Anna Konopka

Concentration of vascular endothelial growth factor in patients with acute coronary syndrome

UNLABELLED Vascular endothelial growth factor (VEGF) is a regulator of vascular formation in physiological and pathological conditions. The aim of our study was to evaluate the value of VEGF as a surrogate marker of myocardial injury in acute ischemic conditions. MATERIALS AND METHODS In 104 consecutive patients with acute coronary syndrome (ACS) with and without ST segment elevation (STEMI and NSTEMI) the plasma and serum human VEGF (hVEGF) concentration was measured two times i.e. immediately after admission due to ACS and 24h later. According to ECG findings and coronary angiography results, patients were divided into three groups. Group A represented major myocardial injury due to ST-segment elevation in precordial leads and/or in I and aVL leads and with left anterior descending (LAD) artery responsible for STEMI symptoms or additionally with significant atherosclerotic lesions (lumen vessel narrowed>50%) in other than LAD coronary arteries. Group B (medium myocardial injury) consisted of patients with ST-segment elevation in II, III and aVF leads and/or ST-segment depression in V2-V3 leads with one-vessel disease and the culprit artery was not LAD. Group C included patients with changes in ECG other than ST-segment elevation independently of the site of atherosclerotic lesions in coronary arteries. RESULTS In all 104 patients with ACS the highest values of serum hVEGF were observed in second measurement (357.9 ± 346 pg/ml, p<0.01). Although in the first measurement, plasma and serum hVEGF concentration did not differentiate groups, the difference between deltas for serum hVEGF was observed (p<0.05). Increased number of neutrophils in the first measurement increased the OR of the high serum hVEGF concentration in the first measurement (OR=1.155; 95%CI: 1.011; 1.32) (p<0.05). The number of neutrophils in the second measurement also revealed significant relationship with high serum hVEGF in the first assessment (OR=1.318, 95%CI: 1.097; 1.583) (p<0.01). Increased values of triglycerides (exceeding the upper limit) were connected with decreased OR of high serum hVEGF concentrations in the first measurement (OR=0.152, 95%CI: 0.033; 0.695, p<0.05). CONCLUSIONS In acute coronary syndrome, serum VEGF concentrations are elevated and can serve as a surrogate marker of myocardial injury. The elevated number of neutrophils increases odds ratio of high VEGF concentrations in ACS. In patients with high concentrations of triglycerides, odds ratio of low level of hVEGF is expected.

Influence of Renin-Angiotensin System Gene Polymorphisms on the Risk of ST-Segment-Elevation Myocardial Infarction and Association with Coronary Artery Disease Risk Factors

AbstractBackground: Recent advances in molecular biology have made it possible to identify numerous polymorphisms of the renin-angiotensin system, which play an important role in the etiology of cardiovascular disease. Objective: The aims of the study were (i) to assess the distribution of the angiotensin II type 1 receptor (AGTR1) gene 1166A/C polymorphism and two polymorphisms of the angiotensinogen (AGT) gene (Met235Thr and Thr174Met) in patients with ST-segment-elevation myocardial infarction (STEMI) who underwent coronary angiography, compared with healthy volunteers; (ii) to determine if there was any correlation between these polymorphisms and risk of STEMI; and (iii) to assess the association of the examined polymorphisms with such classic cardiovascular risk factors as hypertension, diabetes mellitus, obesity (based on a body mass index ≥25 kg/m2), smoking, dyslipidemia, and family history of cardiovascular disease. Methods: A total of 100 patients (mean age 57 ± 10 years [range 31–76 years]; 21% women) with diagnosed STEMI and a control group consisting of 95 healthy volunteers (mean age 38 ± 11 years [range 17–60 years]; 20% women) were investigated for the AGTR1 1166A/C polymorphism and two variants of AGT (Met235Thr and Thr174Met). All patients received standard therapy for STEMI. Results: There were significant differences in the distribution of genotypes and the AGT Met174 allele for AGT Thr174Met polymorphism between patients and healthy subjects (p<0.05). The AGTR1 1166A/C polymorphism genotype frequencies were significantly different in patients with hypertension compared with normotensive individuals. Specifically, the AGTR1 1166 AA genotype was twice as common in patients with hypertension as in those without (67% vs 33%), while the AC and CC genotypes were found predominantly in normotensive patients (p = 0.0016). The variant 1166C allele was much more common in patients without hypertension (67%) than in patients with hypertension (33%; p=0.0006). The variant AGT Thr235 allele was more common in patients without a family history of cardiovascular disease than in patients with this risk factor (p<0.05). The odds ratio (OR) for STEMI in patients with the heterozygous AGT 174 Thr/Met genotype was increased to 1.884 (95% confidence interval [CI] 1.03, 3.446; p<0.05), while the OR calculated for carriers of the AGT Met174 allele was 2.038 (95% CI 1.129, 3.68; p=0.0182). Significant genotypic associations of combinations of reninangiotensin system gene polymorphisms in STEMI were not observed. Conclusions: The most powerful predictive value for STEMI was represented by the Thr/Met genotype and the Met174 allele of the AGT Thr174Met gene polymorphism. In our study, in contrast to observations reported by other authors, the AA genotype of the AGTR1 1166A/C gene polymorphism — much more than other genotypes — was associated with hypertension.

