Inflammatory, Metabolic, and Coagulation Effects on Medial Arterial Calcification in Patients with Peripheral Arterial Disease

Calcium deposits in the vessel wall in the form of hydroxyapatite can accumulate in the intimal layer, as in atherosclerotic plaque, but also in the medial layer, as in medial arterial calcification (MAC) or medial Möenckeberg sclerosis. Once considered a passive, degenerative process, MAC has recently been shown to be an active process with a complex but tightly regulated pathophysiology. Atherosclerosis and MAC represent distinct clinical entities that correlate in different ways with conventional cardiovascular risk factors. As both entities coexist in the vast majority of patients, it is difficult to estimate the relative contribution of specific risk factors to their development. MAC is strongly associated with age, diabetes mellitus, and chronic kidney disease. Given the complexity of MAC pathophysiology, it is expected that a variety of different factors and signaling pathways may be involved in the development and progression of the disease. In this article, we focus on metabolic factors, primarily hyperphosphatemia and hyperglycemia, and a wide range of possible mechanisms by which they might contribute to the development and progression of MAC. In addition, we provide insight into possible mechanisms by which inflammatory and coagulation factors are involved in vascular calcification processes. A better understanding of the complexity of MAC and the mechanisms involved in its development is essential for the development of potential preventive and therapeutic strategies

Inflammatory, Metabolic, and Coagulation Effects on Medial Arterial Calcification in Patients with Peripheral Arterial Disease

Calcium deposits in the vessel wall in the form of hydroxyapatite can accumulate in the intimal layer, as in atherosclerotic plaque, but also in the medial layer, as in medial arterial calcification (MAC) or medial Möenckeberg sclerosis. Once considered a passive, degenerative process, MAC has recently been shown to be an active process with a complex but tightly regulated pathophysiology. Atherosclerosis and MAC represent distinct clinical entities that correlate in different ways with conventional cardiovascular risk factors. As both entities coexist in the vast majority of patients, it is difficult to estimate the relative contribution of specific risk factors to their development. MAC is strongly associated with age, diabetes mellitus, and chronic kidney disease. Given the complexity of MAC pathophysiology, it is expected that a variety of different factors and signaling pathways may be involved in the development and progression of the disease. In this article, we focus on metabolic factors, primarily hyperphosphatemia and hyperglycemia, and a wide range of possible mechanisms by which they might contribute to the development and progression of MAC. In addition, we provide insight into possible mechanisms by which inflammatory and coagulation factors are involved in vascular calcification processes. A better understanding of the complexity of MAC and the mechanisms involved in its development is essential for the development of potential preventive and therapeutic strategies

Ultrazvočni in klasični dejavniki tveganja karotidne ateroskleroze pri bolnikih s sladkorno boleznijo tipa 2

Purpose: We determined the prevalence of the clinical and biochemical risk factors as well as the extent of atherosclerosis in carotid arteries in patients with diabetes mellitus type 2(DMT2). Methods: A total of 289 subjects with DMT2 and 157 healthy subjects were enrolled in this prospective cross-sectional study. Leveles of total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, fasting, blood glucose, fribrinogen, and high-sensitivity C-reactive protein (hsCRP) were measured using standard biochemical methods. Carotid atherosclerosis was assessed by ultrasonography. Intima media thickness (IMT), plaque type and plaque score were also determined.Namen: V raziskavi smo želeli ugotoviti prevalenco biokemičnih in kliničnih dejavnikov tveganja ter razširjenost ateroskleroze karotidnih arterij pri bolnikih s sladkorno boleznijo tipa 2 (SBT2). Metode: V prospektivno presečno študijo smo vključili 289 bolnikov s SBT2 in 157 zdravih preiskovancev. Anamnestične in klinične podatke smo zajeli z enotnim vprašalnikom. Vrednosti celokupnega holesterola, LDL in HDL holesterola, trigliceridov, glukoze, fibrinogena ter visokoobčutljivega C-reaktivnega proteina (CRP) smo določili s standardnimi biokemijskimi postopki. Aterosklerozo karotidnih arterij smo ocenili z ultrazvokom in opredelili debelino intime in medije, tip plakov ter seštevek plakov

Molecular Mechanisms Responsible for Diastolic Dysfunction in Diabetes Mellitus Patients

In diabetic patients, cardiomyopathy is an important cause of heart failure, but its pathophysiology has not been completely understood thus far. Myocardial hypertrophy and diastolic dysfunction have been considered the hallmarks of diabetic cardiomyopathy (DCM), while systolic function is affected in the latter stages of the disease. In this article we propose the potential pathophysiological mechanisms responsible for myocardial hypertrophy and increased myocardial stiffness leading to diastolic dysfunction in this specific entity. According to our model, increased myocardial stiffness results from both cellular and extracellular matrix stiffness as well as cell–matrix interactions. Increased intrinsic cardiomyocyte stiffness is probably the most important contributor to myocardial stiffness. It results from the impairment in cardiomyocyte cytoskeleton. Several other mechanisms, specifically affected by diabetes, seem to also be significantly involved in myocardial stiffening, i.e., impairment in the myocardial nitric oxide (NO) pathway, coronary microvascular dysfunction, increased inflammation and oxidative stress, and myocardial sodium glucose cotransporter-2 (SGLT-2)-mediated effects. Better understanding of the complex pathophysiology of DCM suggests the possible value of drugs targeting the listed mechanisms. Antidiabetic drugs, NO-stimulating agents, anti-inflammatory agents, and SGLT-2 inhibitors are emerging as potential treatment options for DCM

