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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of beta-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.
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PMID:Diabetes mellitus and macrovascular complications. An epidemiological perspective. 139 12

Sufficient evidence exists today pointing to the relationship between high levels of plasma cholesterol and coronary atherosclerosis. Up to now, however, the last criterion for validating the aetiopathogenetic relationship between dyslipidemia and CHD, i.e., the demonstration that reduction of plasma cholesterol reduced the formation or progression of the plaque and the incidence of its fatal or non-fatal cardiac and vascular complications, has been lacking. For more than two decades, numerous trials have had this aim in mind but until very recently results have not been substantiated owing to various deficiencies in the method. Before publication of the NHLBI Task Force of Atherosclerosis, eleven major randomised clinical studies based on hypolipidemia interventions were completed. The three studies involving dietetic interventions were considered non-conclusive overall because of the lack of a double-blind factor and of other important epidemiological criteria. Of three pharmacological trials only two involved studies of primary prevention carried out on a population of hypercholesterolaemics. These produced partial results on certain cardiac end-points but not on total deaths and at times not even on deaths from CHD. Multifactorial studies, finally, were even less demonstrative. Taken together, however, the trials based on hypolipidemia interventions point to interesting though not definitive evidence of a reduction in blood cholesterol levels to reduce the incidence and mortality from CHD. According to the NHLBI, many of these studies lacked important features that were codified and suggested for later studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The lipid hypothesis in the etiopathogenesis of ischemic heart disease: confirmations and doubts resulting from primary prevention trials]. 277 Oct 85

The relationship of dyslipidemia, particularly hypercholesterolemia to coronary heart disease is now well established. Although ischemic heart disease and stroke share many of the same risk factors, the relationship of cholesterol to stroke remains controversial. The 6-year and 12-year follow-up of the MRFIT study showed that elevated cholesterol significantly increased the risk for fatal nonhemorrhagic stroke. Atkins found no evidence that lowering plasma cholesterol influenced the incidence of fatal or nonfatal stroke and regression analysis showed no statistical association between the magnitude of cholesterol reduction and the risk for fatal stroke. We cannot preclude the possibility that more effective cholesterol lowering over a longer period of time might be effective. Hypertension is the most powerful risk factor for stroke. The San Antonio Heart Study reported a clustering of cardiovascular risk factors in individuals who developed hypertension during an eight-year follow-up period (higher levels of BP, fasting TC and LDLC, TG, glucose and insulin, and BMI, less favourable fat deposition, and lower HDL). Insulin resistance may be the unifying factor that results in those phenomena, the so-called syndrome X. The important factor underlying syndrome X may be central or visceral obesity, suggesting that maintenance or attainment of ideal weight would be a powerful preventive factor against both CHD and nonhemorrhagic stroke. There is evidence from the Treatment of Mild Hypertension Study that nutritional/hygienic measures can reduce the syndrome X risk factors and hence the risk of coronary heart disease and stroke.
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PMID:Dyslipidemia and metabolic factors in the genesis of heart attack and stroke. 791 92

Although there is consensus that lipid variables, especially lipoprotein(a), are heritable and that elevated LDL cholesterol levels should be treated, there are no clear definitions of the common familial lipid disorders associated with premature CHD (lipoprotein(a) excess, FCH, familial dyslipidemia, familial hypoalphalipoproteinemia, familial hypercholesterolemia), nor do we have clear guidelines for the treatment of most of these disorders. Implementation of therapy for elevated LDL cholesterol in familial lipid disorders often has not occurred even in the United States. Before recommendations can be made for subjects with lipoprotein(a) excess and HDL deficiency (who often have combined hyperlipidemia or hypertriglyceridemia), prospective studies documenting benefit of CHD risk reduction must be carried out in subjects with lipoprotein(a) excess and HDL deficiency. One such study is being carried out with gemfibrozil in CHD patients with HDL deficiency. Current data do justify treatment of CHD patients with lipoprotein(a) excess with niacin because niacin has been shown to lower lipoprotein(a) levels as well as lower CHD risk mortality in random CHD patients. With regard to CHD patients with or without HDL cholesterol levels less than 35 mg/dL (0.9 mmol/L), efforts should be made to optimize their lipid profile and reduce their LDL cholesterol levels to less than 100 mg/dL (2.6 mmol/L).
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PMID:Familial lipoprotein disorders and premature coronary artery disease. 828 32

