Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the Adult Treatment Panel (ATP) guidelines and strong evidence that reduction of blood cholesterol levels favorably decreases the morbidity and mortality associated with coronary heart disease (CHD), a significant number of patients remain undiagnosed and untreated. With the aggressive detection and evaluation methods ATP III advocates, more than 65 million Americans are now eligible for lipid modification through lifestyle changes and/or drug therapy. Recent data suggest, however, that as many as 50% of all patients do not have their cholesterol assessed and less than 45% receive lipid-modifying therapy. Additionally, more than 75% of patients who receive therapy fail to achieve their National Cholesterol Education Program (NCEP) target low-density lipoprotein cholesterol goal. Persistence with therapy is another challenge, as less than 30% of patients continue with therapy beyond one year. If a realistic attempt is to be made to reduce the CHD risk among Americans, diagnosis of dyslipidemia and treatment to therapeutic targets must be improved.
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PMID:Underidentification and undertreatment issues. 1461 52

Although the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines stress the importance of nonpharmacologic lipid modification interventions such as diet and exercise, the guidelines also recognize that many patients will require drug therapy to achieve low-density lipoprotein cholesterol (LDL-C) target goals. Currently available lipid-modifying drugs include bile acid sequestrants (or resins), fibrates, nicotinic acid, and statins, with each class exerting different effects on the lipid profile. In addition, nonprescription agents such as plant stanols and sterols have been shown to be effective in modifying plasma lipids. Of these agents, the statins are the most effective, most widely prescribed, and best-tolerated form of lipid-lowering drug therapy. New formulations of other drugs, such as niacin and bile acid sequestrants, can also improve treatment regimes and reduce side effects, thereby improving patient compliance with these therapies. In patients who have high levels of LDL-C and triglycerides together with low concentrations of high-density lipoprotein cholesterol (HDL-C), combination therapy may be required. Ezetimibe, a selective cholesterol absorption inhibitor, is the first of a new class of lipid-lowering agents and provides a new agent for the management of patients with dyslipidemia. Data from the ezetimibe clinical development program suggests that this agent can be used alone or in combination with statins to reduce LDL-C, improve compliance, and bring more patients to ATP III target goal.
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PMID:Overview of pharmacologic therapy for the treatment of dyslipidemia. 1461 53

Coronary heart disease (CHD) persists as a major cause of morbidity and mortality in the United States, with more than 40% of all deaths each year directly attributed to the disease. Dyslipidemia is recognized as a major risk factor for the development and progression of CHD, with clinical trials clearly demonstrating the public health and economic benefits of favorable cholesterol modification. As a result of this evidence, the National Cholesterol Education Program (NCEP) has developed guidelines for the detection, evaluation, and treatment of high blood cholesterol in adults. The most recent of the NCEP recommendations, the Adult Treatment Panel III (ATP III) guidelines, were released in May 2001 and build on the earlier editions and reiterate the importance of low-density lipoprotein cholesterol (LDL-C) reduction to modify CHD risk. New features of the guidelines include the identification of CHD risk equivalents; lower treatment target goals; an emphasis on conditions conferring a higher risk for CHD, such as the metabolic syndrome; and a scoring system for calculating CHD risk. The ATP III emphasis on risk assessment will result in a substantial increase in the number of patients considered at risk for CHD and will expand the number eligible for lifestyle and drug intervention.
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PMID:The National Cholesterol Education Program Adult Treatment Panel III guidelines. 1461 51

Since 1988, the National Cholesterol Education Program has identified low-density lipoprotein cholesterol (LDL-C) as the target of therapy; the new Adult Treatment Panel III (ATP III) guidelines continue the tradition of matching the aggressiveness of LDL-lowering therapy according to the risk of coronary heart disease (CHD). A significant change in the new guidelines is the definition of.CHD risk equivalents. and the inclusion of a modified Framingham global risk score. These revisions significantly raise the number of patients who qualify for lipid-lowering therapy. ATP III recognizes statins as the drug of first choice for LDL-C lowering. Statins are proven to be safe and effective for LDL-C reduction and are proven to reduce CHD event rates and mortality. Some patients are not candidates for statin therapy, however, and must rely on nonstatin agents that are less effective in reducing LDL-C, less safe, or poorly tolerated. Consequently, new cholesterol-lowering therapies are needed. Ezetimibe, approved by the U.S. Food and Drug Administration (FDA) in October 2002, is the first in a new class of selective cholesterol absorption inhibitors and offers a novel approach to the treatment of dyslipidemia. Phase 2 data demonstrated that ezetimibe lowers LDL-C by 18% and has a tolerability and short-term safety profile similar to placebo. This paper reviews the cholesterol metabolic pathways and the mechanism of action of the currently available lipid-modifying agents and introduces ezetimibe, the first selective cholesterol absorption inhibitor.
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PMID:A novel therapeutic approach. 1461 54

