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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent trends in the American lifestyle, such as a high-fat diet and inactivity, have promoted the emergence of a metabolic disorder titled syndrome X. Although originally linked to non-insulin-dependent diabetes mellitus (NIDDM) and characterized by insulin resistance, syndrome X is now better described as a cascade of disorders encompassing not only NIDDM, but also hypertension, atherosclerosis, centrally distributed obesity, and dyslipidemia. Further pathology has been linked to syndrome X, such as polycystic ovary disease, microvascular angin, and the presence of acanthosis nigricans. Recognition and appropriate management of syndrome X will prevent deleterious patient outcomes that might occur without continuity of care in treating associated disorders. Pharmacological management of syndrome X includes the use of insulin-sparing antihyperglycemic agents and/or combination therapy and avoidance of several frequently prescribed medications. Clinicians need to initiate renewed efforts to provide lifestyle counselling to promote ideal body weight, since interpretation of research data concerning syndrome X reinforces that serious health consequences will result from obesity and inactivity.
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PMID:Syndrome X. Recognition and management of this metabolic disorder in primary care. 878 76

Hyperinsulinaemia is found in 30% of slim and 75% of obese women with polycystic ovary syndrome. Despite resistance to insulin action in terms of glucose transport, increased insulin levels may cause hyperandrogenaemia by enhancement of androgen production in the ovaries where insulin acts as co-gonadotrophin. Recent interest in insulin resistance results from the recognition that it predisposes to various metabolic abnormalities, and could be involved in the pathogenesis of atherosclerosis. Women with polycystic ovary syndrome frequently have metabolic disturbances associated with insulin resistance, and recent long-term follow-up studies have indicated that they also have a higher incidence of diabetes and hypertension later in life compared with control populations. This review describes the association of hyperinsulinaemia with hyperandrogenism, metabolic and circulatory changes in women with polycystic ovary syndrome. Special emphasis is placed on recent studies of molecular mechanisms of insulin resistance in polycystic ovary syndrome and clinical implications of hyperinsulinaemia in these women.
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PMID:Insulin resistance in polycystic ovary syndrome. 926 4

Atherogenesis in the vasculature is accelerated by changes in the dynamic equilibrium between endogenous tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1). Increased expression of PAI-1, decreased expression of tissue plasminogen activator, or both can lead to decreased fibrinolytic activity and predispose to thrombosis. Increased concentrations of insulin (and proinsulin) in the plasma increase plasma PAI-1, although the mechanisms of this effect are not known. In addition, it has been observed that basal fibrinolytic activity is decreased in patients with type 2 diabetes; this may accelerate atherosclerosis by exposing vascular luminal wall surfaces to persistent and recurrent thrombi. Abnormalities in the vessel wall appear to contribute to the increased risk. There is also evidence that PAI-1 content is increased in atherosclerotic lesions of patients with type 2 diabetes, suggesting that interventions to reduce insulin resistance and improve glycemic control may improve the fibrinolytic response. Clinical studies in patients with polycystic ovary syndrome (characterized by insulin resistance, hyperinsulinemia, ovarian androgen overproduction, and impaired fibrinolytic capacity) demonstrated that treatment with troglitazone, an insulin-sensitizing agent, can markedly reduce blood levels of PAI-1. There is also clinical evidence that these agents may contribute to regression of intimal medial thickness in patients with type 2 diabetes, providing further indication that antidiabetic interventions may help inhibit the progression of early atherosclerotic lesions.
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PMID:Insulin resistance and thrombosis: a cardiologist's view. 1041 58

Recent developments have advanced our knowledge of the role of estrogen in the male. Studies of the mutations in CYP19, the gene encoding aromatase, in six females and two males and a mutant estrogen receptor alpha in a man are described. These observations provide illuminating new insights into the critical role of estrogen in the male (as well as female) in the pubertal growth spurt and skeletal maturation, and in the importance of estrogen sufficiency in the accrual and maintenance of bone mass. The weight of evidence supports an effect of androgens on the latter processes, but this effect has not been quantitated. There is a discordance in the estrogen-deficient male between skeletal growth and skeletal maturation and the accrual of bone mass and density. Estrogen synthesis by the testis is limited before puberty, and estrogen deficiency does not affect the age of pubertal onset. Estrogen deficiency in men leads to hypergonadotropism, macroorchidism, and increased testosterone levels. Estrogen lack has a significant effect on carbohydrate and lipid metabolism, and estrogen resistance was associated with evidence of premature coronary atherosclerosis in a man. These observations have highlighted the role of extraglandular estrogen synthesis and intracrine and paracrine actions. In the human, in contrast to nonprimate vertebrates, aromatase deficiency and estrogen resistance (alpha) does not seem to affect gender identity or psychosexual development. The clinical repercussions of mutations in CYP19 on the fetal-placental unit have highlighted the major role of placental aromatase in the protection of the female fetus from androgen excess, thus preventing androgen-induced pseudohermaphrodism and virilization of the mother. These features are compared with the virilization that occurs in utero in the female spotted hyena. The novel features of the aromatase deficiency syndrome in the affected female--in the fetus, during childhood, and at puberty--are discussed, including virilization at puberty and development of polycystic ovaries. The severity of the syndrome correlates with the severity of impairment of aromatase formation in expression systems. Finally, the structural consequences of missense mutations in CYP19 are described in accordance with a model of the structure of human aromatase.
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PMID:Estrogen: consequences and implications of human mutations in synthesis and action. 1129 27

