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Severity and extension of coronary artery disease in association to plasma fibrinogen levels
Le Goff
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ACTIVATION OF THROMBIN AND FIBRINOLYTIC SYSTEMS AFTER THROMBOLYSIS IN PATIENTS W I T H ACUTE MYOCARDIAL INFARCTION
G.S. Latsios 1, A.T. Anastasopoulou<2, N.V. Michalopoulos 1, A. Papanikitas 1, E. DimoulW, A.G. Georgoulas2, A. Zaharof1.
J2nd Department of Medicine, 22nd Department of Cardiology, Hellenic Red Cross Hospital, Athens, Greece Purpose: To evaluate the thrombin and fibrinolytic system activation in patients treated with thrombolytic agents during the subsequent days after an acute myocardial infarction (AMI). M e t h o d s : We studied 20 consecutive patients (13 male, 7 female, mean age 55 years), who were admitted within 6 hours after the onset of symptoms of AMI. All patients underwent thrombolytic therapy. Two hours after the initiation of thrombolysis and for a total of four days the patients received intravenous heparin; afterwards, intravenous heparin was replaced by subcutaneous low molecular weight heparin. On admission and at 1st, 3rd, 5th, and 7th post AMI day we evaluated the platelet count, prothrombin time, partial thromboplastin time, fibrinogen levels, fibrin D-dimer and fibrin degradation products (FDPs) levels. Results: There were no significant differences regarding platelet count and coagulation times. All patients showed gradual elevation of fibrinogen levels from 1st to 3rd day after AMI, which returned to normal level, between 5th and 7th day. However, we observed an abnormal increase in D-dimer and FDP' s levels only in patients whose clinical and laboratory findings were consistent with a new infarct, while they remained within normal limits in those whose course after AMI was uncomplicated. Conclusions: Patients showing expansion of myocardial necrosis after their first AMI, have a particular rebound activation of the thrombin system, despite thrombolysis and heparin administration, compared to those who have an uncomplicated post AMI course.
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SEVERITY AND EXTENSION OF CORONARY ARTERY DISEASE IN ASSOCIATION TO PLASMA FIBRINOGEN LEVELS
G.S. Latsios 1, A.T. Anastasopoulou<2, N.V. Michalopoulos 1, A. Papanikitas 1, G. Svoukas 1, A.G. Georgoulas2, A. Zaharof1.
J2nd Department of Medicine, 22nd Department of Cardiology, Hellenic Red Cross Hospital, Athens, Greece Aim: To investigate the possible relationship between plasma fibrinogen levels and the severity and extension of coronary artery disease (CAD), as demonstrated by coronary angiography. M e t h o d s : We studied 25 patients (17 male, 8 female, mean age 65 years), who underwent coronary angiography within the first 10 30 days after an acute myocardial infarction. Platelet count, partial thromboplastin time and plasma fibrinogen levels were measured before the performance of cardiac catheterisation. Results: Coronography showed that 8 patients had single vessel disease, 13 patients had two vessel disease and 4 patients had three vessel disease. Plasma fibrinogen levels were significantly higher in patients suffering from three vessel disease (280420 mg/dl), compared to those with two vessel disease (150050 mg/dl) and one vessel disease (26 180 mg/dl). There were no significant differences concerning platelet count and coagulation times between the three groups. Conclusions: Fibrinogen appears to be an important independent risk factor, which correlates strongly not only with the existence of CAD, but also with its extension and severity.
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ABSENCE OF CMV DNA IN ENDARTERECTOMY SPECIMENS BY THE POLYMERASE CHAIN REACTION (PER)
G.S. Latsios, A. Saetta, N.V. Michalopoulos, G. Fanourakis, ES. Davaris.
