- Email: [email protected]
W04.142 Impact of C-reactive protein, leptin and adiponectin on cardiovascular risk factors in Spain
W4
Workshops Cytokines, the adipocyte, and atherosclerosis
Conclusions: AgLDL significantly enhance the effect of LPS on Cox-2 mRNA levels. Fut'thermore, monocytes in a lipidic enriched milieu could have and enhanced Cox-2 mediated-response to inflammatory stimuli.
•
IMPACT OF C-REACTIVE PROTEIN, LEPTIN AND ADIPONECTIN ON CARDIOVASCULAR RISK FACTORS IN SPAIN
M.T. Mat't nez, M. Mart nez, A. L pez, C. Fern ndez, J.L. Gonz lez, C. Zabena, M. Sen'ano. Hospital Cl nico San Carlos, Madrid, Spain
Aims: To study the interaction between C Reactive IS"otein (CRP) adiponectin and leptin levels with cat'diovasculat" risk factors in general Spanish population. Design and Methods: Population: Unrelated, healthy non diabetic individuals (n=724, 54.6% females) identified by crossectional survey in the Spanish province of Segovia (Autonomous Region of Castille-Leon. Central/North Eastern Spain). Anthropometric measurements: Body Mass Index (BMI), Waist Cfl-cumference (WC), Waist/Hip ratio (W/H) (as measut'es of Abdominal Obesity (AO)), Systolic Blood pressure (SBP), Diastolic Blood tS"essure (DBP). Laboratory parameters: Fasting Glucose (FG), lipid profile. Serum Fasting insulin (FI)/Proinsulin (FP)/Leptin (FL)/Adiponectin (APM) by RIAs. CRP serum by nephelometry. Results: 1. Population. Anthropometric/Laboratory data values for Abdominal Obesity (AO), DBP, FG, FI, FP, TG, LDL-C but not HDL-C, FL and APM significantly higher in males than in females (p< 0.05). 2. Sex/BMI adjusted log CRP/log FL in positive association but not to log APM. 3. Linear regression model: dependent variables: log CRP, log FL, log APM. Log CRP positively associated with age, W/H, negatively with HDL-C. Log APM positively associated with age and HDL-C, but negatively with W/H, TG, and FI. Log FL positively associated with W/H, FI. Conclusions: Both CRP/Fasting leptin serum levels have strong, independent association with AO/low HDL-C.Adiponectin is confirmed as a potentially protective cat'diovasculat" risk factor.
M. Palacios, P. Bull, N. Rubio, M. Itoiz, R. Santamar a, I. An'oyo, E. Perez de Cfl'iza, P. Aramburu, M. Garc a San Mart n, M. Sen'ano. Hospital de
Navarra, Centro de Salud de Azpilaga a, Dpto. Epidemiolog a y Salud P blica, Universidad de Navarra, Pamplona, Spain Diabetes mellitus type 2 is a disease with a well known vasculat" risk, and serum concentrations of several inflammatory markers have been found raised in diabetic patients, indicating endothelial dysfunction and cellular activation in vasculat" wall. Objectives: To analyse possible associations of inflammatoly molecules with anthropomeu'ic and clinical pat'ameters. Patients and methods: Fifty six diabetic patients were recruited and routine clinical determinations were recorded. Serum samples were fi'ozen for future determinations. Vascular cell adhesion molecule (s-VCAM-1), intercellulat" adhesion molecule (s-ICAM-1) and monocyte chemoattractant protein (MCP-1) were measut'ed by means of specific enzymoimmunoassays. Results: Almost a half (42.6%) were women and mean age was 63.4-t10.1 yeat's. Mean BMI was 33.6-t- 5.3 kg/m 2, and mean waist ch'cumference was 107.6-t- 10.8 cm. Multiple regression models were fitted with inflammatory mat'kers as dependent variables (outcome), and anthropometric (BMI and waist ch'cumference) and clinical variables (smoking, systolic and diastolic blood pressut'es, LDL cholesterol, HDL cholesterol, Hemoglobin Alc, age and gender) were used as independent vat'iables. These models showed that after adjustments, BMI is positively associated with serum levels of s-ICAM-1 (~ = 14.1 ng/ml; 95% confidence interval [CI]: 2.6-25.6; p<0.02) and s-VCAM-1 (~ = 12.9 ng/ml; 95% CI: 0.85-25; p<0.05), but not with MCP-1 (~ = 4.7 pg/ml; 95% CI: -12.9- 22.3; not significant). Other independent vat'iables in the models showed scarce an marginal associations. Conclusions: Our results suggest that BMI is the clinical pat'ameter in diabetic patients with a higher value in the prediction of vasculat" damage.