Polymorphisms of the PPAR-γ (rs1801282) and Its Coactivator (rs8192673) Have a Minor Effect on Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

Background. The present study was designed to clarify whether common single nucleotide polymorphisms (SNPs) of the Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene (rs1801282) and the Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 (PGC-1α) gene (rs8192673) are associated with markers of carotid and coronary atherosclerosis in Caucasians with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled in the cross-sectional study. Markers of carotid atherosclerosis were assessed ultrasonographically. In 215 out of 595 subjects with T2DM, a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of either rs1801282 or rs8192673 was performed using KASPar assays. Results. In our study, we demonstrated an effect of the rs1801282 on markers of carotid atherosclerosis (presence of plaques) in Caucasians with T2DM in univariate and in multivariable linear regression analyses. Finally, we did not demonstrate any association between either rs1801282 or rs8192673 and markers of coronary atherosclerosis. Conclusions. In our study, we demonstrated a minor effect of the rs1801282 on markers of carotid atherosclerosis (presence of plaques) in Caucasians with T2DM. Moreover, we demonstrated a minor effect of the rs8192673 on CIMT progression in the 3.8-year follow-up in Caucasians with T2DM

Inflammatory and Prothrombotic Biomarkers, DNA Polymorphisms, MicroRNAs and Personalized Medicine for Patients with Peripheral Arterial Disease

Classical risk factors play a major role in the initiation and development of atherosclerosis. However, the estimation of risk for cardiovascular events based only on risk factors is often insufficient. Efforts have been made to identify biomarkers that indicate ongoing atherosclerosis. Among important circulating biomarkers associated with peripheral arterial disease (PAD) are inflammatory markers which are determined by the expression of different genes and epigenetic processes. Among these proinflammatory molecules, interleukin-6, C-reactive protein, several adhesion molecules, CD40 ligand, osteoprotegerin and others are associated with the presence and progression of PAD. Additionally, several circulating prothrombotic markers have a predictive value in PAD. Genetic polymorphisms significantly, albeit moderately, affect risk factors for PAD via altered lipoprotein metabolism, diabetes, arterial hypertension, smoking, inflammation and thrombosis. However, most of the risk variants for PAD are located in noncoding regions of the genome and their influence on gene expression remains to be explored. MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that modulate gene expression at the post-transcriptional level. Patterns of miRNA expression, to some extent, vary in different atherosclerotic cardiovascular diseases. miRNAs appear to be useful in the detection of PAD and the prediction of progression and revascularization outcomes. In conclusion, taking into account one’s predisposition to PAD, i.e., DNA polymorphisms and miRNAs, together with circulating inflammatory and coagulation markers, holds promise for more accurate prediction models and personalized therapeutic options

Strokovna stališča Slovenskega združenja za reproduktivno medicino (SZRM) o menopavzni medicini

Obravnava žensk v obdobju predmenopavze, ob menopavzi in kasneje se je v novem tisočletju pomembno spremenila. Randomizirane klinične raziskave so bistveno omejile indikacije za uvedbo hormonskega zdravljenja (HZ) in s tem menopavzno medicino postavile pred velik izziv. Na srečo so najnovejša dognanja potrdila, da je ob pravilni uporabi in izbiri HZ korist še vedno bistveno večja od tveganja. Zato smo pripravili posodobljena stališča o menopavzni medicini, ki so v skladu z aktualnimi mednarodnimi priporočili in prilagojena posebnostim slovenskega prostora

Influence of manual thrombus aspiration on left ventricular diastolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Introduction. Data on effects of thrombus aspiration on left ventricular diastolic function in ST-elevation myocardial infarction (STEMI) population are scarce. Objective. We sought to compare echocardiographic indices of the diastolic function and outcomes in STEMI patients treated with and without manual thrombus aspiration, in an academic, high-volume percutaneous coronary intervention (PCI) center. Methods. A total of 433 consecutive patients who underwent primary PCI in 2011-2012 were enrolled in the study. Patients were not eligible for the study if they already suffered a myocardial infarction, had been previously revascularized, received thrombolytics, presented with cardiogenic shock, had significant valvular disease, atrial fibrillation or had previously implanted pacemaker. Comprehensive echocardiogram was performed within 48 hours. During follow-up patients’ status was assessed by an office visit or telephone interview. Results. Patients treated with thrombus aspiration (TA+, n=216) had similar baseline characteristics as those without thrombus aspiration (TA-, n=217). Groups had similar total ischemic time (319 ± 276 vs. 333±372 min; p=0.665), but TA+ group had higher maximum values of troponin I (39.5 ± 30.5 vs. 27.6 ± 26.9 ng/ml; p<0.001). The echocardiography revealed similar left ventricular volumes and systolic function, but TA+ group had significantly higher incidence of E/e’>15, as a marker of severe diastolic dysfunction (TA+ 23.1% vs. TA- 15.2%; p=0.050). During average follow-up of 14Ѓ}5 months, major adverse cardiac/ cerebral events occurred at the similar rate (log rank p=0.867). Conclusion. Thrombus aspiration is associated with a greater incidence of severe diastolic dysfunction in unselected STEMI patients treated with primary PCI, but it doesn’t influence the incidence of major adverse cardiovascular events. [Projekat Ministarstva nauke Republike Srbije, br. 175099