Daria Pašalić
Department of Medical Chemistry, Biochemistry and Clinical Chemistry
Zagreb University School of Medicine
Šalata ul 2.
10 000 Zagreb, Croatia
Phone +385 (1) 4590 205; +385 (1) 4566 940
E-mail: dariapasalic [at] gmail [dot] com

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Biasucci LM.S09-1: Pathophysiology of acute coronary syndromes: from vulnerable plaque to vulnerable patient. Biochemia Medica 2009;19(Suppl 1):S69-S70.
Institute of Cardiology, Catholic University of Sacred Heart, Rome, Italia
Corresponding author:lmbiasucci [at] virgilio [dot] it
Several factors are implicated in the transition between stable or asymptomatic coronary artery disease (CAD) and ACS. Among the multiple and complex mechanisms, plaque rupture is considered the trigger event in this process. However, equally common is the finding of fissures or of thrombi superimposed on simple erosion of fibrous plaque. This phenomenon can be considered as a result of endothelial activation or erosion: activated endothelium, in fact, may change from antithrombotic and anti-adhesive to prothrombotic.
Plaque formation is a long-standing process, initiating with lipid and leukocyte infiltration and leading to the artery remodelling. Subsequently the plaque starts to grow into the vessel and there is a reduction of the vessel lumen and of the blood flow. Atherosclerotic plaque prone to dysruption, consists of a lipid-rich core in the central portion of the eccentrically thickened intima, limited by a thin fibrous cap. The core also contains many lipid-laden macrophage foam cells. These cells secrete proteolytic enzimes, as plasminogen activators and matrix metallo-proteinases (MMPs), weakening fibrous cap, and produce large amounts of TF, stimulating thombus formation. Also lymphocytes, mast cells and neutrophils are present in all stages of plaque development and are implicated in the pathological process leading to the development of clinical manifestations.
In addiction to the local factors, implicated in plaque dysruption and instability, one should consider that many ACS patients have more than one unstable coronary lesion. Moreover, post mortem-studies have shown the presence of multiple fissured coronary atherosclerotic plaques in individuals who did not die from cardiac causes. Intravascular ultrasound studies in ACS patients also showed the common presence of multiple fissured plaques.
Moreover, the presence of multiple inflamed coronary plaques and the widespread coronary and myocardial inflammation observed in ACS patients suggest that inflammation may be responsible for simultaneous development of multifocal coronary instability, with or wihout plaque rupture. Since the pionereestic studies by Neri-Serneri and Liuzzo demostrating a causative link between immunity and coronary instability, many others have confirmed the importance of inflammatory markers in ACS. Among different inflammatory markers, C-Reactive Protein has been the most extensively studied, either for the prediction of incident myocardial infarction, CAD and for the prediction of recurrent events in patients with manifest atherosclerotic disease.
The features of the plaque instability, described above, have raised the question of whether is vulnerable, the plaque or the patient. The idea that plaque vulnerability is exclusively a consequence of plaque characteristics is challenged by many observations, from the evidence of multiple vulnerable plaques in the same patients to that of widespread coronary inflammation. The concept of vulnerable patient has important clinical implications.
Growing evidences suggest that plaque rupture is not the only cause of ACS. Mechanisms leading to plaque disruption or activation, in fact, are not confined to the plaque: it is likely that a systemic inflammatory condition, together with hypercoagulability state, activates local hemodynamic, mechanical and immune reactions leading to plaque destabilization.
Christenson RH. S09-2: Biomarkers of acute coronary syndromes and heart failure: Bargin or budget breaker? Biochemia Medica 2009;19(Suppl 1):S71-S72.
