Abstracts / Atherosclerosis 235 (2014) e192–e301
Objectives: The aim of the study was to determine the severity of coronary lesions in patients with type 2 diabetes and critical ischemia of the lower extremities and influence on the postoperative prognosis. Methods: In our center in 2013, 384 patients with type 2 diabetes (163 women and 221 men) aged 56.8 8.2 years were operated on with a diagnosis of gangrene of the lower extremities, without history of myocardial infarction. We evaluated artery lesions using multislice computed tomography (angiography). Results: Duration of diabetes was 8.45.2years, blood glucose 15.56.8 mmol/l, HbA1c was 9.61.8%. Coronary heart disease functional class III was detected in 320(83.3%) patients, class IV in 64 (16.7%). Postoperative period was complicated by acute myocardial infarction in 65(17.2%) patients (Q wave in 38, non-Q wave in 27 cases), 23 (35.3%) were fatal. Frequency of coronary artery lesions, depending on the critical stenosis of the lower limb arteries are presented in table (Table).
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Post hoc analysis showed a difference between GCK-MODY and HNF1AMODY (p¼0.0427). BMI was similar in all three groups – 23.84.4, 24.13.7 and 24.03.8 in GCK-MODY, HNF1A-MODY and controls, respectively (p¼0.6930). Patients and controls were also at the similar age (p¼0.6343). Glycemic control was similar in diabetic groups as in the GCK-MODY group the mean HbA1c was 6.4%0.7, while in HNF1A-MODY patients it reached 6.71.4 (p¼0.9274, p¼0.2169). Conclusion: Both examined MODY groups showed evidence of early atherosclerosis or endothelial dysfunction. Mild hyperglycemia in the GCK-MODY seems to have impact on the occurrence of intermediate atherosclerotic phenotypes. 62 - Aneurysms and other non-atherosclerotic arteriopathies EAS-0607. EXPRESSION OF ADAMTS-1 IN AAA T. Gustafssona, E. Vorkapica, P. Erikssonb, D. Wågsätera a Department of Medicine and Health Science, Linköping University, Linköping, Sweden; b Department of Medicine, Karolinska Institute, Stockholm, Sweden
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Conclusion: Almost all patients with type 2 diabetes and critical limb ischemia had critical stenosis of the coronary arteries. The higher the caliber of affected arteries, the worse postoperative prognosis (17.2% acute myocardial infarction, 35.3% fatal). 61 - Diabetic macro- and microangiopathies EAS-0705. ENDOTHELIAL DYSFUNCTION AND INTIMA-MEDIA THICKNESS IN GCK AND HNF1A MODY PATIENTS M. Szopaa, G. Osmendab, G. Wilkb, B. Matejkoa, T. Guzikb, M.T. Maleckia a Department of Metabolic Diseases, UJCM, krakow, Poland; b Department of Internal and Agricultural Medicine, UJCM, krakow, Poland
Objectives: The most frequent causes of MODY (maturity onset diabetes of the young) are the GCK (glucokinase) and HNF1A gene mutations. Progressive insulin secretory defect and hyperglycaemia are associated with mutations in the gene encoding the transcription factor HNF1A. Heterozygous loss-of-function GCK mutations result in a moderate fasting hyperglycemia. The GCK-MODY patients are usually free from microvascular complications; however, little is known about atherosclerosis and intermediate related phenotypes. We aimed to examine intima-media thickness (IMT) and endothelial function in GCK-MODY and HNF1A-MODY. Methods: 62 GCK-MODY, 40 HNF1A-MODY patients and 44 non-diabetic controls were examined. Carotic artery IMT and brachial artery FMD and NMD (nitroglycerin mediated dilatation) were assessed by ultrasonography. These parameters were compared with test for difference between two groups (t-test or U Mann Whitney test) or three groups (one way analysis of variance ANOVA or the Kruskal-Wallis test with post hoc test). Results: The mean FMD was 11.14.7% in GCK-MODY, 10.05.0 in HNF1AMODY and 14.2 4.9 in the controls (p¼0.0031). The differences between GCK-MODY and HNF1A-MODY vs. controls were significant (p¼0.0043, p¼0.0002, respectively). The average maximum IMT was not different 0.710.17 mm in GCK-MODY, 0.750.14 in HNF1A-MODY, and 0.70,15 in the controls (p¼0.1251). Mean IMT were as follow – 0.620.15 mm in GCKMODY, 0.670.12 in HNF1A-MODY and 0.620.12 in controls (p¼0.0267).
