Coagulation/Fibrinolytic Factors in PCOS - PowerPoint PPT Presentation

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Coagulation/Fibrinolytic Factors in PCOS

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Chronic Anovulation. Hyperandrogenism (Elevated Testosterone) Hirsutism. Obesity ... PCOS is defined as chronic anovulation with clinical or biochemical evidence of ... – PowerPoint PPT presentation

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Title: Coagulation/Fibrinolytic Factors in PCOS


1
Coagulation/Fibrinolytic Factors in PCOS
2
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

3
Carotid IMT in PCOS
Click for larger picture
4
Hemodynamic Measures in PCOS
Click for larger picture
5
Correlation of Various Subclinical CHD Measures
Click for larger picture
6
Interaction of PCOS and Age in IMT
Click for larger picture
7
Lancet 1997 350 (suppl I)15
Click for larger picture
8
Click for larger picture
Lancet 199735021
9
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)

10
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.

11
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

12
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?

13
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

14
Selected Clinical and Lifestyle Factors in PCOS
Cases and Controls- Preliminary Data
CASES (n46)
CONTROLS (n59)
VARIABLES (1993-94 Data)
p ? .05
p ? .001
15
Selected Lipid and Hormone Levels in PCOS Cases
and Controls- Preliminary Data
VARIABLES (1993-4 Data)
CASES (n46)
CONTROLS (n59)
p ? .05
p ? .001
16
Differences in CAI in PCOS Cases vs. Controls by
Age
p 0.004 p 0.021
17
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

18
Regression - Fixed Model
Forced entry of CVD risk factors
P-value of Predictors
Model Adjusted R2
Model Significance
Predictors
Dependent variable CAI
19
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
20
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
21
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.

22
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.

23
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.

24
Evelyn O. Talbott A544 Crabtree Hall Pittsburg,
PA (412) 624-3074
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