Department of Pathology, Medical School, University of Athens, Greece In General: The aim of the present study was the detection of cytomegalovirus in atheromatic carotid plaques. Furthermore, we raised the question whether the presence of the virus is correlated with specific clinical and histological characteristics of each case. Atheromatosis is considered as an inflammatory process of the arterial vessel wall. Recent studies enriched our knowledge regarding the events that trigger the inflammation of the endothelium, the starting event of atheromatosis. There is growing interest
149
on the possible role that infectious organisms, such as Chlamydia spp. and various viruses, might play in this process. Material: Parts from 83 atheromatic plaques were collected. All plaques came from carotid endarterectomy specimens. M e t h o d s : DNA was isolated from the plaques and by means of the polymerase chain reaction (PCR) method and appropriate, CMV specific, primers we tried to amplify specific sequences of the CMV genome. The positive result of the PCR implies presence of CMV DNA in the plaque. The PCR result was verified by the simultaneous use of a positive control, i.e. a sample known to contain CMV DNA. Results: No CMV DNA was detected in all 83 samples. In conclusion, the present study does not confirm the possible role of cytomegalovirus in the process of atheromatosis. ~
CARDIOVASCULAR RISK FACTORS IN TYPE 2 DIABETICS: ROLE OF HYPERTENSION AND FIBRINOGEN
E Lazzari, A. Cappellini. Diabetes Center, Hospital of Cremona, Italy To evaluate the relationships of hypertension (H) (WHO criteria) and plasma fibrinogen (F), both recognized cardiovascular risk factors, with other parameters involved in the development of diabetic complications, we studied 302 consecutive patients with type 2 diabetes mellitus (162 males and 140 females, age 63.8±8.9 years). The prevalence of H was 63% and F levels were higher in hypertensive patients as compared to normotensive ones (353.8±94.4 vs 328.1±81.6 mg/dl, p-0.02).F values were higher in patients with albuminuria> 30 mg/24 h than in those with albuminuria <30 mg/24 h (365.7±92.3 vs 339.4±86.8, p-0.01),being H significantly more prevalent in the formers than in the latters (87.1% vs 72.0%, p-0.002).Body mass index (BMI) was higher in hypertensives than in normotensives (28.2±26.6 vs 26.6±3.6 Kg/m2,p-0.005),whereas fasting glycemia and glycosilated hemoglobin (HbA 1c)(average of the values of the last 5 years) were similar in the 2 groups; no correlation was found between F and each of these parameters. F levels were higher in insulin-treated patients than in non insulin-treated ones (371.5±98.6 vs 338.3±83.7 mg/dl, p-0.005), whereas the prevalence of H was similar in the 2 groups. However, no correlation was found between F levels and mean daily dosage of insulin, which was similar in hypertensive and normotensive patients. Triglycerides, total cholesterol and HDL-cholesterol (HDL-C) were similar in normotensives and hypertensives, and no correlation was observed between these parameters and E However, in patients with HDL-C < 45 mg/dl F was higher in hypertensives than in normotensives (354.4±90.4 vs 321.5±87.5,p-0.03), but it was similar in the 2 groups when HDL-C was > 45 mg/dl. These results indicate: a) an association between hypertension and F in type 2 diabetic patients, particularly in presence of low HDL-C levels and increased albuminuria; b) an association between insulin therapy, probably expression of a more severe diabetic disease, and E These findings could contribute to explain the excess morbidity and mortality observed in these patients, and suggest the possibility to detect patients at high risk of cardiovascular disease. ~
REGULATION OF HUMAN CETP GENE PROMOTER ACTIVITY: ROLE OF MULTIPLE BINDING SITES F O R SP1 AND SP3 TRANSCRIPTION FACTORS
W. Le Goff, M. Gu6rin, L. Petit, M.J. Chapman, J. Thillet. Inserm U551,
Hdpital de la Piti~, Paris, France The cholesteryl ester transfer protein (CETP) is a key factor in plasma reverse cholesterol transport and is implicated in the pathophysiology of atherogenic dyslipidemia. To define the potential regulatory role of the distal promoter region of the human CETP gene, we analyzed the region from -550 to -745 bp by DNase I footprinting and identified a new transcription factor binding site at -690 to -699, which specifically binds both Spl and Sp3. Transient transfection experiments in HepG2 cells demonstrated that this site acts as a repressive element in reducing CETP promoter activity (-22%; p<0.05) and exerts an additive effect with the previously described Spl/Sp3 site at -629, inducing marked repression (-42%; p<0.005) of promoter activity. Furthermore, the repressive effect at the -690 site was enhanced, whereas that at the -629 site was abolished in NCTC cells as compared to the HepG2 cell line, reflecting the 16-fold lower Sp3 level observed in NCTC cells. In the SL2 cell line, which is devoid of transcription factors of the Sp-family, transfection of Spl and Sp3 activated CETP promoter activity through both the -690 and -37 sites but not the -629 site. In addition, we demonstrated that the combined effect of both Spl and Sp3 differentially regulates each of these three sites. Taken together, our results demonstrate
73rd EAS Congress
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ACTIVATION OF THROMBIN AND FIBRINOLYTIC SYSTEMS AFTER THROMBOLYSIS IN PATIENTS W I T H ACUTE MYOCARDIAL INFARCTION
G.S. Latsios 1, A.T. Anastasopoulou<2, N.V. Michalopoulos 1, A. Papanikitas 1, E. DimoulW, A.G. Georgoulas2, A. Zaharof1.