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. An adverse lipid profile has also been observed in PCOS-affected women, suggesting that these individuals may be at increased risk for coronary heart disease at a young age. The objective of the present study was to evaluate subclinical atherosclerosis among women with PCOS and age-matched control subjects. A total of 125 white PCOS cases and 142 controls, aged >/=30 years were recruited. Collection of baseline sociodemographic data, reproductive hormone levels, and cardiovascular risk factors was conducted from 1992 to 1994. During follow-up (1996 to 1999), these women underwent B-mode ultrasonography of the carotid arteries for the evaluation of carotid intima-media wall thickness (IMT) and the prevalence of plaque. A significant difference was observed in the distribution of carotid plaque among PCOS cases compared with controls: 7.2% (9 of 125) of PCOS cases had a plaque index of >/=3 compared with 0.7% (1 of 142) of similarly aged controls (P=0.05). Overall and in the group aged 30 to 44 years, no difference was noted in mean carotid IMT between PCOS cases and controls. Among women aged >/=45 years, PCOS cases had significantly greater mean IMT than did control women (0.78+/-0.03 versus 0.70+/-0.01 mm, P:=0. 005). This difference remained significant after adjustment for age and BMI (P:<0.05). These results suggest that (1) lifelong exposure to an adverse cardiovascular risk profile in women with PCOS may lead to premature atherosclerosis, and (2) the PCOS-IMT association is explained in part by weight and fat distribution and associated risk factors. There may be an independent effect of PCOS unexplained by the above variables that is related to the hormonal dysregulation of this condition.
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PMID:Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women. 1107 46

The emerging public health problem of type 2 diabetes in youth reflects increasing rates of childhood obesity. As in adults, type 2 diabetes in children is part of the insulin resistance syndrome that includes hypertension, dyslipidemia and other atherosclerosis risk factors, and hyperandrogenism seen as premature adrenarche and polycystic ovary syndrome. Studies in children document risk factors for type 2 diabetes and associated cardiovascular risk factors, including obesity, family history, diabetic gestation, and underweight or overweight for gestational age. Genetically determined insulin resistance, or limited beta-cell reserve, has been demonstrated in high risk individuals. This genetic background, considered advantageous in a feast and famine existence (the thrifty genotype), is rendered detrimental with abundant food and physical inactivity, a lifestyle demonstrated to be typical of families of children with type 2 diabetes. Case finding in high risk individuals who are asymptomatic may be an appropriate response to the public health challenge of type 2 diabetes in children, because risk factors for cardiovascular disease are already present at the time of diagnosis. Treatment is dictated by the degree of metabolic derangement and symptoms. The only data on the use of oral hypoglycemic agents in children has been with metformin. Prevention efforts will require community and government involvement to reduce obesity and increase physical activity in the child, as well as adult, population.
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PMID:Increasing incidence of type 2 diabetes in children and adolescents: treatment considerations. 1196 May 10

Women with polycystic ovary syndrome (PCOS) have several cardiovascular disease risk factors. Since hyperhomocysteinemia is associated with early atherosclerosis, it was postulated that the homocysteine levels are higher in PCOS patients than in control subjects which, therefore, may explain the cardiovascular disease risk. Thirty-five women with PCOS and 20 healthy subjects were studied. Endocrine assays, lipid profile, homocysteine and insulin level determinations, and ultrasound evaluation were performed in all subjects. We found significantly higher mean plasma homocysteine concentrations in patients with PCOS as compared with controls (10.4 +/- 4.4 vs. 7.2 +/- 1.5 ng/dl; p < 0.003). These data show that in PCOS early atherosclerosis is not exclusively dependent on hyperinsulinemia and elevated lipid profile - PCOS patients are exposed to significantly higher homocysteine levels which might increase the cardiovascular disease risk.
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PMID:The plasma homocysteine levels are increased in polycystic ovary syndrome. 1205

