The Importance of Lung Ultrasound and IGFBP7 (Insulin-like Growth Factor Binding Protein 7) Assessment in Diagnosing Patients with Heart Failure.

Background: In daily practice, there are problems with adequately diagnosing the cause of dyspnea in patients with heart failure with preserved and mildly reduced ejection fractions (HFpEF and HFmrEF). This study aimed to assess the usefulness of lung ultrasound in diagnosing HFpEF and HFmrEF and determine its correlation with IGFBP7 (insulin-like growth factor binding protein 7), NTproBNP (N-terminal pro-B-type natriuretic peptide), and echocardiographic markers. Methods: The research was conducted on 143 patients hospitalized between 2018 and 2020, admitted due to dyspnea, and diagnosed with HFpEF and HFmrEF. Venous blood was collected from all participants to obtain basic biochemical parameters, NTproBNP, and IGFBP7. Moreover, all participants underwent echocardiography and transthoracic lung ultrasound. Two years after hospitalization a follow-up telephone visit was performed. Results: The number of B-lines in the LUS ≥ 16 was determined with a sensitivity of-73% and specificity of-62%, indicating exacerbation of heart failure symptoms on admission. The number of B-lines ≥ 14 on admission was determined as a cut-off point, indicating an increased risk of death during the 2-year follow-up period. The factors that significantly impacted mortality in the study patient population were age and the difference between the number of B-lines on ultrasound at admission and at hospital discharge. IGFBP7 levels had no significant effect on the duration of hospitalization, risk of rehospitalization, or mortality during follow-up. Conclusions: Lung ultrasonography provides additional diagnostic value in patients with HFpEF or HFmrEF and exacerbation of heart failure symptoms. The number of B-lines ≥ 14 may indicate an increased risk of death.

Myostatin and the Heart.

Myostatin (growth differentiation factor 8) is a member of the transforming growth factor-ß superfamily. It is secreted mostly by skeletal muscles, although small amounts of myostatin are produced by the myocardium and the adipose tissue as well. Myostatin binds to activin IIB membrane receptors to activate the downstream intracellular canonical Smad2/Smad3 pathway, and additionally acts on non-Smad (non-canonical) pathways. Studies on transgenic animals have shown that overexpression of myostatin reduces the heart mass, whereas removal of myostatin has an opposite effect. In this review, we summarize the potential diagnostic and prognostic value of this protein in heart-related conditions. First, in myostatin-null mice the left ventricular internal diameters along with the diastolic and systolic volumes are larger than the respective values in wild-type mice. Myostatin is potentially secreted as part of a negative feedback loop that reduces the effects of the release of growth-promoting factors and energy reprogramming in response to hypertrophic stimuli. On the other hand, both human and animal data indicate that myostatin is involved in the development of the cardiac cachexia and heart fibrosis in the course of chronic heart failure. The understanding of the role of myostatin in such conditions might initiate a development of targeted therapies based on myostatin signaling inhibition.

Multivessel Coronary Artery Disease Complicated by Diabetes Mellitus Has a Relatively Small Effect on Endothelial and Lipoprotein Lipases Expression in the Human Atrial Myocardium and Coronary Perivascular Adipose Tissue.

Endothelial (EL) and lipoprotein (LPL) lipases are enzymes involved in lipoproteins metabolism and formation of atherosclerosis, a pathological feature of coronary artery disease (CAD). This paper examines the role of the lipases in the right atrial appendage (RAA) and coronary perivascular adipose tissue (PVAT) of patients with CAD alone or with accompanying diabetes. Additionally, correlation analysis for plasma concentration of the lipases, apolipoproteins (ApoA-ApoJ) and blood lipids (Chol, HDL-C, LDL-C, TAG) was performed. We observed that CAD had little effect on the lipases gene/protein levels in the RAA, while their transcript content was elevated in the PVAT of diabetic CAD patients. Interestingly, the RAA was characterized by higher expression of EL/LPL (EL: +1-fold for mRNA, +5-fold for protein; LPL: +2.8-fold for mRNA, +12-fold for protein) compared to PVAT. Furthermore, ApoA1 plasma concentration was decreased, whereas ApoC1 and ApoH were increased in the patients with CAD and/or diabetes. The concentrations of ApoC3 and ApoD were strongly positively correlated with TAG content in the blood, and the same was true for ApoB with respect to LDL-C and total cholesterol. Although plasma concentrations of EL/LPL were elevated in the patients with diabetes, CAD alone had little effect on blood, myocardial and perivascular fat expression of the lipases.

Disparities in the Prevalence and Risk Factors for Carotid and Lower Extremities Atherosclerosis in a General Population-Bialystok PLUS Study.

This study was conducted in a representative sample of area residents aged 20-80 years old. The aim of the study was to assess the prevalence of classic risk factors of atherosclerosis in the studied population and to search for new risk factors in these patient subpopulations. A total of 795 people (mean age 48.64 ± 15.24 years, 45.5% male) were included in the study group. Two independent data analyses were performed. In the first analysis, the study group was divided into two subgroups depending on the presence or absence of atherosclerotic plaques in carotid arteries (APCA). APCA were observed in 49.7% of the study group: in the population aged between 41 and 60 years in 49.3%, and those between 61 and 70 years in 86.3%. Patients with APCA were more often diagnosed with arterial hypertension, diabetes, and hypercholesterolemia. In the second analysis, the study group was divided into two subgroups depending on the presence of lower extremities atherosclerotic disease (LEAD). Patients with an ABI (ankle-brachial index) ≤ 0.9 constituted 8.5% of the study group, and they were significantly older, and more often diagnosed with diabetes and APCA. To identify the factors most strongly associated with APCA and an ABI ≤ 0.9, logistic regression was used, with stepwise elimination of variables. The strongest factors associated with APCA were current smoking and diastolic central pressure. We did not note such an association and did not find additional parameters to facilitate the diagnosis of LEAD in asymptomatic patients. The most important observation in our study was the high prevalence of APCA in the study population, especially in the group of young people under the age of 60.

Could inflammation contribute to salivary gland dysfunction in patients with chronic heart failure?

Heart failure (HF) is one of the leading causes of death worldwide. HF results not only in cardiovascular dysfunction, but also numerous pathologies in the oral cavity and salivary glands. The present study is the first to evaluate whether salivary inflammatory and anti-inflammatory factors may be related with the occurrence of hyposalivation in HF patients. We also evaluated the potential of salivary biomarkers in the diagnostics of HF. The study included 30 women with HF and 30 sex- and age-matched healthy controls. We demonstrated significantly higher levels of pro-inflammatory cytokines, anti-inflammatory cytokines, Th1, Th2, Th17, chemokines and growth factors in unstimulated saliva of HF patients compared to controls. However, the results do not indicate dominance of either branch of the immune response. The concentration of selected biomarkers is significantly higher in patients with HF and salivary gland dysfunction compared to patients with normal saliva secretion and healthy subjects (IL-1ß, TNF-α, IL-7, IL-13, INF-γ, IL-12, IL-15, IL-5, IL-6, IL-9, IL-17, MCP-1/CCL-2, EOTAXIN/CCL11, RANTES/CCL5, GM-CSF, VEGF, FGF basic, PDFG-BB). Multivariate regression analysis showed that the content of salivary cytokines, chemokines and growth factors is highly dependent on salivary gland function, i.e. salivary flow rate, total protein content and amylase activity. Using receiver operating characteristic (ROC) analysis, we showed that salivary TNF-α, INF-γ, IL-12 and EOTAXIN/CCL11 differentiated patients with HF and hyposalivation with the highest sensitivity and specificity compared to patients with normal salivary secretion and controls. Interestingly, the content of some pro- and anti-inflammatory mediators in saliva significantly exceeds their concentration in plasma. In addition, salivary biomarker levels do not reflect their plasma content, which may suggest a different nature/severity of inflammatory changes at the central (blood) and local (salivary) levels. Although our study was purely observational, the significantly higher concentration of inflammatory parameters in saliva compared to plasma, as well as the lack of saliva-blood correlation, may suggest increased production/secretion of these compounds in salivary cells of HF patients. ROC analysis did not confirm the diagnostic utility of salivary cytokines and chemokines in the differential diagnosis of HF patients.

Insulin-Like Growth Factor-Binding Protein 7 (IGFBP-7)-New Diagnostic and Prognostic Marker in Symptomatic Peripheral Arterial Disease?-Pilot Study.

