Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a cross-sectional study of 293 nondiabetic patients (169 men and 124 women) referred for the diagnosis and treatment of hyperlipidemia, our specific aim was to determine whether fasting serum insulin independently contributes to the prediction of atherosclerotic cardiovascular disease (ASCVD) status. Of the 169 men and 124 women, 65 (38%) and 44 (35%), respectively, had ASCVD with at least one of the following: unstable angina, myocardial infarction (MI), angioplasty, coronary artery bypass graft (CABG), claudication, transient ischemic attack, or ischemic stroke. In addition, 42% and 38% had fasting hyperinsulinemia (> or =20 microU/mL). Fasting serum insulin of 20 microU/mL or higher was very common in women (59% to 100%) and men (67% to 88%) when hypertension, obesity, top-decile triglyceride (TG), and bottom-decile high-density lipoprotein cholesterol (HDLC) were concurrent in various combinations. ASCVD events (present or absent) were dependent variables in a stepwise logistic regression model with explanatory variables including age, gender, race, hypertension, cigarette smoking, ASCVD in first-degree relatives at age 55 years or less, Quetelet Index, fasting serum insulin, a gender x insulin interaction term, anticardiolipin antibodies (ACLAs) IgG and IgM, total cholesterol to HDLC ratio, TG, lipoprotein(a) [Lp(a)], and homocysteine. The risk odds ratio for ASCVD (109 events and 184 nonevents) for subjects with top-decile insulin (vthe bottom nine deciles) was 3.71, with a 95% confidence interval (CI) of 1.62 to 8.9 (P = .002). For patients with MI and/or CABG and/or angioplasty ([MCA] 63 events and 184 nonevents), the risk odds ratio for top-decile insulin versus the rest was 5.07 (95% CI, 1.83 to 14.8, P = .002). For patients with MCA at age 55 or less, the gender x insulin interaction term was significant (P = .0004); the risk odds ratio for men with top-decile insulin was 13.28 (95% CI, 3.82 to 51.65, P = .0001). Hyperinsulinemia is very common in nondiabetic hyperlipidemic women and men. Fasting serum insulin, a crude, simple, practical, and inexpensive measure, independently and uniformly improved the prediction of ASCVD status beyond traditional risk factors and lipid variables in patients referred for treatment of hyperlipidemia.
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PMID:Contribution of fasting hyperinsulinemia to prediction of atherosclerotic cardiovascular disease status in 293 hyperlipidemic patients. 1058 54

Atherosclerotic cardiovascular disease is a major health problem in the United States. In particular, coronary heart disease (CHD) is the leading cause of death in men and women in the United States, as well as in other industrialized countries. Extensive observational epidemiologic data within and between populations have strongly linked such various factors as untreated hypertension, diabetes, cigarette smoking, and lipid abnormalities to the development of CHD. With respect to lipoprotein parameters, elevated total and low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) have been strongly associated with CHD risk. Emerging evidence suggests that other lipoprotein abnormalities also are associated with premature CHD, including elevated levels of lipoprotein(a), triglyceride-rich lipoproteins such as small very-low-density lipoproteins and intermediate-density lipoproteins, small and dense LDL particles, and the magnitude of postprandial lipemia. Extensive primary and secondary clinical trial evidence has established that favorably altering dyslipidemias through diet and a variety of pharmacologic agents produces clear improvements in CHD end points. The extent of this benefit depends on the presence or absence of clinical atherosclerotic disease, as well as other CHD risk factors, and the severity of one or more lipoprotein abnormalities. CHD patients and individuals with multiple risk factors, but free of clinical CHD, derive the greatest absolute benefit from lipid treatment directed at reducing LDL-C. The dyslipidemias that impart high risk are severely elevated LDL-C (> 200 mg/dL), combined high LDL-C and low HDL-C (< 35 mg/dL), and combined hyperlipidemias (non-HDL-C > 200 mg/dL with low HDL). The purpose of this review is to aid the primary care physician in identifying these important dyslipidemias and to critically analyze the relative importance of various lipoproteins on atherosclerotic risk.
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PMID:Clinical diagnosis of lipid disorders. 1068 61

