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We-P13:331 Complex adaptive response in the metabolic syndrome (MS): Clinical, functional and genetic study
Wednesday, June 21, 2006: Poster Session P13 Metabolic syndrome MS subjects. Whether anti-inflammatory agents may enhance lifestyle modification in ameliorating MS and hence reverses the risk for diabetes and CVD needs exploration.
W e - P 1 3 : 3 2 9 ] S Y M P A T H E T I C ACTIVATION A N D RISK OF A T H E R O S C L E R O S I S IN PATIENTS W I T H DIABETES MELLITUS TYPE 1 T. Zykova, A. Strelkova, K. Balandina, O. Batrakova. Northen State Medical
Universi~, Arkhangelsk, Russia Objective: To reveal correlation between high heart rate in rest in men with DMT- 1and components of metabolic syndrome. Methods: We investigated 27 men age 27.6-t-2.1 with DM T-lduration 1-20 years (average 6.3-t-l.2years). Criteria of inclusion: lack of severe complications-diabetic nephropathy and microalbuminuria (MAIl); retinopathy, except initial manifestations of nonproliferative stage. We estimated weight, growth, circumference waist, circumference thigh, BMI, index waistthigh, blood pressure, heart rate after 15-minute rest; investigated lipid plasma levels: cholesterol, HDL-C, H b A l c . M A I l was determined in 2 night portions when there was negative test on urine infection. Criteria of exclusion: clinical manifestations of neuropathy and atherosclerosis. Results: 12 men had values of heart rate more than 85 beats per minute. Most of patients had decompensation of carbohydrate metabolism- high values of H b A l c 9.1+0.13% before investigation. We haven't revealed correlations between demographic and anthropometric data and heart rate in rest. Heart rate didn't depend on duration and compensation DM. Positive relations were between heart rate in rest and cholesterol (r=0.49, ?=0.04) and MAU(r=0.55, ?=0.02). Negative relation was between heart rate and HDL-C values (r= -0.55, ?=0.02). Conclusion: The presence of correlations between heart rate in rest in men with DM T-land clinical markers of high risk cardiovascular diseases (cholesterol, HDL-C, MAIl) is evidence of availability of sympathetic activation in this cohort and may be serves as earlier marker of atherosclerosis manifestation. F u n d i n g : We confirm the role of heart rate in rest in men with DM T-las characteristic concerned with proatherogenic changes of plasma lipid profile and M A I l reflecting development of nephropathy, cardiovascular risk.
IWe-P13:330 1 AMSYSEOLCOIPAETRI OONX IBDEATSWE ELEENV EP LL AS SAMNAD M E T A B O L I C SYNDROME H. Ghanbari, B. Hassunizadeh, H. Manyam, R. Dandamudi, D. Cunningham, S. David, C. Machado. Providence Hospital and Medical Centers, Southfield,
USA Objective: To investigate the association of plasma myeloperoxidase (MPO) levels measured by Enzyme Immuno Assay (EIA) with the presence of metabolic syndrome (MS). Methods: Patients referred for elective cardiac catheterization were included in the study. Patients with evidence of infection, malignant disease or recent myocardial infaxction were excluded. Five milliliters of hepaxinized plasma from each patient was analyzed by EIA using human MPO antibody. Plasma MPO levels were determined photometrically. MS was defined by the National Cholesterol Education Program (NCEP) criteria. Results: The study comprised of 183 patients. Mean age was 65 -4- 13 years, 62% were males. MS was identified in 66% of patients (120/183). Patients with MS had significantly higher mean MPO levels than patients without MS (279.4 -4- 21.1 pM vs 172.5 -4- 22.8 pM, p=0.002). In patients with MPO levels > 91.6 pM (137/183) the likelihood of having MS was significantly higher than in the group of patients with MPO levels < 91.6 pM (OR, 5.17; 95% CI, 2.53-10.54, p=0.0005). A cut-off value of 91.6 p M for MPO identified the presence of MS with sensitivity of 86% and positive predictive value of 75%. Conclusions: Patients with MS have significantly higher MPO levels than patients without MS. A cut-off value of 91.6 pM for MPO may identify majority of patients with MS with high sensitivity and positive predictive value. The presence of increased MPO levels in patients with MS suggests a role for MPO as a mediator for the inflammatory state associated with MS. Funding: Provided by Providence hospital research department.
