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Query: UMLS:C0004153 (atherosclerosis)
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Women with polycystic ovary syndrome (PCOS) often present for cosmetic and or reproductive symptoms; attention is generally not paid to the future risk of atherosclerosis for these women. Given that Asian Indians are insulin resistant and prone to metabolic syndrome at an earlier age, we assessed glucose/insulin ratio and intimal medial thickness (IMT) in young women with PCOS from south India. In this cross-sectional case control study, we assessed insulin resistance and carotid IMT in 40 women presenting with hyperandrogenic features of PCOS. Insulin resistance was assessed by fasting glucose/insulin ratio and IMT by the Doppler system with electrical linear transducer midfrequency of 12 MHz. Women with PCOS had higher fasting insulin levels (36.58 +/- 17.81 muU/mL, vs. 16.60 +/- 3.22 muU/mL in controls; p < 0.001), higher insulin resistance (glucose/insulin ratio 2.81 +/- 1.47 vs. 5.47 +/- 1.46 in controls; p < 0.001), and greater IMT (0.53 +/- 0.14 mm vs. 0.39 +/- 0.06 mm in controls; p < 0.001). Women with PCOS had a higher body mass index (BMI) (26.46 +/- 5.24 vs. 23.24 +/- 3.05 in controls; p < 0.001), and the differences between PCOS and controls persisted, even among those who had a BMI of less than 25. We concluded that South Indian women with the reproductive abnormalities of PCOS have greater insulin resistance and IMT, and therefore they must be advised about lowering the risk of future vascular disease.
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PMID:Risk of atherosclerosis in women with polycystic ovary syndrome: a study from South India. 1837 Jun 51

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by obesity-related risk factors for cardiovascular disease. The objective of our study was to determine values of key lipid and lipoprotein fractions in PCOS, and their possible relation to insulin resistance. A total of 75 women with PCOS (aged 23.1 +/- 5.1 years, BMI 24.9 +/- 4.7 kg/m(2)), and 56 age- and BMI-matched controls were investigated. In all subjects, basal glucose, cholesterol (total, HDL, and LDL), oxidized LDL (OxLDL), triglycerides, apolipoprotein (apo)A1, apoB, and apoE, nonesterified fatty acids, insulin, testosterone, sex hormone-binding globulin, homeostasis model assessment (HOMA) index, and free androgen index were determined in the follicular phase of the cycle. PCOS patients compared with controls had increased indices of insulin resistance, basal insulin (p < 0.001), and HOMA index (p < 0.001), and worsened insulin resistance-related dyslipidemia with decreased HDL cholesterol (p < 0.01), elevated triglycerides (p = 0.010), and pronounced LDL oxidation (p < 0.001). In conclusion, characteristic dyslipidemia of insulin resistance and unfavorable proatherogenic lipoprotein ratios were present only in women with PCOS and not in controls. Elevated OxLDL and the relation of apoE and nonesterified fatty acids with insulin resistance suggest that women with PCOS are at increased risk for premature atherosclerosis.
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PMID:Lipid and lipoprotein profile in women with polycystic ovary syndrome. 1841 29

Cardiovascular disease (CVD) is the leading cause of death among postmenopausal women. Changes in endothelial function play an important role in the pathophysiology of atherosclerosis, and evidence suggests that interventions to improve endothelial function could modify the rates of progression and the risk of cardiovascular events. In addition, a positive association between markers of endothelial dysfunction and androgenicity has been described in women with polycystic ovary syndrome, suggesting a correlation with the early-onset endothelial dysfunction found in these patients. We performed a cross-sectional study to verify whether endogenous testosterone levels are correlated with markers of inflammation and endothelial function and with anthropometric and metabolic profile in 53 postmenopausal women. Serum testosterone, sex hormone-binding globulin, C-reactive protein (CRP), fibrinogen, and plasma endothelin-1 (ET-1) were determined. Patients were stratified into 2 groups (higher or lower than the mean testosterone levels of the studied sample). Mean age was 55 years (+/-5), and median time since menopause was 5.5 years (interquartile range, 3-8 years). Body mass index and waist circumference were significantly higher in the group with testosterone levels >or=0.49 ng/mL. Median CRP levels were greater in the group with higher testosterone levels (1.17 [0.17-2.36] vs 0.17 [0.17-0.61] mg/L, P = .039). Median ET-1 levels were also higher in women with greater testosterone levels (0.84 [0.81-0.97] vs 0.81 [0.74-0.84] pg/mL, P = .023). An association of testosterone with CRP (r = 0.416, P = .004) and ET-1 (r = 0.323, P = .031) was observed. This association was dependent on homeostasis model assessment index for ET-1 but not CRP. Testosterone was also associated with waist circumference and blood pressure (P = .001). These data suggest that endogenous testosterone levels in recently postmenopausal women may be part of a proatherogenic profile. Longitudinal studies are needed to assess if androgenicity represents a risk factor for cardiovascular disease and the clinical relevance of its association with ET-1 and CRP in this population.
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PMID:Relationship between endogenous testosterone and cardiovascular risk in early postmenopausal women. 1855 38