The prevention of coronary artery disease (CHD) and particularly of myocardial infarction (MI) is based on some well designed strategies aimed at treating both asymptomatic high-risk patients (primary prevention) and patients with established CHD (secondary prevention). A positive impact from primary prevention can be basically achieved trough a reduction in high blood pressure and by correcting dyslipidemia. The benefit can be substantially increased by smoking cessation, increasing physical exercise, reduction of body weight, use of post-menopausal oestrogen, moderate alcohol consumption and use of high doses of vitamin E in those patients who are compliant with the specific strategies. Secondary prevention of MI can be again obtained by controlling blood pressure and reducing serum cholesterol in patients surviving acute MI who can also benefit from the administration of beta-blockers, aspirin and probably ace-inhibitors particularly in presence of left ventricular dysfunction. We suggest that in both arms of prevention, significant results can be achieved mainly by a multifactorial approach capable of correcting all the modifiable risk factors that contribute to the rather complex pathogenesis of CHD.
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PMID:Primary and secondary prevention of myocardial infarction. 874 42

Obesity carries a penalty of an associated adverse cardiovascular risk profile. Largely as a consequence of this, it is associated with an excess occurrence of cardiovascular disease morbidity and mortality. It is concluded on the basis of data from the Framingham study and other large prospective studies that the rate of development of cardiovascular disease rises rapidly in relation to even modest amounts of adiposity. The abdominal pattern of adiposity, and specifically visceral adiposity, appears to be the most hazardous. First identified as a cause of glucose intolerance, abdominal adiposity has been identified as promoting insulin resistance, hypertension and dyslipidemia, as well as CHD. While the impact of epidemic obesity on the health of white Americans is becoming more fully understood, there are important gaps in the knowledge about the nature of influence of adiposity on CHD in large subgroups of the population. The dearth of detailed and long term prospective studies of African-Americans is the most conspicuous shortcoming of the research base. Finally, because there is a great potential benefit of remaining lean or achieving a sustained weight loss when indicated, and given the high prevalence of obesity, research on adiposity prevention and more effective weight reduction methodology are urgently needed.
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PMID:Obesity and coronary heart disease. 888 94

Subjects with diabetes have a greatly increased risk of CHD, which is only partially related to their elevated glucose. Other factors such as insulin resistance and dyslipidemia are likely to be important. The type of dyslipidemia that is most characteristic of type 2 diabetic subjects is elevated triglycerides and decreased HDL cholesterol levels, although all lipoproteins have compositional abnormalities. Surprisingly few good prospective studies of lipoprotein levels in relation to CHD have been done in diabetic subjects. Available studies suggest that low HDL cholesterol may be the most important risk factor for CHD in observational studies. In studies in which total cholesterol and triglyceride were done, cholesterol and triglycerides were risk factors for CHD, although triglycerides were often a stronger predictor. However, the strength of triglyceride as a risk factor for CHD may depend partially on its association with other variables (e.g., hypertension, plasminogen activator inhibitor 1 [PAI-1], etc.). In clinical trials in diabetic subjects, LDL reduction with statins has led to significant reductions in CHD incidence. In addition, overall mortality was reduced with statin therapy, although the results were not statistically significant. Gemfibrozil has led to reductions in CHD incidence in diabetic subjects, although the results were not statistically significant perhaps because of low sample size. Regarding lipoproteins and CHD risk in diabetic patients, the very positive results of statin trials point to LDL cholesterol being more important than previous realized. Apparently, having a borderline high LDL cholesterol (between 130 and 160 mg/dl) in a diabetic patient is equivalent to a much higher LDL cholesterol in terms of CHD risk for a nondiabetic subject. Therefore, the primary target of therapy in diabetic patients is lowering LDL cholesterol (or possibly, non-HDL cholesterol). Statins are the preferred pharmacological agent in this situation. Once LDL cholesterol levels have been lowered, attention can be given to treatment of residual hypertriglyceridemia and low HDL. The goal here is weight reduction and increased exercise. However, for selected patients, combining a fibric acid (or low-dose nicotinic acid) with a statin also can be considered. Reduction of LDL levels should take priority over reduction of triglycerides in combined hyperlipidemia because of the proven safety of the statin class of drugs as well as greater reduction in CHD incidence.
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PMID:Management of dyslipidemia in adults with diabetes. 953 88

