What Causes Atherosclerosis?

by Duane Graveline, MD, MPH

Atherosclerosis is the gradual buildup of plaque in the arteries causing the arterial walls to thicken and harden leading to heart disease and stroke.

One concept of this process is that atherosclerosis is the result of a spectrum of changes starting with free radical damage to the mitochondria of endothelial cells. The endothelium is the inner lining of blood vessels.

Once endothelial cell death occurs the characteristic inflammatory features of platelet activation, macrophage attraction, lymphocyte adhesion and smooth muscle migration is initiated. The result in some cases is the formation of atherosclerotic plaques, causing progressive narrowing of the blood vessel. In other cases, these plaques may rupture, causing sudden death or stroke.

A number of other mechanisms have their proponents. The endothelial acidity theory is proposed by some. Others have proposed that infection is a major contributor, presenting abundant data that certain common micro-organisms are frequently found in cardiovascular lesions, with infection in the tiny vasa vasorum ultimately leading to atherosclerotic plaques.

Still others argue that a deficiency of micronutrients with a breakdown of the arterial wall explains the process of atherosclerosis quite adequately.

In his book, The Homocysteine Revolution, Kilmer McCully proposed that homocysteine elevation appeared to be causative of at least 40% of cardiovascular disease without presenting the actual mechanism.

The same can be said for other factors such as transfats, oxycholesterol and smoking, all of which are associated with excess cardiovascular disease.

My theory that endothelial cell mitochondrial damage is the true cause of atherosclerosis is not unique to me. Dozens of papers now exist in the scientific literature describing this mechanism, but few physicians are aware of them.

The soon to be released new edition of my book "The Dark Side of Statins" focuses on mitochondrial damage in various cells of the body to explain the tendency of statin damage to be permanent.

Why is it, I asked myself, that statin associated peripheral neuropathy is so likely to be permanent and some 60% of myopathy cases also will be permanent?

Previously I had pointed at CoQ10 deficiency as the likely culprit. Why then, when one replenishes CoQ10 to the extreme, is not the damage reversible in some cases?

CoQ10 still remains the culprit, but it is all a matter of timing. If there is an abundance of CoQ10 in the body prior to the administration of statin drugs and one still is actively synthesizing CoQ10, it may be that statin use may proceed for a long time before evidence of CoQ10 deficiency becomes noticeable.

It has not been stressed sufficiently the variation in one's ability to synthesize CoQ10. On average we lose this ability more or less completely during adulthood, so that most people falling comfortably under the title of older, shall we say 50 years of age, will have little of this ability remaining. In this segment of society, the diet is often inadequate in CoQ10 rich foods and the only other source is supplemental.

Statin usage in these older people will have the ability to cause rapid CoQ10 deficiency unless they have been counseled to supplement sufficiently.

Most MDs have no information on what an adequate dose of this supplement is in an older person who has just stopped synthesizing it and is about to be placed on a statin.

Did the drug companies know about this special need? Of course. Merck was even awarded a patent for combining a statin with CoQ10 in 1989.

Within weeks of starting a statin, some of these older patients may begin to suffer the adverse reactions to memory, nerves and muscles from the inhibitory effects of the statin on the mevalonate pathway.

CoQ10 is vital not only as a powerful anti-oxidant to suppress excess free radical damage to mitochondrial DNA, but CoQ10 also is part of the mitochondrial structure, present in both complex one and complex two of the electron transport system. Every cell in our bodies is dependent upon this system.

Once mitochondrial damage occurs there is no reversing it. It is much too late then for CoQ10 and this patient may be one who will suffer prolonged, even permanent, side effects. On the other hand if all patients are properly counseled to take CoQ10 when they first start their statin and take it in sufficient doses for their needs, this "Dark Side of Statins" may not be experienced.

Need I say how little we know about the true needs for CoQ10 in our present climate of statin use where only Canada has bothered to make a general recommendation and in the United States there is nothing. For over 25 years, statins have been prescribed with essentially no alert to the prescribing physicians about special CoQ10 needs.

Now back to endothelial mitochondrial DNA. Every cell in our bodies requires mitochondrial energy and the cells lining our vascular system are no different. Every one of them contains their required share of mitochondria and every one of these cells needs and uses the same CoQ10 as every other body cell.

In the case of endothelial cells, if we damage sufficient DNA, we lose the cell. To lose the cell means a resulting spot of vascular damage; the beginning of atherosclerosis.

It deserves to be repeated that the true effectiveness of statins is based upon anti-inflammation, not cholesterol reduction. Obviously, part of this anti-inflammatory capacity is offset by the consequences of mevalonate blockade and CoQ10 inhibition.

This anti-inflammatory effect of statin drugs was not even dreamed of by the drug companies until Ora Shovman's review in 2001, long after most of these drugs were first marketed.

Only now with the emphasis on the inflammatory marker C-reactive protein, have the drug companies begun to pull away from cholesterol reduction and emphasize anti-inflammation, but with statins, they are far from having an optimal anti-inflammatory drug.

In 2002 we learned the mechanism by which statins induce this anti-inflammatory effect.1 It is because of the effect of statins on nuclear factor kappa B (NF-κB), an intracellular transcriptase already present in the cytoplasm of the cell in an inert form. Recent studies have confirmed these original findings.2

When activated by statins, it enters the nucleus of the cell where it exerts its anti-inflammatory effect. Because it is already present in the cell may explain why only very small doses of a statin appears entirely adequate to activate this system.

Since cholesterol lowering should no longer be the goal, we should strive to have only a minimal effect upon the mevalonate pathway. This would maintain normal cholesterol, CoQ10 and dolichol levels, the reduction of which are the major sources of side effects from statins.

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

1. http://www.ncbi.nlm.nih.gov/pubmed/12018465
2. http://www.ncbi.nlm.nih.gov/pubmed/25005042

Updated June 2016

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