From Cytokine Storm to Cytokine Breeze: Did Lessons Learned from Immunopathogenesis Improve Immunomodulatory Treatment of Moderate-to-Severe COVID-19?

Complex immune response to infection has been highlighted, more than ever, during the COVID-19 pandemic. This review explores the immunomodulatory treatment of moderate-to-severe forms of this viral sepsis in the context of specific immunopathogenesis. Our objective is to analyze in detail the existing strategies for the use of immunomodulators in COVID-19. Immunomodulating therapy is very challenging; there are still underpowered or, in other ways, insufficient studies with inconclusive or conflicting results regarding a rationale for adding a second immunomodulatory drug to dexamethasone. Bearing in mind that a "cytokine storm" is not present in the majority of COVID-19 patients, it is to be expected that the path to the adequate choice of a second immunomodulatory drug is paved with uncertainty. Anakinra, a recombinant human IL-1 receptor antagonist, is a good choice in this setting. Yet, the latest update of the COVID-19 Treatment Guidelines Panel (31 May 2022) claims that there is insufficient evidence to recommend either for or against the use of anakinra for the treatment of COVID-19. EMA's human medicines committee recommended extending the indication of anakinra to include treatment of COVID-19 in adult patients only recently (17 December 2021). It is obvious that this is still a work in progress, with few ongoing clinical trials. With over 6 million deaths from COVID-19, this is the right time to speed up this process. Our conclusion is that, during the course of COVID-19, the immune response is changing from the early phase to the late phase in individual patients, so immunomodulating therapy should be guided by individual responses at different time points.

Is Osteoarthritis Always Associated with Low Bone Mineral Density in Elderly Patients?

Background and Objectives: The relationship between osteoarthritis (OA) and osteoporosis (OP) has been analysed for over four decades. However, this relationship has remained controversial. Numerous observational and longitudinal studies have shown an inverse association between the two diseases and a protective effect of one against the other. On the other hand, some studies show that patients with OA have impaired bone strength and are more prone to fractures. The study's main objective was to determine the bone mineral density (BMD) of the spine and hip (femoral neck) of postmenopausal women of different ages, with radiologically determined OA of the hip and knee, as well as to determine the correlation between BMD values and age in the experimental group. Materials and Methods: The retrospective cohort study included 7018 patients with osteoarthritis of peripheral joints and the spine, examined by a rheumatologist in an outpatient rheumatology clinic at the Institute for Treatment and Rehabilitation, Niska Banja from July 2019 to March 2021. A nested anamnestic study was conducted within the cohort study of patients, and it included two groups: an experimental group composed of 60 postmenopausal women, and a control group composed of the same number of women. Out of 120 patients, 24 did not meet the criteria for the continuation of the study (due to technical errors­radiographic and/or densitometry artefacts). Fifty-six postmenopausal women (aged 45−77 years) with hip and knee radiological OA were examined as an experimental group. The participants were divided into two subgroups according to age (45−60 years and over 61 years). The control group included 40 healthy postmenopausal women of the same age range, without radiological OA, with normal BMD of the hip and spine. All patients with OA met the American College of Radiology (ACR) criteria. OA of the hip and knee was determined radiologically according to Kellgren and Lawrence (K&L) classification, and patients were included in the study if a K&L grade of at least ≥ 2 was present. Hip and spine BMD was measured by dual-energy X-ray absorptiometry (DXA). Results: Compared to the control group, we found statistically significantly lower BMD and T-scores of the spine in older postmenopausal women: BMD (g/cm2), p = 0.014; T-score, p = 0.007, as well as of the hip: BMD (g/cm2), p = 0.024; T-score p < 0.001. The values of BMD and T-score of the spine and hip are lower in more severe forms of OA (X-ray stage 3 and 4, according to K&L), p < 0.001. We found negative correlation between BMD and T-score and age only for the hip: BMD (g/cm2), ρ = 0.378, p = 0.005; T-score ρ = −0.349, p = 0.010. Conclusions: Older postmenopausal women with radiographic hip and knee OA had significantly lower BMD of the hip and spine as compared to the control group without OA, pointing to the need for the prevention and treatment of OA, as well as early diagnosis, monitoring, and treatment of low bone mineral density.

Low-Frequency Magnetic Resonance Imaging Identifies Hand Joint Subclinical Inflammation in Systemic Sclerosis.

