P87 CAROTID ATHEROSCLEROSIS ASSOCIATED WITH LATE-ONSET DEPRESSIVE DISORDERS: RESULTS FROM A LARGE COHORT STUDY

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Atherosclerosis Supplements 11, no. 2 (2010) 17–108

Method and Material: The study enrolled 200 patients with T2DM with a mean age of 54.2±7.62 years. T2DM was defined according to WHO criteria. The follow up period was of 3 years. We measured intima-media thickness at the left and right common carotid at 1 cm of the bifurcation (average of at least 3 determinations) on B-mode ultrasound images with the use of a 10 MHz linear-array transducer and LDL-cholesterol levels every 6 months. Results: The characteristics of the studied group at the beginning and end of the study are presented in Table 1. Table 1

At start After 3 years

LDL-cholesterol (mg/dl)

IMT left (mm)

IMT right (mm)

102.8±12.8 100.2±11.3

10.2±2.3 11.3±2.1

9.8±2.5 10.2±1.9

At 18 patients of the studied group occurred a cardiovascular event during the 3 years of follow up. Conclusions: Patients with T2DM have modified common carotid intimamedia thickness. Cardiovascular events occurred in patients with low levels of LDL-cholesterol. Not only biological parameters are important to follow up in patients with T2DM. Further studies are needed to understand the progression from subclinical to clinical atherosclerotic disease. P84 THE UCL LDLR, PCSK9 & LDLRAP1 VARIANT DATABASES: UPDATE, ANALYSIS & OVERVIEW OF THREE PUBLICLY AVAILABLE FAMILIAL HYPERCHOLESTEROLEMIA GENE DATABASES S. Leigh, T. Jakubcova, R.A. Whittall, S.E. Humphries. Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, University College London, London, UK Aims: To update and analyse the Low Density Lipoprotein Receptor (LDLR) and Pro-Protein Convertase Subtilisin/Kexin Type9 (PCSK9) gene variant databases and to establish and analyse a database for Low Density Lipoprotein Receptor Adaptor Protein1 gene (LDLRAP1) defects in Autosomal Recessive Hypercholesterolemia (ARH). Methods: PubMed literature searches were performed and variant data was loaded onto the Leiden Open Source Variant Database platform on the UCL web server. Predicted effects of amino acid substitutions were assessed using the literature and publicly-available computer programs. Results: The LDLR and PCSK9 databases are available via www.ucl.ac.uk/fh and the LDLRA1 database will be released in spring 2010. The LDLR database lists 1686 variants, representing 1063 unique events. DNA substitutions and small DNA rearrangements continue to represent the majority of variants (65% & 24% respectively); however, a significant number of large rearrangements (~10%) are still reported in LDLR, highlighting the importance of screening for such variants. The PCSK9 database lists 155 variants, representing 101 unique events, PCSK9 variants appear to be equally divided between loss of function, gain of function or functionally neutral variants. The utility of predictive computer programmes is limited for PCSK9 variants because of their varying effects on cholesterol levels. The LDLRA1 database will list >20 variants associated with hypercholesterolemia found predominantly in ARH patients. Conclusion: These three database now list >1100 unique variants associated with aberrant cholesterol levels and provide information relating to pathogenicity, these resources will be of use to researchers and clinicians working in the field of dyslipidaemias. P85 A MUTATION IN SREBF2 GENE IS INVOLVED IN HYPERCHOLESTEROLEMIA AND HYPERGLYCEMIA A.B. Garcia Garcia1,2 , S. Martinez-Hervas1,2,3 , S. Vernia4 , C. Ivorra1 , S. Blesa1,2 , J.C. Martin-Escudero5 , J.F. Ascaso2,3 , R. Carmena2,3 , ´ Investigacion ´ Hospital M. Casado4,6 , J.T. Real2,3 , F.J. Chaves1,2 . 1 Fundacion Cl´ınico Universitario de Valencia. Instituto Sanitario INCLIVA, Valencia, 2 CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), ´ Hospital Cl´ınico Barcelona, 3 Servicio de Endocrinolog´ıa y Nutricion, Universitario de Valencia, 4 Instituto de Biomedicina de Valencia (IBV-CSIC), Valencia, 5 Servicio de Medicina Interna, Hospital R´ıo Hortega, Valladolid, 6 CIBER of Hepatic and Digestive Diseases (CIBEREHD), Barcelona, Spain Autosomal Dominant Hypercholesterolemias (ADH) are a series of diseases characterised by high total and LDL-cholesterol, which predispose to early atherosclerosis. Mutations in several genes are responsible for ADH: LDLR (Familial Hypercholesterolemia), APOB (Familial Defective ApoB), and PCSK9 (ADH type 3). However, 20−30% of ADH patients do not present mutations in any of these genes. Therefore, other unknown genes must be involved in ADH. SREBP2 is a known transcription factor which regulates several genes involved in lipid metabolism. Our objective has been the analysis of SREBF2 gene in a sample of 41 ADH patients without mutations in the known genes, searching for alterations that could be responsible for ADH.

