Serum and Echocardiographic Markers May Synergistically Predict Adverse Cardiac Remodeling after ST-Segment Elevation Myocardial Infarction in Patients with Preserved Ejection Fraction.

Improvement of risk scoring is particularly important for patients with preserved left ventricular ejection fraction (LVEF) who generally lack efficient monitoring of progressing heart failure. Here, we evaluated whether the combination of serum biomarkers and echocardiographic parameters may be useful to predict the remodeling-related outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and preserved LVEF (HFpEF) as compared to those with reduced LVEF (HFrEF). Echocardiographic assessment and measurement of the serum levels of NT-proBNP, sST2, galectin-3, matrix metalloproteinases, and their inhibitors (MMP-1, MMP-2, MMP-3, TIMP-1) was performed at the time of admission (1st day) and on the 10th-12th day upon STEMI onset. We found a reduction in NT-proBNP, sST2, galectin-3, and TIMP-1 in both patient categories from hospital admission to the discharge, as well as numerous correlations between the indicated biomarkers and echocardiographic parameters, testifying to the ongoing ventricular remodeling. In patients with HFpEF, NT-proBNP, sST2, galectin-3, and MMP-3 correlated with the parameters reflecting the diastolic dysfunction, while in patients with HFrEF, these markers were mainly associated with LVEF and left ventricular end-systolic volume/diameter. Therefore, the combination of the mentioned serum biomarkers and echocardiographic parameters might be useful for the prediction of adverse cardiac remodeling in patients with HFpEF.

Adipocytes Directly Affect Coronary Artery Disease Pathogenesis via Induction of Adipokine and Cytokine Imbalances.

This study aimed to investigate the adipokine and cytokine profiles of adipocytes from epicardial and subcutaneous adipose tissues in interconnection with the visceral adipose tissue area and the biochemical and clinical characteristics of patients with coronary artery disease. We assessed 84 patients with coronary artery disease (65 men, 19 women) and divided them into two groups based on the presence of visceral obesity. We sampled epicardial and subcutaneous adipose tissues from the patients with visceral obesity. We then cultured the adipocytes and evaluated their adipokine profiles and pro-inflammatory activity. Results show that the mRNA expression of adiponectin in cultures of epicardial adipocytes from patients with and without visceral obesity was lower than that in subcutaneous adipocytes. Moreover, adiponectin mRNA expression in cultures of subcutaneous and epicardial adipocytes from patients with visceral obesity was lower than that in patients without obesity. For leptin, the reverse pattern was observed, with expression higher in cultures of epicardial adipocytes than in subcutaneous adipocytes and higher in epicardial adipocytes from patients with visceral obesity than in those from subjects without visceral obesity. In addition, in epicardial adipocytes, increased expression of proinflammatory cytokine genes (IL6, TNF) was observed compared with that in subcutaneous adipocytes. In contrast, expression of IL10 was higher in cultures of subcutaneous adipocytes than in epicardial adipocytes. The epicardial adipose tissue area was associated with the presence of higher levels of leptin and TNF-α within adipocytes and serum, increased lipid and carbohydrate metabolism. Coronary artery disease, in the context of the status of epicardial adipocytes, can be characterized as "metabolic inflammation," suggesting the direct involvement of adipocytes in pathogenesis through the development of adipokine imbalances and activation of proinflammatory processes.

Biological markers and cardiac remodelling following the myocardial infarction.

AIM: To assess growth stimulating factor ST2 and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels in the sera of myocardial infraction (MI) patients, and their correlation with the adaptive and maladaptive variants of cardiac remodelling. METHODS: 87 patients (65 male, 22 females; 67±8.36 years) with ST-elevated MI were included in this study, and 67 patients had an adaptive, physiological, while 20 patients had a maladaptive, pathological variant of myocardium remodelling. RESULTS: On day 1, ST2 and NT-proBNP levels were shown to increase 2.4 and 4.5 folds, respectively, compared with those in the control. ST2 levels in patients with maladaptive remodelling were 1.5-fold higher than those in the adaptive remodelling group. On day 12, a decrease in ST2 levels was observed in both groups. NT-proBNP levels increased 1.8 folds in both groups on day 1, compared with those in the controls. Increased ST2 levels on day 1 after MI were shown to increase the risk of maladaptive remodelling 4.5 folds, while high NT-proBNP levels increased this risk 2.3 times. CONCLUSIONS: ST2 level determination allows us to predict the risk of maladaptive remodelling with a higher sensitivity and specificity than using NT-proBNP levels.

