4071 - Calculated LDL by Age Cases vs. Controls 140...

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Unformatted text preview: Calculated LDL by Age Cases vs. Controls 140 Calculated LDL 130 120 110 100 90 80 20 25 30 35 40 Age 45 50 55 Case Control Figure 1 HDLT by Age Cases vs. Controls 70 65 60 HDLT 55 50 45 40 20 25 30 35 40 45 Age 50 55 Case Control Figure 3 Triglycerides by Age Cases vs. Controls 190 Triglycerides 170 150 130 110 90 70 50 20 25 30 35 40 Age 45 50 55 Case Control Figure 5 Insulin by Age Cases vs. Controls 25 20 Insulin 15 10 5 0 20 25 30 35 40 Age 45 50 55 Case Control Figure 6 Androstenedione by Age Cases vs. Controls 330 Androstenedione 280 230 180 130 80 20 25 30 35 40 Age 45 50 55 Case Control Figure 7 Clinic BMI by Age Cases vs. Controls 40 38 36 34 32 30 28 26 24 22 20 20 25 30 35 40 Age 45 50 55 Clinic BMI Case Control Figure 8 Average Diastolic BP by Age Cases vs. Controls 80 78 76 74 72 70 68 66 64 62 60 20 25 30 35 40 Age 45 50 55 Average Diastolic BP Case Control Average Systolic BP by Age Cases vs. Controls 130 Average Systolic BP 125 120 115 110 105 100 95 90 20 25 30 35 40 Age 45 50 55 Case Control Clinic Estradiol 2 by Age Cases vs. Controls 120 110 Estradiol 2 100 90 80 70 60 50 20 25 30 35 40 Age 45 50 55 Case Control 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 Ongoing protocol to evaluate the CHD risk factors and subclinical atherosclerosis as measured by carotid ultrasound in women with PCOS. Research Methodology Clinic Visit (continued) Blood analyte assessment Lipids ( total cholesterol, triglycerides, LDLc, HDLc) Fasting glucose and insulin Fibrinolytic/coagulation parameters tissue plasminogen activator (tPA) plasminogen activator inhibitor (PAI-1) Carotid Atherosclerotic Index (CAI) Represents the overall mean of the mean measurements of carotid intima-media thickness at 8 sites Arterial sites of interest included : left/ right proximal common carotid left/ right distal common carotid left/ right carotid bulb left/ right distal internal carotid Baseline Demographic and Reproductive Factors in PCOS Table 1: Baseline Sociodemographic and Reproductive Factors in PCOS Cases and Controls of Similar Age (1992-1994) Cases (N=125) Mean (SD) or % 37.5 (6.2) 14.4 (2.0) 85.7% 23.0% 15.9% 8.8% 1.6% 1.8 (1.9) 1.0 (1.1) Controls (N=142) Means (SD) or % 39.0 (6.2) 14.6 (2.0) 68.5% 17.5% 17.5% 9.1% 2.1% 2.2 (1.7) 1.9 (1.5) Variables Age (as of 1992-93) Years of Education % Married % Current Smoking % OCP/HRT % Surgical/other % Natural Menopause Number of Pregnancies Number of Live Births p value .050 .401 .044 .459 .512 .918 .152 .082 <.001 Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421 Click for larger picture Baseline Cardiovascular Risk Factors in PCOS Table 2: Selected Baseline Cardiovascular Risk Factors in PCOS Cases and Controls of Similar Age (1992-1994) Cases(N=125) Adjusted Mean (SE) N/A .82 (0.01) 112.2 (1.0) 71.0 (0.7) 195.2 (3.0) 120.1 (2.7) 51.6 (1.2) 8.9 (0.6) 21.2 (1.4) 119.2 (5.7) 1.64 (0.08) 209.2 (9.9) 1.53 (.09) Controls(N=142) Adjusted Mean (SE) N/A .78 (0.01)* 112.0 (1.0) 71.7 (0.7) 189.2 (2.7) 116.4 (2.5) 55.5 (1.1)* 11.4 (0.5)* 16.3 (1.3)* 87.0 (5.4)* 1.05 (0.07)* 158.8 (8.9)* 1.16 (0.09)* Unadj P value <.001 <.001 .038 .155 .042 .059 <.001 <.001 <.001 <.001 <.001 <.001 .005 Variables BMI kg/m2 