) concentration, transthoracic echocardiography (ECHO), and body composition analysis by direct dual-energy X-ray absorptiometry (DEXA). The univariate analysis adjusted by the known affecting factors determined which measurements were independently associated with NT-proBNP concentration. Results: NT-proBNP concentration was positively associated with gynoid fat mass, gynoid/total fat (G/TF) mass index, SHBG and negatively with android/gynoid (A/G) fat mass index, TT and calculated free testosterone (CFT) concentrations. Furthermore, body composition parameters remained independently associated with NT-proBNP levels even after adjusting for CFT and SHBG. Conclusion: In the population without severe cardiovascular disease, the NT-proBNP concentration is independently associated with lower availability of testosterone and higher gynoid fat distribution, which may explain higher NPs levels in females.

Intensification with dipeptidyl peptidase-4 inhibitor, insulin, or thiazolidinediones and risks of all-cause mortality, cardiovascular diseases, and severe hypoglycemia in patients on metformin-sulfonylurea dual therapy: A retrospective cohort study.

BackgroundAlthough patients with type 2 diabetes mellitus (T2DM) may fail to achieve adequate hemoglobin A1c (HbA1c) control despite metformin-sulfonylurea (Met-SU) dual therapy, a third-line glucose-lowering medication—including dipeptidyl peptidase-4 inhibitor (DPP4i), insulin, or thiazolidinedione (TZD)—can be added to achieve this. However, treatment effects of intensification with the medications on the risk of severe hypoglycemia (SH), cardiovascular disease (CVD), and all-cause mortality are uncertain. Study aim was to compare the risks of all-cause mortality, CVD, and SH among patients with T2DM on Met-SU dual therapy intensified with DPP4i, insulin, or TZD.Methods and findingsWe analyzed a retrospective cohort data of 17,293 patients with T2DM who were free from CVD and on Met-SU dual therapy and who were intensified with DPP4i (n = 8,248), insulin (n = 6,395), or TZD (n = 2,650) from 2006 to 2017. Propensity-score weighting was used to balance out baseline covariates across groups. Hazard ratios (HRs) for all-cause mortality, CVD, and SH were assessed using Cox proportional hazard models. Mean age of all patients was 58.56 ± 11.41 years. All baseline covariates achieved a balance across the 3 groups. Over a mean follow-up period of 34 months with 49,299 person-years, cumulative incidences of all-cause mortality, SH, and CVD were 0.061, 0.119, and 0.074, respectively. Patients intensified with insulin had higher risk of all-cause mortality (HR = 2.648, 95% confidence interval [CI] 2.367–2.963, p < 0.001; 2.352, 95% CI 2.123–2.605, p < 0.001) than those intensified with TZD and DPP4i, respectively. Insulin users had the greatest risk of SH (HR = 1.198, 95% CI 1.071–1.340, p = 0.002; 1.496, 95% CI 1.342–1.668, p < 0.001) compared with TZD and DPP4i users, respectively. Comparing between TZDs and DPP4i, TZDs were associated with a higher risk of SH (HR = 1.249, 95% CI 1.099–1.419, p < 0.001) but not all-cause mortality (HR = 0.888, 95% CI 0.776–1.016, p = 0.084) or CVD (HR = 1.005, 95% CI 0.915–1.104, p = 0.925). Limitations of this study included the lack of data regarding lifestyle, drug adherence, time-varying factors, patients’ motivation, and cost considerations. A limited duration of patients intensifying with TZD might also weaken the strength of study results.ConclusionsOur results indicated that, for patients with T2DM who are on Met-SU dual therapy, the addition of DPP4i was a preferred third-line medication among 3 options, with the lowest risks of mortality and SH and posing no increased risk for CVD events when compared to insulin and TZD. Intensification with insulin had the greatest risk of mortality and SH events.

