Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis begins in childhood as deposits of cholesterol and its esters, referred to as fatty streaks, in the intima of large muscular arteries. In some persons and at certain arterial sites, more lipid accumulates and is covered by a fibromuscular cap to form a fibrous plaque. Further changes in fibrous plaques render them vulnerable to rupture, an event that precipitates occlusive thrombosis and clinically manifest disease (sudden cardiac death, myocardial infarction, stroke, or peripheral arterial disease). In adults, elevated non-HDL-cholesterol concentrations, low HDL-cholesterol concentrations, hypertension, smoking, diabetes, and obesity are associated with advanced atherosclerotic lesions and increased risk of clinically manifest atherosclerotic disease. Control of these risk factors is the major strategy for preventing atherosclerotic disease. To determine whether these risk factors also are associated with early atherosclerosis in young persons, we examined arteries and tissue from approximately 3000 autopsied persons aged 15-34 y who died of accidental injury, homicide, or suicide. The extent of both fatty streaks and raised lesions (fibrous plaques and other advanced lesions) in the right coronary artery and in the abdominal aorta was associated positively with non-HDL-cholesterol concentration, hypertension, impaired glucose tolerance, and obesity and associated negatively with HDL-cholesterol concentration. Atherosclerosis of the abdominal aorta also was associated positively with smoking. These observations indicate that long-range prevention of atherosclerosis and its sequelae by control of the risk factors for adult coronary artery disease should begin in adolescence and young adulthood.
 ...
PMID:Origin of atherosclerosis in childhood and adolescence. 1106 73

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.
 ...
PMID:Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women. 1107 46

The aim of this review is to present the current knowledge regarding stroke. It will appear in three parts (in part II the pathogenesis, investigations, and prognosis will be presented, while part III will consist of the management and rehabilitation). In the current part (I) the definitions of the clinical picture are presented. These include: amaurosis fugax, vertebrobasilar transient ischemic attack, and stroke (with good recovery, in evolution and complete). The role of the following risk factors is discussed in detail: age, gender, ethnicity, heredity, hypertension, cigarette smoking, hyperlipidemia, diabetes mellitus, obesity, fibrinogen and clotting factors, oral contraceptives, erythrocytosis and hematocrit level, prior cerebrovascular and other diseases, physical inactivity, diet and alcohol consumption, illicit drug use, and genetic predisposition. In particular, regarding the carotid arteries, the following characteristics are analyzed: atheroma, carotid plaque echomorphology, carotid stenosis, presence of ulcer, local variations in surface deformability, pathological characteristics, and dissection. Finally the significance of the cerebral collateral circulation and the conditions predisposing to cardioembolism and to cerebral hemorrhage are presented.
 ...
PMID:Stroke: epidemiology, clinical picture, and risk factors--Part I of III. 1110 23

Obesity, especially visceral obesity, is associated with a cluster of metabolic complications increasing the risk of type 2 diabetes and coronary heart disease. It has been shown that obese patients characterized by a high accumulation of visceral adipose tissue have increased glycemic and insulinemic responses to an oral glucose load compared to normal weight individuals or to obese individuals with a low accumulation of visceral adipose tissue. Viscerally obese patients are also characterized by an unfavourable plasma lipid profile which includes elevated triglyceride and apolipoprotein B concentrations, reduced HDL-cholesterol levels as well as an increased proportion of small, dense LDL particles. Such alterations in the lipid profile are often observed even in the absence of elevated LDL-cholesterol concentrations. Our work has clearly shown that this cluster of metabolic abnormalities found among viscerally obese patients was associated with a substantial increase in coronary heart disease risk. Our work has also shown that the "metabolic triad" of non-traditional risk factors (hyperinsulinemia, elevated apolipoprotein B levels, increased proportion of small, dense LDL particles) was associated with a 20-fold increase in the risk of coronary heart disease. In this regard, we have been interested in developing simple tools which would allow clinicians to identify at an early stage and at low cost individuals who would be carriers of the atherogenic metabolic triad. We have noted that the measurement and interpretation of waist circumference and of fasting plasma triglyceride levels could allow the identification of a high proportion of carriers of the metabolic triad. Indeed, less than 10% of men with a waist circumference below 90 cm and triglyceride concentrations below 2 mmol/l were characterized by the features of the metabolic triad. However, more than 80% of individuals with a waist circumference above 90 cm and triglyceride levels above 2 mmol/l were carriers of the metabolic triad. Finally, an elevated visceral adipose tissue accumulation has also been associated with a thrombogenic and a pro-inflammatory metabolic profile which would be predictive of an unstable atherosclerotic plaque. Therefore, the stabilisation of the atherosclerotic plaque may represent a legitimate therapeutic objective to reduce the risk of coronary heart disease among patients with visceral obesity. It is proposed that a rather modest weight loss (approximately 10%) could contribute to substantially improve the risk profile of these patients.
 ...
PMID:[Risk factors associated with obesity: a metabolic perspective]. 1114 34

