Context Considerable controversy exists regarding the association of omega-3 polyunsaturated fatty acids (PUFAs) and major cardiovascular end points.Objective To assess the role of omega-3 supplementation on major cardiovascular outcomes. Data Sources MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through August 2012.Study Selection Randomized clinical trials evaluating the effect of omega-3 on allcause mortality, cardiac death, sudden death, myocardial infarction, and stroke.Data Extraction Descriptive and quantitative information was extracted; absolute and relative risk (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I 2 . Subgroup analyses were performed for the presence of blinding, the prevention settings, and patients with implantable cardioverter-defibrillators, and meta-regression analyses were performed for the omega-3 dose. A statistical significance threshold of .0063 was assumed after adjustment for multiple comparisons. Data SynthesisOf the 3635 citations retrieved, 20 studies of 68 680 patients were included, reporting 7044 deaths, 3993 cardiac deaths, 1150 sudden deaths, 1837 myocardial infarctions, and 1490 strokes. No statistically significant association was observed with all-cause mortality (

Objective-Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is a predictor for incident atherosclerotic disease. We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA 2 activity and mass. Methods and Results-In 50 patients with Type IIA dyslipidemia were administered rosuvastatin (10 mg daily), whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy (10 mg daily). Fifty patients with Type IV dyslipidemia were given micronised fenofibrate (200 mg daily). Low-and high-density lipoprotein (LDL and HDL, respectively) subclass analysis was performed electrophoretically, whereas lipoprotein subfractions were isolated by ultracentrifugation. Ezetimibe reduced plasma Lp-PLA 2 activity and mass attributable to the reduction in plasma levels of all LDL subfractions. Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA 2 on dense LDL subfraction (LDL-5 Key Words: hyperlipidemia Ⅲ lipoproteins Ⅲ PAF-acetylhydrolase Ⅲ Lp-PLA 2 Ⅲ ezetimibe Ⅲ fenofibrate Ⅲ rosuvastatin P latelet-activating factor (PAF) acetylhydrolase exhibits a Ca 2ϩ -independent phospholipase A 2 activity and degrades PAF and oxidized phospholipids by catalyzing the hydrolysis of the ester bond at the sn-2 position. 1 PAF-acetylhydrolase in plasma is complexed to lipoproteins 2 ; thus it is also referred as lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ). 3 Lp-PLA 2 is associated mainly with apolipoprotein B (apoB)-containing lipoproteins and primarily with low-density lipoprotein (LDL), whereas a small proportion of circulating enzyme activity is also associated with high-density lipoprotein (HDL). 1,2 ⌻he majority of the LDL-associated Lp-PLA 2 activity is bound to the atherogenic small-dense LDL (sdLDL) particles, 2,4,5 and we recently showed that the enzyme activity is a marker of sdLDL particles in plasma. 6 Lp-PLA 2 is principally produced by hematopoietic cells including monocytes-macrophages. 7,8 Lp-PLA 2 has been identified in atherosclerotic plaques 9 ; however, its role in atherosclerosis is still under investigation. In this regard, it is suggested that this enzyme might have an antiinflammatory role because it degrades and inactivates proinflammatory PAF and oxidized phospholipids 10,11 ; other studies showed that Lp-PLA 2 may have a proinflammatory and proatherogenic role 12 because it generates lysophosphatidylcholine (lysoPC) 3,13 and bioactive oxidized fatty residues. 3 Data from large White population studies demonstrated an independent association between plasma Lp-PLA 2 with cardiovascular disease (CVD) risk. In this regard a recent metaanalysis showed that Lp-PLA 2 is significantly associated with CVD, and the risk estimate appears to be relatively unaffected by adjustment for conventional CVD risk factors. 14 In contrast to total plasma enzyme, which mainly represents ...

RSV and ATV were equally efficacious in achieving LDL-C treatment goals in patients with primary hyperlipidaemia at the initial dose and following dose titration. RSV seems to have a significantly higher HDL-C-raising effect, while ATV lowers serum uric acid levels.

Statins, in addition to their beneficial lipid modulation effects, exert a variety of several so-called "pleiotropic" actions that may result in clinical benefits. Rosuvastatin, the last agent of the class to be introduced, has proved remarkably potent in reducing low-density lipoprotein cholesterol levels. At present, no large-scale primary or secondary prevention clinical trials document either its long-term safety or its effectiveness in preventing cardiovascular events. A substantial number of experimental and clinical studies have indicate favorable effects of rosuvastatin on endothelial function, oxidized low-density lipoprotein, inflammation, plaque stability, vascular remodeling, hemostasis, cardiac muscle, and components of the nervous system. Available data regarding the effects of rosuvastatin on renal function and urine protein excretion do not seem to raise any safety concerns. Whether the established "pleiotropy" and/or lipid-lowering efficacy of rosuvastatin may translate into reduced morbidity and mortality remains to be shown in ongoing clinical outcome trials.

