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INCREASED PLASMA APOLIPOPROTEIN C-III CONCENTRATION PREDICTS CARDIOVASCULAR MORTALITY: THE HOORN STUDY
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Workshops WO10 Genetic and biologic biomarkers for CHD risk determination
modulating PDGF-AA production in foam cells via inhibition of P42/44 ERK1/2 activation. The PDGF-AA regulated by NDRG2 contributes the effects of macrophage on VSMCs proliferation.
WO10 GENETIC AND BIOLOGIC BIOMARKERS FOR CHD RISK DETERMINATION WO10-OR3 CRITICAL APPRAISAL OF THE UTILITY OF CRP MEASUREMENT IN THE PREDICTION OF CARDIOVASCULAR EVENTS T. Shah 1 , J.P. Casas 2 , J.A. Cooper 1 , I. Tzoulaki 3 , R. Sofat 1 , L. Smeeth 2 , J.E. Deanfield 4 , G.D. Lowe 5 , A. Rumley 5 , F.G.R. Fowkes 6 , S.E. Humphries 1 , A.D. Hingorani 1 . 1 Centre for Clinical Pharmacology, University College London, London, UK; 2 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK; 3 Department of Epidemiology and Public Health, Imperial College London, London, UK; 4 Grown Up Congenital Heart Unit, The Heart Hospital, London, UK; 5 Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, UK; 6 Wolfson Unit for Prevention of Peripheral Vascular Diseases, Public Health Sciences, University of Edinburgh, Edinburgh, UK Background: Non-uniform reporting of the relevant relationships has hampered appraisal of the role of C-reactive protein (CRP) measurement for the prediction of later cardiovascular events leading to uncertainty on its clinical utility. Methods: The performance of CRP was assessed in two prospective studies and set in the context of a systematic review of 28 prospective studies involving 84,901 individuals and 9,209 incident cardiovascular events. Information on the predictive performance of CRP was extracted from published studies directly or recalculated using validated methods. Results: The CRP distribution was log-normal and its relationship with risk was continuous across the whole range of values without a threshold. A large proportion of all events were observed among the many individuals with near-average levels of CRP, leading to wide overlap of values among people who suffered events and those who did not. Neither the previously recommended CRP cut-point of 3mg/L nor cut-points based on a pre-specified false-positive rate (FPR) provided useful discrimination. The disease detection rate (sensitivity) was 5.8-15.5%, at a 5% FPR, and area under the ROC curve was only 0.52-0.66. CRP also did not add to discrimination based on the Framingham risk score, nor did it enhance risk stratification using models based on established risk factors. Conclusions: The available evidence does not support measurement of CRP either for discrimination or risk stratification of middle-aged populations at risk of cardiovascular events. Previous guidance on the clinical use of CRP measurement requires revision in light of this new analysis. WO10-OR4 EXTREME LIPOPROTEIN(A) LEVELS AND RISK OF MYOCARDIAL INFARCTION IN THE GENERAL POPULATION - THE COPENHAGEN CITY HEART STUDY P.R. Kamstrup 1 , M. Benn 1 , A. Tybjaerg-Hansen 2 , B.G. Nordestgaard 1 . 1 Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; 2 Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Background: Elevated lipoprotein(a) levels associate with myocardial infarction (MI) in some, but not all studies. Limitations of previous studies include lack of risk estimates for extreme lipoprotein(a) levels, measurements in long-term frozen samples, no correction for regression dilution bias, and lack of absolute risk estimates in the general population. We tested the hypothesis that extreme lipoprotein(a) levels predict MI in the general population, measuring levels shortly after sampling, correcting for regression dilution bias, and calculating hazard ratios and absolute risk estimates. Methods: We examined 9330 men and women from the general population, The Copenhagen City Heart Study. During 10 years follow-up, 498 participants developed MI. Results: In women, multifactorially adjusted hazard ratios for MI for