The determinants of blood levels of estrogen, estrogen metabolites, and relation to receptors and post-transitional effects are the likely primary cause of breast cancer. Very high risk women for breast cancer can now be identified by measuring bone mineral density and hormone levels. These high risk women have rates of breast cancer similar to risk of myocardial infarction. They are candidates for SERM therapies to reduce risk of breast cancer. The completion of the Women's Health Initiative and other such trials will likely provide a definite association of risk and benefit of both estrogen alone and estrogen-progesterone therapy, coronary heart disease, osteoporotic fracture, and breast cancer. The potential intervention of hormone replacement therapy, obesity, or weight gain and increased atherogenic lipoproteinemia may be of concern and confound the results of clinical trials. Estrogens, clearly, are important in the risk of bone loss and osteoporotic fracture. Obesity is the primary determinant of postmenopausal estrogen levels and reduced risk of fracture. Weight reduction may increase rates of bone loss and fracture. Clinical trials that evaluate weight loss should monitor effects on bone. The beneficial addition of increased physical activity, higher dose of calcium or vitamin D, or use of bone reabsorption drugs in coordination with weight loss should be evaluated. Any therapy that raises blood estrogen or metabolite activity and decreases bone loss may increase risk of breast cancer. Future clinical trials must evaluate multiple endpoints such as CHD, osteoporosis, and breast cancer within the study. The use of surrogate markers such as bone mineral density, coronary calcium, carotid intimal medial thickness and plaque, endothelial function, breast density, hormone levels and metabolites could enhance the evaluation of risk factors, genetic-environmental intervention, and new therapies.
 ...
PMID:Estrogens and women's health: interrelation of coronary heart disease, breast cancer and osteoporosis. 1116 38

Obese hypertensive patients with cardiovascular risk factor clustering and increased risk for atherosclerotic disease have increased plasma nonesterified fatty acid levels, including oleic acid (OA), and a more active renin-angiotensin-aldosterone system. Vascular smooth muscle cell (VSMC) migration and proliferation participate in the development of atherosclerotic plaque. OA and angiotensin (Ang) II induce synergistic mitogenic responses in VSMCs through sequential signaling pathways dependent on the activation of protein kinase C (PKC), oxidants (reactive oxygen species, ROS), and extracellular signal-regulated kinase (ERK) activation. We tested the hypotheses that (1) OA and Ang II have additive or synergistic effects on VSMC migration and (2) PKC, ROS, and mitogen-activated protein kinase are critical signaling molecules. OA at 100 micromol/L increases VSMC migration 60+/-10% over control (P:<0.001). Ang II (10(-)(9) mol/L) increases VSMC migration by 62+/-13% and 73% over control, respectively (P:<0.01). Coincubation of cells with OA and Ang II produces a nearly additive increase in VSMC cell migration at 107+/-20% (P:<0.01). Increases in VSMC migration induced by OA alone and combined with Ang II were reduced by PKC inhibition and downregulation. VSMC migration in response to OA alone and with Ang II was also inhibited by N:-acetyl-cysteine, MEK inhibition, and ERK antisense. VSMC migration in response to OA alone or combined with Ang II is dependent on activation of PKC, ROS, and ERK activation, further raising the possibility that increased plasma nonesterified fatty acids and an activated renin-angiotensin-aldosterone system in subjects with the risk factor cluster contribute to accelerated atherosclerosis through a PKC, ROS, and ERK-dependent signaling pathway.
 ...
PMID:Signaling events mediating the additive effects of oleic acid and angiotensin II on vascular smooth muscle cell migration. 1123 Feb 90

Recently, unstable angina, acute myocardial infarction and sudden cardiac death have often been put together under the name 'acute coronary syndromes', because almost all of these conditions have been shown to be caused by thrombotic occlusion of a coronary artery following atherosclerotic plaque disruption. Acute coronary syndromes occur more frequently in the coronary arteries with no significant organic stenosis than in those with a higher degree of stenosis. A plaque prone to disruption has a thin fibrous cap, a large lipid core and increased infiltration of macrophages and T lymphocytes. The elimination or control of risk factors for atherosclerosis such as dyslipidemia, hypertension, smoking, diabetes mellitus, obesity and lack of exercise is essential for the prevention of acute coronary syndromes.
 ...
PMID:[Acute coronary syndromes]. 1130 10

Type 2 diabetes mellitus is a condition associated with an increased risk of coronary artery disease. This condition is currently reaching epidemic proportions in the Western world. Epidemiological studies have shown that insulin resistance and the constellation of metabolic alterations associated with type 2 diabetes mellitus such as dyslipidaemia, systemic hypertension, obesity and hypercoagulability, have an effect on the premature onset and severity of atherosclerosis. Albeit direct, the link between insulin resistance and atherogenesis is rather complex. It is likely that its complexity relates to the interaction between genes that predispose to insulin resistance and genes that independently regulate lipid metabolism, coagulation processes and biological responses of the arterial wall. The rapid development of molecular biology in recent years has resulted in a better understanding of the immune and inflammatory mechanisms that underlie insulin resistance and atherosclerosis. For example, it is known that nuclear transcription factors such as nuclear factor kappa beta and peroxisome proliferator-activated receptor are involved in atherosclerosis. The former modulates gene expression which encodes pro-inflammatory proteins vital for the development of the atheromatous plaque. In the presence of insulin resistance there are multiple activating factors that could explain the early onset and severity of atherosclerosis. Glitazones, the new oral antidiabetic drugs and agonists of peroxisome proliferator-activated receptor, have been shown to improve peripheral insulin sensitivity and to also delay atherosclerosis progression in experimental models. Their beneficial effects have been linked to their anti-inflammatory effect.
 ...
PMID:[Diabetes mellitus, inflammation and coronary atherosclerosis: current and future perspectives]. 1141 81

