Statins Alone or in Combination with Ezetimibe or PCSK9 Inhibitors in Atherosclerotic Cardiovascular Disease Protection

Statins have proved to be very effective in reducing atherosclerotic cardiovascular disease (ASCVD) risk, with no apparent threshold at which low-density lipoprotein cholesterol (LDL-C) lowering is not associated with a reduced risk. Yet, several meta-analyses of statin trials show significant on-treatment residual risk of major cardiovascular (CV) events. This finding points to the unmet needs, in terms of LDL-C targets and ASCVD protection, of statin-treated patients, raising the question of statin combination therapy. Ezetimibe is a cholesterol absorption inhibitor, with the potency to decrease LDL-C for about 10–18%, apolipoprotein B (apoB) for 11–16%, while, in combination therapy with statins, leads to an additional LDL-C lowering of 25%, with a total LDL-C lowering of 34–61%. It is also estimated that 10–20% of patients on statin treatment cannot tolerate them. As a result, adequate doses to achieve treatment target, or as recommended for the patient-specific risk profile, cannot be prescribed. Proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibitors are monoclonal antibodies that inhibit the binding of PCSK9 to LDL-C receptors. Besides a very potent lipid-lowering effect, PCSK9 inhibitors have added ASCVD risk reduction benefit due to a very aggressive LDL-C lowering action, especially beneficial in patients who are intolerant to statins

Prognostic power of normal spect MPI in patients with and without significant CAD

There are two ways to increase myocardial blood flow above the baseline levels. Namely, myocardium is extremely efficient in extracting oxygen from blood. The increase in myocardial oxygen demand and consumption leads to increase of myocardial blood flow and hyperemia. Increasing of oxygen demands may be provoked by exercise or inotropic agents-Dobutamine. Other way is by use of coronary vasodilators: adenosine and dipyridamol. Since 1970s and 1980s, when researchers showed that vasodilators increase coronary blood flow 3 to 5 time above baseline in normally perfused myocardium, these agents were and are wildly used as pharmacologic stressors in MPI SPECT studies. While the mechanism of inducing ischemia by effort is well known, there are several possible mechanisms of ischemia during vasodilator infusion

Rosuvastatin effects on the HDL proteome in hyperlipidemic patients

The advancements in proteomics have provided a better understanding of the functionality of apolipoproteins and lipoprotein-associated proteins, with the HDL lipoprotein fraction being the most studied. The focus of this study was to evaluate the HDL proteome in dyslipidemic subjects without an established cardiovascular disease, as well as to test whether rosuvastatin treatment alters the HDL proteome. Patients with primary hypercholesterolemia or mixed dyslipidemia were assigned to 20 mg/day rosuvastatin and blood samples were drawn at study entry and after 12 weeks of treatment. A label-free LC-MS/MS protein profiling was conducted, coupled with bioinformatics analysis. Sixty-nine HDL proteins were identified, belonging to four main biological function clusters: lipid transport and metabolism; platelet activation, degranulation, and aggregation, wound response and wound healing; immune response; inflammatory and acute phase response. Five HDL proteins showed statistically significant differences in the abundance (Anova ≤ 0.05), before and after rosuvastatin treatment. Platelet factor 4 variant (PF4V1), Pregnancy-specific beta-1-glycoprotein 2 (PSG2), Profilin-1 (PFN1) and Keratin type II cytoskeletal 2 epidermal (KRT2) showed decreased expressions, while Integrin alpha-IIb (ITGA2B) showed an increased expression after treatment with rosuvastatin. The ELISA validation of PFN1 segregated the subjects into responders and non-responders, as PFN1 levels after rosuvastatin were shown to mostly depend on the subjects\u27 inflammatory phenotype. Findings from this study introduce novel insights into the HDL proteome and statin pleiotropism

Comparison of 24 h ECG Holter Monitoring with Real-time Long-term ECG Monitoring System using ECGalert Software and Savvy Single-Lead Patch