TROVE2 strengthens the anti-inflammatory effect via macrophage polarization by estrogen induction in abdominal aortic aneurysm

Abdominal Aortic Aneurysm (AAA) is a severe cardiovascular disease, with high mortality rate after acute rupture of blood vessels. However, the underlying pathogenesis of different morbidity between men and women remains unclear. In the present study, we first selected four datasets including 68 AAA and 32 control samples from published data on GEO database, and analyzed them by data mining. The integrative analysis found a total of 368 differentially expressed genes in E2-related AAA. Next, regulatory mechanism networks among these target genes were predicted, and four genes were identified as key nodes in the network, which play a major role in the immune system. We focused on the role of monocytes/macrophages in the development of cardiovascular diseases to further explore the role of estrogen in the polarization of monocytes/macrophage, the mRNA level of the four genes was validated by RT-PCR in RAW264.7 cells treated with β-estradiol (E2), diarylpropionitrile (DPN), 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), fulvestrant or vehicle. The results showed that the mRNA level and protein level of TROVE2 was significantly increased in estrogen or estrogen receptor agonist-treated groups. Moreover, estrogen affected the transformation of macrophages to M2 phenotype by detecting M1- and M2-related indicator genes at the mRNA level. Flow cytometry demonstrated that the TROVE2 deficiency led to a notable decrease in the level of M2 phenotype marker protein CD206. In conclusion, our results suggest that E2 can promote the expression of TROVE2, which is closely related to the M2-phenotype transformation of macrophages.

Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus.

Neutrophil extracellular traps (NET) are essential in host defense, but are also linked to inflammation and autoimmunity, including in systemic lupus erythematosus (SLE). We recently described that immune complexes (IC) induce NET formation, promoting SLE-like disease in mice. In the current study, we investigated, for the first time to our knowledge, the role of NET in human SLE and their association with disease activity and severity. Levels of NET (myeloperoxidase-DNA complexes) were analyzed in plasma from 4 cross-sectional SLE cohorts (n = 44-142), 1 longitudinal SLE cohort (n = 47), and healthy individuals (n = 100) using ELISA. Type I interferon activity was determined using a cell reporter system. Patients with SLE had elevated levels of NET in circulation compared to healthy controls (p < 0.01). NET levels identified patients with a severe disease phenotype characterized by IC-driven nephritis (p < 0.05). Though not associated with current disease activity (p = 0.20), levels of NET were associated with future increase in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) within 3 months (OR 1.75, p = 0.01), as well as an overall heightened SLEDAI over 1 year (p < 0.01). Finally, levels of NET were associated with arterial events (OR 5.0, p = 0.02) and endothelial cell activation (p < 0.001). NET levels are elevated in patients with SLE, associated with IC-driven disease. NET levels provide significant clinical value in identifying patients at risk of active disease and/or severe disease, including nephritis and cardiovascular disease, and may allow for early interventions.

Lipoprotein apheresis in Germany – Still more commonly indicated than implemented. How can patients in need access therapy?