Objectives: The aim of this work was to determine hand joint inflammation in systemic sclerosis (SSc); patients with rheumatoid arthritis (RA) with hand joint involvement were used as controls. Our investigation also aimed at examining the relationship between these subclinical inflammatory changes in the hands, verified by low-frequency MRI, and clinical (especially cardiopulmonary) manifestations, disease activity, and functional capacity in patients with diffuse cutaneous (dcSSc) and limited cutaneous SSc (lcSSc). Methods: Out of 250 SSc patients, the selection included 82 patients with signs and symptoms of joint involvement, and 35 consecutive RA patients. These patients underwent clinical and laboratory investigations, and hand X-ray and MRI of the dominant hand. Synovitis/tenosynovitis, bone edema, and erosions were investigated, and the bone changes were quantified and scored using the RAMRIS method. HAQ index, modified Rodnan skin score, examination of internal organ involvement, and serological markers for SSc, as well as rheumatoid factor (RF) and cyclic citrullinated peptides antibodies (ACPA), were performed on all experimental group subjects. Results: MRI of the dominant hand showed a significantly higher number of cases with synovitis (78%) than the number of patients with clinically swollen joints (17.1%; p < 0.001); bone edema was found in 62 (75.6%) SSc patients. MRI also showed a higher number of erosions (52; 63.4%) compared to those (22; 27.5%) detected with X-ray (p < 0.001). The average values of the total MRI score of synovitis/edema and erosions in the wrist (p < 0.001) and MCP joints (p < 0.001) were statistically higher in RA than in SSc patients (p < 0.001). The probability of the MRI-detected inflammatory changes was considerably higher in SSc patients who had vascular complications (digital ulceration, OR = 4.68; 95% IP: 1.002−22.25; p < 0.05), in patients with more severe functional impairment (OR = 8.22; 95% IP: 1.74−38.89; p < 0.01), and in patients with active disease (OR = 3.132; 95% IP: 1.027−9.551; p < 0.05). In our investigation, patients with a limited form of the disease and with inflammatory changes on MR more often had higher functional impairment compared to the other group without MRI inflammation. Conclusions: Our data show that in SSc MRI can detect a significant subclinical joint inflammation. RAMRIS confirmed the high degree of joint inflammation in RA, but also revealed a great deal of joint inflammation in SSc. That inflammation is associated with systemic inflammation (disease activity), vascular complications, and more severe forms of the disease, as synovitis cannot be precisely diagnosed by the clinical examination of joints. These results suggest that a careful joint investigation is necessary in SSc, and that in symptomatic patients, MRI may identify joint inflammation. In clinical practice, this evidence might drive to an early targeted therapy, thus preventing joint erosions.

A Discrepancy: Calcium Channel Blockers Are Effective for the Treatment of Hypertensive Left Ventricular Hypertrophy but Not as Effective for Prevention of Heart Failure.

Arterial hypertension (HTN) is important due to its high prevalence, morbidity, and mortality rates. Calcium channel blockers (CCBs) are the first-line antihypertensive drugs. HTN can lead to heart failure (HF) by causing hypertensive left ventricular hypertrophy (HTN LVH). CCBs are recommended for the treatment of HTN LVH. The aim of this study was to analyze the status of CCBs regarding (1) HTN LVH treatment and (2) capability to prevent HTN-induced HF in the guidelines. For this narrative review, the following databases were searched: Medline, Scopus, Science Direct, Springer, SAGE, Wiley, Oxford Journals, Cambridge, and Google Scholar. CCBs are effective antihypertensive drugs and a very good therapeutic option for HTN LVH as they can cause reverse LVH remodeling. Consequently, we may expect that CCBs would prevent HF. However, evidence suggests that CCBs confer less protection from HF than other first-line antihypertensive drugs. A negative inotropic action of nondihydropyridine CCBs may contribute to suboptimal protection against HF. This discrepancy is clinically relevant because CCBs are in one of the two recommended (single pill) combinations for the initial treatment of HTN. LVH is a strong risk factor for HF in HTN patients. When LVH arises, the risk of HF increases dramatically. CCBs are inferior to renin-angiotensin-aldosterone system blockers but still very effective in bringing about regression of HTN LVH; consequently, CCBs are expected to protect from HF. On the contrary, CCBs protect from HF less effectively than other first-line antihypertensive drugs. This discrepancy needs to be investigated further to improve clinical practice.

