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)

Statins have been described as miracle drugs, but such "beatification" is not justified. Changes in lifestyle should be considered the cornerstone in cardiovascular prevention. However, trends in mortality from coronary heart disease have not effectively changed since statins were approved in the United States, while obesity has risen significantly. Have these drugs contributed to a deterioration in lifestyle among those who believe a pill will protect them? Adherence to healthful lifestyle has been shown to be associated with reductions in the rates of coronary disease, diabetes in women, and mortality in elderly. Patients with major lifestyle problems enrolled in recent statin trials were given only drugs, and no statin has ever been compared with a nonatherogenic lifestyle and shown to be superior or additive. Furthermore, there is no evidence for a total mortality benefit in women and elderly persons from dyslipidemia therapy. Side effects are often presented as relative, not absolute risk, and are suggested to be low. However, there is reason to believe that their numbers are much larger in clinical practice where the drugs may be given to most patients usually excluded in randomised trials. Statin-related side effects may be considered as a complication to the primary disease. However, these complaints may be statin therapy related. Finally, the relationship between long-standing statin therapy and cancerogenesis is not fully understood. Investigators should carefully resist the natural tendency to highlight the most positive findings in their studies while minimising harm, especially when commercially sponsored.
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PMID:Questioning the "beatification" of statins. 1732 Feb 17

Statin therapy has been a significant advance in the management of dyslipidemia and atherothrombotic cardiovascular disease with a resultant 30% to 40% reduction in cardiovascular events; however, a significant number of events continue to occur in statin-treated patients, including in patients treated with high-dose statins targeted to achieve mean low-density lipoprotein cholesterol levels in the range of 60 to 80 mg/dL. Therefore, development and testing of new therapies that exploit the vascular protective effects of high-density lipoprotein (HDL) constitutes a rational and complementary approach. A number of HDL-based therapies are in various stages of development and testing. It is hoped that one or more of these new HDL-based therapies, if proven effective and safe, will become a part of our armamentarium against vaso-occlusive cardiovascular disease. A paradigm could emerge in which patients recovering from acute coronary syndromes and at high risk of recurrent events could be treated with rapid-acting HDL-based therapy, such as infusions of recombinant HDL or even HDL delipidation, followed by more sustained long-term HDL-based therapies, such as oral agents and perhaps even HDL-based gene therapy.
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PMID:Emerging HDL-based therapies for atherothrombotic vascular disease. 1737 77

Combined hyperlipidemia results from overproduction of hepatically synthesized apolipoprotein B in very low-density lipoproteins in association with reduced lipoprotein lipase activity. Thus, this condition is typically characterized by concurrent elevations in total cholesterol and triglycerides with decreased high-density lipoprotein cholesterol. High levels of apolipoprotein B-containing lipoproteins, most prominently carried by low-density lipoprotein (LDL) particles, are an important risk factor for coronary heart disease. Statin therapy is highly effective at lowering LDL cholesterol. Despite the benefits of statin treatment for lowering total and LDL cholesterol, many statin-treated patients still have initial or recurrent coronary heart disease events. In this regard, combined therapy with statins and fibrates is more effective in controlling atherogenic dyslipidemia in patients with combined hyperlipidemia than either drug alone. Furthermore, statins and fibrates activate PPARalpha in a synergistic manner providing a molecular rationale for combination treatment in coronary heart disease. Endothelial dysfunction associated with cardiovascular diseases may contribute to insulin resistance so that there may also be additional beneficial metabolic effects of combined statin/fibrates therapy. However, there has been little published evidence that combined therapy is synergistic or even better than monotherapy alone in clinical studies. Therefore, there is a great need to study the effects of combination therapy in patients. When statins are combined with gemfibrozil therapy, this is more likely to be accompanied by myopathy. However, this limitation is not observed when fenofibrate, bezafibrate, or ciprofibrate are used in combination therapy.
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PMID:Vascular and metabolic effects of treatment of combined hyperlipidemia: focus on statins and fibrates. 1765 32

