Anna Lisowska

Apelin in acute myocardial infarction and heart failure induced by ischemia.

Apelin is a recently isolated novel endogenous ligand for the angiotensin-like 1 receptor (APJ). Initial experiments in animal models indicate that the cardiovascular system is the main target of the apelin-APJ system. Apelin plays an opposite role to the renin-angiotensin-aldosterone system as a compensatory mechanism. It is reduced in patients with heart failure, also of ischemic origin. However, only animal studies concern the role of the apelin-APJ system in myocardial ischemia. Less is known about the function of this adipokine in an acute phase of myocardial infarction in human. The apelin-APJ system could perhaps be involved in myocardial protection during acute myocardial ischemia. In the current review we have summarized recent data concerning the role of apelin in acute myocardial infarction and heart failure induced by ischemia.

Decreased free sphingoid base concentration in the plasma of patients with chronic systolic heart failure

PURPOSE In recent years, the role of sphingolipids in pathophysiology of the heart attracted much attention. Ceramide was found to be involved in the pathogenesis of cardiac dysfunction in animal models of ischemia/reperfusion injury, type 2 diabetes and lipotoxic cardiomyopathy. On the other hand, sphingosine-1-phosphate (S1P), has been shown to possess potent cardioprotective properties. The aim of the present study was to examine plasma concentrations of major sphingolipids in patients with chronic heart failure (HF). MATERIAL AND METHODS The subjects were divided into two major groups: 1) with chronic systolic HF (n=47), and 2) healthy age-matched controls (n=15). Patients in the former group were further divided according to the underlying cause of HF (ischemic heart disease or idiopathic dilated cardiomyopathy, n=29 and 18, respectively). RESULTS Plasma concentrations of S1P, sphinganine-1-phosphate and ceramide observed in both groups of HF patients were very close to these noted in the healthy controls, and no statistically significant differences were found. However, the level of free sphingosine and sphinganine in the plasma of patients with HF decreased by 25 and 27%, respectively, as compared to the control subjects. This effect was independent from the underlying cause of HF as the mean concentrations of these sphingoid bases in patients with ischemic and idiopathic HF were virtually the same. CONCLUSIONS We conclude that chronic heart failure is associated with decreased concentration of free sphingoid bases in the plasma. However, despite lower availability of substrates required for synthesis of cardioprotective sphingoid base-1 phosphates, their plasma level remains stable.

Sustained decrease in plasma sphingosine-1-phosphate concentration and its accumulation in blood cells in acute myocardial infarction.

Sphingosine-1-phosphate (S1P) is a cardioprotective sphingolipid present at high concentration in plasma and blood cells. However, effect of the myocardial infarction on S1P metabolism in blood is poorly recognized. Therefore, we aimed to examine the dynamics of changes in concentration of sphingolipids in blood of patients with acute ST-segment elevation myocardial infarction (STEMI). The study was performed on two groups of subjects: healthy controls (n=32) and patients with STEMI (n=32). In the latter group blood was taken upon admission to intensive heart care unit, and then on the second, fifth and thirtieth day, and approximately two years after admission. STEMI patients showed decreased plasma S1P concentration and accumulation of free sphingoid bases and their 1-phosphates in erythrocytes. This effect was already present upon admission, and was maintained for at least thirty days after the infarction. Interestingly, two years post-infarction plasma S1P level recovered only partially, whereas the content of erythrocyte sphingolipids decreased to the values observed in the control subjects. The most likely reason for the observed reduction in plasma S1P level was its decreased release or increased degradation by vascular endothelial cells, as we did not find any evidence for downregulation of S1P synthesis or release by blood cells. We conclude that patients with STEMI are characterized by marked alterations in sphingolipid metabolism in blood which could be a consequence of the infarction itself, the antiplatelet treatment given or both. Our data suggest that cardioprotective action of S1P may be diminished in patients with acute myocardial infarction.

Dose-dependent effect of aspirin on the level of sphingolipids in human blood

PURPOSE Aspirin is an antiplatelet drug which is commonly used in secondary prevention in ischemic heart disease and cerebrovascular events, and in newly diagnosed myocardial infarction. The aim of the present study was to examine effect of aspirin on the level of selected sphingolipid intermediates in plasma, erythrocytes and platelets. MATERIAL AND METHOD Forty two healthy volunteers participated in the study. They were divided into two groups. In one group aspirin was given orally, daily, for one week in a dose of 75 mg (n=25). The subjects from the second group received one 300 mg dose of the drug (n=17). In both groups the blood was taken 4h after the last dose of aspirin. The following sphingolipid intermediates were quantified using high-pressure liquid chromatography: sphinganine, sphingosine, sphingosine-1-phosphate (S1P), sphinganine-1-phosphate (SA1P) and ceramide. RESULTS It was found that lower dose of aspirin increased the level of S1P and ceramide in erythrocytes (by 23 and 37%, respectively) having no effect on plasma and platelet sphingolipid levels. Higher dose of the drug reduced S1P and SA1P concentration in the plasma (by 16 and 10%, respectively). CONCLUSION We conclude that aspirin interferes with sphingolipid metabolism in blood and that this effect depends on a dose of the drug. Since S1P is a potent cardioprotectant, the reduction in its plasma concentration after the loading dose of aspirin could be undesired side effect of the drug.

