Role of imaging

1
Regression of atherosclerosis and related CV
diseases
Jean-Claude Tardif MD, FRCPC, FACC,
FCAHS Director, MHI Research Center Professor of
Medicine UdeM Endowed Research Chair in
Atherosclerosis Montreal Heart Institute Universit
é de Montréal
2
Change in atheroma volume in 6 weeks in
statin-naïve patients
Relative change
Nominal change
0
2
1.21
-0.5
-0.54 0.89
0
-1
-1.5
-2
-2
Adjusted mean SE
Median (IQR)
-2.5
-4
-3
P 0.002
-6
-3.5
P 0.003
-4
-8
-4.5
-4.71 0.96
-9.10
-5
-10
Chronic statin therapy prior to ACS (n 38)
Newly initiated statin therapy following ACS (n
36)
Chronic statin therapy prior to ACS (n 38)
Newly initiated statin therapy following ACS (n
36)
Rodes J and Tardif JC, Am J Cardiol 2009104750-7
3
Substantial Risk of CHD Events Remains for Many
Patients on Statin Therapy
Trial (N) Statin treatment Clinical eventsa Clinical eventsa
Trial (N) Statin treatment Risk reduction vs placebo
WOSCOPSb (6595) Pravastatin 40 mg 31
AFCAPS/TexCAPSb (6605) Lovastatin 20 or 40 mg 37
ASCOT-LLAb (10,305) Atorvastatin 10 mg 36
4Sb (4444) Simvastatin 20 mg 26
CAREc (4159) Pravastatin 40 mg 24
LIPIDc (9014) Pravastatin 40 mg 24
HPSc (20,536) Simvastatin 40 mg 27
PROSPERc (5804) Pravastatin 40 mg 19
Remaining risk
69
63
64
74
76
76
73
81
aNonfatal myocardial infarction and coronary
heart death bPrimary prevention trial
cSecondary prevention trial WOSCOPSWest of
Scotland Coronary Prevention Study
AFCAPS/TexCAPSAir Force/Texas Coronary
Atherosclerosis Prevention Study
ASCOT-LLAAnglo-Scandinavian Cardiac Outcomes
TrialLipid Lowering Arm 4SScandinavian
Simvastatin Survival Study CARECholesterol and
Recurrent Events LIPIDLong-Term Intervention
with Pravastatin in Ischemic Disease HPSHeart
Protection Study PROSPERProspective Study of
Pravastatin in the Elderly at Risk Adapted from
Mahley RW, Bersot TP. In Goodman Gilmans The
Pharmacological Basis of Therapeutics. 11th ed.
New York McGraw-Hill Medical Publishing
Division, 2006933966 Bays HE. Expert Rev
Cardiovasc Ther. 20042485501 Shepherd J et
al. N Engl J Med. 199533313011307 Downs JR et
al. JAMA. 199827916151622 Sever PS et al.
Lancet. 200336111491158 Scandinavian
Simvastatin Survival Study Group. Lancet.
199434413831389 Sacks FM et al. N Engl J Med.
199633510011009 Long-Term Intervention with
Pravastatin in Ischaemic Disease (LIPID) Study
Group. N Eng J Med. 199833913491357 Heart
Protection Study Collaborative Group. Lancet.
2002360722 Shepherd J et al. Lancet.
200236016231630.
4
Risk of death according to presence of metabolic
syndrome
Survival (all-cause)
Survival (CV)
1.0
1.0
p lt 0.0001
p lt 0.0001
0.75
0.75
0.50
0.50
0.25
0.25
No WHO metabolic syndrome WHO metabolic syndrome
No WHO metabolic syndrome WHO metabolic syndrome
0
0
0
5
10
15
20
0
5
10
15
20
Time (years)
Time (years)
No at risk No MS MS
23813 1078
20796 877
17854 673
10978 388
23122 1054
20110 853
17233 651
10611 376
Nigam A, Bourassa MG, Fortier A, Guertin MC,
Tardif JC. Am Heart J 2006 151 514-21
5
Lipoprotein metabolism
LDL receptor
Liver
B
C-II
ACAT
MTP
LPL
C-II
FC
CE
B
B
ApoB
27-hydroxylase
LPL
Oxidation
E
FC ? CE
E
ABCG1
IDL
CD36 SR-A
LDL
ACAT
VLDL
Bile
Cholesterol pool
CETP
PL TP
Intestine
ABC1
A-1
A-1
LCAT
Macrophage
FC
HL
Nascent HDL
ACAT
HDL
CE
IBAT
6
Change in plaque volume
A
30-mm segment, intent-to-treat population
mm3
6
5.1 30.0
p 0.058 (unadjusted) p 0.17 (adjusted)
4
1.9 33.1
2
1.2 24.2
Mean change (SD)
0
-2
-2.5 26.6
-4
Placebo
Avasimibe Avasimibe Avasimibe
50 mg (n 108)
250 mg (n 98)
750 mg (n 117)
(n109)
Tardif et al Circulation 2004 1103372-7
7
A
Long-Term Safety of Intravascular Ultrasound
Disease progression
Coronary change score
New lesions
0
20
-0.02
15
p 0.27
-0.04
10
(mm)
( of patients)
-0.06
p 0.84
p 0.35
5
-0.08
-0.10
0
Instrumented (IVUS-related arteries)
Non-instrumented (Non-IVUS arteries)
J Am Coll Cardiol 200545559-564
8
IVUS assessment - Atherosclerosis regression
20 reduction in plaque burden
Baseline
Follow-up
Plaque volume (mm3) 272.9 EEM volume (mm3) 609.5
Plaque volume (mm3) 197.3 EEM volume (mm3) 445.9
9
Correlations between changes in plaque, vessel
and lumen areas in pts with regression
? Mean vessel area (mm2)
? Mean lumen area (mm2)
6
6
n 227 r 0.64 p lt 0.0001
n 227 r 0.20 p 0.0030
4
4
2
2
0
0
-2
-2
-4
-4
-6
-6
-4
-3.5
-3
-2.5
-2
-1.5
-1
-.5
0
-4
-3.5
-3
-2.5
-2
-1.5
-1
-.5
0
Change in mean plaque area (mm2)
Change in mean plaque area (mm2)
Tardif et al. Am J Cardiol 200698-23-7
10
IVUS results in patients with angiographic
progression vs no progression by QCA in the
IVUS-related artery
Progression No progression
250
p 0.0089
p 0.05
225
226.8 ? 69.9
217.2 ? 72.1
Mean plaque volume (mm3)
200
197.1 ? 73.6
196.0 ? 71.3
175
150
Baseline
Follow-up
P-value for mean change in plaque volume 0.0283
Circulation 20071151851-7
11
Prognostic significance of angiographic
progression of coronary atherosclerosis
Any coronary event ( n 112)
Death or MI (n 40)
1.0
1.0
Non progressors
Non progressors
0.75
0.75
Proportion event free
Proportion event free
p lt 0.001
p lt 0.001
Progressors
0.50
0.50
Progressors
(N 260)
(N 137)
(N 0)
(N 0)
(N 309)
(N 192)
(N 5)
(N 1)
0.25
0.25
0
20
40
60
80
0
20
40
60
80
Months
Months
Circulation 1993 87 1067-75
12
Canadian Atherosclerosis Imaging NetworkClinical
Translation and Practice

