Epidemiological statin

It has been suspected that low concentrations of serum cholesterol might be associated with an increased risk of cancer or overall mortality. All fibrates and statins cause cancer in rodents, but the relevance of this finding to man has been questioned (68). In an epidemiological study these risks were almost non-existent after adjusting for confounding factors. 

The reduction in stroke observed in long-term statin trials despite the lack of association between cholesterol levels and stroke in most epidemiological and observational studies. 

Evidence from well-conducted prospective epidemiological studies does not suggest that consumption of saturated fat and cholesterol is associated with an increased risk of CHD. Randomized clinical trials that reduced the intake of saturated fatty acids and cholesterol and increased the intake of polyunsaturated fatty acids to lower plasma cholesterol levels did not significantly improve CHD or total mortality. The minor improvement in CHD events for trials of the potent cholesterol-lowering statin drugs may result, to an unknown extent, from their pleiotropic effects and cannot be used to justify the lipid hypothesis. 

Although the association between elevated cholesterol and increased risk of AD remains unclear, pharmacologically based epidemiological studies examining statin use have provided informative insights. Statins are a class of drugs known as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase... 

Since the publication of these two early studies, a number of studies have adopted a more prospective cohort approach to the examination of statin use in patients who develop dementia and AD over the course of a set period (usually between 5-10yrs). While many of the subsequent studies described seemingly protective effects in cross-sectional case-control analysis [36,45-51], the majority of prospective cohort analysis failed to identify a reduced risk of dementia in incident cases of dementia or AD [36, 46,47,51[. One notable exception comes from a study that examined a population identified by common AD risk facfors and co-morbidities (e.g., first degree relatives) [52]. In a high AD risk population, statin use was associated with a lowered risk of AD [52]. A summary of the epidemiological findings for stafin use in AD are shown in Table 1. 

Elevated serum cholesterol levels and in particular LDL-cholesterol levels are strongly associated with cardiovascular mortality across the spectrum of epidemiologic studies and pharmacologic intervention studies in primary and secondary prevention trials (Ligure 4.4). In the Cholesterol Treatment Trialists Collaborators meta-analysis of >90,000 patients studied in 14 randomized trials of statin therapy, a reduction in LDL cholesterol of 1 mmol/L (39 mg/dL) was associated with a 12% proportional reduction in all-cause mortality, predominantly driven by a 19% proportional reduction in cardiovascular mortality (45). Among patients with pre-existing heart disease there were 14 fewer deaths per 1000 participants per mmol LDL cholesterol reduction, as well as an approximately 25% reduction in major adverse cardiac events. 

Shepardson NE et al (2011) Cholesterol level and statin use in Alzheimer disease I. Review of epidemiological and preclinical studies. Arch Neurol 68 1385-1392... 

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