Differential metabolic actions of specific statins: clinical and therapeutic considerations.
CONCLUSIONS
Statins, the most widely prescribed drugs in clinical practice, mainly act by reducing the plasma level of low-density lipoprotein (LDL)-cholesterol. A shift in redox homeostasis to an imbalance between reactive oxygen species generation and endogenous antioxidant mechanisms results in oxidative stress that has been implicated in the pathogenesis of various diseases, including those of the cardiovascular system. Beyond their efficacy in lowering LDL cholesterol, statins modulate redox systems that are implicated in the development of atherosclerosis, cardiovascular morbidity, and mortality.


BACKGROUND
Differences in specific statins or their dosages result in differential metabolic actions arising from off-target or unknown mechanisms of action that can have important implications for overall patient morbidity and mortality.


RESULTS
A recent meta-analysis and a combined analysis have suggested that high doses of statins increase the risk of developing type 2 diabetes mellitus, but reduce the risk of cardiovascular events. Thus, it is important to consider the cardiovascular and metabolic context and natural history of diseases when choosing a specific statin therapy for optimal individual patient health over the long term.


CONCLUSIONS
More information is needed regarding the metabolism of statins, and the off-target or unknown actions of statins in affecting insulin resistance and metabolic homeostasis. The differential metabolic effects of specific statins should be considered in formulating optimal therapeutic strategies to reduce not just cardiovascular-related but also overall patient morbidity and mortality.
1 Division of Endocrinology, Seoul National University College of Medicine, Seoul National University Bundang Hospital , Seongnam, Korea.
Soo
S
Lim
Ichiro
I
Sakuma
Michael J
MJ
Quon
Kwang Kon
KK
Koh
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006487:Hemostasis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D018384:Oxidative Stress / Q000187:drug effects
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin