Echocardiographic predictors of stress induced right ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary vasculopathy, right heart structural and functional abnormalities occur even in normoxemic chronic obstructive pulmonary disease (COPD) patients. Despite being associated with functional limitation, exacerbations, and disease progression, their detection and proper management is still delayed. AIM: Our aim was to establish the frequency of stress-induced right ventricular diastolic dysfunction (RVDD) in non-severe COPD patients, free of overt cardiovascular disease, who complain of exertional dyspnea and to look for echocardiographic predictors of it. MATERIALS AND METHODS: We applied cardio-pulmonary exercise testing (CPET) in 104 non-severe, COPD patients. A ramp protocol was performed. Echocardiography was done before and 1-2 min after peak exercise. Cut-off values for stress induced RVDD were E/e' >6. Receiver operating curves were constructed for echo parameters at rest to determine if any of them may discriminate stress induced RV E/e'>6 or <6. Uni- and multivariable linear regression analysis was also performed to assess the predictive power of each of them. A p-value < 0.05 was considered significant. RESULTS: A total of 78% of the patients had stress-induced RVDD. Right atrium volume index (RAVI) (cut-off >20.55 ml/m2; sensitivity - 86%; specificity - 86%), RV wall thickness (RVWT) (cut-off >5.25 mm; sensitivity - 100%; specificity - 63%), and RV E/A ratio at rest (cut-off >1.05; sensitivity - 79.7%; specificity - 90.5%) were the best predictors of stress RV E/e. In univariate regression analysis E/A showed the highest OR 19.73 (95% CI - 18.52-21.01); followed by RAVI - OR 3.82; (95% CI - 2.04-7.14). CONCLUSION: There is a high prevalence of stress-induced RVDD in non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease. RAVI, RVWT, E/A, and E/e' ratio at rest may be used as predictors for stress RVDD and may facilitate patients' risk stratification and proper management.

8-isoprostanes and resistin as markers of vascular damage in non-hypersomnolent obstructive sleep apnoea patients.

BACKGROUND: Oxidative stress and inflammation are assumed as the main pathological triggers for vascular damage in hypersomnolent obstructive sleep apnoea (OSA) patients, whereas their exact role in less symptomatic population is currently unknown. AIM: To determine whether oxidative stress (urinary 8-isoprostane concentration) and inflammation (plasma resistin levels) are associated with vascular damage in non-hypersomnolent (Epworth Sleep Score <11) OSA patients. METHODS: A total of 325 consecutive patients have undergone standard polysomnography, and 256 of them were diagnosed with OSA. Excessive daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). Only 86 patients with ESS <11 participated in the study. The control group was presented by 45 subjects without OSA. Endothelial function was assessed by ultrasonographic measurement of flow-mediated dilatation (FMD). Intima-media thickness (IMT) and ankle-brachial index (ABI) were determined by ultrasonography. Urinary 8-isoprostanes (Cayman Chemical, USA) were measured, applying mass spectrometry. Resistin (RayBio_ Human ResistinCat#:ELH-Resistin-001) plasma levels were detected by ELISA. RESULTS: In patients with OSA, flow-mediated dilatation was significantly lower than in control subjects (4·62% ±1·9) and (7·1% ±2·8), respectively (P: 0·013). The prevalence of plaques in a.carotis communis was higher in OSA (16% versus 4%). The same is observed regarding a.tibialis posterior (81% vs. 29%). The average IMT and ABI in OSA and in the control group were, respectively, (IMT - 800 µm versus. 666 µm); (ABI -1·06 versus 1·20). Urinary isoprostanes were higher in OSA patients (0·091 versus 0·078) and correlated negatively to FMD (r: -0·825, P: 0·00), IMT (r: -0·324, P: 0·003) and ABI (r: -0·226, P: 0·043). No association between resistin and the degree of vascular injury was found. CONCLUSIONS: In comparison with the control group, increased prevalence of endothelial dysfunction and vascular damage was established in OSA patients without excessive daytime sleepiness. Urinary 8-isoprostanes (oxidative stress markers) are closely associated with FMD (endothelial dysfunction), IMT and ABI (vascular damage). Resistin plasma levels correlated neither to FMD, nor to IMT or ABI.

Resistin - the link between adipose tissue dysfunction and insulin resistance in patients with obstructive sleep apnea.

BACKGROUND: Resistin is an adipocytokine, associated with obesity and inflammation. Its exact role in insulin resistance and diabetes in the general population is still controversial. The relation between resistin plasma levels, insulin resistance and risk of impaired glucose metabolism in OSA patients has not been investigated. MATERIALS AND METHODS: Plasma levels of resistin were measured in 67 patients with OSA and impaired glucose metabolism. 34,7% (23/67) had diabetes; 40% (27/67) patients had impаired glucose tolerance(IGT); 25,3%(17/67) had normal glucose metabolism (NGM). The association between resistin, BMI, obesity, markers of insulin resistance, oxidative stress and sleep study characteristics was analysed. The different groups of patients were compared in regards to glucometabolic parameters and biomarkers of oxidative stress - isoprostanes and insulin resistance - free fatty acids (FFA). RESULTS: Plasma levels of resistin were higher in patients with diabetes (6,12 ±5,93ng/ml), compared to those with IGT (3,85±2,81ng/ml, p-0,021) and NGM (3,77±3,23, p-0,043). Resistin did not differ between patients with IGT and NGM (p-0,954). In OSA patients with BMI>40 resistin plasma levels correlated neither to the clinical parameters (BMI, IRI, HOMA-I, HbA1C, AHI, desaturation index), nor to the biomarkers of oxidative stress and insulin resistance. Free fatty acids (0,232>0,177mmol/l, p-0,037) were higher in diabetics in comparison to NGM. CONCLUSIONS: Plasma resistin levels in OSA patients with BMI>40 are independent of insulin resistance and are not associated with the parameters, characterising the oxidative stress or severity of OSA. Resistin could be used in a multiple panel of clinical and biomarkers to discern patients with diabetes from those with IGT; in OSA patients with BMI >40 resistin together with HbA1C could discern patients with diabetes from those with NGM. In OSA patients with BMI >40 FFA and HbA1C are useful clinical markers in assessing the risk of dysglycaemia among patients with normal and IGT.

