Coagulation/Fibrinolytic Factors in PCOS

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

Carotid IMT in PCOS Click for larger picture

Hemodynamic Measures in PCOS Click for larger picture

Correlation of Various Subclinical CHD Measures Click for larger picture

Interaction of PCOS and Age in IMT Click for larger picture

Click for larger picture Lancet 1997; 350 (suppl I):15 Click for larger picture

Click for larger picture Lancet 1997;350:21

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)

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.

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

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?

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

Selected Clinical and Lifestyle Factors in PCOS Cases and Controls- Preliminary Data VARIABLES (1993-94 Data) * p  .05 ** p  .001

Selected Lipid and Hormone Levels in PCOS Cases and Controls- Preliminary Data VARIABLES (1993-4 Data) CASES (n=46) CONTROLS (n=59) * p  .05 ** p  .001

Differences in CAI in PCOS Cases vs. Controls by Age

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

Regression - Fixed Model Forced entry of CVD risk factors: P-value of Predictors Model Adjusted R2 Model Significance Predictors Dependent variable = CAI

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

Regression - PCOS Status Entry of PCOS status to CVD fixed model including LDL: P-value of Predictors Model Adjusted R2 Model Significance Predictors Dependent variable = CAI

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

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.

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.

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