Myocardial infarction is still one of the main causes of mortality and morbidity in Western countries. The advances made in the last 30 years have made it possible to reduce mortality significantly (which is currently below two digits) as well as morbidity. The subject of secondary prevention of myocardial infarction gains particular significance in this context since 10 to 15% of the patients who survive the hospital phase of myocardial infarction die during the first year following discharge and, of these deaths, half occur in the first three months. Therefore, it is necessary to make an early definition of the risk of another coronary event, that is, to make a risk stratification. This should occur throughout hospitalization and should be complete at the time of discharge, never beyond the first weeks of evolution. Bearing in mind the age, sex, coronary risk factors, ischemia persistence, the degree of left ventricular dysfunction and the presence of malignant disrhythmias, there are three risk levels: high; intermediate; and low. An overall approach to secondary prevention of infarction should take into account that, apart from the factors of such high prognostic value (Chapter II) assessed in the definition of risk groups, the measures to reduce reinfarction and sudden death (Chapter III) and the control of the risk factors for heart disease (Chapter IV) should also be considered. The principal late complications of infarction with significant prognostic influence are described in Chapter III: left ventricular dysfunction; rhythm disturbances and residual ischemia. The diagnostic criteria and therapeutic objectives are considered in each of the groups with relevance to consolidated advances according to the modern concept of evidence based medicine, according to international regulations. The grading of scientific evidence into three distinct categories (A, B and C), based on five levels of evidence classified from I to V, is presented accordingly in relation to the therapeutic proposals. Chapter III deals with a set of therapeutic interventions used in secondary prevention because they reduce reinfarction and sudden death: platelet antiaggregants; anticoagulants; Beta blockers; calcium channel blockers; antioxidants and nitrates. A concept of particular clinical significance is presented for each of these groups of drugs. The last part contains an eminently clinical overall review of the principal advances in coronary risk factor control, new therapeutic acquisitions in atherosclerotic disease with natural relevance to hypolipidemic agents and statins, which apart from controlling the plasmatic levels of cholesterol, also stabilize the atherosclerotic plaque and reduce acute coronary events significantly. Apart from dyslipidemia, the classic risk factors are: smoking; hypertension; obesity; diabetes and sedentary life. In each case, reference is made to the general measures and specific approaches, as well as the pharmacological therapy according to evidence based medicine. The recommended attitudes are pointed out. The role of cardiac rehabilitation and postmenopausal hormone replacement therapy are also discussed in the last part of these recommendations, in which the on-going controversy regarding hormone replacement therapy is pointed out in view of the results of more recent clinical trials.
 ...
PMID:[Secondary prevention in acute myocardial infarction]. 1147 86

Visceral obesity is associated with metabolic abnormalities that increase the risk of type 2 diabetes and coronary heart disease. Obese patients with a substantial accumulation of visceral adipose tissue are characterized by higher insulinaemic and glycaemic responses during an oral glucose challenge as well as by a deteriorated plasma lipoprotein-lipid profile compared with individuals with normal body weights or obese subjects with low levels of visceral adipose tissue. Results of the Quebec Cardiovascular Study have shown that the cluster of metabolic disturbances observed among subjects with visceral obesity (hyperinsulinaemia, hyperapolipoprotein B and small, dense low-density lipoprotein (LDL) particles) is associated with a 20-fold increase in the risk of coronary heart disease in a sample of middle-aged men followed over 5 years. Therefore, we have developed a simple screening approach in order to help physicians and health professionals identify at low cost individuals who would be characterized by this cluster of atherogenic abnormalities. We found that the simultaneous presence of an elevated waist girth combined with moderate hypertriglyceridaemia ('hypertriglyceridaemic waist') could adequately identify a large proportion (approximately 80%) of carriers of the above triad of atherogenic metabolic abnormalities (hyperinsulinaemia, hyperapolipoprotein B and small, dense LDL particles). Finally, there is evidence suggesting that the risk of an acute coronary syndrome in these viscerally obese patients may not always be related to the extent of coronary artery stenosis, providing further support to the notion that additional markers of thrombosis/inflammation should be considered. Thus, the stabilization of the atherosclerotic plaque, rather than its regression may even become a more legitimate and feasible therapeutic objective for the management of the coronary heart disease risk in the viscerally obese patient. Although these notions are based on a plausible metabolic rationale, randomized trials with proper end-points will be needed to determine the clinical benefits associated with the management of visceral obesity and related metabolic complications.
 ...
PMID:Health consequences of visceral obesity. 1173 Jan 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>