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

Obstructive sleep apnea (OSA) is a prevalent disorder particularly among middle-aged, obese men, although its existence in women as well as in lean individuals is increasingly recognized. Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, sleep apnea has been treated as a 'local abnormality' of the respiratory track rather than as a 'systemic illness.' In 1997, we first reported that the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. Also, we reported a positive correlation between IL-6 or TNFalpha plasma levels and the body-mass-index (BMI). In subsequent studies, we showed that IL-6, TNFalpha, and insulin levels were elevated in sleep apnea independently of obesity and that visceral fat, was the primary parameter linked with sleep apnea. Furthermore, our findings that women with the polycystic ovary syndrome (PCOS) (a condition associated with hyperandrogenism and insulin resistance) were much more likely than controls to have sleep disordered breathing (SDB) and daytime sleepiness, suggests a pathogenetic role of insulin resistance in OSA. Other findings that support the view that sleep apnea and sleepiness in obese patients may be manifestations of the Metabolic Syndrome, include: obesity without sleep apnea is associated with daytime sleepiness; PCOS and diabetes type 2 are independently associated with EDS after controlling for SDB, obesity, and age; increased prevalence of sleep apnea in post-menopausal women, with hormonal replacement therapy associated with a significantly reduced risk for OSA; lack of effect of continuous positive airway pressure (CPAP) in obese patients with apnea on hypercytokinemia and insulin resistance indices; and that the prevalence of the metabolic syndrome in the US population from the Third National Health and Nutrition Examination Survey (1988-1994) parallels the prevalence of symptomatic sleep apnea in general random samples. Finally, the beneficial effect of a cytokine antagonist on EDS in obese, male apneics and that of exercise on SDB in a general random sample, supports the hypothesis that cytokines and insulin resistance are mediators of EDS and sleep apnea in humans. In conclusion, accumulating evidence provides support to our model of the bi-directional, feed forward, pernicious association between sleep apnea, sleepiness, inflammation, and insulin resistance, all promoting atherosclerosis and cardiovascular disease.
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PMID:Sleep apnea is a manifestation of the metabolic syndrome. 1589 51

The new millennium has brought intense focus of interest on the risk of cardiovascular disease in women. The polycystic ovary syndrome (PCOS) is a common endocrine disorder in women characterised by hyperandrogenism and oligomenorrhoea. Most women with PCOS also exhibit features of the metabolic syndrome, including insulin resistance, obesity and dyslipidaemia. While the association with type 2 diabetes is well established, whether the incidence of cardiovascular disease is increased in women with PCOS remains unclear. Echocardiography, imaging of coronary and carotid arteries, and assessments of both endothelial function and arterial stiffness have recently been employed to address this question. These studies have collectively demonstrated both structural and functional abnormalities of the cardiovascular system in PCOS. These alterations, however, appear to be related to the presence of individual cardiovascular risk factors, particularly insulin resistance, rather than to the presence of PCOS and hyperandrogenaemia per se. However, given the inferential nature of the evidence to date, more rigorous cohort studies of long-term cardiovascular outcomes and clinical trials of risk factor modification are required in women with PCOS.
Atherosclerosis 2006 Apr
PMID:Cardiovascular disease in the polycystic ovary syndrome: new insights and perspectives. 1631 10

The Polycystic Ovary Syndrome (PCOS) affects 6 to 10% of women of childbearing age. Insulin resistance and hyperinsulinemia are present in nearly all PCOS patients and play a central role in the development of both hyperandrogenism and metabolic syndrome (MS). MS occurs in approximately 43% of PCOS patients, raising the cardiovascular risk to up seven fold in these patients. Several serum, functional and structural markers of endothelial dysfunction and subclinical atherosclerosis were described in PCOS patients, even those young and non-obese. However, despite the fact that PCOS adversely affects the cardiovascular profile, long-term studies did not demonstrate a consistent raise in cardiovascular mortality, which seems to be more observed in the post-menopausal period. Recently, oral contraceptives are being substituted for insulin sensitizing agents (metformin and glitazones) in the PCOS treatment, due to their effects on insulin resistance and cardiovascular risk.
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PMID:[Polycystic ovary syndrome, metabolic syndrome, cardiovascular risk and the role of insulin sensitizing agents]. 1793 74

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

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

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired cortisol biosynthesis, with or without aldosterone deficiency, and androgen excess. Patients with the classic (severe) form also have epinephrine deficiency. Patients with CAH have an increased prevalence of risk factors for cardiovascular disease including obesity, hypertension, and insulin resistance. Androgen excess in women appears to be an additional risk factor for cardiovascular disease. Carotid intima-media thickness, a measure of subclinical atherosclerosis, also has been found to be increased in adults with CAH. The multiple hormonal imbalances present in the adult woman with CAH, in combination with chronic glucocorticoid therapy, contribute to cardiovascular disease risk. Further investigation of the predisposition to cardiovascular disease in women with CAH is warranted. Longitudinal studies are needed, and interventions targeting obesity, insulin resistance, hypertension, and hyperandrogenism may offer improved outcome.
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PMID:Cardiovascular disease risk in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. 1953 65