Hepatocyte growth factor—a new marker for prognosis in acute coronary syndrome

This study was designed to check the properties of hepatocyte growth factor (HGF) as a new marker of myocardial necrosis. Materials and method. In one hundred and four patients with acute coronary syndrome (ACS), plasma human HGF (hHGF) concentrations were assessed twice, i.e. just after admission to hospital and 24 h afterwards. The primary composite endpoint was assessed at three-month follow-up. Results. The maximal concentration of hHGF (1902 pg/ml) was reached at the time of admission to hospital due to ACS with significant decrease 24 h after the first measurement (705 pg/ml p < 0.0001). hHGF levels in ST segment elevation myocardial infarction (STEMI) were higher than in non-ST segment elevation myocardial infarction (NSTEMI) and in patients who reached composite primary endpoint (33 patients—4211 pg/ml) vs. event-free 71 patients (1013 pg/ml p < 0.01). The correlation between values of hHGF and N-terminal prohormone B-type natriuretic peptide and cardiac troponin I was revealed. Conclusion. HGF is a very early, good marker of myocardial necrosis and a sensitive short- and long-term prognostic factor in ACS.

Stroke prevention in atrial fibrillation patients in Poland and other European countries: insights from the GARFIELD-AF registry

BACKGROUND Atrial fibrillation (AF) is the most common clinically-significant arrhythmia in the adult population, and it is a strong independent risk factor for cerebrovascular accidents. Patients with non-valvular AF are five times more likely to suffer a stroke. Despite the clear recommendations for anticoagulant therapy, many clinicians are still reluctant to provide routine oral anticoagulation to patients with AF, despite the potential clinical benefits. AIM To compare Polish and European populations of patients with AF and the every-day practice of stroke prevention in Poland and in the rest of Europe. METHODS We analysed the baseline data from the two first cohorts of patients enrolled in the GARFIELD-AF registry (an ongoing prospective, multicentre, international registry of patients newly diagnosed with AF) in Poland and in the rest of Europe. RESULTS Polish AF patients are generally younger (median age 67 years in both cohorts vs. 73 in cohort 1 in the rest of Europe and 72 in cohort 2), but they carry a burden of more concomitant diseases. There are some noticeable differences in stroke prevention between Poland and the rest of Europe. The use of vitamin K antagonists (VKAs) is generally higher in other European countries in both cohorts (in Poland 41.7% in cohort 1 and 36.9% in cohort 2 vs. 55.5% in cohort 1 and 41.9% in cohort 2 in the rest of Europe). Meanwhile, it is generally more common in Poland to treat patients with both VKAs and antiplatelets (in cohort 1 20.4% of patients in Poland received vs. 12.0% in the rest of Europe). A total of 5.6% of patients in cohort 1 in Poland receive no antithrombotic treatment (it means: no VKA, oral factor Xa or thrombin inhibitors, antiplatelets), meanwhile in other countries it amounts to 8.5%. The usage of non-vitamin K oral anticoagulants is growing in Poland similarly to the other European countries. CONCLUSIONS The GARFIELD-AF registry data shows how distant everyday clinical practice is from the guidelines. It shows that still in Poland, as well as in the rest of Europe, too many patients with low stroke risk are treated with anticoagulants, while too frequently patients at high stroke risk are left with no stroke prevention. Although the tendency to use non-vitamin K oral anticoagulants is growing comparably in Poland and in the rest of Europe, the proportion of patients with intermediate and high stroke risk is not growing and more patients at low stroke risk are treated with anticoagulants.