The National Cholesterol Education Program Adult Treatment Panel III has provided a clinical definition for the metabolic syndrome that is practical for use in an office setting. Identification and treatment of the metabolic syndrome is of enormous public health importance because it is associated with a marked elevation in coronary heart disease risk and affects nearly 25% of adults in the United States. First-line therapy is lifestyle modification, which includes body weight reduction, increased physical activity, and moderation of the dietary glycemic load. Drug treatments focusing on the major components of the syndrome (atherogenic dyslipidemia, hypertension, and a prothrombotic state) have demonstrated efficacy for reducing coronary heart disease events. Fibrates seem to be particularly effective in patients for whom a disturbance of the triglyceride-high-density lipoprotein axis is the primary lipid disorder. Fibrates also appear to influence a number of emerging risk factors, including hemostatic and inflammatory markers and indicators of improved vascular wall biology, which may contribute to their cardioprotective effects.
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PMID:Fibrates for treatment of the metabolic syndrome. 1466 7

The purpose of this cross-sectional analysis is to examine modifiable CVD risk factors in relation to menopausal status, age, and length of residence in the U.S. of midlife women from the former Soviet Union. The analysis includes baseline data for 193 women, aged 40-70, who lived in the U.S. fewer than 8 years and were enrolled in an ongoing four-year study of post-immigration health and behavior change. Data collection was conducted in women's homes or other community locations. The presence of seven health risk indicators (obesity, dyslipidemia, high blood pressure, diabetes mellitus, sedentary lifestyle, smoking, and excessive alcohol use) was assessed. In addition, Framingham 10 year risk scores for heart disease, and the presence of metabolic syndrome, were calculated using recent National Cholesterol Education Program (ATP-III) guidelines. Consistent with the age distribution, 60% of the women were postmenopausal. Four risk indicators (obesity, dyslipidemia, high blood pressure, and sedentary lifestyle) were identified as significant areas of concern. Although the Framingham risk scores did not seem excessively high, almost 25% of the women had metabolic syndrome. Older and postmenopausal women had significantly higher scores on all risk estimates. When age and menopausal status were held constant, menopausal status remained an independent contributor for the number of CVD risk indicators. Issues specific to this group of women because of their pre- and post-migration lifestyles are discussed in relation to their CVD risk status.
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PMID:Cardiovascular disease risk factors and menopausal status in midlife women from the former Soviet Union. 1466 3

This is a prospective evaluation of the effect of structured care of dyslipidemia with atorvastatin (strict implementation of guidelines) versus usual care (physician's standard of care) on morbidity and mortality of patients with coronary heart disease (CHD) and diabetes mellitus (DM). From 1600 consecutive CHD patients randomized to either form of care in the GREek Atorvastatin and CHD Evaluation Study (GREACE), 313 had DM: 161 in the structured care arm and 152 in the usual care arm. All patients were followed up for a mean of 3 years. In the structured care group, patients were treated with atorvastatin to achieve the National Cholesterol Education Program (NCEP) low-density lipoprotein cholesterol (LDL-C) treatment goal of <2.6 mmol/L (100 mg/dL). Primary endpoints were all-cause and coronary mortality, coronary morbidity, and stroke. In the structured care group, 156 patients (97%) were taking atorvastatin (10-80 mg/day; mean, 23.7 mg/day) throughout the study; the NCEP LDL-C treatment goal was reached by 150 patients (93%). Only 17% (n=26) of the usual care patients were on long-term hypolipidemic drug treatment and 4% (n=6) reached the NCEP LDL-C treatment goal. During the study, 46 of 152 (30.3%) CHD patients with DM on usual care experienced a major vascular event or died versus 20 of 161 (12.5%) patients on structured care; relative risk reduction (RRR) 58%, p<0.0001. RRR for all-cause mortality was 52%, p=0.049; coronary mortality 62%, p=0.042; coronary morbidity 59%, p<0.002; and stroke 68%, p=0.046. Event rate curves started deviating from the sixth treatment month and the RRR was almost 60% by the 12th month. RRRs remained at that level until the end of the study, when they became statistically significant. The cost/life-year gained with structured care was estimated at 6200 US dollars. In CHD patients with DM, structured care of dyslipidemia with atorvastatin to achieve the NCEP LDL-C treatment goal, reduces all-cause and coronary mortality, coronary morbidity, and stroke by more than one half within a 3-year period, in comparison to usual care. Clinical benefit is manifested as early as the sixth month of treatment.
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PMID:Early benefit from structured care with atorvastatin in patients with coronary heart disease and diabetes mellitus. 1466 56