Poster Presentations

We have identified the alteration c.−405A>G, present in patient 104. This mutation was thought to be pathogenic because: 1. It cosegregates with the disease in the family (5 healthy individuals and 7 patients). 2. It has not been found in a sample of 429 healthy controls. 3. Functional studies on cells transfected with plasmids containing the variation have shown that this mutation increases transcription of the gene. Surprisingly, this mutation also cosegregated with higher glucose levels in the family. An OGTT was performed in 4 family carriers and 28 controls (matched by age, gender and BMI). Carriers presented significantly higher fasting plasma glucose (108±9 mg/dL) than controls (89±32 mg/dL), p  0.05. To our knowledge, SREBF2 has not been involved in glucose metabolism in humans. In conclusion mutations in the SREBF2 gene may result in hereditary hypercholesterolemia (phenotype ADH) and hyperglycemia. P86 PARAOXONASE-2 GENE (PON2) S311C POLYMORPHISM ASSOCIATED WITH TYPE 2 DIABETIC MELLITUS AND CORONARY HEART DISEASE T. Peerapatdit1 , A. Likidlilid2 , N. Hobang2 , D. Tresukosol1 , S. Ratanamaneechat3 . 1 Medicine, 2 Biochemistry, 3 Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Objective: The variant of the PON2 gene at S311C in exon 9 can lead to dyslipidemia and increase risk for DM, CHD, or both. Therefore, we investigate the associations of S311C polymorphism in type 2 DM with and without CHD compared with healthy control subjects. Materials and Methods: The study included 149 unrelated control subjects, 155 type 2 DM without CHD and 147 type 2 DM with CHD > 50% epicardial stenosis. gDNA was extracted from leukocyte and the variant was determined by PCR-RFLP. Results: All genotypes of PON2 S311C polymorphism were in consistent with an expected population of Hardy–Weinberg equilibrium. There was a significantly higher frequency of the CC genotype in type 2 DM with and without CHD when compared with control group (p = 0.01 and 0.04, respectively). While, C allele frequencies were not different among all three groups. The risks for DM and CHD were assessed and found that the CC genotype appeared to be the risk of both type 2 DM with and without CHD with odds ratio 5.12 (95% CI:1.44– 18.22), p = 0.01 and 4.08 (95% CI:1.13–14.77), p = 0.04, respectively. Conclusions: There were associations between the PON2 S311C polymorphism and type 2 DM with and without CHD. It was also found that the CC genotype of this polymorphism was significantly higher in type 2 DM with and without CHD than in healthy control. It was possible that the CC genotype can accelerate the development of both type 2 DM and CHD in this population studied. P87 CAROTID ATHEROSCLEROSIS ASSOCIATED WITH LATE-ONSET DEPRESSIVE DISORDERS: RESULTS FROM A LARGE COHORT STUDY A. Seldenrijk1 , H. van Hout2 , H. van Marwijk2 , E. de Groot3 , J. Gort3 , C. Rustemeijer4 , M. Diamant5 , B. Penninx1 . 1 Psychiatry, 2 General Practice, VU University Medical Center, 3 Vascular Medicine and Vascular Imaging, Academic Medical Center, University of Amsterdam, 4 Internal Medicine, Amstelland Hospital, 5 Diabetes Center, Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands Objectives: Carotid intima-media thickness (CIMT) and plaque presence have been established as markers of systemic atherosclerosis. This study examined whether high CIMT and plaque presence were more prevalent among persons with a lifetime diagnosis of depressive or anxiety disorders (n = 470) than in controls (n = 179), using data from a subcohort (mean age = 46 yrs, 65% women) of the Netherlands Study of Depression and Anxiety (NESDA). In addition, the role of disorder characteristics (severity, duration, age of onset) was examined. Methods: Depressive and anxiety disorders were diagnosed using the DSM-IV based CIDI interview. CIMT and plaque information were obtained using an Acuson Aspen ultrasound instrument with a 5−10MHz broadband transducer. Regression analyses adjusted for sociodemographics, lifestyle and health factors were conducted to investigate the association between psychopathology and carotid atherosclerosis. Results: Depressive or anxiety disorders were not associated with CIMT or plaque presence. However, of the disorder characteristics, age of onset of depressive disorder was strongly associated with CIMT (0.01 mm per 10 yrs, p = .006) and plaque presence (OR = 1.34 per 10 yrs, 95% CI =1.02–1.76, p = .04). As compared to controls, depressed persons with early onset (< 40 yrs) had no increased plaque presence, but those with late onset (40 yrs) had a 1.80 fold increased plaque risk (95% CI =0.87–3.73, p = .11). Conclusion: These findings suggest that a higher atherosclerosis prevalence may be specific for late-onset depressive disorders. This adds to accumulating evidence that late-onset depression, as compared to early-onset depression, has a distinct pathophysiology involving a vascular component.