Polycystic ovary syndrome (PCOS), a common reproductive endocrine condition manifests at puberty, and is characterized by hyperandrogenism, chronic anovulation, and obesity. PCOS cases exhibit an adverse coronary heart disease (CHD) profile at an early age, including insulin resistance, dyslipidemia and increased central adiposity. It can be hypothesized that the menopausal transition, whether natural or surgical, may provide an additional "insult", resulting in greater cumulative risk to their vasculature. Coronary artery calcification (CAC), a measure of subclinical atherosclerosis (SCA), was measured by electron beam tomography in 149 PCOS cases and 166 controls (mean age 47.3 and 49.4 respectively). Cases had a higher prevalence of CAC (63.1%) compared to controls (41.0%), (p = 0.037) after adjustment for age and BMI. A total of 22 cases and 39 controls had undergone natural menopause, 12 cases and 26 controls underwent surgical menopause (with biochemical confirmation) and 115 cases and 101 controls reported being currently premenopausal. There was a significant difference in CAC values between cases and controls in all three-menopause categories including pre-menopausal, surgically induced and natural menopause (p < 0.001). Duration since menopause (years) and use of hormone replacement therapy were not different between cases and controls for the two menopause groups. Logistic regression was carried out with CAC (< or = 10 vs > 10) as the dependent variable, and independent variables: PCOS status, current age, BMI, and menopausal status, (pre-menopause, surgical and natural menopause) and selected CHD risk factors. The data indicate that women with PCOS exhibit significantly increased CAC compared to controls after adjustment for age and BMI and menopausal status. PCOS status and fasting glucose were significant risk factors for CAC (p < 0.05). Both natural and surgical menopause were independent risk factors for CAC as well (p < 0.01). HDLT was of borderline significance, p < 0.10. Further follow-up of this cohort will be valuable in determining whether PCOS status continues to affect cardiovascular risk as they undergo the menopausal transition.
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PMID:Is there an independent effect of polycystic ovary syndrome (PCOS) and menopause on the prevalence of subclinical atherosclerosis in middle aged women? 1856 21

The polycystic ovary syndrome (PCOS) affects 5-10% of all premenopausal women. It is diagnosed by a combination of oligo-amenorrhea and hyperandrogenism (NIH criteria) or by the presence of two out of three of: oligo-amenorrhea, hyperandrogenism, polycystic ovaries on ultrasound (Rotterdam criteria). PCOS is associated with obesity, insulin resistance and dyslipidemia. Different patterns of dyslipidemia can be present, both in lean and obese PCOS. Low HDL-cholesterol, with or without elevated TG, is the most prominent lipid abnormality. In addition, smaller HDL and LDL particles and elevated postprandial TG responses are reported. Hyperandrogenism, anovulation and insulin resistance affect multiple steps in lipid metabolism in PCOS, as will be discussed. Surrogate markers for atherosclerosis are consistently abnormal in PCOS, while studies on clinical CVD endpoints are limited and non-conclusive. The (pharmaco-) therapy of dyslipidemia in PCOS will be discussed. In addition, the effects of other PCOS related (pharmaco-) therapies, primarily aimed at hyperandrogenism, anovulation or insulin resistance, on lipid metabolism will be addressed.
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PMID:Cardiometabolic abnormalities in the polycystic ovary syndrome: pharmacotherapeutic insights. 1860 48

