- Email: [email protected]
Short term effects of atorvastatin on coagulation and inflammation
Rizos occlusive disease. Blood samples were obtained after an overnight fast for measurement of cCAMs, lipoproteins, and other clinical-chemistry parameters, cCAM levels were determined by the use of monoclonal antibodybased enzyme-linked immunosorbent assays (R&D Systems, Europe Ltd, Abington, United Kingdom). Amongst the circulating adhesion molecules, cVCAM-1 is uniquely elevated in elderly persons with different risk for atherosclerosis including subjects of the average population, vegetarians, and both patients with coronary heart disease and peripheral arterial occlusive disease. With respect to cICAM-1, an age dependent elevation was found in the control subjects included in the study, cE-selectin levels were not correlated with age. Moreover, no associations of cCAMs with serum lipid and lipoprotein levels were found. In conclusion, cVCAM-1 is an agedependent parameter independent of cardiovascular risk.
•
LIPID STUDY L E I P Z I G (LSL): EVALUATION OF CARDIOVASCULAR RISK FACTOR PROFILE ON POPULATION BASIS
V. Richter 1, E Rassoul 1, K. Purschwitz 1, E. Richter 2, M. Michel 2, S. Riedel 2, G. Schreinicke 2, R. Schwarz2, E Jucker2, K. Wenzel 1, J. Thiery 1. Jlnstitute of Laboratory Medicine, 2Institute for Occupational
Medicine and Social Medicine, University of Leipzig, Germany Population based lipid screening projects were initiated in the city of Leipzig including more than 30,000 subjects. The objectives of the Lipid Study Leipzig (LSL) were to evaluate the risk factor profile and its dependence on age, nutrition and social factors. LSL was performed at community centers, work sites and schools. The study included capillary blood cholesterol measurements and the determination of HI)L-cholesterol using the drychemistry Reflotron system (Roche Diagnostics, Mannheim). Furthermore, measurement of blood pressure, body-mass-index, and the evaluation of several risk factors for atherosclerosis was included. The mean cholesterol concentration and the total:HDL cholesterol ratio showed the expected age dependence, with maximum values within the decade 6 0 ~ 0 years. A strong influence of physical inactivity and generally unhealthy life-style in determining lipid profile in childhood and adolescence was found. Furthermore, investigations in schools showed correlations between cardiovascular risk factors and the sociale structure. In the city of Leipzig, the mean cholesterol level of subjects younger than 50 years of age was virtually unchanged between 1991 and 2001. However, a decreased mean cholesterol level and a decreased prevalence of cholesterol levels more than 250 mg/dl in subjects older than 50 years of age was found as compared to 10 years ago. In conclusion, LSL showed an improvement of the cardiovascular risk with respect to plasma cholesterol in the last 10 years.
•
SHORT TERM EFFECTS OF ATORVASTATIN ON COAGULATION AND INFLAMMATION
W..E Riesen 1, W. Korte 1, H. Engler 1, G. Noseda 2. Jlnstitute for Clinical
Chemistry and Hematology, Kantonsspital, St. Gallen; 2Ospedale Della Beata Vergine, Mendrisio, Switzerland Statins are known to display anti-coagulant and anti-inflammatory properties. These properties might be important with respect to the use of statins in acute coronary syndromes, which has been proven to show beneficial effects. Accordingly, we studied the effects of Atorvastatin on D-dimer and Fibrin Monomer as markers of fibrin generation, C-reactive protein (CRP) and serum amyloid A as merkers of inflammation in patients with CHD or cholesterol values above 6.5 mmol/1 in the presence of additional coronary risk factors. At one month, D-dimer decreased by 25% (p - 0.001), and Fibrin Monomer by 45% (p - 0.029) in patients within the upper quartile. Both parameters were unchanged in the lower three quartiles. The median decrease in CRP was 23% (p- 0.001) SAA decreased by 12% after 1 month (p- 0.01). The full decrease of D-dimer, Fibrin Monomer and CRP was complete at 1 month, while SAA showed an additional decrease after 3 months totaling 24%. These data indicate that Atorvastatin has a beneficial short term effect on the activation of coagulation as well inflammation. The decrease in SAA furthermore indicates that the effect of Atorvastatin is not a direct effect on CRP bur rather a true anti-inflammatory effect.
