Hyperlipidemias: Liberopoulos EN

Liberopoulos EN, Florentin M, Mikhailidis DP, Elisaf MS. · University of Ioannina, Medical School, Department of Internal Medicine, Ioannina, Greece. · Expert Opin Drug Saf. · Pubmed #18983218 No free full text.

Abstract: BACKGROUND: Hypercholesterolemia is a major risk factor for cardiovascular disease. OBJECTIVE: Treatment with hypolipidemic agents reduces the risk of vascular events both in primary and secondary prevention. Although compliance with lipid-lowering therapy is an important determinant of cardiovascular clinical outcomes, relatively little attention is being paid to this issue by physicians. METHODS: We searched the literature using Pubmed up to 5 August 2008. RESULTS: Compliance with lipid-lowering therapy is poor in clinical practice, especially in primary prevention. As many as 6 out of 10 patients may stop taking statins during the first 6 months following initiation of treatment. Poor compliance has been associated with worse clinical outcome and increased cardiovascular morbidity and mortality. Importantly, statin withdrawal may be even worse compared with not taking statins at all. Several strategies may increase treatment adherence. CONCLUSIONS: Poor compliance with lipid-lowering treatment is an important health issue that has been associated with unfavorable cardiovascular outcome. Increasing adherence rates should become a major concern for physicians.

Florentin M, Liberopoulos EN, Elisaf MS. · Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · Int J Clin Pract. · Pubmed #18173814 No free full text.

Abstract: OBJECTIVE: Ezetimibe is a relatively new lipid lowering agent, which is indicated for the treatment of primary hypercholesterolaemia, either as monotherapy or in combination with other hypolipidaemic drugs. The objective of the present article was to review the side effects attributed to ezetimibe administration and discuss their possible underlying mechanisms. Moreover, we aimed to comment on the possible drug interactions of ezetimibe and present current guidelines regarding its safe use. METHODS: Relevant articles were identified through a PubMed search (up to June 2007). RESULTS: Compelling evidence from the majority of the data reviewed here showed that adverse effects associated with ezetimibe use are few and mild without having been associated with serious clinical outcomes. In most studies ezetimibe has not been associated with increased rates of myopathy or rhabdomyolysis, whether used alone or in combination with statins, although there have been some case reports of myopathy attributed to this agent. Moreover, ezetimibe has been associated with mild elevations of liver transaminases, mainly in combination with a statin. Other side effects are extremely rare. It should be noted, however, there are no long-term safety data or outcome studies for ezetimibe yet. CONCLUSIONS: Ezetimibe is a safe alternative option for hyperlipidaemic patients intolerant to other lipid lowering drugs as well as a beneficial supplementary agent for patients who do not reach the recommended serum cholesterol level with their current hypolipidaemic treatment. However, as is the case with all new medications, physicians should be alert to recognise adverse effects associated with ezetimibe and report them to regulatory authorities.

Milionis HJ, Liberopoulos EN, Elisaf MS, Mikhailidis DP. · Department of Clinical Biochemistry, Vascular Disease Prevention Clinics, Royal Free Hospital, Pond Street, London NW3 2QG, UK. · Curr Hypertens Rep. · Pubmed #17519121 No free full text.

Abstract: Hypertension and hyperlipidemia, two powerful risk factors of cardiovascular disease (CVD), often coexist. Therefore, treatment should consider the beneficial properties of drugs used to treat either condition. Statins, the mainstay of lipid-lowering therapy, result in a significant clinical benefit both in primary and secondary CVD prevention. In addition to their hypolipidemic capacity, other properties may contribute to statin-induced benefits. Clinical and experimental evidence indicates that statins may modulate blood pressure (BP). The mechanisms by which statins reduce BP seem to be largely independent of their lipid effects. Although small, reductions in BP are possibly clinically relevant. Large landmark studies confirm that statins can reduce CVD risk in hypertensive patients. These findings suggest that statins could be prescribed as an adjunct in treating hypertension with dyslipidemia or even in patients with "normal" cholesterol levels. Whether the effect of statins on BP is accompanied by an additional decrease in clinical outcomes needs to be investigated in long-term, large-scale trials.

Milionis HJ, Liberopoulos EN, Achimastos A, Elisaf MS, Mikhailidis DP. · Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · J Hum Hypertens. · Pubmed #16511505 No free full text.

Abstract: The assessment of global cardiovascular risk is an essential step in the management of atherosclerotic disease prevention. Among the risk factors to be addressed are hypertension and hyperlipidaemia; these commonly coexist. A neutral or lipid-friendly antihypertensive agent is probably useful in the presence of lipid abnormalities. Similarly, statins have been shown to decrease cardiovascular risk in hypertensive patients. There is also experimental and clinical evidence that statins have blood pressure (BP)-lowering effects. In this review, we discuss the beneficial effects of statins on BP, and provide an overview of the underlying pathophysiology. We also consider the evidence justifying the use of statins in the management of hypertensive patients.

