Workshops W2 Genes and environment: nutrigenetics
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CD40L changes vs. control group, vWF activity significantly increased in GF group by days 7, 14, but no difference was observed between groups. Conclusions: Early administration of GF in patients with NSTEACS was not associated with positive changes ofCRP orCD40L levels compared with control group. Moreover vWF activity increased in GF group, not in control.
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W01-P-016 I PLAQUE STABILITY IN RELATION TO SERUM I
LIPIDS AND T R E A T M E N T W I T H ATORVASTATIN
V. Wiklund z, J. Solem 2, M. Levin 1, T. Kadsson 2, M. Schannong 3, P. Albertsson 2. ] Wallenberg laboratory, Sahlgrenska Academy, GSteborg
Swdden; 2The Cardiovascular Institute, Sahlgrenska Academy, Gi~teborg, Sweden; ~Department of Medicine, Pfizer AB, Ttiby, Sweden Aim: To analyze plaque stability in relation to serum lipids, inflammation markers and statin treatment. Method: 29 patients with stable angina pectoris were randomised to treatment with atorvastalin 80 mg od or placebo treatment for ten weeks before PCI with directed atherectomy. Atherectomy specimens were analysed with immunohistochemistry for cellular composition, inflammatory activity and lipid and collagen content. Tissue specimens were obtained from 22 subjects. Serum levels of lipoproteins and inflammation markers were analysed. Results: The compositions of tissue specimens agree well with the concept of lipid-rich inflammatory active and unstable plaques as opposed to the stable plaques, rich in collagen and in smooth muscle cells. There were inverse correlations between content of extracellular matrix and cellularity. There were also inverse correlations between macrophage content and smooth muscle cells or collagen content, while there was a positive correlation between macrophage content and MMP9. Atorvastatin treatment reduced the content of T-lymphocytes in the plaques. High apoAI levels were associated with markers for plaque stability such as high collagen or low macrophage and MMP9 content. Conclusion: Atorvastatin reduced T-lymphocyte content in plaque, indicating a modulation of the immune response. ApoAI was associated with several markers for plaque stability suggesting that high levels of apoAI and HDL are associated with a reduced risk for plaque rupture.
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I W02-1S-001 I DOES M O L E C U L A R GENETICS A F F E C T CLINICAL P R A C T I C E ? R. Poledne. Laboratory for Atherosclerosis Research, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Objective: Coronary heart disease (CHD) has both genetic and environmental components. A large number of association studies of the candidate geue of individual risk factors for premature coronary atherosclerosis and its clinical complications have been published with rather conflicting results. Results: It is generally agreed that the E4 allele in the apoE gene is associated with an increased LDL cholesterol concentration, and individuals with E4+ genotypes are more sensitive to a dietary change. We have been able to reproduce these results in the whole Czech population as well. But when only hypercholesterolemic individuals were selected from a large Czech population sample (n=2000), individuals with E4+ genotypes elicit very low sensitivity (or very high resistance) to dietary treatment. Although the E4+ genotype represents an increased risk of CHD, it has not been found more frequently among young myocardial infarction (MI) survivors. One possible explanation might be that MI is a multifactorial disease, and proinflammatory status (as determined by high-sensitive CRP concentrations) has been found to be an additional risk. Individuals with E4+ genotypes show lower CRP concentrations than the most frequent E3/3 genotype but, in linear regression analysis, this genetic effect was largely offset by environmental factors such as BMI and smoking. Conclusions: Based on these data, we can reasonably conclude that, although molecular genetics has substantially expanded our recent knowledge, it has been unable to modify the clinical practice of CHD treatment and prevention.