Women with polycystic ovary syndrome (PCOS) have chronic low level inflammation which can increase the risk of atherogenesis. We evaluated the status of circulating macrophage migration inhibitory factor (MIF), a proinflammatory cytokine involved in atherogenesis, in women with PCOS and weight-matched controls. Two-way analysis of variance models adjusted for age were fit to evaluate the effect of PCOS status (PCOS vs. controls) and weight-class (obese vs. lean) on MIF and other parameters. MIF levels were significantly (p<0.001) higher in women with PCOS (lean: 37.7+/-10.6 ng/ml; obese: 54.6+/-15.2 ng/ml) compared to controls (lean: 4.8+/-0.6 ng/ml; obese: 17.5+/-8.0 ng/ml) regardless of weight-class. CRP levels were significantly (p<0.001) higher in obese subjects (PCOS: 6.2+/-1.9 mg/l; controls: 6.7+/-1.4 mg/l) compared to lean subjects (PCOS: 0.9+/-0.4 mg/l; controls: 0.2+/-01 mg/l) after controlling for PCOS status. MIF levels directly correlated with % truncal fat (r=0.41, p<0.05), and plasma levels of CRP (r=0.42, p=0.05), LH (r=0.45, p=0.04), testosterone (r=0.53, p<0.008), androstendione (r=0.58, p<0.005). IS(OGTT) inversely correlated with plasma levels of MIF (r=-0.51, p<0.02) and CRP (r=-0.73, p<0.001). Circulating MIF is elevated in PCOS independent of obesity, but both PCOS and obesity contribute to a proatherogenic state. In PCOS, abdominal adiposity and hyperandrogenism may exacerbate the risk of atherosclerosis.
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PMID:Elevated circulating levels of macrophage migration inhibitory factor in polycystic ovary syndrome. 2059 2

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is characterized by chronic hyperandrogenic anovulation leading to symptoms of hirsutism, acne, irregular menses, and infertility. Multiple metabolic and cardiovascular risk factors are associated with PCOS, including insulin resistance, obesity, type 2 diabetes, hypertension, inflammation, and subclinical atherosclerosis. However, current treatments for PCOS are only moderately effective at controlling symptoms and preventing complications. This article describes how the physiological effects of major complementary and alternative medicine (CAM) treatments could reduce the severity of PCOS and its complications. Acupuncture reduces hyperandrogenism and improves menstrual frequency in PCOS. Acupuncture's clinical effects are mediated via activation of somatic afferent nerves innervating the skin and muscle, which, via modulation of the activity in the somatic and autonomic nervous system, may modulate endocrine and metabolic functions in PCOS. Chinese herbal medicines and dietary supplements may also exert beneficial physiological effects in PCOS, but there is minimal evidence that these CAM treatments are safe and effective. Mindfulness has not been investigated in PCOS, but it has been shown to reduce psychological distress and exert positive effects on the central and autonomic nervous systems, hypothalamic-pituitary-adrenal axis, and immune system, leading to reductions in blood pressure, glucose, and inflammation. In conclusion, CAM treatments may have beneficial endocrine, cardiometabolic, and reproductive effects in PCOS. However, most studies of CAM treatments for PCOS are small, nonrandomized, or uncontrolled. Future well-designed studies are needed to further evaluate the safety, effectiveness, and mechanisms of CAM treatments for PCOS.
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PMID:The physiological basis of complementary and alternative medicines for polycystic ovary syndrome. 2148 75

PAF and PAF-like oxidized phospholipids hydrolysed by platelet-activating factor (PAF) acetylhydrolase (AH) are potent lipid mediators involved in inflammation and atherosclerosis. Apolipoprotein (apo) E-containing high-density lipoprotein (HDL) has antioxidant, anti-inflammatory and anti-atherogenic properties. The study investigated apoE-containing HDL-associated PAF-AH (HDL-PAF-AH) and total (apoE-containing+apoE-poor) HDL-PAF-AH activities as well as malondialdehyde (MDA) concentration in 291 patients with polycystic ovary syndrome (PCOS) using the Rotterdam consensus criteria and 281 control women. Compared with the control women, patients with hyperandrogenism+oligo/anovulation+polycystic ovaries (PCO) or hyperandrogenism+PCO had lower total, apoE-containing and apoE-poor HDL-PAF-AH activities, while those with oligo/anovulation+PCO showed decreased total and apoE-poor HDL-PAF-AH activities. Other factors including insulin resistance and obesity in PCOS had the adverse effects associated with the HDL-PAF-AH activities. Serum MDA concentration was associated with PCOS, hyperandrogenism, insulin resistance and hypertriglyceridaemia in patients with PCOS. Decreased total and apoE-containing HDL-PAF-AH activities and increased serum MDA concentration may contribute to the pathogenesis of PCOS and potentially link to related complications responsible for oxidative stress and inflammation such as an increased risk for type 2 diabetes mellitus and/or future cardiovascular diseases in PCOS patients.
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PMID:Apolipoprotein E-containing HDL-associated platelet-activating factor acetylhydrolase activities and malondialdehyde concentrations in patients with PCOS. 2219 3


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