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A. Roussin MD ATHEROTHROMBOSE Stratification du risque vasculaire Marqueurs carotidiens. Emphase sur IMT Application pratique et Consensus canadien 2006.

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Presentation on theme: "A. Roussin MD ATHEROTHROMBOSE Stratification du risque vasculaire Marqueurs carotidiens. Emphase sur IMT Application pratique et Consensus canadien 2006."— Presentation transcript:

1 A. Roussin MD ATHEROTHROMBOSE Stratification du risque vasculaire Marqueurs carotidiens. Emphase sur IMT Application pratique et Consensus canadien 2006 André Roussin MD, FRCP, Internal medicine Director, Vascular Lab, Notre-Dame Hospital (CHUM) Associate Professor of medicine and Researcher University of Montreal ChairPresident TIGC.ORGSSVQ.ORG

2 A. Roussin MD André Roussin MD Disclosures AstraZeneca AstraZeneca Bristol-Myers Squibb Bristol-Myers Squibb Boeringher-Ingelheim Boeringher-Ingelheim GlaxoSmithKline GlaxoSmithKline Leo Pharma Leo Pharma Merck Frosst Merck Frosst Pfizer Pfizer Roche Diagnostics Roche Diagnostics Schering Canada Schering Canada sanofi aventis sanofi aventis I have been on advisory boards or received honorarium as consultant or speaker or received research funds from the following companies:

3 A. Roussin MD 1 Libby P. Circulation. 2001;104:365-372 234567 HUMAN ATHEROGENESIS From yellow streak to plaque and thrombosis

4 A. Roussin MD Inflammation markers Koenig W, Khuseyinova N. ATVB 2007; 27: 15-26

5 A. Roussin MD ASO and Drug Interventions Napoli C et al. Circulation 2006; 114: 2517-27

6 A. Roussin MD Cardiovascular disease worldwide CVD (CAD, Stroke and PAD) is the leading cause of death worldwide 1 CVD (CAD, Stroke and PAD) is the leading cause of death worldwide 1 CVD contributed in 2001 nearly one third of all global deaths 1-2 CVD contributed in 2001 nearly one third of all global deaths 1-2 3 Risk factors are responsible for > 75% of all CVD worldwide 1 3 Risk factors are responsible for > 75% of all CVD worldwide 1 Elevated cholesterol Elevated cholesterol Smoking Smoking High blood pressure High blood pressure Of the three, elevated cholesterol carries the greatest attributable risk for CAD 3 Of the three, elevated cholesterol carries the greatest attributable risk for CAD 3 1.WHO. World Health report 2002 2.American Heart Association: statistical fact sheet 2003 3.Wilson P et al. Circ 1998; 97:1837-1847

7 A. Roussin MD Risque de développer MCAS pendant la vie FemmeHomme0.50.5 0.20.2 Age (années) 40 50 60 70 8090 6555 1/10 1/10 Lloyd-Jones, Lancet 1999; 353: 89-92

8 A. Roussin MD Notion « traditionnelle » de risque vasculaire Consensus Canadien sur les Dyslipidémies Calcul du risque de coronaropathie à 10 ans ASO présente ASO présente Coronaropathie (MCAS) Coronaropathie (MCAS) Maladie artérielle périphérique Maladie artérielle périphérique ASO carotidienne (ICT, AVC isch., plaque) ASO carotidienne (ICT, AVC isch., plaque) Patients > 30 ans avec Diabète sucré Patients > 30 ans avec Diabète sucré Dyslipidémie sévère Dyslipidémie sévère Hypercholestérolémie familiale (LDL) Hypercholestérolémie familiale (LDL) Hypoalphalipoprotéinémie familiale (HDL) Hypoalphalipoprotéinémie familiale (HDL) Tous les autres Tous les autres Préciser le risque avec les tables de Framingham du NCEP III Préciser le risque avec les tables de Framingham du NCEP III RisqueÉlevé

9 A. Roussin MD Risque cardiovasculaire Framingham modifié NCEP III Pour calculer le risque dIM et de mortalité CV Points pour un homme AgePoints 20-34-9 35-39-4 40-440 45-493 50-546 55-598 60-6410 65-6911 70-7412 75-7913 PointsTotalCholesterolAge20-39Age40-49Age50-59Age60-69Age70-79 <4.1400000 4.15-5.1943210 5.2-6.1975310 6.2-7.296421 >7.21118531 1. Age 2. Total Cholesterol (mmol/L) according to age

