Statin Therapy: Rethinking Benefits and Risks

A recent 30-page manuscript provides an exhaustive review of the evidence for the efficacy and safety of statin therapy.

The authors of this excellent review provide some context for the relative value of statins.

The note that putting 10000 individuals with a history of a vascular event on a statin drug for 5 years would prevent 1,000 subsequent events. This is an example of secondary prevention--preventing another adverse outcome in those already experiencing an adverse event.

But the statin drugs also appear very powerful in primary prevention-preventing a first event in those at high risk for vascular disease. They estimate putting 10,000 individuals at high risk for vascular events on statins would result in prevention of 500 vascular events over five years.

This review provides an up-to-date review of the safety of statins and generally supports the therapy as very low risk.

One proposed adverse event of statin therapy is concern about memory and cognition. However, the authors note that well-designed studies of statin therapy in older individuals find no evidence of adverse cognitive effects compared to placebo.

They argue that:

"..given the weight of evidence against adverse effects of statin therapy on memory or other adverse effects of cognition, it would now be appropriate for regulatory authorities to consider removal from the lists of potential adverse effects on the drug labels so that patients are not inappropriately deterred from using statin therapy." (emphasis mine).

The authors go on to emphasize the potential adverse public health consequences of misleading claims regarding the safety of the statin drug class.

This excellent review is likely to lead to further discussion about extending the indications for statin use in the general population.

This review also supports discussion between individuals and their physicans on the appropriateness of statin therapy as part of a disease prevention progra.

Readers with more interest in this topic can access the full free-text manuscript by clicking on the link in the citation below.

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Photo of osprey in flight is from my photography files.

Collins R, Reith C, Emberson J et al.  (2016). Interpretation of the evidence for the efficacy and safety of statin therapy Lancet : http://dx.doi.org/10.1016/S0140-6736(16)31357-5

Fitness, Hippocampus and Forgetting

Hippocampus in Green from 3D Brain iPad App

Cardiorespiratory fitness appears to be associated with a variety of benefits in cognitive functioning.  The mechanisms for this benefit are unclear.  Association studies do not provide evidence for the pathways between related variables.  For understanding pathways, clinical trials, longitudinal studies and multivariate approaches are more powerful approaches.

Amanda Szabo and colleagues at the University of Illinois at Urbana-Champaign recently published a multivariate study looking at fitness, hippocampus and forgetting in a group of elderly adults in the journal Neuropsychology.  The hippocampus is a brain region known to crucial to working memory.  Changes in hippocampal volume have been linked to age-related cognitive decline and the development of Alzheimer's disease.

The key elements of design in this study included:
Subjects: 158 older adults with a mean age of 66.5 years
Variables: Fitness level as measured by VO2 estimate from a graded exercise test, brain hippocampal volume from a brain 3T MRI scan, spatial working memory task, subjective rating of forgetfulness (Frequency of Forgetting Questionnaire)
Statistics: Path analysis examining direct and indirect effects of fitness on hippocampal volume, working memory test performance and subject rating of forgetfulness using the comparative fit index (CFI)

The authors started with a presumed pathway model for the mechanism of the relationship between fitness and forgetfulness in the following pathway:

• fitness levels predict hippocampal volume
• hippocampal volumes predicts working memory function performance
• working memory performance predicts subjective forgetfulness

Fitness levels were associated with a variety of sociodemographic and medical variables at baseline including: self-reported physical activity, presence of hypertension, cardiovascular disease, body mass index, education level, gender and age.  These baseline variables were evaluated and controlled in the final pathway analysis.

The authors found their predicted model held up in the analysis: "cardiorespiratory fitness is associated with the frequency of forgetting indirectly through its influence on hippocampal volume and, in turn, spatial working memory".

The study noted fitness level is not the sole determinant of hippocampal atrophy.  Age alone is an independent contributor of hippocampal atrophy.  Fitness may reduce the effects of age-related hippocampal atrophy and forgetfulness but it is unable to reverse the effect.

So fitness is not a panacea but it appears to be an important factor in maintaining cognitive function in later life.  Now, I just wonder if my wife can help me find my running shoes?

3D Brain image of the hippocampus in green screen shot from the author's collection.

Szabo, A., McAuley, E., Erickson, K., Voss, M., Prakash, R., Mailey, E., Wójcicki, T., White, S., Gothe, N., Olson, E., & Kramer, A. (2011). Cardiorespiratory fitness, hippocampal volume, and frequency of forgetting in older adults. Neuropsychology, 25 (5), 545-553 DOI: 10.1037/a0022733