Beta Blockers can Mask not only Hypoglycemia but also Hypotension.

BACKGROUND: Beta-adrenergic (ß-AR) receptor blockers (BBs) are an essential class of drugs as they have numerous indications. On the other hand, they have numerous unwanted effects that decrease the compliance, adherence, and persistence of this very useful group of drugs. OBJECTIVE: The paper aims to analyze the possibility that an unnoticed side effect may contribute to a less favorable pharmacologic profile of BBs, e.g., a diminished reaction to a sudden fall in BP. METHODS: We searched two medical databases for abstracts and citations (Medline and SCOPUS). Moreover, we searched the internet for drug prescription leaflets (of the individual BBs). RESULTS: Whichever cause of stress is considered, the somatic manifestations of stress will be (partially) masked if a patient takes BB. Stress-induced hypercatecholaminemia acts on ß-AR of cardiomyocytes; it increases heart rate and contractility, effects suppressed by BBs. The answers of the organism to hypoglycemia and hypotension share the main mechanisms such as sympathetic nervous system activation and hypercatecholaminemia. Thus, there is a striking analogy: BBs can cover up symptoms of both hypoglycemia (which is widely known) and of hypotension (which is not recognized). It is widely known that BBs can cause hypotension. However, they can also complicate recovery by spoiling the defense mechanisms in hypotension as they interfere with the crucial compensatory reflex to increase blood pressure in hypotension. CONCLUSION: Beta blockers can cause hypotension, mask it, and make recovery more difficult. This is clinically important and deserves to be more investigated and probably to be stated as a warning.

Immunomonitoring of Monocyte and Neutrophil Function in Critically Ill Patients: From Sepsis and/or Trauma to COVID-19.

Immune cells and mediators play a crucial role in the critical care setting but are understudied. This review explores the concept of sepsis and/or injury-induced immunosuppression and immuno-inflammatory response in COVID-19 and reiterates the need for more accurate functional immunomonitoring of monocyte and neutrophil function in these critically ill patients. in addition, the feasibility of circulating and cell-surface immune biomarkers as predictors of infection and/or outcome in critically ill patients is explored. It is clear that, for critically ill, one size does not fit all and that immune phenotyping of critically ill patients may allow the development of a more personalized approach with tailored immunotherapy for the specific patient. In addition, at this point in time, caution is advised regarding the quality of evidence of some COVID-19 studies in the literature.

Diabetic Cardiomyopathy: Clinical and Metabolic Approach.

BACKGROUND: Having in mind that diabetes mellitus (DM) and obesity are some of the greatest health challenges of the modern era, diabetic cardiomyopathy (DCM) is becoming more and more recognized in clinical practice. Main Text: Initially, DM is asymptomatic, but it may progress to diastolic and then systolic left ventricular dysfunction, which results in congestive heart failure. A basic feature of this DM complication is the absence of hemodynamically significant stenosis of the coronary blood vessels. Clinical manifestations are the result of several metabolic disorders that are present during DM progression. The complexity of metabolic processes, along with numerous regulatory mechanisms, has been the subject of research that aims at discovering new diagnostic (e.g. myocardial strain with echocardiography and cardiac magnetic resonance) and treatment options. Adequate glycaemic control is not sufficient to prevent or reduce the progression of DCM. Contemporary hypoglycemic medications, such as sodium-glucose transport protein 2 inhibitors, significantly reduce the frequency of cardiovascular complications in patients with DM. Several studies have shown that, unlike the above-stated medications, thiazolidinediones and dipeptidyl peptidase-4 inhibitors are associated with deterioration of heart failure. CONCLUSION: Imaging procedures, especially myocardial strain with echocardiography and cardiac magnetic resonance, are useful to identify the early signs of DCM. Research and studies regarding new treatment options are still "in progress".

Electrocardiographic criteria which have the best prognostic significance in hypertensive patients with echocardiographic hypertrophy of left ventricle: 15-year prospective study.

