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

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.
Expert Rev Cardiovasc Ther 2005 Mar
PMID:Lifestyle modification and endothelial function in obese subjects. 1585 97

Atherosclerosis and its complications still represent the major cause of death in developed countries. Statins have revolutionized the treatment of dyslipidemia and demonstrated their ability to reduce and prevent coronary morbidity and mortality. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol synthesis. The effectiveness and rapidity of statin-induced decreases in coronary events led to the speculation that statins possess cholesterol-independent effects. Since mevalonate produced by the HMG-CoA reductase is not only the precursor of cholesterol, but also of non steroidal isoprenoid compounds, such as the farnesyl pyrophosphate and the geranylgeranyl pyrophosphate, statins also regulate the small signaling proteins, Ras and Rho. Thus, inhibition of these prenylated proteins might account for the non-lipid lowering effects of statins. In this review, we describe the numerous beneficial pleiotropic effects of statins that could modulate atherogenesis.
Curr Drug Targets Cardiovasc Haematol Disord 2005 Apr
PMID:Cholesterol-independent effects of statins in inflammation, immunomodulation and atherosclerosis. 1585 54

Excessive fat (adiposity) and dysfunctional fat (adiposopathy) constitute the most common worldwide epidemics of our time -- and perhaps of all time. Ongoing efforts to explain how the micro (adipocyte) and macro (body organ) biologic systems interact through function and dysfunction in promoting Type 2 diabetes mellitus, hypertension and dyslipidemia are not unlike the mechanistic and philosophical thinking processes involved in reconciling the micro (quantum physics) and macro (general relativity) theories in physics. Currently, the term metabolic syndrome refers to a constellation of consequences often associated with excess body fat and is an attempt to unify the associations known to exist between the four fundamental metabolic diseases of obesity, hyperglycemia (including Type 2 diabetes mellitus), hypertension and dyslipidemia. However, the association of adiposity with these metabolic disorders is not absolute and the metabolic syndrome does not describe underlying causality, nor does the metabolic syndrome necessarily reflect any reasonably related pathophysiologic process. Just as with quantum physics, general relativity and the four fundamental forces of the universe, the lack of an adequate unifying theory of micro causality and macro consequence is unsatisfying, and in medicine, impairs the development of agents that may globally improve both obesity and obesity-related metabolic disease. Emerging scientific and clinical evidence strongly supports the novel concept that it is not adiposity alone, but rather it is adiposopathy that is the underlying cause of most cases of Type 2 diabetes mellitus, hypertension and dyslipidemia. Adiposopathy is a plausible Theory of Everything for mankind's greatest metabolic epidemics.
Expert Rev Cardiovasc Ther 2005 May
PMID:Adiposopathy, metabolic syndrome, quantum physics, general relativity, chaos and the Theory of Everything. 1588 67

According to the current evidence, the fastest growing proportion of patient populations seeking healthcare is those over 65 years of age. Coronary artery disease and subclinical atherosclerosis are highly prevalent in this group of patients and are strongly linked to dyslipidemia, a well-established risk factor for atherosclerosis. Treating dyslipidemia in this group of patients requires specific knowledge and understanding of common dyslipidemias and the relative safety of various pharmacologic agents in the presence of possible multiple comorbidities. Lifestyle modification remains the first step in the treatment of dyslipidemia; however, it can be difficult to sustain and achieve acceptable compliance in the elderly and it is best used in combination with drug therapy. Statins are widely accepted as the first-line therapy. Several recent studies have demonstrated that statins are safe and effective in the elderly. However, it is important to note that there is very limited data regarding the effects of dyslipidemia treatment on morbidity and mortality in patients over 85 years of age. In summary, the clinicians must recognize that the presence of dyslipidemia in the elderly poses substantial risk of coronary events and stroke. The available evidence has demonstrated that in most elderly patients who are at increased risk for cardiovascular morbidity and mortality, treatment of dyslipidemia with appropriate therapy reduces the risk, and when used carefully with close monitoring for safety, the treatment is generally well tolerated. With increasing life expectancy, it is critical for physicians to recognize the importance of detection and treatment of dyslipidemia in the elderly.
Expert Rev Cardiovasc Ther 2005 May
PMID:Dyslipidemia and lipid-lowering therapy in the elderly. 1588 73

