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 diabetes, 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. Conclusion: Data of variable quantity and quality support the use of statins as adjuncts in the treatment of nonmacrovascular diseases. (Clin Ther. 2004;26:337-351)