THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
0
5
10
15
20
25
30
1990 2020
MillionsofDeaths
fromCardiovascularCauses
Western countries
Non-Western (developing)
countries
5
9
6
19
DEATHS FROM CARDIOVASCULAR CAUSES,
WORLDWIDE, IN 1990 AND ESTIMATED FOR 2020
KS Reddy. NEJM 2004; 350:2438
Prevalence of Obesity & Diabetes in the U.S.
1990/19911990/1991 20002000
ejt 0901–120
Mokdad et al., JAMA 286:1195–1200, 2001Mokdad et al., JAMA 286:1195–1200, 2001
No DataNo Data < 4%< 4% 4%-6%4%-6% > 6%> 6%
No DataNo Data < 10%< 10% 10%-14%10%-14% 15%-19%15%-19% ≥≥ 20%20%
ObesityObesity
DiabetesDiabetes
0
10
20
30
40
50
Hypertri-
glycerinemia
Low
HDL
Hyper-
glycemia
Central
Obesity
Male
Female
Prevalence(%)
Hyper-
tension
METABOLIC ABNORMALITIES
AMERICAN ADOLESCENTS (12-19 Y)1
1
NHANES III - n=1960
S.D.de Ferranti et al., Circ 2004; 110:2494
THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA. Within This Context
Orlando, March 05, 2005
ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
2.Chronic Atherothrombosis
2. CAD Equivalents
HRAP- Subclinical
MRI / CT
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP – Risk Frs
CACS / CRP
1.Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
METHODS TO ASSESS PLAQUE VULNERABILITY
Intravascular ultrasound
Three-dimensional reconstruction
Ultrasound elastography
Intravascular ultrasound flow measurements
Virtual histology
Angiography
Direct visualization
Optical coherence tomography
RAMAN (near infrared) spectroscopy
Thermography
Computed tomography
Contrast
Ultrafast
Magnetic Resonance
Phase Contrast
Nuclear
Intravascular
B Meier. Heart 2004; 90:1395
HIGH RISK PLAQUES - HRP
HIGH RISK BLOOD - HRB
BURDEN OF ATHEROTHROMBOSIS DISEASE - BAD
a) HRP / HRB / BAD - Systemic
b) HRP – Abundant
c) HRP AND HRB – Regionally Different
Maseri A, Fuster V, Circulation 2003; 107: 2068
Fuster V, Kim RJ, Circulation 2005 (In Press)
ACS (N=198) & SYSTEMIC ENDOTHELIAL DYSFUNCTION (FBF) – 5 DAYS 1
ADJUSTED RISK FACTORS, CV EVENTS (DEATH, MI, STROKE)- Av 4 YRS
Fichtlscherer et al., Circ 2004; 110:1926 (Frankfurt)
70
80
90
100
0 365 730 1095 1460 1825
days of follow up
Proportionofpatients
withouCVevents(%)
Logrank test p<0.03
Acetylcholine - dose - response
70
80
90
100
0 365 730 1095 1460 1825
days of follow up
Proportionofpatients
withouCVevents(%)
Logrank test p<0.08
Sodium nitroprusside - dose - response
≥ 35.0 (1. quartile)
< 34.9 (2. quartile)
< 24.3 (3. quartile)
< 15.6 (4. quartile)
≥ 31.6 (1. quartile)
< 31.5 (2. quartile)
< 18.7 (4. quartile)
< 24.1 (3. quartile)
1
Improved response at 8 weeks adds to the prediction (ACH)
CAD (ACS 54%) - CULPRIT VESSEL / LESION – N=843
NON-STENOTIC YELLOW PLAQUES / THROMBUS – N=1253
0
20
40
60
80
100
1 2 3
Color Grade of Plaque
PrevalenceofThrombosis
*
† ‡
(%)
*P=.0003 vs grade 1. †P<.0001 vs grade 1. ‡P<.0001 vs grade 2
Y Ueda et al., AHJ 2004; 148:842 (Osaka)
CAROTID ACTIVE PLAQUES (ENDARTERECTOMY)
CAP RUPTURE AND CAP EROSION BY STUDY GROUP
ICTB (LG Spagnoli et al.) JAMA 2004; 292:1895 (Rome, Mineapolis, Mayo)
C Yuan et al Circ 2002;105:181 (Seattle) – MRI – Several Plaques
No. of Plaques (%) P Val
Ipsilat. Stroke With TIA Asymptom. Stroke vs Stroke vs TIA vs
(n=96) (n=91) (n=82) TIA Asympt. Asympt.
Thromb. active % 74.0 35.2 14.6 <.001 <.001 .002
Cap rupture 66.7 23.1 13.4 <.001 <.001 .004
Cap erosion 7.3 12.1 1.2 .51 .09 .03
THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomatic to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
Chronic Atherothrombosis
CHD Equivalents
HRAP- Subclinical
CT / MRI
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP – Risk Frs
CACS / CRP
Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
2.Chronic Atherothrombosis
2. CAD Equivalents
HRAP- Subclinical
MRI / CT
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP – Risk Frs
CACS / CRP
1.Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
x
Patient Transport In-hospital Reperfusion
2004
2014
0 1 2 3
A B C D
Hours
Methods of Speeding Time to Reperfusion:
A B C D
Media Campaign 911 Expansion Regionalization PCI-Eluted Stents
Patient Education Pre-hosp. Rx MI protocol New devices / demand
1. MI - TIME TO REPERFUSION – 2005, 2015
X New antithrombotics, Myoc-Imaging., AICD, RF modification
x
X
1. ACS – A PRE-HOSPITAL POLYPILL
V Fuster 2005
Definite ACS with
Possible ACS Definite ACS High risk/intervention
Tx R Bl. Tx R Bl. Tx R Bl
+ +
Clopidogrel - Like Clopidogrel - Like
+ +
Oral Fr Xa Inhib Oral Fr Xa Inhib
+ +
Statin Statin
+
Oral Antithrombin
2. CAD EQUIVALENTS, CHRONIC ATHEROTHROMBOSIS
AND A POLYPILL
• ASA
• CLOPIDOGREL
• STATINS / LDL- C (HDL- C)
• ACE INHIBITORS
• BEHAVIOR MODIFICATION
• INTERVENTION (PCI VS CABG): LIFE QUALITY VS QUANTITY
CHALLENGES: COMPLIANCE, COSTS
THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
Chronic Atherothrombosis
CHD Equivalents
HRAP- Subclinical
CT / MRI
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP – Risk Frs
CACS / CRP
Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
CHD RISK IN WOMEN - FRAMINGHAM SCORING (FRS) - 10 y
Age, y HDL cholesterol
< 35 -9 ≥ 60 -3
35-39 -4 50-59 0
40-44 0 45-49 1
45-49 3 35-44 2
50-54 6 < 35 5
55-59 7 Syst BP
60-64 8 < 120 -3
65-69 8 120-129 0
70-74 8 130-139 1
Cholesterol 140-149 2
< 160 -2 > 160 3
169-199 0 Diabetes
200-239 1 No 0
240-279 2 Yes 4
≥ 280 3 Smoking
No 0
Yes 2
Points
0
1
2
3
4
5
6
7
8
9
10
11
12
13
>14
Total CHD
(%)
2
3
4
5
7
8
10
13
16
20
25
31
37
45
> 53
Hard CHD
(%)
2
2
3
4
5
6
7
9
13
16
20
25
30
35
> 45
Grundy SM, Pasternak R, Greenland P, Smith S, Fuster V, Circ 1999; 100:1481
ATP III - Aggressive Rx: Framingham, Diabetes, Metab. Synd: obese, BP, HDL, TC, Gluc
- Physical inactivity JAMA 2001; 285:2475
Longitudinal View
Ca++
BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
Multi Slice Black Blood Imaging
Rapid Extended Coverage (REX) Turbo Spin Echo Technique
Mid heart Aorta- 12 slices
Descriptive
StatisticsParameter No Mean St dev Min Max Range
Age 100 54.3 20.55 9 87 78
Framingham
Score
44 7.27 3.99 1 20 19
10-Year Risk 42 0.118 0.069 0.03 0.31 0.28
Total Chol 84 199.9 57.3 105 366 261
LDL 83 120.7 54.5 46 303 257
HDL 84 53.2 16.8 20 100 80
TGC 83 139.3 122.9 32 891 859
HbA1C 20 6.75 1.57 4.7 10.9 6.2
BMI 82 25.98 5.2 15.1 42.5 27.3
BSA (m2
) 80 1.89 0.30 1.13 2.85 1.72
BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
Comparing Framingham Risk Factor Score and
Coronary Artery Disease (CAD)
0
2
4
6
8
10
12
14
NO YES
CAD
FraminghamScore
p = 0.447
BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
Comparing Wall Area (mm2
) and
Coronary Artery Disease (CAD)
Wall Area Aorta - CAD
100
150
200
250
300
NO YES
CAD
WADA
p <
0.001
*
BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
CAD (N=167) – STATIN vs NIACIN / STATIN
CIMT
-0.01
0
0.01
0.07
0.02
0.03
0.04
0.05
0.06
Placebo PlaceboER Niacin ER Niacin
No DM / MS DM / MS Present
ChangeinCIMT(mm±SEM)
ARBITER 2 (AJ Taylor et al.) Circ 2004; 110:3510
THE FREEDOM TRIAL
FUTURE REVASCULARIZATION EVALUATION
IN PATIENTS WITH DIABETES MELLITUS:
OPTIMAL MANAGEMENT OF MULTIVESSEL DISEASE
Risk Factor modification and Rx are critical.
1) BAD-MRI: Diabetics vs Non Diabetics
NHLBI 2005 (PI V Fuster)
THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
0
10
20
30
40
50
60
70
80
90
100
MRI (1st) Histology
Percent
66.3 64
23.7
5.1 5
20.3
6.3 9.4
CAROTID PLAQUE COMPOSITION
(AS PERCENTAGE OF THE WALL)
Fibrous Tissue
Lipid Necrotic Core
Loose Matrix
Calcification
T Saam et al., ATVB 2005; 25:234 – In Vivo (Seattle, Wash)
M Shinnar et al., ATVB 1999; 19:2756 - Ex Vivo (New York)
MRI (no fat sat)
MRI (fat sat)
LAD
Lumen
LV
RV
RVOT
LAD WallX-ray angiogram
LAD
~6 mm max wall thickness
Fayad ZA et al.
Circ. 2000;102;506-510
Eccentric (“lipid-rich”)
MRI - Plaque Composition
Baseline 24 months follow up
R Corti, J J Wentzel, Z A Fayad, J J Badimon, V Fuster 2005 (Subm)
A ) MRI-LIPID LOWERING (SIMVASTATIN 20 or 80 mg/d)
AND REGRESSION OF ATHEROSCLEROSIS
R Corti, ZA Fayad, V Fuster, et al. Circ. 2001;104:249-252
R Corti, V Fuster, ZA Fayad, JJ Badimon et al. Circ 2002;106:2884
Independent of dose, LDL-C < 100 mg/dl had more regresion
Corti, J J Wentzel, Z A Fayad, J J Badimon, V Fuster 2005 (Subm)
R Corti, J J Wentzel, Z A Fayad, J J Badimon, V Fuster 2005 (Subm) PROVE IT
- TIMI 22 (C Cannon et al.), NEJM 2004; 350:15 - Clinical
Abdominal
Aorta
Thoracic
Aorta Baseline MRI Repeat MRI
after 12 months
treatment
3 contiguous slice
(no interslice gap
Lower corner
of Th9
Upper corner
of L4
Total vascular area
Lumen area
Maximal
vessel wall thickness
Minimal
vessel wall thickness
Yonemura A; Momiyama Y; Fayad ZA et al. JACC 2005;45:733-42
MRI - ATHEROSCLEROSIS AORTA – ATORVASTATIN (12mo,N=40)
-60
-
40
-20
0
20
40
60
80
ΔVWA
Thoracic Aorta Abdominal Aorta(%)
-60 -50 -40 -30 -20 -10 0
ΔLDL-C (%)
r=0.64
P<0.001
-60 -50 -40 -30 -20 -10 0
ΔLDL-C (%)
-60
-
40
-20
0
20
40
60
80
ΔVWA
(%)
r=0.34
P<0.005
5-mg dose
20-mg dose
Yonemura A; Momiyama Y; Fayad ZA et al. JACC 2005;45:733-42
MRI - ATHEROSCLEROSIS AORTA – ATORVASTATIN (12mo,N=40)
Baseline 12 months
A)
B)
LDL-C(mg/dl) VWA(mm
C)
D)
316
↓
195
-38%
161
↓
107
-34%
110
↓
79
-28%
224
↓
202
-10%
20 mg/day
5 mg/day
230
↓
180
-20%
212
↓
130
-39%
95
↓
109
+15%
119
↓
129
+9%
20 mg/day
5 mg/day
Yonemura A; Momiyama Y; Fayad ZA et al. JACC 2005;45:733-42
B) MRI - HDL-Cholesterol
Rabbit / IV HDL, Apo E / HDL, Rabbit / PPAR-y /
Fenofibrate
1
10
J.X. Rong et al. Circ 2001;104:2447
High-chol. Diet
Simv. + PPAR-y
Badimon JJ, Badimon L, Fuster V, JCI 1990; 85:1234, 1990
Rong JX et al Circ 2001;104:2447
PPARs in Atherosclerosis:
Castrillo A et. al. J Clin Invest. 2004;114:1538.
A C Li et al. J Clin Invest 2004;114:1564
PPAR signaling pathways influence
macrophage gene expression and
foam cell formation
T2WPDWT1W
ClusterRGB
l
nc
iph
fc
lf
df
pvf
l
nc
iph
fc
lf
df
pvf
l-lumen
nc-necrotic core
iph-intra plaque
hemorrhage
fc-fibrocellular
tissue
df-dense fibrous
tissue
lf=loose fibrous
tissue
pvf-perivascular
fat
Itskovich VV, Samber D, Mani V, et al Magn Reson Med 2004; 52: 515
In-Vivo Cluster Analysis for Plaque Characterization
THE FREEDOM TRIAL
FUTURE REVASCULARIZATION EVALUATION
IN PATIENTS WITH DIABETES MELLITUS:OPTIMAL
MANAGEMENT OF MULTIVESSEL DISEASE
2) MRI-Diabetics: Reversibility, Statins-PPAR
NHLBI 2005 (PI V Fuster)
THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
Cell & Molecular MRI Targets
In Atherothrombotic Plaques
Lipinski MJ, Fuster V, Fisher EA, Fayad ZA, Nature Cardiov. Med. 2004;1:1
Targeted Contrast Agent - Approaches
Choudhury RP; Fuster V; Fayad ZA Nature Drug Disc. 2004;3:1
Lipid Rich Atherosclerotic Rabbit 24h
Post Gadofluorine
n=10 NZW
Atherosclerotic rabbits
No Enhancement in
Controls (n=6)
Pre Contrast
24 H Post
Gadofluorine
Sirol, M et. al. Circulation 2004; 109: 2890 – AHA 2004 -
Pre-contrast 48 hours post-contrast1 hr post-contrast 24 hr post-contrast
20x
lumen
wall
40x
Frias JC, Fayad ZA, Fuster V et al. ISMRM 2004
rHDL-Gd-DTPA-DMPE-NBD conjugate (green)
rHDL-Gd-DTPA-DMPE
apoE-KO mice, 4.36 mmol/kg, 9.4T MRM
In Vivo Detection of Macrophages
in Human Carotid Atheroma
Use of Post-Ultrasmall Superparamagnetic Particles of Iron (USPIO) MRI
Pre-USPIO
Post-USPIO
24h
Post-USPIO
36h
Areas of USPIO accumulation (Pearls staining, b)
colocalizing with
areas of high macrophage content (MAC 387 stain, c)
in the fibrous cap region
Trivedi AR et al. Stroke 2004; 35: 1631
Pre Contrast
Post Contrast
3 day old thrombus
Crush injured left
carotid artery
30 minutes
P.I.
60 minutes P.I.