The aim of our study was to evaluate the importance of insulin-like growth-factor-binding protein 7 (IGFBP-7) as a potential marker of symptomatic peripheral artery disease (PAD) occurrence. The study group consisted of 145 patients with diagnosed PAD, who qualified for the invasive treatment. The control group consisted of 67 individuals representing the local population and an ischemic heart disease (IHD) group of 88 patients after myocardial infarction or percutaneous coronary intervention. Patients with PAD had significantly higher IGFBP-7 concentrations than control group (1.80 ± 1.62 vs. 1.41 ± 0.45 ng/mL, p = 0.04). No significant differences between PAD patients and IHD patients were found (1.80 ± 1.62 vs. 1.76 ± 1.04 ng/mL, p = 0.783). Patients with multilevel PAD presented significantly higher IGFBP-7 concentrations than patients with aortoiliac PAD-median 1.18 (IQR 0.48-2.23) vs. 1.42 ng/mL (0.71-2.63), p = 0.035. In the group of patients who died or had a major adverse cardiovascular event (MACE) during six months of follow-up, a statistically significant higher IGFBP-7 concentration was found (median 2.66 (IQR 1.80-4.93) vs. 1.36 ng/mL (IQR 0.65-2.34), p = 0.004). It seems that IGFBP-7 is elevated in patients with atherosclerotic lesions-regardless of their locations. Further research should be conducted to verify IGFBP-7 usefulness as a predictor of MACE or death.

ECG in the clinical and prognostic evaluation of patients with pulmonary arterial hypertension: an underestimated value.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease leading to right ventricular (RV) failure and manifests in decreasing exercise tolerance. Our study aimed to assess the usefulness of electrocardiographic parameters reflecting right heart hypertrophy as predictors of clinical status in PAH. METHODS: The retrospective analysis included 26 patients, mean 49 ± 17 years of age, diagnosed with PAH, and eligible to undergo cardiopulmonary exercise test (CPET). The relations between ECG values and parameters obtained in procedures such as six-minute walk test (6-MWT), echocardiography, right heart catheterization (RHC), and CPET were analyzed. RESULTS: P-wave amplitude in lead II correlated positively with CPET parameter of respiratory response: minute ventilation to carbon dioxide production slope (VE/VCO2 slope; r = 0.436, p = 0.029) and echocardiographic estimated RA pressure (RAP; r = 0.504, p = 0.02). RV Sokolow-Lyon index (RVSLI) positively correlated with echocardiographic parameters reflecting RV function, overload, and afterload-tricuspid regurgitation pressure gradient (TRPG; r = 0.788, p < 0.001), RV free wall thickness (r = 0.738, p < 0.001), and mean pulmonary arterial pressure (mPAPECHO; r = 0.62, p = 0.0016), respectively, as well as VE/VCO2 slope (r = 0.593, p = 0.001) and mPAP assessed directly in RHC (mPAPRHC; r = 0.469, p = 0.0497). R-wave in lead aVR correlated positively with TRPG (r = 0.719, p < 0.001), mPAPECHO (r = 0.446, p = 0.033), and several hemodynamic criteria of PAH diagnosis: positively with mPAPRHC (r = 0.505, p = 0.033) and pulmonary vascular resistance (r = 0.554, p = 0.026) and negatively with pulmonary capillary wedge pressure (r = -0.646, p = 0.004). QRS duration correlated positively with estimated RAP (r = 0.589, p = 0.004), vena cava inferior diameter (r = 0.506, p = 0.016), and RA area (r = 0.679, p = 0.002) and negatively with parameters of exercise capacity: peak VO2 (r = -0.486, p = 0.012), CPET maximum load (r = - 0.439, p = 0.025), and 6-MWT distance (r = -0.430, p = 0.046). ROC curves to detect intermediate/high 1-year mortality risk (based on ESC criteria) indicate RVSLI (cut-off point: 1.57 mV, AUC: 0.771) and QRS duration (cut-off points: 0.09 s, AUC: 703 and 0.1 s, AUC: 0.759) as relevant predictors. CONCLUSION: Electrocardiography appears to be an important and underappreciated tool in PAH assessment. ECG corresponds with clinical parameters reflecting PAH severity.

IGFBP7 Concentration May Reflect Subclinical Myocardial Damage and Kidney Function in Patients with Stable Ischemic Heart Disease.

The objective of this study was to determine the associations between insulin-like growth-factor-binding protein 7(IGFBP7) concentrations and concentrations of troponin T(TnT), N-terminal pro-B-type natriuretic peptide(NT-proBNP) and the parameters of kidney function in patients with stable ischemic heart disease(IHD). The IHD group consisted of 88 patients, and the population group comprised 66 subjects without a history of IHD. IGFBP7, TnT and NTproBNP concentrations were measured. The IGFBP7 value was considerably higher in the IHD group (1.76 ± 1 ng/mL vs. 1.43 ± 0.44 ng/mL, respectively, p = 0.019). Additionally, IHD subjects had a significantly higher concentration of TnT and NTproBNP. In both groups there was a significant correlation between IGFBP7 and serum parameters of kidney function (creatinine concentration: population gr. r = 0.45, p < 0.001, IHD gr. r = 0.86, p < 0.0001; urea concentration: population gr. r = 0.51, p < 0.0001, IHD gr. r = 0.71, p < 0.00001). No correlation between IGFBP7 and microalbuminuria or the albumin to creatinine ratio in urine was found. Moreover, there was a significant correlation between IGFBP7 concentration and markers of heart injury/overload-TnT and NT-BNP(r = 0.76, p < 0.001 and r = 0.72, p < 0.001, respectively). Multivariate regression analysis in joint both revealed that the IGFBP7 concentration is independently associated with urea, creatinine and TnT concentrations (R2 for the model 0.76). IHD patients presented significantly higher IGFBP7 concentrations than the population group. Elevated IGFBP7 levels are associated predominantly with markers of kidney function and myocardial damage or overload.

Echocardiographic Assessment of Right Ventricular-Arterial Coupling in Predicting Prognosis of Pulmonary Arterial Hypertension Patients.

In response to an increased afterload in pulmonary arterial hypertension (PAH), the right ventricle (RV) adapts by remodeling and increasing contractility. The idea of coupling refers to maintaining a relatively constant relationship between ventricular contractility and afterload. Twenty-eight stable PAH patients (mean age 49.5 ± 15.5 years) were enrolled into the study. The follow-up time of this study was 58 months, and the combined endpoint (CEP) was defined as death or clinical deterioration. We used echo TAPSE as a surrogate of RV contractility and estimated systolic pulmonary artery pressure (sPAP) reflecting RV afterload. Ventricular-arterial coupling was evaluated by the ratio between these two parameters (TAPSE/sPAP). In the PAH group, the mean pulmonary artery pressure (mPAP) was 47.29 ± 15.3 mmHg. The mean echo-estimated TAPSE/sPAP was 0.34 ± 0.19 mm/mmHg and was comparable in value and prognostic usefulness to the parameter derived from magnetic resonance and catheterization (ROC analysis). Patients who had CEP (n = 21) had a significantly higher mPAP (53.11 ± 17.11 mmHg vs. 34.86 ± 8.49 mmHg, p = 0.03) and lower TAPSE/sPAP (0.30 ± 0.21 vs. 0.43 ± 0.23, p = 0.04). Patients with a TAPSE/sPAP lower than 0.25 mm/mmHg had worse prognosis, with log-rank test p = 0.001. the echocardiographic estimation of TAPSE/sPAP offers an easy, reliable, non-invasive prognostic parameter for the comprehensive assessment of hemodynamic adaptation in PAH patients.

Polish Multicenter Registry (Pol-LAS-SE registry). Stress echocardiography in low-gradient aortic stenosis in Poland: numbers, settings, results, complications and clinical practice.

BACKGROUND: The diagnostic workup of low-gradient aortic stenosis (LG AS) is a challenge in clinical practice. AIMS: Our goal was to assess the diagnostic value of stress echocardiography (SE) performed in patients with undefined LG AS with low and preserved ejection fraction (EF) and the impact of its result on therapeutic decisions in Polish third level of reference. METHODS: All the patients with LG AS and with SE performed were recruited in 16 Polish cardiology departments between 2016 and 2019. The main exclusion criteria were as follows: moderate or severe aortic or mitral regurgitation and mitral stenosis. RESULTS: The study group included 163 patients (52% males) with LG AS who underwent SE for adequate diagnostic and therapeutic decision. In 14 patients DSE was non-diagnostic. The mean aortic valve (AV) pressure gradient was 24.1 (7.3) mm Hg, while an AV area was 0.86 (0.2) cm2. Among 149 patients with conclusive DSE, severe AS was found in 59.8%, pseudo-severe in 22%, and moderate AS in 18%. There were no cases of death or vascular events related to DSE. Among 142 patients 63 (44%) patients had an aortic valve intervention in a follow-up (median: 208 days; lower-upper quartile: 73-531 days). Based on the result of the DSE test, severe AS was significantly more often associated with qualification to interventional treatment compared to the moderate and pseudo-severe subgroups (P <0.0001). CONCLUSIONS: The DSE test in severe AS is a valuable diagnostic tool in patients with LG AS in Poland.

Salivary Gland Dysfunction in Patients with Chronic Heart Failure Is Aggravated by Nitrosative Stress, as Well as Oxidation and Glycation of Proteins.

