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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
PCOS Cases N= 50
Controls N = 56
P value
PAI-1 ng/ml 27.6 18.8 .026 TPA ng/ml 11.0 9.9 .127 Factor VII % 128.0 132.0 .648 D-Dimer ng/ml 99.7 106.3 .715 Fragment 1.2 nM 1.16 1.23 .575 CRP g/ml 2.14 2.45 .414
The Alternative Hypothesis: Conversely, PCOS women may be protected from Conversely, PCOS women may be protected from
later life onset of CHD by the altered hormonal later life onset of CHD by the altered hormonal profile that includes increased estrone from profile that includes increased estrone from peripheral conversion of androgen in adipose and peripheral conversion of androgen in adipose and other tissueother tissue
This profile could be responsible for the This profile could be responsible for the inconsistencies observed between investigations of inconsistencies observed between investigations of risk factors in PCOS and the McKeigue retrospective risk factors in PCOS and the McKeigue retrospective follow-up of mortalityfollow-up of mortality
Carotid IMT in PCOSTable 6: Carotid IMT results for PCOS cases and controls
Cases Controls IMT (mm) *
N Mean ±SE Age-BMI Adj. Mean (CI)
N Mean ± SE Age-BMI Adj Mean (CI)
p-value*
Total 125 .70 ± .01 .70 (.68-.73) 142 .68 ± .01 .67 (.65-69) .299 30-44 yr 78 .65 ± .01 .65 (.62-.69) 82 .66 ± .01 .64 (.61.67) .565 45+ yr 47 .78 ± .03 .77 (.74-.81) 60 .70 ± .01 .71(.68-.75) .005 *statistical test performed on transformed variable Reprinted with Permission pending from Arteriosclerosis, Thrombosis, and Vascular Biology 2000, 20:2414-2421.
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Hemodynamic Measures in PCOSTable 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 Baseline)
7.33 (5.71) 7.15 (4.17)
FMD=Flow mediated Vasodilation **p<.01
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Correlation of Various Subclinical CHD Measures
Table 8. Correlations of IMT, Carotid Plaque, and Endothelial Function Measures in PCOS Cases and Controls
Cases Controls FMD LD baseline FMD LD baseline IMT .003 .142 -.012 -.161* Carotid Plaque (y/n) .038 .031 -.105 -.028
*borderline significant 0.05<p<.10
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Interaction of PCOS and Age in IMT
0.5
0.55
0.6
0.65
0.7
0.75
0.8
0.85
30-39 40-44 45-49 >=50
Age Groups (years)
IMT
(mm
)
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
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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 Polycystic Ovary Syndrome (PCOS) is associated
with an increased prevalence of cardiovascular with an increased prevalence of cardiovascular disease risk factors (Wild, !988; Slowinska-disease risk factors (Wild, !988; Slowinska-Srezednicka, 1991; Talbott and Guzick, 1995)Srezednicka, 1991; Talbott and Guzick, 1995)
PCOS women have evidence of metabolic PCOS women have evidence of metabolic derangements similar to Syndrome X (derangements similar to Syndrome X (LDLc, LDLc, HDLc, HDLc, triglycerides, triglycerides, insulin, insulin, central adiposity, central adiposity, hypertension, and Type II diabetes)hypertension, and Type II diabetes)
Introduction (cont.) Since LDLc is an important determinant of Since LDLc is an important determinant of
atherosclerosis in women, the increased atherosclerosis in women, the increased LDLc levels seen in younger PCOS LDLc levels seen in younger PCOS suggests that these women may be at suggests that these women may be at increased risk for subclinical and clinical increased risk for subclinical and clinical atherosclerosis at an earlier age than the atherosclerosis at an earlier age than the general female population.general female population.
Characteristics of PCOS
Chronic AnovulationChronic Anovulation Hyperandrogenism Hyperandrogenism
(Elevated (Elevated Testosterone)Testosterone)
HirsutismHirsutism
ObesityObesity Insulin ResistanceInsulin Resistance InfertilityInfertility
Affects 5 to 10 percent of US Women, and the condition is marked by:
Research Questions Do women with PCOS have evidence of Do women with PCOS have evidence of
subclinical atherosclerosis as demonstrated by subclinical atherosclerosis as demonstrated by an increase in carotid intima-media thickness?an increase in carotid intima-media thickness?
If so, can the increase in carotid intima-media If so, can the increase in carotid intima-media thickness be linked to the various thickness be linked to the various cardiovascular risk factors seen in PCOS cardiovascular risk factors seen in PCOS women?women?