University of Maryland School of Medicine, Baltimore, MD, USA
Corresponding author:rchristenson [at] umm [dot] edu
Cardiovascular disease is the accounts for over 800,000 deaths, 6 million hospitalizations and has an estimated cost of over $71 billion annually in the US. Most acute cardiovascular events are due to the “acute coronary syndromes” (ACS), a continuum of disease ranging from unstable angina to frank myocardial infarction (MI). Congestive heart failure (CHF), affects over 5.3 million Americans, is responsible for č1 million hospitalizations and 285,000 deaths each yearly at an annual cost burden of $29.6 billion. Biomarkers of ACS and HF have revolutionized the diagnosis, risk stratification and management of these conditions. The question to be addressed by this talk is “has utilization of biomarkers been a bargain or a bust in these conditions?”.
Current guidelines for biochemical marker testing will be utilized to identify the recommended use of necrosis biomarkers in suspected ACS patients and for testing BNP or NT-proBNP in suspected CHF patients. Costs for testing in compliance with guidelines will be compared with strategies used prior to establishment of these guidelines. The assumed cost of troponin and CK-MB is $18, and $5 for total CK.
The Global Task Force has redefined the diagnosis of MI as detection of the rise and/or fall in cardiac troponin with at least one value above the 99th percentile of the upper reference limit together with evidence of myocardial ischemia. NACB guidelines recommend troponin measurement in all patients having signs and symptoms consistent with ACS for MI diagnosis, risk stratification and management. In the context of CHF, BNP or NT-proBNP testing is recommended in the acute setting to rule out or to confirm the diagnosis of heart failure among patients presenting with ambiguous signs and symptoms. Prior to the MI redefinition and guidelines, three tests were commonly performed: cardiac troponin, CK-MB and total creatine kinase activity. Before availability of BNP and NT-proBNP, CHF was diagnosed using clinical tools alone. A randomized controlled trial compared BNP testing with no BNP testing, finding a significantly shorter hospital stay and savings of about $1,500 in patients who received BNP testing.
Assuming 5 million patients would receive troponin testing at $18 per test, the total cost is $90 million. Thus guideline-compliant testing potentially results in a savings of $135 million. For BNP testing, assuming 500,000 patients per year have ambiguous signs and symptoms of CHF, there is a potential savings of $750 million. Utilization of cardiac markers in accordance with guidelines is a clearly a bargain and could potentially save the US healthcare $900 million annually.
Dvornik Š.S09-3: BNP and cardiovascular markers in emergency laboratory diagnostic. Biochemia Medica 2009;19(Suppl 1):S72-S73.
Department of laboratory diagnostics, Rijeka Clinical Hospital Centre, Rijeka, Croatia
Corresponding author:laboratorij [at] kbc-rijeka [dot] hr
Cardiovascular diseases are presently the leading causes of death in industrialized countries. Large proportion of all acute hospitalizations are the patients with chest pain, and distinguishing those with acute coronary syndrome (ASC) from all patients with suspected cardiac pain still represents great diagnostic challenge.
The basic pathophysiological mechanism in most ACS is atherosclerotic plaque rupture with differing degrees of thrombosis and distal embolisation, resulting in myocardial underperfusion, ischemia and myocardial cell injury. The leading symptom that initiates the diagnostic and therapeutic cascade is chest pain, but the classification of patients is based on the electrocardiogram (ECG) and there are two categories of patients. In the first group are patients with typical acute chest pain, persistent ST-segment elevation (> 20 min) and probably total coronary occlusion (STEMI). In the second group are the patients with acute chest pain but without persistent ST-segment elevation or no ECG changes at all (NSTE-ACS). The diagnosis of NSTE-ACS is more difficult to established, it is more frequent than STEMI, and mortality of STEMI and NSTE-ACS after 6 months is comparable.
During last years a number of guidelines and recommendations were published in order to help physicians to make decisions in ACS patient management, to prevent mortality and to reduce health care costs. Nevertheless, new studies constantly challenge the current recommendations. A great number of novel biomarkers have been investigated in order to explore their usefulness as diagnostic tools or for risk stratification. All these markers reflect different pathophysiological aspects of ACS as myocardial cell injury, inflammation, platelet activation or neurohormonal activation.
cTnT and cTnI are the preferred markers of myocardial injury. They are the best biomarkers to predict short term (30 days) as well as long-term outcome and they are useful for selecting appropriate treatment. hsCRP is a marker of inflammation, elevated levels are predictive of long-term mortality, but it has no role for diagnosis of ACS.