Chronic heart failure (HF) is an important clinical, social, and economic problem. A key role in HF progression is played by oxidative stress. Free oxygen radicals, formed under the conditions of hypoxia and reperfusion, participate in myocardial stunning and other forms of post-reperfusion damage. HF patients also suffer from disorders connected with saliva secretion. However, still little is known about the mechanisms that impair the secretory function of salivary glands in these patients. In the presented study, we were the first to compare the antioxidant barrier, protein glycoxidation, and nitrosative/nitrative stress in non-stimulated (non-stimulated whole saliva (NWS)) and stimulated (SWS) saliva of HF patients. The study included 50 HF patients with normal saliva (NS) secretion (n = 27) and hyposalivation (HS) (n = 23), as well as an age- and gender-matched control group (n = 50). We demonstrated that, in NWS of HF patients with HS, the concentration of low-molecular-weight non-enzymatic antioxidants decreased (↓total polyphenols, ↓ascorbic acid, ↓reduced glutathione, ↓albumin) compared to HF patients with normal saliva (NS) secretion, as well as the control group (except albumin). We also observed increased content of protein glycoxidation products (↑dityrosine, ↑kynurenine, ↑glycophore) in NWS and SWS of HF patients with HS compared to healthy controls. Interestingly, the content of dityrosine, N-formylkynurenine, and glycophore in NWS was also significantly higher in HF patients with HS compared to those with NS secretion. The concentration of NO was considerably lower, while the levels of peroxynitrite and nitrotyrosine were significantly higher in NWS and SWS of HF subjects with HS compared to the controls. Salivary gland dysfunction occurs in patients with chronic HF with the submandibular salivary glands being the least efficient. Oxidative/nitrosative stress may be one of the mechanisms responsible for the impairment of salivary gland secretory function in HF patients.

Prognostic role of PET/MRI hybrid imaging in patients with pulmonary arterial hypertension.

OBJECTIVE: Right ventricular (RV) function is a major determinant of survival in patients with pulmonary arterial hypertension (PAH). Metabolic alterations may precede haemodynamic and clinical deterioration. Increased RV fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) was recently associated with progressive RV dysfunction in MRI, but the prognostic value of their combination has not been established. METHODS: Twenty-six clinically stable patients with PAH (49.9±15.2 years) and 12 healthy subjects (control group, 44.7±13.5 years) had simultaneous PET/MRI scans. FDG uptake was quantified as mean standardised uptake value (SUV) for both left ventricle (LV) and RV. Mean follow-up time of this study was 14.2±7.3 months and the clinical end point was defined as death or clinical deterioration. RESULTS: Median SUVRV/SUVLV ratio was 1.02 (IQR 0.42-1.21) in PAH group and 0.16 (0.13-0.25) in controls, p<0.001. In PAH group, SUVRV/SUVLV significantly correlated with RV haemodynamic deterioration. In comparison to the stable ones, 12 patients who experienced clinical end point had significantly higher baseline SUVRV/SUVLV ratio (1.21 (IQR 0.87-1.95) vs 0.53 (0.24-1.08), p=0.01) and lower RV ejection fraction (RVEF) (37.9±5.2 vs 46.8±5.7, p=0.03). Cox regression revealed that SUVRV/SUVLV ratio was significantly associated with the time to clinical end point. Kaplan-Meier analysis showed that combination of RVEF from MRI and SUVRV/SUVLV assessment may help to predict prognosis. CONCLUSIONS: Increased RV glucose uptake in PET and decreased RVEF identify patients with PAH with worse prognosis. Combining parameters from PET and MRI may help to identify patients at higher risk who potentially benefit from therapy escalation, but this hypothesis requires prospective validation.

Galectin-3 as the Prognostic Factor of Adverse Cardiovascular Events in Long-Term Follow up in Patients after Myocardial Infarction-A Pilot Study.