HMG-CoA reductase inhibitors (statins) are the mainstay in the pharmacologic management of dyslipidemia. Since they are widely prescribed, their safety remains an issue of concern. Rosuvastatin has been proven to be efficacious in improving serum lipid profiles. Recently published data from the JUPITER study confirmed the efficacy of this statin in primary prevention for older patients with multiple risk factors and evidence of inflammation. Rosuvastatin exhibits high hydrophilicity and hepatoselectivity, as well as low systemic bioavailability, while undergoing minimal metabolism via the cytochrome P450 system. Therefore, rosuvastatin has an interesting pharmacokinetic profile that is different from that of other statins. However, it remains to be established whether this may translate into a better safety profile and fewer drug-drug interactions for this statin compared with others. Herein, we review evidence with regard to the safety of this statin as well as its interactions with agents commonly prescribed in the clinical setting. As with other statins, rosuvastatin treatment is associated with relatively low rates of severe myopathy, rhabdomyolysis, and renal failure. Asymptomatic liver enzyme elevations occur with rosuvastatin at a similarly low incidence as with other statins. Rosuvastatin treatment has also been associated with adverse effects related to the gastrointestinal tract and central nervous system, which are also commonly observed with many other drugs. Proteinuria induced by rosuvastatin is likely to be associated with a statin-provoked inhibition of low-molecular-weight protein reabsorption by the renal tubules. Higher doses of rosuvastatin have been associated with cases of renal failure. Also, the co-administration of rosuvastatin with drugs that increase rosuvastatin blood levels may be deleterious for the kidney. Furthermore, rhabdomyolysis, considered a class effect of statins, is known to involve renal damage. Concerns have been raised by findings from the JUPITER study suggesting that rosuvastatin may slightly increase the incidence of physician-reported diabetes mellitus, as well as the levels of glycated hemoglobin in older patients with multiple risk factors and low-grade inflammation. Clinical trials proposed no increase in the incidence of neoplasias with rosuvastatin treatment compared with placebo. Drugs that antagonize organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin are more likely to interact with this statin. Clinicians should be cautious when rosuvastatin is co-administered with vitamin K antagonists, cyclosporine (ciclosporin), gemfibrozil, and antiretroviral agents since a potential pharmacokinetic interaction with those drugs may increase the risk of toxicity. On the other hand, rosuvastatin combination treatment with fenofibrate, ezetimibe, omega-3-fatty acids, antifungal azoles, rifampin (rifampicin), or clopidogrel seems to be safe, as there is no evidence to support any pharmacokinetic or pharmacodynamic interaction of rosuvastatin with an...

Sudden cardiac death, which is mainly associated with the presence of life-threatening ventricular arrhythmias, is a common 'killer' among patients with coronary artery disease. Moreover, atrial fibrillation is the most common arrhythmia encountered in the clinical practice. The beneficial effect of statins on cardiovascular morbidity and mortality is well-established, while the exact role of this class of drugs against arrhythmias remains unclear. This review discusses the effect of statin treatment on arrhythmias that are commonly seen in the clinical setting. The underlying pathophysiological mechanisms are also overviewed. Compelling evidence from the majority of the studies reviewed shows that statins exhibit a protective effect against the occurrence of ventricular arrhythmias and atrial fibrillation.

Non-alcoholic fatty liver disease (NAFLD) is a common health problem with a high mortality burden due to its liver-and vascular-specific complications. It is associated with obesity, high-fat diet as well as with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). Impaired hepatic fatty acid (FA) turnover together with insulin resistance are key players in NAFLD pathogenesis. Peroxisome proliferator-activated receptors (PPARs) are involved in lipid and glucose metabolic pathways. The novel concept is that the activation of the PPARα subunit may protect from liver steatosis. Fenofibrate, by activating PPARα, effectively improves the atherogenic lipid profile associated with T2DM and MetS. Experimental evidence suggested various protective effects of the drug against liver steatosis. Namely, fenofibraterelated PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore, fenofibrate reduces hepatic insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-alcoholic steatohepatitis pathogenesis. These include tumor necrosis factor-α, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Consequently, fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that fenofibrate can limit liver steatosis associated with high-fat diet, T2DM and obesity-related insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small, fenofibrate was used as a part of multifactorial approach, while histological data were absent. In this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology.

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