78th EAS Congress

Atherosclerosis Supplements 11, no. 2 (2010) 17–108

Supported by NHF grant 2006B258 P88 CARDIOVASCULAR FUNCTION AND PSYCHOLOGICAL DISTRESS IN URBANISED BLACK SOUTH AFRICANS: THE SABPA STUDY N. Mashele1 , J.M. Van Rooyen1 , L. Malan1 , J.C. Potgieter2 , Hypertension in African Research Team (HART). 1 Physiology, 2 Psychology, North-West University, Potchefstroom, South Africa The increased prevalence of cardiovascular disease (CVD) risk factors in SubSaharan Africa has increased the prevalence of CVD in this region but whether psychological distress contributes to this observed increased risk remains largely unclear. Objective: The aim of this study was to investigate the association between psychological distress and CVD risk in urbanised black South African men (n = 101) and women (n = 99). Methods: Resting cardiovascular variables were obtained by making use of the Finometer device and 24 hour ambulatory blood pressure measurements with the Cardiotens apparatus. The psychological questionnaires assessed the perception of health (General Health Questionnaire; GHQ-28) and depression status (DSM-IV criteria). The resting ECG (NORAV PC-1200) was used to determine left ventricular hypertrophy (LVH) by making use of the Cornell product. Confounders included age, obesity, alcohol, smoking and physical activity. Results: The hypertensive group were more overweight with lower vascular compliance and higher LVH (only men) compared to the normotensive groups. In hypertensive men, perception of health (somatic symptoms) was positively associated with blood pressure, while in hypertensive women it was associated with heart rate. Major depression was associated with LVH in hypertensive men and mean arterial pressure in hypertensive women. LVH and depression showed Odds ratios of 1.02 [95% CI 0.997–1.05] and 1.15 [95% CI 1.01–1.32] respectively, in predicting hypertension in women. Conclusions: Psychological distress was associated with higher blood pressure in hypertensive African men but also with development of left ventricular hypertrophy in hypertensive African men and women. Keywords: Depression; perception of health; cardiovascular function; urbanised Africans; hypertension. P89 FATTY ACIDS IN SERUM PHOSPHOLIPIDS AND CAROTID INTIMA-MEDIA THICKNESS IN SPANISH SUBJECTS WITH PRIMARY DYSLIPIDEMIA 1 A. Sala-Vila1 , M. Cofan ´ 1 , A. Perez-Heras ´ , I. Nu´ nez ˜ 2 , R. Gilabert2 , M. Junyent1 , R. Mateo-Gallego3 , A. Cenarro3 , F. Civeira3 , E. Ros1 . 1 Lipid Unit; Nutrition and Endocrinology Survey, 2 Diagnosing Imaging Center, Institut ` d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Cl´ınic, Barcelona, 3 Lipid Unit, Hospital Miguel Servet, Zaragoza, Spain Introduction: n-3 Long-chain polyunsaturated fatty acids (n-3LC-PUFA) protect from coronary heart disease (CHD). Spain shares with Japan both low fatal and non-fatal CHD rates and high seafood intake. Objective: To investigate the relationship between n-3LC-PUFA status in serum phospholipids as biomarkers of seafood intake and carotid atherosclerosis