10 A. Roussin MD Points Age20-39Age40-49Age50-59Age60-69Age70-79 Non-Smoker00000 Smoker85311 3. Smoking according to ageHDL-CPoints>1.55 1.30-1.540 1.04-1.291 <1.042 4. HDL-C Sys BP UntreatedTreated<12000 120-12901 130-13912 140-15912 >16023 5. Blood Pressure according to treatment Risque cardiovasculaire Framingham modifié NCEP III Pour calculer le risque dIM et de mortalité CV Points pour un homme

11 A. Roussin MD Points 10-year Risk 01 11 21 31 41 52 62 73 84 95 106 118 1210 1312 1416 1520 1625 >17>30 High Risk: > 20% Medium Risk: 10-20% Low Risk: < 10% Pour calculer le risque dIM et de mortalité CV Pour un homme

12 A. Roussin MD INTERHEART Risk of AMI associated with Risk Factors in the Overall Population ODDS RATIO Risk factor % Cont % Cases OR (99% CI) adj for age, sex, smok OR (99% CI) adj for all ApoB/ApoA-1 (5 v 1) 20.033.5 3.87 (3.39, 4.42) 3.25 (2.81, 3.76) Curr smoking 26.845.2 2.95 (2.72, 3.20) 2.87 (2.58, 3.19) Diabetes7.518.4 3.08 (2.77, 3.42) 2.37 (2.07, 2.71) Hypertension21.939.0 2.48 (2.30, 2.68) 1.91 (1.74, 2.10) Abd Obesity (3 v 1) 33.346.3 2.22 (2.03, 2.42) 1.62 (1.45, 1.80) Psychosocial-- 2.51 (2.15, 2.93) 2.67 (2.21, 3.22) Veg & fruits daily 42.435.8 0.70 (0.64, 0.77) 0.70 (0.62, 0.79) Exercise19.314.3 0.72 (0.65, 0.79) 0.86 (0.76, 0.97) Alcohol Intake 24.524.0 0.79 (0.73, 0.86) 0.91 (0.82, 1.02) All combined -- 129.2 (90.2, 185.0) All combined (extremes) 333.7 (230.2, 483.9) Yusuf S et al. Lancet 2004; 364: 937-52

13 A. Roussin MD INTERHEART Risk of AMI associated with Risk Factors in the Overall Population POPULATION ATTRIBUTABLE RISK Risk factor % Cont % Cases PAR 1 (99% CI) PAR 2 (99% CI) ApoB/ApoA-1(5 v 1) 20.033.5 54.1 (49.6, 58.6) 49.2 (43.8, 54.5) Curr smoking 26.845.236.4(33.9,39.0)35.7,(32.5,39.1) Diabetes7.518.5 12.3 (11.2, 13.5) 9.9 (8.5, 11.5) Hypertension21.939.0 23.4 (21.7, 25.1) 17.9 (15.7, 20.4) Abd Obesity (3 v 1) 33.346.3 33.7 (30.2, 37.4) 20.1 (15.3, 26.0) Psychosocial-- 28.8 (22.6, 35.8) 32.5 (25.1, 40.8) Veg & fruits daily 42.435.8 12.9 (10.0, 16.6) 13.7 (9.9, 18.6) Exercise19.314.3 25.5 (20.1, 31.8) 12.2 (5.5, 25.1) Alcohol24.524.0 13.9 (9.3, 20.2) 6.7 (2.0, 20.2) Combined-- 90.4 (88.1, 92.4) Yusuf S et al. Lancet 2004; 364: 937-52

14 A. Roussin MD INTERHEART Risk of AMI with Multiple Risk Factors SmkDMHTNApoB/A1+2+3 All 4 +Ob+PS All RFs 2.9 2.4 1.9 3.3 13.0 42.3 68.5 182.9 333.7 1 2 4 8 16 32 64 128 256 512 OR (99% CI) Yusuf S et al. Lancet 2004; 364: 937-52

15 A. Roussin MD Notion « élargie » risque vasculaire Incluant le Consensus Canadien sur les Dyslipidémies Ajoutant les facteurs de risque « émergents » MCAS familiale précoce: RR = 1.7 à 2 MCAS familiale précoce: RR = 1.7 à 2 ApoB, Lp(a), LDL dense, ApoA1 ApoB, Lp(a), LDL dense, ApoA1 Syndrome métabolique Syndrome métabolique Marqueurs sub-cliniques d'ASO: Marqueurs sub-cliniques d'ASO: ITH, ECG effort, Plaques et Intima-media ITH, ECG effort, Plaques et Intima-media Facteurs de risque émergents Facteurs de risque émergents hsCRP, homocystéine hsCRP, homocystéine

16 A. Roussin MD Risk factors: markers and / or activators Atherosclerosis Atherothrombosis Stroke - MI - Death IM Plaque Stenosis Thrombosis Triggering Factors Inflammation Factors Procoagulant Factors Endothelial Factors Cells, Intercellular + intracellular signaling, proteins-enz. actions Smoking, Diabetes, LDL/oxLDL, HBP, AgII/AT1, Shear stress TF, PAI-1 / tPA and TxA 2 / Prostacycline imbalances

17 A. Roussin MD New insights: What has been improved 1970-198019902000 WeightBMI Waist circumference HBP > 160 HBP goal: 140 Ideal BP: 120 Chol + TG LDL + HDL + TG LDL + TC/HDL + ApoB DiabetesDiabetes Diabetes + Met. Syndrome SmokingSmokingSmoking SedentarismSedentarismFitness CAD CAD + Stroke CAD + Stroke + PAD

18 A. Roussin MD New insights: What has been added Sub-clinical markers Sub-clinical markers Ankle-Brachial Index Ankle-Brachial Index Micro-albuminuria Micro-albuminuria Carotid intima-media thick. Carotid intima-media thick. Coronary calcification Coronary calcification Sub-clinical markers Sub-clinical markers Ankle-Brachial Index Ankle-Brachial Index Micro-albuminuria Micro-albuminuria Carotid intima-media thick. Carotid intima-media thick. Coronary calcification Coronary calcification Serological markers Serological markers hs-CRP hs-CRP Lipoprotein(a) Lipoprotein(a) Homocysteine Homocysteine Insulinemia Insulinemia sLp-PLA 2 sLp-PLA 2 Serological markers Serological markers hs-CRP hs-CRP Lipoprotein(a) Lipoprotein(a) Homocysteine Homocysteine Insulinemia Insulinemia sLp-PLA 2 sLp-PLA 2

19 A. Roussin MD CCS position statement 2006 Treatment of dyslipidemia and prevention of CVD Adapté de: Can J Cardiol 2006; 22 (11): 913-927 Niveau de risque Risque MCAS en 10 ans Recommendations But du traitementObjectifaccessoire LDL-Cmmol/LCT/HDLBaisse de LDL-C Apo B Élevé 20 % 20 % ou ASO ou Diabète Cible primaire < 2.0 Cible secondaire < 4.0 > 50% < 0.85 Modéré 10 - 19% Traiter si 3.5 3.5 Traiter si 5.0 5.0 > 40% < 1.05 Bas < 10% Traiter si 5.0 5.0 Traiter si 6.0 6.0 < 1.2

20 A. Roussin MD Ultrasonographie carotidienne Évaluation de lASO et stratification de risque CV Faible coût Faible coût Accessible Accessible Non-invasive Non-invasive Imagerie excellente Imagerie excellente Quantitative Quantitative Reproductible Reproductible Mesure lASO intimale avant la sténose angiographique Mesure lASO intimale avant la sténose angiographique Faible coût Faible coût Accessible Accessible Non-invasive Non-invasive Imagerie excellente Imagerie excellente Quantitative Quantitative Reproductible Reproductible Mesure lASO intimale avant la sténose angiographique Mesure lASO intimale avant la sténose angiographique Épaisseur Intima-Media Épaisseur Intima-Media Intima-media thickness Intima-media thickness IMT IMT Épaisseur de plaque Épaisseur de plaque Surface de plaque Surface de plaque Volume de plaque Volume de plaque Sténose Sténose Type de plaque: Type de plaque: Échogénicité Échogénicité Homogénéité Homogénéité Épaisseur Intima-Media Épaisseur Intima-Media Intima-media thickness Intima-media thickness IMT IMT Épaisseur de plaque Épaisseur de plaque Surface de plaque Surface de plaque Volume de plaque Volume de plaque Sténose Sténose Type de plaque: Type de plaque: Échogénicité Échogénicité Homogénéité Homogénéité

21 A. Roussin MD Ultrasound Examination of the Carotid Artery B-mode ultrasound Skin External carotid Internal carotid 1.0 cm 0.5-1.0 cm 1.0 cm Bifurcation Common carotid Near Wall Periadventitia-adventitiaAdventitia-mediaIntima-lumen Far Wall Adventitia-periadventitiaMedia-adventitiaLumen-intima Smilde TJ et al. Lancet 2001; 357: 577-581