Objectives: Accelerated breakdown of connective tissue, i.e. extracellular matrix, is a feature of many pathological conditions involving inflammation. Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease involving leukocyte infiltration that produce and secrete cytokines and proteases responsible for degradation of the extracellular matrix. Matrix components of the vessel wall include elastin, collagens and proteoglycans such as versican. A disintegrin and metalloprotease with thrombospondin motif type I (ADAMTS-1) is highly expressed in the aorta and cleaves versican, promoting VSMC migration. The aim of this project is to investigate the expression, localisation and regulation of ADAMTS-1 in AAA development. Methods: Gene expression of ADAMTS-1 was determined by real-time RTPCR. Immunohistochemical analysis was used to localize ADAMTS-1 to specific cell types. AAA was induced experimentally in mice, using two different, complementary models: CaCl2 and angiotensin II. Results: Gene expression of ADAMTS-1 was highly reduced in aortas from human AAA. Immunohistochemical analysis of ADAMTS-1 localised it to smooth muscle cells and endothelial cells and confirmed reduced expression of ADAMTS-1. Gene expression of ADAMTS-1 was also reduced in mice with AAA. Conclusion: Our preliminary data shows that expression of ADAMTS-1 is reduced during aneurysm formation, probably due to phenotypic modulation or apoptosis of smooth muscle cells. Further studies using ADAMTS1 transgenic mice could help to elucidate the role of ADAMTS-1 in aneurysm formation in more detail. 64 - Intervention into physical activity EAS-0582. THE EFFECT OF MODERATE EXERCISE ON THE AFFINITY TRIGLYCERIDE-RICH LIPOPROTEINS FOR LIPOPROTEIN LIPASE
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K. Ghafouri, M. Caslake, J.MR. Gill Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom Objectives: Exercise-induced reductions in VLDL1 concentration are mediated by increased catabolism, rather than reduced hepatic production. This may be facilitated by compositional changes to VLDL1 particles that increase their affinity for clearance from the circulation. The aim of the study was therefore to determine the effect of moderate exercise on the affinity of triglyceride (TG)-rich lipoproteins for lipoprotein lipase (LPL). Methods: Ten overweight/obese middle-aged men underwent two oral fat tolerance tests (OFTT), in random order. On the afternoon prior to the OFTT, subjects either walked on a treadmill for 90 min at w50% maximal oxygen
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Abstracts / Atherosclerosis 235 (2014) e192–e301
uptake or performed no exercise. Multiple blood samples were taken during and after OFTT for separation of chylomicron (Sf 400) and VLDL1 (Sf 60-400) and VLDL2 (Sf 20-60) Lipoprotein fractions (at concentration 0.6 mmol.l-1) were incubated with LPL in Tris-HCl buffer for intervals from 530 min and the release of NEFA was measured. The rate of NEFA release was used to assess affinity of the lipoproteins for hydrolysis by LPL. Results: The concentration of TG in VLDL1 were significantly reduced after exercise by 40% in fasted state and by 36% in postprandial state; Chylomicron-TG was reduced by 33% (all P¼0.01). The affinity of VLDL1 particles for LPL increased significantly post-exercise in both fasted (NEFA release: Control 133 mmol.l-1.min-1, Exercise 255 mmol.l-1.min-1 p¼0.01) and postprandial (Control 82 mmol.l-1.min-1, Exercise 204 mmol.l-1.min-1 p¼0.0005) states. Conclusion: The affinity of VLDL1 particles for LPL appears to increase after exercise, in line with the study hypothesis. The affinity of VLDL1 for LPL also appeared to decrease in the postprandial compared with fasted state. This is worthy of further investigation.
Methods: We allocated 42 overweight and obese sedentary individuals to an exercise intervention program, consisting of hiking downwards a predefined route in the Austrian Alps over two months. For the opposite way, a cable car was used where compliance was recorded electronically. The difference in altitude was 540 metres; the distance was covered three to five times a week. A matched group of 12 individuals served as a control group. Metabolic profiles were obtained at baseline and after the two months period. Results: Compared to baseline, 8 weeks of eccentric endurance exercise significantly lowered serum alanine aminotransferase (ALT; 3623 vs. 3118 U/l; p Conclusion: We conclude that eccentric exercise is a promising new exercise modality which significantly lowers liver enzymes in overweight and obese individuals and therefore is of interest as a therapeutic intervention in non-alcoholic fatty liver disease patients.