This project was partly supported through Research Project MZ CR." CEZ:L17/O0023001 and LNOOA069MSMT CR
I W02-1S-002 I GENETICS, I i
WO1-P-0171I LIPID AND DYSTROPHIC-NECROTIC UNSTABLE PLAQUES IN A C U T E CORONARY SYNDROME S. Zhdanov, T.P. Shlychkova, S.P. Veselova. Cardiovascular Pathology,
Russian Cardiology Research Centre, Moscow, Russia Changes occurring in coronary arteries in acute coronary syndrome (ACS) are highly polymorphic. The relationship between various types of unstable plaques and clinical manifestations of ACS was not studied sufficiently. Purpose: Investigate specific pathomorphological features of unstable plaques in ACS. Methods: Cross sections (5-mm intervals) of coronary arteries from 60 people died of acute myocardial infarction and unstable angina at the age of 41-79 years were examined using histological and immunomorphological methods. Plaque structure, lipids and cells were studied. Remits: Destructive changes in the cap and thrombus were always present in unstable plaque. Two major types of unstable plaques were identified: lipid (70% cases) and dystrophic-necrotic (30%). Lipid unstable plaques were characterized by a thin fibrous cap over a large atheromatous nucleus and decreased contents of collagen and smooth muscle cells, infiltration with lipids and monocytes/macrophages. Unstable dystrophicnecrotic plaque had a pronounced fibrous cap with small lipid content and was characterized by necrotic areas and calcifications. Atheromatous nucleus occupied <50% of its area. Generally, pronounced cell reaction was observed at the periphery of necroses sometimes with inflammatory erosions. Unstable lipid plaques were more frequent in hypercholesterolemia (73.8% vs. 27.7%), while the occurrence of dystrophic-necrotic plaques was higher in arterial hypertension (88.9% vs.59.5%). Conclusion: There are two major variants of unstable plaques in ACS: lipid and dystrophic-necrotic which include all described changes in coronary arteries in this syndrome.
GENES A N D ENVIRONMENT: NUTRIGENETICS
DIET AND HEALTHY AGING: THE IMPORTANCE O F CARDIOVASCULAR DISEASE PREVENTION
J.M. Ordovas. Nutrition and Genomics Laboratory. JM-USDA-HNRCA at
Tufts Univ., Boston, MA, USA The most economical and successful approach to achieve healthy aging comes from disease prevention. It has been estimated that removal of the major disease risk factors will increase global healthy life expectancy by 9.3 years. Specifically, when it comes to ischaemic heart disease, this should result in a reduction in population disease of 80-87% and on mortality of 77-84%. Most of those risk factors are driven by a combination of genetic and environmental factors interacting with each other to produce the biochemical or clinical phenotypes and the disease risk. Therefore, we need to highlight that most gene markers for cardiovascular disease (CVD) are not determinant of disease, but predisposing factors in combination with unhealthy environmental exposures. Thus, the relevance of understanding the cross-talk between genes and environment and more specifically with dietary factors. At this regard, nutrigenetics is emerging as a multidisciplinary field focusing on studying the interactions between nutritional, genetic factors, and health outcomes. The ultimate goal is to elaborate efficient individual dietary intervention strategies aimed to preventing disease and thus achieving healthy aging. Our studies, using a wide array of population and intervention studies have found already significant evidence for associations between CVD risk factors and specific alleles at candidate genes. More important, we have found significant interactions between dietary factors, genetic variants and biochemical markers of CVD. The traditional approach of recommending low fat, low cholesterol diets for the entire population has been the subject of heated discussion and controversy. Now, based on the accumulating knowledge, we can begin to characterize individuals that may respond better to one type of recommendation or another. Therefore, a low fat, low cholesterol strategy may be especially beneficial for lowering plasma cholesterol levels for subjects carrying the apoE4 allele at the APOE gene. Moreover, HDL concentrations are determined also by dietary, behavioral and genetic factors. We have demonstrated significant interactions at the APOA 1, CETP and LIPC genes modulating the effects of dietary fats on HDL-C concentrations. This knowledge could pave the way for most successful dietary recommendations based on genetic factors that
75th EAS Congress, 23-26 April 2005, Prague, Czech Republic