Poster Sessions PO19 Novel and classical CV risk factors and markers tive role in atherosclerosis through induction of antibodies to oxidized-LDL (Ox-LDL) in mice. Our aim was to investigate plasma IL-5 levels in humans and to assess the relationship between plasma IL-5 levels, antibody titers to Ox-LDL and early subclinical atherosclerosis as measured by carotid artery intima-media wall thickness (IMT). Methods and Results: The plasma IL-5 levels and antibody titers to Ox-LDL were measured from 1044 Finnish middle-aged subjects with chemiluminescent ELISA. IMT was measured from the internal carotid artery (ICA), the bifurcation enlargement (BIF) and the common carotid artery (CCA). IL-5 plasma levels were significantly (p=0.001) higher in men (195 ± 5 pg/ml) than in women (142 ± 5 pg/ml). There was a positive association among all the study subjects between plasma IL-5 levels and IgG and IgM antibody titers to copper oxidized LDL and MDA-LDL, the strongest correlation being between IgM to MDA-LDL (p<0.001). In the association studies between different IL-5 quartiles, IL-5 was negatively associated to bifurcational IMT. After adjustments for age, gender, smoking, systolic blood pressure, LDL and CRP IL-5 stayed as an independent determinant of the mean bifurcational IMT (p=0.012). Conclusions: Our data show that human plasma IL-5 levels are related to antibodies binding to Ox-LDL and to decreased subclinical atherosclerosis. These results are in line with the earlier findings in mice and support the concept of the protective role of IL-5 in atherosclerosis. COLLAGEN INDUCED ACCELERATED PLATELET AGGREGATION AS A POSSIBLE CAUSE FOR RESTENOSIS AFTER STENT IMPLANTATION IN PAOD
T. Gary 1 , A. Gries 2 , E. Pilger 1 , G. Seinost 1 , M. Brodmann 1 . 1 Division of Angiology, Medical University of Graz, Graz, Austria; 2 Institute of Physiology, Medical University of Graz, Graz, Austria Background: Restenosis after stenting of the peripheral arteries, despite maximum therapy with platelet aggregation inhibitors is an unsolved problem. In a prospective study we tried to evaluate if patients with a high grade restenosis after stenting of the peripheral arteries do have an accelerated platelet aggregation despite of maximum therapy with platelet aggregation inhibitors compared with patients without restenosis. Methods: Citrated whole blood from patients + restenosis (7 patients in each group with a comparable follow up period) after endovascular stenting of the lower limbs was mixed 1:1 with 0.9% NaCl and preincubated for 5 minutes at 37°C. Platelet aggregation was initiated with 1, 2 and 5 μg/ml collagen or 3, 5 and 10 μg/ml ADP and monitored by measuring electric impedance [Amplitude (Ohm), Lag-Time] using a whole blood aggregometer model 590 (Chrono-Log Corp., Havertown PA, USA). Results: With the addition of 5 μg/ml collagen we found a tendency to accelerated platelet aggregation in the restenosis group. The amplitude in the restenosis group was 10.6 + 3.7 Ohm compared to 10.00 + 3.3 Ohm in patients without stenosis. For Lag Time and with the addition of 2μg/ml Collagen we achieved similar results. When platelet aggregation was initiated with ADP we found no difference between the two groups. Conclusion: We conclude that the ADP induced platelet aggregation seems to have no influence on the formation of a restenosis after stent implantation in the peripheral arteries, it seems to be influenced by collagen induced platelet aggregation. PO19-521
ASSOCIATION OF ADIPONECTIN WITH HDL AND TRIGLYCERIDES SERUM LEVELS IN WOMEN WITH NORMAL AND IMPAIRED OGTT
G. Hroussalas 1 , E. Kassi 2 , I. Delimaris 1 , M. Dalamaga 2 , K. Kazanis 1 , A. Zachari 1 , A. Dionyssiou-Asteriou 1,2 . 1 Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece; 2 Department of Clinical Biochemistry, Medical School, University of Athens, Athens, Greece Background: Adiponectin is involved in glucose homeostasis and lipid metabolism. It increases insulin sensitivity and has anti-atherogenic/antiinflammatory effects. In the present study we investigated the association of serum adiponectin levels with the cardiovascular risk factors, cholesterol, HDL and triglycerides in relation to BMI and impaired glucose tolerance. Methods: Thirty, in total, overweight/obese postmenopausal women were included. Fifteen with normal glucose metabolism (NGT), age 48-69 years, BMI 28-32, waist circumference 82-104 cm and fifteen