BackgroundAlthough lipid-lowering drugs, especially statins, and recently also PCSK9 inhibitors can reduce LDL cholesterol (LDL-C) and decrease the risk for cardiovascular disease (CVD) including coronary artery disease (CAD) events most efficiently, only 5–10% of high-risk cardiovascular patients reach the target values recommended by international guidelines. In patients who cannot be treated adequately by drugs it is possible to reduce increased LDL-C and/or lipoprotein(a) (Lp(a)) values by the use of lipoprotein apheresis (LA) with the potential to decrease severe CVD events in the range of 70%->80%. Even in Germany, a country with well-established reimbursement guidelines for LA, knowledge about this life-saving therapy is unsatisfactory in medical disciplines treating patients with CVD.Starting in 1996 our aim was to offer LA treatment following current guidelines for all patients in the entire region of our clinic as standard of care. MethodsBased on the experience of our large apheresis competence center overlooking now nearly 80,000 LA treatments in the last two decades, we depict the necessary structure for identification of patients, defining indication, referral, implementation and standardisation of therapy as well as for reimbursement. LA is unfamiliar for most patients and even for many practitioners and consultants. Therefore nephrologists performing more than 90% of LA in Germany have to form a network for referral and ongoing medical education, comprising all regional care-givers, general practitioners as well as the respective specialists and insurances or other cost bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. The German Lipid Association (Lipid-Liga) has implemented the certification of a lipidological competence center as an appropriate way to realize such a network structure. ResultsWorking as a lipidological and apheresis competence center in a region of 400,000 to 500,000 inhabitants, today we treat 160 patients in the chronic LA program. In spite of the availability of PCSK9 inhibitors since 2015, LA has remained as an indispensable therapeutic option for targeted lipid lowering treatment. An analysis of nearly 37,000 LA treatments in our own center documented a >80% reduction of cardiovascular events in patients treated by regular LA when comparing with the situation before the start of the LA therapy.We have implemented the concept of an apheresis competence center characterised by ongoing medical education with a focus on lipidological and cardiovascular aspects, interdisciplinary networking and referral. ConclusionsIncidence and prevalence of LA patients in our region demonstrate that based on our ongoing patient-centered approach the access of patients in need to LA is substantially above the German average, thus contributing to an extraordinary reduction of cardiovascular events in the population we in particular feel responsible for.

Association of Echocardiography Before Major Elective Non-Cardiac Surgery With Improved Postoperative Outcomes - Possible Implications for Patient Care.

Whether preoperative echocardiography improves postoperative outcomes is not well established, so we examined the value of echocardiographic assessment on the onset of postoperative heart failure (HF), and determining which patients benefitted most from undergoing echocardiography prior to major elective non-cardiac surgery.Methods and Results:We identified all patients aged 50 years and older who had major elective non-cardiac surgery, and excluded patients with previously identified severe cardiovascular disease. The primary endpoint was the onset of HF during hospitalization. A total of 806 patients were included in the analysis. During hospitalization, 49 patients (6%) reached the primary endpoint. Within the matched cohort, preoperative echocardiography was associated with a statistically significant decrease in postoperative HF (hazard ratio: 0.46, P=0.01). In subgroup analyses, age, sex, body surface area, hypertension, diabetes mellitus, prior HF, surgical type, chronic kidney disease, pulmonary disease, and malignancy influenced the association of echocardiography with postoperative HF. The use of echocardiography in elderly patients with certain risk factors was associated with improved postoperative outcomes. The basis for this finding remains to be determined; particularly whether echocardiography is simply a marker of a population with better outcomes or whether it leads to better management that improves outcomes.

Prevalence of risk factors of cardiovascular complications in elderly women with left breast cancer

The purpose to study the risk factors for elderly women with left breast cancer at the stage of chemotherapy and radiotherapy in the context of daily clinical practice for early detection of possible cardiovascular complications and optimization of therapy.&#x0D; Material and methods. 69 women with HER2 neu negative left breast cancer without severe cardiovascular disease were examined. The first group included 39 elderly patients (67.7 3.8 years). The second group consisted of 34 middle-aged patients (49.8 5.7 years). In addition to the risk assessment according to the Score scale, additional factors including psychosocial factors were studied. The examination was carried out before the start of treatment, after the end of the course of doxorubicin in a cumulative dose of up to 360 mg/m2 and after the completion of radiation therapy 3D conformal radiation therapy SOD 39 Gr.&#x0D; Results. In elderly patients, risk factors such as obesity, increased cholesterol, and hypertension were significantly more common. In both study groups, low physical activity was revealed associated with both cancer itself and the treatment. All examined patients had moderate reactive anxiety on the Spielberger-Hanin scale. Elderly patients showed high level of personal anxiety; the number of points scored 49.3 3.6. According to the Score scale, a moderate risk was detected in 18 (58.1%) and a high risk in 13(41.9%) elderly patients. After doxorubicin treatment asymptomatic systolic dysfunction was detected in 8 (20.5%) patients (decrease in EF50%), 21 (75%) diastolic dysfunction with relaxation slowdown (E/A1). In 9 (23.1%) of the women without reducing the EF fibrotic changes in the myocardium of the left ventricle was revealed. In 8 (20.5%) women a thickening of the pericardial layer was revealed.&#x0D; Conclusion. The findings suggest the need for a personalized approach and assessment of risk factors in patients of different age groups with left breast cancer at the stage of preparation and conduct of chemoradiotherapy. This highlights the need for enhanced history collection and consideration of not only key but also additional risk factors. The results of the study can be used in the work of practical health care institutions for the planning, development, implementation and control of chemoradiography safety in terms of preventing cardiovascular complications.