J2nd Department of Medicine, 22nd Department of Cardiology, Hellenic Red Cross Hospital, Athens, Greece Purpose: To evaluate the thrombin and fibrinolytic system activation in patients treated with thrombolytic agents during the subsequent days after an acute myocardial infarction (AMI). M e t h o d s : We studied 20 consecutive patients (13 male, 7 female, mean age 55 years), who were admitted within 6 hours after the onset of symptoms of AMI. All patients underwent thrombolytic therapy. Two hours after the initiation of thrombolysis and for a total of four days the patients received intravenous heparin; afterwards, intravenous heparin was replaced by subcutaneous low molecular weight heparin. On admission and at 1st, 3rd, 5th, and 7th post AMI day we evaluated the platelet count, prothrombin time, partial thromboplastin time, fibrinogen levels, fibrin D-dimer and fibrin degradation products (FDPs) levels. Results: There were no significant differences regarding platelet count and coagulation times. All patients showed gradual elevation of fibrinogen levels from 1st to 3rd day after AMI, which returned to normal level, between 5th and 7th day. However, we observed an abnormal increase in D-dimer and FDP' s levels only in patients whose clinical and laboratory findings were consistent with a new infarct, while they remained within normal limits in those whose course after AMI was uncomplicated. Conclusions: Patients showing expansion of myocardial necrosis after their first AMI, have a particular rebound activation of the thrombin system, despite thrombolysis and heparin administration, compared to those who have an uncomplicated post AMI course.
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SEVERITY AND EXTENSION OF CORONARY ARTERY DISEASE IN ASSOCIATION TO PLASMA FIBRINOGEN LEVELS
G.S. Latsios 1, A.T. Anastasopoulou<2, N.V. Michalopoulos 1, A. Papanikitas 1, G. Svoukas 1, A.G. Georgoulas2, A. Zaharof1.
J2nd Department of Medicine, 22nd Department of Cardiology, Hellenic Red Cross Hospital, Athens, Greece Aim: To investigate the possible relationship between plasma fibrinogen levels and the severity and extension of coronary artery disease (CAD), as demonstrated by coronary angiography. M e t h o d s : We studied 25 patients (17 male, 8 female, mean age 65 years), who underwent coronary angiography within the first 10 30 days after an acute myocardial infarction. Platelet count, partial thromboplastin time and plasma fibrinogen levels were measured before the performance of cardiac catheterisation. Results: Coronography showed that 8 patients had single vessel disease, 13 patients had two vessel disease and 4 patients had three vessel disease. Plasma fibrinogen levels were significantly higher in patients suffering from three vessel disease (280420 mg/dl), compared to those with two vessel disease (150050 mg/dl) and one vessel disease (26 180 mg/dl). There were no significant differences concerning platelet count and coagulation times between the three groups. Conclusions: Fibrinogen appears to be an important independent risk factor, which correlates strongly not only with the existence of CAD, but also with its extension and severity.
•
ABSENCE OF CMV DNA IN ENDARTERECTOMY SPECIMENS BY THE POLYMERASE CHAIN REACTION (PER)
G.S. Latsios, A. Saetta, N.V. Michalopoulos, G. Fanourakis, ES. Davaris.