Patients with type 2 diabetes mellitus have a greater risk of cardiovascular disease than nondiabetic individuals. These patients are often insulin resistant and have an associated clustering of risk factors that contribute to cardiovascular disease. The risk factors include dyslipidemia, hypertension, altered hemostasis, and chronic inflammation. A primary objective in the management of type 2 diabetes mellitus is normalization of blood glucose levels; however, some of the oral drugs used to control blood glucose levels have significant effects on these risk factors. In this article, we review the current data involving the modification of these cardiovascular risk factors by the biguanide (metformin), the thiazolidinediones (troglitazone, rosiglitazone, and pioglitazone), the alpha-glucosidase inhibitors (miglitol, acarbose), and the insulin secretagogs (glyburide [glibenclamide], glipizide, chlorpropamide, tolbutamide, tolazamide, glimepiride, repaglinide, and nateglinide). Generally, the thiazolidinediones improve hemostasis and endothelial function and reduce blood pressure, while having variable effects on dyslipidemia. Metformin improves dyslipidemia and altered hemostasis and decreases plasma C-reactive protein levels with little or no effect on blood pressure. Data on the effects of the alpha-glucosidase inhibitors and insulin secretagogs are sparse; however, these drugs appear to have little or no effect on cardiovascular risk factors.
Am J Cardiovasc Drugs 2005
PMID:Cardiovascular risk factors associated with insulin resistance: effects of oral antidiabetic agents. 1590 Dec 7

Although circumstantial evidence supports raising high-density lipoprotein cholesterol (HDLC) in patients with low levels of HDLC, the scarcity of event-based trials has led to uncertainty with regard to the benefit of high-density lipoprotein (HDL)-raising therapy. Based on the National Cholesterol Education Program guidelines, therapy for dyslipidemia is focused initially on targeting low-density lipoprotein cholesterol (LDLC), and in patients with hypertriglyceridemia, secondarily on targeting non-HDLC. When HDLC remains low, the decision to target HDLC depends on the assessment of risk of cardiovascular events. We often consider drug therapy specifically to raise HDLC in high-risk patients, such as those with established atherosclerotic vascular disease, type 2 diabetes, or a Framingham risk score of 20% or above. The majority of high-risk patients require drug therapy, usually a statin, to achieve aggressive LDLC and non-HDLC goals, and thus many patients with low HDLC are candidates for statin therapy. However, a second drug is often required to achieve substantial HDL raising. Although no formal goals for HDLC exist, reasonable goals are HDLC greater than 40 mg/dL in men and greater than 50 mg/dL in women. We often add either niacin or a fibrate to a statin in high-risk patients with low HDLC levels. Targeting HDLC with pharmacologic therapy is a more difficult decision in moderate-risk patients, in whom therapy must be highly individualized.
Curr Treat Options Cardiovasc Med 2005 May
PMID:Current Drug Options for Raising HDL Cholesterol. 1591

The metabolic syndrome is defined as a condition characterized by a set of clinical criteria: insulin resistance, visceral obesity, atherogenic dyslipidemia, and hypertension. The major risk factors leading to the epidemic of this syndrome in the United States are visceral obesity, physical inactivity, and an atherogenic diet. The available current evidence suggests that the first step in management of patients with metabolic syndrome should be focused on lifestyle modifications (eg, weight loss and physical activity). The treatment should be based on two major components: behavioral change to reduce caloric intake and an increase in physical activity. A realistic goal for weight reduction should be 7% to 10% over 6 to 12 months. The general dietary recommendations include low intake of saturated fats, trans fats and cholesterol, and diets with low glycemic index. Soy protein could be more beneficial than animal protein in weight reduction and correction of dyslipidemia. Physical activity is associated with successful weight reduction and these therapeutic lifestyle changes can reduce by half the progression to new-onset diabetes in patients with metabolic syndrome. Physical activity recommendations should include practical, regular, and moderated regimens of exercise, with a daily minimum of 30 to 60 minutes. An equal balance between aerobic exercise and strength training is advised. Medication therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals. There is no single best therapy and the treatment should consist of treatment of individual component(s). Atherogenic dyslipidemia should be controlled with statins if there is concomitant increase in low-density lipoprotein cholesterol and if indicated with combination therapy, including fibrates, nicotinic acid, bile acid-binding resins, or ezetimibe. Drugs such as thiazolidinediones and renin-angiotensin system blockers are a few of the available agents in this category. Some evidence suggests that angiotensin-converting enzyme inhibitors and b blockers are more beneficial for treatment of hypertension in patients with metabolic syndrome. Patients with metabolic syndrome also have elevations in fibrinogen and other coagulation factors leading to prothrombotic state and aspirin may be beneficial for primary prevention in these patients. The new developments in the treatment of metabolic syndrome with drugs, such as peroxisome proliferator-activated receptor agonists, will broaden the horizons of the current treatment options in metabolic syndrome.
Curr Treat Options Cardiovasc Med 2005 May
PMID:Current Treatment Options for the Metabolic Syndrome. 1591 5