22 A. Roussin MD Façons de déterminer la valeur dun marqueur de risque Vasan R S. Circ 2006; 113: 2335-2362

23 A. Roussin MD Considérations avant ladoption dun marqueur de risque CV Vasan R S. Circ 2006; 113: 2335-2362

24 A. Roussin MD Marqueurs structurels et fonctionnels de risque CV Vasan R S. Circ 2006; 113: 2335-2362

25 A. Roussin MD Reproducibility of non-invasive ultrasonic measurement of carotid atherosclerosis The Asymptomatic Carotid Artery Plaque Study (ACAPS) 858 patients 858 patients 12 measurements in each patient 12 measurements in each patient Repeated at 1 month Repeated at 1 month Within and between sonographer variation Within and between sonographer variation 858 patients 858 patients 12 measurements in each patient 12 measurements in each patient Repeated at 1 month Repeated at 1 month Within and between sonographer variation Within and between sonographer variation Stroke 1992, Aug 23 (8), 1062-8 Mean IMT difference (exam 2-exam 1) 0.13 mm Mean IMT difference (exam 2-exam 1) 0.13 mm 90% of patients – mean difference < 0.2 mm 90% of patients – mean difference < 0.2 mmResult Highly reproducible measurement Highly reproducible measurement B-mode ultrasound can monitor small rates of lesion progression B-mode ultrasound can monitor small rates of lesion progression Mean IMT difference (exam 2-exam 1) 0.13 mm Mean IMT difference (exam 2-exam 1) 0.13 mm 90% of patients – mean difference < 0.2 mm 90% of patients – mean difference < 0.2 mmResult Highly reproducible measurement Highly reproducible measurement B-mode ultrasound can monitor small rates of lesion progression B-mode ultrasound can monitor small rates of lesion progression

26 A. Roussin MD Protocoles pour Épaisseur Intima-Media (IMT) 12 point manual measurement 12 point manual measurement Near and far wall of CCA, ICA, Bulb Near and far wall of CCA, ICA, Bulb Near and far wall of CCA, ICA Near and far wall of CCA, ICA Far wall of CCA Far wall of CCA Mean of maximal IMT measurement Mean of maximal IMT measurement Mean of mean IMT measurement Mean of mean IMT measurement Manual VS automated edge detection Manual VS automated edge detection Plaque thickness summed Plaque thickness summed Plaque area summed Plaque area summed Plaque volume summed Plaque volume summed Adapted from Weingert M SSVQ 2006

27 A. Roussin MD IMT Reproducibility of Measurement Intra observer variability lower in studies limited to common carotid artery far wall (± 0.02 mm) VS multiple measurements at different carotid sites (± 0.06 mm) Intra observer variability lower in studies limited to common carotid artery far wall (± 0.02 mm) VS multiple measurements at different carotid sites (± 0.06 mm) Studies using automated computerized IMT measurement rather than manual cursor placement have best reproducibility. Studies using automated computerized IMT measurement rather than manual cursor placement have best reproducibility. Adapted from Weingert M SSVQ 2006

28 A. Roussin MD IMT: quantitative vs caliper

29 A. Roussin MD IMT and 70% Coronary Stenosis Sensitivity vs Specificity IMT ofSensitivitySpecificity 0.6 mm 95%20% 0.8 mm 55%60% 1.0 mm 20%90% Aminbaklish A. et al. Clin. Invest. Med 1999; 22:265-274

30 A. Roussin MD Evaluating Atherosclerosis by IMT measurement Anatomy 0.80 mm 0.02 mm Courtesy E. Braunwald Buithieu J /

31 A. Roussin MD 12 point manual measurement Far wall of Common Carotid Artery Near and far wall of CCA, ICA Near and far wall of CCA, ICA, Bulb Mean of maximal IMT measurement Mean of mean IMT measurement Manual / automated edge detection Summation of plaque thickness Summation of plaque area Summation of plaque volume Evaluating Atherosclerosis by IMT measurement Methodology CCA ICA ECA Bulb CCA ICA 10 mm Buithieu J /

32 A. Roussin MD ECG gating ECG gating Diastole Diastole distal CCA distal CCA Mean IMT over Mean IMT over 100 pts along at least 1 cm Avoids pulsatile deformation of wall thickness Avoids pulsatile deformation of wall thickness Observer independent Observer independent Better precision/reproducibility : Intermeasurement Δ = 3 % Better precision/reproducibility : Intermeasurement Δ = 3 % Evaluating Atherosclerosis by computerized IMT measurement AutomatedComputerizedmethod Buithieu J /