Dietary Guidelines have emerged over the past 30 years recommending that Americans limit their consumption of total fat and saturated fat as one way to reduce the risk of a range of chronic diseases. However, a low-fat diet is not a no-fat diet. Dietary fat clearly serves a number of essential functions. For example, maternal energy deficiency, possible exacerbated by very low-fat intakes (< 15% of energy), is one key determinant in the etiology of low birth weight. The debate continues over recommendations for limiting total fat and saturated fatty acid intake in children. Recent evidence indicates that diets with adequate energy providing less than 30% of energy from fat are sufficient to promote normal growth and normal sexual maturation. More attention needs to be devoted to the effect of dietary fat reduction on the nutrient density of children's diets. The association between dietary fat and CHD has been extensively studied. Diets high in saturated fatty acids and trans fatty acids increase LDL cholesterol levels, and in turn, the risk of heart disease. The relationship between high-carbohydrate/low-fat diets and CHD is more ambiguous because high-carbohydrate diets induce dyslipidemia in certain individuals. Obesity among adults and children is now of epidemic proportions in the United States. High-fat diets leading to excessive energy intakes are strongly linked to the increasing obesity in the United States. However, the prevalence of obesity has increased during the same time period that dietary fat intake (both in absolute terms and as a percentage of total dietary energy) has decreased. These trends suggest that a concomitant decrease in total dietary energy and modifications of other lifestyle factors, such as physical activity, also need to be emphasized. Obesity is also an independent risk factor for the development of diabetes. The current availability of fat-modified foods offers the potential for dietary fat reduction and treatment of the comorbidities associated with diabetes. However, to date, few studies have documented the effectiveness of fat-modified foods as part of a weight loss regimen or in reduction in CHD risks among individuals with diabetes mellitus. The association between total dietary fat and cancer is still under debate. While there is some evidence demonstrating associations between dietary fat intake and cancers of the breast, prostate, and colon, there are serious methodologic issues, including the difficulty in differentiating the effects of dietary fat independent of total energy intake. Reported total fat and saturated fatty acid intakes as a percentage of total energy have been declining over the past 30 years in the United States. Despite this encouraging trend, the majority of individuals--regardless of age--do not report consuming a diet that meets the levels of fat and saturated fatty acids recommended by the Dietary Guidelines for Americans. On a relative basis, saturated fat intake has gone down less than has total fat intake. Individuals of all ages who report consuming a diet with < or = 30% of energy from fat consistently have lower energy intakes. Given the increasing rates of obesity in the United States at an earlier and earlier age, dietary fat reduction may be an effective part of an overall strategy to balance energy consumption with energy needs. In each of the age/gender groups reporting consumption of < or = 30% of energy from fat and less than 10% of energy from saturated fatty acids, fat-modified foods play a more important role in their diets than for people who are consuming higher levels of fat and saturated fat. The data are clear than fat-modified foods make a more significant contribution to diets of consumers with low-fat intakes. While one cannot argue cause and effect from the results presented, the patterns of fat-modified foods/low-fat intakes are consistent. The focus on overall diet quality is often lost in the national obsession with lowering fat inta
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PMID:Dietary fat consumption and health. 962 78