Effect of different doses of statins on the development of type 2 diabetes mellitus in patients with myocardial infarction.

BACKGROUND: Cardiovascular diseases and type 2 diabetes mellitus (T2DM) may have common developmental mechanisms associated with lipid metabolism disorders. Dyslipidemia and progression of atherosclerosis in people with T2DM are accompanied by an increase in cardiovascular mortality. This study examined the dose-dependent action of atorvastatin on carbohydrate metabolism and adipokine status in patients within 12 months after myocardial infarction (MI). METHODS: A total of 156 male MI patients who had received atorvastatin 20 mg/day (78 patients) or 40 mg/day (78 patients) starting from day 1 of onset were enrolled. Glucose, insulin, C-peptide, resistin, adiponectin, and ghrelin levels were measured at baseline, day 12, and months 3 and 12. Patients were monitored for new incidences of T2DM for 12 months after MI. RESULTS: For acute phase MI, patients had moderate insulin resistance, hyperglycemia, and hyper-insulinemia, high leptin and resistin levels, and low ghrelin and adiponectin levels. Atorvastatin 20 mg/day was more effective at correcting the imbalances. Patients taking atorvastatin 40 mg/day (group 2) following MI showed increases in levels of glucose, insulin, and C-peptide and insulin resistance progression after 12 months of therapy, as evidenced by increased quantitative insulin sensitivity check index scores and detection of new T2DM cases. CONCLUSION: Atorvastatin improved adipokine profiles and ghrelin levels, with low doses showing more significant effects. Atorvastatin dose prescribed for MI patients should take into account the degree of insulin resistance and adipokine status.

Serum neutrophil gelatinase-associated lipocalin the estimation of hospital prognosis in patients with ST-elevated myocardial infarction.

We aimed to assess the clinical significance of serum levels of neutrophil gelatinase-associated lipocalin (sNGAL) for predicting in-hospital outcomes in patients with ST-elevated myocardial infarction (STEMI). Patients admitted within 24 hours of developing STEMI clinical symptoms were evaluated for sNGAL on hospitalization days 1 and 12. Recurrent myocardial infarction, early post-infarction angina, acute cerebrovascular accident, and death were assessed as adverse outcomes during hospitalization. The actors associated with adverse outcome were evaluated using univariate and multivariate regression analysis. Among the 260 STEMI patients included, 32% had ≥1 adverse in-hospital outcome, and significantly higher sNGAL on day 12, (but not on day 1) compared to sNGAL in patients with favorable outcome (p = 0.033). Type-2 diabetes mellitus, age > 60 years, reduced glomerular filtration rate during hospitalization, and high sNGAL on day 12 were identified as risk factors for adverse in-hospital outcome, associated with a 14% increase for each 1-year increment in age after 60 years, and a dramatic increase (3.2 times) for high sNGAL on day 12, with sNGAL ≥ 1.046 ng/ml indicating complicated hospitalization course. sNGAL concentration on the 12th day was associated with the existing adverse outcomes, acting as a marker of MI severity.

Serum neutrophil gelatinase-associated lipocalin has an advantage over serum cystatin C and glomerular filtration rate in prediction of adverse cardiovascular outcome in patients with ST-segment elevation myocardial infarction.

BACKGROUND: The aim of this study was to assess significance of serum neutrophil gelatinase-associated lipocalin (sNGAL) and cystatin C (sCC) in prediction of adverse cardiovascular outcome after ST-segment elevation myocardial infarction (STEMI). METHODS: We recruited 357 consecutive patients who were admitted to the hospital within 24 h after onset of STEMI. On the 1st and 12th-14th day after hospital admission, we measured levels of sNGAL and sCC. We also determined presence of renal dysfunction (RD), defined as glomerular filtration rate < 60 mL/min/1.73 m2. After 3 years of follow-up, we performed a logistic regression and assessed the value of RD, sNGAL, and sCC in prediction of combined endpoint, defined as cardiovascular death or any cardiovascular complication. RESULTS: RD, sCC level ≥ 1.9 mg/L, and sNGAL level ≥ 1.25 ng/mL on the 12th-14th day of hospitalization were associated with a 1.6-fold, 1.9-fold, and 2.9-fold higher risk of adverse cardiovascular outcome, respectively. Area under the ROC curve was the highest for the model based on sNGAL level compared to the models based on sCC level or RD presence. CONCLUSIONS: Measurement of sNGAL level in patients with STEMI on the 12th-14th day after hospital admission may improve prediction of adverse cardiovascular outcome.