Galectin-3 (Gal-3) is a new independent risk factor in the development and severity of coronary artery disease (CAD). The aim of the study was to evaluate whether Gal-3 concentration has prognostic value and if it reflects the progression of atherosclerosis in carotid arteries in patients with CAD after acute myocardial infarction (AMI). The analysis included 110 patients who were hospitalized due to AMI, treated with primary coronary intervention (PCI) and further attended a follow-up visit, and 100 healthy volunteers. The Gal-3 concentration and carotid ultrasound were evaluated at baseline and on a follow-up visit. We found that the Gal-3 concentration in the group with hyperlipidemia decreased during the observation (10.7 vs. 7.9 ng/mL, p = 0.00003). Patients rehospitalized during follow up had higher concentration of Gal-3 in the acute phase of myocardial infarction (MI) (10.7 vs. 7.2 ng/mL, p = 0.02; 10.1 vs. 8.0 ng/mL, p = 0.002, respectively). In the group of patients who had none of the following endpoints: subsequent MI, PCI, coronary artery bypass grafting (CABG) or stroke, there was a decrease in Gal-3 concentration at the follow-up visit. Parameters affecting the frequency of a composite endpoint occurrence are: the presence of atheromatous plaque in the carotid artery (p = 0.017), Gal-3 (p = 0.004) and haemoglobin (p = 0.03) concentration. In multivariate analysis, only Gal-3 concentration higher than 9.2 ng/mL at discharge was associated with a nine-fold increase of risk of composite endpoint occurrence (p = 0.0005, OR = 9.47, 95% CI 2.60-34.45). A significant decrease in Gal-3 concentration was observed in the group of patients after AMI without the endpoint occurrence during observation.

Salivary Oxidative Stress Increases With the Progression of Chronic Heart Failure.

The aim of the study was to evaluate the rate of reactive oxygen species (ROS) production, antioxidant barrier, and oxidative damage in non-stimulated (NWS) and stimulated (SWS) saliva as well as plasma/erythrocytes of 50 patients with chronic heart failure (HF) divided into the two subgroups: NYHA II (33 patients) and NYHA III (17 patients). The activity of superoxide dismutase and catalase was statistically increased in NWS of HF patients as compared to healthy controls. The free radical formation, total oxidant status, level of uric acid, advanced glycation end products (AGE), advanced oxidation protein products and malondialdehyde was significantly elevated in NWS, SWS, and plasma of NYHA III patients as compared to NYHA II and controls. We were the first to demonstrate that with the progression of HF, disturbances of enzymatic and non-enzymatic antioxidant defense, and oxidative damage to proteins and lipids occur at both central (plasma/erythrocytes) and local (saliva) levels. In the study group, we also observed a decrease in saliva secretion, total salivary protein and salivary amylase activity compared to age- and gender-matched control group, which indicates secretory dysfunction of salivary glands in patients with HF. Salivary AGE may be a potential biomarker in differential diagnosis of HF.

The Gene and Protein Expression of the Main Components of the Lipolytic System in Human Myocardium and Heart Perivascular Adipose Tissue. Effect of Coronary Atherosclerosis.

The aim of our study was to examine the regulation of triacylglycerols (TG) metabolism in myocardium and heart perivascular adipose tissue in coronary atherosclerosis. Adipose triglyceride lipase (ATGL) is the major TG-hydrolase. The enzyme is activated by a protein called comparative gene identification 58 (CGI-58) and inhibited by a protein called G0/G1 switch protein 2 (G0S2). Samples of the right atrial appendage and perivascular adipose tissue were obtained from two groups of patients: 1-with multivessel coronary artery disease qualified for coronary artery bypass grafting (CAD), 2-patients with no atherosclerosis qualified for a valve replacement (NCAD). The mRNA and protein analysis of ATGL, HSL, CGI-58, G0S2, FABP4, FAT/CD36, LPL, ß-HAD, CS, COX4/1, FAS, SREBP-1c, GPAT1, COX-2, 15-LO, and NFκß were determined by using real-time PCR and Western Blot. The level of lipids (i.e., TG, diacylglycerol (DG), and FFA) was examined by GLC. We demonstrated that in myocardium coronary atherosclerosis increases only the transcript level of G0S2 and FABP4. Most importantly, ATGL, ß-HAD, and COX4/1 protein expression was reduced and it was accompanied by over double the elevation in TG content in the CAD group. The fatty acid synthesis and their cellular uptake were stable in the myocardium of patients with CAD. Additionally, the expression of proteins contributing to inflammation was increased in the myocardium of patients with coronary stenosis. Finally, in the perivascular adipose tissue, the mRNA of G0S2 was elevated, whereas the protein content of FABP-4 was increased and for COX4/1 diminished. These data suggest that a reduction in ATGL protein expression leads to myocardial steatosis in patients with CAD.

Insulin-like growth factor-binding protein 7 (IGFBP 7) as a new biomarker in coronary heart disease.