Department of Pathology, Medical School, University of Athens, Greece In General: The aim of the present study was the detection of cytomegalovirus in atheromatic carotid plaques. Furthermore, we raised the question whether the presence of the virus is correlated with specific clinical and histological characteristics of each case. Atheromatosis is considered as an inflammatory process of the arterial vessel wall. Recent studies enriched our knowledge regarding the events that trigger the inflammation of the endothelium, the starting event of atheromatosis. There is growing interest
149
on the possible role that infectious organisms, such as Chlamydia spp. and various viruses, might play in this process. Material: Parts from 83 atheromatic plaques were collected. All plaques came from carotid endarterectomy specimens. M e t h o d s : DNA was isolated from the plaques and by means of the polymerase chain reaction (PCR) method and appropriate, CMV specific, primers we tried to amplify specific sequences of the CMV genome. The positive result of the PCR implies presence of CMV DNA in the plaque. The PCR result was verified by the simultaneous use of a positive control, i.e. a sample known to contain CMV DNA. Results: No CMV DNA was detected in all 83 samples. In conclusion, the present study does not confirm the possible role of cytomegalovirus in the process of atheromatosis. ~
CARDIOVASCULAR RISK FACTORS IN TYPE 2 DIABETICS: ROLE OF HYPERTENSION AND FIBRINOGEN
E Lazzari, A. Cappellini. Diabetes Center, Hospital of Cremona, Italy To evaluate the relationships of hypertension (H) (WHO criteria) and plasma fibrinogen (F), both recognized cardiovascular risk factors, with other parameters involved in the development of diabetic complications, we studied 302 consecutive patients with type 2 diabetes mellitus (162 males and 140 females, age 63.8±8.9 years). The prevalence of H was 63% and F levels were higher in hypertensive patients as compared to normotensive ones (353.8±94.4 vs 328.1±81.6 mg/dl, p-0.02).F values were higher in patients with albuminuria> 30 mg/24 h than in those with albuminuria <30 mg/24 h (365.7±92.3 vs 339.4±86.8, p-0.01),being H significantly more prevalent in the formers than in the latters (87.1% vs 72.0%, p-0.002).Body mass index (BMI) was higher in hypertensives than in normotensives (28.2±26.6 vs 26.6±3.6 Kg/m2,p-0.005),whereas fasting glycemia and glycosilated hemoglobin (HbA 1c)(average of the values of the last 5 years) were similar in the 2 groups; no correlation was found between F and each of these parameters. F levels were higher in insulin-treated patients than in non insulin-treated ones (371.5±98.6 vs 338.3±83.7 mg/dl, p-0.005), whereas the prevalence of H was similar in the 2 groups. However, no correlation was found between F levels and mean daily dosage of insulin, which was similar in hypertensive and normotensive patients. Triglycerides, total cholesterol and HDL-cholesterol (HDL-C) were similar in normotensives and hypertensives, and no correlation was observed between these parameters and E However, in patients with HDL-C < 45 mg/dl F was higher in hypertensives than in normotensives (354.4±90.4 vs 321.5±87.5,p-0.03), but it was similar in the 2 groups when HDL-C was > 45 mg/dl. These results indicate: a) an association between hypertension and F in type 2 diabetic patients, particularly in presence of low HDL-C levels and increased albuminuria; b) an association between insulin therapy, probably expression of a more severe diabetic disease, and E These findings could contribute to explain the excess morbidity and mortality observed in these patients, and suggest the possibility to detect patients at high risk of cardiovascular disease. ~
REGULATION OF HUMAN CETP GENE PROMOTER ACTIVITY: ROLE OF MULTIPLE BINDING SITES F O R SP1 AND SP3 TRANSCRIPTION FACTORS
W. Le Goff, M. Gu6rin, L. Petit, M.J. Chapman, J. Thillet. Inserm U551,
Hdpital de la Piti~, Paris, France The cholesteryl ester transfer protein (CETP) is a key factor in plasma reverse cholesterol transport and is implicated in the pathophysiology of atherogenic dyslipidemia. To define the potential regulatory role of the distal promoter region of the human CETP gene, we analyzed the region from -550 to -745 bp by DNase I footprinting and identified a new transcription factor binding site at -690 to -699, which specifically binds both Spl and Sp3. Transient transfection experiments in HepG2 cells demonstrated that this site acts as a repressive element in reducing CETP promoter activity (-22%; p<0.05) and exerts an additive effect with the previously described Spl/Sp3 site at -629, inducing marked repression (-42%; p<0.005) of promoter activity. Furthermore, the repressive effect at the -690 site was enhanced, whereas that at the -629 site was abolished in NCTC cells as compared to the HepG2 cell line, reflecting the 16-fold lower Sp3 level observed in NCTC cells. In the SL2 cell line, which is devoid of transcription factors of the Sp-family, transfection of Spl and Sp3 activated CETP promoter activity through both the -690 and -37 sites but not the -629 site. In addition, we demonstrated that the combined effect of both Spl and Sp3 differentially regulates each of these three sites. Taken together, our results demonstrate
73rd EAS Congress