Brain natriuretic peptides are biochemical markers for neurohumoral activation of heart. They are highly sensitive and specific markers for left ventricular dysfunction. Recently, there is a great interest for emergency determination of BNP. They are helpful in differentiating between cardiac and non-cardiac dyspnoea at hospital admission, and they are markers for long-term prognosis, but have limited value for selecting appropriate treatment and initial risk stratification.
Several studies demonstrated that combined use of markers may significantly help in risk stratification.
Point of care testing (POCT) for biochemical markers in emergency rooms are recommended, since diagnose in ASC patients should be made as soon as possible. They have to be implemented if central laboratory cannot provide results within one hour. They are easy to perform, results are usually reliable, no special skills are required, but adequate training is necessary.
Among number of novel biomarker that have been studied during last years there are biomarkers of oxidative stress (myeloperoxidase), marker of inflammation and thrombosis (soluble CD40 ligand), markers of endothelial dysfunction (endothelin and adhesion molecules) and inflammation markers (IL-6, IL-1, TNF-alfa). Their usefulness as diagnostic tools and for risk stratification still has to be established.
Vrkić N.S09-4:Lipoprotein metabolism disorders in psychiatric patients. Biochemia Medica 2009;19(Suppl 1):S74-S75.
University Department of Chemistry, Sestre Milosrdnice University Hospital, Zagreb, Croatia
Corresponding author:nvrkic [at] gmail [dot] com
Lipids have several important functions in the central nervous system. They are constituents of the neuronal membrane, play a significant role in the process of neurotransmission and in the second messenger system in the brain.
Psychiatric patients are very heterogeneous group with various type of lipid abnormalities. Most of the patients are under a higher risk for atherosclerosis, metabolic syndrome and weight gain. Estimation of blood lipids and lipoproteins have a great predictive value in determing coronary heart disease risk.
Low concentration of cholesterol, apo A-I and HDL-cholesterol, increased level of homocysteine were found in patients with schizophrenia, anxiety disorders, antisocial personality, borderline personality disorder, suicidal or aggressive behavior as well as in population with antisocial behavior with criminal history. Depressed patients with suicid attempts have lower serum cholesterol (in men, not in women). This finding support the hypothesis that major depression is accompanied by impaired or reversed cholesterol transport. Low cholesterol level is believed to enhance the risk of depression due to the neuronal dysfunction occurring be cause of changes in microviscosity of the cellular membrane or disorders in signal transduction. The other, cytokine hypothesis suggests the pathophysiology of depression by means of changes of hypophyseal-adrenal axis as a consequence of the effect of cytokines. Cytokines influence the metabolism of lipids, by means of influencing the effect of lipoprotein-lipase which affects the metabolism of lipids.
Patients with related PTSD (postraumatic stress disorder) had higher cholesterol, LDL-cholesterol, triglycerides and lower HDL-cholesterol. Atherosclerosis index and established risk factor for atherosclerosis are higher in PTSD than in the health.
Hypercholesterolaemia and elevated LDL-cholesterol is commom finding in patients with anorexia nervosa. LDL particles are significantly more enriched in cholesterol and triglycerides. Elevated cholesterol is due to an increase in LDL-cholesterol which is mostly determinated by the severe loss of body fat and the resulting changes in thyroid hormones. Hormones increased lipolysis and decreased endogenous cholesterol synthesis with resulting decrease in LDL removal, decrease cholesterol catabolism which contribute to higher LDL-cholesterol and decrease bile acid synthesis.