Essential hypertension is, at least in many subjects, associated with a decrease in insulin sensitivity, whereas glycemic control is (still) normal. Metaanalyses of hypertension intervention studies revealed different efficacy of treatment on cerebral (cerebrovascular accidents [CVA]) and cardiac (coronary heart disease [CHD]) morbidity and mortality. Although CVA were reduced to an extent similar to that anticipated, the decrease in CHD was less than expected. These differences are likely to be caused by the different impact of concomitant cardiovascular risk factors, such as dyslipidemia, impaired glucose tolerance, and non-insulin-dependent diabetes mellitus on CHD and CVA. Frequently these cardiovascular risk factors are ineffectively controlled in hypertensive patients, and moreover, some of the widely used antihypertensive agents have unfavorable side effects and further deteriorate these particular metabolic risk factors. Therefore, the metabolic side effects of antihypertensive treatment have received more attention. During the past few years, studies demonstrated that most antihypertensive agents modify insulin sensitivity in parallel with alterations in the atherogenic lipid profile. Alpha1-blockers and angiotensin converting enzyme inhibitors were shown to either have no impact on or even improve insulin resistance and the profile of atherogenic lipids, whereas most of the calcium channel blockers were found to be metabolically inert. The diuretics and beta-adrenoreceptor antagonists further decrease insulin sensitivity and worsen dyslipidemia. The mechanisms by which beta-adrenoreceptor antagonist treatment exert its disadvantageous effects are not fully understood, but several possibilities exist: significant body weight gain, reduction in enzyme activities (muscle lipoprotein lipase and lecithin cholesterol acyltransferase), alterations in insulin clearance and insulin secretion, and, probably most important, reduced peripheral blood flow due to increase in total peripheral vascular resistance. Recent metabolic studies found beneficial effects of the newer vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. In many hypertensive patients, elevated sympathetic nerve activity and insulin resistance are a deleterious combination. Although conventional beta-blocker treatment was able to take care of the former, the latter got worse; the newer vasodilating beta-blocker generation seems to be capable of successfully treating both of them.
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PMID:Antihypertensive therapy and insulin sensitivity: do we have to redefine the role of beta-blocking agents? 979 45

Insulin action starts with binding to a membrane receptor (insulin receptor-tyrosine kinase) and with activating an insulin receptor substrate 1 (IRS-1) and substrate 2 (IRS-2). Insulin receptors interact at least with three cascade reactions, phosphorylating G proteins and IRS-1, that activate PLC "ras" and PI-3-K. NIDDM can be defined as a disease caused by defective transduction of insulin signals and IR as a complex phenotype manifesting itself, emphasized by individual and environmental factors, in the cellular systems of signal transduction. IRS is a syndrome characterized by NIDDM, hypertension, visceral obesity, CHD: the X syndrome. Up to day the described mutations of the insulin-receptor gene are rare (e.g. the leprechaunism): genetic IR. Obesity is the principal cause of IR by receptorial and post-receptorial defects: metabolic IR. The obese skeletal muscle shows a reduction of insulin receptor and IRS-1 phosphorylation and of PI-3-K activation; the scarce expression of these proteins would determine the muscular IR. IR is a pattern of essential hypertension. Hypertension, dyslipidemia and abnormality of glucose metabolism are linked by IR. The so called high erythrocyte Na(+)-Li+ counter-transport is a new biochemical marker for IR and hypertension. These drugs can reduce IR: metformin, sulphonilureas, fibrats, dexfenfluramine, troglitazone, doxazosin, ACE-inhibitors.
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PMID:[Insulin resistance. Receptor and post-receptor abnormalities]. 984 54


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