Waist:hip ratio SBP mm Hg DBP mm Hg CHOL mg/dL LDLc mg/dL HDLt mg/dL HDL2 mg/dL Insulin U/mL TRIG mg/dL Total T nmol/dL AD ng/dL LH/FSH *Adj. p value <.001 Mean (SE) 30.1 (0.7) .84 (0.01) 113.9 (1.3) 72.3 (1.0) 196.5 (2.7) 122.1 (2.6) 50.1 (1.3) 8.2 (0.6) 23.7 (2.1) 124.1 (7.7) 1.65 (0.10) 208.8 (12.4) 1.52 (0.09) Mean (SD) 26.5 (0.5) .77 (0.01) 110.4 (1.1) 70.6 (0.7) 188.3 (2.9) 115.0 (2.6) 56.8 (1.2) 11.9 (0.6) 14.0 (0.9) 82.2 (3.7) 1.04 (0.04) 158.5 (6.6) 1.16 (0.09) Arteriosclerosis, Thrombosis, and Click for larger picture Vascular Biology, 2000;20:2414-2421 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. Scoring was as follows: 0= no stenosis, 1 = small stenosis <30% of vessel area, 2= 1 medium stenosis between 30-50% of vessel area or multiple small stenoses and 3=1 large stenosis >50% or multiples with at 1 medium stenosis. These were summed to create an overall plaque index. Plaque Index in PCOS Table 3: Plaque Index results for PCOS cases and controls Cases % Controls % 84.5 11.3 3.5 0.7 91.5 6.1 1.2 1.2 75.0 18.3 6.7 0.0 Plaque index n Total: 0 98 78.4 1 14 11.2 2 4 3.2 3+ 9 7.2 30-44 yr : 0 66 84.6 1 8 10.3 2 2 2.6 3+ 2 2.6 45+ yr : 0 32 68.1 1 6 12.8 2 2 4.3 3+ 7 14.9 * p value presented for Chi Square Test n 120 16 5 1 75 5 1 1 45 11 4 0 p-value* .050 .607 .019 Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421 Click for larger picture Carotid IMT in PCOS by Age and BMI ns 0,8 0,75 0,7 0,65 0,6 BMI: LT 26 ns .219 .040 Case Control GE 26 LT 26 GE 26 Age: < 45 years > 45 years Univariate Regression of IMT and Baseline CHD Risk Factors- summary 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: BMI, DBP, SBP, insulin, W:H, age, TRIG 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 Regression Modeling of IMT in PCOS Women and Controls a45 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 Regression Modeling of IMT in PCOS Women and Controls a45 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 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 Multivariate Regression Models of IMT- Effect of PCOS Models adjusted for age and BMI 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 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 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). 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 PCOSIMT 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. Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421 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. 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. Arteriosclerosis, Thrombosis, and Vascular Biology, 2000;20:2414-2421 Calcification Scores in PCOS Table 9: Distribution of Coronary and Aortic Calcification Scores in PCOS Cases and Controls* Cases Coronary Controls Score 0 1-10 11-50 50-300 300+ % 46.4 46.4 3.6 0.0 3.6 Aortic % 57.1 7.1 14.3 10.7 10.7 Coronary % 75.9 17.2 6.0 0.0 0.0 Aortic % 69.0 13.8 10.3 6.9 0.0 13 13 1 0 1 16 2 4 3 3 22 5 2 0 0 20 4 3 2 0 C2 (any vs. none) = 5.2 (p=.022) and 0.9 (p=.355) for coronary and aortic calcification, respectively. * Coronary= coronary calcification score; Aortic= aortic calcification score Click for larger picture 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. 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. ...
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