in Spanish subjects at risk for CHD. Design: In a cross-sectional study, 451 asymptomatic subjects (261 men, 190 women, mean age 45 years) with primary dyslipidemia had fatty acids measured in serum phosphatidylcholine and carotid intima-media thickness (IMT) determined by ultrasound. Fatty food and seafood intake was evaluated in a random subsample of 70 participants. Results: Phosphatidylcholine fatty acid composition and mean daily consumption of olive oil (39 g) and seafood (76 g) were similar to those reported for Spanish populations. Multiple regression analyses showed that eicosapentaenoic + docosahexaenoic acids (b = −0.094, P = 0.015) and oleic acid (b = −0.107, P = 0.005) proportions were inversely related to mean common carotid artery IMT after adjustment for cardiovascular risk factors, statin use and other fatty acids. In similar models, a-linolenic acid related inversely to bifurcation and internal carotid artery (ICA)-IMT, while linoleic acid was directly related to ICA-IMT (P < 0.05, all). Conclusion: Increasing phospholipid proportions of n-3LC-PUFA, oleic acid and a-linolenic acid are associated with less atherosclerosis in subjects with primary dyslipidemia. High intakes of seafood and olive oil might explain in part the Spanish paradox of low CHD rates in face of a high burden of cardiovascular risk factors. P90 RECLASSIFICIATION OF 10 YEAR CHD RISK COMPARED BY PRESENCE OF CAROTID PLAQUE AND HIGH CRP V. Gudnason1,2 , S. Halldorsdottir1 , B. Thorsson1 , T. Aspelund1,2 . 1 Icelandic Heart Association Research Institute, Kopavogur, 2 University of Iceland, Reykjavik, Iceland Introduction: Carotid plaque and CIMT are used as surrogate markers for CAD. The REFINE Reykjavik Study is a population based study where the objective is to refine cardiovascular risk evaluation.

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Aims: To compare reclassificiation within categories of 10 year Reykjavik study CHD risk using presence of carotid plaque and high CRP levels. Methods: Since 2006, 4025 subjects (51% women) aged 35−69 have been recruited from a random sample stratified by sex and age from the greater Reykjavik Area, with a response rate of 70%. Carotid plaque and CIMT were measured using ultrasound. At least moderate plaque defined the presence of plaque and high CIMT >75%. 3437 apparently healthy men without CHD history or statin use were analysed for10-year CHD risk based on classical risk factor levels and then reclassified by presence of carotid plaque and having high CRP (3 mg/L). All results were population weighted. Results: The table shows estimated prevalence of plaque, CIMT, high CRP, and combinations of conditions in men. Results were comparable for women. Table: Reclassification of CHD risk in men 10-year CHD risk categories

0−3%

3−6%

6−10%

10+ %

Total

Plaque

1.2%

4.9%

10.1%

25.3%

8.4%

Plaque or high IMT (>75%)

7.8%

21.0%

45.7%

66.9%

29.6%

CRP3 mg/L

10.3%

17.0%

19.6%

28.9%

17.3%

CRP3 mg/L AND plaque

0.2%

1.1%

1.5%

9.2%

2.3%

CRP3 mg/L AND (Plaque or high IMT)

