Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis.

Cardiovascular disease (CVD) remains a prominent cause of global mortality, primarily driven by atherosclerosis. Diabetes mellitus, as a modifiable risk factor, significantly contributes to atherogenesis. Monocyte recruitment to the intima is a critical step in atherosclerotic plaque formation, involving chemokines and adhesion molecules such as selectins, ICAM-1, and MCP-1. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are a promising group of drugs for reducing cardiovascular risk in diabetic patients, prompting investigation into their mechanisms of action. This interventional study enrolled 50 diabetes patients with atherosclerotic plaque, administering GLP-1RA for 180 days. Serum concentrations of MCP-1, ICAM-1, and L-selectin were measured before and after treatment. Anthropometric and biochemical parameters were also assessed. GLP-1RA treatment resulted in significant improvements in anthropometric parameters, glycemic control, blood pressure, and biochemical markers of liver steatosis. Biomarker laboratory analysis revealed higher baseline levels of MCP-1, ICAM-1, and L-selectin in diabetic patients with atherosclerotic plaque compared to healthy controls. Following treatment, MCP-1 and L-selectin levels decreased significantly (p < 0.001), while ICAM-1 levels increased (p < 0.001). GLP-1RA treatment in diabetic patients with atherosclerotic plaque leads to favorable changes in serum molecule levels associated with monocyte recruitment to the endothelium. The observed reduction in MCP-1 and L-selectin suggests a potential mechanism underlying GLP-1RA-mediated cardiovascular risk reduction. Further research is warranted to elucidate the precise mechanisms and clinical implications of these findings in diabetic patients with atherosclerosis.

Influence of Dulaglutide on Serum Biomarkers of Atherosclerotic Plaque Instability: An Interventional Analysis of Cytokine Profiles in Diabetic Subjects-A Pilot Study.

Background and Objectives: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably macrovascular ones like coronary artery, cerebrovascular, and peripheral artery diseases, which contribute to over 50% of diabetes mortality. Atherosclerosis, linked to hyperglycemia-induced endothelial dysfunction, is pivotal in cardiovascular disease development. Cytokines, including pentraxin 3 (PTX3), copeptin, lipoprotein(a) [Lp(a)], and matrix metalloproteinase-9 (MMP-9), influence atherosclerosis progression and plaque vulnerability. Inhibiting atherosclerosis progression is crucial, especially in diabetic individuals. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), increasingly used for type 2 diabetes, show promise in reducing the cardiovascular risk, sparking interest in their effects on atherogenesis. This study sought to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on biomarkers that indicate the instability of atherosclerotic plaques. These biomarkers include pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9), and lipoprotein(a) [Lp(a)]. Materials and Methods: A total of 34 participants, ranging in age from 41 to 81 years (with an average age of 61), who had been diagnosed with type 2 diabetes mellitus (with a median HbA1c level of 8.8%), dyslipidemia, and verified atherosclerosis using B-mode ultrasonography, were included in the study. All subjects were eligible to initiate treatment with a GLP-1 RA-dulaglutide. Results: Significant reductions in anthropometric parameters, blood pressure, fasting glucose levels, and HbA1c levels were observed posttreatment. Moreover, a notable decrease in biochemical markers associated with atherosclerotic plaque instability, particularly PTX3 and MMP-9 (p < 0.001), as well as Lp(a) (p < 0.05), was evident following the GLP-1 RA intervention. Conclusions: These findings underscore the potential of GLP-1 RAs in mitigating atherosclerosis progression and plaque vulnerability, thus enhancing cardiovascular outcomes in individuals with type 2 diabetes mellitus.

Impact of Glucagon-Like Peptide 1 Receptor Agonists on Biochemical Markers of the Initiation of Atherosclerotic Process.