ADHESION MOLECULES CHANGES AFTER A HEALTH EDUCATION PROGRAM IN OBESE DIABETICS
M. Palacios, N. Rubio, P. Bull, M.J. Urbina, L. Tom s, C. I igo, J.A. Cabeza, J.I. Yoldi, C. Donlo, M. Sen'ano. Servicio de Bioqu mica,
Centro de Salud de Azpilaga a, Dpto. Epidemiolog a y Salud P blica, Hospital de Navarra, Universidad de Navarra, Pamplona, Spain Raised levels of adhesion molecules have been proposed as prognostic mat'kers of atherosclerosis, also in diabetic patients. Objectives: to study changes in the serum levels of the adhesion molecules induced by lifestyle changes. Patients and methods: Fifty six patients diagnosed of diabetes mellitus type 2 with a Body Mass Index (BMI) above 30 kg/m 2 were included. During six weeks a program of health education on diabetes self cat'e and management was developed. Vasculat" cell adhesion molecule (s-VCAM1) and intercellulat" adhesion molecule (s-ICAM-1) were measut'ed by enzymoimmunoassay. Results: Mean age was 63.4-4- 10.1 years, and 57.4% were men. BMI reduced fi'om 33.64- 5.3 to 32.94- 5.4 kg/m 2 (p<0.001) and waist cfl'cumference diminished fi'om 107.64- 10.7 to 105.14- 12.3 cm (p<0.001) after the 12 weeks period. Significant reductions were found in systolic and diastolic at'terial blood pressut'e, hemoglobin Alc, LDL cholesterol, but not in HDL cholesterol and triglycerides. Strikingly, s-ICAM-1 and s-VCAM-1 changes after intervention were opposite, s-ICAM-1 showed a significant reduction (254.24- 94.4 to 171.44- 41.4 ng/ml; p<0.001), indicating a lower level of endothelial dysfunction, s-VCAM-1 increased also significantly (151.44107.7 to 2514- 110.2 ng/ml; p<0.001). Conclusions: This inverse behaviout" of adhesion molecules in diabetic patients remain to be explained, but some previous reports indicate a higher physiopathologic role of s-ICAM-1, while s-VCAM-1 serum levels were not associated with objective measures of atherosclerosis. After these assessments, it would be suggested that changes in diabetic and obese patients obtained throughout short health education program would diminish vasculat" risks.
33
~ B O D Y MASS INDEX IS ASSOCIATED WITH MARKERS OF VASCULAR INFLAMMATION IN DIABETIC PATIENTS
~ ~
Pistamaltzian
SERUM LEVELS OF ASYMMETRIC DINIETHYLARGININE (ADMA) EXHIBIT SHARP DECLINE FROM CHILDHOOD TO ADOLESCENCE, W H I C H IS ATTENUATED IN OBESITY AND TYPE I DIABETES
S. Pilz, H. Hubmann, A. Meinitzer, M. Borkenstein, H. Mangge. Dept. of
Laboratory Medicine, Medical University of Graz, Graz, Austria Background and methods. AsymmeU'ical dimethylarginine (ADMA), a major inhibitor of NO synthase, is considered as a novel risk factor linking endothelial dysfunction and atherosclerosis. To evaluate ADMA in earliest stages of atherosclerosis, we measut'ed serum ADMA levels by means of high pressut'e lipid chromatography (HPLC)in obese juveniles and in juveniles with type I diabetes as compared to healthy, normal weighted, age matched conu'ols. The obese juveniles and the diabetics were identified in a previous study to show an increased intima media thickness of common cat'otid arteries paralelled by an increased low grade inflammation. Results. A sharp, age related, decrease of ADMA fi'om childhood to adolescence was observed in the controls, but not in the obese juveniles o1"the diabetics. ADMA was significantly negative cola'elated with alkaline phosphatase (AP) and body length suggesting a link between ADMA and body growth. Fut'therrnore, a negative cola'elation between ADMA and diameter of carotid at'teries was observed. So fat', no cola'elations were found between pleatherosclerotic vasculat" abnorrnalities (i.e.IMT) and ADMA levels in the obese and diabetic cohort. Condusion. To the best of out"knowledge, this is the first observation of a significant decrease of peripheral ADMA levels fi'om childhood to adolescence. Metabolic and/or hemodynamic regulation processes associated with body growth may lead to this phenomenon. The attenuated decrease of ADMA in the obese and diabetics remains to be clarified - endothelial alteration may be involved.
CORRELATION BETWEEN IL-1[3, IL-6 AND HDL SERUM LEVELS N. Pistamaltzian, A. Regli, T. Drosos, C. Caroni, E. Kosioni, P. Ligoura, P. Zografos, I. Konstantinidis. Pammakaristos Hospital, NTUA, Athens,
Greece Objectives: To investigate the cola'elation between pro-inflammatory cy-
74th EAS Congress, 17-20 April 2004, Seville, Spain
iiiiii..".O.'iiiiiiiiiiiiiiii
iiiiii.-O.'iiiiiiiiiiiiiiii
Workshops Cytokines, the adipocyte, and atherosclerosis
Conclusions: AgLDL significantly enhance the effect of LPS on Cox-2 mRNA levels. Fut'thermore, monocytes in a lipidic enriched milieu could have and enhanced Cox-2 mediated-response to inflammatory stimuli.