Biochemical markers of type 2 diabetes as a late complication of myocardial infarction: a case-control study.

INTRODUCTION: On average, 19-23% of patients with acute myocardial infarction (MI) suffer from type 2 diabetes mellitus, which is newly diagnosed in a significant number of patients. Both classic carbohydrate metabolism and lipid metabolism may be promising diagnostic markers for insulin resistance in acute coronary syndrome. MATERIAL AND METHODS: Two hundred patients (130 males and 70 females aged 61.4 ±1.12 years) with ST-segment elevation MI were included in the study. Patients were divided into two groups based on manifestations of diabetes: (1) 171 patients without diabetes within 1 year after MI; and (2) 29 patients with manifestations of diabetes. The control group comprised 33 people without diseases of the cardiovascular system and diabetes and was matched by age and gender with patients. RESULTS: In patients with an imbalanced adipokine state during the acute phase of MI, we noted an increased concentration of free fatty acids (p > 0.05) and reduced ghrelin levels (p > 0.05) and activation of the proinflammatory and thrombotic potentials of blood plasma. Patients who developed diabetes 1 year after MI showed hospital stays with more pronounced changes in the study parameters. CONCLUSIONS: The most informative biochemical parameters associated with the development of diabetes at 1 year after MI were adiponectin, retinol protein, ghrelin, tumor necrosis factor α, and plasminogen activator inhibitor.

Relationship key factor of inflammation and the development of complications in the late period of myocardial infarction in patients with visceral obesity.

BACKGROUND: Cytokines play an significant role in regulating non-specific inflammatory response involved in many pathological processes. The current study tested the hypothesis that myocardial infarction in patients with obesity can lead to increased production of proinflammatory cytokines and unfavorable course of the pathological process. METHODS: The study recruited 232 male patients with ST-elevated myocardial infarction. The mean age of the patients was 58.7 (52.2-69.9) years. All the patients were assigned to two groups according to the computed tomography findings: 1 (n = 160) patients with visceral obesity (VO), and 2 (n = 72) patients without VO. Interleukins were measured in blood serum on days 1 and 12 after MI. RESULTS: All patients with MI demonstrated elevated levels of proinflammatory markers and reduced anti-inflammatory markers in the in-hospital period. The results suggested that among all studied inflammatory markers IL-6 (OR 1.9; 95% CI (1.6-2.8) and CRP (OR 1.3; 95% CI (1.1-1.8) were closely related to VO. One year after MI adverse cardiovascular outcome frequently occurred in patients with VO. There were two cardiac deaths (3.1%), 6 cases (9.3%) of recurrent MI, 19 cases (29.6%) of repeated hospitalizations for unstable angina, whereas only 2 patients without VO (6.6%) were hospitalized for unstable angina. The results of the logistic regression analysis demonstrated that IL-6, IL-12, and IL-10 had the highest predictive value for occurrence of adverse cardiovascular events in patients with VO. CONCLUSION: Cytokine profile in MI patients with VO is characterized by an imbalance caused by elevated pro-inflammatory interleukins and decreased anti-inflammatory interleukins. Obesity in patients was associated with a marked increase in IL-6 and CRP levels.

Early Effects of Treatment Low-Dose Atorvastatin on Markers of Insulin Resistance and Inflammation in Patients with Myocardial Infarction.

Dyslipidemia is one of the primary causes of cardiovascular disease. Therefore, attention has been focused on the development of drugs that normalize lipid levels and exert an effect on markers of atherothrombosis, insulin resistance (IR), and inflammation. Atorvastatin is a drug with not only lipid-lowering potential, but it has multiple non-lipid effects. This study aimed to evaluate atorvastatin effects on lipid, adipokine, IR, and inflammatory statuses in patients with myocardial infarction (MI) in an in-hospital setting. This study included 66 patients with confirmed ST-segment elevation MI, who were treated with atorvastatin 20 mg/day starting on day 1 of MI, without any dose changes. The comparison group consisted of 60 patients receiving standard anti-anginal and anti-thrombotic therapy. During the hospital stay, both groups showed a reduction in total cholesterol level and free fatty acids and increased concentrations of apolipoprotein A, especially those patients receiving atorvastatin. On day 1 of MI, patients in both groups had elevated levels of leptin by 2.9- to 3.3-fold, but the leptin levels decreased by 40.3% and were significantly lower than in patients not taking statins. The treatment with atorvastatin was associated with a decrease in C-reactive protein and interleukin-6 by 23.1 and 49.2%, respectively, compared with baseline values. In the group of patients on standard therapy, there was a decrease of interleukin-6 by 31.7%. Atorvastatin administered early on during hospitalization to patients with MI contributed to the improvement of lipid, adipokine and pro-inflammatory statuses and decreased IR.