PURPOSE: The role of insulin-like growth factor-binding protein-7 (IGFBP-7) in atherosclerosis is still not well-known. The objective of this study was to find out the following: 1) whether IGFBP-7 may act as a biomarker of coronary artery disease (CAD) occurrence and extent; 2) whether IGFBP-7 is potentially related to the classical and new markers of cardiovascular risk (carotid intima-media thickness - cIMT); 3) whether IGFBP-7 may be a marker of mortality in the group of patients with myocardial infarction (MI). MATERIALS/METHODS: The study group consisted of 212 patients with MI and 75 patients with stable CAD, the control group included 100 healthy volunteers. IGFBP-7 serum concentration was measured. RESULTS: IGFBP-7 value was considerably higher in the study group (MI and CAD patients - 35.1 ng/ml (P = 0.000001) and 32.7ng/ml (P = 0.0001), respectively), than in the controls - 25.2ng/ml. No statistically significant differences between IGFBP-7 concentrations in the MI and CAD group were found. No relationship between IGFBP-7 and the coronary lesions advancement in the study group was observed. No changes in IGFBP-7 concentration in the MI patients during hospitalization were observed. In the group of MI patients who died during follow-up, a considerably higher cIMT values were found whereas no statistically significant difference was observed in relation to IGFBP-7 (34.6 vs. 35.2 ng/ml). CONCLUSIONS: IGFBP-7 is a good biomarker of CAD occurrence but not of its advancement. We demonstrated the existence of the relation between higher IGFBP-7 concentration and the selected classical risk factors of cardiovascular events as well as cIMT values. IGFBP-7 cannot serve as a marker of acute ischemia. Also, IGFBP-7 was not confirmed as a predictor of mortality in the MI patients.

Increased platelet content of SDF-1alpha is associated with worse prognosis in patients with pulmonary prterial hypertension.

Inflammatory processes and platelet activity play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). Enhanced IL-6 signaling and higher concentration of stromal-derived factor alpha (SDF-1) have been previously shown to be linked with prognosis in PAH. We hypothesized that platelets of PAH patients have higher content of IL-6 and SDF-1 and thus are involved in disease progression. We enrolled into study 22 PAH patients and 18 healthy controls. Patients with PAH presented significantly higher plasma concentrations and platelet contents of IL-6, sIL-6R, and SDF-1 than healthy subjects (platelet content normalized to protein concentration: IL-6 (0.85*10-10 [0.29 - 1.37] vs. 0.45*10-10 [0.19-0.65], sIL-6R 1.54*10-7 [1.32-2.21] vs. 1.14*10-7 [1.01-1.28] and SDF-1 (2.72*10-7 [1.85-3.23] vs. 1.70*10-7 [1.43-2.60], all p < 0.05). Patients with disease progression (death, WHO class worsening, or therapy escalation, n = 10) had a significantly higher platelet SDF-1/total platelet protein ratio (3.68*10-7 [2.45-4.62] vs. 1.69*10-7 [1.04-2.28], p = 0.001), with no significant differences between plasma levels. Kaplan-Meier analysis revealed that patients with higher platelet SDF-1/total platelet protein ratio had more frequently deterioration of PAH in the follow-up (15.24 ± 4.26 months, log-rank test, p = 0.01). Concentrations of IL-6, sIL-6 receptor and SDF-1 in plasma and platelets are elevated in PAH patients. Higher content of SDF-1 in platelets is associated with poorer prognosis. Our study, despite of limitation due to small number of enrolled patients, suggests that activated platelets may be an important source of cytokines at the site of endothelial injury, but their exact role in the pathogenesis of PAH requires further investigation.

The significance of diminished sTWEAK and P-selectin content in platelets of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by proliferative changes in pulmonary arteries. There is growing evidence suggesting that soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and P-selectin could be involved in PAH development and progression. Here we investigate whether circulating platelets may be a source of sTWEAK and contribute to diminished availability of sTWEAK and P-selectin in PAH patients. We have prospectively enrolled two independent study groups of stable patients with confirmed PAH and age matched controls: derivation (10 PAH; 15 controls) and validation (20 PAH; 12 controls). P-selectin and sTWEAK concentrations were measured in platelet-poor plasma and platelet lysate. To avoid procedural bias, in each group we employed different protocols for platelet isolation. Consistently, both in derivation and validation groups PAH patients presented significantly lower sTWEAK content in platelets than control group with no significant differences in plasma levels. Similarly, patients presented comparable to controls plasma P-selectin concentrations and lower concentration in platelet lysate. Kaplan-Meier analysis revealed that patients with low platelet sTWEAK/total protein concentration ratio had more frequently detoriation of PAH in the follow-up (16.51 ±â€¯3.32 months), log-rank test, p = .03. Patients diagnosed with pulmonary arterial hypertension present diminished sTWEAK and P-selectin storage capacity in platelets. Thrombocytes appear to be a major source of sTWEAK that could be released upon local injury and its decreased availability could have an impact on pathophysiology and prognosis in PAH.