AIM: The aim of the study was to show non-inferiority of the single-channel ECGalert system to the gold standard (ECG Holter) in the detection of arrhythmias over the total wear time of both devices. METHODS: A prospective study enrolled a total of 165 patients hospitalized at the University Clinic of Cardiology, who underwent simultaneous single-channel ECG recording with ECGAlert system and a conventional 24 h Holter monitor on the 1st day and continued ECGAlert monitoring for few more days, under assignment of the doctor or at the wish of the patient. RESULTS: A total of 165 patients were included in the study, 61.2% male, mean age of 58.4 ± 12.7 years. Mean duration of ECG Holter monitoring was 23.2 ± 0.5 h and mean duration of ECGalert/Savvy monitoring was 64.6 ± 31.2. During the first 24 h of simultaneous ECG monitoring with both methods, no statistically significant difference was found in arrhythmia detection. Over the total wear time of both devices, the ECGalert system detected significantly more AF episodes as compared to Holter (p < 0.000). ECGalert demonstrated significantly lower detection rate of false pauses (0.001). However, false detection of episodes of VT or AF was significantly higher in ECGalert system versus Holter (p < 0.000 and p < 0.000 respectively). Patients were more satisfied with ECGalert system, due to lesser interference in daily activities. CONCLUSION: The ECGalert system demonstrated superiority over traditional Holter monitoring in arrhythmia detection in the total monitoring period, but not in the first 24 h

Successful Industry-University Collaborations in Manufacturing Technology

Historically, many Japanese manufacturing companies have independently developed manufacturing technologies such as advanced processes and equipment, methods of analyzing manufacturing phenomena, and production management and quality control systems, which maintain the competitiveness of product development and production. Most of these companies are beginning to recognize the importance of collaborating with universities, where advanced technologies and methodologies are researched, as a way to adapt to the short lead-time requirements for research and development in manufacturing technology. Because of the many challenges to the success of joint research, the anticipated results are not always obtained. In this paper, key factors for the success of industry-university collaboration in the manufacturing technology field are discussed by demonstrating actual successful cases carried out by Toshiba and the University of Maryland

Antiphospholipid Syndrome - A Case Report of Pulmonary Thromboembolism, Followed with Acute Myocardial Infarction in Patient with Systemic Sclerosis

AIM: We are presenting an uncommon case of pulmonary embolism, followed with an acute myocardial infarction, in a patient with progressive systemic sclerosis. CASE PRESENTATION: A female 40 years of age was admitted with signs of pulmonary embolism, confirmed with CT scan, which also reviled a thrombus in the right ventricle. The patient had medical history of systemic sclerosis since the age of 16 years. She suffered an ischemic stroke 6 years ago, but she was not taking any anticoagulant or antithrombotic medications ever since. She received a treatment with thrombolytic therapy, and subsequent UFH, but, on the second day after receiving fibrinolysis, she felt chest pain accompanied with ECG changes consistent for ST-segment elevation myocardial infarction (STEMI). Urgent coronary angiography was undertaken, which reviled cloths causing total occlusion in 4 blood vessels, followed with thromboaspiration, but without successful reperfusion. Several hours later the patient developed rapid deterioration with letal ending. During the very short hospital course, blood sampling reviled presence of antiphospholipid antibodies. CONCLUSION: The acquired antiphospholipid syndrome is common condition in patients with systemic autoimmune diseases, but relatively rare in patients with systemic sclerosis. Never the less, we have to be aware of it when treating the patients with systemic sclerosis

Determination of Hsp 70 as one of the important inputs in the detection and definition of the degree of myocardial ischemic events

Background: Atherosclerosis induced myocardial ischemia should be as soon as possible confirmed in aim of further protocols. Oxidative stress, through various inflammatory events induces processes involved in repairing the damage. Determination of Heat shock proteins(Hsp)70, involved in this issue give useful data since they induce mechanisms that take part in protein remodeling so can repair the impaired myocardium integrity. Hypoxia and re-oxygenation alter the distribution of cardiac proteins through changes in mRNA so, cardiac myocytes try to protect themselves by regulating antioxidant proteins and stress proteins. Therefore, the determinations of Hsp70 antibodies indicate necrosis, but also witness the initiation of the repair processes of damage. Methods: Study involves group (200) patients suspected for AMI. Standard laboratory protocol was carried out for confirming or dismiss the AMI diagnosis including, photometric determination of cardiac enzymes, (CK, CKMB), MEIA principle for estimation of cardiac markers. Determination of concentration of Hsp70Ab was performed with ELISA technique. Results: Standard statistical analysis showed a positive correlation of Hsp 70 level and CRP with increase cTnT and cTnI values at patients with confirmed AMI (67% of patients). Also, we found an elevated level of Hsp70 in the majority of patients with AP/NSAP (96.7%) and in patients with pulmonary disease (100%). Level of Hsp 70 vs control group shows 15 fold increases at the patients with AP/NSAP, but more important is even 26fold increase at the patients with AMI. Results are significant in aspect of estimation of level of damage, according to some previous data that which detected the path of activation and transduction of the signals through different protein kinase pathological processes. Conclusion: Our results and the prevalence of detected increased Hsp 70Ab at 67 % of patients with AMI testify of engagement of this proteins in cardiac proteins recovering processes. The higher prevalence in patients with AP speaks about the chronic condition at the patients and therefore our recommendation, supported by other data, is to monitor the level of these proteins in patients with AP in order to avoid unwanted, unfavorable outcomes for such patients

