HDL and Arterial Wall
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1 JIFA January 31th 2014 HDL and Arterial Wall P-J TOUBOUL INSERM698 Bichat University
2 Conflict of Interest M Ath intellectual property owner Involvement in R & D for atherosclerosis software developments
3 HDL-C as a marker HDL-C, LDL-C & CCA-IMT are independent markers of future CVE. LDL lowering is associated with CVE incidence reduction Epidemiological association between HDL C, triglycerides levels and risk of CV disease.
4 HDL-C and CHD
5 HDL and Stroke Risk : Systematic Review 10 Prospective cohort studies (n=238,739) : 11 to 15% decreased stroke risk per 10 mg/dl increase in HDL-C Amarenco et al. Atherosclerosis. 2008;196:489-96
6 Stroke Risk and LDL Lowering Each 1 mmol (39 mg) LDL-C reduction reduced the risk of stroke by 21% (95% CI 6.3 to 33.5%, p<0.001) Total n=165,732 Amarenco P, Labreuche J. Lancet Neurol. 2009; 8:453-63
7 Emerging Risk Factor Collaboration Risk of Stroke JAMA. 2009;302:
8 Anti-Atherosclerotic effect
9 Atherogenesis Endothelial dysfunction & IMT Foam Cells - Plaque Thrombus Glass, Cell 2001,104:
10 HDL-C and vascular protective properties Promote cholesterol efflux from macrophages in the artery wall Anti-oxidant Anti-thrombotic Anti-inflammatory Improve endothelial function & repair Improve diabetic control Others
11 Plaque Occurrence (%) IMT & Plaque : the EVA Study Q1 d'eim Q2-3 d'eim , ,3 19,3 25,4 15,6 8,4 11,3 6,2 All Men Women Baseline CCA-IMT predicts plaque occurence C Bonithon Kopp P-J Touboul ATVB 1996
12 IMT and Plaque : EVA Study Zureik, Ducimetiere, Touboul, et al. ATVB 2000;20:
13 Rationale for the HDL/IMT evaluation Association between HDL-C reduction and CV events Prooven association between LDL increase and CV events Statistical association between LDL level decrease and risk of stroke. Inverse association between IMT values and stroke in prospective studies
14 Methods Data from 6 cross sectional Ultrasound studies All observational, 5 published and one stopped Same ultrasound methodology to minimize variability : Following same IMT definition ( Mannheim consensus) Edge detection IMT measurement Same training of all investigators involved in these studies Image acquisition done on the same software Data were processed at the same core lab (Intelligence in Medical Technologies )
15 Methods (II) Risk factors definition : - BP : > mmhg or current bpld treatment - Dyslipidemia : LDL-C > 160mg/dL ( Friedewald formula ) or current lld treatment. - Diabetes Blood glucose > 126mg/dL or current treatment for Diabetes ( I or II) - Family history of MI ( < 55 y-o for men, <65 y-o for women ) - Early menopausis ( <40 y-o) - Lipid parameters all obtained at inclusion time. Touboul P-J, Labreuche J, Bruckert E & al Atherosclerosis232 (2014) 65-71
16 IMT Measurement Draw a line parallell to the far or near wall
17 Methods (III) Ultrasound: - CCA IMT on both CCA far walls - Angle with the best view - 10mm lenght in a region free of plaque - QI > or = Mean of right and left CCA IMT was computed. Touboul P-J, Labreuche J, Bruckert E & al Atherosclerosis232 (2014) 65-71
18 Populations Touboul P-J, Labreuche J, Bruckert E & al Atherosclerosis232(2014) 65-71
19 Main Results of this meta analysis Total Population : patients with complete information Individual meta analysis Mean age 51, 49% men Across the studies : mean HDL ranged from 46 to 61 mg/dl Touboul P-J, Labreuche J, Bruckert E & al Atherosclerosis232(2014) 65-71
20 CCA-IMT and Quintiles of HDL-C,Triglyceride levels Touboul P-J, Labreuche J, Bruckert E & al Atherosclerosis232(2014) 65-71
21 HDL/IMT associations according to LDL Levels LDL-C <100 mg/dl LDL-C mg/dl LDL-C >100 mg/dl Touboul P-J, Labreuche J, Bruckert E & al Atherosclerosis232(2014) 65-71
22 New Trends in Atherosclerotic Evaluation Meta-analysis of CIMT change in 48 Randomized Studies Results From a Carotid Intima-Media Thickness Trial as a Decision Tool for Launching a Large Scale M&M Trial Circulation CV imaging
23 New Trends in Atherosclerotic Evaluation 24 Results From a Carotid Intima-Media Thickness Trial as a Decision Tool for Launching a Large Scale Morbidity and Mortality Trial Circulation CV imaging 2013
24 Conclusion CCA-IMT evolution might be a powerfull endpoint for the evaluation of HDL-C raising agents. Longitudinal studies including prospective IMT and plaque evaluation and clinical outcome should be done to confirm these data IMT change and plaque occurrence might be in the future the first step to go for anti atherosclerotic drugs evaluation. Touboul P-J, Labreuche J, Bruckert E & al Atherosclerosis232(2014) 65-71
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