Association of dyslipidemia and effects of statins on nonmacrovascular diseases.
BACKGROUND
Statins have mechanisms of action that expand their effects beyond cholesterol lowering and atherosclerotic medical conditions.


OBJECTIVE
This review summarizes clinical evidence for the association of dyslipidemia and the effects of statin use on aortic stenosis, Alzheimer's dementia (AD), osteoporosis, prevention of diabetes mellitus (DM), diabetic retinopathy, age-related macular degeneration, and diabetic/nondiabetic nephropathy.


METHODS
An English-language literature search was conducted using MEDLINE (1966-June 2003). Bibliographies of retrieved articles were reviewed. Search terms included statin, HMG-CoA reductase inhibitors, aortic stenosis, Alzheimer's dementia, osteoporosis, prevention of diabetis, diabetic retinopathy, age-related macular degeneration, diabetic nephropathy, and nondiabetic nephropathy.


RESULTS
Three retrospective cohort trials have shown an association between statin use and the progression of aortic stenosis; one of these trials observed a 45% decrease in aortic valve area in 1 year. In AD, one cross-sectional analysis found 60% to 73% lower AD rates in lovastatin or pravastatin recipients ( P<0.001 ). Of the multiple observational studies on the effect of statins on fracture risk, some have shown a decreased risk, with an odds ratio as low as 0.50 (95% CI, 0.33-0.76); others have demonstrated no association. A post hoc analysis of the West of Scotland Coronary Prevention Study found a 30% reduction in the development of DM ( P=0.042 ), but this was not duplicated in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm. A small clinical trial of 6 patients (11 eyes) demonstrated improved retinal hard exudates with pravastatin treatment in patients with diabetic retinopathy. In a cross-sectional analysis, age-related macular degeneration was found to be less common among statin users than nonusers (4% [ 1/27 ] vs 22% [ 76/352 ]; P=0.02. Multiple small clinical trials of 19 to 56 patients with diabetic and nondiabetic nephropathy at various stages generated inconsistent results for an association between statin use and decreased albumin excretion rate and decreased rate of decline in glomerular filtration.


CONCLUSIONS
Data of variable quantity and quality support the use of statins as adjuncts in the treatment of nonmacrovascular diseases.
Baghdasarian
Sarkis B
SB
Cardiovascular Medicine Department, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. sarkisbmd@ameritech.net
Jneid
Hani
H
Hoogwerf
Byron J
BJ
D000544:Alzheimer Disease / Q000150:complications / Q000517:prevention & control; D001024:Aortic Valve Stenosis / Q000150:complications / Q000517:prevention & control; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000517:prevention & control; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy*; D007674:Kidney Diseases / Q000150:complications / Q000517:prevention & control; D008268:Macular Degeneration / Q000150:complications / Q000517:prevention & control; D010024:Osteoporosis / Q000150:complications / Q000517:prevention & control
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors