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Erling Falk: CV
SalarySalary Cardiovascular pathologist
Aarhus University, Denmark
Main interestMain interest Vulnerable p...
Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72
Risk factorsRisk factors
• S-cholS-chol ≥≥240 mg/dl240 mg/dl
• BP >140/90BP >140/90
• SmokingSmoking
• DiabetesDiabetes
≥1...
Risk factorsRisk factors
• S-cholS-chol ≥≥240 mg/dl240 mg/dl
• BP >140/90BP >140/90
• SmokingSmoking
• DiabetesDiabetes
≥1...
Nearly all adult Americans have
≥1 risk factor, regardless of CHD
JAMA 2003;290:891-7
Predictive power of ≥1 risk factor for CHD
PLR <2.0:
Low positive predictive power AM Weissler.
JAMA 2004;291:299-300
BMJ 1999;319:1562-5
Relative distributions of risk factors
22 000 men, 10-year follow-up22 000 men, 10-year follow-up
Wald NJ, Law MR.Wald NJ,...
Relative distributions of risk factors
22 000 men, 10-year follow-up22 000 men, 10-year follow-up
Wald NJ, Law MR.Wald NJ,...
Pepe et al. Am J Epidemiol 2004;159:882-90Pepe et al. Am J Epidemiol 2004;159:882-90
Pepe et al. Am J Epidemiol 2004;159:882-90Pepe et al. Am J Epidemiol 2004;159:882-90
Eradication of Heart Attack
dream or reality?dream or reality?
• Most heart attack is preventable
Heart attack remains the...
• Most heart attack is preventable
• Heart attack remains the #1 killer
Traditional approach has failed
Eradication of Hea...
• Most heart attack is preventable
• Heart attack remains the #1 killer
Traditional approach has failedTraditional approac...
• Most heart attack is preventable
• Heart attack remains the #1 killer
Traditional approach has failedTraditional approac...
Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72
Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72
Vulne...
Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72
Vulne...
Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72
Vulne...
Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72
Vulne...
Table 1. The most common polymorphisms in the hemostatic
system and their associations with intermediate phenotypes and
at...
Figure 1. A schematic of the ECGI procedure.A schematic of the ECGI procedure.
(a) ECG electrode vest for obtaining body s...
Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72
Vulne...
Lancet 2004
364:937-52
Lancet 2004
364:937-52
Major risk factors account for MI!
but they are ”useless” for prediction!
Why?
Individual vulnerabi...
Lancet 2004
364:937-52
Major risk factors account for MI!
but they are ”useless” for prediction!
Why?Why?
Individual vulne...
Lancet 2004
364:937-52
Major risk factors account for MI!
but they are ”useless” for prediction!
Why?Why?
Individual susce...
Atherosclerosis and CHD
risk factors vs susceptibilityrisk factors vs susceptibility
Sir Winston Churchill, 91Sir Winston Churchill, 91  Jim Fixx, 53Jim Fixx, 53 ♥♥
J RumbergerJ Rumberger
Atherosclerosis ...
The 1st
SHAPE Task Force Advisory Meeting, Aug 6-7, 2004, Santa MonicaSanta Monica
Photo by: Asif Ali
… just a few …
From: Morteza Naghavi, M.D. [mailto:mn2@vp.org]
Sent: Thu 2/24/2005 7:47 AM
To: Erling Falk; John Rumberger; Kaul, Sanjay ...
Risk assessment and stratification
Risk factor/office-basedNCEP
, 10-year risk
Intermediate Risk
10-20%
High Risk
>20%
Lo...
Risk assessment and stratification
Risk factor/office-basedNCEP
, 10-year risk
Intermediate Risk
10-20%
High Risk
>20%
Lo...
Risk assessment and stratification
Risk factor/office-basedNCEP
, 10-year risk
Intermediate Risk
10-20%
High Risk
>20%
S...
Risk assessment and stratification
Risk factor/office-basedNCEP
, 10-year risk
Intermediate Risk
10-20%
High Risk
>20%
S...
Susceptibility
VulnerableVulnerable
PatientPatient
~10% risk/y~10% risk/y
Susceptibility
PROVE IT–TIMI 22
VulnerableVulnerable
PatientPatient
~10% risk/y~10% risk/y
Recurrent events
Best Marker of Susceptibility to CHD
prevalent arterial diseaseprevalent arterial disease
CHD risk equivalentsCHD risk equ...
CHD risk equivalentsCHD risk equivalents
NCEP ATP III
Best Marker of Susceptibility to CHD
prevalent arterial diseasepreva...
Susceptibility
VulnerableVulnerable
PatientPatient
~10% risk/y~10% risk/y
Definition of
at-risk population
AHA’s Heart Disease and Stroke Statistics – 2004 Update
www.americanheart.org/downloadable/heart/1079736729696HDSStats2004...