elevated lipoprotein(a) levels were 1.1(95% confidence interval 0.6-1.9) for 5-29 mg/dL (22nd-66th percentile), 1.7(1.0-3.1) for 30-84 mg/dL (67th89th percentile), 2.6(1.2-5.9) for 85-119 mg/dL (90th-95th percentile), and 3.6(1.7-7.7) for ≥120 mg/dL (>95th percentile) versus levels <5 mg/dL (<22nd percentile). Equivalent values in men were 1.5(0.9-2.3), 1.6(1.0-2.6), 2.6(1.2-5.5), and 3.7(1.7-8.0). Absolute 10-year risks of MI were 10% and 20% in smoking, hypertensive women above 60 years of age with lipoprotein(a) levels of <5 and ≥120 mg/dL, respectively. Equivalent values in men were 19% and 35%. Conclusions: We observed a stepwise increase in risk of MI with increasing levels of lipoprotein(a), with no evidence of a threshold effect. Extreme lipoprotein(a) levels predict a 3-4 fold increase in risk of MI in the general population, and absolute 10-year risks of 20% and 35% in high-risk women and men. WO10-OR5 INCREASED PLASMA APOLIPOPROTEIN C-III CONCENTRATION PREDICTS CARDIOVASCULAR MORTALITY: THE HOORN STUDY P.G. Scheffer 1 , T. Teerlink 1 , J.M. Dekker 2 , B. G 2 , G. Nijpels 2 , M. Diamant 3 , P.J. Kostense 4 , C.D.A. Stehouwer 5 , R.J. Heine 3 . 1 VU University Medical Center, Department of Clinical Chemistry, Amsterdam, The Netherlands; 2 VU University Medical Center, Institute for Research In Extramural Medicine, Amsterdam, The Netherlands; 3 VU University Medical Center, Department of Endocrinology/Diabetes Center, Amsterdam, The Netherlands; 4 VU University Medical Center, Department of Clinical Epidemiology and Biostatistics, Amsterdam, The Netherlands; 5 Department of Medicine, Division of General Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands Background and aims: Hypertriglyceridaemia is a cardiovascular risk factor. Apolipoprotein C-III (apo C-III) inhibits lipoprotein lipase, and is therefore an important determinant of the catabolic rate of triglyceriderich lipoproteins. We studied the predictive value of plasma apo C-III concentration for cardiovascular mortality in a large population-based study. Methods: This prospective study was performed in 2244 participants (aged 49 to 77) of the Hoorn Study. Apo C-III concentration was measured in baseline plasma samples by an immunoturbidimetric assay. During 15 years of follow-up, 504 individuals died: 231 of cardiovascular mortality, 180 of cancer, and 93 of other causes. The association between apo C-III concentration and mortality was studied by Cox proportional-hazards regression analysis. Results: Higher plasma apo C-III concentrations were observed in women compared to men and in subjects with abnormal glucose metabolism compared to individuals with a normal glucose metabolism (both P<0.01). After correction for age and sex, the cardiovascular mortality increased significantly (P<0.05) across quartiles of apo C-III (Table). Further adjustment for HDL-cholesterol, LDL-cholesterol, triglycerides, BMI, waist-to-hip ratio, SBP, smoking, and glucose metabolism did not influence this association. High apo C-III was not related to non-cardiovascular mortality.
Conclusions: Our data indicates that an elevated apo C-III concentration in plasma, independently of traditional risk factors, predicts cardiovascular mortality. WO10-OR6 SMALL DENSE LDL CHOLESTEROL, HDL PARTICLES, INSULIN, ADIPONECTIN, AND GLYCATED ALBUMEN AS PROSPECTIVE CHD RISK FACTORS IN THE FRAMINGHAM STUDY E.J. Schaefer 1 , M. Ai 1 , S. Otokozawa 1 , B.F. Asztalos 1 , C.C. White 2 , S. Demissie 2 , A. Cupples 2 . 1 Lipid Metabolism Laboratory, Tufts University, Boston, MA, USA; 2 Division of Epidemiology and Statistics, Boston University and The Framingham Heart Study, Boston, MA, USA Background and Aims: Standard coronary heart disease (CHD) risk factors
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
Workshops WO10 Genetic and biologic biomarkers for CHD risk determination
modulating PDGF-AA production in foam cells via inhibition of P42/44 ERK1/2 activation. The PDGF-AA regulated by NDRG2 contributes the effects of macrophage on VSMCs proliferation.
