Calcium score CAC vs Carotid IntimaMedia Thickness CIMT in predicting cardiovascular events

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Calcium score (CAC) vs Carotid Intima-Media
Thickness (CIMT) in predicting cardiovascular
events
GIM Conference June 17th, 2009 Presented by
Michael Luc
Folsom AR, Kronmal RA, Detrano RC, et al.
Coronary artery calcification compared with
carotid intima-media thickness in the prediction
of cardiovascular disease incidence the
Multi-Ethnic Study of Atherosclerosis (MESA).
Arch Intern Med. 2008168(12)13331339.
www.kgu.de/zrad, vanha.med.utu.fi
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Background The Detection Gap

• 10-year risk of CVD event traditionally
  determined by risk factors only
• Affects management in statin therapy, pre-op,
  etc.
• However, 1/3 of CVD events are not predicted by
  traditional (Framingham) risk factors
• Other Methods to assess for atherosclerosis
• Serum biomarkers CRP, IL-6, MMP1, lipoprotein
  a, homocysteine, fibrinogen
• Imaging carotid intima-media thickness (CIMT),
  coronary artery calcium score (CAC)

Gerber, TC and Taylor, AJ. Carotid Intima-Media
Thickness Can it Close the Detection Gap for
Cardiovascular Risk? Mayo Clinic Proceedings.
March 200984(3)218-220.
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2008 ASE Recommendations for Caroitid-Intima
Media Thickness Scanning

• Consider scanning in patients aged 4070 years,
  without a condition that indicates high CVD risk,
  AND
• Intermediate CVD risk (ie, 620 10-year risk of
  event by Framingham data)
• Family history of premature CVD in a first-degree
  relative
• Individuals older than 60 years with severe
  abnormalities in a single risk factor who
  otherwise would not be candidates for
  pharmacotherapy
• Women younger than 60 years with less than 2 CVD
  risk factors
• Imaging should not be performed if the results
  would not be expected to alter therapy.

Stein JS, Korcarz CE, Post WS. Use of Carotid
Ultrasound to Identify Subclinical Vascular
Disease and Evaluate Cardiovascular Disease Risk
Summary and Discussion of the American Society of
Echocardiography Consensus Statement. Preventive
Cardiology. Winter 2009. 34-38.
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2007 ACC/AHA Expert Consensus on Coronary Artery
Calcium (CAC) Score

• It may be reasonable to consider use of CAC
  measurement in asymptomatic patients with
  intermediate CHD risk (between 10 and 20 events
  per 10-yrs) if
• it would classify patients into a higher risk
  status
• AND if subsequent patient management would be
  modified.
• CAC scanning is not recommended in high or low
  risk groups.

Greenland P, Bonow RO, Brundage BH, et al
American College of Cardiology Foundation
Clinical Expert Consensus Task Force (ACCF/AHA
Writing Committee to Update the 2000 Expert
Consensus Document on Electron Beam Computed
Tomography) Society of Atherosclerosis Imaging
and Prevention Society of Cardiovascular
Computed Tomography. ACCF/AHA 2007 clinical
expert consensus document on coronary artery
calcium scoring by computed tomography in global
cardiovascular risk assessment and in evaluation
of patients with chest pain a report of the
American College of Cardiology Foundation
Clinical Expert Consensus Task Force (ACCF/AHA
Writing Committee to Update the 2000 Expert
Consensus Document on Electron Beam Computed
Tomography). Circulation. 2007115(3)402-426.
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Study Objectives

• This study is the largest to date comparing CIMT
  vs CAC score using outcomes data
• Objectives
• To determine the ability of CIMT and CAC to
  predict CVD events after correction for
  traditional risk factors
• To determine which is better to predict CVD
  events

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Methods

• Study design - Prospective cohort study
• Exclusion criteria - Anyone with CVD
• Patients received maximum carotid IMT and CAC
  score at baseline in 2000-2002
• Six field centers in major cities in the U.S.
• Endpoints - Risk of new CVD events including
  coronary heart disease, stroke, and death from
  CVD
• Follow-up Greatest follow-up was 5 years

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Results

• Age - 45 to 84 years
• Ethnic groups - white (38), black (28),
  Hispanic (22), or Asian (12)
• n6698 (analyzed out of 6,814 that were
  recruited)
• 222 CVD (CHD and stroke) events detected in 5
  yrs.
• 159 CHD events (61 cases of myocardial
  infarction, 81 cases of angina, 3 cases of
  resuscitated cardiac arrest, 13 CHD deaths)
• 59 stroke events (some had overlap with CHD
  events)

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Analysis

• Overall, CAC score was more strongly associated
  with CVD events than IMT
• Variables standardized in order to normalize
  distributions for better comparison
• ln(CAC score 1)
• z-score of maximum CIMT (number of SD away from
  mean)

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Risks of Overall Events (n222) with an elevated
CAC score or CIMT Hazard Ratios

• Adjustment for age, sex, and race - Hazard ratios
  (95 CI) for each 1 standard deviation increase
• Standardized CIMT 1.3 (1.1-1.4)
• Standardized CAC score 2.1 (1.8-2.5)
• Adjustment for all risk factors (age, sex, race,
  smoking, diabetes, blood pressure, lipids, and
  statin use)
• Standardized CIMT 1.2 (1.0-1.3)
• Standardized CAC score 1.9 (1.6-2.2)

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Risks of MI, Angina, or Cardiac Death (n159)
with an elevated CAC score or CIMT Hazard Ratios

• Adjustment for age, sex, and race - Hazard ratios
  (95 CI) for each 1 standard deviation increase
• Standardized CIMT 1.1 (1.0-1.4)
• Standardized CAC score 2.5 (2.1-3.1)
• Adjustment for all risk factors (age, sex, race,
  smoking, diabetes, blood pressure, lipids, and
  statin use)
• Standardized CIMT 1.1 (1.0-1.3)
• Standardized CAC score 2.3 (1.9-2.8)

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Risks of Stroke (n59) with an elevated CAC score
or CIMT Hazard Ratios

• Adjustment for age, sex, and race - Hazard ratios
  (95 CI) for each 1 standard deviation increase
• Standardized CIMT 1.4 (1.2-1.8)
• Standardized CAC score 1.1 (0.8-1.5)
• Adjustment for all risk factors (age, sex, race,
  smoking, diabetes, blood pressure, lipids, and
  statin use)
• Standardized CIMT 1.3 (1.1-1.7)
• Standardized CAC score 1.1 (0.8-1.4)

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Risks of Overall Events in Framingham
Intermediate-Risk Group ONLY (n81) with an
elevated CAC score or CIMT Hazard Ratios

• Adjustment for all risk factors (Age, sex, race,
  smoking, diabetes, blood pressure, lipids, and
  statin use)
• Standardized CIMT 1.4 (1.1-1.6)
• Standardized CAC score 1.8 (1.4-2.2)

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Discussion

• In asymptomatic 45-84 y.o. US adults, CAC score
  may be better than CIMT for screening of those
  with intermediate risk.
• Also, on the side, in this MESA study there are
  substantial ethnic differences in CAC score
  (highest in whites) and to a lesser degree for
  IMT (highest in African Americans).

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Discussion Strengths

• Multiethnic sample
• Standardization across multiple centers
• Adjustment for traditional risk factors
• Reliance on outcomes data of events (MI, death,
  angina) vs surrogate end points such as
  subclinical atherosclerosis

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Discussion Weaknesses

• Relatively short follow-up period (5 years)
• Relatively small number of strokes in study
• Statistical distribution difference between IMT
  and CAC, with 50 of CAC score being 0
• Outcomes data incl. angina with MI and death
• Patients informed of CAC and IMT scores at
  baseline may have influenced pts to alter risk
  factors, especially since 17 of those with high
  CAC score were referred to their primary MDs vs
  1 of those with high IMT.

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Conclusion

• In conclusion, although whether and how to use
  bioimaging tests for subclinical atherosclerosis
  remains a topic of debate, this study found that
  CAC score was a better predictor of subsequent
  CVD events than was carotid IMT.

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Application Screening?

• WHO Screening criteria (1968)
• x Important health problem
• x Accepted treatment for recognized disease
• x Facilities for diagnosis and treatment
• x Suitable latent and symptomatic stage
• x Suitable test or examination
• x Natural history of condition understood
• x Agreed on policy on whom to treat
• x Case finding should be continuous process
• Cost of finding economically balanced with
  overall health does it add that much over
  traditional RF?
• Test acceptable to population

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Application Clinical practice

• More data is needed, more event data before a
  rigorous cost-benefit analysis can be done
• Consider differences in radiation exposure, cost,
  and availability
• IMT can be done in office with handheld and is
  cheaper overall but requires more operator skill
  (ultrasound)
• CAC requires radiation exposure but from this
  study is a better predictor of cardiac events

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Thank you!

• Questions?

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