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Atherosclerosis Supplements 11, no. 2 (2010) 17–108
(n = 30) and acute myocardial infarction (AMI) group (n = 31). Blood samples for measurement of Lp-PLA2 , CRP and IL-6 were taken before coronary angiography. Results: Serum Lp-PLA2 levels in CHDs were significantly higher than that in controls (P < 0.01). Compared with SAP group, the levels were also significantly increased in UAP group and AMI group (P < 0.01), higher levels remained significant after adjustment for traditional risk factors; No statistical significance was found in Lp-PLA2 levels between patients with AMI and UAP (P>0.05); Serum Lp-PLA2 level was positively correlated with CRP (r = 0.722, P < 0.01), and IL-6 level (r = 0.665, P < 0.01) by bivariate correlation analysis. Conclusion: The serum levels of Lp-PLA2 may be used as a parameter to predict severity of inflammation in coronary heart diseases. Keywords: Lipoprotein-associated Phospholipase A2 ; Coronary Heart Disease; Inflammation P74 ROLES OF THE METABOLIC SYNDROME AND CORONARY ATHEROSCLEROSIS IN SUBCLINICAL INFLAMMATION P. Rein1,2,3 , C.H. Saely1,2,3 , S. Beer1,2,3 , A. Vonbank1,2,3 , H. Drexel1,2,3,4 . 1 Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), 2 Academic Teaching Hospital Feldkirch, Feldkirch, Austria, 3 Private University of the Pricipality of Liechtenstein, Triesen, Liechtenstein, 4 Drexel University College of Medicine, Philadelphia, PA, USA Background: The metabolic syndrome (MetS) and stable coronary artery disease (CAD) frequently coincide; the individual contributions of these entities to subclinical inflammation are unknown. Methods: We enrolled 1010 consecutive patients undergoing coronary angiography for the evaluation of suspected or established stable CAD. The MetS was defined according to the AHA revision of the NCEP ATP-III criteria; coronary stenoses with lumen narrowing 50% were considered significant. Results: From our patients 564 (55.8%) had significant CAD and 459 (45.4%) had the MetS; the prevalence of significant CAD was higher in patients with the MetS than in subjects without the MetS (59.5% vs. 52.8%; p = 0.034). Serum CRP did not differ significantly between patients with significant CAD and subjects without significant CAD (p = 0.706), but it was significantly higher in MetS patients than in those without the MetS (p < 0.001). Regarding the individual MetS traits, the MetS criteria low HDL-C (p < 0.001), large waist circumference (p = 0.007) and high glucose (p = 0.023) but not the high triglycerides (p = 0.813) and high blood pressure criteria (p = 0.170) proved significantly associated with CRP. When all MetS traits were entered simultaneously into one ANCOVA model, only the HDL-C criterion independently of age, gender, LDL-C, smoking, cardiovascular medications and of all other MetS criteria proved independently associated with CRP (F=44.19; p < 0.001). Conclusions: CRP is strongly associated with the MetS but not with angiographically diagnosed coronary atherosclerosis. The overall association of the MetS with subclinical inflammation is driven by the low HDL cholesterol feature. P75 A NOVEL ANTHROPOMETRIC MEASURE FOR PREDICTING ALL-CAUSE MORTALITY ¨ ˚ A. Rosenblad, J. Leppert, G. Nilsson. Center for Clinical Research Vaster as, ¨ ˚ Sweden Uppsala University, Vaster as, Purpose: To compare the predictive ability for all-cause mortality of the novel anthropometric measure Waist-Hip-Height Ratio (WHHR) with Body Mass Index (BMI), Waist Circumference (WC), Waist-Hip Ratio (WHR) and Waist-Height Ratio (WHtR). Methods: Men and women aged 40 and 50 from the county of Vastmanland, ¨ Sweden were examined during the years 1990−99 (participation rate=48%). All-cause mortality was followed up until August 2008. For persons with complete anthropometric measures (n = 33493, men = 48%), Cox regression was performed for BMI, WC, WHR, WHtR and WHHR (defined as WHR divided by height). Multivariate adjustment added age, diabetic status, smoking, systolic and diastolic blood pressure, heart rate and glucose level. The predictive ability was calculated with a Pseudo R2 -measure and compared to WHHR using bootstrap. Table: Predictive ability of anthropometric measures Univariate
Multivariate (change from model without anthropometric measure)