Molecular Imaging of Fibrin with MR
Chronic Rabbit Model
Thrombus
in Left CCA
fibrin MRA
Fayad ZA
Imaging Science Laboratories
Control
H&E
Sirol M. et al. Circulation 2005 (In Press)
Diabetes and PAD - Proposed Sequence for an
Integrated Plaque (IP)-MRI Diagnostic Protocol
Combination of multi-weighted, post-Gadolinium and post-USPIO imaging
Dellegrottaglie S, Mani V, Fayad Z, Moreno P, Fuster V, Rajagopalan S. 2005
PDW MRI of the
Superficial femoral
artery
THE FREEDOM TRIAL
FUTURE REVASCULARIZATION EVALUATION
IN PATIENTS WITH DIABETES MELLITUS:
OPTIMAL MANAGEMENT OF MULTIVESSEL DISEASE
3) MRI - Contrast Enhanced PAD
NHLBI 2005 (PI V Fuster)
THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
Chronic Atherothrombosis
CHD Equivalents
HRAP- Subclinical
CT / MRI
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP- Risk Frs
CACS / CRP
Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
CHD RISK IN WOMEN - FRAMINGHAM SCORING (FRS) - 10 y
Age, y HDL cholesterol
< 35 -9 ≥ 60 -3
35-39 -4 50-59 0
40-44 0 45-49 1
45-49 3 35-44 2
50-54 6 < 35 5
55-59 7 Syst BP
60-64 8 < 120 -3
65-69 8 120-129 0
70-74 8 130-139 1
Cholesterol 140-149 2
< 160 -2 > 160 3
169-199 0 Diabetes
200-239 1 No 0
240-279 2 Yes 4
≥ 280 3 Smoking
No 0
Yes 2
Points
0
1
2
3
4
5
6
7
8
9
10
11
12
13
>14
Total CHD
(%)
2
3
4
5
7
8
10
13
16
20
25
31
37
45
> 53
Hard CHD
(%)
2
2
3
4
5
6
7
9
13
16
20
25
30
35
> 45
Grundy SM, Pasternak R, Greenland P, Smith S, Fuster V, Circ 1999; 100:1481
ATP III - Aggressive Rx: Framingham, Diabetes, Metab. Synd: obese, BP, HDL, TC, Gluc
- Physical inactivity JAMA 2001; 285:2475

Dr fuster's slides part i

  • 1.
    THE EPIDEMIC OFCVD – NEED FOR NEW APPROACHES Epidemiology and Change in Emphasis - From the High Risk Plaque to the High Risk Symptomatic Patient - From the High Risk Asymptomati to the Intermediate and Low Risk Patient HRSP - Therapeutic Polypill & Single Pill HRAP - BAD, Diagnostic MR Imaging - BAD, Diagnostic & Rx - MR Plaque Composition - BAD, Diagnostic Molecular MR Contrast Enhanced, IRAP - Diagnostic CACS & CRP Biomarkers LRAP - Government, Polymeal, Children SHAPE & AEHA. Orlando, March 05, 2005
  • 2.
    0 5 10 15 20 25 30 1990 2020 MillionsofDeaths fromCardiovascularCauses Western countries Non-Western(developing) countries 5 9 6 19 DEATHS FROM CARDIOVASCULAR CAUSES, WORLDWIDE, IN 1990 AND ESTIMATED FOR 2020 KS Reddy. NEJM 2004; 350:2438
  • 3.
    Prevalence of Obesity& Diabetes in the U.S. 1990/19911990/1991 20002000 ejt 0901–120 Mokdad et al., JAMA 286:1195–1200, 2001Mokdad et al., JAMA 286:1195–1200, 2001 No DataNo Data < 4%< 4% 4%-6%4%-6% > 6%> 6% No DataNo Data < 10%< 10% 10%-14%10%-14% 15%-19%15%-19% ≥≥ 20%20% ObesityObesity DiabetesDiabetes
  • 4.
  • 5.
    THE EPIDEMIC OFCVD – NEED FOR NEW APPROACHES Epidemiology and Change in Emphasis - From the High Risk Plaque to the High Risk Symptomatic Patient - From the High Risk Asymptomati to the Intermediate and Low Risk Patient HRSP - Therapeutic Polypill & Single Pill HRAP - BAD, Diagnostic MR Imaging - BAD, Diagnostic & Rx - MR Plaque Composition - BAD, Diagnostic Molecular MR Contrast Enhanced, IRAP - Diagnostic CACS & CRP Biomarkers LRAP - Government, Polymeal, Children SHAPE & AEHA. Within This Context Orlando, March 05, 2005
  • 7.
    ATHEROTHROMBOSIS: APPROACH IN2005 Aggressive Intervention3 Effective Prevention1 2.Chronic Atherothrombosis 2. CAD Equivalents HRAP- Subclinical MRI / CT Low Risk Modified from V Fuster, Circulation 1999; 99:1132 IRAP – Risk Frs CACS / CRP 1.Acute Coronary Syndromes Early Detection 2 HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y LOW RISK: FRS - < 0.5%y - < 5% 10 y
  • 8.
    METHODS TO ASSESSPLAQUE VULNERABILITY Intravascular ultrasound Three-dimensional reconstruction Ultrasound elastography Intravascular ultrasound flow measurements Virtual histology Angiography Direct visualization Optical coherence tomography RAMAN (near infrared) spectroscopy Thermography Computed tomography Contrast Ultrafast Magnetic Resonance Phase Contrast Nuclear Intravascular B Meier. Heart 2004; 90:1395
  • 9.