The metabolic syndrome (MS) is a frequent cause of coronary artery disease (CAD), and recently the National Cholesterol Education Program Adult Treatment Panel III suggested its diagnosis in the presence of 3 to 5 quantitatively defined markers. Because the consequences of the MS are likely related to the number and diversity of markers, we studied the relation between the number of markers-the MS score-and the degree of abdominal obesity, risk factor profile, and severity of CAD. One thousand one hundred eight subjects of a mostly white population with symptoms of CAD (793 men and 315 women; 58.1 +/- 9.8 years of age) were divided into 6 groups based on their MS scores. A low high-density lipoprotein cholesterol level was the most frequently observed marker, followed by increased blood pressure, triglycerides, waist circumference, and fasting glucose. As the MS score increased so did abdominal obesity, parameters of "nontraditional" dyslipidemia with surrogate markers of dense low-density lipoprotein and high-density lipoprotein particles, blood pressure, fasting glucose, insulin, and the homeostatic model assessment insulin resistance index. Similarly, an increasing MS score was significantly related to more severe coronary angiographic alterations and higher frequencies of unstable angina, myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. Therefore, the MS score provides a clinically useful index of MS severity and the associated atherosclerotic risk factor profile. It also correlates with the angiographic severity of CAD and its clinical complications.
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PMID:Effect of increasing metabolic syndrome score on atherosclerotic risk profile and coronary artery disease angiographic severity. 1471 40

The metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances in metabolism, autonomic function, and health-related behaviors. However, physiological processes linking the components of the metabolic syndrome remain obscure. The current study examined associations of central nervous system serotonergic function with each metabolic syndrome risk variable, the metabolic syndrome, and physical activity. The subjects were 270 adult volunteers who participated in a study of cardiovascular disease risk factors and neurobehavioral functioning. Central serotonergic responsivity was indexed as the prolactin (PRL) response evoked by the serotonin-releasing agent, fenfluramine. Across the sample, low PRL response was associated with greater body mass index, higher concentrations of triglycerides, glucose, and insulin, higher systolic and diastolic blood pressure, greater insulin resistance, and less physical activity (P < 0.03-0.001). There also existed an inverse linear relationship between PRL response and the number of metabolic syndrome risk factors individuals possessed (P for trend = 0.002). Finally, a 1 SD decline in PRL response was associated with an odds ratio for the metabolic syndrome of 2.05 (95% confidence interval, 1.10-3.83; P = 0.002) and 5.70 (95% confidence interval, 1.69-19.25; P = 0.005), according to the definitions of the National Cholesterol Education Program and the World Health Organization, respectively. These findings reveal a heretofore unrecognized association between reduced central serotonergic responsivity and the metabolic syndrome.
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PMID:Low central nervous system serotonergic responsivity is associated with the metabolic syndrome and physical inactivity. 1471 60

Dyslipidemia, characterized by elevated serum levels of triglycerides and reduced levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol, has been recognized in patients with human immunodeficiency virus (HIV) infection. It is thought that elevated levels of circulating cytokines, such as tumor necrosis factor-alpha and interferon-alpha, may alter lipid metabolism in patients with HIV infection. Protease inhibitors, such as saquinavir, indinavir and ritonavir, have been found to decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with a syndrome of fat redistribution, insulin resistance, and hyperlipidemia. Elevations in serum total cholesterol and triglyceride levels, along with dyslipidemia that typically occurs in patients with HIV infection, may predispose patients to complications such as premature atherosclerosis and pancreatitis. It has been estimated that hypercholesterolemia and hypertriglyceridemia occur in greater than 50% of protease inhibitor recipients after 2 years of therapy, and that the risk of developing hyperlipidemia increases with the duration of treatment with protease inhibitors. In general, treatment of hyperlipidemia should follow National Cholesterol Education Program guidelines; efforts should be made to modify/control coronary heart disease risk factors (i.e. smoking; hypertension; diabetes mellitus) and maximize lifestyle modifications, primarily dietary intervention and exercise, in these patients. Where indicated, treatment usually consists of either pravastatin or atorvastatin for patients with elevated serum levels of LDL-C and/or total cholesterol. Atorvastatin is more potent in lowering serum total cholesterol and triglycerides compared with other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but it is also associated with more drug interactions compared with pravastatin. Simvastatin and lovastatin are significantly metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended for coadministration with protease inhibitors. A fibric acid derivative (gemfibrozil or fenofibrate) should be used in patients with primary hypertriglyceridemia. However, it must be kept in mind that protease inhibitors, such as nelfinavir and ritonavir, induce enzymes involved in the metabolism of the fibric acid derivatives and may, therefore, reduce the lipid-lowering activity of coadministered gemfibrozil or fenofibrate. In certain patients HMG-CoA reductase inhibitors may be used in combination with fibric acid derivatives but patients should be carefully monitored for liver and skeletal muscle toxicity. Select patients may experience improvements in serum lipid levels when their offending protease inhibitor(s) is/are exchanged for efavirenz, nevirapine, or abacavir; however each patient's virologic and immunologic status must be taken closely into consideration.
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PMID:Management of protease inhibitor-associated hyperlipidemia. 1472 85


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