Effectiveness of Vitamin K antagonist for secondary prophylaxis of brain stroke in patients with atrial fibrillation in routine public care settings

Vitamin K antagonists are the mainstay for prevention of strokes in patients with atrial fibrillation (AF) world-wide. Yet estimates on its effectiveness are heterogeneous and reveal stark differences between different health-care systems. The aim of the present study was to assess the laboratory parameters for achieving the goal of the therapy (Time in therapeutic range – TTR) and to describe the effectiveness of the therapy in real-time setting. Methods : Patients treated in our clinic, with confirmed AF were considered in the study. The study was prospective observational study by design, where the participants were assessed at baseline for known risk factors for stroke, diagnosis for atrial fibrillation, use of anticoagulant medication and presence of identifiable ischemic lesions in the brain with non-contrast computed tomography (NCCT). The drug of choice was acenocoumarol, with planned monthly measurements of INR with the duration of 6 months, and the study was concluded with additional NCCT at the end, in order to assess for differences. Results : 96 patients finished the observation. The mean age of the patients was 64.5 years (SD = 6.36), and 50 (52%) were male. Regarding the INR measurement, we collected data from 88.2% of the planed measurements; 69.7% of the patients achieved TTR above 60%. Cross-comparison between groups (TTR 60%) revealed that the first group had statistically significant higher proportion of patients with newly registered lesions on NCCT (p-value < 0.05). Conclusion: Acenocoumarol is the only therapeutic VKA option in our country, despite the availability of other VKA antagonists that show better indices for effectiveness. Our sample confirmed that the proper use of VKA significantly reduces the incidence of new NCCT ischemic lesions in conditions of routine public health care

Added Value of Modified Anderson–Wilkins Acuteness Score in Prognostication of Patients with Acute Myocardial Infarction

BACKGROUND: Electrocardiogram (ECG) signs on admission can serve as a prognostic marker in patients treated for myocardial infarction (MI). AIM: The aim of the study was to determine the predictive role of modified Anderson–Wilkins (MAW) ECG score of acuteness on the extent of myocardial injury, left ventricular (LV) remodeling, and clinical outcome in patients with acute MI. METHODS: Prospective, observational cohort study on patients treated for MI at the University Clinic for Cardiology. Subjects were analyzed for their demographic, clinical, ECG, LV functional, angiographic variables, course of treatment, and in-hospital outcome. MAW score was calculated for each patient. Patients were comparatively analyzed divided in two groups (score &lt;3 and ≥3). RESULTS: One hundred fifty patients (70% males and 30% females), aged 60.9 years were included in the study. Sixty-eight patients had MAW score &lt;3 (mean 1.7), and 82 had score ≥3 (mean 3.5), p&gt;0.001. Patients with ST-segment elevation MI had OR 2.1 (p&gt;0.000), and patients with multiple locations (excluding anterior) had OR 2.1 (p &gt; 0.000) of having MAW score ≥3. They received mechanical reperfusion 1.9 (p = 0.032) times more often. High MAW score was associated with stress hyperglycemia (OR 2.1; p = 0.032); low potassium (OR 2.8; p = 0.032), lower creatinine (p = 0.050), and higher NT-proBNP (OR 2.5; p = 0.050). High MAW score was associated with decreased LV function and increased LV dimensions on the follow-up echocardiography (p = 0.050 and 0.012, respectively). CONCLUSION: ECG is an important prognostic tool in MI patients. ECG-derived MAW score demonstrates a strong correlation with stress hyperglycemia, potassium, creatinine, and natriuretic peptides level and can serve as an early marker of LV remodeling after MI