• Correlation of coronary and carotid
  atherosclerosis and their changes over time and
  links with clinical outcomes
• 2000 patients undergoing coronary angiography,
  IVUS (with virtual histology) and carotid
  ultrasound (IMT and plaques) at baseline and 24
  months
• 5-year follow-up for cardio/cerebrovascular
  events
• NIRS, PET/CT, MRI and microvascular substudies
• Genomic (including miRNAs) and biomarker biobanks
• Proteomic and metabolomic analyses
• Application of this knowledge and framework in
  clinical trials of novel anti-atherosclerotic
  agents

13
Beyond statin-induced LDL-C reduction

• CETP inhibitors
• HDL infusions/mimetics
• 5-LO/FLAP inhibitors
• PLA2 inhibitors
• Serpins
• Heart rate reduction?

Tardif JC, Heinonen T. Nature Clin Pract CV Med
20063366-7
14
INHIBITION OF ATHEROSCLEROSIS BY HDL
HDL INHIBITS ADHESION MOLECULE EXPRESSION
Monocyte
HDL INHIBITS MCP-1 EXPRESSION
LDL
Adhesion Molecule
MCP-1
LDL
HDL INHIBITS OXIDATION OF LDL
Cytokines
MODIFIED LDL
Foam Cell
Macrophage
HDL PROMOTES CHOLESTEROL EFFLUX
15
Effects of rApo-A1 Milano on coronary
atherosclerosis
Change in atheroma volume
Change in atheroma volume
0
1
-4
0.14 3.09
-2.9 23.3
0
-8
mm3

-12
-0.73 2.75
-1
-12.6 15.3
-1.06 3.17
-14.1 39.5
-16
-15.1 50.6
-1.29 3.48
p 0.97
p 0.02
p 0.007
p lt 0.001
p 0.03
p 0.45
p 0.02
-20
-2
Placebo (n 11)
15 mg/kg (n 21)
45 mg/kg (n 15)
Combined (n 36)
Placebo (n 11)
15 mg/kg (n 21)
45 mg/kg (n 15)
Combined (n 36)
ETC-216
ETC-216
JAMA 2003 2902292-2300
16
Change in atheroma volume on IVUS
The ERASE trial
Median percent change
Median nominal change
0
0
-0.5
-1
pNS
pNS
-1
-2.33
-2
-1.62
-1.5
P0.04
p 0.07

mm3
-2
-3
-2.5
-4
-3
-3.41
-5.34
-5
-3.5
p lt 0.0001
p lt 0.0001
-4
-6
CSL-111 (n 89)
Placebo (n 47)
CSL-111 (n 89)
Placebo (n 47)

• Plaque volume at baseline 146.0 mm3 for CSL-111,
  151.4 mm3 for placebo
• Interval between IVUS examinations 43 6 days
  in both groups

Tardif et al. JAMA 20072971675-82
17
Changes in plaque characterization indexes
The ERASE trial
Arc index
Inner perimeter index
0.02
0.02
0.0137
0.0128
0.01
0.01
Least square means
Least square means
0
0
-0.0083
-0.0097
-0.01
-0.01
p 0.01
p 0.01
-0.02
-0.02
CSL-111
Placebo
CSL-111
Placebo
Tardif et al. JAMA 20072971675-82
18
Changes in coronary score on QCA
The ERASE trial
0
There was a significant interaction between study
treatment and baseline coronary score (p 0.03)
-0.02
CSL-111 40 mg/kg
Least square means (mm)
-0.04
p 0.03
-0.06
Placebo
-0.08
1.76 mm 1st quartile
2.00 mm Median
2.26 mm 3rd quartile
Coronary score at baseline
JAMA 20072971675-82
19
Lipoprotein metabolism
LDL receptor
Liver
B
C-II
ACAT
MTP
LPL
C-II
FC
CE
B
B
ApoB
27-hydroxylase
LPL
Oxidation
E
FC ? CE
E
ABCG1
IDL
CD36 SR-A
LDL
ACAT
VLDL
Bile
Cholesterol pool
CETP
PL TP
Intestine
ABC1
A-1
A-1
LCAT
Macrophage
FC
HL
Nascent HDL
ACAT
HDL
CE
IBAT
20
ILLUSTRATE Primary endpoint Change in Percent
Atheroma Volume
0,35
p 0.72
0,3
0,25
Changein percent atheroma volume
0,19
0,2
0,15
0,12
0,1
0,05
0
Atorvastatinmonotherapy
Torcetrapib-atorvastatin
LS Mean change
p value from ANCOVA
Nissen, Tardif, et al. N Engl J Med 2007
3561304-16
21
ILLUMINATE - Primary Endpoint Time to First
MCVE Kaplan-Meier Plot
Hazard Ratio 1.25
100
P0.001
98
Event Free ()
96
94
Atorvastatin (A) events 373 Torcetrapib/Atorvas
tatin (T/A) events 464
92
90
0
90
180
270
360
450
540
630
720
810
Days from Randomization
Major cardiovascular event CHD death, non-fatal
MI, stroke or hospitalization for unstable angina
NEJM 20073572109-2122
22
Post-hoc Exploratory Analyses in the
Torcetrapib/Atorvastatin Group
Hazard ratios for CHD Death or Non-Fatal MI by
quintile of on-trial HDL-C (referent group is
HDL-C lt 60 mg/dL stratum)
1.00
1.0
0.8
0.67
Plt0.05

