Copyright © 2003 by the European Society of Cardiology.
Review article
Statin effects beyond lipid lowering—are they clinically relevant?
a Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN, USA
b Division of Cardiology, University Hospital, Basel, Switzerland
c Division of Hypertension, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN, USA
d Department of Medicine, University of Naples, Italy
e Department of Medicine-0682, University of California, San Diego, CA, USA
Received May 2, 2002;
accepted June 12, 2002
* Corresponding author. Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel.: +1-507-255-4152; fax: +1-507-255-2550
lerman.amir@mayo.edu
Key Words: Statins • Lipid-independent effects • Isoprenoids • Clinical relevance
| The first 150 words of the full text of this article appear below. |
1. Introduction
Currently, five different statins (simvastatin,pravastatin, lovastatin, fluvastatin, and atorvastatin) are approved for treatment of hypercholesterolemia in humans and two new compounds (rosuvastatin and NK-104) are under investigation.1,2 Despite differences in their pharmacokinetic profiles, all statins have at least onecharacteristic in common: they block the conversion of HMG-CoA to mevalonic acid with consecutive attenuation of the biosynthesis of cholesterol (Fig. 1), which is associated with a reduction in serum total and low-density lipoprotein (LDL) cholesterol of as much as 20–31 and 28–42% during chronic treatment.3 Because of these properties, statins have become the most widely prescribed lipid-lowering drugs in patients with elevatedserum cholesterol levels. Several large trialsdemonstrated that statins are not only safe and well tolerated but also significantly decrease cardiovascular morbidity and mortality in hypercholesterolemic patients in both primary and secondary prevention.4–8 However, the striking benefit achieved with statin treatment in patients with a wide range of cholesterol
2. Lipid-independent statin effects in vitro and in animal models
2.1. Effect on endothelial function
2.2. Effect on nitric oxide bioavailability
2.3. Effect on endothelin-1 synthesis
2.4. Antioxidant effect
2.5. Antiinflammatory effect
2.6. Effect on macrophage activation and proliferation
2.7. Effect on smooth muscle cell proliferation and apoptosis
2.8. Effect on platelets and the coagulation/fibrinolytic system
2.9. Effect on neovascularization
2.10. Effect on myocardial hypertrophy, fibrosis, and cardiomyocyte protection
3. Lipid-independent statin effects in humans
3.1. Problems of translating results of experimental studies to clinical practice
3.2. Indirect evidence for the existence of lipid-independent statin effects in humans
3.3. Direct evidence for the existence of lipid-independent statin effects in humans
3.4. Potentially harmful lipid-independent statin effects and drug safety
3.5. Variation of pleiotropy between statins or class effect?
3.6. Conclusion
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