The Clinical Relevance of Low-Density-Lipoproteins Size Modulation by Statins

Abstract

The predominance of small, dense low density lipoproteins (LDL) has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III; in fact, LDL size seems to be an important predictor of cardiovascular events and progression of coronary heart disease. Several studies have also shown that the therapeutical modulation of LDL size is of great benefit in reducing the risk of cardiovascular events. Hypolipidemic treatment is able to alter LDL subclass distribution and statins are currently the most widely used lipid-lowering agents. Statins are potent inhibitors of hydroxy-methyl-glutaryl-coenzyme A reductase, the rate-limiting enzyme in hepatic cholesterol synthesis and are the main drugs of choice for the treatment of elevated plasma LDL cholesterol concentrations. Statins potentially lower all LDL subclasses (e.g., large, medium and small particles); thus, their net effect on LDL subclasses or size is often only moderate. However, a strong variation has been noticed among the different agents: analyses of all published studies suggest a very limited role of pravastatin and simvastatin in modifying LDL size and their subclasses, while fluvastatin and atorvastatin seem to be much more effective agents. Finally, rosuvastatin, the latest statin molecule introduced in the market, seems to be promising in altering LDL subclasses towards less atherogenic particles.

Small, dense low‐density lipoproteins (LDL) are predictors of cardio‐ and cerebro‐vascular events in subjects with the metabolic syndrome

“…It is known that the therapeutical modulation of low HDL-cholesterol and high triglycerides significantly reduce cardiovascular risk [3] and lipid-lowering agents are also effective in reducing levels of small, dense LDL [26][27][28]. Dietary management is also of importance in such category of high-risk subjects [29,30].…”

Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin

“…However, in our study, 12 responders and two non-responders were treated with lipid-lowering agents, and most of these patients (11/12 responders and 1/2 non-responders) used HMG-CoA reductase inhibitors (statins). Several studies have shown that low-density lipoprotein (LDL) size rather than plasma LDL level is more correlated with insulin resistance and eventual progression of coronary heart disease (Rizzo and Berneis 2006). Although the efficacy of modifying LDL size is different among agents (fluvastatin and atorvastatin seem to be much more effective agents than pravastatin and simvastatin), statins moderately lower all LDL subclasses, and, somehow, this process seems to make metformin more effective.…”

Effects of Different Statin Treatments on Small Dense Low-Density Lipoprotein in Patients with Metabolic Syndrome

“…Since atherogenic dyslipidemia generally appears prior to clinical manifestations of MetS, treatment strategies have focused on the pharmacological approach, with reports that patients with atherogenic dyslipidemia may benefit from statins 19) . Moreover, different statins have been described to have different effects on sd-LDL 8) . The aims of the present study were to compare the outcomes of different statin treatments used to lower LDL-C in patients with MetS on sd-LDL, which is one of the most important components of dyslipidemia in these patients, and to test whether this can be regarded as a class effect.…”

“…Novel statins with more potent LDL-C-lowering effects 20) are known to demonstrate partial differences in their non-LDL effects compared to previous statins 8) . Ai et al 21) found, in 271 hyperlipidemic patients, that 6 weeks of maximal-dose rosuvastatin (40 mg/day) and atorvastatin (80 mg/day) treatments provided significant and beneficial change throughout the lipoprotein particle spectrum, and that rosuvastatin was significantly more effective in reducing sd-LDL levels than atorvastatin ( 53% vs. 46%).…”

“…It has been suggested that treatments affecting LDL sub-groups reduce the risk for atherosclerosis, and that the measurement of LDL-particle size is beneficial in the treatment and clinical assessment of patients at high risk for coronary artery disease 7) . The effects of statins on sd-LDL as potent inhibitors of the enzyme hydroxy-methyl-glutaryl coenzyme-A-reductase are generally controversial and it has been proposed that novel statins, having a more potent LDL-C-lowering effect, are more effective in the modification of LDL size and sub-groups 8) . A…”