•
IMPACT OF C-REACTIVE PROTEIN, LEPTIN AND ADIPONECTIN ON CARDIOVASCULAR RISK FACTORS IN SPAIN
M.T. Mat't nez, M. Mart nez, A. L pez, C. Fern ndez, J.L. Gonz lez, C. Zabena, M. Sen'ano. Hospital Cl nico San Carlos, Madrid, Spain
Aims: To study the interaction between C Reactive IS"otein (CRP) adiponectin and leptin levels with cat'diovasculat" risk factors in general Spanish population. Design and Methods: Population: Unrelated, healthy non diabetic individuals (n=724, 54.6% females) identified by crossectional survey in the Spanish province of Segovia (Autonomous Region of Castille-Leon. Central/North Eastern Spain). Anthropometric measurements: Body Mass Index (BMI), Waist Cfl-cumference (WC), Waist/Hip ratio (W/H) (as measut'es of Abdominal Obesity (AO)), Systolic Blood pressure (SBP), Diastolic Blood tS"essure (DBP). Laboratory parameters: Fasting Glucose (FG), lipid profile. Serum Fasting insulin (FI)/Proinsulin (FP)/Leptin (FL)/Adiponectin (APM) by RIAs. CRP serum by nephelometry. Results: 1. Population. Anthropometric/Laboratory data values for Abdominal Obesity (AO), DBP, FG, FI, FP, TG, LDL-C but not HDL-C, FL and APM significantly higher in males than in females (p< 0.05). 2. Sex/BMI adjusted log CRP/log FL in positive association but not to log APM. 3. Linear regression model: dependent variables: log CRP, log FL, log APM. Log CRP positively associated with age, W/H, negatively with HDL-C. Log APM positively associated with age and HDL-C, but negatively with W/H, TG, and FI. Log FL positively associated with W/H, FI. Conclusions: Both CRP/Fasting leptin serum levels have strong, independent association with AO/low HDL-C.Adiponectin is confirmed as a potentially protective cat'diovasculat" risk factor.
M. Palacios, P. Bull, N. Rubio, M. Itoiz, R. Santamar a, I. An'oyo, E. Perez de Cfl'iza, P. Aramburu, M. Garc a San Mart n, M. Sen'ano. Hospital de
Navarra, Centro de Salud de Azpilaga a, Dpto. Epidemiolog a y Salud P blica, Universidad de Navarra, Pamplona, Spain Diabetes mellitus type 2 is a disease with a well known vasculat" risk, and serum concentrations of several inflammatory markers have been found raised in diabetic patients, indicating endothelial dysfunction and cellular activation in vasculat" wall. Objectives: To analyse possible associations of inflammatoly molecules with anthropomeu'ic and clinical pat'ameters. Patients and methods: Fifty six diabetic patients were recruited and routine clinical determinations were recorded. Serum samples were fi'ozen for future determinations. Vascular cell adhesion molecule (s-VCAM-1), intercellulat" adhesion molecule (s-ICAM-1) and monocyte chemoattractant protein (MCP-1) were measut'ed by means of specific enzymoimmunoassays. Results: Almost a half (42.6%) were women and mean age was 63.4-t10.1 yeat's. Mean BMI was 33.6-t- 5.3 kg/m 2, and mean waist ch'cumference was 107.6-t- 10.8 cm. Multiple regression models were fitted with inflammatory mat'kers as dependent variables (outcome), and anthropometric (BMI and waist ch'cumference) and clinical variables (smoking, systolic and diastolic blood pressut'es, LDL cholesterol, HDL cholesterol, Hemoglobin Alc, age and gender) were used as independent vat'iables. These models showed that after adjustments, BMI is positively associated with serum levels of s-ICAM-1 (~ = 14.1 ng/ml; 95% confidence interval [CI]: 2.6-25.6; p<0.02) and s-VCAM-1 (~ = 12.9 ng/ml; 95% CI: 0.85-25; p<0.05), but not with MCP-1 (~ = 4.7 pg/ml; 95% CI: -12.9- 22.3; not significant). Other independent vat'iables in the models showed scarce an marginal associations. Conclusions: Our results suggest that BMI is the clinical pat'ameter in diabetic patients with a higher value in the prediction of vasculat" damage.