Current Study Population Women participating in Phase II of the Women participating in Phase II of the
Cardiovascular Health and Risk Measurement Cardiovascular Health and Risk Measurement Study (CHARM, 1997-98)Study (CHARM, 1997-98)
Cases and controls represent the initial 1/3 of the Cases and controls represent the initial 1/3 of the women recruited for Phase II participation (46 women recruited for Phase II participation (46 Cases with PCOS and 59 Controls)Cases with PCOS and 59 Controls)
PCOS is defined as chronic anovulation with PCOS is defined as chronic anovulation with clinical or biochemical evidence of clinical or biochemical evidence of hyperandrogenism without other identified causeshyperandrogenism without other identified causes
Selected Clinical and Lifestyle Factors in PCOS Cases and Controls- Preliminary Data
Age (Current) 42 8 43 7BMI 26.7 6.8 32.5 9.8**Diastolic Blood Pressure (mmHg)
70.2 8.6 74.4 12.2*
Currently Smoking 13 (28.3%) 8 (13.6%)Hormone Use 1 (2.2%) 15 (25.4%)**
VARIABLES(1993-94 Data)
CASES(n=46)
CONTROLS(n=59)
* p .05** p .001
Selected Lipid and Hormone Levels in PCOS Cases and Controls- Preliminary Data
HDLc (mg/dL) 51.8 14.7 58.7 12.9*LDLc (mg/dL) 122.6 31.6 111.5 28.7Triglycerides (mg/dL) 114.0 73.3 78.5 34.1*HDL2 (mg/dL) 7.9 5.5 12.4 7.6**Insulin (U/L) 25.8 19.5 13.8 9.6**FSH (IU/L) 6.3 7.6 13.5 24.9*Total Testosterone(ng/dL)
2.6 1.2 1.0 0.5**
VARIABLES(1993-4 Data)
CASES(n=46)
CONTROLS(n=59)
* p .05** p .001
Differences in CAI in PCOS Cases vs. Controls by Age
0.75 *
0,7 0.69
0,66
0.79 **
0,71
0,580,6
0,620,640,660,68
0,70,720,740,760,78
0,8C
AI (
mm
)
All < 40 years >= 40 years
PCOS Controls* p = 0.004
** p = 0.021
Analysis of CAI Predictors in PCOS Cases and Controls
Employed a multiple linear regression model with Employed a multiple linear regression model with forced entry of predictorsforced entry of predictors
Dependent variable: CAIDependent variable: CAI Independent variables in the fixed model included: Independent variables in the fixed model included:
age, BMI, DBP, smoking and hormone useage, BMI, DBP, smoking and hormone use Lipids and insulin were added separately to the fixed Lipids and insulin were added separately to the fixed
model to determine the change in Rmodel to determine the change in R22
PCOS status was added to the final model to evaluate PCOS status was added to the final model to evaluate attenuation of the relationships by case statusattenuation of the relationships by case status
Regression - Fixed Model
Age .000 .406 .000BMI .004DBP .042Hormone .517Smoking .350
PredictorsP-value
of PredictorsModel
Adjusted R2Model
Significance
Forced entry of CVD risk factors:
Dependent variable = CAI
Regression - Lipids and Insulin
CHOL .138 .414 .000TRIG .403 .404 .000HDL .377 .405 .000LDL .095 .418 .000Insulin .689 .408 .000
PredictorsP-value
of PredictorsModel
Adjusted R2Model
Significance
Individual entry of lipids and insulin to CVD fixed model:
Dependent Variable = CAI
Regression - PCOS Status
Age .000 .437 .000BMI .024DBP .065Hormone .883Smoking .349LDL .155PCOS .043
Predictors P-valueof Predictors
ModelAdjusted R2
ModelSignificance
Entry of PCOS status to CVD fixed model including LDL:
Dependent variable = CAI
Conclusions PCOS women demonstrate increased carotid PCOS women demonstrate increased carotid
intima-media thickness compared to age matched intima-media thickness compared to age matched controls at a relatively young age (< 40 years).controls at a relatively young age (< 40 years).
However, the most striking evidence of subclinical However, the most striking evidence of subclinical atherosclerosis in PCOS appears in the atherosclerosis in PCOS appears in the 40 year 40 year age group.age group.
Conclusions (cont.)
Age, BMI, and diastolic blood pressure are Age, BMI, and diastolic blood pressure are significant predictors of CAI in womensignificant predictors of CAI in women
Atherosclerotic potential in the younger PCOS Atherosclerotic potential in the younger PCOS women is mediated by in part by higher LDLc women is mediated by in part by higher LDLc levels and increased BMI.levels and increased BMI.
Implications
Since abnormal LDLc levels and increased Since abnormal LDLc levels and increased BMI appear to contribute to subclinical BMI appear to contribute to subclinical atherosclerosis in PCOS, interventions atherosclerosis in PCOS, interventions directed at decreasing LDLc and controlling directed at decreasing LDLc and controlling weight in younger PCOS women may weight in younger PCOS women may improve the later-life cardiovascular risk improve the later-life cardiovascular risk profile in this high risk population.profile in this high risk population.
Evelyn O. TalbottA544 Crabtree HallPittsburg, PA(412) 624-3074