with impaired glucose tolerance (IGT),age 53-69 years, BMI 29-40, waist circumference 87-115 cm. OGTT with 75gr was performed in the morning. Adiponectin was evaluated by ELISA at time 0-60-120 min of OGTT. Serum glucose, insulin, total-cholesterol, HDL, triglycerides were measured in automated analyzer (Roche Diagnostics). Insulin resistance(HOMA)/sensitivity(QUICKI) indexes were also calculated. Results: There was no correlation between adiponectin and BMI or waist circumference in both groups. In subjects with NGT fasting adiponectin levels were negatively correlated with HOMA (p=0.04) and positively with QUICKI (p=0.015). A positive correlation between adiponectin and HDL (r=0.737, p=0.003) and a negative between adiponectin and triglycerides (r= -0.633, p=0.01) were also found. In subjects with IGT the only correlation was a positive one between adiponectin and HDL (r=0.600, p=0.018). During OGTT there was not significant change of adiponectin levels in both groups. Conclusions: Adiponectin seems to exerts its antiatherogenic effect, at least in part, through its involvement on triglycerides and HDL metabolism. In the group with IGT the relationship of adiponectin with triglycerides does not exist implying disturbance of glucose and fatty acids metabolism. PO19-522
HIGH PLASMA ADIPONECTIN CONCENTRATION IN HEAVY ALCOHOL DRINKERS IS ASSOCIATED WITH HIGH HDL CHOLESTEROL AND LOW VLDL TRIGLYCERIDES
S.M. Makela 1 , M. Ala-Korpela 2 , T. Salonurmi 1 , M.J. Savolainen 1 , M.L. Hannuksela 1 . 1 Department of Internal Medicine, Clinical Research Center, University of Oulu, Oulu, Finland; 2 Laboratory of Computational Engineering, Systems Biology and Bioinformation Technology, Helsinki University of Technology, Helsinki, Finland Background: Adiponectin, an adipocyte-derived cytokine, has been recently suggested to have an important role in the pathophysiology of atherosclerosis. Adiponectin can suppress the secretion of inflammatory cytokines, such as TNF-alpha. Moreover, adiponectin may inhibit the formation of foam cells. Plasma adiponectin concentrations are lower in patients with coronary artery disease than in control subjects. The effects of alcohol consumption on plasma adiponectin levels are still controversial. Objective: To study the effects of alcohol consumption on plasma adiponectin consentrations in heavy alcohol drinkers and controls. Plasma adiponectin concentration was measured in 49 male alcohol drinkers (median alcohol intake 155 g/day) and 46 control men (11 g/day). Results: Mean plasma adiponectin concentration was 58% higher in the heavy alcohol drinkers (13.3 ± 4.0 ng/ml) than in the controls (8.4 ± 2.6 ng/ml) (P < 0.001, ANCOVA adjusted for BMI). Plasma adiponectin concentration correlated with HDL-C concentration after adjustment for BMI in the heavy alcohol drinkers (r = 0.444, P < 0.01) and in the controls (r = 0.519, P < 0.001). In addition, adiponectin was inversely correlated with VLDL-TG concentration (r = -0.507, P < 0.01) in the heavy alcohol drinkers after adjustment for BMI Conclusions: In addition to high plasma HDL cholesterol concentration, high plasma adiponectin concentration is likely one of the anti-atherogenic features in heavy alcohol drinkers. PO19-523
RELATIONSHIP BETWEEN ANKLE-BRACHIAL INDEX AND CHRONIC RENAL DISEASE IN HYPERTENSIVE SUBJECTS WITH NO KNOWN CARDIOVASCULAR DISEASE
J. Mostaza 1 , A. De la Pena 2 , E. Gonzalez-Sarmiento 3 , F. Vega-Rollan 4 , E. Rodilla 5 , A. Mangas 6 , J. Linares 7 , F. Carrasco 8 . 1 Atherosclerosis Unit, Hospital Carlos III, Madrid, Spain; 2 Internal Medicine Department, Hospital Son Llatzer, Palma de Mallorca, Spain; 3 Internal Medicine Department, Hospital Clinico de Valladolid, Valladolid, Spain; 4 Internal Medicine Department, Hospital Comarcal Del Bierzo, Leon, Spain; 5 Internal Medicine Department, Hospital de Sagunto, Valencia, Spain; 6 Internal Medicine Department, Hospital Puerta Del Mar, Cadiz, Spain; 7 Internal Medicine Department, Hospital Vigen de La Salud, Toledo, Spain; 8 Internal Medicine Department, Hospital La Inmaculada de Huercal-Overa, Almería, Spain Background: Both, decreased glomerular filtration rate (GFR) and albuminuria are associated with an elevated prevalence of peripheral artery disease (PAD). However, the combined effects of these alterations have not been previously evaluated.