33 A. Roussin MD The Atherosclerosis Risk in Communities (ARIC) Study Predictive Value of CIMT: Methodology Chambless LE & al. Am J Epidemiol 1997. 146:483-494 Prospective, multicenter study Prospective, multicenter study N = 12841 aged 45 - 64 y (72.5 ± 5.5) N = 12841 aged 45 - 64 y (72.5 ± 5.5) 7289 women, 5552 men 7289 women, 5552 men No evidence of CV disease at enrollment No evidence of CV disease at enrollment Median follow-up 5.2 years Median follow-up 5.2 years Mean CIMT over 1 cm - far walls of Right & Left CCA-Bulb-ICA Mean CIMT over 1 cm - far walls of Right & Left CCA-Bulb-ICA CCA ICA ECA 10 mm Bulb Buithieu J /

34 A. Roussin MD The Atherosclerosis Risk in Communities (ARIC) Study Predictive Value of CIMT for Myocardial Infarct / Death Chambless LE & al. Am J Epidemiol 1997. 146:483-494 Age and Gender adjusted CHD incidence/1000 patient-year CIMT (mm) Mean F-up 5.2 y Buithieu J /

35 A. Roussin MD The Atherosclerosis Risk in Communities (ARIC) Study Predictive Value of CIMT for Stroke Chambless LE & al. Am J Epidemiol 2000. 151:478-487 Age and Gender adjusted Stroke incidence/1000 patient-year CIMT (mm) Mean F-up 7.2 y Buithieu J /

36 A. Roussin MD The Atherosclerosis Risk in Communities (ARIC) Study Predictive Value of CIMT by incremental value CIMT (mean of CCA-Bulb-ICA) increment is associated with increased hazard rate ratio (HRR) CIMT (mean of CCA-Bulb-ICA) increment is associated with increased hazard rate ratio (HRR) Chambless LE & al. Am J Epidemiol 1997. 146:483-494 Chambless LE & al. Am J Epidemiol 2000. 151:478-487 Increment CHDStroke MenWomenMenWomen 0.19 mm 1.171.38 0.18 mm 1.211.36 Buithieu J /

37 A. Roussin MD The Atherosclerosis Risk in Communities (ARIC) Study Predictive Value of CIMT by strata CIMT (mean of CCA-Bulb-ICA) increased hazard rate ratio (HRR) vs CIMT < 0.6 mm Chambless LE & al. Am J Epidemiol 1997. 146:483-494 Chambless LE & al. Am J Epidemiol 2000. 151:478-487 CIMT CHDStroke MenWomenMenWomen > 1.0 mm (Yes/No) 1.202.621.782.02 > 1.0 mm 2.157.402.594.32 0.80 - 0.99 mm 2.443.352.083.14 0.70 - 0.79 mm 1.563.561.261.73 0.60 - 0.69 mm 1.212.530.792.07 Hypertension2.1 Diabetes2.5 Current smoking 1.3 Buithieu J /

38 A. Roussin MD The Atherosclerosis Risk in Communities (ARIC) Study Predictive Value of CIMT: Conclusions N = 15 792 patients N = 15 792 patients CIMT measurements CIMT measurements Reproducible Reproducible Independent predictor of adverse cardiovascular events after adjustment for: Independent predictor of adverse cardiovascular events after adjustment for: Age, sex, race, center, BMI, waist-hip ratio, sporting activity Age, sex, race, center, BMI, waist-hip ratio, sporting activity Diabetes, LDL, HDL, hypertension, smoking Diabetes, LDL, HDL, hypertension, smoking Fibrinogen, WBC, LVH Fibrinogen, WBC, LVH Chambless LE & al. Am J Epidemiol 1997. 146:483-494 Chambless LE & al. Am J Epidemiol 2000. 151:478-487

39 A. Roussin MD Predicting clinical coronary events: role of Carotid IMT CLAS Sub-Study 133 patients: 8.8 year follow-up 133 patients: 8.8 year follow-up Close correlation between far wall CCA-IMT and changes in catheterization Close correlation between far wall CCA-IMT and changes in catheterization Progression of IMT correlated with: Progression of IMT correlated with: 1)Progression of CAD 2)Increased coronary events Absolute IMT thickness and progression of IMT more strongly correlated with coronary events than Absolute IMT thickness and progression of IMT more strongly correlated with coronary events than 1)Changes in lipid levels 2)Lesion changes on coronary catheterization Result: every 0.03 mm increase in IMT increases risk of coronary event 3.1 % Result: every 0.03 mm increase in IMT increases risk of coronary event 3.1 % Hodis H.N. et al Ann Int Med 1998; 128:262-269