BACKGROUND: Electrocardiography is the first-choice technique for detecting left ventricular hypertrophy in patients with arterial hypertension. It is necessary to know the probable outcome for every patient during the treatment, with the aim of improving cardiovascular event prevention. HYPOTHESIS: Certain electrocardiographic criteria for left ventricular hypertrophy may predict outcomes of patients with left ventricular hypertrophy during a 15-year follow-up. METHODS: Fifteen-year prospective study of 83 consecutive patients (53 male and 30 female; mean age 55.3 ± 8.1) with echocardiographic left ventricular hypertrophy (left ventricular mass index 170.3 ± 31.6 g/m2 ). Electrocardiographic left ventricular hypertrophy was determined by means of Gubner-Ungerleider voltage, Lewis voltage, voltage of R wave in aVL lead, Lyon-Sokolow voltage, Cornell voltage and Cornell product, voltage RV6 and RV5 ratio, Romhilt-Estes score, Framingham criterion and Perugia criterion. RESULTS: One or more composite events were registered in 32 (38.5%) patients during 15-year follow-up. Positive Lyon-Sokolow score (17.6% vs. 47.3%; P < 0.05), Lewis voltage (9.8% vs. 21.9%; P < 0.05), Cornell voltage (15.7% vs. 37.5%; P < 0.05), and Cornell product (9.8% vs. 34.4%; P < 0.01) were more frequent in a group of patients with composite events. Odd ratio for Cornell product was 4.819 (95% CI 1.486-15.627). CONCLUSION: Patients with echocardiographic left ventricular hypertrophy who had positive Lewis voltage, Lyon-Sokolow voltage, Cornell voltage, and Cornell product showed worse 15-year outcome. The strongest predictor of cardiovascular events was positive result of Cornell product.

Beta blocker rebound phenomenon is important, but we do not know its definition, incidence or optimal prevention strategies.

The aim of this review is to analyze whether there is a need for scientific information about the beta blocker (BB) rebound phenomenon; whether such information is available; and, if it is, how detailed is the BB rebound phenomenon explained in the guidelines and papers? A narrative review is used due to the lack of valid randomized clinical trials (RCTs) on the topic, which are needed for a meta-analysis. The BB rebound phenomenon can have dangerous consequences. The discontinuation of a BB leads to a fourfold increased risk of events related to coronary artery disease in hypertensive patients; it increases in-hospital mortality in heart failure patients; it can precipitate angina pectoris attack; and it increases the risk for death and rehospitalization in patients who survive acute myocardial infarction. Consequently, being considered in the guidelines, the BB rebound phenomenon is believed to be clinically relevant (by experts in the field). This is in sharp contrast with the lack of any additional relevant information about the BB rebound phenomenon in the various important guidelines. For example, we lack a consensus about the precise definition. Moreover, data about the incidence and optimal prevention strategies are lacking for the phenomenon (which is sometimes life-threatening). The BB rebound phenomenon is an additional reason why it is very important to test the prognosis of patients following the cessation of long-term medicaments in RCTs, particularly for BBs.

Predictors of Cardiovascular Events in Hypertensive Patients with High Cardiovascular Risk.

Background and objectives: A long-term therapeutic strategy in hypertensive patients equally depends on measured arterial blood pressure values and total determined cardiovascular risk. The aim of the adequate hypertensive patient treatment is both the reduction in arterial blood pressure and the reduction of all preexisting modifiable risk factors, prevention of target organs damage, and adverse cardiovascular events. The aim of this study was to determine independent predictors of cardiovascular events in patients with hypertension and high cardiovascular (CV) risk, and whether the modifiable risk factors could affect long-term prognosis in the studied population. Materials and Methods: This prospective study included 142 hypertensive patients (65% females), mean age 63.1±8 years, with high CV risk. Each participant was followed for 6.2 years. Results: During the follow-up period, the incidence of non-fatal and fatal CV events was 19.7%, CV mortality 7%, and total mortality 9.9%. Our multivariate analysis showed that plaques in both carotid arteries (p = 0.042), diabetes mellitus (p = 0.042) and cholesterol at the beginning of the study (p = 0.016) were significantly associated with an increased risk of CV events. Patients' age (p = 0.009), intima-media thickness (p = 0.001) and diabetes mellitus (p = 0.042) were significantly associated with an increased risk of CV mortality, and age (p = 0.007) and cholesterol (p = 0.002) were independent variables significantly associated with increased total mortality rates. Conclusions: The results of the present study showed that the main predictors of adverse CV events in high-risk hypertensive patients were years of age, cholesterol levels, diabetes, intima-media thickness, and carotid arteries plaques.