Influence of Some Cardiovascular Risk Factors on the Expression of Platelet Glycoprotein IIb/IIIa Receptors in Patients with Myocardial Infarction Treated with Antiplatelet Drugs under Primary Percutaneous Coronary Intervention

AbstractBackground: Platelet glycoprotein (GP) IIb/IIIa receptors are involved in platelet aggregation and acute thrombus formation. Changes in the expression of GP IIb/IIIa receptors are an important but little-explored aspect of antiplatelet therapy. Understanding these changes may be particularly relevant for elucidating the mechanisms and effects of GP IIb/IIIa antagonist therapy, and may help to establish methods to identify patients most likely to benefit from the use of GP IIb/IIIa blockade, or those especially prone to its thrombotic complications. The aim of this study was to evaluate the influence of common cardiovascular risk factors on the expression of GP IIb/IIIa receptors in patients with ST-segment-elevation myocardial infarction (STEMI) who received antiplatelet treatment under primary percutaneous coronary intervention (PCI). Materials and Methods: The study group consisted of 30 patients with STEMI who underwent PCI and who received antiplatelet treatment with aspirin (acetylsalicylic acid), a loading dose of clopidogrel and, if necessary, abciximab. The expression of platelet GP receptors was estimated by measuring the changes in the number of platelet antigens: CD41a (GP IIb/IIIa) and CD61 (GP IIIa). The assessments were performed in whole blood and on isolated platelets before and up to 24 hours after initiation of the antiplatelet therapy. The relationships between expression of platelet GP receptors and risk factors such as hypertension, smoking, diabetes mellitus, dyslipidemia, and family history of cardiovascular disease were examined using statistical analyses. Results: Before antiplatelet treatment, non-smokers had more receptors than smokers when antigen numbers were measured in whole blood. After treatment, the number of CD41a antigens present on isolated platelets significantly increased in non-smokers and in patients without dyslipidemia (p = 0.05). At the same time, the number of CD61 antigens increased in all patients except for those with diabetes. In patients without hypertension, the number of CD61 antigens (whole-blood measurement) increased considerably, and the difference between the patients with and without hypertension was significant (p = 0.01). The results of the study revealed that, after the treatment, the numbers of CD61 antigens were higher in patients without dyslipidemia and lower in patients with dyslipidemia compared with the results obtained from the preceding measurements. These different numbers of CD61 antigens significantly distinguished these two groups of patients from each other (p = 0.01). Conclusion: Non-smokers with STEMI have significantly higher expression of GP IIb/IIIa and IIIa receptors than do smokers. Up to 24 hours after the start of antiplatelet treatment, the number of GP IIb/IIIa receptors on the platelet surface did not depend on common cardiovascular risk factors such as hypertension, diabetes, smoking, and dyslipidemia. Patients without hypertension and without dyslipidemia tended to have more of only one component of the GP IIb/IIIa complex (i.e. GP IIIa, as represented by the antigen CD61) than the patients with these risk factors.