    HIGH RISK PLAQUES- HRP HIGH RISK BLOOD - HRB BURDEN OF ATHEROTHROMBOSIS DISEASE - BAD a) HRP / HRB / BAD - Systemic b) HRP – Abundant c) HRP AND HRB – Regionally Different Maseri A, Fuster V, Circulation 2003; 107: 2068 Fuster V, Kim RJ, Circulation 2005 (In Press)
  • 10.
    ACS (N=198) &SYSTEMIC ENDOTHELIAL DYSFUNCTION (FBF) – 5 DAYS 1 ADJUSTED RISK FACTORS, CV EVENTS (DEATH, MI, STROKE)- Av 4 YRS Fichtlscherer et al., Circ 2004; 110:1926 (Frankfurt) 70 80 90 100 0 365 730 1095 1460 1825 days of follow up Proportionofpatients withouCVevents(%) Logrank test p<0.03 Acetylcholine - dose - response 70 80 90 100 0 365 730 1095 1460 1825 days of follow up Proportionofpatients withouCVevents(%) Logrank test p<0.08 Sodium nitroprusside - dose - response ≥ 35.0 (1. quartile) < 34.9 (2. quartile) < 24.3 (3. quartile) < 15.6 (4. quartile) ≥ 31.6 (1. quartile) < 31.5 (2. quartile) < 18.7 (4. quartile) < 24.1 (3. quartile) 1 Improved response at 8 weeks adds to the prediction (ACH)
  • 11.
    CAD (ACS 54%)- CULPRIT VESSEL / LESION – N=843 NON-STENOTIC YELLOW PLAQUES / THROMBUS – N=1253 0 20 40 60 80 100 1 2 3 Color Grade of Plaque PrevalenceofThrombosis * † ‡ (%) *P=.0003 vs grade 1. †P<.0001 vs grade 1. ‡P<.0001 vs grade 2 Y Ueda et al., AHJ 2004; 148:842 (Osaka)
  • 12.
    CAROTID ACTIVE PLAQUES(ENDARTERECTOMY) CAP RUPTURE AND CAP EROSION BY STUDY GROUP ICTB (LG Spagnoli et al.) JAMA 2004; 292:1895 (Rome, Mineapolis, Mayo) C Yuan et al Circ 2002;105:181 (Seattle) – MRI – Several Plaques No. of Plaques (%) P Val Ipsilat. Stroke With TIA Asymptom. Stroke vs Stroke vs TIA vs (n=96) (n=91) (n=82) TIA Asympt. Asympt. Thromb. active % 74.0 35.2 14.6 <.001 <.001 .002 Cap rupture 66.7 23.1 13.4 <.001 <.001 .004 Cap erosion 7.3 12.1 1.2 .51 .09 .03
  • 14.
    THE EPIDEMIC OFCVD – NEED FOR NEW APPROACHES Epidemiology and Change in Emphasis - From the High Risk Plaque to the High Risk Symptomatic Patient - From the High Risk Asymptomatic to the Intermediate and Low Risk Patient HRSP - Therapeutic Polypill & Single Pill HRAP - BAD, Diagnostic MR Imaging - BAD, Diagnostic & Rx - MR Plaque Composition - BAD, Diagnostic Molecular MR Contrast Enhanced, IRAP - Diagnostic CACS & CRP Biomarkers LRAP - Government, Polymeal, Children SHAPE & AEHA. Orlando, March 05, 2005
  • 15.
    ATHEROTHROMBOSIS: APPROACH IN2005 Aggressive Intervention3 Effective Prevention1 Chronic Atherothrombosis CHD Equivalents HRAP- Subclinical CT / MRI Low Risk Modified from V Fuster, Circulation 1999; 99:1132 IRAP – Risk Frs CACS / CRP Acute Coronary Syndromes Early Detection 2 HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y LOW RISK: FRS - < 0.5%y - < 5% 10 y
  • 16.
    THE EPIDEMIC OFCVD – NEED FOR NEW APPROACHES Epidemiology and Change in Emphasis - From the High Risk Plaque to the High Risk Symptomatic Patient - From the High Risk Asymptomati to the Intermediate and Low Risk Patient HRSP - Therapeutic Polypill & Single Pill HRAP - BAD, Diagnostic MR Imaging - BAD, Diagnostic & Rx - MR Plaque Composition - BAD, Diagnostic Molecular MR Contrast Enhanced, IRAP - Diagnostic CACS & CRP Biomarkers LRAP - Government, Polymeal, Children SHAPE & AEHA. Orlando, March 05, 2005
  • 17.
    ATHEROTHROMBOSIS: APPROACH IN2005 Aggressive Intervention3 Effective Prevention1 2.Chronic Atherothrombosis 2. CAD Equivalents HRAP- Subclinical MRI / CT Low Risk Modified from V Fuster, Circulation 1999; 99:1132 IRAP – Risk Frs CACS / CRP 1.Acute Coronary Syndromes Early Detection 2 HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y LOW RISK: FRS - < 0.5%y - < 5% 10 y
  • 18.
    x Patient Transport In-hospitalReperfusion 2004 2014 0 1 2 3 A B C D Hours Methods of Speeding Time to Reperfusion: A B C D Media Campaign 911 Expansion Regionalization PCI-Eluted Stents Patient Education Pre-hosp. Rx MI protocol New devices / demand 1. MI - TIME TO REPERFUSION – 2005, 2015 X New antithrombotics, Myoc-Imaging., AICD, RF modification x X
  • 19.