The strengths and weaknesses of non-invasive parameters obtained by echocardiography and cardiopulmonary exercise testing in comparison with the hemodynamic assessment by the right heart catheterization in patients with pulmonary hypertension.

PURPOSE: Pulmonary hypertension (PH) diagnosis requires invasive assessment by right heart catheterization (RHC), but screening and monitoring are performed using non-invasive methods: echocardiography and cardiopulmonary exercise testing (CPET). The aim of the study was to assess correlations between the parameters obtained in non-invasive testing and RHC in patients with PH of different etiologies. MATERIAL/METHODS: The study included 53 medical records of PH patients (32 women) aged 29-81 years. We analyzed correlations between RHC (systolic pulmonary artery pressure (sPAP), diastolic pulmonary artery pressure (dPAP), pulmonary vascular resistance (PVR), cardiac output (CO)) and echocardiographic (tricuspid annular plane systolic excursion (TAPSE), sPAP) and CPET parameters (end-tidal oxygen and carbon dioxide pressures (PetO2, PetCO2), ventilation efficiency (VE/VCO2) slope). RESULTS: Echocardiographic estimation correlated well with RHC measurement of sPAP (r=0.65, P<0.001). TAPSE correlated with PVR assessed with thermodilution method (r=-0.5, P=0.005), dPAP (r=-0.53, P=0.002) and CO (r=0.53, P=0.002). PVR assessed with thermodilution and Fick methods showed positive correlation with PetO2 (r=0.74, P<0.001 and r=0.72, P<0.001) and negative correlation with PetCO2 (r=-0.59, P=0.004 and r=-0.64, P=0.002) at the anaerobic threshold. VE/VCO2 slope correlated with dPAP (r=0.43, P=0.04) and PVR calculated with both methods (r=0.52, P=0.01 and r=0.52, P=0.02). CONCLUSIONS: Simple cardiac function indicators obtained by commonly used non-invasive methods allow only approximate estimation of the main hemodynamic RHC-derived parameters: sPAP, CO and PVR. Obtained results suggest the relationship between RV dysfunction and ventilation abnormalities in PH patients.

Predictive value of Galectin-3 for the occurrence of coronary artery disease and prognosis after myocardial infarction and its association with carotid IMT values in these patients: A mid-term prospective cohort study.

OBJECTIVE: The role of Galectin-3(Gal-3) in atherosclerosis progression has not been definitely acknowledged. The aim of the study was to establish the following: whether Gal-3 may act as an independent risk factor of coronary artery disease (CAD) occurrence and its advancement, if Gal-3 has potential relations with classical and new markers of cardiovascular risk (carotid intima-media thickness (cIMT), and whether Gal-3 may be a marker of mortality in the group of patients with myocardial infarction (MI) during mid-term follow-up. PATIENTS AND METHODS: The study group was composed of 233 patients with MI and 100 patients with a stable CAD. Selected risk factors were assessed, Gal-3 concentrations and cIMT were measured. The control group was composed of 100 healthy individuals. RESULTS: In the study group (MI and CAD patients) Gal-3 concentration was significantly higher than in the controls--median 7.9 ng/ml (p = 0.0001) and 10.7 ng/ml (p = 0.00001) vs. 5.5 ng/ml, respectively. Patients with 3-vessel disease had higher levels of Gal-3 than patients with 1-or 2-vessel disease (9.2 ng/ml vs 7.4 ng/ml, p = 0.003). In the group of MI patients who died during the follow-up (average period - 2.8 years), we found a significantly higher concentration of Gal-3 (20.0 ng/ml vs 8.0 ng/ml, p = 0.0005) and cIMT values (common carotid artery(CCA): 1.4 ± 0.4 mm vs. 1.0 ± 0.3 mm, p = 0.03; carotid bulb(CB): 2.3 ± 0.5 mm vs. 1.9 ± 0.4 mm, p = 0.009). In the model of multivariate logistic regression analysis, the variables influencing the mortality after MI during follow-up were: age>65 years, Gal-3 concentration>8.7 ng/ml, IMT values and plaque occurrence in CB, previous MI and EF<40%. CONCLUSIONS: Gal-3 is an independent risk factor of CAD occurrence, but cIMT values are better markers of CAD advancement. Both Gal-3 concentration>8.7 ng/ml and IMT values in CB were an independent predictive indicators of increased risk of all-cause mortality in patients after MI during mid-term follow up.