Coagulation/Fibrinolytic Factors in PCOS

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Coagulation/Fibrinolytic Factors in PCOS
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The Alternative Hypothesis

• Conversely, PCOS women may be protected from
  later life onset of CHD by the altered hormonal
  profile that includes increased estrone from
  peripheral conversion of androgen in adipose and
  other tissue
• This profile could be responsible for the
  inconsistencies observed between investigations
  of risk factors in PCOS and the McKeigue
  retrospective follow-up of mortality

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Carotid IMT in PCOS
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Hemodynamic Measures in PCOS
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Correlation of Various Subclinical CHD Measures
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Interaction of PCOS and Age in IMT
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Lancet 1997 350 (suppl I)15
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Click for larger picture
Lancet 199735021
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Introduction

• Polycystic Ovary Syndrome (PCOS) is associated
  with an increased prevalence of cardiovascular
  disease risk factors (Wild, !988
  Slowinska-Srezednicka, 1991 Talbott and Guzick,
  1995)
• PCOS women have evidence of metabolic
  derangements similar to Syndrome X (?LDLc, ?
  HDLc, ? triglycerides, ?insulin, ?central
  adiposity, hypertension, and Type II diabetes)

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Introduction (cont.)

• Since LDLc is an important determinant of
  atherosclerosis in women, the increased LDLc
  levels seen in younger PCOS suggests that these
  women may be at increased risk for subclinical
  and clinical atherosclerosis at an earlier age
  than the general female population.

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Characteristics of PCOS
Affects 5 to 10 percent of US Women, and the
condition is marked by

• Chronic Anovulation
• Hyperandrogenism (Elevated Testosterone)
• Hirsutism

• Obesity
• Insulin Resistance
• Infertility

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Research Questions

• Do women with PCOS have evidence of subclinical
  atherosclerosis as demonstrated by an increase in
  carotid intima-media thickness?
• If so, can the increase in carotid intima-media
  thickness be linked to the various cardiovascular
  risk factors seen in PCOS women?

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Current Study Population

• Women participating in Phase II of the
  Cardiovascular Health and Risk Measurement Study
  (CHARM, 1997-98)
• Cases and controls represent the initial 1/3 of
  the women recruited for Phase II participation
  (46 Cases with PCOS and 59 Controls)
• PCOS is defined as chronic anovulation with
  clinical or biochemical evidence of
  hyperandrogenism without other identified causes

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Selected Clinical and Lifestyle Factors in PCOS
Cases and Controls- Preliminary Data
CASES (n46)
CONTROLS (n59)
VARIABLES (1993-94 Data)
p ? .05
p ? .001
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Selected Lipid and Hormone Levels in PCOS Cases
and Controls- Preliminary Data
VARIABLES (1993-4 Data)
CASES (n46)
CONTROLS (n59)
p ? .05
p ? .001
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Differences in CAI in PCOS Cases vs. Controls by
Age
p 0.004 p 0.021
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Analysis of CAI Predictors in PCOS Cases and
Controls

• Employed a multiple linear regression model with
  forced entry of predictors
• Dependent variable CAI
• Independent variables in the fixed model
  included age, BMI, DBP, smoking and hormone use
• Lipids and insulin were added separately to the
  fixed model to determine the change in R2
• PCOS status was added to the final model to
  evaluate attenuation of the relationships by case
  status

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Regression - Fixed Model
Forced entry of CVD risk factors
P-value of Predictors
Model Adjusted R2
Model Significance
Predictors
Dependent variable CAI
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Regression - Lipids and Insulin
Individual entry of lipids and insulin to CVD
fixed model
P-value of Predictors
Model Adjusted R2
Model Significance
Predictors
Dependent Variable CAI
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Regression - PCOS Status
Entry of PCOS status to CVD fixed model including
LDL
Model Adjusted R2
Model Significance
P-value of Predictors
Predictors
Dependent variable CAI
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Conclusions

• PCOS women demonstrate increased carotid
  intima-media thickness compared to age matched
  controls at a relatively young age (lt 40 years).
• However, the most striking evidence of
  subclinical atherosclerosis in PCOS appears in
  the ? 40 year age group.

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Conclusions (cont.)

• Age, BMI, and diastolic blood pressure are
  significant predictors of CAI in women
• Atherosclerotic potential in the younger PCOS
  women is mediated by in part by higher LDLc
  levels and increased BMI.

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Implications

• Since abnormal LDLc levels and increased BMI
  appear to contribute to subclinical
  atherosclerosis in PCOS, interventions directed
  at decreasing LDLc and controlling weight in
  younger PCOS women may improve the later-life
  cardiovascular risk profile in this high risk
  population.

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Evelyn O. Talbott A544 Crabtree Hall Pittsburg,
PA [phone]