The aim of the study were to answer the question 1.) Whether circulating pro-inflammatory markers of endothelial dysfunction and due to chronic low-grade inflammation of obesity, are altered in untreated lean, young relatively healthy polycystic ovary syndrome (PCOS) patients in comparison with healthy controls; 2.) Whether postprandial plasma concentration pattern of ghrelin and PYY can be predictable as risk factors for atherosclerosis and depend of obesity. Forty young women with PCOS were divided in two groups: 19 lean and 21 obese. The control group included 20 lean, healthy volunteers. Plasma total and active ghrelin, total PYY and PYY(3-36), serum adiponectin and insulin were measured using RIA technique, serum sCD40L, visfatin, sP-, sE-selectins, resistin by EIA. Composition of test meal was: 527 kcal total and consisted of 24.1% fat, 54.4% carbohydrate and 21.5% protein. Total and active ghrelin and total PYY were significantly lower in obese PCOS women, whereas active ghrelin was also significantly lower in lean PCOS women compared to controls. Postprandial plasma total ghrelin levels decrease were blunted in lean and obese compared to controls (12.8 % and 18.2% vs 28.2 %). Postprandial plasma active ghrelin decreased in lean and obese PCOS groups (49.9 % and 44.1 %) and controls (63.8 %). PCOS subjects exhibited smaller rises in postprandial levels of total PYY. Postprandial plasma PYY(3-36) levels increased in obese PCOS women (30.9 %) and controls (41%), whereas lean PCOS women exhibited blunted increase (11.5%). sCD40L levels increased, whereas adiponectin decreased in PCOS groups independently, whereas rise in visfatin, sE- and sP-selectin and the fall in adiponectin was associated with obesity. sP- and sE -selectins correlated positively with obesity. In summary, our study provides the first evidence that lean untreated young PCOS women contribute to the so called "pancreatic islet adaptation to insulin resistance" because of ghrelin and PYY profiles. We confirmed existing of low-grade chronic inflammation in early stage of visceral obesity in lean PCOS patients. The lost endogenous "islet adaptation to insulin resistance" may lead to endothelial dysfunction and promote acceleration of atherosclerosis.
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PMID:Postprandial response of ghrelin and PYY and indices of low-grade chronic inflammation in lean young women with polycystic ovary syndrome. 1881 36

Platelet hyporesponsiveness to the anti-aggregatory effects of nitric oxide (NO) occurs commonly in association with myocardial ischemia and coronary risk factors, often co-exists with endothelial dysfunction and represents an independent marker of long-term cardiovascular risk. We sought to determine whether polycystic ovary syndrome (PCOS), which has been postulated as a cardiovascular risk factor in women, is independently associated with this phenomenon. Twenty-four young women with PCOS (mean age 32.1+/-1.3) were evaluated in lean (n=12) and obese (n=12) subgroups, and compared with age-matched lean normals (n=12). Platelet aggregation and its inhibition by the nitric oxide donor sodium nitroprusside (SNP) were assessed and compared with vascular endothelial function. Plasma concentrations of malondialdehyde (MDA), N(G),N(G)-dimethyl-L-arginine (ADMA) and hs-CRP were measured as markers of oxidative stress, endothelial dysfunction and inflammation, respectively. Circulating endothelial progenitor cell (EPC) counts were also documented. In both PCOS subgroups, which demonstrated hyperaggregability to ADP, responses to SNP inhibition of aggregation (the principal end-point of the study) were significantly impaired (P<0.01 for both), as were their endothelium-dependent vascular responses to salbutamol (P<0.05 for both). However, vasomotor responses to nitroglycerin and circulating EPC counts did not vary between groups. PCOS subjects also had significantly elevated ADMA, MDA and hs-CRP levels relative to normals (all P<0.05). Impairment of SNP response remained unaltered after mean 30+/-2.4 months follow-up in PCOS subjects. We conclude that in PCOS subjects, independent of obesity and associated insulin resistance, profound and reproducible impairment of platelet responsiveness to NO is an additional component of cardiovascular homeostatic disturbance.
Atherosclerosis 2009 Jun
PMID:Polycystic ovary syndrome is associated with severe platelet and endothelial dysfunction in both obese and lean subjects. 1902 16

Women before menopause are at relatively lower risk of cardiovascular disease (CVD) compared with age-matched men and after menopause this gender advantage disappears. Androgen has been known to be an independent factor contributing to the higher male susceptibility to CVD, through adverse effects on lipids, blood pressure, and glucose metabolism. High androgen levels also contribute to CVD development in women with polycystic ovary syndrome as well as androgen abusing athletes and body builders. On the other hand, decline in androgen levels, as a result of ageing in men, is associated with hypertension, diabetes and atherosclerosis. Postmenopausal women, particularly those with oophorectomy are generally in low levels of sex hormones and androgen insufficiency is independently associated with the higher incidence of atherosclerosis in postmenopausal women. Androgen testosterone therapy (ATT) has been commonly used to improve well-being and libido in aging men with low androgen levels. The therapy has been demonstrated also to effectively reduce atherogenesis in these people. The use of ATT in postmenopausal women has increased in recent years and to date, however, the cardiovascular benefits of such therapy in these women remain uncertain. This review focuses on research regarding the impact of endogenous androgens and ATT on the cardiovascular physiology and CVD development in postmenopausal women.
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PMID:Cardiovascular physiology of androgens and androgen testosterone therapy in postmenopausal women. 1927 79