WO10 GENETIC AND BIOLOGIC BIOMARKERS FOR CHD RISK DETERMINATION WO10-OR3 CRITICAL APPRAISAL OF THE UTILITY OF CRP MEASUREMENT IN THE PREDICTION OF CARDIOVASCULAR EVENTS T. Shah 1 , J.P. Casas 2 , J.A. Cooper 1 , I. Tzoulaki 3 , R. Sofat 1 , L. Smeeth 2 , J.E. Deanfield 4 , G.D. Lowe 5 , A. Rumley 5 , F.G.R. Fowkes 6 , S.E. Humphries 1 , A.D. Hingorani 1 . 1 Centre for Clinical Pharmacology, University College London, London, UK; 2 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK; 3 Department of Epidemiology and Public Health, Imperial College London, London, UK; 4 Grown Up Congenital Heart Unit, The Heart Hospital, London, UK; 5 Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, UK; 6 Wolfson Unit for Prevention of Peripheral Vascular Diseases, Public Health Sciences, University of Edinburgh, Edinburgh, UK Background: Non-uniform reporting of the relevant relationships has hampered appraisal of the role of C-reactive protein (CRP) measurement for the prediction of later cardiovascular events leading to uncertainty on its clinical utility. Methods: The performance of CRP was assessed in two prospective studies and set in the context of a systematic review of 28 prospective studies involving 84,901 individuals and 9,209 incident cardiovascular events. Information on the predictive performance of CRP was extracted from published studies directly or recalculated using validated methods. Results: The CRP distribution was log-normal and its relationship with risk was continuous across the whole range of values without a threshold. A large proportion of all events were observed among the many individuals with near-average levels of CRP, leading to wide overlap of values among people who suffered events and those who did not. Neither the previously recommended CRP cut-point of 3mg/L nor cut-points based on a pre-specified false-positive rate (FPR) provided useful discrimination. The disease detection rate (sensitivity) was 5.8-15.5%, at a 5% FPR, and area under the ROC curve was only 0.52-0.66. CRP also did not add to discrimination based on the Framingham risk score, nor did it enhance risk stratification using models based on established risk factors. Conclusions: The available evidence does not support measurement of CRP either for discrimination or risk stratification of middle-aged populations at risk of cardiovascular events. Previous guidance on the clinical use of CRP measurement requires revision in light of this new analysis. WO10-OR4 EXTREME LIPOPROTEIN(A) LEVELS AND RISK OF MYOCARDIAL INFARCTION IN THE GENERAL POPULATION - THE COPENHAGEN CITY HEART STUDY P.R. Kamstrup 1 , M. Benn 1 , A. Tybjaerg-Hansen 2 , B.G. Nordestgaard 1 . 1 Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; 2 Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Background: Elevated lipoprotein(a) levels associate with myocardial infarction (MI) in some, but not all studies. Limitations of previous studies include lack of risk estimates for extreme lipoprotein(a) levels, measurements in long-term frozen samples, no correction for regression dilution bias, and lack of absolute risk estimates in the general population. We tested the hypothesis that extreme lipoprotein(a) levels predict MI in the general population, measuring levels shortly after sampling, correcting for regression dilution bias, and calculating hazard ratios and absolute risk estimates. Methods: We examined 9330 men and women from the general population, The Copenhagen City Heart Study. During 10 years follow-up, 498 participants developed MI. Results: In women, multifactorially adjusted hazard ratios for MI for