40 A. Roussin MD Predicting clinical coronary events: role of Carotid IMT CLAS Sub-Study CIMT directly associated with higher risk for future MI and CHD death CHD Risk Non fatal MI, Coronary Death, Revascularization Carotid Intima-Media Thickness (mm) Hodis HN & al. Ann Intern Med 1998. 128:262-269 N = 146 CABG p < 0.001 Buithieu J /

41 A. Roussin MD Predicting clinical coronary events: role of Carotid IMT progression CLAS Sub-Study CIMT progression directly associated with higher risk for future MI and CHD death CHD Risk Non fatal MI, Coronary Death, Revascularization CIMT progression (mm/y) Hodis HN & al. Ann Intern Med 1998. 128:262-269 N = 146 CABG p < 0.001 Buithieu J /

42 A. Roussin MD Cardiovascular Health Study (NHLBI) Predictive Value of CIMT: methodology Prospective, multicenter study Prospective, multicenter study N = 4476 aged > 65 y (72.5 ± 5.5) N = 4476 aged > 65 y (72.5 ± 5.5) Male 38.8 %, Caucasian 84.8 % Male 38.8 %, Caucasian 84.8 % No evidence of CV disease at enrollment No evidence of CV disease at enrollment Median follow-up 6.2 years Median follow-up 6.2 years Maximal CIMT mean of near & far walls of R + L CCA Maximal CIMT mean of near & far walls of R + L CCA Maximal CIMT mean of near & far walls of R + L ICA Maximal CIMT mean of near & far walls of R + L ICA OLeary D & al N Eng J Med 1999;.340: 14-22 Buithieu J /

43 A. Roussin MD Cardiovascular Health Study (NHLBI) Predictive Value of CIMT for Myocardial Infarction & Stroke Cumulative Event-free Rate (%) 100 95 90 0 85 80 75 02 1 3 76 54 Years 1st Quintile 2nd Quintile 3rd Quintile 4th Quintile 5th Quintile 5 % 25 % OLeary D & al N Eng J Med 1999;.340: 14-22 Buithieu J /

44 A. Roussin MD Cardiovascular Health Study (NHLBI) Predictive Value of CIMT for Myocardial Infarction & Stroke Quintiles Myocardial Infarction or Stroke (Rate per 1000 Person-Years) OLeary D & al N Eng J Med 1999;.340: 14-22 Buithieu J /

45 A. Roussin MD Cardiovascular Health Study (NHLBI) Predictive Value of CIMT for Myocardial Infarction & Stroke CIMT - CCA Quintile Thickness (mm) MI-CVA Rate (%) at 7 y Adjusted Relative Risk * MI - CVA MICVA 1 < 0.87 5.21.001.001.00 2 0.87 - 0.96 9.31.491.791.33 3 0.97 - 1.05 9.01.291.401.21 4 1.06 - 1.17 13.21.762.071.39 5 > 1.18 18.72.222.462.13 * Relative Risk adjusted for age, sex, sBP, HTN, Atrial fibrillation, Diabetes OLeary D & al N Eng J Med 1999;.340: 14-22 Buithieu J /

46 A. Roussin MD The Rotterdam Study Comparative Predictive Value for Incident Myocardial Infarction Population-based cohort Population-based cohort N = 6389 aged > 55 (69.3 ± 9.2) N = 6389 aged > 55 (69.3 ± 9.2) Male 38.1 %, Caucasian 100 % Male 38.1 %, Caucasian 100 % No prior MI or revascularization No prior MI or revascularization Mean Follow-up 4.2 years Mean Follow-up 4.2 years van der Meer IM & al. Circ 2004. 109:1089-1094

47 A. Roussin MD The Rotterdam Study Comparative Predictive Value for Incident Myocardial Infarction Carotid - Ultrasonography Carotid - Ultrasonography Maximal CIMT mean of near and far wall of left & right CCA Maximal CIMT mean of near and far wall of left & right CCA Carotid plaque - weighted score Carotid plaque - weighted score Aorta - Lateral abdominal X-ray Aorta - Lateral abdominal X-ray Calcifications - length of affected area Calcifications - length of affected area 0cm, <1.0, 1.0-2.5, 2.5-4.9, 5.0-9.9, 10.0cm 0cm, <1.0, 1.0-2.5, 2.5-4.9, 5.0-9.9, 10.0cm Lower extremities - Ankle-Brachial Index (ABI) Lower extremities - Ankle-Brachial Index (ABI) 1.50-1.21, 1.21-1.10, 1.10-0.97, 0.97-0.00 1.50-1.21, 1.21-1.10, 1.10-0.97, 0.97-0.00 Composite atherosclerosis score van der Meer IM & al. Circ 2004. 109:1089-1094 ?