Atherosclerosis stands out as one of the leading causes of global mortality. The inflammatory response against vascular wall components plays a pivotal role in the atherogenic process. The initiation of this process is notably driven by oxidized low-density lipoprotein (oxLDL) and a range of pro-inflammatory cytokines, with interleukin-1ß (Il-1ß) and tumor necrosis factor α (TNFα) emerging as particularly significant in the early stages of atherosclerotic plaque formation. In recent years, researchers worldwide have been diligently exploring innovative therapeutic approaches for metabolic diseases, recognizing their impact on the atherogenesis process. Our study aimed to investigate the influence of glucagon-like peptide 1 receptor agonists (GLP-1RA) on cytokine concentrations associated with the initiation of atherosclerotic plaque formation in a group of patients with type 2 diabetes and dyslipidemia. The study encompassed 50 subjects aged 41-81 (mean: 60.7), all diagnosed with type 2 diabetes, dyslipidemia and confirmed atherosclerosis based on B-mode ultrasound. Following a 180-day treatment with dulaglutide or semaglutide, we observed a statistically significant reduction in biochemical markers (oxLDL, TNFα and Il-1ß) associated with the initiation of the atherosclerotic process (p < 0.001) within our study group. In addition to the already acknowledged positive effects of GLP-1RA on the metabolic parameters of treated patients, these drugs demonstrated a notable reduction in proinflammatory cytokine concentrations and may constitute an important element of therapy aimed at reducing cardiovascular risk.

Does Therapy with Glucagon-like Peptide 1 Receptor Agonists Have an Effect on Biochemical Markers of Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD)? Pleiotropic Metabolic Effect of Novel Antidiabetic Drugs in Patients with Diabetes-Interventional Study.

Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) is associated with the excessive collection of lipids in hepatocytes. Over 75% of diabetes patients typically have MASLD, and, at the same time, the presence of MASLD increases the risk of diabetes by more than two times. Type 2 diabetes and MASLD are independent cardiovascular disease (CVD) risk factors. New diabetes treatment should also take into account pleiotropic effects that reduce cardiovascular risk. The aim of our study is to investigate whether analogs of GLP1 receptors have a pleiotropic metabolic effect and global impact to decrease cardiovascular risk, and also reduce the risk of hepatic fibrosis in patients with MASLD. This study involved 41 patients with diabetes and dyslipidemia who also had atherosclerotic plaque and hepatic steatosis verified by ultrasonography and who were eligible to begin one of the GLP1 receptor agonists treatments. We observed a statistically significant decrease in: BMI (p < 0.001) waist and hip circumference (p < 0.001), glycated hemoglobin (p < 0.001) and creatinine (p < 0.05). Additionally, we obtained a decrease in FIB-4 (p < 0.001) and in the De Ritis (AST/ALT aminotransferase ratio) (p < 0.05). The positive correlation between the FIB-4 value and BMI, WHR, waist circumference and the De Ritis index was observed. In conclusion, semaglutide and dulaglutide had a beneficial effect on metabolic and cardiovascular risk factors in patients with type 2 diabetes. These medications had a positive effect on MASLD biochemical markers.

The Effect of PCSK9 Inhibition on the Stabilization of Atherosclerotic Plaque Determined by Biochemical and Diagnostic Imaging Methods.

Atherosclerosis is a multifactorial, progressive, chronic inflammatory disease. Ultrasound and magnetic resonance imaging are the most accurate predictors of atherosclerotic plaque instability (MRI). Cytokines such as osteopontin, osteoprotegerin, and metalloproteinase 9 could be used as the most recent markers to identify and track the efficacy of anti-atherosclerotic therapy. Patients with USG and MRI-verified unstable atherosclerotic plaque were included in the study. Biomarker concentrations were measured and compared before and after PCSK9 inhibitor therapy. Additionally, concentrations prior to treatment were correlated with MRI images of the carotid artery. After treatment with alirocumab, the concentrations of MMP-9 (p < 0.01) and OPN, OPG (p < 0.05) decreased significantly. Furthermore, the results of OPN, OPG, and MMP 9 varied significantly depending on the type of atherosclerotic plaque in the MRI assay. In stable atherosclerotic plaques, the concentrations of OPN and OPG were greater (p < 0.01), whereas the concentration of MMP9 correlated with the instability of the plaque (p < 0.05). We demonstrated, probably for the first time, that alirocumab therapy significantly decreased the serum concentration of atherosclerotic plaque markers. In addition, we demonstrated the relationship between the type of atherosclerotic plaque as determined by carotid MRI and the concentration of these markers.