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.

Myocardial perfusion and intima-media thickness in patients with subclinical hypothyroidism.

PURPOSE The data concerning the relation between subclinical hypothyroidism (SH) and the risk of cardiovascular disease are divergent. We aimed to assess myocardial perfusion in contrast-enhanced echocardiography and intima-media thickness (IMT) in patients with SH. MATERIAL/METHODS Forty females with SH without symptoms of coronary artery disease and 15 healthy female volunteers were examined. Echocardiographic evaluation of the left ventricle function as well as carotid and femoral IMT complex measurements were performed at baseline. Thereafter, dobutamine stress echocardiography with myocardial perfusion assessment at rest and on the peak of stress test was performed. SonoVue® intravenous bolus as a contrast medium was used. The myocardial perfusion was assessed by quantitative method using Q-LAB Philips software (ROI modality). The perfusion index was calculated (a number of left ventricle segments with improved perfusion/a number of all segments). RESULTS A mean IMT value in the SH group was significantly higher than in the controls (0.7 mm vs. 0.38 mm, p=0.001). Myocardial perfusion at rest and at the peak of stress test was significantly lower in the SH patients as compared to the controls (at rest 120 Db in SH vs. 181 Db in controls, p=0.039 and at the peak of stress 115 Db and 188 Db, p=0.01, respectively). The perfusion index was not significantly worse in the SH group (p=0.6). IMT values negatively correlated with the myocardial perfusion index at the peak of stress (r=-0.54, p=0.014). CONCLUSIONS In patients with SH contrast-enhanced echocardiographic examination revealed myocardial hypoperfusion and increased IMT. Our results may suggest that the patients with SH are at risk of the development of cardiovascular disease.

Adiponectin – An independent marker of coronary artery disease occurrence rather than a degree of its advancement in comparison to the IMT values in peripheral arteries

OBJECTIVE The aim of the study was to establish whether adiponectin may act as an independent risk factor of coronary artery disease (CAD) and if adiponectin has potential relations with a new marker of cardiovascular risk -intima-media thickness (IMT). METHODS 165 patients, who had undergone coronary angiography due to symptoms of CAD were enrolled. Selected clinical and biochemical risk factors were assessed, adiponectin concentrations and IMT were measured. RESULTS A significantly lower adiponectin concentrations in the CAD group, as compared to the controls, were found. Adiponectin concentration did not correlate with a degree of coronary vessels changes advancement. No correlation between adiponectin concentrations and IMT values in the studied peripheral arteries were found. The value of 9.8 ug/ml has been assigned as a cut-off value. Adiponectin concentrations <9.8 μg/ml had the highest positive predictive value (PPV=95.7%) and specificity (90.9), but low sensitivity (30.8). In the multilogistic regression analysis significant variables influencing the appearance of CAD were found: HDL-C (p=0.011, OR=0.88, 95%CI 0.80-0.97), IMT in CCA (p=0.0048, OR=5.25, 95%CI 1.65-16.75), IMT in CFA (p=0.015, OR=1.65, 95%CI 1.10-2.48 ), and adiponectin concentration <9.8 μg/ml (p=0.032, OR=28.95, 95%CI 1.31-641.48). CONCLUSIONS Adiponectin is an independent risk factor of coronary artery disease occurrence, but not its advancement. No correlation between adiponectin concentration and IMT values in peripheral arteries was shown.