Inflammatory cytokines at admission--independent prognostic markers in patients with acute coronary syndrome and hyperglycaemia.

BACKGROUND: The clinical significance of inflammatory cytokines as independent prognostic markers in patients with acute coronary syndrome (ACS) and hyperglycaemia remains uncertain. AIM: To determine the value of inflammatory biomarkers as independent prognostic indicators and their relation with hyperglycaemia in ACS patients. METHODS: TNF-α and hsCRP were defined 48 h after admission and indicators for hyperglycaemia were calculated in 256 consecutive patients with ACS. A correlation analysis with standard clinical variables--EF, maximum CK, CK-MB, troponin and different indices for hyperglycaemia was performed. Patients were followed up for 12 months. RESULTS: Baseline TNF-α correlated neither to EF, nor to the enzymes for myocardial necrosis (P>0.05). In contrast, hsCRP correlated negatively with EF (P=0.001) and positively with maximum CK, CK-MB, troponin (P=0.0001) irrespectively of the glucose status. TNF-α was associated with fasting glycaemia, HGI and TAG (P=0.033/0.041/0.018) and hsCRP-with indicators for acute, persistent and chronic glycaemia in all patients. Moreover, hsCRP was an independent marker for six-month survival (P=0.024). TAG was a stronger six-month survival predictor than hsCRP (P=0.010/0.024). CONCLUSION: hsCRP and TNF-α have clinical significance regardless of the glucose metabolic status. hsCRP is an independent marker for six-month survival. TAG is the better predictor for poor outcome than hsCRP.

Clinical significance of hyperglycaemia in acute coronary syndrome patients.

BACKGROUND: The clinical significance of moment measurements (admission and fasting glycaemia), persistent (hyperglycaemic index, HGI; time average glucose, TAG; mean glucose; maximum glucose) or chronic hyperglycaemia (HbA1c), estimated average glucose, eAG) is still elusive in clinical practice. AIM: To identify the clinical significance of hyperglycaemia in ACS. METHODS: The study included 226 consecutive patients with ACS. Indicators for hyperglycaemia were defined, calculated and a correlation analysis with standard parameters-EF, maximum CPK, maximum CPK-MB and troponin was performed. Patients were followed up for 12 months. RESULTS: Indicators for persistent and chronic hyperglycaemia correlated neither to ejection fraction, nor to the enzymes for myocardial necrosis (P > 0.05). In contrast, acute hyperglycaemia correlated negatively with ventricular systolic dysfunction (P = 0.001/0.007) and positively with maximum CPK, MB and troponin (P = 0.0001/0.008). TAG was an independent predictor for 6-month re-hospitalization (P = 0.027) because of cardiac complications. CONCLUSION: Glycaemia at admission and fasting glucose could be used as metabolic surrogate markers for ventricular systolic dysfunction and TAG as an independent surrogate marker for six-month re-hospitalization. None of the indicators for hyperglycaemia could be used as independent prognostic factors for survival. Hyperglycaemia rather reflects an underlying impairment in glucose metabolism.

Expression analysis of angiogenesis-related genes in Bulgarian patients with early-stage non-small cell lung cancer.

AIMS AND BACKGROUND: Angiogenesis is a key process in the early stages of tumor development. In this study we aimed to evaluate the expression of a panel of angiogenesis-related genes in a group of Bulgarian patients with early-stage non-small cell lung cancer (NSCLC). METHODS AND STUDY DESIGN: We analyzed the expression of 84 genes associated with the angiogenic process in 12 NSCLCs of two histological subtypes: 7 adenocarcinomas and 5 squamous cell carcinomas. Eight peripheral nontumorous tissues were used as controls. We performed real-time PCR on pathway-specific gene arrays (SABiosciences). RESULTS: Our pilot study identified upregulated genes in early-stage NSCLC including growth factors (TGFA and EFNA3), the adhesion molecule THBS2, cytokines and chemokines (MDK, CXCL9, CXCL10), and the serine protease PLAU. Several genes showed downregulation including one growth factor (FIGF), the receptors for growth factors TEK and S1PR1 as well as adhesion molecules (COL4A3 and CDH5), the cytokine IL6, the matrix protein LEP and the transcription factor NOTCH4. The study demonstrated deregulated genes specific for the two histological subtypes including the transcription factor HAND2, which was overexpressed in squamous cell carcinomas but not adenocarcinomas. CONCLUSIONS: Despite the limited number of patients, our results demonstrated the potential of angiogenesis-related genes as biomarkers in the early stages of NSCLC development.