0.57
0.6


CHD Death or Non-Fatal MI (Hazard Ratio)
0.47
0.43
0.4
0.2
0
lt60
60-70
71-80
81-93
gt93
Quintiles of HDL-C (mg/dL) at Month 3
Cox proportional hazard model adjusted for age,
gender and baseline HDL-C. Excludes 265 patients
with missing month 3 HDL-C. Preliminary analysis
initiated and authorised by P Barter and
conducted by Pfizer
23
Lack of Effect of Dalcetrapib vs Torcetrapib on
Aldosterone Secretion
24
The dal-HEART Programdalcetrapib HDL Evaluation,
Atherosclerosis Reverse cholesterol Transport

• The dal-HEART Program tests a novel hypothesis
  enhancing HDL efficacy through CETP modulation
  treats the underlying disease of atherosclerosis
  and will attenuate CV risk

dal-OUTCOMES1 15,600 patients recently
hospitalizedfor ACS To evaluate the effect of
dalcetrapib on CVoutcomes RECRUITMENT COMPLETE
dal-VESSEL2 450 patients withCHD or CHD
riskequivalent To evaluate the effect of
dalcetrapib onendothelial function and blood
pressure, measured by FMD and ABPM RECRUITMENT
COMPLETE
dal-PLAQUE3 130 patients withCHD To evaluate the
effect of dalcetrapib oninflammation, plaque
size and burden, measured by PET/CT and
MRI RECRUITMENT COMPLETE
dal-PLAQUE-24 900 patients withCAD To evaluate
the effect of dalcetrapib onatherosclerotic
disease progression, assessed by IVUS and carotid
B-mode ultrasound RECRUITING
1Schwartz et al. Am Heart J 2009158896-901
2http//clinicaltrials.gov/ct2/show/NCT00655538
Accessed April 1st 20103http//clinicaltrials.go
v/ct2/show/NCT00655473 Accessed April 1st 2010
4http//clinicaltrials.gov/ct2/show/NCT01059682
Accessed April 1st 2010 .
25
DAL-OUTCOMES Study DesignA double-blind,
randomized, placebo-controlled, parallel group,
multi-centre study in 15,600 patients recently
hospitalized for ACS
Double-blind
Until 1600 events occur but at least a minimum
of2 years
Single-blind Placebo Run-in 4-12 Weeks
Placebo
Visit 1
Visit 2
Visit 3randomization1 1
Follow up1st year every 3 monthsFollowing
years every 4 months
26
dal-PLAQUE-2 Study Design

• Objective to assess the effect of dalcetrapib
  versus placebo on atherosclerotic disease
  progression in patients with CAD
• A double-blind, randomized, placebo-controlled,
  parallel-group multicenter study in 900 patients
  with CAD

Double-blind
dalcetrapib 600 mg
Pre-rando phase Screening phase up to 8
weeksBaseline IVUS, QCA and CIMT
placebo
Background of contemporary evidence-basedtherapy
for CAD and CV risk factors
Primary endpoints IVUS and CIMT at 24
monthsOther assessments CIMT at 612 months
QCA at 24 months
Randomization
24 months
27
dal-PLAQUE-2Primary endpoints

• Co-primary endpoints
• Nominal change from baseline to study end in
  coronary percent atheroma volume (PAV) for all
  anatomically comparable slices in a 30-mm segment
  of the target coronary artery assessed by IVUS
• Rate of change from baseline to study end in
  intima-media thickness (IMT), defined as the per
  scan average of the far wall MEAN IMT values of
  the right and left common carotid, carotid bulb
  and internal carotid arterial segments as
  assessed by carotid B-mode ultrasound

