Dragan Dincic

THERAPEUTIC APPROACH IN PATIENTS WITH A FLOATING THROMBUS IN THE RIGHT HEART

BACKGROUND The occurrence of a floating thrombus in the right heart, although rare, is a life-threatening condition requiring a specific approach. In most cases, these thrombi are a result of embolization from deep venous thrombosis, and have lodged temporarily in the right heart. The management of this condition is variable, depending on whether or not there is a thrombus entrapped within a foramen ovale (FO). OBJECTIVES To present the management of 2 patients with a free-floating thrombus in the right heart, and a third patient with an entrapped thrombus in the FO. CASE REPORTS Two patients with a free-floating thrombus in the right atrium who were treated with thrombolytic therapy had an immediate excellent outcome. The patient with a thrombus entrapped within the FO was scheduled for surgical removal of the thrombus due to an unacceptable risk of systemic embolization if treated with thrombolytic and anticoagulant therapy. Unfortunately, he developed an ischemic stroke on the fifth day of presentation, just a few hours before the scheduled surgery, despite meticulous monitoring of continuous heparin infusion with activated partial thromboplastin time. CONCLUSION Thrombolytic therapy is recommended in patients with a free-floating thrombus in the right heart. However, in patients with a thrombus entrapped within an FO, delaying surgical removal of the thrombus may be deleterious due to unpredictable systemic embolization.

The association of ACE I/D gene polymorphism with severe carotid atherosclerosis in patients undergoing carotid endarterectomy

Introduction: The ACE I/D polymorphism was mostly investigated in association with intima-media thickness, rarely with severe atherosclerotic phenotype. Materials and methods: We investigated the association of I/D polymorphism with severe carotid atherosclerosis (CA) (stenosis > 70%) in asymptomatic and symptomatic patients undergoing carotid endarterectomy. The 504 patients subjected to endarterectomy and 492 healthy controls from a population in Serbia were investigated as a case-control study. Results: The univariate logistic regression analysis revealed ACE DD as a significant risk factor for severe CA (odds ratio [OR] = 1.3, 95% confidence interval [CI] 1.0–1.7, p = 0.04). After adjustment for the common risk factors (age, hypertension, smoking, and HDL) ACE was no longer significant. However, we found a significant independent influence of DD genotype on plaque presence in a normotensive subgroup of patients (OR 1.8, CI 1.2–3.0, p = 0.01, corrected for multiple testing). In symptomatic patients D allele carriers were significantly more frequent compared with asymptomatic patients (OR 1.6 CI 1.0–2.6, p = 0.05). Conclusions: Our data suggests that ACE I/D is not an independent risk factor for severe CA. On the other hand, a significant independent genetic influence of ACE I/D appeared in normotensive and symptomatic patients with severe CA. This should be considered in further research toward resolving the complex genetic background of severe CA phenotype.

Apolipoprotein(a) gene polymorphisms (TTTTA)n and G/A-914 affect Lp(a) levels in ischemic heart disease patients from Serbia

SummaryOBJECTIVES: Lipoprotein(a) (Lp(a)) concentration is determined primarily by the apolipoprotein(a) (apo(a)) gene. The pentanucleotide (TTTTA)n repeat and G/A-914 polymorphisms are in the 5′ promoter region of the apo(a) gene. To elucidate whether these polymorphisms affect Lp(a) levels, a total of 211 Serbian adults were investigated. DESIGN: One hundred and eleven patients with ischemic heart disease and 100 healthy controls were genotyped and Lp(a) levels determined. RESULTS: Lp(a) concentrations differed according to the (TTTTA)n genotypes: among those having at least one allele 8, patients had significantly higher Lp(a) values than controls. A decreasing trend of Lp(a) values was associated with the –914A allele in controls but the opposite was true in patients. Patients with genotype TTTTA allele 8/AA-914 had significantly higher Lp(a) values than those without allele 8/AA (p < 0.05). The >8>8/GG genotype was not detected. Significant linkage disequilibrium between (TTTTA)n and G/A-914 polymorphism (p < 0.001) was found. In multivariate regression analysis, the G/A-914 polymorphism significantly (p < 0.05) affected Lp(a) levels in patients, after taking into account the (TTTTA)n polymorphism. CONCLUSION: These results indicate that (TTTTA)n and G/A-914 polymorphisms affect Lp(a) levels in ischemic heart disease as a consequence of the linkage disequlibrium.ZusammenfassungZIEL: Das Lipoprotein(a) (Lp(a)) wird hauptsächlich vom Apolipoprotein(a)-(Apo(a)-)-Gen bestimmt. Im 5′-Promotor-Gen des Apo(a)-Gens bestehen Pentanukleotid-(TTTTA)n-Wiederholungs- und G/A-914-Polymorphismen. Ziel dieser Studie war es, einen möglichen Einfluss dieser Polymorphismen auf die Lp(a)-Konzentrationen zu erfassen. DESIGN DER STUDIE: Bei 111 Patienten mit ischämischer Herzerkrankung und bei 100 Kontrollpersonen erfolgte eine entsprechende Genotypisierung und eine Bestimmung der Lp(a)-Spiegel. ERGEBNISSE: Die Lp(a)-Konzentrationen unterschieden sich entsprechend der (TTTTA)n-Genotypen: Von den Personen, die wenigstens ein Allel aufwiesen, hatten 8 Personen signifikant höhere Lp(a)-Spiegel als die Kontrolle. Ein abnehmender Trend für Lp(a)-Spiegel bestand in Abhängigkeit vom Vorkommen des –914A-Allels bei den Kontrollen – dieser Trend war aber bei den Patienten entgegengesetzt. Patienten mit dem TTTTA-Allel-8/AA-914-Genotyp hatten signifikant höhere Lp(a)-Spiegel als jene ohne dieses Allel (p < 0.05). Der >8>8/GG-Genotyp wurde nicht gefunden. Es bestand ein signifikantes (p < 0,001) Koppelungs-Ungleichgewicht zwischen dem (TTTTA)n- und dem G/A-914-Polymorphismus. Unter Berücksichtigung des (TTTTA)n-Polymorphismus beeinflusste der G/A-914-Polymorphismus die Lp(a)-Spiegel unserer Patienten (multivariate Regressionsanalyse) signifikant (p < 0,05). SCHLUSSFOLGERUNGEN: Unsere Ergebnisse zeigen, dass (TTTTA)n- und G/A-914-Polymorphismen die Lp(a)-Spiegel von Patienten mit ischämischer Herzerkrankung als Folge des beobachteten Koppelungs-Ungleichgewichtes beeinflussen.