76th Congress of the European Atherosclerosis Society, June 10–13, 2007, Helsinki, Finland
POSTER SESSIONS
PO19-520
145
146
Poster Sessions PO19 Novel and classical CV risk factors and markers
Methods: Patients with hypertension and with no known vascular disease (n=955; mean age 66 years; 56% males) were selected from internal medicine outpatient clinics distributed throughout Spain. Cardiovascular risk factors, urinary albumin excretion and the ankle-brachial index (ABI) were assessed in all participants. GFR was estimated according to the Cockroft-Gault equation. Results: Of the study population, 62% had diabetes, 23.8% a GFR <60 ml/min/1.73 m2 and 43.8% had albuminuria. The prevalence of ABI <0.9 was greater in those subjects with a GFR <60 ml/min/1.73 m2 (37.4% vs. 24.3%; p<0.0001) and in those who had albuminuria (32.2% vs. 23.3%; p=0.001). In subjects with both alterations, the prevalence of ABI <0.9 was 45.7%. Multivariate analysis indicated that the factors independently associated with low ABI were age (OR 1.06; 95%CI: 1.03 to 1.08; p<0.0001), triglyceride concentration (OR 1.003; 95%CI: 1.001 to 1.005; p=0.001), presence of albuminuria (OR 1.61,; 95%CI: 1.18 to 2.20; p=0.003), smoking habit (OR 1.72; 95%CI: 1.13 to 2.63; p=0.012) and a GFR <60 ml/min/1.73 m2 (OR 1.47; 95%CI: 1.01 to 2.17; p=0.049). Conclusion: In subjects with hypertension and without known vascular disease, reduced GFR and albuminuria are independently associated with an ABI <0.9. Their combined presence characterizes a subgroup of the population with an elevated prevalence of PAD who could benefit from early diagnosis and treatment. PO19-524
PROSPECTIVE EVALUATION OF THE ROLE OF THE ATHEROSCLEROSIS ON CEREBRAL ATROPHY: PILOT STUDY
S.H. Erbay 1 , M.G. O’Callaghan 2 , P. Shah 1 , J. Kini 3 , J. Basset-Midle 4 . of Radiology, Tufts-New England Medical Center, NEMC # 299, Boston, MA, USA; 2 Department of Radiology, University of Washington, Harborview Medical Center, Seattle, WA, USA; 3 Department of Radiology, Massachusetts General Hospital, Boston, MA, USA; 4 Department of Biostatistics, Tufts-New England Medical Center, Boston, MA, USA 1 Department
Purpose: Our purpose was to study the association between the atherosclerosis measured by arterial calcium on CT and cerebral atrophy demonstrated by brain MRI. Materials and Methods: Institutional review board approval was obtained for this prospective study. 21 consecutive patients presenting with acute stroke-like symptoms who are scheduled to have brain MRI were recruited on a voluntary basis. ECG gated helical CT scans were obtained from cardiac apex through the Circle of Willis to determine the arterial calcium load, reliable index of underlying atherosclerosis. Extracranial arterial calcium content was measured quantitatively by a special software available in our CT scanner. Intracranial calcium was graded qualitatively. Brain MRI was independently evaluated to identify cortical and central atrophy. Cerebral ischemic changes such as acute, chronic infarcts and periventricular hyperintensity are also recorded. Demographics and cardiovascular risk factors were evaluated in all subjects. Relationship between CT demonstrated atherosclerosis and cerebral ischemic changes, brain atrophy patterns were evaluated both without and with adjustment for age and hypertension. Results: 20 out of 21 patients were included in final study group. There was no correlation between atherosclerotic calcium measures and cortical atrophy, ischemic findings. Both intra-cranial and extra-cranial atherosclerosis had partial correlation with central atrophy (R=0.43 and R=0.52 respectively). After adjustment for age, only intra-cranial atherosclerosis maintained a partial correlation with central atrophy (R=0.41). This correlation did not reach statistically significant level however (p=0.10) Conclusions: Intracranial atherosclerosis demonstrated a possible correlation with central atrophy.