    1. ACS –A PRE-HOSPITAL POLYPILL V Fuster 2005 Definite ACS with Possible ACS Definite ACS High risk/intervention Tx R Bl. Tx R Bl. Tx R Bl + + Clopidogrel - Like Clopidogrel - Like + + Oral Fr Xa Inhib Oral Fr Xa Inhib + + Statin Statin + Oral Antithrombin
  • 20.
    2. CAD EQUIVALENTS,CHRONIC ATHEROTHROMBOSIS AND A POLYPILL • ASA • CLOPIDOGREL • STATINS / LDL- C (HDL- C) • ACE INHIBITORS • BEHAVIOR MODIFICATION • INTERVENTION (PCI VS CABG): LIFE QUALITY VS QUANTITY CHALLENGES: COMPLIANCE, COSTS
  • 21.
    THE EPIDEMIC OFCVD – NEED FOR NEW APPROACHES Epidemiology and Change in Emphasis - From the High Risk Plaque to the High Risk Symptomatic Patient - From the High Risk Asymptomati to the Intermediate and Low Risk Patient HRSP - Therapeutic Polypill & Single Pill HRAP - BAD, Diagnostic MR Imaging - BAD, Diagnostic & Rx - MR Plaque Composition - BAD, Diagnostic Molecular MR Contrast Enhanced, IRAP - Diagnostic CACS & CRP Biomarkers LRAP - Government, Polymeal, Children SHAPE & AEHA. Orlando, March 05, 2005
  • 22.
    ATHEROTHROMBOSIS: APPROACH IN2005 Aggressive Intervention3 Effective Prevention1 Chronic Atherothrombosis CHD Equivalents HRAP- Subclinical CT / MRI Low Risk Modified from V Fuster, Circulation 1999; 99:1132 IRAP – Risk Frs CACS / CRP Acute Coronary Syndromes Early Detection 2 HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y LOW RISK: FRS - < 0.5%y - < 5% 10 y
  • 23.
    CHD RISK INWOMEN - FRAMINGHAM SCORING (FRS) - 10 y Age, y HDL cholesterol < 35 -9 ≥ 60 -3 35-39 -4 50-59 0 40-44 0 45-49 1 45-49 3 35-44 2 50-54 6 < 35 5 55-59 7 Syst BP 60-64 8 < 120 -3 65-69 8 120-129 0 70-74 8 130-139 1 Cholesterol 140-149 2 < 160 -2 > 160 3 169-199 0 Diabetes 200-239 1 No 0 240-279 2 Yes 4 ≥ 280 3 Smoking No 0 Yes 2 Points 0 1 2 3 4 5 6 7 8 9 10 11 12 13 >14 Total CHD (%) 2 3 4 5 7 8 10 13 16 20 25 31 37 45 > 53 Hard CHD (%) 2 2 3 4 5 6 7 9 13 16 20 25 30 35 > 45 Grundy SM, Pasternak R, Greenland P, Smith S, Fuster V, Circ 1999; 100:1481 ATP III - Aggressive Rx: Framingham, Diabetes, Metab. Synd: obese, BP, HDL, TC, Gluc - Physical inactivity JAMA 2001; 285:2475
  • 24.
    Longitudinal View Ca++ BAD (FayadZA, Mani V, Fuster V et al.) 2005 Multi Slice Black Blood Imaging Rapid Extended Coverage (REX) Turbo Spin Echo Technique Mid heart Aorta- 12 slices
  • 25.
    Descriptive StatisticsParameter No MeanSt dev Min Max Range Age 100 54.3 20.55 9 87 78 Framingham Score 44 7.27 3.99 1 20 19 10-Year Risk 42 0.118 0.069 0.03 0.31 0.28 Total Chol 84 199.9 57.3 105 366 261 LDL 83 120.7 54.5 46 303 257 HDL 84 53.2 16.8 20 100 80 TGC 83 139.3 122.9 32 891 859 HbA1C 20 6.75 1.57 4.7 10.9 6.2 BMI 82 25.98 5.2 15.1 42.5 27.3 BSA (m2 ) 80 1.89 0.30 1.13 2.85 1.72 BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
  • 26.
    Comparing Framingham RiskFactor Score and Coronary Artery Disease (CAD) 0 2 4 6 8 10 12 14 NO YES CAD FraminghamScore p = 0.447 BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
  • 27.
    Comparing Wall Area(mm2 ) and Coronary Artery Disease (CAD) Wall Area Aorta - CAD 100 150 200 250 300 NO YES CAD WADA p < 0.001 * BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
  • 28.
    CAD (N=167) –STATIN vs NIACIN / STATIN CIMT -0.01 0 0.01 0.07 0.02 0.03 0.04 0.05 0.06 Placebo PlaceboER Niacin ER Niacin No DM / MS DM / MS Present ChangeinCIMT(mm±SEM) ARBITER 2 (AJ Taylor et al.) Circ 2004; 110:3510
  • 29.
    THE FREEDOM TRIAL FUTUREREVASCULARIZATION EVALUATION IN PATIENTS WITH DIABETES MELLITUS: OPTIMAL MANAGEMENT OF MULTIVESSEL DISEASE Risk Factor modification and Rx are critical. 1) BAD-MRI: Diabetics vs Non Diabetics NHLBI 2005 (PI V Fuster)
  • 30.
    THE EPIDEMIC OFCVD – NEED FOR NEW APPROACHES Epidemiology and Change in Emphasis - From the High Risk Plaque to the High Risk Symptomatic Patient - From the High Risk Asymptomati to the Intermediate and Low Risk Patient HRSP - Therapeutic Polypill & Single Pill HRAP - BAD, Diagnostic MR Imaging - BAD, Diagnostic & Rx - MR Plaque Composition - BAD, Diagnostic Molecular MR Contrast Enhanced, IRAP - Diagnostic CACS & CRP Biomarkers LRAP - Government, Polymeal, Children SHAPE & AEHA. Orlando, March 05, 2005
  • 31.