Men
Women
Men
Poster Presentations
Results: During follow up 1301 persons (4%, men = 58%) died. The predictive ability was highest for WHHR followed by WHR, WHtR, WC and BMI. The difference was usually significant or close to significant using a one-sided p-value <0.05. Conclusions: WHHR performs better than WHR, WHtR, WC and BMI in predicting all-cause mortality. P76 PREGNANCY OUTCOMES IN FAMILIAL HYPERCHOLESTEROLEMIA WITH SPECIAL EMPHASIS ON PRETERM DELIVERY, BIRTH WEIGHT AND CONGENITAL MALFORMATIONS. A REGISTRY-BASED STUDY I. Toleikyte1 , K. Retterstøl2 , T.P. Leren3 , P.O. Iversen1 . 1 Department of Nutrition, Faculty of Medicine, University of Oslo, 2 Lipid Clinic, 3 Medical Genetics Laboratory, Oslo University Hospital, Rikshospitalet, Oslo, Norway Background and Aims: Circumstantial findings have linked hypercholesterolemia to preterm delivery and offspring with low birth weight, but firm data are lacking. Hence, the aim of this study was to examine whether women with familiar hypercholesterolemia (FH) have a higher risk of adverse birth outcomes compared to women in the general population. Study design and subjects: We identified 1,871 genetically verified FH women of fertile age from the Medical Genetics Laboratory-Registry at Oslo University Hospital. This data-set was coupled to that of the Medical Birth Registry of Norway, identifying women who had been pregnant and their birth outcomes between 1967 and 2006. The obtained data were compared to corresponding data from the general population in Norway, comprising about 2.3 million births, for the same period. Results: The registry-match resulted in 2,319 births of 1,102 women with heterozygous FH. Compared with the general population the FH population did not have significantly higher risk of i. giving birth prematurely (<37 gestational weeks), ii. delivering children with low birth weight (<2,500 g), or iii. having children with congenital malformations. The introduction of statins in 1992 in the treatment of hypercholesterolemia did not significantly increase the incidence of the three outcomes (i−iii) in the FH population, when comparing the period 1979–1991, i.e. before and the period 1999–2006, i.e. after statin introduction. Conclusion: FH women are apparently not at a higher risk of either preterm or low birth weight outcomes or births with congenital malformations than are women in the general population. P77 PROTHROMBOGENESIS IN SUBJECTS WITH METABOLIC SYNDROME AND CENTRAL OBESITY A.A. Razak, T.S. Tengku Ismail, M.R. Mohamad Taib, M. Mustafa Kamal, S. Abd Muid, M.T. Osman, K. Yusoff, H. Nawawi. Faculty of Medicine, Universiti Teknologi MARA, Shah Alam, Malaysia Background: Metabolic syndrome (MS) represents a cluster of abnormalities associated with an increased risk of coronary heart disease which may be partially explained by enhanced prothrombogenesis. Objective: The aim of the study was to evaluate the levels of prothrombogenic markers in MS subjects with different glycaemic status and centrally obese subjects. Methods: A total of 262 subjects (Mean±SD: 52±11, 90 Males) were recruited and divided into 5 groups: MS with normoglycaemia (MSNG), MS with impaired fasting glucose (MSIFG), MS with diabetes (MSDM), central obesity without MS (OBXMS) and non-MS control (NC). In addition, MSNG, MSIFG and MSDM were grouped as all MS group with a total number of 157. The blood levels of fibrinogen, homocysteine, tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were evaluated. Results: MSNG group compared to NC group had higher fibrinogen (p < 0.05), homocysteine (p < 0.005), tPA (p < 0.05) and PAI-1 (p < 0.05). MSIFG group compared to NC group had higher homocysteine (p < 0.05) and tPA (p < 0.005). MSDM group compared to NC group had higher homocysteine (p < 0.05), tPA (p < 0.001) and PAI-1 (p < 0.05). In addition, All MS group compared to NC group had higher homocysteine (p < 0.005), tPA (p < 0.001) and PAI-1 (p < 0.01). OBXMS group compared to NC group had higher homocysteine (p < 0.05). Conclusions: MS irrespective of glycaemic status have enhanced prothrombogenesis compared to control. There is also enhanced prothrombogenesis in central obesity, suggesting a vital role of waist circumference in obesity-related health risk.