Statin-treatment of fructose-fed/insulin resistant hamsters was recently shown to ameliorate metabolic dyslipidemia and hepatic VLDL overproduction. Here, we provide evidence that rosuvastatin treatment of insulin resistant hamsters can induce improvements in hepatic and whole body insulin sensitivity. Treatment with 10 mg/kg/day rosuvastatin for 10 days significantly reduced fasting insulin (-59%) and triglyceride (-50%) levels in fructose-fed hamsters (p<0.05). Following an intraperitoneal (IP) glucose challenge, rosuvastatin-treated hamsters exhibited enhanced glucose clearance compared to untreated hamsters maintained on the high-fructose diet (area under curve (AUC)=1772+/-223 mM min vs. 2413+/-253 mM min, respectively; p<0.002) with a significant reduction in 2h post-challenge glucose (n=5, p<0.02). Rosuvastatin-treatment also significantly improved sensitivity to an IP insulin challenge (AUC=314+/-39 mM min vs. 195+/-22 mM min for rosuvastatin-treated and fructose-fed hamsters, respectively; p<0.04, n=3). At the molecular level, significant increases in tyrosine-phosphorylation of the hepatic insulin receptor and IRS-1 were observed for rosuvastatin-treated hamsters (+37% and +58%, respectively) compared to fructose-fed controls following an intravenous (IV) bolus of insulin (p<0.05). Increases in insulin receptor and IRS-1 phosphorylation were also observed in muscle and adipose tissue. Analysis of hepatic Akt phosphorylation and mass revealed a small (25%) increase in serine phosphorylation of Akt with no significant change in Akt mass, although serine-phosphorylation and mass of Akt2 were significantly increased (+32%, p=0.03, and +42%, p=0.01, respectively). Interestingly, expression of PTP-1B, a key negative regulator of insulin signaling, showed a non-significant trend toward reduction in liver and was significantly reduced in adipose tissue (-20% and -37%, respectively). Taken together, these data suggest that statin-treatment increases whole body and peripheral tissue insulin sensitivity via improved cellular insulin signal transduction.
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PMID:Effect of rosuvastatin on insulin sensitivity in an animal model of insulin resistance: evidence for statin-induced hepatic insulin sensitization. 1809 97

Trials have revealed that cardiovascular risk is not uniform in the population, but is distributed in a "risk pyramid." Diabetic patients with prior cardiovascular disease (CVD) are at greatest risk. Nondiabetic patients with CVD, diabetic patients without CVD, and subjects with the metabolic syndrome form the next three risk categories. The presence of insulin resistance-related metabolic abnormalities is a common denominator in this risk pyramid. Insulin resistance is a core defect in type 2 diabetes and the metabolic syndrome. Because insulin resistance may cause the atherogenic dyslipidemia that is commonly associated with these conditions, therapeutic strategies that combat insulin resistance could substantially reduce cardiovascular risk. Evidence suggests that defects in mitochondrial oxidative phosphorylation (which may be inherited, age related, or lifestyle acquired) may play a critical role in the pathogenesis of insulin resistance. Reduced mitochondrial oxidative phosphorylation can be partially reversed by improved diet, increased exercise, and administration of peroxisome proliferator-activated receptor-alpha agonists (omega-3 fatty acids and fibrates). Statin therapy has demonstrated clinical benefits in insulin-resistant patients but residual cardiovascular risk remains elevated. Fibrates also improve the lipid profile and reduce cardiovascular risk in a variety of insulin-resistant populations. Affected individuals should be targeted for therapeutic lifestyle intervention. Patients with atherogenic dyslipidemia who have developed insulin resistance, the metabolic syndrome, or type 2 diabetes should receive more intensive interventions including, where appropriate, statin-fibrate combination therapy, to comprehensively modify the lipid profile together with aggressive control of blood pressure and glucose to minimize risk in this very high-risk population.
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PMID:New concepts in dyslipidemia in the metabolic syndrome and diabetes. 1837 Jul 48

The prevalence of type 2 diabetes mellitus continues to increase rapidly. Persons with diabetes face a 2-fold greater absolute risk of cardiovascular disease (CVD) than those without diabetes. Many diabetic patients die before reaching the hospital after a cardiovascular event. Use of statin therapy for intensive control of diabetic dyslipidemia has produced relative reductions in CVD risk of about 25% in randomized, controlled clinical trials. This is true even though low-density lipoprotein cholesterol, the primary target of statin therapy, might not be markedly elevated in diabetic patients. Most patients with diabetes or diabetes plus established CVD warrant intensive statin therapy. Statin therapy has the ability to achieve low-density lipoprotein cholesterol goals recommended in treatment guidelines. Alone or in combination with an additional lipid-lowering drug, statins may also improve triglyceride and high-density lipoprotein cholesterol abnormalities in patients with diabetes.
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PMID:Do people with diabetes need statins? 1866 8