The insulin resistance syndrome, a cluster of potent risk factors for atherosclerotic cardiovascular disease and type 2 diabetes in adults, is composed of hyerinsulinemia, obesity, hypertension and hyperlipidemia. In addition, left ventricular hypertrophy and its precursor increased left ventricular mass, is known to be a powerful predictor of adverse cardiovascular events, both as an independent risk factor and by association with the insulin resistance syndrome. Obesity appears to have a major role in the relations between the components of the insulin resistance syndrome, and their association with increased heart mass. Of significant impact in the adult population, atherosclerotic cardiovascular disease and death are rarely seen in the young, but the pathologic processes and risk factors associated with its development have been shown to begin during childhood. Recent studies revealed the presence of components of the insulin resistance syndrome also in children and adolescents, however, their associations are not well understood. A direct link between obesity and insulin resistance has also been reported in the young, as has the link between insulin resistance and abnormal lipid profile. There is an increasing amount of data to show that being overweight during childhood and adolescence is significantly associated with insulin resistance, abnormal lipids and elevated blood pressure in young adulthood. Weight loss in these situations results in a decrease in insulin concentration and an increase in insulin sensitivity toward normalcy. Moreover, it has been determined that increased left ventricular mass is present in childhood, and is related to other risk factors, namely obesity and insulin resistance. Based on current knowledge, it is reasonable to suggest that weight control, and lifestyle modification, could alter the incidence of the syndrome of insulin resistance, and improve the risk profiles for cardiovascular disease as children make the transition toward adolescence and young adulthood.
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PMID:Insulin resistance and cardiovascular risk in the pediatric patient. 1122 44

Vascular injury is a ubiquitous phenomenon which can be both occult (such as with hyperlipidemia) and overt (such as with angioplasty). While the exact pathophysiology differs between acute and chronic atherosclerosis, both lesions can be mechanistically explained by the vasculature's exaggerated response to injury. Pharmacological attempts to treat atherosclerotic cardiovascular disease can be categorised by their role in modifying this inflammatory response. This manuscript reviews current therapy for cardiovascular injury at two levels: the chronic smouldering atheromatous lesion and intimal hyperplasia associated with acute vascular intervention. In addition, future therapeutic strategies, based within this inflammatory paradigm, are discussed.
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PMID:Current approaches to therapy for vascular injury. 1133 20

Management of the conventional cardiovascular risk factors is insufficient to prevent the dramatic increase in atherosclerotic cardiovascular morbidity and mortality in patients with renal failure. Folate recently received attention as a potential alternative treatment option to decrease the excess cardiovascular risk in the uremic population. Folate administration is the principal treatment modality for hyperhomocysteinemia. Hyperhomocysteinemia is prevalent in more than 85% of patients with end-stage renal disease (ESRD) and is independently associated with increased odds for atherosclerotic cardiovascular disease. Several attempts have been made to normalize homocysteine levels in uremic patients with folate-based vitamin regimens. Although supraphysiologic doses of folic acid afford greater reductions in homocysteine levels than standard doses, the response to treatment is generally only partial and the large majority of ESRD patients have residual hyperhomocysteinemia. Several defects in folate metabolism have been described in uremia, which may explain the relative folate resistance in patients with renal failure, but their clinical relevance remains uncertain. It appears unlikely that the hyperhomocysteinemia in ESRD can be cured solely with folic acid supplements, since folate does not affect the prolonged plasma elimination of homocysteine, which is the primary defect in homocysteine metabolism in uremia. Folate restores endothelial dysfunction, associated with hyperlipidemia, diabetes and hyperhomocysteinemia. The beneficial effect appears to be independent of its homocysteine-lowering capacity and is possibly related to an improved bioavailability of nitric oxide. However, folate has failed to improve endothelial dysfunction in uremic patients. In the ESRD population, multiple metabolic and hemodynamic abnormalities adversely affect endothelial function. In addition, irreversible structural vascular disease already may be present. Folate should, therefore, probably be an integral part of an "endothelial protective regimen," consisting of lipid-lowering agents, antihypertensives and antioxidant vitamins and started very early in patients with renal failure. Before large-scale folate administration can be recommended, effects on hard endpoints of cardiovascular disease need to be demonstrated in randomized trials. Such trials are currently underway in patients with normal renal function at high risk for cardiovascular disease, and one trial has recently been initiated in stable renal transplant recipients.
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PMID:Is folate a promising agent in the prevention and treatment of cardiovascular disease in patients with renal failure? 1263 Nov 53

Objective: To describe conceptions of the management of hyperlipidaemia and assess changes in conceptions after an educational intervention.- Setting and subjects: Primary care in Sweden. Twenty doctors at community health centres.- Methods: Within an educational experiment evaluating the effects of 'group detailing' by community pharmacists at 67 health centres, a selected sample of doctors were interviewed on two occasions, one and a half year apart, regarding their views on atherosclerotic cardiovascular disease and hyperlipidaemia. Half of the doctors had, in between the interviews, participated in four educational group sessions, where information was presented and discussed regarding the national recommendations on the management of hyperlipidaemia. Applying a phenomenographic approach, the variation of conceptions was described regarding six domains: general attitude to cardiovascular disease, risk factors, prevention of ischaemic heart disease, role of blood lipids, treatment of hyperlipidaemia, and screening for hypercholesterolaemia.- Outcome measures: Descriptions of categories of conceptions and changes of conceptions to ones in line with the treatment guidelines for individual doctors and for the two groups of doctors.- Results: There was a variation of conceptions in all six domains in both groups of doctors. The doctors' conceptions in the intervention group changed significantly to ones in line with the treatment recommendations (p < 0.01), which was not the case in the control group. A significant number of doctors in the intervention group changed at least one of the six conceptions to ones in concordance with the recommendations (p = 0.011). Although doctors in the control group also changed conceptions, this change was not statistically significant.- Conclusions: The doctors' conceptions changed significantly after 'group detailing' on management of hyperlipidaemia. Qualitative changes of conceptions may be used as outcome measures when evaluating the impact of an information activity directed at health care professionals.
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PMID:Changing Primary Care Doctors' Conceptions - A Qualitative Approach to Evaluating an Intervention. 1238