Women
Anthropometric measure
Pseudo R2
P-value
Pseudo R2
P-value
Pseudo R2 increase
P-value
Pseudo R2 increase
P-value
WHHR
0.142
ref.
0.163
ref.
0.020
ref.
0.023
ref.
WHR
0.117
0.023
0.146
0.098
0.016
0.100
0.019
0.175
WHtR
0.075
<0.001
0.125
0.041
0.007
0.014
0.014
0.089
WC
0.047
<0.001
0.105
0.010
0.004
0.010
0.010
0.051
BMI
0.014
<0.001
0.053
<0.001
0.000
0.007
0.002
0.012
P78 METABOLIC SYNDROME AND SUBCLINICAL ATHEROSCLEROSIS IN YOUNG ADULTS E.E. Babes, V.V. Babes, M.I. Popescu, A. Ardelean. Faculty of Medicine, Oradea, Romania Background: The metabolic syndrome (MS) is a constellation of interrelated metabolic risk factors that directly promote the development of atherosclerotic cardiovascular disease.
78th EAS Congress
Atherosclerosis Supplements 11, no. 2 (2010) 17–108
The aim of the study was to investigate the correlation between MS and subclinical atherosclerosis (SA) in a group of young adults. Methods: We evaluated 102 young healthy adults (age 20−40 y, 58 men) with at least one cardiovascular risk factor. We determined: smoking status, BMI, waist circumference (WC), blood pressure (BP), glucose, lipid profile. SA was assessed with two indicators: endothelial dysfunction evaluated by brachial flow mediated dilation (FMD) and carotid intimae-media-thickness (CIMT). MS was defined according to NCEP ATP III criteria. Results: MS was present in 17 subjects (16.7%). CIMT values were higher in subjects with MS, 0.54±0.03 mm vs. 0.48±0.08 mm (p < 0.0001). In multiple regression analysis independent predictors for CIMT remained: BP (r = 0.48, p = 0.0002); HDL cholesterol (r = −0.37, p = 0.0009), glucose (r = 0.21, p = 0.0006) and WC (r = 0.3, p = 0.014). FMD was significantly lower in subjects with MS, 4.25±2.32% vs 8.33±3.29% (p < 0.0001). In multiple regression analysis independent predictors for FMD were: glucose (r = −0.19, p = 0.0094); HDL-cholesterol (r = 0.28, p = 0.007) and BP (r = −0.34, p = 0.0095). Conclusions: MS in young adults is associated with increased prevalence of SA. Endothelial dysfunction is an important arterial abnormality in young subjects with MS. High BP, low HDL-cholesterol and hyperglycemia are especially powerful predictors of increased CIMT and endothelial dysfunction. Central obesity appears to be correlated with CIMT. These findings supports the importance of screening and early intervention in young adults with MS. P79 ATHEROSCLEROTIC DISEASE LOCATION AND DISPARITIES IN THE CONTROL AND TREATMENT OF CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH TYPE 2 DIABETES I. Gouni-Berthold1 , K. Bestehorn2 , W. Krone1 , H.K. Berthold3 . 1 Department of Internal Medicine II, University of Cologne, Cologne, 2 MSD Sharp & Dohme, Haar, 3 Charite University Medicine Berlin, Berlin, Germany Aims: To assess differences in the control and intensity of medication treatment of CVD risk factors in patients with type 2 diabetes, depending on their atherosclerotic disease territory (coronary artery disease, [CAD]; cerebrovascular disease, [CBVD]; or peripheral arterial disease, [PAD]). Methods: Cross-sectional analysis of 17,571 patients with type 2 diabetes with prevalent atherosclerotic disease. Endpoints included uncontrolled CVD risk factors [SBP 140 mmHg; LDL-C 130 mg/dl; and HbA1c 8%] and high intensity of medication treatment (use of two or more classes of antihypertensive agents, one or more lipid-lowering agents and of two or more oral hypoglycemic agents or insulin) in patients with uncontrolled CVD risk factors. Multipleadjusted ORs were calculated for CAD, CBVD, and PAD after adjusting for sex, age, BMI, current smoking, and diabetes duration. Results: Proportions of patients with uncontrolled