1. Calculated LDL by Age Cases vs. Controls Figure 1

2. HDLT by Age Cases vs. Controls Figure 3

3. Triglycerides by Age Cases vs. Controls Figure 5

4. Insulin by Age Cases vs. Controls Figure 6

5. Androstenedione by Age Cases vs. Controls Figure 7

6. Clinic BMI by Age Cases vs. Controls Figure 8

7. Average Diastolic BP by Age Cases vs. Controls

8. Average Systolic BP by Age Cases vs. Controls

9. Clinic Estradiol 2 by Age Cases vs. Controls

10. Study Population:PCOS and the Risk of CHD,Part II (l996-99) 160 PCOS cases and 160 controls 30+ years of age participating in PHASE II (1996-1999) of the Cardiovascular Health and Risk Measurement (CHARM) Study 160 PCOS cases and 160 controls 30+ years of age participating in PHASE II (1996-1999) of the Cardiovascular Health and Risk Measurement (CHARM) Study Ongoing protocol to evaluate the CHD risk factors and subclinical atherosclerosis as measured by carotid ultrasound in women with PCOS. Ongoing protocol to evaluate the CHD risk factors and subclinical atherosclerosis as measured by carotid ultrasound in women with PCOS.

11. Research Methodology Clinic Visit (continued) Clinic Visit (continued)  Blood analyte assessment  Lipids ( total cholesterol, triglycerides, LDLc, HDLc)  Fasting glucose and insulin  Fibrinolytic/coagulation parameters tissue plasminogen activator (tPA)tissue plasminogen activator (tPA) plasminogen activator inhibitor (PAI-1)plasminogen activator inhibitor (PAI-1)

12. Carotid Atherosclerotic Index (CAI) Represents the overall mean of the mean measurements of carotid intima-media thickness at 8 sites Represents the overall mean of the mean measurements of carotid intima-media thickness at 8 sites Arterial sites of interest included : Arterial sites of interest included :  left/ right proximal common carotid  left/ right distal common carotid  left/ right carotid bulb  left/ right distal internal carotid

13. Baseline Demographic and Reproductive Factors in PCOS Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421 Click for larger picture

14. Baseline Cardiovascular Risk Factors in PCOS Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421 Click for larger picture

15. Plaque Indexed was also scored: Plaque was defined as a distinct area protruding into the vessel lumen with at least 50% or > thickness than the surrounding area. Plaque was defined as a distinct area protruding into the vessel lumen with at least 50% or > thickness than the surrounding area. Scoring was as follows: 0= no stenosis, 1 = small stenosis 50% or multiples with at 1 medium stenosis. Scoring was as follows: 0= no stenosis, 1 = small stenosis 50% or multiples with at 1 medium stenosis. These were summed to create an overall plaque index. These were summed to create an overall plaque index.

16. Plaque Index in PCOS Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421 Click for larger picture

17. Carotid IMT in PCOS by Age and BMI ns ns.219.040 45 years BMI: Age:

18. Univariate Regression of IMT and Baseline CHD Risk Factors- summary Risk factors included: Risk factors included:  PCOS, BMI, hormone use, smoking status, LDL, HDL, DBP, SBP, insulin, W:H, age, total T, and TRIG In the total group and less than 45 years of age, significant risk factors included: In the total group and less than 45 years of age, significant risk factors included:  BMI, DBP, SBP, insulin, W:H, age, TRIG In women 45 years or greater, significant risk factors included: In women 45 years or greater, significant risk factors included:  PCOS, BMI, LDL, SBP, insulin, TRIG Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421

19. Regression Modeling of IMT in PCOS Women and Controls  45 years Models 1 PCOS Age 2 PCOS Age BMI 3 PCOS Age BMI LDL Beta.309.021.206.022.017.227.020.014.003 SE.095.013.100.013.006.099.013.006.002 Sig.002.107.042.092.008.024.124.030.048 Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421