Expression of Platelet Surface Receptors and Early Changes in Platelet Function in Patients with STEMI Treated with Abciximab and Clopidogrel versus Clopidogrel Alone

BackgroundPlatelets play a crucial role in the pathogenesis of acute coronary syndromes (ACS). The efficacy of antiplatelet treatment is pivotal in the success of percutaneous coronary intervention (PCI) performed in patients with ACS.ObjectiveThe aim of the study was to investigate the effects of clopidogrel with or without abciximab on the expression of platelet surface receptors and platelet function in patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI.Materials and methodsThirty patients with STEMI were included in the study. During acute primary coronary intervention, patients received aspirin (acetylsalicylic acid) and clopidogrel in a loading dose of 300mg. Clopidogrel was the only antiplatelet therapy used by nine patients (group B). Twenty-one patients (group A) received additional abciximab. Blood samples were collected and analyzed twice: before and up to 22 hours after administration of antiplatelet therapy. The platelet aggregation was established as primary platelet-related hemostasis (closure time [CT] assessed using the PFA100 system). The absolute number of platelet surface antigens as CD41a, CD42a, CD42b, CD61, and CD62P were determined by flow cytometry analysis.ResultsThe study revealed a statistically significant increase in CT induced by adenosine diphosphate and adrenaline (epinephrine) +130 seconds (p < 0.0001) and +94 seconds (p < 0.0001), respectively, in group A patients post-therapy. While in group B the parameters of CT did not change after treatment. In addition, the absolute number of CD41a antigens (glycoprotein [GP] IIb/IIIa) increased significantly after treatment in group A. No significant changes were observed after treatment in the expression of CD62P (P-selectin) antigens in either treatment group. There was a significant reduction in the percentage of CD62P-positive platelets in group B after antiplatelet therapy.ConclusionsThe absolute number of GP IIb/IIIa receptors increases and platelets are not activated up to 12 hours after cessation of abciximab therapy. Treatment of STEMI patients undergoing PCI with a loading dose of clopidogrel reduces the percentage of active platelets but does not influence the CT.

Hepatocyte growth factor — the earliest marker of myocardial injury in ST-segment elevation myocardial infarction

BACKGROUND Hepatocyte growth factor (HGF) concentration increases in the first few hours of myocardial infarction (MI). AIM (1) To illustrate human HGF (hHGF) plasma concentration during the first 24 h of ST segment elevation myocardialinfarction (STEMI); (2) To estimate the odds ratio of STEMI in the context of hHGF measurements; (3) To describe the normalconcentration of hHGF in healthy subjects. METHODS The study groups consisted of 73 STEMI patients and 11 healthy volunteers. In all the patients, we took bloodsamples for hHGF twice, i.e. on admission to hospital and 24 h later. RESULTS The median value of hHGF in healthy volunteers was 666 pg/mL (576; 760 pg/mL). In STEMI, the highest values of hHGF were observed in the first measurement. An increase of 1 pg/mL in hHGF level increased STEMI odds ratio by 0.2%. CONCLUSIONS In acute MI, of the known biomarkers, hHGF rises the earliest and very promptly returns to normal values.

Polymorphisms of angiotensin II type 1 receptor gene and those of angiotensinogen point at culprit artery in ST-segment elevation myocardial infarction

UNLABELLED The aim of the study was to determine whether the presence of angiotensin II type 1 receptor 1166A/C gene polymorphism and two polymorphisms of angiotensinogen, namely Met235Thr and Thr174Met, pointed at the culprit artery in patients with ST-segment elevation myocardial infarction (STEMI). METHODS The AGTR1 1166A/C polymorphism and two AGT gene polymorphisms, Met235Thr and Thr174Met, were assessed in 100 patients with STEMI. RESULTS The odds ratio (OR) of circumflex artery (CRX) responsible for STEMI was 3.49 (95% CI: 1.1-10.8, p<0.05) for MetThr genotype for AGT Met235Thr gene and 4.54 (95% CI: 1.5-14.2, p<0.01) for ThrMet genotype for AGT Thr174Met gene. Homozygous ThrThr genotype for AGT Thr174Met gene reduced OR of CRX as culprit artery in STEMI (OR=0.29, 95% CI: 0.1-0.9, p<0.05). However, the highest OR that increased up to 13.71 (95% CI: 1.58-119.3) was shown in case of right coronary artery and C/C genotype for AGTR1 1166A/C gene. CONCLUSIONS Polymorphism of AGTR1 1166A/C gene can point at the right coronary artery as infarct-related artery in STEMI. Polymorphisms of AGT Met235Thr and AGT Thr174Met genes are able to mark increased or reduced odds ratio of circumflex artery as culprit artery in STEMI.