Protective and therapeutic effects of Trianthema portulacastrum against atherosclerosis in male albino rats via G-protein-coupled receptor 124

Atherosclerosis is a severe cardiovascular disease characterized by narrowing of the lumen, plaque formation, and blood flow turbulence as a result of cholesterol and lipid accumulation in the inner lining of arteries. Bishkhapra (Trianthema portulacastrum Linn.) is a well-known common weed belonging to the family Aizoaceae. Several bioactive compounds have been isolated from this weed and widely used against several diseases. The present study evaluated the protective and therapeutic efficacies of T. portulacastrum against atherosclerosis in a rat model. The animals were divided into the sham, control (diabetes- + atherosclerosis-inducing diet), 100 mg/kg T. portulacastrum treatment, 200 mg/kg T. portulacastrum treatment, and positive control groups. Blood glucose, cholesterol, triglyceride, and other lipid parameters, as well as the expression of G-protein-coupled receptor 124 (GPR124), were measured. Glucose, cholesterol, and triglycerides were significantly reduced to near normal levels. The serum levels of fibrinogen, sVCAM-1, and oxidized low density lipoproteins were substantially increased in control rats. Treatment with the T. portulacastrum extract reversed these levels to near normal levels. The mRNA expression of GPR124 was increased by 150% in the control group. However, treatment with T. portulacastrum extract decreased the mRNA expression up to 40% compared with the control group. Rats treated with 100 and 200 mg/kg T. portulacastrum extract showed a decrease in GPR124 protein expression by 9.5% and 33.3%, respectively. Taken together, the results suggest that an extract of T. portulacastrum is effective against atherosclerosis in streptozotocin-induced diabetic rats.

NEW METHODS FOR PREDICTING OUTCOMES AND COMPLICATIONS IN PATIENTS WITH ATRIAL FIBRILLATION

Aim:assessment of the capabilities of “machine learning” methods in predicting remote outcomes in patients with non-valvular atrial fibrillation (AF).Methods.From 2015 to 2016 234 patients with non-valvular AF were included in the study (median age 72 (65; 79) years; 50.0% men). During the median follow-up of 2.9 (2.7; 3.2) years 42 patients died, 9 patients had non-fatal acute cerebral circulatory disorders and 3 patients had non-fatal myocardial infarction (MI). These events in 52 subjects (22.2% from all patients included) were combined into a combined endpoint (death and a nonfatal cardiovascular accident at the stage of remote observation). The first 184 patients comprised a “training” group. The next 50 patients formed the “test” group. The following methods of «machine learning» were used in the analysis: classification trees, linear discriminant analysis, the k-nearest neighbor method, support vectors method, neural network.Results.Long-term outcomes were influenced by age, known traditional risk factors for cardiovascular diseases, the presence of these diseases, changes in intracardiac hemodynamics and heart chambers as evaluated by echocardiography, the presence of concomitant anemia, advanced stages of chronic kidney disease, and the administration of drugs associated with a more severe cardiovascular disease progression (amiodarone, digoxin). The best prognosis was created using the model of linear discriminant analysis, the complex neural network model, and the support vector machine.Conclusion.Modern methods aimed at prognosis estimation seem to be of great potential for cardiology. These methods include big data analysis and machine learning technologies. The methods require further evaluation and con firmation, and in the future they may allow correcting cardiovascular risks, using data from real clinical practice and evidence-based medicine at the same time.