Liberopoulos EN, Daskalopoulou SS, Mikhailidis DP, Wierzbicki AS, Elisaf MS. · Department of Internal Medicine, Medical School, University of Ioannina, Greece. · Curr Med Res Opin. · Pubmed #15801994 No free full text.

Abstract: BACKGROUND: Statin therapy has been shown to significantly decrease vascular events and overall mortality in primary and secondary prevention trials. This review considers the pharmacology, nonlipid-lowering effects and clinical trial evidence of fluvastatin based on a survey of PubMed entries. FINDINGS: Recent clinical data show that treatment with fluvastatin is associated with a variety of benefits in different high-risk populations along with a good safety profile. Fluvastatin exerts non-lipid lowering-associated pleiotropic effects in both clinical and experimental studies. Furthermore, an extended-release formulation of fluvastatin with a favourable pharmacokinetic profile is available. CONCLUSION: Treatment with fluvastatin offers a convenient, safe and evidence-based approach to managing dyslipidaemias and preventing vascular events.

Bairaktari ET, Tzallas CS, Tsimihodimos VK, Liberopoulos EN, Miltiadous GA, Elisaf MS. · Biochemistry Laboratory, University Hospital, Ioannina, Greece. · J Cardiovasc Risk. · Pubmed #10353071 No free full text.

Abstract: OBJECTIVE: To evaluate and compare the influences of micronized fenofibrate and atorvastatin on serum lipid profile, including lipoprotein(a) levels, and on fibrinogen levels in a large group of patients with primary mixed hyperlipidemia (serum total and low-density lipoprotein cholesterol levels > 240 and 160 mg/dl, respectively, and serum triglyceride level > 200 mg/dl). METHODS: This was a 16-week, open-label, parallel-design study conducted in our lipid clinic. After a 6-week dietary baseline phase, we implemented a treatment phase, during which patients received 10 mg/day atorvastatin (n = 45) or 200 mg/day micronized fenofibrate (n = 46) for 16 weeks. Patients were assigned to one of the drugs in sequential orders. Serum lipid profiles, including levels of lipoprotein(a) and fibrinogen, as well as muscle and liver enzymes, were measured during screening, and during weeks -4, -2, 0, 8, and 16 of the treatment period. RESULTS: Atorvastatin was more effective than was micronized fenofibrate at lowering levels of total and low-density lipoprotein cholesterol, whereas fenofibrate was more effective at lowering levels of triglycerides, and raising levels of high-density lipoprotein cholesterol and apolipoprotein A1. However, micronized fenofibrate could significantly decrease plasma fibrinogen levels, whereas atorvastatin evoked a small increase. CONCLUSION: Both atorvastatin in small doses and micronized fenofibrate are effective for improving serum lipid profiles of patients with mixed hyperlipidemia. However, there are considerable differences between the two drugs concerning their influences on plasma fibrinogen levels.

Christidis DS, Liberopoulos EN, Kakafika AI, Miltiadous GA, Liamis GL, Kakaidi B, Tselepis AD, Cariolou MA, Elisaf MS. · Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · Arch Med Res. · Pubmed #17416287 No free full text.

Abstract: BACKGROUND: Decreased paraoxonase 1 (PON1) and increased total serum lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activities are suggested to be risk factors for vascular disease. Common PON1 genetic polymorphisms (Q192R and L55M) significantly affect PON1 activity and may also influence high-density lipoprotein (HDL)-associated Lp-PLA(2) activity. However, little is known about the possible effect of PON1 common genetic polymorphisms on the response of lipids as well as PON1 and Lp-PLA(2) activities to treatment with statins. METHODS: Two hundred two hypercholesterolemic patients were treated with fluvastatin 40 mg/day. Fasting serum lipids, Q192R and L55M PON1 polymorphisms as well as PON1 and Lp-PLA(2) (total serum and HDL-associated) activities were determined before and after 6 months of treatment. RESULTS: Fluvastatin treatment did not affect HDL-cholesterol or apolipoprotein (apo) AI but resulted in significant decreases in total cholesterol, triglycerides, low-density lipoprotein-cholesterol, apo B and apo E, as well as total serum Lp-PLA(2) activity. In contrast, PON1 activity significantly increased. None of these changes was influenced by Q192R or L55M PON1 polymorphisms. Overall, HDL-Lp-PLA(2) did not change but L55M polymorphism significantly influenced its response to fluvastatin. Specifically, LL homozygotes experienced a significant increase, while M carriers (LM or MM) experienced a non-significant decrease in HDL-Lp-PLA(2) activity (p = 0.030 between groups). CONCLUSIONS: Q192R and L55M PON1 polymorphisms did not affect the response of lipids, PON1 and total serum Lp-PLA(2) to treatment with a statin. However, L55M PON1 polymorphism significantly modulated the response of HDL-Lp-PLA(2). It should be noted that this is an association study and therefore provides no proof but only indication that PON1 may also exert Lp-PLA(2) activity in HDL.