1.1%

4.2%

9.9%

21.3%

7.4%

Conclusion: High CRP is frequent in all risk categories, but has little overlap with evidence of carotid artherosclerosis in either men or women. P91 INSTABILITY OF CORONARY PLAQUES IS CLINICALLY AND ANGIOGRAPHICALLY ASSOCIATED WITH SPECIFIC CRP-RECEPTOR SUBTYPE D. Raaz-Schrauder1 , L. Klinghammer1 , A.B. Ekici2 , M. Herrmann3 , W.G. Daniel1 , A. Reis2 , C.D. Garlichs1 . 1 Cardiology and Angiology, 2 Institute of Human Genetics, 3 Medical Clinic III, University Hospital Erlangen, Erlangen, Germany Purpose: Clinical outcome in patients with acute coronary syndromes (ACS) is strongly influenced by inflammation and its central mediator C-reactive protein (CRP). Recently, Fcc receptor IIa (FccRIIa) has been identified as the receptor for CRP. The aim of our study was to assess whether patients with ACS show a specific genetic subtype for FccRIIa (i.e. the allele H131 with weak CRP binding or R131 with strong CRP binding). Additionally, analyses of patients’ coronary angiograms evaluated the association of FccRIIa genetic subtype with appearance of intracoronary thrombus. Methods: We conducted a genetic association study among 701 consecutive patients with first event of ACS compared to 467 patients with stable angina pectoris. All patients were genotyped for a frequent functional polymorphism of the mature FccRIIa. Moreover, angiographic analyses classified patients’ angiograms according to the type and grade of stenoses as well as the presense of intracoronary thrombus. Results: The FccRIIa R/R131 genotype was significantly associated with ACS as the first manifestation of CAD (P = 1.2×10−9, odds ratio 2.86, 95% CI: 2.06–3.99) compared to the non-R/R131 genotype. Coronary angiograms of ACS patients with the FccRIIa R/R131 genotype showed significantly higher frequencies of intracoronary thrombus and more complex lesions as compared to ACS patients with non-R/R131. Conclusions: Our data show a genetic association of the FccRIIa R/R131 genotype with a more frequent occurrence of ACS as the first manifestation of CAD. Moreover, coronary lesions of ACS patients with this genotype show significantly higher complexity and frequently contain thrombus. P92 ENDOTHELIAL FUNCTION ASSESSED BY PERIPHERAL ARTERY TONOMETRY IS A DETERMINANT OF CAROTID INTIMAE-MEDIA THICKNESS REGARDLESS OF FRAMINGHAM RISK SCORE R. Ferre´ 1 , G. Aragones ` 2 , N. Plana1 , J. Merino2 , M. Heras2 , B. Coll3 , R. Cos2 , L. Masana1 . 1 Internal Medicine. Unitat de Medicina Vascular i Metabolisme, Hospital Sant Joan. Universitat Rovira i Virgili. CIBERDEM., 2 Unitat de Recerca de L´ıpids, Universitat Rovira i Virgili, CIBERDEM, Reus, 3 Hospital Arnau de Vilanova, Lleida, Spain Peripheral artery tonometry (PAT) seems to be a reliable clinical method to assess endothelial function (EF). Its correlation with carotid intimae-media thickness (cIMT) in patients with intermediate cardiovascular (CV) risk as assessed by the Framingham Risk Score (FRS) has not been established. Objective: To assess EF using PAT in patients with intermediate CV risk by FRS and determine its association with cIMT. Design: We studied 248 patients with intermediate CV risk and no history of cardiovascular disease. EF by PAT, cIMT and a physical exam, as well as anthropometrical and biochemical studies were performed. Results: EF assessed by PAT, along with LDL and age, was the main predictor of increased cIMT. PAT values were independent of FRS. PAT was lower in men than women (P = 0.025). Smokers also had a lower PAT (P = 0.004). In a bivariate correlation analysis, the PAT ratio was inversely associated with waist