risk factors were significantly different among disease locations. Decreased odds of having lipids not controlled were observed in patients with CAD, while decreased odds of having SBP not controlled were observed in patients with PAD. PAD was associated with the highest odds of hyperglycemia not being controlled. Intensification of treatment was observed in lipid and glycemia management but not in hypertension management independent of disease location. In all disease locations, intensifying antihypertensive medication is worse than intensifying lipid or glycemia treatment. Conclusions: In subjects with type 2 diabetes and atherosclerotic disease, control of modifiable CVD risk factors but not intensity of medication treatment is modified by atherosclerotic disease territory. Intensity of medication treatment is different between risk factors. P80 XANTHELASMAS PREDICT RISK OF ISCHEMIC HEART DISEASE, MYOCARDIAL INFARCTION, AND OVERALL DEATH IN THE GENERAL POPULATION M. Christoffersen1 , R. Frikke-Schmidt1 , P. Schnohr2 , B.G. Nordestgaard2,3 , A. Tybjærg-Hansen1,2 . 1 Dept. Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, 2 The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen, 3 Dept. Clinical Biochemistry, Herlev Hospital, Herlev, Denmark Introduction: Xanthelasmas are cholesterol deposits of the eyelids. Some similarity has been seen experimentally between the formation of xanthelasmas and the formation of the atherosclerotic plaque, which has led to the question of whether xanthelasmas may be a cutaneous marker of atherosclerosis. Objective: We examined the hypothesis that presence of xanthelasmas are associated with increased risk of myocardial infarction (MI), ischemic heart disease (IHD), and overall death in the general population. Methods: A total of 12,939 individuals from the Danish general population, who had presence or absence of xanthelasmas registered at baseline, were followed for up to 33 years; 1,903 individuals developed MI, 3,761 individuals developed IHD, and 8,663 individuals died during follow up. Follow-up was 100% complete. We excluded individuals with IHD diagnosis at baseline. Results: Xanthelasmas were associated with multivariate adjusted hazard ratios of 1.84 (95% CI, 1.41–2.39) and 1.29 (95% CI, 1.00–1.66) for MI in women and men, respectively. Corresponding hazard ratios for IHD were 1.56 (95% CI,
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1.29–1.84) and 1.24 (95% CI, 1.02–1.59). Multivariate adjusted hazard ratios for overall death in individuals with xanthelasmas were 1.18 (95% CI, 1.03–1.35) in women and 1.13 (95% CI, 0.99–1.30) in men. Conclusion: Presence of xanthelasmas predict risk of MI, IHD, and overall death in individuals initially free of IHD independent of other risk factors including plasma cholesterol levels. Moreover, the risk of IHD and MI is more pronounced in women compared to men. P81 MIF-DEFICIENCY REDUCES CHRONIC INFLAMMATION IN ADIPOSE TISSUE AND IMPAIRS INSULIN RESISTANCE AND ASSOCIATED ATHEROSCLEROSIS IN A MODEL OF COMBINED DISEASE R. Kleemann1 , L. Verschuren2 , P.Y. Wielinga1 , P. Voshol3 , M. van Erk2 , G. Fingerle-Rowson4 , K. Willems van Dijk5 , M. Ouwens5 , J. Bernhagen6 , R. Bucala7 , T. Kooistra2 . 1 TNO BioSciences, 2 Vascular and Metabolic Diseases, TNO Quality of Life, Leiden, The Netherlands, 3 Cambridge, Cambridge, UK, 4 University of Cologne, Cologne, Germany, 5 LUMC, Leiden, The Netherlands, 6 RWTH Aachen, Aachen, Germany, 7 Yale University School of Medicine, Yale, CT, USA Chronic inflammation in white adipose tissue (WAT) is positively associated with obesity, insulin resistance (IR) and the development of type-2 diabetes. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) is an essential, upstream component of the inflammatory cascade. We examined whether MIF is required for the development of obesity, IR, glucose intolerance and atherosclerosis in the LDL-receptor-deficient (Ldlr−/− ) mouse model of disease. Ldlr−/− −mice developed IR and glucose intolerance within 15-w while Mif−/− Ldlr−/− littermates were protected. MIF-deficiency did not affect obesity and lipid risk factors but specifically reduced inflammation in WAT and liver, as reflected by lower plasma SAA and fibrinogen levels at baseline and under inflammatory conditions. Conversely, MIF stimulated the in vivo expression of human-CRP, an inflammation marker and risk factor of IR and cardiovascular-disease. In WAT, MIF-deficiency reduced nuclear c-Jun levels and improved insulin sensitivity; MIF-deficiency also reduced macrophage accumulation in WAT and blunted the expression of proteins that regulate macrophage infiltration (ICAM-1, CD44). Mechanistic parallels to WAT were observed in aorta, where the absence of MIF reduced monocyte adhesion, macrophage lesion content and atherosclerotic lesion size. P82 THE CLINICAL STUDY OF HEART RATE VARIABILITY AND THE SERIOUS EXTENT OF CORONARY ARTERY LESIONS IN CORONARY HEART DISEASE G. Tian. Department of Cardiology, The Second Affiliated Hospital of Nanhua University, HengYang, China Objective: To find more diagnostic methods for coronary heart diseases (CHDs), we investigated the relation between them through analysis of heart rate variability and the serious extent of coronary artery lesions in CHDs. Methods: 120 patients were selected randomly, and were divided into four groups, including stable angina pectoris (SAP) group (n = 30), unstable angina pectoris (UAP) group (n = 30), ST-segment elevation myocardial infarction (STEMI) group (n = 30) and non-ST-segment elevation myocardial infarction (NSTEMI) group (n = 30). Besides, there were 31 healthy people as normal control group. All cases were, within 24 hours, checked by dynamic electrocardiogram (DCG). CHDs were checked by coronary arteriography. The results were analyzed with the statistics software of SPSS 13.0. Results: 1. HRV was low one by one in STEMI group, NSTEMI group, UAP group and SAP group as compared with each other or normal control group, and all of the difference were significant (P < 0.01). 2. With the increase of the severity of coronary artery lesions, the index of HRV which were reflected the function of sympathetic nervous system (SDNN, SDANN, SDNN Index) obviously decreased, but the other index of Heart Rate Variability (HRV) reflected by the function of parasympathetic nervous system (RMSSD, pNN50) were not obviously changed. Conclusion: HRV can be looked as a no-traumatic index to get the message of the serious extent of coronary artery lesions indirectly. Keywords: Heart Rate Variability; Coronary Artery Lesion; Coronary Heart Disease. P83 LDL-CHOLESTEROL AND CARDIOVASCULAR EVENTS IN PATIENTS WITH DIABETES MELLITUS TYPE 2 C. Tudor1 , A. Iana1 , R.A. Jeberean2 , A. Petrus1 , R. Buzas1 . 1 Internal Medicine, 2 Psihiatry, University Hospital Municipal Timisoara, Timisoara, Romania Background and Aims: Type 2 diabetes mellitus (T2DM) is increasingly prevalent worldwide, conferring major burdens on health and health care costs. Development of atherosclerotic cardiovascular disease (CVD) is the principal complication in type 2 DM and a major cause of morbidity and mortality. The aim of the study was to asses the influence of LDL-cholesterol and common carotid intima-media thickness (IMT) on cardiovascular events in patients with T2DM without clinical changes of CVD.