Serum adiponectin and markers of endothelial dysfunction in stable angina pectoris patients undergoing coronary artery bypass grafting (CABG)

PURPOSE It has been established that endothelial dysfunction (ED) occurs after coronary artery bypass grafting (CABG). The aim of the study was to assess whether adiponectin may act as a novel marker of ED and its potential relations with new markers of ED: novel cell adhesion molecule CD146, a natural anti-thrombin glycoprotein - thrombomodulin (TM) and the well-established ED marker - Von Willebrand factor (VWF) in coronary artery disease (CAD) patients undergoing CABG. MATERIAL/METHODS 45 CAD patients undergoing elective CABG were included in the study. RESULTS In the study group the concentration of adiponectin and CD146 before the surgery were significantly lower than in the control group - 6.06 μg/ml ± 3.06 vs. 19.0 μg/ml ± 6.4 and 303.2 ng/ml ± 28.7 vs. 328.1 ng/ml ± 22.6 (p<0.05). Significant increase of adiponectin and CD146 concentration 3 months after CABG vs. before the surgery was found. Adiponectin concentration 3 months after CABG correlated with VWF, TM, CD146, and a number of grafts. CD146 before and 3 months after CABG correlated significantly with adiponectin, VWF activity as well as the statins therapy after the surgery. CONCLUSIONS In CAD patients undergoing CABG new markers of endothelial cell dysfunction as adiponectin and CD146 are significantly lower compared to healthy volunteers. Significant increase in adiponectin and CD146 concentration 3 months after CABG vs. before the surgery was found. However adiponectin concentrations 3 months after CABG were still significantly lower compared to healthy individuals, whereas CD146 concentration returned to the values comparable to the control.

Iatrogenic femoral pseudoaneurysms - a simple solution of inconvenient problem?

PURPOSE A femoral artery pseudoaneurysm - is the most common complication associated with invasive coronary interventions. The aim of the study was to analyze the effectiveness of various methods used for femoral pseudoaneurysm treatment and to assess how routine use of radial approach leads to reduction of these site complications. METHODS The study comprised 1854 consecutive patients who were hospitalized in years 2005-2008 and underwent coronary angiography (with or without angioplasty) via femoral artery access. Since 2009 routine radial approach has been introduced for both coronary angiography and angioplasty. In patients with symptoms suggesting entry site complications Doppler ultrasound was performed. RESULTS Femoral access site complications requiring additional procedures were observed in 63 patients (3.4%): in 56 femoral pseudoaneurysms (88.8%) and in 7 arteriovenous fistulas (11.1%) were diagnosed (all appeared after coronary angioplasty). The patients were treated in following ways: standard compression with an elastic bandage prolonged to 12 hours - in 14 cases (25%), ultrasound guided compression - in 13 patients (23.2%), finger compression followed by standard compression with an elastic bandage prolonged to 12 hours or ice compress - in 10 patients (17.8%), surgical treatment - in 3 patients (5.3%). Only 2 patients required thrombin injection (3.6%). Since the time routine radial approach was introduced extreme reduction in the rate of local complications was registered. CONCLUSION Although iatrogenic femoral pseudoaneurysms following invasive percutaneous coronary interventions are still important complications, most of them can be treated conservatively. It seems that radial access completely eliminates the risk of this complication.

The importance of intima-media thickness (IMT) measurements in monitoring of atherosclerosis progress after myocardial infarction.

PURPOSE Intima-media thickness (IMT) assessed in peripheral arteries correlates with presence and progression of atherosclerosis in coronary arteries. IMT measurements may help to select high risk patients and evaluate the efficacy of the therapy used. AIM The aim of the study was to assess the usefulness of ultrasonographic measurement of IMT in atherosclerosis progress monitoring in patients after myocardial infarction (MI). PATIENTS AND METHODS 70 men (mean age 52.8 ± 8.4) treated with PCI due to acute myocardial infarction, were enrolled in the study. All subjects underwent ultrasound examination of the IMT complex of: common carotid artery (CCA), carotid bulb and common femoral artery (CFA) during hospitalization and follow-up period (3.83 ± 1.29 years). RESULTS During the follow-up 3 patients (4.3%) were not on any medications, 8 pts (11.4%) were on reduced doses of β-blocker, statin or ACE-I (non-compliant pts.). The others (compliant) - 59 pts (84.3%) received standard pharmacological treatment after MI. Nevertheless, an increase of IMT complex value after follow-up compared to initial IMT values of all examined peripheral arteries was observed (respectively: IMT CCA - 0.91 ± 0.26 vs 1.10 ± 0.36, p=0.002, IMT of carotid bulb - 1.31 ± 0.55 vs 1.82 ± 0.69, p=0.012, IMT CFA - 1.38 ± 0.64 vs 1.97 ± 0.75, p=0.014). Non-compliant patients had statistically significant higher IMT values after follow-up when compared to compliant subjects (1.62 vs 1.20, p= 0.017). Patients with higher IMT values were reported to have cardiac events more frequently during the follow-up (p<0.05). CONCLUSIONS Our results provide evidence that ultrasonographic IMT complex assessment of peripheral arteries in everyday clinical practice allows monitoring efficacy of pharmacological therapy in CAD patients after MI. They also suggest treatment intensification if necessary.