•
193
ATTENUATION OF CIRCADIAN BLOOD PRESSURE RHYTHM IS INDEPENDENT DETERMINANT OF DEVELOPMENT OF ATHEROSCLEROSIS IN HYPERTENSION
T.M. Ripp, S.E. Pekarski, V.E Mordovin, S.V. Triss. Tomsk Institute of
Cardiology, Tomsk, Russia Increased blood pressure (BP) imposes a greater mechanical stress on vascular wall and thus accelerates development of atherosclerotic lesions in hypertension. Number of studies have demonstrated that the atherosclerotic changes in large arteries are positively and significantly related to BP level. However, this relationship generally explains no more than 10 20% of the variability of those changes (correlation coefficients are typically within 0.3 0.4 range for all indices) leaving 80% for other causes. We suggested that abnormality of circadian rhythm of BP might be another independent cause of the development of atherosclerosis in arterial wall. Objective. To investigate whether distal carotid intima-media thickness, which is frequently used as a semiquantitative score for carotid atherosclerosis severity, is associated with abnormalities of circadian rhythm of BP in essential hypertensives. Methods: We performed ABPM study and measured intima-media thickness (IMT) of the distal common carotid artery in 83 patients (44 men and 39 women, age 49.2±6.2) with uncomplicated essential hypertension of grade II-III. Nocturnal fall of blood pressure calculated using 23:00 7:00 nighttime period was taken as quantitative index of circadian BP rhythm. Results: Significant positive correlation was found between IMT and nocturnal fall of both systolic and diastolic BP (r--0.41, p-0.009 and r--0.38, p-0.013 respectively). The relationship for nocturnal fall of systolic BP remained significant in multiple regression model after inclusion of 24-hr systolic BP mean (partitial r--0.28, p-0.033). Conclusion: These data show that attenuation of circadian BP rhythm may be independent factor of the development of atherosclerosis in hypertension. ~1]
ISOLATION AND CHARACTERIZATION OF CDNAS ENCODING SCAVENGER RECEPTOR CLASS B TYPE I AND H IN RABBIT
A. Ritsch, R. Gander, R Eller, W..A. Schgor, B. Foger, U. Stanzl, J.R. Patsch. University of lnnsbruck, Austria Introduction: The scavenger receptor class B type I (SR-BI) mediates the
selective uptake of HDL cholesterol and plays a role in HDL metabolism, reverse cholesterol transport, and whole body homeostasis. A splice variant of SR-BI called SR-BII was isolated in rodents and humans. In this report we describe, for the first time, isolation and analysis of rabbit cDNA fragments encoding SR-BI and SR-BII, respectively. M e t h o d s and Results: A set of degenerate primers designed based on highly conserved regions of chinese hamster, mouse, rat, and bovine SRBI were used to amplify a 530 bp fragment from reverse transcribed total rabbit liver RNA. This fragment was subsequently used to design primers for isolation of the remaining 5 / and 3 / cDNA fragments by RACE-PCR. Two different 3 ~ fragments were isolated encoding for isoforms I and II, respectively. Rabbit SR-BI cDNA showed a much higher similarity to the human homologue than the corresponding fragments of rodents. Conclusion: The lipoprotein profile in plasma of rabbits is much closer to the human system, when compared to that of the so-called 'HDL animals' mouse and rat. Additionally, rabbit SR-BI shows much higher homology to the human protein than those of mouse and rat, the animal models commonly employed to study SR-BI function in vivo. The molecular cloning of rabbit SR-BI and SR-BII, reported for the first time in the present study, therefore, will help us to elucidate the role of SR-BI in cholesterol homeostasis, which in turn may provide unique insights into human atherogenesis. ~-~
EFFECTS OF ANTIHYPERTENSIVE AND HYPOLIPIDEMIC D R U G S ON PLASMA AND HDL-ASSOCIATED PAF-ACETYLHYDROLASE ACTIVITY
