Statin Use and the Elderly

More and more evidence has accumulated warning that less not more is the correct prescription for the use of statins in the elderly. Mark R Goldstein, Luca Mascitella and Cornando Brigato, MDs from the U.S. and Italy, report in the BMJ letters, (9 January 2009), that, "We do not share the protective optimism of statin therapy in the elderly, since statin therapy in this group has increased cancer at the expense of decreasing cardiovascular disease. Moreover, recent investigations offer insight why this might occur.

They cite the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial, a large randomized study that has specifically investigated a statin compared to placebo for the prevention of cardiovascular disease in the elderly, with mean age at trial entry of 75 years, revealing the increase in cancer mortality equaled in magnitude to the decrease in cardiovascular mortality, leaving all-cause mortality unchanged.

They describe the mechanism of statin induced immunosuppression of peripheral regulatory T cells (Tregs) as the likely reason for this, resulting in impairment of innate anti-tumor immune responses, resulting in increased cancer incidence. They report that Treg numbers in many solid tumors predict a worse survival prognosis.
At the same time the Netherlands reported in the BMJ, 8 January, that homocysteine may be the best predictor of CV risk in the elderly, not cholesterol and the other usual signs of risk such as high blood pressure, diabetes and obesity. This study confirms what many had already suspected - that the Framingham Risk Score (FRS) is not very accurate at predicting risk in this age group.

Dr. Wouter de Ruijter (Leiden University Medical Center, the Netherlands) and colleagues report their findings on this challenge to traditional concepts of care. "We found the FRS does not predict cardiovascular mortality in those 85 and older, and we think perhaps this problem with conventional standards begins even earlier than age 85." From their study, homocysteine seems a very good candidate instead of measuring classical risk factors. Those in the upper-third tertile of the homocysteine range had a very large five-year cardiovascular mortality risk.

They acknowledge that this current study could not establish a cutoff point for homocysteine above which treatment would be recommended, nor is there any indication that lowering homocysteine in this age group would be beneficial - all research on this approach so far has shown it to be an ineffective strategy.
"These preliminary findings call for validation and, if confirmed, could eventually lead to a revision of current guidelines," he said, "and it is absolutely useless to measure BP and total cholesterol for primary prevention in the elderly."
Of 302 participants (215 women and 87 men), 108 died during follow-up, and 32% of these (35/108 deaths) were from cardiovascular causes. Classic risk factors used in the FRS did not predict. Homocysteine remains a potent predictor of risk.
"Homocysteine has for four decades been in the center of our attention for cardiovascular risk," de Ruijter told heartwire. "It is a good predictor of cardiovascular risk in younger age groups, and we have shown here that it keeps on doing so in the very elderly."

The message in these studies has to do with the futility of using cholesterol as a marker for treatment in the elderly because the increased cancer risk from statins completely negates any decreased cardiovascular risk and suggests the possibility that low dose statins at anti-inflammatory doses, to minimize blockage of the mevalonate pathway, may become the treatment of choice in the elderly.                  

You might recall, I have said many times that most of the serious side effects, including sensitivity to cancer, are from the inevitable effect of statins on synthesis of CoQ10 and dolichols, which share the mevalonate pathway for cholesterol synthesis.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

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