Glucose levels as a prognostic marker in patients with ST-segment elevation myocardial infarction: a case-control study.

BACKGROUND: Patients with myocardial infarction (MI) have a high mortality. Therefore, new risk markers and predictors of an adverse outcome for MI are required. The role of hyperglycemia in the development of cardiovascular complications in MI patients is still unclear. METHODS: A total of 529 consecutive patients with the diagnosis of ST-segment elevation acute coronary syndrome within 24 h of the onset of symptoms were included in the study. All of the patients underwent blood glucose measurement at admission to hospital. The glycemic profile, including measurement of blood glucose levels early in the night and in the morning (3 a.m. and 5 a.m.), was assessed in 77 patients with diabetes on days 6-10 of the course of MI to monitor the efficiency of blood glucose-lowering therapy and to detect hypoglycemic episodes. RESULTS: In-hospital mortality showed relationship between the level of blood glucose on admission and in-hospital mortality in patients with MI with ST-segment elevation in combination with diabetes mellitus. There was a direct linear relationship between blood glucose levels and in-hospital mortality in patients without diabetes. CONCLUSION: Episodes of hypoglycemia recorded in MI patients with diabetes in the hospital stage of treatment do not determine the prognosis, but enable identification of patients with an unfavorable course in the postinfarction period.

Prognostic Value of Soluble ST2 During Hospitalization for ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Studying the role of soluble ST2 (sST2) during hospitalization for myocardial infarction (MI) can be helpful for predicting the course of the hospitalization and development of complications. METHODS: We included 88 patients with MI (median age, 58 yr). Depending on the course of the hospitalization, the patients were divided into two groups: the favorable (n=58) and unfavorable (n=30) outcome groups. On days 1 and 12 after MI, serum sST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured by ELISA. RESULTS: On day 1, the concentrations of sST2 and NT-proBNP increased 2.4- and 4.5-fold, compared with the controls. Measurements on day 12 showed a significant decrease in the sST2 level (P=0.001), whereas the NT-proBNP level did not change. On day 1, the sST2 level in the unfavorable outcome group was 2-fold higher than that in the favorable outcome group and 3.7-fold higher than in the controls. On day 12, the marker level decreased in both groups. On day 1, the NT-proBNP level in the unfavorable outcome group was 6.8-fold higher than in the controls and 1.8-fold higher than in the favorable outcome group. On day 12, the level of NT-proBNP remained elevated in both groups. Determining the levels of both sST2 and NT-proBNP increases their diagnostic significance (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.7-3.2; areas under curve [AUC] 0.89; P=0.004). CONCLUSIONS: The level of sST2 is a more sensitive indicator during MI hospitalization than NT-proBNP.

Serum Galectin and Renal Dysfunction in ST-Segment Elevation Myocardial Infarction.

This study aimed to evaluate the association between serum galectin levels and renal dysfunction in relation to in-hospital prognosis and unfavorable prognosis 1 year after ST-elevated myocardial infarction (STEMI). Patients were assigned to two groups according to the cystatin C-based estimate of GFR on day 12 after STEMI: (1) STEMI patients with normal renal function (GFR based on cystatin C levels = 60 mL/min/1.73 m(2)) and (2) those with renal dysfunction (RD) (GFR based on cystatin C levels <60 mL/min/1.73 m(2)). A decrease in GFR estimated from the CKD-EPI equation on day 12 was more frequently found in patients with a reduced GFR based on cystatin C levels (41.9%) compared with those without RD (21.3%). Galectin levels exceeded the cut-off value (17.8 ng/mL) in 50.6% of cases in the group with GFR <60 mL/min/1.73 m(2) and in 32% of cases in the group with a normal GFR. The presence of RD and elevated galectin levels >17.8 ng/mL on day 12 after MI are independent predictors of an adverse prognosis at 1 year in STEMI patients. Elevated galectin levels are directly correlated with the presence of early postinfarction angina.

The role of adipose tissue and adipokines in the manifestation of type 2 diabetes in the long-term period following myocardial infarction.