E. Rizos 1, V. Tsimihodimos1, A. Tambaki 2, A. Kakafika 1, A. Tselepis2, J. Goudevenos 1, C. Siamopoulos1, M. Elisaf1. JDepartment of Internal
Medicine, Medical School, University of Crete, Heraklion," 2Laboratory of Biochemistry, School of Chemistry, University of loannina, Greece Plasma Platelet Activating Factor-Acetylhydrolase (PAF-AH) is a phospholipase A2 which circulates in plasma in association with lipoproteins. From a pathophysiological point of view PAF-AH may be considered either as an antiatherogenic (since it degrades PAF and oxidized phospholipids)
73rd EAS Congress
•
LIPID STUDY L E I P Z I G (LSL): EVALUATION OF CARDIOVASCULAR RISK FACTOR PROFILE ON POPULATION BASIS
V. Richter 1, E Rassoul 1, K. Purschwitz 1, E. Richter 2, M. Michel 2, S. Riedel 2, G. Schreinicke 2, R. Schwarz2, E Jucker2, K. Wenzel 1, J. Thiery 1. Jlnstitute of Laboratory Medicine, 2Institute for Occupational
Medicine and Social Medicine, University of Leipzig, Germany Population based lipid screening projects were initiated in the city of Leipzig including more than 30,000 subjects. The objectives of the Lipid Study Leipzig (LSL) were to evaluate the risk factor profile and its dependence on age, nutrition and social factors. LSL was performed at community centers, work sites and schools. The study included capillary blood cholesterol measurements and the determination of HI)L-cholesterol using the drychemistry Reflotron system (Roche Diagnostics, Mannheim). Furthermore, measurement of blood pressure, body-mass-index, and the evaluation of several risk factors for atherosclerosis was included. The mean cholesterol concentration and the total:HDL cholesterol ratio showed the expected age dependence, with maximum values within the decade 6 0 ~ 0 years. A strong influence of physical inactivity and generally unhealthy life-style in determining lipid profile in childhood and adolescence was found. Furthermore, investigations in schools showed correlations between cardiovascular risk factors and the sociale structure. In the city of Leipzig, the mean cholesterol level of subjects younger than 50 years of age was virtually unchanged between 1991 and 2001. However, a decreased mean cholesterol level and a decreased prevalence of cholesterol levels more than 250 mg/dl in subjects older than 50 years of age was found as compared to 10 years ago. In conclusion, LSL showed an improvement of the cardiovascular risk with respect to plasma cholesterol in the last 10 years.
•
SHORT TERM EFFECTS OF ATORVASTATIN ON COAGULATION AND INFLAMMATION
W..E Riesen 1, W. Korte 1, H. Engler 1, G. Noseda 2. Jlnstitute for Clinical
Chemistry and Hematology, Kantonsspital, St. Gallen; 2Ospedale Della Beata Vergine, Mendrisio, Switzerland Statins are known to display anti-coagulant and anti-inflammatory properties. These properties might be important with respect to the use of statins in acute coronary syndromes, which has been proven to show beneficial effects. Accordingly, we studied the effects of Atorvastatin on D-dimer and Fibrin Monomer as markers of fibrin generation, C-reactive protein (CRP) and serum amyloid A as merkers of inflammation in patients with CHD or cholesterol values above 6.5 mmol/1 in the presence of additional coronary risk factors. At one month, D-dimer decreased by 25% (p - 0.001), and Fibrin Monomer by 45% (p - 0.029) in patients within the upper quartile. Both parameters were unchanged in the lower three quartiles. The median decrease in CRP was 23% (p- 0.001) SAA decreased by 12% after 1 month (p- 0.01). The full decrease of D-dimer, Fibrin Monomer and CRP was complete at 1 month, while SAA showed an additional decrease after 3 months totaling 24%. These data indicate that Atorvastatin has a beneficial short term effect on the activation of coagulation as well inflammation. The decrease in SAA furthermore indicates that the effect of Atorvastatin is not a direct effect on CRP bur rather a true anti-inflammatory effect.
