4081 - Coagulation/Fibrinolytic Factors in PCOS Table 4:...

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Unformatted text preview: Coagulation/Fibrinolytic Factors in PCOS Table 4: Differences in Coagulation/Fibrinolytic Factors in PCOS Cases vs. Controls (Adjusted for Age and Body Mass Index) Coagulation Factor PAI-1 ng/ml TPA ng/ml Factor VII % D-Dimer ng/ml Fragment 1.2 nM CRP g/ml PCOS Cases N= 50 27.6 11.0 128.0 99.7 1.16 2.14 Controls N = 56 18.8 9.9 132.0 106.3 1.23 2.45 P value .026 .127 .648 .715 .575 .414 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 Table 6: IMT (mm) * Carotid IMT results for PCOS cases and controls Cases N Mean SE Controls N Mean SE Age-BMI Adj Mean (CI) .67 (.65-69) .64 (.61.67) .71(.68-.75) pvalue* .299 .565 .005 Age-BMI Adj. Mean (CI) Total 125 .70 .01 .70 (.68-.73) 142 30-44 yr 78 .65 .01 .65 (.62-.69) 82 45+ yr 47 .78 .03 .77 (.74-.81) 60 *statistical test performed on transformed variable .68 .01 .66 .01 .70 .01 Reprinted with Permission pending from Arteriosclerosis, Thrombosis, and Vascular Biology 2000, 20:2414-2421. Click for larger picture Hemodynamic Measures in PCOS Table 7: Hemodynamic Measurements in PCOS Cases and Controls Caucasian Only, 30+ Years of Age TOTAL N=95 N=116 Cases Controls Age 42.6 (6.0) 43.7 (6.2) Baseline Blood Pressure: Systolic mmHg 118.9 (16.7) 115.8 (16.6) Diastolic mmHg 75.7 (11.3) 73.4 (9.7) Pulse Pressure Values 43.2 (14.4) 42.4 (14.3) Baseline Lumen Diameter (mm) 3.09 (.50)** 2.88 (.37) Lumen Diameter at 30 seconds 3.21 (.53)** 3.00 (.38) Lumen Diameter at 60 seconds 3.23 (.50)** 3.01 (.39) Lumen Diameter at 90 seconds 3.19 (.47)** 2.99 (.39) Lumen Diameter at 12 0 seconds 3.20 (.50)** 2.98 (.39) Lumen Diameter at 150 seconds 3.19 (.51)** 2.97 (.38) Lumen Diameter 180 seconds 3.14 (.47)** 2.95 (.38) Lumen Diameter Peak 3.29 (.52) 3.08 (.39) FMD (% increase in Lumen Diameter from 7.33 (5.71) 7.15 (4.17) Baseline) FMD=Flow mediated Vasodilation **p<.01 Click for larger picture Correlation of Various Subclinical CHD Measures Table 8. Correlations of IMT, Carotid Plaque, and Measures in PCOS Cases and Controls Cases FMD LD baseline IMT .003 .142 Carotid Plaque (y/n) .038 .031 *borderline significant 0.05<p<.10 Endothelial Function FMD -.012 -.105 Controls LD baseline -.161* -.028 Click for larger picture Interaction of PCOS and Age in IMT 0.85 0.8 0.75 IMT (mm) 0.7 0.65 0.6 0.55 0.5 30-39 40-44 45-49 >=50 Age Groups (years) Figure 1: Interaction between PCOS and age in the determination of IMT (Cases = solid, Controls = hatched) (PCOS X age interaction p =.031) Reprinted with Permission from Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421 Click for larger picture Lancet 1997; 350 (suppl I):15 Click for larger picture Lancet 1997;350:21 Click for larger picture 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 Obesity Insulin Resistance Infertility (Elevated Testosterone) Hirsutism 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 intimamedia 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 CASES CONTROLS (1993-94 Data) (n=46) (n=59) Age (Current) BMI Diastolic Blood Pressure (mm Hg) Currently Smoking Hormone Use * p < .05 ** p .001 42 8 26.7 6.8 70.2 8.6 13 (28.3%) 1 (2.2%) 43 7 32.5 9.8** 74.4 12.2* 8 (13.6%) 15 (25.4%)** Selected Lipid and Hormone Levels in PCOS Cases and Controls- Preliminary Data VARIABLES CASES CONTROLS (1993-4 Data) HDLc (mg/dL) LDLc (mg/dL) Triglycerides (mg/dL) (n=46) 51.8 14.7 122.6 31.6 114.0 73.3 (n=59) 58.7 12.9* 111.5 28.7 78.5 34.1* HDL2 (mg/dL) Insulin ( U/L) FSH (IU/L) Total Testosterone (ng/dL) * p < .05 ** p .001 7.9 5.5 25.8 19.5 6.3 7.6 2.6 1.2 12.4 7.6** 13.8 9.6** 13.5 24.9* 1.0 0.5** Differences in CAI in PCOS Cases vs. Controls by Age 0,8 0,78 0,76 0,74 0,72 0,7 0,68 0,66 0,64 0,62 0,6 0,58 0.79 ** 0.75 * 0,7 0,71 0.69 0,66 CAI (mm) * p = 0.004 ** p = 0.021 All PCOS < 40 years Controls >= 40 years 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 Regression - Fixed Model Forced entry of CVD risk factors: P-value Model Model of Predictors Adjusted R2 Significance .000 .004 .042 .517 .350 .406 .000 Predictors Age BMI DBP Hormone Smoking Dependent variable = CAI Regression - Lipids and Insulin Individual entry of lipids and insulin to CVD fixed model: P-value Model Model of Predictors Adjusted R2 Significance .138 .403 .377 .095 .689 .414 .404 .405 .418 .408 .000 .000 .000 .000 .000 Predictors CHOL TRIG HDL LDL Insulin Dependent Variable = CAI Regression - PCOS Status Entry of PCOS status to CVD fixed model including LDL: Predictors Age BMI DBP Hormone Smoking LDL PCOS P-value of Predictors .000 .024 .065 .883 .349 .155 .043 Model Adjusted R2 .437 Model Significance .000 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 ...
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This note was uploaded on 02/23/2012 for the course PHARM 290 taught by Professor Staff during the Fall '10 term at Rutgers.

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