Dr falk's slides  part i
Dr falk's slides  part i
Dr falk's slides  part i
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Dr falk's slides part i

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Dr falk's slides part i

  1. 1. Erling Falk: CV SalarySalary Cardiovascular pathologist Aarhus University, Denmark Main interestMain interest Vulnerable plaques coronary thrombosis, and ACS COICOI None! Major limitationsMajor limitations Limited insight in imaging, epidemiology, statistics prediction models, cost-effectiveness analyses etc etc
  2. 2. Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72
  3. 3. Risk factorsRisk factors • S-cholS-chol ≥≥240 mg/dl240 mg/dl • BP >140/90BP >140/90 • SmokingSmoking • DiabetesDiabetes ≥1 RF in >87%1 RF in >87% of CHD casesof CHD cases JAMA 2003;290:891-7
  4. 4. Risk factorsRisk factors • S-cholS-chol ≥≥240 mg/dl240 mg/dl • BP >140/90BP >140/90 • SmokingSmoking • DiabetesDiabetes ≥1 RF in >87%1 RF in >87% of CHD casesof CHD cases JAMA 2003;290:891-7 Major risk factors account for CHD!
  5. 5. Nearly all adult Americans have ≥1 risk factor, regardless of CHD JAMA 2003;290:891-7
  6. 6. Predictive power of ≥1 risk factor for CHD PLR <2.0: Low positive predictive power AM Weissler. JAMA 2004;291:299-300
  7. 7. BMJ 1999;319:1562-5
  8. 8. Relative distributions of risk factors 22 000 men, 10-year follow-up22 000 men, 10-year follow-up Wald NJ, Law MR.Wald NJ, Law MR. BMJ. 2003;BMJ. 2003; 326:1419-326:1419- ~80% overlap!~80% overlap! Serum cholesterol (mmol/l) Diastolic blood pressure (mm/Hg)
  9. 9. Relative distributions of risk factors 22 000 men, 10-year follow-up22 000 men, 10-year follow-up Wald NJ, Law MR.Wald NJ, Law MR. BMJ. 2003;BMJ. 2003; 326:1419-326:1419- ~80% overlap!~80% overlap! Serum cholesterol (mmol/l) Diastolic blood pressure (mm/Hg) Intermediate
  10. 10. Pepe et al. Am J Epidemiol 2004;159:882-90Pepe et al. Am J Epidemiol 2004;159:882-90
  11. 11. Pepe et al. Am J Epidemiol 2004;159:882-90Pepe et al. Am J Epidemiol 2004;159:882-90
  12. 12. Eradication of Heart Attack dream or reality?dream or reality? • Most heart attack is preventable Heart attack remains the #1 killer Traditional approach has failed
  13. 13. • Most heart attack is preventable • Heart attack remains the #1 killer Traditional approach has failed Eradication of Heart Attack dream or reality?dream or reality?
  14. 14. • Most heart attack is preventable • Heart attack remains the #1 killer Traditional approach has failedTraditional approach has failed Eradication of Heart Attack dream or reality?dream or reality?
  15. 15. • Most heart attack is preventable • Heart attack remains the #1 killer Traditional approach has failedTraditional approach has failed Eradication of Heart Attack dream or reality?dream or reality?
  16. 16. Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72
  17. 17. Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72 Vulnerable plaque (Part I) + Vulnerable blood & myocardium (Part II, Oct 14) → Vulnerable patient: high risk of near-term  (Part III)
  18. 18. Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72 Vulnerable plaque (Part I) + Vulnerable blood & myocardium (Part II, Oct 14) → Vulnerable patient: high risk of near-term  (Part III)
  19. 19. Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72 Vulnerable plaque (Part I) + Vulnerable blood & myocardium (Part II, Oct 14) → Vulnerable patient: high risk of near-term  (Part III) From:From: Morteza NaghaviMorteza Naghavi , M.D. [mailto:mn2@vp.org], M.D. [mailto:mn2@vp.org] Sent:Sent: Tue 3/1/2005 2:26 AMTue 3/1/2005 2:26 AM … in case of symptomatic or post-ACS population we all know the balance between components of vulnerability (i.e. plaque – blood – myocardium) shifts toward increasing the role of blood and myocardium.
  20. 20. Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72 Vulnerable plaque (Part I) + Vulnerable blood & myocardium (Part II, Oct 14) → Vulnerable patient: high risk of near-term  (Part III) Diabetes and MS:Diabetes and MS: Vulnerable blood↑ HypertensionHypertension && LVH:LVH: Vulnerable myocardium↑
  21. 21. Table 1. The most common polymorphisms in the hemostatic system and their associations with intermediate phenotypes and atherothrombosis disease. Table from B Voetsch and J Loscalzo. ATVB 2004. Juan Badimon, SHAPE Report 2005
  22. 22. Figure 1. A schematic of the ECGI procedure.A schematic of the ECGI procedure. (a) ECG electrode vest for obtaining body surface potentials (bottom) and thoracic CT with the vest on the patient to obtain the geometries of the heart surface and the vest electrodes (top). (b) CT transverse slices showing heart contours (red) and body-surface electrodes (shiny dots). (c) Meshed heart-torso geometry. (d) Sample ECG signals obtained from mapping system. (e) Spatial representation of BSPM (body surface potentials). (f) ECGI software package (CADIS). (g) Examples of noninvasive ECGI images, including epicardial potentials, electrograms and isochrones. Electrode vest measures ECG potentials Instrumentation setup Transverse CT Images Body Surface potentials Heart-torso geometry 224-channel ECG CT provides geometry a b c d e f g Electrode vest measures ECG potentials Instrumentation setup Transverse CT Images Body Surface potentials Heart-torso geometry 224-channel ECG CT provides geometry a b c d e f g Yoram Rudy, SHAPE Report 2005
  23. 23. Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72Circulation. VP Consensus Document. 2003 Oct 7;108:1664-72 Vulnerable plaque (Part I) + Vulnerable blood & myocardium (Part II, Oct 14) →→ Vulnerable patient: high risk of near-termVulnerable patient: high risk of near-term  (Part III)(Part III)
  24. 24. Lancet 2004 364:937-52
  25. 25. Lancet 2004 364:937-52 Major risk factors account for MI! but they are ”useless” for prediction! Why? Individual vulnerability varies greatly! Protective factors?
  26. 26. Lancet 2004 364:937-52 Major risk factors account for MI! but they are ”useless” for prediction! Why?Why? Individual vulnerability varies greatly! Protective factors?
  27. 27. Lancet 2004 364:937-52 Major risk factors account for MI! but they are ”useless” for prediction! Why?Why? Individual susceptibilitysusceptibility varies greatly! Protective factors?
  28. 28. Atherosclerosis and CHD risk factors vs susceptibilityrisk factors vs susceptibility
  29. 29. Sir Winston Churchill, 91Sir Winston Churchill, 91  Jim Fixx, 53Jim Fixx, 53 ♥♥ J RumbergerJ Rumberger Atherosclerosis and CHD risk factors vs susceptibilityrisk factors vs susceptibility
  30. 30. The 1st SHAPE Task Force Advisory Meeting, Aug 6-7, 2004, Santa MonicaSanta Monica Photo by: Asif Ali … just a few …
  31. 31. From: Morteza Naghavi, M.D. [mailto:mn2@vp.org] Sent: Thu 2/24/2005 7:47 AM To: Erling Falk; John Rumberger; Kaul, Sanjay M.D.; HHecht@aol.com; Kaul, Sanjay M.D.; Diamond, George, MD Cc: lshaw@acrionline.org; Kaul, Sanjay M.D.; JamieM@pfizer.com; Dmlmdphd@aol.com; Jasenka.Demirovic@uth.tmc.edu; Shah, Prediman Krishan Subject: RE: Association vs classification Let's not forget the most important question, the short- term prediction (<5y) in search of the Vulnerable Patient. We didn't start SHAPE just to engineer a new paradigm. The concept of search for the Vulnerable Patient, those at a very high risk of a near term event is by itself a new paradigm and requires new approaches. Preventive cardiology today does not have any recognition for this group and put them all together with high risk. ……
  32. 32. Risk assessment and stratification Risk factor/office-basedNCEP , 10-year risk Intermediate Risk 10-20% High Risk >20% Low(er) Risk <10% CHDCHD && equivalentsequivalents
  33. 33. Risk assessment and stratification Risk factor/office-basedNCEP , 10-year risk Intermediate Risk 10-20% High Risk >20% Low(er) Risk <10% RR ~2RR ~2 CHDCHD && equivalentsequivalents
  34. 34. Risk assessment and stratification Risk factor/office-basedNCEP , 10-year risk Intermediate Risk 10-20% High Risk >20% Susceptibility-based, near-term risk Low(er) Risk <10% VPVP CHDCHD && equivalentsequivalents
  35. 35. Risk assessment and stratification Risk factor/office-basedNCEP , 10-year risk Intermediate Risk 10-20% High Risk >20% Susceptibility-based, near-term risk VPVP Low(er) Risk <10% Very Low Risk* No disease Severity of disease, susceptibilitysusceptibility *Optimal risk factors CHDCHD && equivalentsequivalents
  36. 36. Susceptibility VulnerableVulnerable PatientPatient ~10% risk/y~10% risk/y
  37. 37. Susceptibility PROVE IT–TIMI 22 VulnerableVulnerable PatientPatient ~10% risk/y~10% risk/y Recurrent events
  38. 38. Best Marker of Susceptibility to CHD prevalent arterial diseaseprevalent arterial disease CHD risk equivalentsCHD risk equivalents NCEP ATP III
  39. 39. CHD risk equivalentsCHD risk equivalents NCEP ATP III Best Marker of Susceptibility to CHD prevalent arterial diseaseprevalent arterial disease
  40. 40. Susceptibility VulnerableVulnerable PatientPatient ~10% risk/y~10% risk/y
  41. 41. Definition of at-risk population
  42. 42. AHA’s Heart Disease and Stroke Statistics – 2004 Update www.americanheart.org/downloadable/heart/1079736729696HDSStats2004UpdateREV3-19-04.pdf M W

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