Women with polycystic ovary syndrome (PCOS) have chronic low-level inflammation that can increase the risk of atherogenesis. We measured circulating proatherogenic inflammatory mediators in women with PCOS (8 lean: body mass index, 18-25 kg/m(2); 8 obese: body mass index, 30-40 kg/m(2)) and weight-matched controls (8 lean, 8 obese). Blood samples were obtained fasting and 2 hours after glucose ingestion to measure interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), matrix metalloproteinase-2, plasminogen activator inhibitor-1 (PAI-1), and activated nuclear factor kappaB in mononuclear cells. Truncal fat was determined by dual-energy x-ray absorptiometry. Fasting MCP-1 levels were elevated in lean women with PCOS compared with lean controls (159.9 +/- 14.1 vs 121.2 +/- 5.4 pg/mL, P < .02). Hyperglycemia failed to suppress matrix metalloproteinase-2 in lean women with PCOS compared with lean controls (1.7 +/- 1.2 vs -4.8 +/- 1.6 pg/mL, P < .002). Among women with PCOS, obese individuals exhibited higher fasting sICAM-1 (16.1 +/- 0.8 vs 10.5 +/- 1.0 ng/mL, P < .03) and PAI-1 (6.1 +/- 0.7 vs 3.4 +/- 0.8 ng/mL, P < .03) levels. Trend analysis revealed higher (P < .005) IL-6, sICAM-1, CRP, PAI-1, systolic and diastolic blood pressures, triglycerides, fasting insulin, and homeostasis model assessment of insulin resistance index in women with PCOS compared with weight-matched controls, and the highest levels in the obese regardless of PCOS status. Fasting MCP-1 levels correlated with activated nuclear factor kappaB during hyperglycemia (P < .05) and androstenedione (P < .004). Truncal fat correlated with fasting IL-6 (P < .004), sICAM-1 (P < .006), CRP (P < .0009), and PAI-1 (P < .02). We conclude that both PCOS and obesity contribute to a proatherogenic state; but in women with PCOS, abdominal adiposity and hyperandrogenism may exacerbate the risk of atherosclerosis.
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PMID:Evidence of proatherogenic inflammation in polycystic ovary syndrome. 1937 63

This special issue of AJP is focused on research using nonhuman primates as models to further the understanding of women's health. Nonhuman primates play a unique role in translational science by bridging the gap between basic and clinical investigations. The use of nonhuman primates in biomedical research challenges our resolve to treat all life as sacred. The scientific community has responded by developing ethical guidelines for the care and the use of primates and clarifying the responsibility of investigators to insure the physical and psychological well-being of nonhuman primates used in research. Preclinical investigations often involve the use of animal models. Rodent models have been the mainstay of biomedical science and have provided enormous insight into the workings of many mammalian systems that have proved applicable to human biological systems. Rodent models are dissimilar to primates in numerous ways, which may limit the generalizability to human biological systems. These limitations are much less likely in nonhuman primates and in Old World primates, in particular, Macaques are useful models for investigations involving the reproductive system, bioenergetics, obesity and diabetes, cardiovascular health, central nervous system function, cognitive and social behavior, the musculoskeletal system, and diseases of aging. This issue considers primate models of polycystic ovary syndrome; diet effects on glycemic control, breast and endometrium; estrogen, reproductive life stage and atherosclerosis; estrogen and diet effects on inflammation in atherogenesis; the neuroprotective effects of estrogen therapy; social stress and visceral obesity; and sex differences in the role of social status in atherogenesis. Unmet research needs in women's health include the use of diets in nonhuman primate studies that are similar to those consumed by human beings, primate models of natural menopause, dementia, hypertension, colon cancer, and frailty in old age, and dedicated colonies for the study of breast cancer.
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PMID:The unique value of primate models in translational research. Nonhuman primate models of women's health: introduction and overview. 1950 47


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