    0 10 20 30 40 50 60 70 80 90 100 MRI (1st) Histology Percent 66.364 23.7 5.1 5 20.3 6.3 9.4 CAROTID PLAQUE COMPOSITION (AS PERCENTAGE OF THE WALL) Fibrous Tissue Lipid Necrotic Core Loose Matrix Calcification T Saam et al., ATVB 2005; 25:234 – In Vivo (Seattle, Wash) M Shinnar et al., ATVB 1999; 19:2756 - Ex Vivo (New York)
  • 32.
    MRI (no fatsat) MRI (fat sat) LAD Lumen LV RV RVOT LAD WallX-ray angiogram LAD ~6 mm max wall thickness Fayad ZA et al. Circ. 2000;102;506-510 Eccentric (“lipid-rich”) MRI - Plaque Composition
  • 33.
    Baseline 24 monthsfollow up R Corti, J J Wentzel, Z A Fayad, J J Badimon, V Fuster 2005 (Subm) A ) MRI-LIPID LOWERING (SIMVASTATIN 20 or 80 mg/d) AND REGRESSION OF ATHEROSCLEROSIS R Corti, ZA Fayad, V Fuster, et al. Circ. 2001;104:249-252 R Corti, V Fuster, ZA Fayad, JJ Badimon et al. Circ 2002;106:2884
  • 34.
    Independent of dose,LDL-C < 100 mg/dl had more regresion Corti, J J Wentzel, Z A Fayad, J J Badimon, V Fuster 2005 (Subm)
  • 35.
    R Corti, JJ Wentzel, Z A Fayad, J J Badimon, V Fuster 2005 (Subm) PROVE IT - TIMI 22 (C Cannon et al.), NEJM 2004; 350:15 - Clinical
  • 36.
    Abdominal Aorta Thoracic Aorta Baseline MRIRepeat MRI after 12 months treatment 3 contiguous slice (no interslice gap Lower corner of Th9 Upper corner of L4 Total vascular area Lumen area Maximal vessel wall thickness Minimal vessel wall thickness Yonemura A; Momiyama Y; Fayad ZA et al. JACC 2005;45:733-42 MRI - ATHEROSCLEROSIS AORTA – ATORVASTATIN (12mo,N=40)
  • 37.
    -60 - 40 -20 0 20 40 60 80 ΔVWA Thoracic Aorta AbdominalAorta(%) -60 -50 -40 -30 -20 -10 0 ΔLDL-C (%) r=0.64 P<0.001 -60 -50 -40 -30 -20 -10 0 ΔLDL-C (%) -60 - 40 -20 0 20 40 60 80 ΔVWA (%) r=0.34 P<0.005 5-mg dose 20-mg dose Yonemura A; Momiyama Y; Fayad ZA et al. JACC 2005;45:733-42 MRI - ATHEROSCLEROSIS AORTA – ATORVASTATIN (12mo,N=40)
  • 38.
    Baseline 12 months A) B) LDL-C(mg/dl)VWA(mm C) D) 316 ↓ 195 -38% 161 ↓ 107 -34% 110 ↓ 79 -28% 224 ↓ 202 -10% 20 mg/day 5 mg/day 230 ↓ 180 -20% 212 ↓ 130 -39% 95 ↓ 109 +15% 119 ↓ 129 +9% 20 mg/day 5 mg/day Yonemura A; Momiyama Y; Fayad ZA et al. JACC 2005;45:733-42
  • 39.
    B) MRI -HDL-Cholesterol Rabbit / IV HDL, Apo E / HDL, Rabbit / PPAR-y / Fenofibrate 1 10 J.X. Rong et al. Circ 2001;104:2447 High-chol. Diet Simv. + PPAR-y Badimon JJ, Badimon L, Fuster V, JCI 1990; 85:1234, 1990 Rong JX et al Circ 2001;104:2447
  • 40.
    PPARs in Atherosclerosis: CastrilloA et. al. J Clin Invest. 2004;114:1538. A C Li et al. J Clin Invest 2004;114:1564 PPAR signaling pathways influence macrophage gene expression and foam cell formation
  • 41.
    T2WPDWT1W ClusterRGB l nc iph fc lf df pvf l nc iph fc lf df pvf l-lumen nc-necrotic core iph-intra plaque hemorrhage fc-fibrocellular tissue df-densefibrous tissue lf=loose fibrous tissue pvf-perivascular fat Itskovich VV, Samber D, Mani V, et al Magn Reson Med 2004; 52: 515 In-Vivo Cluster Analysis for Plaque Characterization
  • 42.
    THE FREEDOM TRIAL FUTUREREVASCULARIZATION EVALUATION IN PATIENTS WITH DIABETES MELLITUS:OPTIMAL MANAGEMENT OF MULTIVESSEL DISEASE 2) MRI-Diabetics: Reversibility, Statins-PPAR NHLBI 2005 (PI V Fuster)
  • 43.