419
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W e - P 1 3 : 3 3 1 / C O M P L E X A D A P T I V E R E S P O N S E IN T H E M E T A B O L I C S Y N D R O M E (MS): C L I N I C A L , FUNCTIONAL AND GENETIC STUDY V. Palmieri, E Portincasa, I. Grattagliano, A. Genovese, G. Caxdinale, G. Palasciano. Clinica Mediea Augusto MurH, Universi~ of Bat4, BaH, Italy The MS is a clinical disorder that involves multiple organs and systems in reciprocal interactions (it therefore a typical example of a complex systemic disorder). A systemic approach to the analysis of MS is important in order to characterize its pathological mechanisms and to establish an adequate therapeutic approach. Objectives of this ongoing study are to characterize the complex adaptive response in the MS; to establish the relationship between MS and pathological associated conditions; to define the existence of mitochondrial genoma alterations in subjects affected by different phenotypes of MS. A cohort of almost 100 MS patients and their relatives with or without MS has undergone to clinical evaluation (by neural networks methodology), functional evaluation (glycidic and cardiovascular homeostasis by glucose and blood pressure continuous monitoring, redox state: Vitamin E and C, Vitamin C, Glutathione, Homocysteine, malondyaldeide), study of prevalence of associated factors (gallstones and NASH), evaluation of mitochondrial genoma (extraction of DNA from blood cells and analysis of variant by PCR and restriction enzyme digestion). Main preliminary results show that: 1) in pts with maternal inheritance for MS, no 4291 variant of mtDNA, previously associated to MS, has been found while one polymorphism not explicable dy data present in literature has been found and is under further analysis by the screening of the entire mtDNA; 2) early alterations of g l y d d i c homeostasis - impaired glucose tolerance, late hypoglycaemic response to oral glucose load - are present in patients with MS and no basal glycemic alterations; 3) the existence of alterations of antioxidant systems (reduction of vitamins C and E) and of oxidation (malondyaldeide) in patients with MS that have no cardiovascular complications.
We-P13:332
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U R I C A C I D IS A S S O C I A T E D W I T H C O R O N A R Y ARTERY CALCIFCIATION AMONG ASYMPTOMATIC MEN WITH METABOLIC SYNDROME
• ~ R.D. Santos 1 , K. Naslr ~, R. Orakzal"~~ , S. Orakzal"~~ , R. Meneghelo 3 , J.A.M. Carvalho 3, R. B l u m e n t h a l4. / Heart bzstitute bwor Universi~ of Sao
Paulo, Sao Paulo, Brazil: 2 Universi~ of Pittsburgh, Pittsburgh, USA." 3Prm'entive Medicine Center Albert Einstein Hospital, Sao Paulo, Brazil: 4johns Hopkins Medical btstitutions, Baltimore, USA B a c k g r o u n d : There is suggestion that elevated uric a d d (UA) is a risk factor for cardiovascular disease. Whether UA is just an innocent bystander in proximity to vascular events in patients who have an abnormal metabolic profile or whether it has an independent mechanistic action is unclear. In this study we aim to assess the association of increasing UA levels with coronary artery calcification (CAC), a specific marker for coronary atherosclerosis in asymptomatic men according with the metabolic syndrome (MS) status. Methods a n d Results: We evaluated 371 subjects (48-t-7 yrs.) that were submitted to a routine medical evaluation that included CAC quantification by electron beam tomography. After adjusting for age, cholesterol, and smoking status; the odds ratios (95%CI) of quartiles of UA for MS were 1.0, 1.13 (0.53-2.41), 2.0 (0.95-4.17), and 3.60 (1.78-7.28). After adjusting for age, LDL-C, and smoking status, the odds ratio (95%CI) for subjects in the second, third and fourth quartiles of UA level with 0.89 (0.47-1.67), 0.92 (0.47-1.81), and 1.74 (0.90-1.81), respectively. UA in the highest quartile (high UA) was significantly associated with increased CAC prevalence with an odds ratio of 1.85 (95% CI, 1.11-3.19, p=0.027) adjusted for the same covariates with lower (normal UA) as reference. Multivariate analysis using the same covariates demonstrated high UA to be associated with CAC in men with MS (OR: 3.02 95%CI; 1.08-8.48, p=0.035) but not in men without it (OR 1.32, 95%CI 0.68-2.59,p=0.4). C o n d u s i o n s : In asymptomatic men with the MS, UA was independenlty associated with CAC.
XIV bztetTtational Symposium on Atherosclerosis, Rome, Italy, June 18-22, 2006
W e - P 1 3 : 3 2 9 ] S Y M P A T H E T I C ACTIVATION A N D RISK OF A T H E R O S C L E R O S I S IN PATIENTS W I T H DIABETES MELLITUS TYPE 1 T. Zykova, A. Strelkova, K. Balandina, O. Batrakova. Northen State Medical
Universi~, Arkhangelsk, Russia Objective: To reveal correlation between high heart rate in rest in men with DMT- 1and components of metabolic syndrome. Methods: We investigated 27 men age 27.6-t-2.1 with DM T-lduration 1-20 years (average 6.3-t-l.2years). Criteria of inclusion: lack of severe complications-diabetic nephropathy and microalbuminuria (MAIl); retinopathy, except initial manifestations of nonproliferative stage. We estimated weight, growth, circumference waist, circumference thigh, BMI, index waistthigh, blood pressure, heart rate after 15-minute rest; investigated lipid plasma levels: cholesterol, HDL-C, H b A l c . M A I l was determined in 2 night portions when there was negative test on urine infection. Criteria of exclusion: clinical manifestations of neuropathy and atherosclerosis. Results: 12 men had values of heart rate more than 85 beats per minute. Most of patients had decompensation of carbohydrate metabolism- high values of H b A l c 9.1+0.13% before investigation. We haven't revealed correlations between demographic and anthropometric data and heart rate in rest. Heart rate didn't depend on duration and compensation DM. Positive relations were between heart rate in rest and cholesterol (r=0.49, ?=0.04) and MAU(r=0.55, ?=0.02). Negative relation was between heart rate and HDL-C values (r= -0.55, ?=0.02). Conclusion: The presence of correlations between heart rate in rest in men with DM T-land clinical markers of high risk cardiovascular diseases (cholesterol, HDL-C, MAIl) is evidence of availability of sympathetic activation in this cohort and may be serves as earlier marker of atherosclerosis manifestation. F u n d i n g : We confirm the role of heart rate in rest in men with DM T-las characteristic concerned with proatherogenic changes of plasma lipid profile and M A I l reflecting development of nephropathy, cardiovascular risk.
IWe-P13:330 1 AMSYSEOLCOIPAETRI OONX IBDEATSWE ELEENV EP LL AS SAMNAD M E T A B O L I C SYNDROME H. Ghanbari, B. Hassunizadeh, H. Manyam, R. Dandamudi, D. Cunningham, S. David, C. Machado. Providence Hospital and Medical Centers, Southfield,
USA Objective: To investigate the association of plasma myeloperoxidase (MPO) levels measured by Enzyme Immuno Assay (EIA) with the presence of metabolic syndrome (MS). Methods: Patients referred for elective cardiac catheterization were included in the study. Patients with evidence of infection, malignant disease or recent myocardial infaxction were excluded. Five milliliters of hepaxinized plasma from each patient was analyzed by EIA using human MPO antibody. Plasma MPO levels were determined photometrically. MS was defined by the National Cholesterol Education Program (NCEP) criteria. Results: The study comprised of 183 patients. Mean age was 65 -4- 13 years, 62% were males. MS was identified in 66% of patients (120/183). Patients with MS had significantly higher mean MPO levels than patients without MS (279.4 -4- 21.1 pM vs 172.5 -4- 22.8 pM, p=0.002). In patients with MPO levels > 91.6 pM (137/183) the likelihood of having MS was significantly higher than in the group of patients with MPO levels < 91.6 pM (OR, 5.17; 95% CI, 2.53-10.54, p=0.0005). A cut-off value of 91.6 p M for MPO identified the presence of MS with sensitivity of 86% and positive predictive value of 75%. Conclusions: Patients with MS have significantly higher MPO levels than patients without MS. A cut-off value of 91.6 pM for MPO may identify majority of patients with MS with high sensitivity and positive predictive value. The presence of increased MPO levels in patients with MS suggests a role for MPO as a mediator for the inflammatory state associated with MS. Funding: Provided by Providence hospital research department.
419
1
W e - P 1 3 : 3 3 1 / C O M P L E X A D A P T I V E R E S P O N S E IN T H E M E T A B O L I C S Y N D R O M E (MS): C L I N I C A L , FUNCTIONAL AND GENETIC STUDY V. Palmieri, E Portincasa, I. Grattagliano, A. Genovese, G. Caxdinale, G. Palasciano. Clinica Mediea Augusto MurH, Universi~ of Bat4, BaH, Italy The MS is a clinical disorder that involves multiple organs and systems in reciprocal interactions (it therefore a typical example of a complex systemic disorder). A systemic approach to the analysis of MS is important in order to characterize its pathological mechanisms and to establish an adequate therapeutic approach. Objectives of this ongoing study are to characterize the complex adaptive response in the MS; to establish the relationship between MS and pathological associated conditions; to define the existence of mitochondrial genoma alterations in subjects affected by different phenotypes of MS. A cohort of almost 100 MS patients and their relatives with or without MS has undergone to clinical evaluation (by neural networks methodology), functional evaluation (glycidic and cardiovascular homeostasis by glucose and blood pressure continuous monitoring, redox state: Vitamin E and C, Vitamin C, Glutathione, Homocysteine, malondyaldeide), study of prevalence of associated factors (gallstones and NASH), evaluation of mitochondrial genoma (extraction of DNA from blood cells and analysis of variant by PCR and restriction enzyme digestion). Main preliminary results show that: 1) in pts with maternal inheritance for MS, no 4291 variant of mtDNA, previously associated to MS, has been found while one polymorphism not explicable dy data present in literature has been found and is under further analysis by the screening of the entire mtDNA; 2) early alterations of g l y d d i c homeostasis - impaired glucose tolerance, late hypoglycaemic response to oral glucose load - are present in patients with MS and no basal glycemic alterations; 3) the existence of alterations of antioxidant systems (reduction of vitamins C and E) and of oxidation (malondyaldeide) in patients with MS that have no cardiovascular complications.
We-P13:332
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U R I C A C I D IS A S S O C I A T E D W I T H C O R O N A R Y ARTERY CALCIFCIATION AMONG ASYMPTOMATIC MEN WITH METABOLIC SYNDROME
• ~ R.D. Santos 1 , K. Naslr ~, R. Orakzal"~~ , S. Orakzal"~~ , R. Meneghelo 3 , J.A.M. Carvalho 3, R. B l u m e n t h a l4. / Heart bzstitute bwor Universi~ of Sao
Paulo, Sao Paulo, Brazil: 2 Universi~ of Pittsburgh, Pittsburgh, USA." 3Prm'entive Medicine Center Albert Einstein Hospital, Sao Paulo, Brazil: 4johns Hopkins Medical btstitutions, Baltimore, USA B a c k g r o u n d : There is suggestion that elevated uric a d d (UA) is a risk factor for cardiovascular disease. Whether UA is just an innocent bystander in proximity to vascular events in patients who have an abnormal metabolic profile or whether it has an independent mechanistic action is unclear. In this study we aim to assess the association of increasing UA levels with coronary artery calcification (CAC), a specific marker for coronary atherosclerosis in asymptomatic men according with the metabolic syndrome (MS) status. Methods a n d Results: We evaluated 371 subjects (48-t-7 yrs.) that were submitted to a routine medical evaluation that included CAC quantification by electron beam tomography. After adjusting for age, cholesterol, and smoking status; the odds ratios (95%CI) of quartiles of UA for MS were 1.0, 1.13 (0.53-2.41), 2.0 (0.95-4.17), and 3.60 (1.78-7.28). After adjusting for age, LDL-C, and smoking status, the odds ratio (95%CI) for subjects in the second, third and fourth quartiles of UA level with 0.89 (0.47-1.67), 0.92 (0.47-1.81), and 1.74 (0.90-1.81), respectively. UA in the highest quartile (high UA) was significantly associated with increased CAC prevalence with an odds ratio of 1.85 (95% CI, 1.11-3.19, p=0.027) adjusted for the same covariates with lower (normal UA) as reference. Multivariate analysis using the same covariates demonstrated high UA to be associated with CAC in men with MS (OR: 3.02 95%CI; 1.08-8.48, p=0.035) but not in men without it (OR 1.32, 95%CI 0.68-2.59,p=0.4). C o n d u s i o n s : In asymptomatic men with the MS, UA was independenlty associated with CAC.
XIV bztetTtational Symposium on Atherosclerosis, Rome, Italy, June 18-22, 2006