Drugs in the same class are generally thought to be therapeutically equivalent because of similar mechanisms of action (the so-called "class effect"). However, statins differ in multiple characteristics, including liver and renal metabolism, half-life, effects on several serum lipid components, bioavailability and potency. Some are fungal derivatives, and others are synthetic compounds. The percentage absorption of an oral dose, amount of protein binding, degree of renal excretion, hydrophilicity, and potency on a weight basis is variable. These differences may be even greater in diabetic patients, who may present diabetes-induced abnormalities in P450 isoforms and altered hepatic metabolic pathways. Thus, it is obvious that head-to-head comparisons between different statins are preferable than trial-to-trial comparisons. Such assessments are of utmost importance, especially in cases in which specific populations with a distinct lipid profile and altered metabolic pathways, like diabetics, are studied. It should be specially pinpointed that patients with metabolic syndrome and diabetes constitute also a special population regarding their atherogenic dyslipidemia, which is usually associated with low HDL-cholesterol, hypertriglyceridemia and predominance of small dense LDL-cholesterol. Therefore, these patients may benefit from fibrates or combined statin/fibrate treatment. This policy is not accomplished since in the real world things are more complex. Trials would require very large sample sizes and long-term follow-up to detect significant differences in myocardial infarction or death between two different statins. Moreover, the fact that new compounds are under several phases of research and development represents an additional drawback for performing the trials. Ideally, head-to-head trials regarding clinically important outcomes should be conducted for all drugs. Nonetheless, the desirability of performing such trials, which epitomize modern evidence-based medicine, is frequently superseded by the feasibility dictated by pragmatic and economic circumstances. In the latter case, in absence of solid systematic documentation of comparable health benefits and long-term safety, both researchers and practicing physicians should allude to the weight of scientific endorsement behind the arguments and seek for the possible strengths and weaknesses intrinsic to each specific study. In any case, conclusions based on surrogate endpoints cannot completely substitute head-to-head comparisons regarding patients' outcome.
Cardiovasc Diabetol 2005 Jun 07
PMID:Statins research unfinished saga: desirability versus feasibility. 1594 71

Dyslipidemia, fundamental to the atherosclerotic process, is now a readily correctable risk factor with established efficacy of treatment for reducing risk of CHD and strokes. The current focus on LDL-cholesterol for risk assessment needs to be broadened to accommodate the two-way traffic of cholesterol entering and leaving the arterial intima reflected by the LDL/HDL ratio or the Total/HDL ratio. The choice of lipid therapy should be individualized to take into account the presence of the metabolic syndrome and the lipid profile of the patient. The intensity of therapy and goals should be linked to multivariable risk, particularly in those with modest lipid values. Cardiovascular risk factor clustering is pronounced for each lipid, is promoted by adiposity and greatly influences its CHD hazard. Global risk assessment taking clustering into account is essential for efficient preventive management of lipids. More attention needs to be afforded the absolute risk reduction attainable and must recognize that the number needed to treat to prevent one event increases the lower the lipid value, the lower global risk and the healthier the subject.
Curr Med Chem Cardiovasc Hematol Agents 2005 Jul
PMID:Risk stratification of dyslipidemia: insights from the Framingham Study. 1597 83

Reduction of low-density lipoprotein cholesterol (LDL-C) with statin therapy is currently identified in treatment guidelines as the primary focus for patients with or at risk of coronary heart disease (CHD). Yet despite effective statin therapy there is still an unacceptably high residual coronary risk. A substantial proportion of patients with CHD have mixed dyslipidemia, including low levels of high-density lipoprotein cholesterol (HDL-C), an independent and predictive risk factor for CHD. Although effective in reducing LDL-C, statin therapy has only modest effects in raising HDL-C. Fibrate therapy is an alternative lipid-modifying strategy, and is effective in reducing CHD mortality and morbidity, with the magnitude of clinical benefit similar to statin therapy. Multi-drug therapy with complementary mechanisms of action has been proposed as a means of improving lipid-modifying efficacy. Nicotinic acid is the most potent agent for increasing HDL-C and also substantially reduces LDL-C and triglycerides. Addition of nicotinic acid to statin therapy would be a logical management approach, given the potential for complementary therapeutic benefit. The clinical benefits of this combination are supported by the results of the HDL Atherosclerosis Treatment Study, which showed reduction of 60-90% in the incidence of major coronary events when both agents were administered. In addition, combination treatment led to angiographic regression of stenosis, compared with placebo, rather than slowed progression as previously reported with statin monotherapy. Given that the prevalence of low HDL-C, particularly amongst individuals with CHD, is higher than previously anticipated, combining nicotinic acid and a statin represents an innovative approach to further reducing CHD risk.
Cardiovasc Drugs Ther 2005 Mar
PMID:Beyond the statins: new therapeutic perspectives in cardiovascular disease prevention. 1602 32


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