Initial clinical, laboratory and radiological features of SARS-CoV-2-infected patients and their impact on the course of the disease.

BACKGROUND: On March 11, 2020, coronavirus disease (COVID-19) was declared a global threat by the World Health Organization (WHO). It quickly became apparent that reducing inpatient mortality rates and early phase prediction of possible deterioration or severe disease course relied on finding more specific biomarkers. OBJECTIVES: This retrospective study assessed initial clinical, laboratory and radiological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and explored their impact on mortality and the course of the disease. Such efforts aimed to facilitate the identification of high-risk patients and to improve the formulation of treatment plans for these individuals. MATERIAL AND METHODS: The cohort comprised 111 consecutive adult inpatients diagnosed with COVID-19 and hospitalized in the Internal Medicine Ward of the University Clinical Center of prof. K. Gibinski of the Medical University of Silesia in Katowice, Poland, a COVID-19 Treatment Unit, between November 16, 2020 and February 15, 2021. All available clinical, laboratory and radiological findings were extracted from electronic records and assessed as possible risk factors for poor prognosis. RESULTS: Clinicasl and radiological features with higher frequency in COVID-19 non-survivors included older age, history of smoking, concomitant cardiovascular diseases, low oxygen saturation (SpO2), and high infection risk assessed on admission as well as high opacity score, percentage of opacity and percentage of high opacity in computed tomography. Non-survivors had decreased serum lymphocytes, monocytes, calcium, magnesium, and hemoglobin oxygen saturation. They also had increased red cell distribution width (RDW), C-reactive protein (CRP), procalcitonin, alkaline phosphatase (ALP), creatinine, blood urea nitrogen (BUN), D-dimer, troponin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, as well as a base deficit. CONCLUSIONS: This retrospective study identified several markers associated with a fatal course of COVID-19. The early assessment of SARS-CoV-2-infected inpatients should consider these markers.

The Impact of Various Methods of Obesity Treatment on the Quality of Life and Mental Health-A Narrative Review.

Obesity, defined as body mass index (BMI) ≥ 30 kg/m2, is one of the most important public health problems. Over one billion people are obese, including 650 million adults, which is 13% of the worldwide population, according to the World Health Organization (WHO). Similar to obesity, mental disorders such as depression and anxiety are huge social problems with serious health implications. There are numerous studies proving a strong link between the prevalence of obesity and depressive disorders, and being overweight is also associated with decreased health-related quality of life (HRQoL). Due to the broad negative impact of obesity on a patient's health, proper treatment is crucial. Currently, the literature describes many methods of treatment such as dietary treatment, pharmacotherapy using glucagon-like peptide-1 (GLP-1) analogs, orlistat, naltrexone/bupropion (NB), or finally bariatric surgery. The most commonly used methods of obesity treatment significantly improve the patient's quality of life and reduce the symptoms of depression and anxiety. The aim of our study was to summarize the knowledge about the impact of known and commonly used methods of obesity treatment (e.g., dietary treatment, bariatric surgery, and pharmacological treatment) on mental health and quality of life. For this purpose, we will try to review the current scientific data, originating from international reports.

Impact of Alirocumab on Release Markers of Atherosclerotic Plaque Vulnerability in Patients with Mixed Hyperlipidemia and Vulnerable Atherosclerotic Plaque.

