Sensitivity to perioperative ischemia/reperfusion injury in male and female donor myocardium.

Many functions of the cardiovascular apparatus are affected by gender. The aim of our study was find out whether markers of cell death present in the donor myocardium differ in male and female hearts. The study involved 81 patients undergoing heart transplantation from September 2010 to January 2013. Patients were divided into two groups: male allograft (n=49), and female allograft (n=32). Two types of myocardial cell death were analyzed. High-sensitive cardiac troponin T as a necrosis marker and protein bcl-2, caspase 3 and TUNEL as apoptosis markers were measured. We observed a significantly higher level of high-sensitive cardiac troponin T after correcting for predicted ventricular mass in female donors before transplantation as well as in the female allograft group after transplantation throughout the monitored period (P=0.011). There were no differences in apoptosis markers (bcl-2, caspase 3, TUNEL) between male and female hearts before transplantation. Both genders showed a significant increase of TUNEL-positive myocytes one week after transplantation without differences between the groups. Moreover, there were no differences in caspase 3 and bcl-2 expression between the two groups. Our results demonstrated the presence of necrotic and apoptotic cell death in human heart allografts. High-sensitive cardiac troponin T adjusted for predicted ventricular mass as a marker of myocardial necrosis was higher in female donors, and this gender difference was even more pronounced after transplantation.

The importance of age and statin therapy in the interpretation of Lp-PLA(2) in ACS patients, and relation to CRP.

C-reactive protein (CRP) is a marker of arterial inflammation while lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is related to plaque instability. The aim of this study was to evaluate the correlation between the risk of unstable plaque presenting as acute coronary syndrome (ACS) and Lp-PLA(2), and to assess the influence of statins on interpretation of Lp-PLA(2). A total of 362 consecutive patients presenting to the emergency department (ED) with acute chest pain suggestive of ACS were evaluated by cardiologists as STEMI, NSTEMI, or unstable angina, and non-ACS. Serum biomarkers measured on admission: troponin I, C-reactive protein (Abbott), and Lp-PLA(2) (DiaDexus). Four groups were defined according to the final diagnosis and history of statin medication: ACS/statin-; ACS/statin+; non-ACS/statin-; non-ACS/statin+. Lp-PLA(2) was highest in ACS/statin- group; statins decreased Lp-PLA(2) both in ACS and non-ACS of about 20 %. Lp-PLA(2) was higher in ACS patients in comparison with non-ACS patients group without respect to statin therapy (p<0.001). Lp-PLA(2) predicted worse outcome (in terms of acute coronary syndrome) effectively in patients up to 62 years; limited prediction was found in older patients. C-reactive protein (CRP) failed to discriminate four groups of patients. Statin therapy and age should be taken into consideration while interpreting Lp-PLA(2) concentrations and lower cut-off values should be used for statin-treated persons.

Association of metabolic and genetic factors with cholesterol esterification rate in HDL plasma and atherogenic index of plasma in a 40 years old Slovak population.

We assessed association between novel biomarkers of cardiovascular disease and conventional factors in 40 years old subjects (208 men and 266 women) from the general population of Slovakia. FER(HDL) (cholesterol esterification rate in HDL plasma), AIP--Atherogenic Index of Plasma [Log(TG/HDL-C)] as markers of lipoprotein particle size, and CILP2, FTO and MLXIPL polymorphisms, were examined in relation to biomarkers and conventional risk factors. Univariate analyses confirmed correlation between AIP, FER(HDL) and the most of measured parameters. Relations between AIP and CILP2, FTO and MLXIPL were not significant. However, CILP2 was significantly related to FER(HDL) in both genders. In multivariate analysis BMI was the strongest correlate of AIP levels. In multivariate model variability of FER(HDL) was best explained by AIP (R(2) = 0.55) in both genders with still significant effect of CILP2 SNP in men. In a model where AIP was omitted, TG levels explained 43 % of the FER(HDL) variability in men, while in women HDL-C was the major determinant (42 %). In conclusions, FER(HDL) and AIP related to the known markers of cardiovascular risk provide means to express their subtle interactions by one number. Our novel finding of association between CILP2 polymorphism and FER(HDL) supports its role in lipid metabolism.

[High sensitivity cardiac troponin assays 2009: clinical potential, current practice and benefits, the future]. / High-sensitivity metody stanovení srdecních troponinu 2009: klinický potenciál, soucasná praxe a prínos, perspektiva.

