Predictors of Subclinical Atherosclerosis among Asymptomatic Low Risk Individuals

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Predictors of Subclinical Atherosclerosis among
Asymptomatic Low Risk Individuals

• Grewal J, Anand S, Islam S, Lonn E for the
  SHARE Investigators
• Atherosclerosis. 2007 Aug 3 Epub ahead of
  print

SHARE
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Background

• Framingham Risk Estimation (FRE) is the most
  commonly used method for the assessment of
  cardiovascular risk
• Components of FRE include
• Age
• Sex
• Low density lipoprotein (LDL)
• High density lipoprotein (HDL)
• Blood Pressure
• Smoking
• Diabetes

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Background

• FRE does not identify all patients at risk of
  CHD, missing many individuals who may benefit
  from aggressive preventive management
• Carotid intimal media thickness (IMT) is a
  validated measure of subclinical atherosclerosis
  (SCA) and has been shown to be a strong predictor
  of cardiac events. (1,2)

1 OLeary DH et al. NEJM 199934014-22 2
Chambless LE et al. Am J Epidemiology
1997146483-94
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Carotid IMT Predicts Coronary Events
The Kuopio Ischemic Heart Study
1227 middle-aged Finnish men Average
follow-up 1 year

Relative Hazard of Acute MI
Salonen et al, KIHD, Arterioscl Thromb
1991111245
Carotid Morphology
For each 1 mm increase in carotid IMT the risk of
MI increased 2.14 fold
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The Role of Carotid IMT in Predicting Coronary
Events and Stroke
The Cardiovascular Health Study
5858 subjects 65 yrs 4476 subjects - no CVD
at baseline Follow-up 6.2 years
Unadjusted cumulative event-free rates for the
combined endpoint MI and stroke by quintiles of
IMT
OLeary et al. NEJM, 199934014-22.
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Carotid IMT Predicts Major Coronary Events
The Atherosclerosis Risk in Communities (ARIC)
Study

• 7,289 women and 5,552 men aged 45-64 yrs from 4
  US communities.
• Median follow-up 5.2 yrs

Chambless LE, et al. Am J Epidemiol 1997
146483-494
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Objectives

• To determine what proportion of individuals at
  low risk of CHD by FRE have significant SCA as
  measured by carotid IMT.
• To identify predictors of SCA in the low risk
  FRE group

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Methods

• 1,285 adults of South Asian, Chinese, European,
  and Aboriginal ancestry were randomly sampled
  from 4 communities in Canada between 1996-2000 as
  part of the Study of Health Assessment and Risk
  in Ethnic groups (SHARE). (3)
• Participants with documented CVD and diabetes
  were excluded (n260) as were those with
  suboptimal ultrasound images (n10) leaving 1,015
  participants

3 Anand el al. Lancet 2000 356 279-284.
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Methods

• Measurements of conventional and novel risk
  factors for vascular disease were performed
• Age, sex, cholesterol profile, glucose profile,
  family history
• Lpa, Apo (B)
• Ankle Brachial index, Waist Hip Ratio
• Norepinephrine, PAI-1, WBC, Fibrinogen
• Homocysteine, CRP
• Urine creatinine, cortisol and albumin
• Exercise, Alcohol consumption and Fruit/Vegetable
  intake
• Hormone Replacement, Menstruation in the last
  year
• SCA was measured by B-mode Carotid Ultrasound

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Carotid IMT
Near Wall
Flow Divider
BIF
CCA
ICA
Far Wall
1cm 1cm 1cm
Mean Max IMT (mmIMT) RCFRCNRBFRBN.../12
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Methods

• Excess SCA was defined as mean maximal carotid
  intima media thickness (mmIMT) gt 75th percentile
  for age, gender and ethnicity
• Participants risk of CHD was classified based on
  10-year FRE
• Low lt10
• Medium 10.1-20
• High gt 20.1
• Statistical Analysis
• Univariate and Multivariate Logistic Regression
• Stepwise Multiple Regression

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ResultsCharacteristics of Subjects classified by
the Framingham Risk Model as medium/high risk and
low risk, with and without SCA
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ResultsCharacteristics of Subjects classified by
the Framingham Risk Model as medium/high risk and
low risk, with and without SCA
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ResultsPredictors of Atherosclerosis (IMT as a
continuous variable in the Low FRE group (n752)
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ResultsPredictors of Atherosclerosis (IMT as a
continuous variable in the Low FRE group
continued (n752)
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ResultsPredictors of SCA defined as mean maximal
IMT gt 75th percentile for age, gender and
ethnicity in the low risk group (n752)
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Conclusions

• Our main finding is the high prevalence of SCA in
  a low-risk multiethnic Canadian population.
• Indeed, 23 of individuals classified as low-risk
  for CHD by FRE had SCA.
• This is in contrast to the expectation, that most
  individuals classified as low risk, would be in
  the lower carotid IMT distribution.
• Systolic blood pressure and apolipoprotein B were
  predictive of SCA in our study, while none of the
  other novel and lifestyle factors improved the
  prediction of SCA.

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Conclusions

• Moreover, the prevalence of SCA was similar
  across ethnic groups, including European
  Caucasians, for whom the Framingham model should
  be most accurate.
• Therefore, conventional risk stratification using
  the Framingham model misses an important
  proportion of individuals at risk of future CV
  events as discussed in the introduction.

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Conclusions

• In our study the prevalence of SCA among low-risk
  subjects by FRE tended to be higher among women
  and female sex emerged as an independent
  predictor of SCA.
• We believe that this finding reflects limitations
  of the Framingham risk model, which classifies
  most young and middle-aged women as being at low
  risk for CV events, although many may have
  subclinical vascular disease and their life-time
  risk may be substantial.
• The role of carotid IMT measurements of SCA in
  defining management strategies and outcomes
  requires further evaluation