Statins Work by Reduction of Inflammation not Cholesterol

Published in Nutrition, Metabolism & Cardiovascular Diseases (2008) is yet another study documenting the anti-inflammatory benefit of statins used for secondary prevention.

Using the intima/media thickness (IMT) of the carotid artery as a marker, Baldassarre and colleagues of Milan again report what I have been saying for years: "Cholesterol and other lipids are irrelevant to the process of artherosclerosis." Inflammation is the cause and treatment must be directed towards inflammation.

In this well designed and comprehensive study 85 stable post myocardial infarction patients were assessed as to baseline and follow-up ultra-sound IMT measurements of their carotid arteries, serum lipid determinations and comprehensive measurements of serum inflammatory, coagulation and activation markers before being placed on Lipitor (20mg/daily) and followed for up to two years.

A number of similar studies had been done by other groups using dose ranges of Lipitor from 10mg up to 80mg. All these studies showed the same result - progressive decrease in IMT thickness due to diminished inflammatory, coagulation and activation markers with no evidence whatsoever for serum lipid involvement in this benefit. They also showed the same degree of IMT benefit whether 10mg/day was used or 80.

Additionally they showed the most useful markers of benefit to be hsCRP (high sensitive C reactive protein), IL-8 and IL18 (Interleukin) for the inflammatory markers and fibrinogen and MMP9 (matrix metalloproteinase-9) for the coagulation factors and sE-selectin (soluble E-selectin) of the activation markers. I cite this only to give readers a feel for how sophisticated this study was. Suffice it to say that each of these markers are commonly known in research circles and give evidence for various aspects of the body's inflammatory and healing response.

It has been only eight years since Ora Shovman announced to the world "The Anti-inflammatory and Immunomodulatory Properties of Statins." Until that time no physician had the slightest awareness of this. It was assumed that whatever benefit came of statin use was based on cholesterol reduction.

One would have thought that the drug companies might have reacted to this a bit - perhaps announce to the medical community that this direct anti-inflammatory effect could be expected. But no, not a word! Instead they said nothing and did nothing when in truth they were already suspecting cholesterol reduction was not the entire issue.

Longitudinal studies were proving substantial cardiovascular benefit even in the absence of significant cholesterol reduction. Obviously statins were doing something more. Only now when study after study is proving the irrelevance of cholesterol lowering to statin benefit are they moving closer to this anti-inflammatory effect and beginning to get behind this CRP movement with the emphasis on inflammation suppression.

I may be cynical here but five years ago I predicted that if they played their cards right they might slide inflammation in and cholesterol out and never miss a statin sale.

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