The upstream stimulatory factor (USF) proteins are ubiquitously expressed and, as such, represent unusual candidates for involvement in disorders of carbohydrate and lipid metabolism. Nonetheless, a recent study has reported an association between specific alleles of USF1 and familial combined hyperlipidaemia, a common disorder that substantially increases the risk of premature atherosclerotic cardiovascular disease. USF1 might, therefore, also contribute to the metabolic syndrome. The use of chromatin immunoprecipitation methodologies combined with promoter microarray assays will help to define the transcriptional networks that underlie whole-body glucose and lipid homeostasis.
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PMID:USF1 implicated in the aetiology of familial combined hyperlipidaemia and the metabolic syndrome. 1531 Apr 55

Low-density lipoprotein cholesterol has a well-established role in atherogenesis and the development of coronary heart disease. However, despite effective lowering of low-density lipoprotein cholesterol, many patients continue to have cardiovascular events. It has subsequently emerged that several additional dyslipidemic states promote atherogenesis. In particular, the atherogenic lipoprotein phenotype comprising an elevation of triglycerides and triglyceride-rich lipoproteins; decreased concentrations of high-density lipoprotein cholesterol; and increased small, dense low-density lipoprotein cholesterol, in addition to impaired postprandial lipemia, have been demonstrated to have profound effects on the arterial wall. As such, these factors have become important targets in the development of effective strategies to prevent atherosclerotic cardiovascular disease.
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PMID:The emerging role of lipoproteins in atherogenesis: beyond LDL cholesterol. 1547 40

The high-cholesterol/high-fat Western diet has abetted an epidemic of atherosclerotic cardiovascular disease, the leading cause of death in industrialized nations. Liver X receptors (LXRs) are oxysterol sensors that are required for normal cholesterol and triglyceride homeostasis, yet synthetic LXR agonists produce undesirable hypertriglyceridemia. Here we report a previously unrecognized role for hepatic LXRalpha in the links between diet, serum lipids, and atherosclerosis. A modest increase in hepatic LXRalpha worsened serum lipid profiles in LDL-receptor null mice fed normal chow but had the opposite effect on lipids and afforded strong protection against atherosclerosis on a Western diet. The beneficial effect of hepatic LXRalpha was abrogated by a synthetic LXR agonist, which activated SREBP-1c and its target genes. Thus, the interplay between diet and hepatic LXRalpha is a critical determinant of serum lipid profiles and cardiovascular risk, and selective modulation of LXR target genes in liver can ameliorate hyperlipidemia and cardiovascular disease.
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PMID:Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalpha. 1605 77

Nonalcoholic fatty liver disease (NAFLD) refers to a wide picture of liver damage, ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. The epidemiological studies demonstrated an association of NAFLD with obesity, type 2 diabetes and hyperlipidemia. Under this light the metabolic syndrome (MS), including NAFLD, obesity, central fat distribution, diabetes, dyslipidemia, hypertension and atherosclerotic cardiovascular disease (CVD) can be considered the link to explain the presence of vascular diseases in patients with NAFLD. In NHANES III, the authors demonstrated that the presence of MS was associated with increased risk of myocardial infarction, stroke or both. In a prospective study on 1209 Finnish middle-aged men without CVD or diabetes at baseline, Lakka showed that MS per se is associated with an increased risk of CVD and all-cause mortality. Finally the Atherosclerosis Risk in Communities (ARIC) confirmed that subjects with MS were 2 times more likely to have prevalent coronary heart disease. From a pathophysiological point of view, growing evidences implicate the oxidative stress as the unifying mechanism for many CVD risk factors. Under this light there is emerging evidence suggesting that there is a significant increase in vascular oxidative stress in patients with MS, with the presence of endothelial dysfunction in the early stage of the syndrome. Indeed, the inflammation process evidentiated in these patients is initiated at the endothelial level, stressing the key role of this active and dynamic tissue in the pathophysiological pathways. Under this light the endothelium can be considered as the last effector of a multi-syndrome and the main target of all the future studies focused on the underlying mechamisms of this complex network. Because of the potential serious public health impact, the comprehension of these patophysiological pathways will be crucial to design new preventive measures and therapeutic strategies.
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PMID:Hepatic steatosis and vascular disease. 1623 88


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