48 A. Roussin MD The Rotterdam Study Comparative Predictive Value for Incident Myocardial Infarction Incident MI : 258 / 6389 = 4.0 % van der Meer IM & al. Circ 2004. 109:1089-1094

49 A. Roussin MD Carotid Plaque Predictive value 76 asymptomatic patients 76 asymptomatic patients Aged 35-65 Aged 35-65 TC > 6.5 TC > 6.5 Stress test, cath, carotid ultrasound Stress test, cath, carotid ultrasound 1 Plaque: 64% 1 Plaque: 64% 57% had critical CAD 57% had critical CAD Positive predictive value for coronary atherosclerosis: 76% Positive predictive value for coronary atherosclerosis: 76% No Plaque Women: none had CAD Women: none had CAD Men: - with positive stress test – 21% significant CAD Men: - with positive stress test – 21% significant CAD Giral P. et al. Am J Card 1999; 84: 14-17

50 A. Roussin MD PLAQUE AREA CAD rather than Stroke prediction Spence JD & al. Stroke 2002. 33(12):2910-2922 Buithieu J /

51 A. Roussin MD PLAQUE AREA Stoke and MI risk Plaque Area (cm2) Stroke alone Stroke and MI 5 y Risk (%) RR RR 0.00 - 0.11 1.61.04.81.0 0.12 - 0.45 2.31.49.31.9 0.46 - 1.18 3.92.412.32.5 1.19 - 6.73 4.02.414.02.9 Spence JD & al. Stroke 2002. 33(12):2910-2922 Buithieu J /

52 A. Roussin MD PLAQUE AREA Regression vs Progression Spence JD & al. Stroke 2002. 33(12):2910-2922 Buithieu J /

53 A. Roussin MD PLAQUE AREA Progression Spence JD & al. Stroke 2002. 33(12):2910-2922 Buithieu J /

54 A. Roussin MD PLAQUE AREA Predictor for MI and CVA CIMT : mostly medial thickness Medial hypertrophy related to HTN Correlation w LVH > CAD predicts CVA > MI CIMT : mostly medial thickness Medial hypertrophy related to HTN Correlation w LVH > CAD predicts CVA > MI Plaque area : intimal process related to ASO High associated with coronary plaque predicts MI more strongly Plaque area : intimal process related to ASO High associated with coronary plaque predicts MI more strongly CIMT : mostly medial thickness Medial hypertrophy related to HTN Correlation w LVH > CAD predicts CVA > MI CIMT : mostly medial thickness Medial hypertrophy related to HTN Correlation w LVH > CAD predicts CVA > MI Plaque area : intimal process related to ASO High associated with coronary plaque predicts MI more strongly Plaque area : intimal process related to ASO High associated with coronary plaque predicts MI more strongly Spence JD & al. Stroke 2002. 33(12):2910-2922

55 A. Roussin MD PLAQUE VOLUME N = 21N = 17 Ainsworth CD & al. Stroke 2005. 36-1904-1909 Buithieu J /

56 A. Roussin MD IMT vs Plaque area vs Plaque volume CIMT Hypertension Hypertension Total Plaque Area Smoking Smoking Plasma cholesterol Plasma cholesterol Total Plaque Volume Diabetes Diabetes Al-Shali & al. Atherosclerosis 2005-178:319-325 Buithieu J /

57 A. Roussin MD Plaque roughness IMT roughness N = 15 healthy (24.9 ± 2.3) N = 22 healthy (62.9 ± 3.5) N = 46 CAD (62.0 ± 9.2) Schmidt-Trucksass A & al. Atherosclerosis 2003. 166:57-65 * p < 0.05 ** p < 0.01AUCSE p level CIMT mean 0.660.070.03 CIMT max 0.710.070.01 IMT roughness 0.800.070.00YounghealthyOlderhealthyCAD CIMT mean 0.550.77**0.88 CIMT max 0.650.87**1.01 IMT roughness 0.0350.040*0.075** Imaging Research laboratories Stroke Prevention and Atherosclerosis Research Centre Robarts Research Institute, London, Ontario, Canada Buithieu J /

58 A. Roussin MD Reference Values for CIMT (75th percentile) 0.0 0.2 0.4 0.6 0.8 1.0 1.2 CIMT (mm) Age (years) Redberg R & al. JACC Task Force #3. J Am Coll Cardiol 2003. 41:1886-1898 Buithieu J /

59 A. Roussin MD IMT selon lâge De Groot Circ. 2004; 109 (suppl): 111:33-38 AgeIMT (years)(mm) 100.53 200.55 300.58 400.60 500.64 600.73 700.78 800.80 AgeIMT (years)(mm) 100.53 200.55 300.58 400.60 500.64 600.73 700.78 800.80 Familial HC Normal controls From Weingert M, SSVQ 2006