Background and Objectives: Atherosclerosis is a disease in the pathogenesis of which plasma factors apart from elevated cholesterol levels play a keyrole. Such factors include osteopontin (OPN), osteoprotegerin (OPG), and metalloproteinases (MMPs), which are factors that may be responsible for the stabilization of atherosclerotic plaque. The aim of this study was to assess the effect of modern lipid-lowering therapy by using proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitor on the concentrations of these factors. Materials and Methods: The study included people suffering from dyslipidemia who were eligible to start alirocumab therapy. In this group, the concentrations of OPN, OPG, and MMPs were assessed before the initiation of therapy and after three months of its duration. Results: In the study, we observed a statistically significant reduction in the concentrations of OPN, OPG (p < 0.001), and metalloproteinase 2 (MMP-2) (p < 0.05) after the applied therapy. Moreover, we noticed that in the group of patients soon to start alirocumab therapy, the concentrations of these factors were higher compared to the control group (p < 0.001). Conclusions: The results of our study show that therapy with alirocumab significantly reduces the concentration of factors that affect atherosclerotic plaque vulnerability, which may explain their important role in reducing cardiovascular risk in patients undergoing this therapy.

Impact of PCSK9 Inhibition on Proinflammatory Cytokines and Matrix Metalloproteinases Release in Patients with Mixed Hyperlipidemia and Vulnerable Atherosclerotic Plaque.

Atherosclerosis is a disorder in which, in addition to high cholesterol levels, several plasma factors play a significant role in its development. Among these cytokines and molecules are interleukin 6 (IL-6), interleukin 18 (IL-18), tumor necrosis factor α (TNF-α), metalloproteinase 2 (MMP-2), and metalloproteinase 9 (MMP-9), all of which may contribute to the stabilization of atherosclerotic plaque. The purpose of this study was to determine the effect of advanced lipid-lowering therapy on the levels of these determinants by utilizing proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors in patients with verified high-risk atherosclerotic plaque. Methods: The study involved patients with dyslipidemia who had the presence of unstable atherosclerotic plaque verified by ultrasonography and who were eligible to begin alirocumab treatment. The levels of IL-6, IL, 18, TNF-α, and MMPs were determined in this group before and after three months of therapy. After treatment, a statistically significant decrease in concentrations of Il-18, Il-6, TNF-α (p < 0.001) and MMP-2 (p < 0.05) was observed. Additionally, we observed that the concentrations of these markers were significantly higher in the group of patients prior to initiating therapy than in the control group. Our study's results suggest that PCSK-9 inhibitor therapy significantly reduces the concentration of factors influencing the stability of atherosclerotic plaque, which may explain their essential importance in reducing cardiovascular risk in patients receiving this treatment.

Plasma Concentrations of New Biochemical Markers of Atherosclerosis in Patients with Dyslipidemia-A Pilot Study.

Background and Objectives: The process of atherosclerotic plaque formation and its destabilisation is a process in which many proteins and cytokines are involved. Examples of such proteins are osteopontin (OPN), osteoprotegerin (OPG), metalloproteinases (MMPs) and myeloperoxidase (MPO). The aim of our study is to compare the concentrations of the above-mentioned markers in the plasma of patients with the confirmed presence of rupture plaque in comparison with the plasma of healthy people. Materials and Methods: The study included people suffering from dyslipidemia in whom the presence of unstable atherosclerotic plaque was confirmed by ultrasound. The concentrations of OPN, OPG, MPO, metalloproteinase 2 (MMP-2), and metalloproteinase 9 (MMP-9) in the plasma of these people were determined and compared with the concentrations of these proteins in the plasma of healthy people. Results: Levels of MMP-2, MMP-9 (p < 0.001), OPN, and OPG (p < 0.05) were statistically significantly lower in the group of healthy people than in the study group. Differences in MPO concentration were not statistically significant (p = 0.073). Conclusions: In the plasma of people with confirmed presence of rupture plaque, the concentrations of OPN, OPG, and MMPs are higher compared to the group of healthy people, which may suggest the use of these proteins as novel markers of the presence of unstable atherosclerotic plaque.