Women with polycystic ovary syndrome (PCOS) have a clustering of cardiovascular risk factors, such as obesity, lipid abnormalities, impaired glucose tolerance, insulin resistance, and hypertension. Exercise is reported to lower the incidence of cardiac events. The effect of exercise on plasma homocysteine concentrations, an independent cardiovascular risk factor, has not been previously reported in women with PCOS. We examined the effects of exercise on plasma total homocysteine concentrations in young overweight or obese PCOS women [age (mean +/- SD), 30.6 +/- 6.6 yr; body mass index, 35.49 +/- 7.57 kg/m(2)]. Twenty-one women consented to a 6-month exercise program; 12 women (exercisers) adhered to the program, whereas 9 (nonexercisers) did not. In both groups of women, the following parameters were recorded at baseline and 6 months: body mass index, waist-to-hip ratio, and aerobic capacity (maximal oxygen consumption); blood samples were taken after an overnight fast for plasma total homocysteine, insulin, and other biochemical parameters. A significant decrease in plasma total homocysteine concentrations (P < 0.001) and waist-to-hip ratio (P = 0.041) and a significant increase in maximal oxygen consumption (P = 0.019) were recorded at 6 months, compared with baseline in the exercise group. This decrease in homocysteine was not explained by changes in anthropometric or biochemical parameters. In contrast, no significant changes in any of the variables were observed in the nonexercise group. Our study has provided the first evidence that regular exercise significantly lowers plasma homocysteine in young overweight or obese women with PCOS, a group at increased risk of premature atherosclerosis. The precise mechanism by which exercise is associated with a reduction in homocysteine remains to be elucidated.
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PMID:Exercise decreases plasma total homocysteine in overweight young women with polycystic ovary syndrome. 1236 25

The emerging epidemic of type 2 diabetes (T2DM) in young people reflects increasing rates of obesity and parallels the increasing frequency of T2DM in adults. As in adults, T2DM in children is part of the insulin resistance syndrome that includes hyperandrogenism seen as premature adrenarche and polycystic ovary syndrome, hypertension, dyslipidemia, and other atherosclerosis risk factors. Recent studies in children document risk factors for T2DM, and associated cardiovascular risk factors, including obesity, family history, diabetic gestation, and underweight or overweight for gestational age. Genetically determined insulin resistance or limited beta-cell reserve has been demonstrated in high-risk individuals, including first-degree relatives of girls with premature adrenarche. This genetic background, considered advantageous in a feast-and-famine existence (the thrifty genotype), is rendered detrimental with abundant food and physical inactivity, a lifestyle demonstrated to be typical of families of children with T2DM. The increasing incidence of T2DM in children and adolescents threatens to become a major public health problem. Risk factors for cardiovascular disease, hypertension, hyperlipidemia, and microalbuminuria are present at diagnosis of T2DM in Native American adolescents, indicating that insulin resistance has been present for some time before the diagnosis of diabetes was made. Case finding is likely to be beneficial in high-risk youths. Treatment is the same as that of adults. The only data on use of oral hypoglycemic agents in children have been with metformin. Community and governmental efforts to educate all children and their parents about the need for physical activity and dietary modification are essential to control this epidemic.
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PMID:Type 2 diabetes in children. 1276 53

Women with polycystic ovary syndrome (PCOS) are often assumed, a priori, to be at increased risk for cardiovascular disease (CVD), given the high prevalence of the metabolic syndrome X among them. There is, however, no single definition of PCOS, and for that reason a comparison of studies that have analyzed its association with CVD is compromised from the start. Long-term studies of well characterized women with PCOS are lacking, and the link to primary cardiovascular events such as stroke or myocardial infarction remains more speculative than substantive. Epidemiological studies that have focused on isolated signs and stigmata of PCOS, such as polycystic ovaries, hyperandrogenism, or chronic anovulation, have found mixed results. There are studies that suggest a slight increase in cardiovascular events in women with polycystic ovaries, with perhaps stronger evidence between an increased risk of cardiovascular events in women with menstrual irregularity. However, there is little evidence for an association between hyperandrogenism per se and cardiovascular events. Furthermore, there are less data to substantiate an increased risk of events in women with PCOS identified on the basis of a combination of signs and symptoms, such as hyperandrogenic chronic anovulation. The existing data suggest that PCOS may adversely affect or accelerate the development of an adverse cardiovascular risk profile, and even of subclinical signs of atherosclerosis, but it does not appear to lower the age of clinical presentation to a premenopausal age group. Future studies to identify the risk of cardiovascular events in women with PCOS will benefit from clear and extensive phenotyping of PCOS abnormalities at baseline, from a prospective design, from larger sample sizes, and from longer follow-up.
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PMID:Polycystic ovary syndrome and cardiovascular disease: a premature association? 1278 1


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