20. Regression Modeling of IMT in PCOS Women and Controls  45 years (cont.) Models 4 PCOS Age BMI SBP 5 PCOS Age BMI DBP 6 PCOS Age BMI TRIG Beta.174.013.016.002.178.014.017.002.195.021.016.033 SE.101.013.007.004.102.013.007.006.105.013.007.090 Sig.088.322.037.535.085.287.024.699.068.113.030.716 Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421

21. Regression Modeling of IMT in PCOS Women and Controls >45 years (cont.) Models 7 PCOS Age BMI W:H 8 PCOS Age BMI Insulin Beta.167.014.018.045.124.023.018.068 SE.104.013.006.309.109.013.008.094 Sig.112.314.007.883.256.094.034.471 Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421

22. Multivariate Regression Models of IMT- Effect of PCOS Models adjusted for age and BMI Models adjusted for age and BMI Risk factors explored include: Risk factors explored include:  PCOS, LDL, SBP, DBP, TRIG, W:H, insulin In the total group PCOS was not a significant predictor of IMT. SBP was only significant independent predictor. In the total group PCOS was not a significant predictor of IMT. SBP was only significant independent predictor. In women less than 45 years of age PCOS was not a significant predictor of IMT. SBP and DBP were significant independent predictors. In women less than 45 years of age PCOS was not a significant predictor of IMT. SBP and DBP were significant independent predictors. Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421

23. Multivariate Regression Models of IMT- Effect of PCOS (cont.) In women 45 years or greater PCOS was a significant predictor of IMT, independent of age and BMI (p=.042). In women 45 years or greater PCOS was a significant predictor of IMT, independent of age and BMI (p=.042). With the addition of LDL, this relationship became more significant (p=.024). Both LDL and PCOS exerted independent significant effects. With the addition of LDL, this relationship became more significant (p=.024). Both LDL and PCOS exerted independent significant effects. With the addition of SBP, DBP or TRIG, the PCOS- IMT relationship remained borderline significant (p=.068-.088). With the addition of SBP, DBP or TRIG, the PCOS- IMT relationship remained borderline significant (p=.068-.088). The addition of insulin or W:H eliminated the significance of PCOS as an independent predictor of IMT. The addition of insulin or W:H eliminated the significance of PCOS as an independent predictor of IMT. Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421

24. Regression Summary: Fasting insulin and W:H appear to attenuate the relationship of PCOS and IMT, suggesting that at least part of the PCOS-IMT association in middle aged PCOS women may be driven by central obesity and hyperinsulinemia. Fasting insulin and W:H appear to attenuate the relationship of PCOS and IMT, suggesting that at least part of the PCOS-IMT association in middle aged PCOS women may be driven by central obesity and hyperinsulinemia. There may be an independent effect of PCOS on IMT mediated by low peak estradiol levels or hormonal dysregulation. There may be an independent effect of PCOS on IMT mediated by low peak estradiol levels or hormonal dysregulation. An increase in IMT is apparent even in thinner PCOS cases. An increase in IMT is apparent even in thinner PCOS cases. Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421

25. Calcification Scores in PCOS Click for larger picture

26. Conclusions : The epidemiologic studies to date have been mainly consistent in their findings of increases in cardiovascular risk factors in women with PCOS. These have however been largely cross-sectional. The epidemiologic studies to date have been mainly consistent in their findings of increases in cardiovascular risk factors in women with PCOS. These have however been largely cross-sectional. Subclinical measures have shown increases in women >45 and this would imply a common source long incubation “latency” effect of increases in CHD RF in younger PCOS women over time. Subclinical measures have shown increases in women >45 and this would imply a common source long incubation “latency” effect of increases in CHD RF in younger PCOS women over time. However, a prospective study following a larger cohort of women with PCOS is needed to determine if there is a true increased risk of CHD events. However, a prospective study following a larger cohort of women with PCOS is needed to determine if there is a true increased risk of CHD events.