•
193
ATTENUATION OF CIRCADIAN BLOOD PRESSURE RHYTHM IS INDEPENDENT DETERMINANT OF DEVELOPMENT OF ATHEROSCLEROSIS IN HYPERTENSION
T.M. Ripp, S.E. Pekarski, V.E Mordovin, S.V. Triss. Tomsk Institute of
Cardiology, Tomsk, Russia Increased blood pressure (BP) imposes a greater mechanical stress on vascular wall and thus accelerates development of atherosclerotic lesions in hypertension. Number of studies have demonstrated that the atherosclerotic changes in large arteries are positively and significantly related to BP level. However, this relationship generally explains no more than 10 20% of the variability of those changes (correlation coefficients are typically within 0.3 0.4 range for all indices) leaving 80% for other causes. We suggested that abnormality of circadian rhythm of BP might be another independent cause of the development of atherosclerosis in arterial wall. Objective. To investigate whether distal carotid intima-media thickness, which is frequently used as a semiquantitative score for carotid atherosclerosis severity, is associated with abnormalities of circadian rhythm of BP in essential hypertensives. Methods: We performed ABPM study and measured intima-media thickness (IMT) of the distal common carotid artery in 83 patients (44 men and 39 women, age 49.2±6.2) with uncomplicated essential hypertension of grade II-III. Nocturnal fall of blood pressure calculated using 23:00 7:00 nighttime period was taken as quantitative index of circadian BP rhythm. Results: Significant positive correlation was found between IMT and nocturnal fall of both systolic and diastolic BP (r--0.41, p-0.009 and r--0.38, p-0.013 respectively). The relationship for nocturnal fall of systolic BP remained significant in multiple regression model after inclusion of 24-hr systolic BP mean (partitial r--0.28, p-0.033). Conclusion: These data show that attenuation of circadian BP rhythm may be independent factor of the development of atherosclerosis in hypertension. ~1]
ISOLATION AND CHARACTERIZATION OF CDNAS ENCODING SCAVENGER RECEPTOR CLASS B TYPE I AND H IN RABBIT
A. Ritsch, R. Gander, R Eller, W..A. Schgor, B. Foger, U. Stanzl, J.R. Patsch. University of lnnsbruck, Austria Introduction: The scavenger receptor class B type I (SR-BI) mediates the
selective uptake of HDL cholesterol and plays a role in HDL metabolism, reverse cholesterol transport, and whole body homeostasis. A splice variant of SR-BI called SR-BII was isolated in rodents and humans. In this report we describe, for the first time, isolation and analysis of rabbit cDNA fragments encoding SR-BI and SR-BII, respectively. M e t h o d s and Results: A set of degenerate primers designed based on highly conserved regions of chinese hamster, mouse, rat, and bovine SRBI were used to amplify a 530 bp fragment from reverse transcribed total rabbit liver RNA. This fragment was subsequently used to design primers for isolation of the remaining 5 / and 3 / cDNA fragments by RACE-PCR. Two different 3 ~ fragments were isolated encoding for isoforms I and II, respectively. Rabbit SR-BI cDNA showed a much higher similarity to the human homologue than the corresponding fragments of rodents. Conclusion: The lipoprotein profile in plasma of rabbits is much closer to the human system, when compared to that of the so-called 'HDL animals' mouse and rat. Additionally, rabbit SR-BI shows much higher homology to the human protein than those of mouse and rat, the animal models commonly employed to study SR-BI function in vivo. The molecular cloning of rabbit SR-BI and SR-BII, reported for the first time in the present study, therefore, will help us to elucidate the role of SR-BI in cholesterol homeostasis, which in turn may provide unique insights into human atherogenesis. ~-~
EFFECTS OF ANTIHYPERTENSIVE AND HYPOLIPIDEMIC D R U G S ON PLASMA AND HDL-ASSOCIATED PAF-ACETYLHYDROLASE ACTIVITY
E. Rizos 1, V. Tsimihodimos1, A. Tambaki 2, A. Kakafika 1, A. Tselepis2, J. Goudevenos 1, C. Siamopoulos1, M. Elisaf1. JDepartment of Internal
Medicine, Medical School, University of Crete, Heraklion," 2Laboratory of Biochemistry, School of Chemistry, University of loannina, Greece Plasma Platelet Activating Factor-Acetylhydrolase (PAF-AH) is a phospholipase A2 which circulates in plasma in association with lipoproteins. From a pathophysiological point of view PAF-AH may be considered either as an antiatherogenic (since it degrades PAF and oxidized phospholipids)
73rd EAS Congress