Gazi IF, Filippatos TD, Tsimihodimos V, Saougos VG, Liberopoulos EN, Mikhailidis DP, Tselepis AD, Elisaf M. · Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · Lipids. · Pubmed #17069348 No free full text.

Abstract: The hypertriglyceridemic waist (HTGW) phenotype (hypertriglyceridemia and increased waist circumference) has been proposed as an inexpensive tool to monitor individuals with the atherogenic metabolic triad, hyperinsulinemia, hyperapobetalipoproteinemia, and increased levels of small, dense LDL (sdLDL) particles. We assessed the association of the HTGW phenotype with the metabolic syndrome (MetSyn) and the atherogenic metabolic triad in inhabitants (n = 260) of northwestern Greece attending the Outpatient Lipid Clinic of the University Hospital of Ioannina. The LDL subfractions were assessed using the Lipoprint LDL System. HTGW (+) individuals had a more adverse lipid and lipoprotein profile compared with HTGW (-) individuals. Moreover, HTGW (+) subjects had elevated levels of sdLDL-C, as well as decreased mean and peak LDL particle size compared with HTGW (-) subjects. To our knowledge, this is the first report documenting the sdLDL-C abnormality in HTGW (+) subjects. Among men (n = 105), 52.3% of the MetSyn (+) individuals and 66.7% of the HTGW (+) individuals had the metabolic triad. Among women (n = 155), the corresponding percentages were 42.3% and 50.0%. Only 22.2% and 10.6% of the MetSyn (-) subjects (men and women, respectively) and 19.6% and 15.2% of the HTGW (-) subjects (men and women, respectively) had the atherogenic metabolic triad. In conclusion, the HTGW (+) phenotype is associated with a hostile lipid profile that includes higher levels of sdLDL-C and decreased LDL particle size. The HTGW phenotype, compared with the MetSyn criteria, can provide an easy and inexpensive tool to monitor patients characterized by an adverse lipid and lipoprotein profile.

Christidis DS, Liberopoulos EN, Kakafika AI, Miltiadous GA, Cariolou M, Ganotakis ES, Mikhailidis DP, Elisaf MS. · Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · J Cardiovasc Pharmacol Ther. · Pubmed #17056835 No free full text.

Abstract: Although the effect of apolipoprotein E gene polymorphism on the response to treatment with statins has been studied, the results are conflicting. Moreover, little is known about the possible effect of apolipoprotein E alleles on the response to treatment with fibrates. The purpose of this study was to evaluate the effect of apolipoprotein E polymorphism on lipid-lowering response to treatment with atorvastatin and fenofibrate in patients with different types of dyslipidemia. The study population included 136 patients with heterozygous familial hypercholesterolemia (type IIA dyslipidemia) treated with atorvastatin (20 mg/day) and 136 patients with either primary hypertriglyceridemia (type IV dyslipidemia) or mixed hyperlipidemia (type IIB dyslipidemia) treated with micronized fenofibrate (200 mg/day). Overall, no significant associations were detected between apolipoprotein E genotype and response to treatment with atorvastatin. In patients treated with fenofibrate, significant associations were noted between apolipoprotein E genotype and changes in apolipoprotein B, apolipoprotein E and triglyceride levels. Specifically, in apolipoprotein E2, apolipoprotein E3, and apolipoprotein E4 individuals, apolipoprotein B reductions were 22%, 17%, and 8%, respectively (P = .003); apolipoprotein E reductions were 45%, 20%, and 15%, respectively (P = .006); whereas triglyceride reductions reached 53%, 36%, and 33%, respectively (P = .033). In conclusion, apolipoprotein E genotype had no significant effect on the response to treatment with atorvastatin in patients with heterozygous familial hypercholesterolemia, but in patients with primary hypertriglyceridemia or mixed hyperlipidemia, there was a clear association between apolipoprotein E genotype and response to treatment with fenofibrate.

Milionis HJ, Liberopoulos EN, Elisaf MS. · Department of Internal Medicine, Medical School, University of Ioannina, Greece. · Diabetes Metab. · Pubmed #11353883 links to  free full text

Abstract: Several pharmacological agents are associated with hyperlipidemia. Tamoxifen is an example of a drug-induced increase of serum triglyceride levels. However, there are only scarce reports on how inborn errors in lipid metabolism as well as secondary dyslipidemias, including diabetes mellitus, influence the hypertriglyceridemic effect of tamoxifen. Herein, we describe a case of a breast cancer patient receiving tamoxifen who presented with remarkable hypertriglyceridemia in the context of diabetes mellitus. We also provide a brief review of the relevant literature and discuss the mechanisms underlying the pathogenesis of hypertriglyceridemia related to tamoxifen.

Milionis HJ, Bairaktari ET, Liberopoulos EN, Elisaf MS. · No affiliation provided · Am J Cardiol. · Pubmed #11463061 No free full text.

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