Arterial hypertension in the elderly

More than half of the individuals older than 65 are affected by hypertension. Isolated systolic hypertension, characterized by an increase in systolic arterial pressure without an increase in diastolic one, is the most frequent type of hypertension in persons over 50 years of age. It occurs de novo or after a long period of inadequately treated systolicdiastolic arterial hypertension. The main reason for its occurence is many years mediated increase in stiffness of the large elastic arteries. This structural change is responsible for the occurrence of high systolic pressure in the following two ways: by blood ejection from the left ventricle into the stiff arterial system of decreased distensibility, and by the increase in the pulse wave velocity with the reflection wave occurring during late systole. The increased peripheral vascular resistance, sympathetic stimulation and activities of the Renin Angiotensin Aldosteron (RAA) system play a less significant role in the incidence of arterial hypertension in the elderly than is the case with individuals affected by structural and functional changes of the aorta. Previously, vascular stiffness and an increase in systolic pulse pressure were considered as a part of the aging process and there was no insistence on treating this type of hypertension. Nowadays, when it is known that arterial hypertension in the elderly increases the risk of cardiovascular diseases three to four times more than in younger persons, it is insisted that this significant risk factor be corrected. In addition to necessary life style modifications, the advantage in medical treatment is given to thiazide diuretics and dihydropiridines from the group of calcium channel blockers. The therapy should be always adjusted to comorbidities. Elderly persons are defined as individuals at the age of 65 and older. They represent a growing segment of the population. In 1990, elderly persons comprised 13% of the total population of the USA and it is estimated that until 2040 they will constitute 20% of the population . As regards the number of elderly persons, Serbia is ranked as the fourth country in the world, after Greece, Italy and Japan. According to the data of the Statistical Office of the Republic of Serbia, approximately 17.24% of the population was elderly at the end of the last century, and it is estimated that this number will increase to 30% as far as 2025 . Similarly, the percentage of very old persons (older than 85) is constantly growing and it is assumed that there will be 16 million very old persons in the world by the middle of the 21 century . More than half of the individuals over 65 years of age have hypertension . The principal reason for the increased incidence of arterial hypertension in the elderly is the growing number of persons suffering from isolated systolic hypertension (ISH), which is also the most frequent type of hypertension found in this age group 3, . Isolated systolic hypertension is defined as an elevated systolic blood pressure ≥ 140 mmHg with the diastolic pressure value < 90 mmHg. Much more significant fact than the increased incidence of the elderly is the fact that the elderly with arterial hypertension, wheter it is isolated systolic or both systolic and diastolic, are at three to four times higher risk to develop cardiovascular diseases than young individuals. It is an important risk factor for stroke, heart failure, coronary artery disease, terminal renal failure and death .

Fibrinogen kao faktor rizika za ishemijsku bolest srca

Mesto fibrinogena u razvoju ateroskleroze i arterijske tromboze je verovatno znacajno jer on ucestvuje i u procesu nastanka i rasta plaka modulise hemoreoloske osobine krvi, a cini i osnovu koaguluma tokom procesa tromboze. Koncentracija fibrinogena u krvi je dobar nezavisan prognosticki parametar za razvoj akutnog infarkta miokarda, kako kod zdravih odraslih osoba, tako i kod koronarnih bolesnika. Nivo fibrinogena u krvi je delimicno genetski determinisan, ali i brojni faktori spoljasnje sredine uticu na njegov nivo. Vrlo je bitan odnos između fibrinogena i nekih drugih važnih faktora rizika. Fibrinogen i holesterol imaju izgleda sinergisticki ucinak na razvoj akutnog koronarnog sindroma. Moguce je da je fibrinogen jedna od najznacajnijih spona između pusenja i koronarne bolesti. Veoma je mali broj lekova koji se mogu dugorocno primenjivati i smanjiti nivo fibrinogena u krvi, tako da za sada ne postoje klinicke studije o vrednosti ovakve terapije u lecenju i prevenciji akutnih koronarnih sindroma. Shodno tome sve dok se ne dokaže da se smanjenjem nivoa fibrinogena u krvi smanjuje rizik za ispoljavanje koronarne bolesti, njegova uloga kao faktora rizika ostaje nedovoljno definisana.