Plasma Concentrations of Cytokines in Patients with Combined Hyperlipidemia and Atherosclerotic Plaque before Treatment Initiation-A Pilot Study.

Background and Objectives: The formation and destabilization of atherosclerotic plaques is a complex process involving several proteins and cytokines. Interleukin 6 (IL-6), interleukin 18 (IL-18), and tumor necrosis factor (TNF-α) are examples of such cytokines. The goal of our research is to compare the concentrations of the above-mentioned indicators in the plasma of patients with verified high-risk atherosclerotic plaque to the plasma levels of healthy people before lipid lowering therapy. Materials and Methods: Patients with dyslipidemia who had the presence of unstable atherosclerotic plaque verified by ultrasonography were included in the study. The concentrations of IL-6, IL-18 and TNF-α in the plasma of these people were determined and compared with the concentrations of these cytokines in the plasma of the control group. Results: Levels of lipid panel, IL-6 and IL-18 were significantly lower in the group of healthy people than in the study group. Conclusions: The concentrations of IL-6 and IL-18 in the plasma of patients with ruptured plaque are higher than in the plasma of healthy people, suggesting that these cytokines as a panel might be used as new indicators of the presence of unstable atherosclerotic plaque.

Effect of PCSK9 Inhibitors on Hemostasis in Patients with Isolated Hypercholesterolemia.

Background: In addition to reducing plasma lipids, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may produce numerous nonlipid-related pleiotropic effects. The purpose of this trial was to determine the efficacy of PCSK9 inhibitors alone in patients with isolated hypercholesterolemia. Methods: The trial enrolled 21 individuals with isolated hypercholesterolemia and atherosclerosis who received alirocumab for 90 days (150 mg every two weeks). Lipids, glucose homeostasis factors, and hemostatic markers were measured in the plasma at baseline and after treatment. Results: The PCSK9 inhibitor administered to these patients reduced plasma levels/activity of fibrinogen (from 3.6 ± 0.5 to 2.9 ± 0.4 g/L, p < 0.01), factor VII (from 143.8 ± 16.7 to 114.5 ± 14.1%, p < 0.01) and plasminogen activator inhibitor-1 (PAI-1) (from 74.9 ± 13.9 to 52.8 ± 9.1 ng/mL, p < 0.001) without a significant reduction in von Willebrand factor levels, and it tended to prolong the partial thromboplastin and prothrombin times. Conclusion: Our findings indicate that treatment with PCSK9 inhibitors has a multipotential effect on fibrinolysis and coagulation in patients with isolated hypercholesterolemia and that this medication may have some future benefits in patients who are statin-intolerant or contraindicated to statin use.

Fungal infection mimicking COVID-19 infection - A case report.

For the last 2 years, one of the most frequent causes of respiratory failure is coronavirus disease 2019 (COVID-19). The symptoms are not specific. Imaging diagnostics, especially high-resolution computed tomography, is a diagnostic method widely used in the diagnosis of this disease. It is important to emphasize that not only SARS-CoV-2 infection may manifest as interstitial pneumonia. Other diseases such as other viral, fungal, atypical bacterial pneumonia, autoimmune process, and even cancer can also manifest as ground-glass opacities or consolidations in the imaging of the lungs. In this case report, we described a patient who manifested many symptoms that seemed to be COVID-19. However, all performed antigen and polymerase chain reaction tests were negative. The diagnostics must have been extended. Microbiological and mycological blood cultures and sputum cultures were performed. Blood cultures were negative but in sputum, Candida albicans and Candida glabrata were identified. Targeted therapy with fluconazole was implemented with a satisfactory result. The patient was discharged from the hospital in a good general condition with no complaints.