28
British Journal of Pharmacology 2008 154765-773
29
Aortic valve area during treatment
Control
26

plt0.05 plt0.01

25
Treated

24
23
Aortic valve area (mm2)
22
21
20
19
18
Days
17
0
5
10
15
Stop cholesterol diet Vit D2 Start ApoA-I
mimetic peptide treatment
Br J Pharmacol 2008154765-773
30
The dual PPAR agonist aleglitazar and change in
HDL-C
Placebo
0.05
0.15
0.3
0.6
Pioglitazone
plt 0.0001
plt 0.0001
plt 0.0001
plt0.0014
p0.0312
? BL of HDL - C
n
54
54
53
54
57
54
31
14
Aleglitazar 150 µg Provides Beneficial Effects
onCardiovascular Biomarkers
PAI-1 (µg/mL)
hsCRP (mg/dL)
Fibrinogen (mg/dL)
Placebo Aleglitazar 150 µg Pioglitazone 45 mg
Fibrinogen baseline (mg/dL) 337.25 342.92 328.67
hsCRP baseline (mg/dL) 4.97 3.85 4.00
PAI-1 baseline (µg/mL) 22.26 22.67 22.30
32
ALECARDIO Study Design
Treatment Period at least 2.5 years
4 weeks
Run-in Period 26 ( 6) weeks
Follow-up
Aleglitazar 150 µg
Index ACS Event
Screened Patients
Placebo
Standard of care (diabetes and other CV risk
factors)
33
Potential therapeutic targets in CV diseases
34
VIA-2291 Decreases ex Vivo Whole Blood LTB4
Production from Baseline through Week 12
p lt 0.0001 ANCOVA Change from Baseline
160,000.00
140,000.00
Placebo
25mg
50mg
100mg
120,000.00
100,000.00
Mean LTB4 Production pg/ml
80,000.00
60,000.00

40,000.00

20,000.00

0.00
-2
0
2
4
6
8
10
12
14
Study Weeks
Error Bars represent 95 CI
Tardif et al. Circulation Cardiovasc Imaging
20103298-307
35
Significant Decrease in hs-CRP in VIA-2291 100 mg
Group versus Placebo at 24 Weeks
36
Change in non-calcified plaque volume and
patients with new plaque lesions on serial
coronary CT scans in the VIA-2291 groups versus
placebo at 24 Weeks
Plaque volume (mm3)
Pts with new plaques ()
7
30
5
25
p lt 0.01
p lt 0.01
3
20
1
15
-1
10
-3
5
-5
0
Placebo
All VIA-2291
Placebo
All VIA-2291
Tardif et al. Circulation Cardiovasc Imaging
20103298-307
37
Serp-1 Phase 2a Results Myocardial Enzymes
Troponin I Adjusted Geometric Mean
CK-MB Adjusted Geometric Mean
CK-MB (ng/ml)
Troponin I (ng/ml)

• Dose-dependent reduction in biomarkers of cardiac
  damage observed in the first 24 hours

Tardif et al. Circulation Cardiovasc
Interventions 2010 (in press)
38
Mortality by resting heart rate
Overall mortality
CV mortality
1.0
1.0
0.9
0.9
0.8
0.8
0.7
0.7
Cumulative survival
0.6
0.6
0.5
0.5
0
5
10
15
20
0
5
10
15
20
Years after enrolment
Years after enrolment
Adjusted for age, gender, hypertension, diabetes,
smoking, NDCV, ejection fraction, recreational
activity, medications including ?-blockers, plus
BMI for CV mortality
Diaz A, Bourassa MG, Guertin MC, Tardif JC. Eur
Heart J 2005 26 967-74
39
Ivabradine prevents endothelial dysfunction
associated with dyslipidemia in mice
RENAL
CEREBRAL
100
60
Wild type Dyslipidemia DLIvabradine
Wild type Dyslipidemia DLIvabradine
WT
90
WT
50

80

DL
DL


70
DL IVA
DL IVA
40
60

Dilation ( of maximal dilation)
Dilation ( of maximal dilation)

50
30


40


20
30
20
10
10
0
0
0.001
0.01
0.1
1
10
0.0001
0.001
0.01
0.1
1
10
ACh (?M)
ACh (?M)
Emax P lt 0.05 vs. to WT P lt 0.05 vs. to DL
pD2 P lt 0.05 vs. WT and DL
Drouin et al. Br J Pharmacol. 2008154749-757.
40
TED at trough of drug activity
INITIATIVE
Ivabradine vs atenolol
E (95 CI) P for non inferiority
n
Favors ATE
Favors IVA
IVA 5 mg bid vs ATE 50 mg od at M1
595 286
6.7 (-7.4 20.8) p lt 0.0001
IVA 7.5 mg bid vs ATE 100 mg od at M4
300 286
10.3 (-8.3 28.8) p lt 0.0001
IVA 10 mg bid vs ATE 100 mg od at M4
298 286
15.7 (-2.9 34.3) p lt 0.0001
0
- 35 sec
35 sec
Equivalence interval
Tardif JC et al. Eur Heart J 2005 262529-36
41
Ivabradine increases all ETT parameters in
patients already receiving beta-blockers
889 stable angina patients, 20 countries
Ivabradine atenolol
60
Plt0.001
Plt0.001
Placebo atenolol
50
40
Plt0.001
Plt0.001
Change in ETT criteria (s) at 4 months
30
20
10
0
Total exercise duration
Time to limiting angina
Time to angina onset
Time to 1mm ST segment depression
Evaluated at trough of drug activity
Tardif JC, et al. Eur Heart J. 200930540-548.
42
Effect of Ivabradine on hospitalisationfor fatal
and non-fatal MI (HR 70 bpm)
with hospitalisation for fatal and non-fatal MI
8
Hazard ratio 0.64 (0.49 0.84) RR -36
Placebo
6
P 0.001
4
2
Ivabradine
0
0
0.5
1
1.5
2
0
Years
Lancet Online August 31, 2008.
43
Primary composite endpoint (CV death or hospital
admission for worsening HF)
Cumulative frequency ()
40
HR 0.82 (0.750.90) P lt 0.0001
Placebo
18
30
Ivabradine
20
10
0
0
6
12
18
24
30
Months
Swedberg K, et al. Lancet. 2010online August 29.
44