BACKGROUND: This study aimed to evaluate the markers of insulin resistance and adipokine status in patients with visceral obesity during hospitalization following myocardial infarction (MI) and assess the disturbances of carbohydrate metabolism present 1 year after MI onset. METHODS: 94 male patients with MI were recruited. The exclusion criteria were as follows: age less than 50 or greater than 80 years, the presence of type 2 diabetes mellitus (T2DM), and a prior history of pronounced renal failure.Obesity types were defined according to body mass index (BMI), waist circumference (WC) and visceral adipose tissue (VAT) area. Glucose, insulin, adiponectin, leptin, and insulin resistance (IR) index were measured on days 1 and 12 after the onset of MI. New-onset type 2 diabetes was assessed 1 year after MI onset. RESULTS: According to computed tomography assessments of all study patients, 69 % of patients with MI suffered from visceral obesity. The VAT area was more closely associated with the risk of developing type 2 diabetes compared with the obesity parameters, BMI and WC. Patients with a VAT area greater than 130 cm(2) had a 3.6-fold higher risk of developing type 2 diabetes. The presence of IR and hyperleptinemia increased the risk of developing diabetes in the post-MI period 3.5 and 3.7 times, respectively, in patients with visceral obesity compared with patients without visceral obesity. CONCLUSION: Visceral obesity is associated with IR, a 5.7-fold increase in leptin levels and a high risk of developing type 2 diabetes 1 year after MI onset.

Dose-dependent effects of atorvastatin on myocardial infarction.

BACKGROUND: Dyslipidemia is a key factor determining the development of both myocardial infarction (MI) and its subsequent complications. Dyslipidemia is associated with endothelial dysfunction, activation of inflammation, thrombogenesis, and formation of insulin resistance. Statin therapy is thought to be effective for primary and secondary prevention of complications associated with atherosclerosis. METHODS: This study examined 210 patients with Segment elevated MI (ST elevated MI) who were treated with atorvastatin from the first 24 hours after MI. Group 1 (n=110) were given atorvastatin 20 mg/day. Group 2 (n=100) were given atorvastatin 40 mg/day. At days 1 and 12 after MI onset, insulin resistance levels determined by the homeostasis model assessment of insulin resistance index, lipid profiles, and serum glucose, insulin, adipokine, and ghrelin levels were measured. RESULTS: Free fatty acid levels showed a sharp increase during the acute phase of MI. Treatment with atorvastatin 20 mg/day, and especially with 40 mg/day, resulted in a decrease in free fatty acid levels. The positive effect of low-dose atorvastatin (20 mg/day) is normalization of the adipokine status. Administration of atorvastatin 20 mg/day was accompanied with a statistically significant reduction in glucose levels (by 14%) and C-peptide levels (by 38%), and a decrease in the homeostasis model assessment of insulin resistance index on day 12. CONCLUSION: Determination of atorvastatin dose and its use during the in-hospital period and subsequent periods should take into account changes in biochemical markers of insulin resistance and adipokine status in patients with MI.

Multivessel coronary artery disease, free fatty acids, oxidized LDL and its antibody in myocardial infarction.

BACKGROUND: Free fatty acids (FFA), oxidized low-density lipoprotein (LDL) and its antibodies, lipid profile markers, which are formed under oxidative stress, play an important role in atherosclerotic disease. Assess the levels of these markers in myocardial infarction patients depending on the extent of coronary artery disease (CAD). METHODS: ST-elevation MI patients with hemodynamically significant stenoses of ≥ 75% in one, two, three, or more coronary arteries were examined. The patients were divided into three groups according to the severity of coronary lesions. Patients had a ≥ 75% stenotic lesion in one coronary artery (group 1, n=135), two coronary arteries (group 2, n=115), or three or more coronary arteries (group 3, n=150). The control group comprised healthy subjects (n=33). RESULTS: FFA levels on day 1 from MI onset were higher in groups 1, 2, and 3 compared with controls. On day 1 from MI onset, oxidized LDL levels were significantly higher in groups 2 and 3 than those in controls (both р=0.001). Oxidized LDL levels were significantly higher in patients with multivessel CAD compared with those with single-vessel CAD on days 1 and 12. Antibody levels increased with the number of affected arteries. CONCLUSION: High levels FFA, oxidized LDL and its antibody, lipid profile markers, and parameters of the pro/antioxidant systems persist during the subacute phase of MI.