    THE EPIDEMIC OFCVD – NEED FOR NEW APPROACHES Epidemiology and Change in Emphasis - From the High Risk Plaque to the High Risk Symptomatic Patient - From the High Risk Asymptomati to the Intermediate and Low Risk Patient HRSP - Therapeutic Polypill & Single Pill HRAP - BAD, Diagnostic MR Imaging - BAD, Diagnostic & Rx - MR Plaque Composition - BAD, Diagnostic Molecular MR Contrast Enhanced, IRAP - Diagnostic CACS & CRP Biomarkers LRAP - Government, Polymeal, Children SHAPE & AEHA. Orlando, March 05, 2005
  • 44.
    Cell & MolecularMRI Targets In Atherothrombotic Plaques Lipinski MJ, Fuster V, Fisher EA, Fayad ZA, Nature Cardiov. Med. 2004;1:1
  • 45.
    Targeted Contrast Agent- Approaches Choudhury RP; Fuster V; Fayad ZA Nature Drug Disc. 2004;3:1
  • 46.
    Lipid Rich AtheroscleroticRabbit 24h Post Gadofluorine n=10 NZW Atherosclerotic rabbits No Enhancement in Controls (n=6) Pre Contrast 24 H Post Gadofluorine Sirol, M et. al. Circulation 2004; 109: 2890 – AHA 2004 -
  • 47.
    Pre-contrast 48 hourspost-contrast1 hr post-contrast 24 hr post-contrast 20x lumen wall 40x Frias JC, Fayad ZA, Fuster V et al. ISMRM 2004 rHDL-Gd-DTPA-DMPE-NBD conjugate (green) rHDL-Gd-DTPA-DMPE apoE-KO mice, 4.36 mmol/kg, 9.4T MRM
  • 48.
    In Vivo Detectionof Macrophages in Human Carotid Atheroma Use of Post-Ultrasmall Superparamagnetic Particles of Iron (USPIO) MRI Pre-USPIO Post-USPIO 24h Post-USPIO 36h Areas of USPIO accumulation (Pearls staining, b) colocalizing with areas of high macrophage content (MAC 387 stain, c) in the fibrous cap region Trivedi AR et al. Stroke 2004; 35: 1631
  • 49.
    Pre Contrast Post Contrast 3day old thrombus Crush injured left carotid artery 30 minutes P.I. 60 minutes P.I. Molecular Imaging of Fibrin with MR Chronic Rabbit Model Thrombus in Left CCA fibrin MRA Fayad ZA Imaging Science Laboratories Control H&E Sirol M. et al. Circulation 2005 (In Press)
  • 50.
    Diabetes and PAD- Proposed Sequence for an Integrated Plaque (IP)-MRI Diagnostic Protocol Combination of multi-weighted, post-Gadolinium and post-USPIO imaging Dellegrottaglie S, Mani V, Fayad Z, Moreno P, Fuster V, Rajagopalan S. 2005 PDW MRI of the Superficial femoral artery
  • 51.
    THE FREEDOM TRIAL FUTUREREVASCULARIZATION EVALUATION IN PATIENTS WITH DIABETES MELLITUS: OPTIMAL MANAGEMENT OF MULTIVESSEL DISEASE 3) MRI - Contrast Enhanced PAD NHLBI 2005 (PI V Fuster)
  • 52.
    THE EPIDEMIC OFCVD – NEED FOR NEW APPROACHES Epidemiology and Change in Emphasis - From the High Risk Plaque to the High Risk Symptomatic Patient - From the High Risk Asymptomati to the Intermediate and Low Risk Patient HRSP - Therapeutic Polypill & Single Pill HRAP - BAD, Diagnostic MR Imaging - BAD, Diagnostic & Rx - MR Plaque Composition - BAD, Diagnostic Molecular MR Contrast Enhanced, IRAP - Diagnostic CACS & CRP Biomarkers LRAP - Government, Polymeal, Children SHAPE & AEHA. Orlando, March 05, 2005
  • 53.
    ATHEROTHROMBOSIS: APPROACH IN2005 Aggressive Intervention3 Effective Prevention1 Chronic Atherothrombosis CHD Equivalents HRAP- Subclinical CT / MRI Low Risk Modified from V Fuster, Circulation 1999; 99:1132 IRAP- Risk Frs CACS / CRP Acute Coronary Syndromes Early Detection 2 HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y LOW RISK: FRS - < 0.5%y - < 5% 10 y
  • 54.
    CHD RISK INWOMEN - FRAMINGHAM SCORING (FRS) - 10 y Age, y HDL cholesterol < 35 -9 ≥ 60 -3 35-39 -4 50-59 0 40-44 0 45-49 1 45-49 3 35-44 2 50-54 6 < 35 5 55-59 7 Syst BP 60-64 8 < 120 -3 65-69 8 120-129 0 70-74 8 130-139 1 Cholesterol 140-149 2 < 160 -2 > 160 3 169-199 0 Diabetes 200-239 1 No 0 240-279 2 Yes 4 ≥ 280 3 Smoking No 0 Yes 2 Points 0 1 2 3 4 5 6 7 8 9 10 11 12 13 >14 Total CHD (%) 2 3 4 5 7 8 10 13 16 20 25 31 37 45 > 53 Hard CHD (%) 2 2 3 4 5 6 7 9 13 16 20 25 30 35 > 45 Grundy SM, Pasternak R, Greenland P, Smith S, Fuster V, Circ 1999; 100:1481 ATP III - Aggressive Rx: Framingham, Diabetes, Metab. Synd: obese, BP, HDL, TC, Gluc - Physical inactivity JAMA 2001; 285:2475

Editor's Notes

  • #25 DLMP
  • #33 .
  • #49 Post-USPIO MRI can be used to identify macrophages accumulation within the plaque in vivo