• Population
• Outpatients with stable CAD without LVSD (EF gt
  40) or clinical signs of HF, with appropriate CV
  medication

Methods Events 4.5 per year in the placebo
group 1070 primary composite endpoints
(cardiovascular death and non fatal MI N 11
330, mean follow up 2.5 years RRR 18, a
bilateral 5, power 90
45
Canadian Atherosclerosis Imaging NetworkHearts
and Minds

• Stems from CIHRs 2007 consensus conference on
  imaging
• Five-year (2008-2013) 10M operating grant from
  CIHR
• Infrastructure grant 25M from CFI in June 2009
• Unique network combining in vivo imaging of
  vessel wall disease, end-organ disease, clinical
  and pathological endpoints
• Enables cross-sectional and longitudinal clinical
  studies of coronary, carotid and peripheral
  vascular beds
• International resource for studying the natural
  history of atherosclerosis and novel therapeutic
  interventions

46
Canadian Atherosclerosis Imaging Network
CAIN one imaging network for one entire country

• Imaging Core Analysis Laboratories (vascular)
• IVUS, 3-D US, QCA, MDCT, MRI, PET/CT, SPECT
• Imaging Core Analysis Laboratories (end-organ)
• Pan-canadian network of 45 partner sites
• Data coordinating and image repository center
  (MHICC)
• Genetic, pharmacogenomic and biomarker biobanks
• Proteomic and metabolomic analyses
• Tissue samples

47
CAINResearch themes

• Vascular biology of atherosclerotic plaque
• Vascular imaging technology development and
  assessment
• Translation to clinical research and clinical
  practice

Hearts and Minds
48
Canadian Atherosclerosis Imaging Network1-
Vascular Biology of Atherosclerotic Plaque

• Assess natural history of the plaque from 3 time
  points (MRI)
• Plaque initiation, progression and complication
• Evaluate inflammation, neovascularization and
  hemorrhage
• Determine the role of stimuli such as Db and
  hyperlipidemia
• Study the genetics of atheroma
• Assess the role of hypertension, hemodynamics and
  the interaction with blood constituents at the
  site of plaque rupture

49
Canadian Atherosclerosis Imaging Network2-
Vascular Imaging Technology Development and
Assessment

• Validation of developing technologies through
  quantitative histological examination of surgical
  specimens
• Includes
• Carotid ultrasound - surface morphology, plaque
  vulnerability and plaque volume
• 18FDG-PET metabolic activity and inflammation
• Ultrasound microbubbles plaque neovascularity

50
Canadian Atherosclerosis Imaging Network3-
Translation to Clinical Research/Practice

• Correlation of coronary and carotid
  atherosclerosis and their changes over time and
  links with clinical outcomes
• 2000 patients undergoing coronary angiography,
  IVUS (with virtual histology) and carotid
  ultrasound (IMT and plaques) at baseline and 24
  months
• 5-year follow-up for cardio/cerebrovascular
  events
• NIRS, PET/CT, MRI and microvascular substudies
• Genomic (including miRNAs) and biomarker biobanks
• Proteomic and metabolomic analyses
• Application of this knowledge and framework in
  clinical trials of novel anti-atherosclerotic
  agents

51
Canadian Atherosclerosis Imaging Network
CAIN one imaging network for one entire country

• www.canadianimagingnetwork.org
• therese.heinonen_at_mhicc.org

52
www.gainresearch.net