Erythropoietin-stimulating agent (ESA) hyporesponsiveness is aggravated by chronic inflammation in maintenance hemodialysis (MHD) patients. Dyslipidemia is prevalent in MHD patients. Statin therapy has been demonstrated to not only be effective in lowering lipid levels, but also numerous pleiotropic effects including anti-inflammatory, anti-fibrotic and endothelial function improvement. Recently, a retrospective study has shown that statin therapy decreases ESA requirements in MHD patients. We conducted a prospective study to analyze the effect of statin therapy on ESA hyporesponsiveness, and especially emphasized its anti-inflammatory benefits in MHD patients. This prospective study enrolled 30 patients with baseline cholesterol >220 mg/dl. Low-dose atorvastatin (10 mg/day) was prescribed for 12 weeks. We prospectively recorded patients' biochemistry and hematological profiles, ESA prescription and some inflammatory markers at baseline, 4 weeks and 12 weeks. Statistically significant changes were noted after 4 and 12 weeks of statin therapy for cholesterol (272.5 +/- 41.1 to 184.4 +/- 37.6 and 196.4 +/- 40.2 mg/dl, p < 0.05) and ESA hyporesponsiveness, which demonstrated as erythropoietin to hematocrit ratio (EHR) (129.3 +/- 58.2 to 122.3 +/- 53.5 and 121.0 +/- 53.3 EPO U/Hct/week, p < 0.05). Mean values for proinflammatory cytokines included interleukin-6 and tumor necrotic factor-alpha levels decreased by 30.8 and 10.6%, respectively. Thus, these data suggest that statin therapy may improve ESA hyporesponsiveness in dialysis patients. This improvement in ESA hyporesponsiveness is associated with the effects of statins on inflammation.
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PMID:Atorvastatin increases erythropoietin-stimulating agent hyporesponsiveness in maintenance hemodialysis patients: role of anti-inflammation effects. 1897 40

Dyslipidemia is an important complication affecting kidney transplant recipients. Statins, the first-line therapy, are often insufficient. Ezetimibe may be effective in combination with statin therapy. We performed a retrospective study to determine the safety and efficacy of ezetimibe treatment in addition to statin therapy among 27 stable renal transplant patients with uncontrolled hypercholesterolemia. We obtained fasting lipid profiles at 3 and 6 months before ezetimibe therapy, while the patients were receiving statins at maximum tolerated doses. Statin doses were stable during the study. All patients received ezetimibe (10 mg) once daily. Fasting lipid profile, kidney function, liver enzymes, creatine kinase, and immunosuppressive drug levels were obtained at baseline as well as at 3 and 6 months post-ezetimibe initiation. Combination therapy resulted in median reductions in total cholesterol of 29% (interquartile range [IQR] 12-39; P = .0001) and 28% (IQR 9-38; P = .0001); in low-density lipoprotein cholesterol of 34% (IQR 16-61; P = .0001) and 44% (IQR 24-56; P = .0001); and in triglycerides of 14% (IQR 4-31; P = .01) and 19% (IQR 1-37; P = .006) at 3 and 6 months post-ezetimibe therapy, respectively. There were no significant differences in high-density lipoprotein cholesterol, renal function, proteinuria, creatine kinase, amylase, liver function, body mass index, or drug levels. There were no adverse drug reactions that mandated treatment withdrawal. When combined with statin therapy ezetimibe seemed to be a safe and effective treatment for uncontrolled dyslipidemia among renal transplant patients.
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PMID:Ezetimibe in the treatment of uncontrolled hyperlipidemia in kidney transplant patients. 1910 Apr 21

Statin therapy reduces the incidence of cardiovascular (CV) disease by 30-40%. However, some risk of unprevented CV complications still persists. Thus, new drugs that when associated to the statins favorably modify the lipid profile and further reduce CV risk are needed. In this clinical commentary, we review the role of other lipids (HDL cholesterol and triglycerides) in CV risk and those potentially useful agents that could be added to statins. Fibrates are especially effective to decrease triglycerides, whilst niacin has a global effect, decreasing LDL cholesterol and triglycerides and is the most effective drug to increase HDL cholesterol. The association of statins plus niacin may be the immediate future to tackle the comprehensive treatment of dyslipidemia and potentially further reduce the risk of CV disease.
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PMID:[New challenges in the treatment of dyslipidemia and cardiovascular risk]. 1948 Jul 81

Statin treatment targeting low-density lipoprotein (LDL) cholesterol is widely used for cardiovascular risk reduction, but many statin users still face greatly elevated risks. Some experts advocate additional therapy that targets high-density lipoprotein (HDL) cholesterol. However, the size of the patient group that could benefit from HDL cholesterol or triglyceride therapy has not been reported. Using observational data from a large health maintenance organization, 5,158 patients were identified who initiated dyslipidemia pharmacotherapy from July 2004 to June 2006, continued therapy for 1 year, and had full lipid panels within 6 months before and 9 to 15 months after therapy initiation. Therapy (primarily statins) reduced the proportion of patients not at LDL cholesterol goals from 77% to 22% and the proportion with high triglyceride levels from 34% to 20%. HDL cholesterol levels were unchanged (49% and 50% were less than normal levels before and after therapy, respectively) in the aggregate and in high-risk subgroups (patients with coronary artery disease, diabetes, and 10-year heart disease risk >20%). After therapy, 29% of high-risk patients still had multiple lipid abnormalities. In conclusion, current dyslipidemia therapy substantially improved LDL cholesterol goal attainment in this cohort, but low HDL cholesterol levels were unaffected. About half the patients starting statins could be candidates for additional therapy targeting non-LDL cholesterol lipid fractions.
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PMID:Frequency of obtaining national cholesterol education program adult treatment panel III goals for all major serum lipoproteins after initiation of lipid altering therapy. 1996 78


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