Using Semantic Web Technologies to Enable Cancer Genomics Discovery at Petabyte Scale.

Increased efforts in cancer genomics research and bioinformatics are producing tremendous amounts of data. These data are diverse in origin, format, and content. As the amount of available sequencing data increase, technologies that make them discoverable and usable are critically needed. In response, we have developed a Semantic Web-based Data Browser, a tool allowing users to visually build and execute ontology-driven queries. This approach simplifies access to available data and improves the process of using them in analyses on the Seven Bridges Cancer Genomics Cloud (CGC; www.cancergenomicscloud.org). The Data Browser makes large data sets easily explorable and simplifies the retrieval of specific data of interest. Although initially implemented on top of The Cancer Genome Atlas (TCGA) data set, the Data Browser's architecture allows for seamless integration of other data sets. By deploying it on the CGC, we have enabled remote researchers to access data and perform collaborative investigations.

Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia?

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet count (MPV/PC) ratio are readily available parameters that might have discriminative power regarding outcome. The aim of our study was to assess prognostic value of these biomarkers regarding outcome in critically ill patients with secondary sepsis and/or trauma. METHODS: A total of 392 critically ill and injured patients, admitted to surgical ICU, were enrolled in a prospective observational study. Leukocyte and platelet counts were recorded upon fulfilling Sepsis-3 criteria and for traumatized Injury Severity Score > 25 points. Patients were divided into four subgroups: peritonitis, pancreatitis, trauma with sepsis, and trauma without sepsis. RESULTS: NLR and MPV/PC levels were significantly higher in nonsurvivors (AUC/ROC of 0.681 and 0.592, resp., in the peritonitis subgroup; 0.717 and 0.753, resp., in the pancreatitis subgroup); MLR and PLR did not differ significantly. There was no significant difference of investigated biomarkers between survivors and nonsurvivors in trauma patients with and without sepsis except for PLR in the trauma without sepsis subgroup (significantly higher in nonsurvivors, AUC/ROC of 0.719). Independent predictor of lethal outcome was NLR in the whole cohort and in the peritonitis subgroup as well as MPV in the pancreatitis subgroup. Also, there were statistically significant differences in MPV/PC, MLR, and PLR values regarding nature of bacteremia. In general, the lowest levels had been found in patients with Gram-positive blood cultures. CONCLUSIONS: NLR and MPV were very good independent predictors of lethal outcome. For the first time, we demonstrate that nature of bacteremia influences MPV/PC, MLR, and PLR. In heterogeneous cohort subgroup, analysis is essential.

Significance of asymptomatic hyperuricemia in patients after coronary events.

The goal of the present study was to determine the prevalence of hyperuricemia in patients with coronary artery disease (CAD), within three months after coronary events. Also, we aimed to determine whether the presence of hyperuricemia holds correlation with severe CAD, overall heart functioning and risk factors for CAD. The study included 505 consecutive CAD patients, 385 males and 120 females, aged 60.9 ± 9.6 years, with a mean body mass index (BMI) 28.0 ± 3.7 kg/m2. All patients were admitted to specialized cardiovascular rehabilitation within three months post-acute myocardial infarction (AMI) without revascularization (32.6%), percutaneous coronary intervention (PCI) with myocardial infarction (32.1%) and with coronary bypass graft (35.3%). The mean value of serum acidum uricum (SUA) was 345.5 ± 100.3 µmol/L, where 115 (22.8%) patients had asymptomatic hyperuricemia. Patients with asymptomatic hyperuricemia had significantly higher average number of risk factors, lower HDL cholesterol and higher creatinine and triglycerides levels, lower ejection fraction (EF). Multivariate stepwise analysis revealed that five parameters were capable to predict SUA levels. We can conclude that in patients with CAD, SUA levels are independently associated with BMI, triglyceride and creatinine levels and negatively with EF. Thus, one can say that asymptomatic hyperuricemia is not significantly associated with the severity of CAD.

Sodium-glucose Cotransporter 2 Inhibitors: Potential Cardiovascular and Mortality Benefits.