60 A. Roussin MD IMT conclusion 1 Atherosclerosis is a diffuse disease Detection in one vascular bed highly associated with atherosclerosis in other beds Detection in one vascular bed highly associated with atherosclerosis in other beds Carotid atheroma associated with increased risk of vascular events in direct relationship to extent of atherosclerosis Carotid atheroma associated with increased risk of vascular events in direct relationship to extent of atherosclerosis IMT 1 mm vs. < 1 mm, associated with 5-fold increased risk of CAD IMT 1 mm vs. < 1 mm, associated with 5-fold increased risk of CAD Risk for CVA and MI correlate with carotid IMT independent of standard risk factors (ARIC) Risk for CVA and MI correlate with carotid IMT independent of standard risk factors (ARIC) Adapted from Weingert M SSVQ 2006

61 A. Roussin MD IMT conclusion 2 Progression and relations Normal progression is 0.02-0.05 mm/year Normal progression is 0.02-0.05 mm/year Direct relationship between number of risk factors and IMT Direct relationship between number of risk factors and IMT Direct relationship between IMT and CAD and cardiac events as well as stroke Direct relationship between IMT and CAD and cardiac events as well as stroke Burk, G.I. et al Stroke 1995; 26:386-391 OLeary, D.H. et al NEJM, 1999; 340:14-25 Mannami, T. et al Arch.-Int. Med 2000; 160: 2297-2303 Hodes, H.N. et al Ann Int Med 1998; 128: 262-269

62 A. Roussin MD IMT conclusion 3 Carotid IMT: Associations IMT augmentation is associated with: White matter lesions on MRI White matter lesions on MRI Coronary disease on catheterization Coronary disease on catheterization EBCT coronary artery calcification EBCT coronary artery calcification LVH on echocardiogram LVH on echocardiogram Microalbuminuria in diabetics Microalbuminuria in diabetics Peripheral Vascular Disease Peripheral Vascular Disease Adapted from Weingert M SSVQ 2006

63 A. Roussin MD IMT conclusion 4 Carotid IMT: Usefulness Reflects impact of multiple risk factors Reflects impact of multiple risk factors Mirrors atherosclerotic burden Mirrors atherosclerotic burden Predictor of cardiovascular and neurological events Predictor of cardiovascular and neurological events Can reclassify patient to higher risk category, worthy of more aggressive treatment Can reclassify patient to higher risk category, worthy of more aggressive treatment

64 A. Roussin MD Recommended Recommended Physical examination Physical examination Ankle-brachial index Ankle-brachial index Possibly useful in subjects at moderate risk Possibly useful in subjects at moderate risk Carotid ultrasonography Carotid ultrasonography Electrocardiography Electrocardiography Graded exercise testing in Men > 40 with risk factors Graded exercise testing in Men > 40 with risk factors Recommendations for the Management of Dyslipidemia and the Prevention of Cardiovascular Disease: 2003 Update Diagnosis of Asymptomatic Atherosclerosis Genest JG & al. Can Med Assoc J 2003. 168(9):921-924

65 A. Roussin MD Not currently recommended based on available evidence Not currently recommended based on available evidence Flow-mediated vasodilatation Flow-mediated vasodilatation Plethysmography Plethysmography Arterial compliance Arterial compliance Electron beam CT scanning Electron beam CT scanning MRI scanning MRI scanning Intravascular ultrasonography Intravascular ultrasonography Recommendations for the Management of Dyslipidemia and the Prevention of Cardiovascular Disease: 2003 Update Diagnosis of Asymptomatic Atherosclerosis Genest JG & al. Can Med Assoc J 2003. 168(9):921-924

66 A. Roussin MD 2006 Position Statement Recommendations for the Diagnosis and Treatment of Dyslipidemia and Prevention of Cardiovascular Disease Useful non-invasive investigations in the intermediate risk category to detect subclinical atherosclerosis and/or to further define future CAD risk Useful non-invasive investigations in the intermediate risk category to detect subclinical atherosclerosis and/or to further define future CAD risk Ankle-Brachial Index (ABI) Ankle-Brachial Index (ABI) Carotid ultrasound Carotid ultrasound Graded exercise testing (GXT) Graded exercise testing (GXT) Electrocardiogram (ECG) Electrocardiogram (ECG) MacPherson R & al. Can J Cardiol October 2006. In Press Class IIa, Level of evidence C Class IIb, Level of evidence C


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