cardiovascular diseases (CVD) are, however, scarce and contradictory. The aim of our study is to assess whether serum MMP-8, tissue inhibitor of metalloproteinase-1 (TIMP-1) and/or MMP-8/TIMP-1 ratio could predict CVD deaths. Methods: We analysed the association of serum MMP-8 and TIMP-1 concentrations in a population-based prospective sample of 1018 Finnish men (aged 46-64 years) of the Kuopio Ischaemic Heart Disease Study with the follow-up time of 10 years. Results: MMP-8 concentrations or MMP-8/TIMP-1 ratios were higher in men with prevalent CVD or subclinical atherosclerosis [intima-media thickness (IMT) ≥ 1 mm] at baseline than those without. In men free of CVD at baseline (n=905), MMP-8 concentrations predicted death from coronary heart disease (CHD) or CVD with multivariate odds ratios (95% CI, p) of 1.11 (1.01-1.23, 0.037) and 1.10 (1.00-1.20, 0.045) per 10 μg/l increase, respectively. In men with no prevalent CVD but with subclinical atherosclerosis at baseline, elevated serum MMP-8 concentration and MMP-8/TIMP-1 ratio (highest quartile vs. lower quartiles) predicted CVD death with relative risks of 3.4 (1.03-11.03, p=0.044) and 2.0 (0.94-6.37, p=0.095), respectively. Serum TIMP-1 concentrations alone had no predictive value for CVD death. Conclusions: The results indicate that serum MMP-8 concentrations are elevated in prevalent or subclinical atherosclerosis and that elevated MMP-8 concentrations predict the worst cardiovascular outcome. PO19-526
N. Fiotti, N. Altamura, M. Moretti, S. Wasserman, P. Pitacco, G. Guarnieri, C. Giansante. Dept. of Clinical Morphological and Technological Sciences, Trieste Background and Aim: MMPs play a relevant role in structure and stability of atherosclerotic plaques. Atherosclerotic plaques triggering ACS show increased expression of MMP-1, MMP-3 and MMP-9. Regulation of MMPs is also plaid by genetic polymorphisms of MMP-1 (G+/G- at -1563) MMP-3 (4A/5A- at –1612), and MMP-9 (13-27 CA repeats around -90). The aim of this study was to correlate the clinical outcome of NSTEACS, with genetic polymorphism of MMP-1, MMP-3 and MMP-9. Methods: One hundred patients admitted with the diagnosis of NSTEACS were observed and in hospital MACES recorded and compared in relation to genetic polymorphism of MMPs determined by capillary electrophoresis. Results: Forty-seven patients had a MACE during hospitalisation. MACE risk was reduced in carriers of MMP-1 G+ (O.R. 0.21, 95%C.I. 0.08-0.56) compared to carriers of G-/G- genotype, and increased in carriers of MMP-9 microsatellites longer than 21 repeats (O.R. 3.9, 95%C.I. 1.69-9.06) compared to carriers of 21 or less repeats. MMP-3 4A polymorphism was not associated to increased risk of MACE (O.R. 0.89 95% C.I.0.37-2.16). Haplotype analysis suggests a synergistic activity of genotypes in increasing the risk of MACE: carriers of MMP-1 G-/MMP-9 >21 repeats at the highest risk (O.R. 10.86, 95% C.I. 2.1-50) while the combination MMP-1 G+/MMP-9 <22 repeats seems to be protective (O.R. 0.2 95% C.I. 0.08-0.5). Conclusions: MMP-1 and MMP-9 polymorphism are implicated in the development of MACE in NSTEACS. Haplotype analysis suggests a cross talk between these MMPs in determining the occurrence of the complications. PO19-527
PO19-525
ELEVATED SERUM MMP-8 CONCENTRATIONS IN MEN WITH SUBCLINICAL ATHEROSCLEROSIS PREDICT CVD DEATH
A.M. Tuomainen 1 , K. Nyyssonen 2 , J.A. Laukkanen 2 , T. Tervahartiala 1 , T.P. Tuomainen 2 , J.T. Salonen 2 , T. Sorsa 1 , P.J. Pussinen 1 . 1 Institute of Dentistry, University of Helsinki, Helsinki, Finland; 2 Research Institute of Public Health, University of Kuopio, Kuopio, Finland Objective: In cell culture studies matrix metalloproteinase-8 (MMP-8 or collagenase-2) thins the protecting fibrous cap of the atherosclerotic plaque, and expression studies show MMP-8 to localize in the shoulder region of the cap. Results on the association of serum MMP-8 concentrations and
MATRIX METALLOPROTEASE HAPLOTYPE INFLUENCES THE IN-HOSPITAL CLINICAL OUTCOME OF NSTEACS
ROLE OF THE ARTERIAL STENOSIS IN AN ATHEROSCLEROSIS
M.V. Beraia 1 , F.I. Todua 2 . 1 MRI Dept., Institute of Medical Radiology, Tbilisi, Georgia; 2 Institute of Medical Radiology, Tbilisi, Georgia Purpose: To study the blood flow features in the aortic arch and reveal the initial factors of atherogenesis and goals for arterial stenosis. Methods: 15 normal men (age from 27 to 35years) have been investigated by magnetic resonance angiography. The phase images were carried out using Siemens-Avanto device. 1.5T. fl2D, TR-24.6ms, TE-1.5ms, SL6; TR-47ms, TE- 2.7ms. TA 19.30, SL6. with the inspiratory breath hold and ECG triggering. The research of hemodynamic parameters was carried out in different sites and the opposite walls of the aortic arch with the area ≈ 0.7cm2 .
76th Congress of the European Atherosclerosis Society, June 10–13, 2007, Helsinki, Finland