BACKGROUND: The impact of overt diabetes and poor glycemic control on the risk of cardiovascular disease is well established. Among patients with type 2 diabetes, several studies demonstrated a significant increase in coronary artery disease-related death and cardiovascular events associated with HbA1c levels of greater than 7% compared with lower levels. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion. OBJECTIVES: To summarize data on the potential mechanisms of SGLT-2 inhibition that could exert cardiovascular benefits in patients with diabetes mellitus. METHOD: We conducted an in-depth literature search of SGLT-2 inhibitors and potential cardiovascular benefits and mechanisms that mediate those effects. RESULTS: In diabetes, expression of the SGLT-2 genes is up-regulated and renal threshold increased, resulting in increased glucose reabsorption from glomerular filtrate, reducing urinary glucose excretion and worsening hyperglycemia. SGLT-2 inhibition should offer potential cardiovascular protection in diabetic patients via attenuating hyperglycemia, blood pressure, body weight, hyperuricemia, and diabetic nephropathy. CONCLUSION: The initial data of SGLT-2 inhibitors suggest beneficial effects on cardiovascular risk among patients with diabetes mellitus. Several mechanisms are hypothesized to mediate the abovementioned benefits. Future randomized, controlled studies are needed in order to unveil the contribution of each mechanism to these outcomes.

Impact of metabolic syndrome on clinical severity and long-term prognosis in patients with myocardial infarction with ST-segment elevation.

AIMS: The aim of this study is to evaluate the impact of metabolic syndrome (MetS) on clinical severity and long-term prognosis in patients with myocardial infarction with ST-segment elevation (STEMI). METHODS: We examined 507 patients with STEMI, who were admitted for primary percutaneous coronary intervention classified according to the presence of MetS using American Heart Association and the National Heart, Lung, and Blood Institute definition. After applying these criteria, the patients were categorized into groups as patients with MetS and without MetS. We compared baseline characteristics, clinical findings, and outcomes between these groups. During the 48-month follow-up, we collected data about major adverse cardiac events (MACE) and mortality. RESULTS: The MetS group comprised 217 patients with MetS (mean age = 60.71 ± 11.52 years; 59 females), while the control group comprised 290 subjects (mean age = 57.50 ± 10.95 years; 54 females). The patients with and without MetS had similar parameters of clinical severity of STEMI but differed in severe coronary artery disease. During the follow-up period, a significantly higher percentage of myocardial infarction (6.91% vs 2.06%) and new revascularization (16.59% vs 8.97%) was recorded in the MetS group. On multivariate analysis, MetS was independently associated with MACE (HR = 1.834, 95% CI = 1.162-2.896, p = 0.009) but not with mortality (HR = 1.603, 95% CI = 0.864-2.973, p = 0.134). Among cardiovascular events that compose MACE, MetS was associated with new revascularization (HR = 2.204, 95% CI = 1.273-3.815, p=0.005). CONCLUSION: The presence of MetS in patients with STEMI is an independent risk factor for MACE, and this syndrome is strongly associated with new revascularization.

Predictive value of metabolic syndrome definitions in patients with myocardial infarction with ST segment elevation - are they all the same?

OBJECTIVES: We sought to determine the predictive power of metabolic syndrome (MS) definitions on the prognosis in patients with myocardial infarction with ST-segment elevation (STEMI). METHODS: We prospectively included 507 patients with STEMI who were admitted for primary percutaneous coronary intervention and could be identified for MS using the AHA-NHLBI, NCEP-ATP III and IDF definitions. After applying these criteria, we divided the group in patients with MS and without MS; we compared baseline characteristics, clinical findings and outcomes among these patients. RESULTS: The prevalence of MS was lowest with the NCEP-ATP III definition (37.87%), followed by the AHA-NHLBI definition (42.80%) and highest when using the IDF definition (44.38%). During follow-up, the occurrence of new myocardial infarction and new revascularization was significantly higher in patients with MS. Only in a group of patients with MS according to the NCEP-ATP III definition, a higher number of strokes were recorded. Multivariate analysis shows that MS according to the NCEP-ATP III definition was an independent predictor for MACE (OR 1.830, 95% CI 1.238-2.704, p = .002) but not for mortality. CONCLUSION: Metabolic syndrome according to the NCEP-ATP III definition was associated with increased risk of the development of new cardiovascular events among the patients with STEMI.