ADHESION MOLECULES CHANGES AFTER A HEALTH EDUCATION PROGRAM IN OBESE DIABETICS
M. Palacios, N. Rubio, P. Bull, M.J. Urbina, L. Tom s, C. I igo, J.A. Cabeza, J.I. Yoldi, C. Donlo, M. Sen'ano. Servicio de Bioqu mica,
Centro de Salud de Azpilaga a, Dpto. Epidemiolog a y Salud P blica, Hospital de Navarra, Universidad de Navarra, Pamplona, Spain Raised levels of adhesion molecules have been proposed as prognostic mat'kers of atherosclerosis, also in diabetic patients. Objectives: to study changes in the serum levels of the adhesion molecules induced by lifestyle changes. Patients and methods: Fifty six patients diagnosed of diabetes mellitus type 2 with a Body Mass Index (BMI) above 30 kg/m 2 were included. During six weeks a program of health education on diabetes self cat'e and management was developed. Vasculat" cell adhesion molecule (s-VCAM1) and intercellulat" adhesion molecule (s-ICAM-1) were measut'ed by enzymoimmunoassay. Results: Mean age was 63.4-4- 10.1 years, and 57.4% were men. BMI reduced fi'om 33.64- 5.3 to 32.94- 5.4 kg/m 2 (p<0.001) and waist cfl'cumference diminished fi'om 107.64- 10.7 to 105.14- 12.3 cm (p<0.001) after the 12 weeks period. Significant reductions were found in systolic and diastolic at'terial blood pressut'e, hemoglobin Alc, LDL cholesterol, but not in HDL cholesterol and triglycerides. Strikingly, s-ICAM-1 and s-VCAM-1 changes after intervention were opposite, s-ICAM-1 showed a significant reduction (254.24- 94.4 to 171.44- 41.4 ng/ml; p<0.001), indicating a lower level of endothelial dysfunction, s-VCAM-1 increased also significantly (151.44107.7 to 2514- 110.2 ng/ml; p<0.001). Conclusions: This inverse behaviout" of adhesion molecules in diabetic patients remain to be explained, but some previous reports indicate a higher physiopathologic role of s-ICAM-1, while s-VCAM-1 serum levels were not associated with objective measures of atherosclerosis. After these assessments, it would be suggested that changes in diabetic and obese patients obtained throughout short health education program would diminish vasculat" risks.
33
~ B O D Y MASS INDEX IS ASSOCIATED WITH MARKERS OF VASCULAR INFLAMMATION IN DIABETIC PATIENTS
~ ~
Pistamaltzian
SERUM LEVELS OF ASYMMETRIC DINIETHYLARGININE (ADMA) EXHIBIT SHARP DECLINE FROM CHILDHOOD TO ADOLESCENCE, W H I C H IS ATTENUATED IN OBESITY AND TYPE I DIABETES
S. Pilz, H. Hubmann, A. Meinitzer, M. Borkenstein, H. Mangge. Dept. of
Laboratory Medicine, Medical University of Graz, Graz, Austria Background and methods. AsymmeU'ical dimethylarginine (ADMA), a major inhibitor of NO synthase, is considered as a novel risk factor linking endothelial dysfunction and atherosclerosis. To evaluate ADMA in earliest stages of atherosclerosis, we measut'ed serum ADMA levels by means of high pressut'e lipid chromatography (HPLC)in obese juveniles and in juveniles with type I diabetes as compared to healthy, normal weighted, age matched conu'ols. The obese juveniles and the diabetics were identified in a previous study to show an increased intima media thickness of common cat'otid arteries paralelled by an increased low grade inflammation. Results. A sharp, age related, decrease of ADMA fi'om childhood to adolescence was observed in the controls, but not in the obese juveniles o1"the diabetics. ADMA was significantly negative cola'elated with alkaline phosphatase (AP) and body length suggesting a link between ADMA and body growth. Fut'therrnore, a negative cola'elation between ADMA and diameter of carotid at'teries was observed. So fat', no cola'elations were found between pleatherosclerotic vasculat" abnorrnalities (i.e.IMT) and ADMA levels in the obese and diabetic cohort. Condusion. To the best of out"knowledge, this is the first observation of a significant decrease of peripheral ADMA levels fi'om childhood to adolescence. Metabolic and/or hemodynamic regulation processes associated with body growth may lead to this phenomenon. The attenuated decrease of ADMA in the obese and diabetics remains to be clarified - endothelial alteration may be involved.
CORRELATION BETWEEN IL-1[3, IL-6 AND HDL SERUM LEVELS N. Pistamaltzian, A. Regli, T. Drosos, C. Caroni, E. Kosioni, P. Ligoura, P. Zografos, I. Konstantinidis. Pammakaristos Hospital, NTUA, Athens,
Greece Objectives: To investigate the cola'elation between pro-inflammatory cy-
74th EAS Congress, 17-20 April 2004, Seville, Spain
iiiiii..".O.'iiiiiiiiiiiiiiii
iiiiii.-O.'iiiiiiiiiiiiiiii