Pleiotropic Effects of Statins: Untapped Potential for Statin Pharmacotherapy.

BACKGROUND: Statins are effective for primary and secondary prevention of atherosclerotic cardiovascular disease. They also have systemic anti-inflammatory and immunomodulating properties suggesting potential utility for improving clinical outcomes for a wide range of diseases. The literature provides data suggesting benefit in patients with comorbidities associated with contrast-induced nephropathy (CIN), chronic obstructive pulmonary disease (COPD), pneumonia, head injury, neurological disease (e.g. Alzheimer's and Parkinson's disease), prostate cancer, nuclear cataract and spinal cord injury. This systematic review evaluates the current evidence supporting the potential benefit of statins outside their customary role of attenuating cardiovascular risk reduction. METHODS: The electronic databases MEDLINE, EMBASE, and clinicaltrials.gov were searched for studies published January 2000 - March 2018 reporting comorbidity reduction associated with statin use. RESULTS: Fifty-eight publications that satisfied our selection criteria (based on the PRISM guidance for systematic reviews) were selected and included case-control, cohort, cross-sectional and observational studies as well as systematic reviews and meta-analyses. Ten studies addressed statin use and incidence of CIN after coronary imaging; 8 addressed statin use in patients with COPD; 14 addressed statin use and comorbidity reduction associated with head injury and/or a neurological disease disorder; 5 addressed the association between statin use and nuclear cataract; 9 addressed the association between statin use and prostate/colorectal cancer; 9 studies addressed the role of statin use in treating infections; and 3 addressed the association between statin use and spinal cord injury related survival rate. CONCLUSION: Overall, the literature supports beneficial pleiotropic effects of statin use in contrastinduced nephropathy, head injury, Alzheimer's and Parkinson's disease, nuclear cataract, prostate cancer, infection management, and spinal cord injury. Further investigation is warranted, and randomized clinical trials are needed to confirm the clinical utility suggested by the reported studies included in this meta-analysis.

Candidate-Gene Study of Functional Polymorphisms in SLCO1B1 and CYP3A4/5 and the Cholesterol-Lowering Response to Simvastatin.

Cholesterol-lowering response to 40 mg simvastatin daily for 6 weeks was examined for associations with common genetic polymorphisms in key genes affecting simvastatin metabolism (CYP3A4 and CYP3A5) and transport (SLCO1B1). In white people (n = 608), SLCO1B1 521C was associated with lesser reductions of total and low-density lipoprotein cholesterol. Associations between SLCO1B1 521C and cholesterol response were not detected in African Americans (n = 333). Associations between CYP3A4*22 or CYP3A5*3 and cholesterol response were not detected in either race, and no significant race-gene or gene-gene interactions were detected. As several of the analyses may have been underpowered (especially the analyses in the African American cohort), the findings not suggesting an association should not be considered conclusive and warrant further investigation. The finding regarding SLCO1B1 521C in whites was consistent with several previous reports. SLCO1B1 521C resulted in a diminished cholesterol-lowering response, but a marginal effect size limits utility for predicting simvastatin response.