Altogether, psychiatric patients developed lipid and bodily abnormalities after beginning treatment with antipsychotic drugs. Antipsychotics have the capability to cause an increase in serum leptin levels (hormone that is mainly produced by adipocytes). Leptin may also act on peripheral tissues by inhibiting cellular lipid metabolism. However, obesity in humans is generally associated with high serum leptin levels and a probable leptin resistance in the hypothalamus, resulting in increased appetite and weight. In addition, hyperleptinaemia may alter peripheral insulin resistance and has been suggested to be a link between obesity and insulin resistance. The vast majority of the studies reports concerning some antipsychotics treatment is associated primarily with an increase only in triglyceride and the others show both hypertriglyceridaemia and hypercholesterolaemia. Antipsychotic agents increase apoA-I levels as part of their therapeutic actions which suggest that the decreased levels of apoA-I may be associated with the pathology of schizophrenia.
Some studies report differential diagnostics role of lipids. Serum concentrations of lipids and lipoproteins could be intend as biomarkers to differentiate clinical subtypes of depressive disorders.
Fišić E.S09-5: Acute stroke – role of laboratory diagnostic. Biochemia Medica 2009;19(Suppl 1):S75-S76.
Department of laboratory diagnostics, Rijeka Clinical Hospital Centre, Rijeka, Croatia
Corresponding author:elizabeta [dot] fisic [at] ri [dot] t-com [dot] hr
Acute stroke is rapid forming local neurologic lack or sometimes global damage of brain function. It begins with injured part of brain tissue because of blocked brain vein with clog and interruption of circulation or because of cracking vein with bleeding in brain. It is a leading cause of death and disability in Croatia.
After CVI one third of patients get well until complete independently with minor consequence, one third of them have permanent invalidity and one third died in moment of CVI. CVI in every patient is separate, depends on numerous factors, from side of brain which is hit with attack to the general health condition.
Medical treatment of patients with stroke is very complex and multidisciplinary. Early differentiation between ischemic from hemorrhagic stroke is extremly important for acute therapy, subsequent treatment of the patient and for ultimate outcome. The most important diagnostic procedure for acute stroke are computerized tomography (CT) or magnetic resonance (MRI). CT could distinquish ischemic or hemorrhagic stroke, but interpretation of brain imaging appearances can be difficult, they see the early changes after a stroke in the first few hours, but it can be overlooked early signs if ischemia or smaller lesions are not displayed. Today, the diagnosis of ischemic stroke is based on an experienced stroke clinician’s examination of the patient, supplemented by the result of brain imaging (CT). In spite of this, the clinicians are often uncertain whether the diagnosis of stroke is secure enough with the support of image display, which is often not enough to set the correct diagnosis and thus initiate appropriate treatment.
In the last ten years searching for biomarkers in blood or cerebro-spinal fluid has been intensive. Those biomarkers should help in diagnosis of stroke and in distinquishing ischemic from hemorrhagic stroke. Many blood markers, about 60, have been proposed for the diagnosis of stroke in the acute settings. Some of them are highly correlated with stroke: markers of inflammation (matrix metalloproteinase-9: MMP-9, vascular cell adhesiom molecule: VCAM, interleukine-6 (IL-6), marker of impaired hemostasis and thrombosis (von Willebrandt factor) a marker of glial activation (S100β, mielin basic protein: MBP, neuron specific enolase: NSE). Several of this mediators, including IL-6, are elevated within hours after ischemia and corelate with infarct volume, but such inflammatory markers lack the specificity necessary for a useful diagnostic test.
The search for a rapid serum diagnostic tests of ischemic brain injury remains important in the management of acute stroke, although faces difficulties. The blood-brain barrier slows the release of brain tissue proteins into blood, delaying the release of glial and neuronal proteins. Many potential blood markers of cerebral ischemia and inflammation are found in other conditions that may mimic stroke (myocardial infarction, brain infection). Also, the volume of damaged tissue may not correlate with disability (it depends of part of the brain). Another difficulties are in conection with methodological quality (standardization and quality control). Inspite of these, using a combination of biomarkers may be a feasible strategy to improve the diagnosis of brain stroke in the acute phase.