At present, determination of cardiac troponins (cTn) is the biomarker method of choice for diagnostics and risk stratification in patients with a myocardial injury. Past clinical practice had provided sound evidence that low cTn concentrations, measured with unacceptable imprecision by the currently used methods, hold important clinical, diagnostic and stratification potential. The new generation cTn assays, so called high-sensitivity assays, enable determination of very low cTn concentrations with satisfactory analytical precision and open the way to early identification of small but often prognostically important myocardial damage. Introduction of high-sensitivity cTn assays in practice is, however, associated with some difficulties: their superior diagnostic sensitivity to identify small injuries to myocardium is often linked to lower specificity, higher incidence of elevated cTn concentrations is frequently associated with less obvious clinical symptomatology (overdiagnosis), resulting in greater demand for further patient assessment (overcrowding), repeated analyses and trend monitoring of cTn fluctuation. These initial difficulties cannot lessen the by now indisputable, established benefit of high-sensitivity cTn assays that we briefly describe in the present paper.

Biological activity and clinical implications of the matrix metalloproteinases.

The family of human matrix metalloproteinases (MMPs) comprises several tightly regulated classes of proteases. These enzymes and their specific inhibitors play important roles in tumour progression and the metastatic process by facilitating extracellular matrix degradation. As scientific understanding of the MMPs has advanced, therapeutic strategies focusing on blocking these enzymes by matrix metalloproteinase inhibitors have rapidly developed. Low molecular weight tissue inhibitors of matrix metalloproteinase (TIMPs) represent a new therapeutic approach for the treatment of individual types of cancer. This paper aims to briefly summarize current knowledge about the role of MMPs in select non- tumorous lesions, tumor invasion and metastasis. The perspectives in therapeutic intervention in cancer are also mentioned. The role of MMPs in diagnosis and prognosis of colorectal and thyroid cancer is discussed in detail.

[Serum amyloid A as an effective marker for the assessment of surgical trauma and risk of post-operative complications]. / Sérový amyloid A jako efektivní marker stupne operacní záteze a rizika komplikací.

OBJECTIVE: To analyze relations among acute phase reactants in a group of 40 women operated for uterine myom by laparoscopy and open surgery. DESIGN: Prospective study. METHODS: Plasma concentrations of C-reactive protein (CRP), serum amyloid A (SAA) and interleukin 6 (IL-6) were measured together with leukocytes in blood before operation, 24 and 72 hours post operation, respectively. RESULTS: Leukocytes and IL-6 displayed minimal response and decreased quickly after operation to preoperative levels. Concentrations of CRP and SAA remained increased after operation. There were no relationships between leukocytes and acute phase reactants. Normal leukocytes 72 hours post operation were found in 1/3 of women with increased at least one acute phase reactants and in 1/4 of women with increased at least two markers. Typ of surgery, surgical stress and length of surgery were related to the concentration of CRP, IL-6 and SAA. CONCLUSION: Changes in SAA 24 hours after operation are similar to CRP and IL-6. Surgical stress, length of operation and possible risk 72 hours after operation are best predicted by CRP and SAA (at that time IL-6 and leukocytes are practically normal). Maximal increase was found for SAA concentrations. Thus SAA seems to be suitable marker of early postoperative complications.

[Cardiovascular risk and estrogens]. / Kardiovaskulární riziko a estrogeny.

OBJECTIVE: To describe relations among postmenopause, hormonal therapy, lipid metabolism and risk of cardiovascular diseases. DESIGN: Search and analysis of relevant data from medical literature. METHODS: Analysis of the relation between serum lipid profile and postmenopausal changes, evaluation of positive and negative effects of estrogens on vascular wall and lipid metabolism, analysis of methods for the assessment of cardiovascular risk and evaluation of recent guidelines. RESULTS: Postmenopause is connected with significant changes in lipid metabolism, serum lipid profile and with increased risk of cardiovascular diseases. Deficit of estrogens influences lipid metabolism negatively. However, estrogen substitution has both positive and negative effects on vascular wall. Negative effects are: increased occurence of postprandial hyperlipidemia with increased triglycerides, generation of aterogenous small dense LDL particles, increased risk of inflammatory changes in vascular wall and procoagulation situation. CONCLUSION: Hormonal therapy can display some positive effects of vascular wall. However, recent data evaluate hormonal substitution with regard to atherosclerosis and cardiovascular problems as less benefitial or even risky.