Insight into the Evolving Role of PCSK9.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the last discovered member of the family of proprotein convertases (PCs), mainly synthetized in hepatic cells. This serine protease plays a pivotal role in the reduction of the number of low-density lipoprotein receptors (LDLRs) on the surface of hepatocytes, which leads to an increase in the level of cholesterol in the blood. This mechanism and the fact that gain of function (GOF) mutations in PCSK9 are responsible for causing familial hypercholesterolemia whereas loss-of-function (LOF) mutations are associated with hypocholesterolemia, prompted the invention of drugs that block PCSK9 action. The high efficiency of PCSK9 inhibitors (e.g., alirocumab, evolocumab) in decreasing cardiovascular risk, pleiotropic effects of other lipid-lowering drugs (e.g., statins) and the multifunctional character of other proprotein convertases, were the cause for proceeding studies on functions of PCSK9 beyond cholesterol metabolism. In this article, we summarize the current knowledge on the roles that PCSK9 plays in different tissues and perspectives for its clinical use.

The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders.

Statins are among the most widely used drug classes in the world. Apart from their basic mechanism of action, which is lowering cholesterol levels, many pleiotropic effects have been described so far, such as anti-inflammatory and antiatherosclerotic effects. A growing number of scientific reports have proven that these drugs have a beneficial effect on the functioning of the nervous system. The first reports proving that lipid-lowering therapy can influence the development of neurological and psychiatric diseases appeared in the 1990s. Despite numerous studies about the mechanisms by which statins may affect the functioning of the central nervous system (CNS), there are still no clear data explaining this effect. Most studies have focused on the metabolic effects of this group of drugs, however authors have also described the pleiotropic effects of statins, pointing to their probable impact on the neurotransmitter system and neuroprotective effects. The aim of this paper was to review the literature describing the impacts of statins on dopamine, serotonin, acetylcholine, and glutamate neurotransmission, as well as their neuroprotective role. This paper focuses on the mechanisms by which statins affect neurotransmission, as well as on their impacts on neurological and psychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), vascular dementia (VD), stroke, and depression. The pleiotropic effects of statin usage could potentially open floodgates for research in these treatment domains, catching the attention of researchers and clinicians across the globe.

High rates of undiagnosed and untreated osteoporosis in postmenopausal women receiving medical services in the area of Upper Silesia.

INTRODUCTION: High social cost and high risk of disability make postmenopausal osteoporosis one of major public health problem in the 21st century. The aim of this study was to assess frequency of undiagnosed and untreated osteoporosis in postmenopausal women in the Upper Silesia Region of Poland. Additionally, we compare estimation of the 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HF) based on fracture risk assessment tool (FRAX) with and without bone mineral density (BMD). MATERIAL AND METHODS: The survey included 450 postmenopausal women (age 65 ±11 years). A detailed questionnaire included demographic and anthropometric data, comorbidity, history of previous low-energy fractures, family medical history, and treatment for osteoporosis. The FRAX calculator was used to estimate the risk of MOF and HF. RESULTS: Osteoporosis was previously diagnosed in 23.7% women. Of those 70.2% were receiving vitamin D, 27% calcium preparations, 33% bisphosphonates, and 22% were untreated. Only 42.2% women with previous fractures had been diagnosed with osteoporosis and 42.8% received any treatment. 12.5% women with FRAX-BMD ≥ 10% had no risk factors of osteoporosis and < 10% risk of MOF and HF in FRAX without BMD. CONCLUSIONS: Osteoporosis often remains undiagnosed and untreated in postmenopausal women. There is a great need to popularize FRAX without BMD calculator among physicians, especially GPs, as the risk calculation justify the implementation of antiosteoporotic therapy. Women with burden of risk factors of fractures and borderline FRAX without BMD values, should be referred to a densitometry examination, as having greater risk of fracture than shown by FRAX without BMD.