Hepatocyte growth factor concentration during the first day of acute coronary syndrome

Hepatocyte growth factor (HGF) can be produced by various cells and elicits multiple biological responses such as motility, proliferation, morphogenesis and survival in a cell type-dependent fashion. Apart from its physiological importance, HGF may contribute to many organ diseases [1–3]. We have already shown that conversely to routinely measured biomarkers of myocardial injury, human HGF (hHGF) increases to high levels in the very early phase of acute coronary syndrome (ACS) and then decreases rapidly during the first 24 h of ACS [4]. As described in our previous article, we measured hHGF concentration only twice, namely at admission and 24 h later [4]. We decided to establish the dynamicity of hHGF level changes on the first day of myocardial injury and to determine the usefulness of its measurement in the case of untimely complications. In 4 patients with ST-segment elevation myocardial infarction (STEMI) and in 2 patients with non ST-segment elevation myocardial infarction (NSTEMI), who were eligible for coronary angiography and, possibly, primary percutaneous coronary intervention (PPCI), hHGF measurements were repeated 10 times during the first day of ACS and once at discharge from hospital (Figure 1). Each subject expressed their informed consent to participate in the study. Patients’ informed consent and the protocol of the study were approved by the Institutional Local Ethics Committee. Patients’ detailed particulars are presented in the Table I. Figure 1 Human HGF concentrations in six patients with ACS Table I Detailed description of six patients with ACS Human HGF was determined in plasma using the Quantikine Elisa kit from R&D Systems, Minneapolis, MN, USA. The mean value of hHGF evaluated in EDTA plasma using the Quantikine Elisa kit and presented in the manufacturers brochure as a reference value was 787 pg/ml (range: 469-1113 pg/ml). In the first measurement, as illustrated in the Figure 1, a marked increase in hHGF levels was observed in STEMI patients. Very high values (maximally about 20 000 pg/ml) were reduced to almost normal values within 5 h from the first measurement. In NSTEMI patients, even in the first assessment we did not observe very high levels of hHGF, and during the first 24 h of ACS, hHGF levels were stable. Contrary to patients with an uncomplicated acute course of STEMI, 2 patients with serious cardiovascular events in the acute stage of myocardial infarction, namely cardiac arrest and early reocclusion of the coronary artery, revealed a second increase of hHGF levels during the first 24 h of ACS (Figure 1). We have already revealed that during the first 24 h of ACS HGF showed properties comparable with troponin I and N-terminal prohormone B-type natriuretic peptide (NT-proBNP), which are routinely used as markers of ischemic myocardial damage and risk stratification in patients with impaired left ventricular function [4–7]. Troponin I reached peak values and confirmed myocardial necrosis when hHGF levels were already at a normal level [4]. Now, the very high hHGF values were observed in patients admitted within the first 2 h of STEMI presentation (patients 5 and 6) (Figure 1, Table I). In this aspect, the observed changes in hHGF concentrations in the early stage of myocardial infarction are a great advantage of this diagnostic method. The time from the onset of ACS symptoms to treatment, effectiveness of reperfusion therapy measured as grade of flow in the infarct-related artery, and medical therapy applied during PPCI influence the levels of biomarkers [5, 8]. We supposed that in our study hHGF re-elevation was connected with acute complications of ACS. Due to the small number of patients we cannot definitely prove this relationship. We hope that subsequent research will confirm our preliminary observations. In conclusion, we found that: (1) in all our patients the highest hHGF values were observed at admission due to symptoms of acute coronary syndrome, (2) hHGF concentrations were reduced to normal values very quickly (within 5 h from the first measurement), (3) severe complications in the acute stage of STEMI most likely resulted in an additional increase in hHGF levels.

A severe complication after ST-segment elevation myocardial infarction (Part 2)

We report the case of a 70-year-old woman with ST-segment elevation myocardial infarction of the anterior wall, complicated by ventricular septal rupture (two septal defects--VSDs) with symptoms of cardiogenic shock. After 6 weeks of conservative treatment with inotropes and intra-aortic balloon support, the patient underwent surgical repair of VSDs with good clinical outcome.