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EAS-0567. VOLUNTARY EXERCISE SLOWS THE PROGRESSION OF ESTABLISHED ANGIOTENSIN II-DEPENDENT ADVANCED ATHEROSCLEROTIC LESIONS
EAS-0551. METABOLIC BENEFITS OF ECCENTRIC ENDURANCE EXERCISE IN OVERWEIGHT AND OBESE INDIVIDUALS P. Reina, C.H. Saelya, A. Vonbanka, S. Geller-Rhombergb, A. Leihererb, H. Drexelb a
Academic Teaching Hospital Feldkirch, Department of Internal Medicine & Cardiology, Feldkirch, Austria; b Academic Teaching Hospital Feldkirch, Vivit-Institute, Feldkirch, Austria Objectives: Eccentric endurance exercise (e.g. hiking downwards) is less strenuous than concentric exercise (e.g. hiking upwards) but data on its potential to reduce cardiovascular risk are scarce. Methods: We allocated 68 overweight and obese sedentary individuals to an exercise intervention program, consisting of hiking downwards the same route over two months. For the opposite way, a cable car was used where compliance was recorded electronically. The difference in altitude was 540 meters; the distance was covered three to five times a week. A matched group of 12 individuals served as a control group. Fasting and postprandial metabolic profiles were obtained at baseline and after the two months period. Results: Compared with baseline, eccentric endurance exercise significantly lowered fasting glucose (9917 vs. 9613 mg/dl; p¼0.036) as well as glucose tolerance following the oral intake of 75g glucose (25049 vs. 22854 mg*dl-1 h; p-1 h; p 2; p¼0.004) but not in the control group (p¼0.237). Conclusion: Eccentric endurance exercise is a promising new exercise modality with favorable effects on both fasting and postchallenge metabolism. 64 - Intervention into physical activity EAS-0552. SIGNIFICANT IMPACT OF ECCENTRIC ENDURANCE EXERCISE ON LIVER ENZYMES IN OVERWEIGHT AND OBESE INDIVIDUALS P. Reina, A. Vonbanka, C.H. Saelya, A. Leihererb, H. Drexelb a Academic Teaching Hospital Feldkirch, Department of Internal Medicine & Cardiology, Feldkirch, Austria; b Academic Teaching Hospital Feldkirch, Vivit-Institute, Feldkirch, Austria
Objectives: Elevated liver enzymes are highly prevalent in overweight and obese patients, reflect the presence of non-alcoholic fatty liver disease, and are associated with an increased risk of diabetes and cardiovascular events. Liver enzymes can be lowered by physical exercise, but many overweight patients are not willing or not able to engage in strenuous exercise regimens. Eccentric endurance exercise (e.g. hiking downwards) is less strenuous than concentric exercise (e.g. hiking upwards) but its effects on liver enzymes are unknown.
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M. Pellegrin, J.F. Auber, K. Bouzourene, C. Amstutz, L. Mazzolai Division of Angiology, University Hospital of Lausanne, Lausanne, Switzerland Objectives: We have previously demonstrated that exercise training prevents the development of Angiotensin (Ang) II-induced atherosclerosis and vulnerable plaques in ApoE-/- mice. In the present study, we investigated whether exercise attenuates the progression of established Ang IIdependent atherosclerosis. Methods: ApoE-/- mice were subjected to left renal artery clipping (2kidney, 1-clip [2K1C] renovascular hypertension model) for 4 weeks to induce the formation of Ang II-mediated advanced and vulnerable lesions. Subsequently, 2K1C mice were randomized into either a sedentary control group (SED) or an exercise group (voluntary wheel running, EX) for 4 more weeks. Hemodynamic parameters, lesions size, plaque composition, and gene expression of adhesion molecules (VCAM-1, ICAM-1), cytokines (IL-18, IL-1b, TNF-a, IL-10, IL-4), markers of Th1/Th2 balance (T-bet/Gata3), and markers of M1/M2 macrophage balance (CD11c/CD206) in aortic and/or spleen tissues were determined at the end of the study. Results: Average daily distance covered by EX mice was 7.10.4 km. Mean blood pressure and plasma renin activity did not significantly differ between the 2 groups. Aortic plaque size was significantly reduced by 66% in EX as compared to SED (0.630.15% vs 1.880.27%, P<0.01). EX significantly reduced by 45% macrophage plaque content (13.41.9% vs 24.24.2% in SED, P<0.05). Neither a-smooth muscle actin plaque content, nor lipid core size was affected by EX. EX significantly downregulated aortic mRNA expression of VCAM-1 and ICAM-1 (P<0.05). Spleen mRNA expression of pro-inflammatory cytokines IL18 and IL-1b significantly decreased whereas expression of anti-inflammatory cytokine IL-4 significantly increased with EX (P<0.05). Expression markers of Th1/Th2 and M1/M2 balances was not modulated by EX. Conclusion: Voluntary exercise is effective in slowing the progression of established Ang II-dependent advanced lesions. Underlying molecular mechanisms include decreased expression of vascular pro-atherogenic adhesion molecules as well as pro-inflammatory cytokines at the systemic level. 64 - Intervention into physical activity EAS-0981. TGF BETA AND DIFFERENT DIETS: THE KEY TO THE CARDIOVASCULAR HEALTH? B. Ruiza, R. Torob, M. Quezada-Feijood, C. Rodriguez-Lealc, I. Tinococ, V. Aragonc, M. Monsalvoc, A. Mangasb a Internal Medicine, Hospital Universitario Puerta Del Mar Cadiz, El Puerto De Santa Maria, Spain; b Medicine, Medicine Faculty, Cadiz, Spain; c Internal