No abstract

Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (density [] = 1.019-1.044 g/ml), and sdLDL ( = 1.044-1.063 g/ml) were determined in the fed state by using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL, +45%; lbLDL, +131%; and sdLDL, +97%), without a change in production. On placebo, 25% of TRL apoB-100 was catabolized directly, 37% was converted to lbLDL, and 38% went directly to sdLDL; rosuvastatin did not alter these distributions. During both phases, sdLDL apoB-100 was catabolized more slowly than lbLDL apoB-100 ( < 0.01). Proteomic analysis indicated that rosuvastatin decreased apoC-III and apoM content within the density range of lbLDL ( < 0.05). In our view, sdLDL is more atherogenic than lbLDL because of its longer plasma residence time, potentially resulting in more particle oxidation, modification, and reduction in size, with increased arterial wall uptake. Rosuvastatin enhances the catabolism of apoB-100 in both lbLDL and sdLDL.

Cardiovascular disease (CVD) is a growing burden across the world. In Asia and the Middle East, in particular, CVD is among the most prevalent and debilitating diseases. Dyslipidemia is an important factor in the development of atherosclerosis and associated cardiovascular events, and so effective management strategies are critical to reducing overall cardiovascular risk. Multiple dyslipidemia guidelines have been developed by international bodies such as the European Society of Cardiology/European Atherosclerosis Society and the American College of Cardiology/American Heart Association, which all have similarities in practice recommendations for the optimal management of dyslipidemia. However, they differ in certain aspects including pharmacological treatment, lifestyle modification and the target levels used for low-density lipoprotein cholesterol. The evidence behind these guidelines is generally based on data from Western populations, and their applicability to people in Asia and the Middle East is largely untested. As a result, practitioners within Asia and the Middle East continue to rely on international evidence despite population differences in lipid phenotypes and CVD risk factors. An expert panel was convened to review the international guidelines commonly used in Asia and the Middle East and determine their applicability to clinical practice in the region, with specific recommendations, or considerations, provided where current guideline recommendations differ from local practice. Herein, we describe the heterogeneous approaches and application of current guidelines used to manage dyslipidemia in Asia and the Middle East. We provide consensus management recommendations to cover different patient scenarios, including primary prevention, elderly, chronic kidney disease, type 2 diabetes, documented CVD, acute coronary syndromes and family history of ischemic heart disease. Moreover, we advocate for countries within the Asian and Middle East regions to continue to develop guidelines that are appropriate for the local population.

Studies have reported an increased risk of developing diabetes in subjects receiving statins versus placebo. Our purpose was to compare the effects of maximal doses of rosuvastatin and atorvastatin on plasma levels of the insulin, glycated albumin (GA), adiponectin (ADN), and C reactive protein (CRP) versus baseline in hyperlipidemic patients. We studied 252 hyperlipidemic men and women who were randomized to receive atorvastatin 80 mg/day or rosuvastatin 40 mg/day over a 6-week period. Atorvastatin and rosuvastatin were both highly effective in lowering low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels, with rosuvastatin being more effective than atorvastatin in raising high density lipoprotein cholesterol (HDL-C). Atorvastatin and rosuvastatin at maximum dosage both significantly (p<0.05) raised median insulin levels by 5.2% and 8.7% respectively from baseline. However, only atorvastatin increased GA levels from baseline (+0.8% for atorvastatin vs −0.7% for rosuvastatin, p=0.002). Both atorvastatin and rosuvastatin caused significant (p<0.001) and similar median reductions in CRP of −40% and −26% as compared to baseline values respectively. However, there was no statistical significant difference between the two groups in ADN changes from baseline (−1.5% vs −4.9%, p=0.15). In conclusion, our data indicated that maximum dosage of atorvastatin or rosuvastatin therapy significantly lower CRP levels, but also moderately increase insulin levels.