elevated lipoprotein(a) levels were 1.1(95% confidence interval 0.6-1.9) for 5-29 mg/dL (22nd-66th percentile), 1.7(1.0-3.1) for 30-84 mg/dL (67th89th percentile), 2.6(1.2-5.9) for 85-119 mg/dL (90th-95th percentile), and 3.6(1.7-7.7) for ≥120 mg/dL (>95th percentile) versus levels <5 mg/dL (<22nd percentile). Equivalent values in men were 1.5(0.9-2.3), 1.6(1.0-2.6), 2.6(1.2-5.5), and 3.7(1.7-8.0). Absolute 10-year risks of MI were 10% and 20% in smoking, hypertensive women above 60 years of age with lipoprotein(a) levels of <5 and ≥120 mg/dL, respectively. Equivalent values in men were 19% and 35%. Conclusions: We observed a stepwise increase in risk of MI with increasing levels of lipoprotein(a), with no evidence of a threshold effect. Extreme lipoprotein(a) levels predict a 3-4 fold increase in risk of MI in the general population, and absolute 10-year risks of 20% and 35% in high-risk women and men. WO10-OR5 INCREASED PLASMA APOLIPOPROTEIN C-III CONCENTRATION PREDICTS CARDIOVASCULAR MORTALITY: THE HOORN STUDY P.G. Scheffer 1 , T. Teerlink 1 , J.M. Dekker 2 , B. G 2 , G. Nijpels 2 , M. Diamant 3 , P.J. Kostense 4 , C.D.A. Stehouwer 5 , R.J. Heine 3 . 1 VU University Medical Center, Department of Clinical Chemistry, Amsterdam, The Netherlands; 2 VU University Medical Center, Institute for Research In Extramural Medicine, Amsterdam, The Netherlands; 3 VU University Medical Center, Department of Endocrinology/Diabetes Center, Amsterdam, The Netherlands; 4 VU University Medical Center, Department of Clinical Epidemiology and Biostatistics, Amsterdam, The Netherlands; 5 Department of Medicine, Division of General Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands Background and aims: Hypertriglyceridaemia is a cardiovascular risk factor. Apolipoprotein C-III (apo C-III) inhibits lipoprotein lipase, and is therefore an important determinant of the catabolic rate of triglyceriderich lipoproteins. We studied the predictive value of plasma apo C-III concentration for cardiovascular mortality in a large population-based study. Methods: This prospective study was performed in 2244 participants (aged 49 to 77) of the Hoorn Study. Apo C-III concentration was measured in baseline plasma samples by an immunoturbidimetric assay. During 15 years of follow-up, 504 individuals died: 231 of cardiovascular mortality, 180 of cancer, and 93 of other causes. The association between apo C-III concentration and mortality was studied by Cox proportional-hazards regression analysis. Results: Higher plasma apo C-III concentrations were observed in women compared to men and in subjects with abnormal glucose metabolism compared to individuals with a normal glucose metabolism (both P<0.01). After correction for age and sex, the cardiovascular mortality increased significantly (P<0.05) across quartiles of apo C-III (Table). Further adjustment for HDL-cholesterol, LDL-cholesterol, triglycerides, BMI, waist-to-hip ratio, SBP, smoking, and glucose metabolism did not influence this association. High apo C-III was not related to non-cardiovascular mortality.
Conclusions: Our data indicates that an elevated apo C-III concentration in plasma, independently of traditional risk factors, predicts cardiovascular mortality. WO10-OR6 SMALL DENSE LDL CHOLESTEROL, HDL PARTICLES, INSULIN, ADIPONECTIN, AND GLYCATED ALBUMEN AS PROSPECTIVE CHD RISK FACTORS IN THE FRAMINGHAM STUDY E.J. Schaefer 1 , M. Ai 1 , S. Otokozawa 1 , B.F. Asztalos 1 , C.C. White 2 , S. Demissie 2 , A. Cupples 2 . 1 Lipid Metabolism Laboratory, Tufts University, Boston, MA, USA; 2 Division of Epidemiology and Statistics, Boston University and The Framingham Heart Study, Boston, MA, USA Background and Aims: Standard coronary heart disease (CHD) risk factors
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey