United Kingdom Life Insurance Meeting Skin Sterol

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United Kingdom Life Insurance MeetingSkin Sterol

• May 21st, 2008

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What Is Skin Sterol (Cholesterol)?

• Skin tissue cholesterol
• 11 of total body cholesterol
• Second only to bile as a means for excreting
  cholesterol
• Important role in barrier function of skin
• Derived from
• epithelial steroidogenesis
• diffusion from circulation via specific uptake
• Skin turnover approx. 30 days
• Provides incremental cardiovascular risk
  information
• Independent of serum lipids

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Skin Sterol is .

• Sampled non-invasively
• Fasting not required
• Correlated with risk of cardiovascular disease
• Exercise stress test outcome
• Angiographic plaque
• Coronary calcium
• Carotid IMT

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Skin Sterol is also.

• Elevated in subjects with higher levels of
  inflammatory markers
• Elevated in subjects with a prior history of MI
  or CABG
• Associated with metabolic syndrome (together with
  hsCRP)
• Additive to Framingham in predicting multivessel
  disease

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How is Skin Sterol Measured?

• PREVU POC
• Does not require fasting or a blood sample
• Measured at point-of-care directly on the palm
• Measured with digitonin-HRP detector and HRP
  substrate

• PREVU LT
• Does not require fasting or a blood sample
• Measured in the laboratory from a tape stripped
  skin sample
• Measured with digitonin-HRP detector and HRP
  substrate
• Protein determined to ensure adequate sample

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Sampling by Tape Stripping
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Assays for Skin Sterol and Protein
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• 9,055 eligible subjects applying for life
  insurance in the United States
• Provided informed consent
• Skin samples taken by parameds and shipped to
  Quest Diagnostics for testing
• Demographics captured
• Serum lipids and risk factors acquired
• Compare to Framingham Risk Score
• Future opportunity for all cause death data from
  study population

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Risk PredictionThe CAD Prevention Iceberg
gt 20, CAD or Diabetes Mellitus
Estimated 10-Yr Risk
10 - 20
lt 10
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Descriptive Statistics of Study Population (mean
1 SD or population)
Cotinine gt 0.3
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Skin Sterol Categorization

• Adjusted for age and gender
• Low skin sterol lowest quintile
• Intermediate skin sterol quintiles 2-4
• High skin sterol highest quintile

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But

• In the US insurance companies typically do not
  use Framingham Risk score to estimate risk of CAD
  in their clients
• Blood lipids, notably TCHDL appear to be used
  more frequently to rate clients

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Study Findings

• Skin sterol is correlated with Framingham risk
  score in tobacco users
• Skin sterol is associated with elevated TCHDL
• More powerful relationship in tobacco users
• Tobacco users with high skin sterol are more
  likely to have multiple elevated cardiovascular
  risk factors
• Tobacco users with low skin cholesterol are
  similar to non-tobacco users in terms of
  cardiovascular risk factors

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Skin Sterol Application 1

• Test all applicants for skin sterol and oral
  fluid cotinine
• Reflex to blood on subjects with positive
  cotinine and elevated skin sterol (2.6)
• gt15 subjects will have at least 2 elevated lipid
  markers
• Potential additional benefit of full serum panel
  on risk enriched population, e.g. other markers

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Skin Sterol Application 2

• Test all applicants for skin sterol (and oral
  fluid cotinine?)
• Permit subjects with skin sterol in quintile 1 to
  screen in to a better risk class, no reflex
  test needed
• Less than 4 will have TCHDL gt6
• More competitive pricing

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PREPARE Clinical Publication

• Skin Sterol Predicts TC/HDL and hsCRP in Low
  Risk Subjects A Tool for Preventative Screening
• Presented at the AHA, ATVB Meeting, April 2008
• Dennis Sprecher MD, John Mancini MD
• Top quartile of skin sterol at significantly
  increased risk of elevated TCHDL vs lowest
  quartile with odds ratio of 1.43 (plt0.001)
• High skin sterol predicted high hsCRP with odds
  ratio of 1.35 (plt0.001) vs lowest quartile
• Conclusion This simple, non-invasive test may
  be useful in identifying higher risk individuals
  who would benefit from further risk factor
  assessment.

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Regulatory Status

• PREVU LT
• CE Mark obtained
• Cleared in Canada
• FDA pending