LDL cholesterol, statins, and plaque regression

The ASTEROID Trial reported in 2006 examined the effects of LDL cholesterol reduction using the statin drug, rosuvastatin (Crestor), with coronary atherosclerosis quantified and tracked with intracoronary ultrasound. The Track Your Plaque report, New study confirms: LDL of 60 mg reverses plaque, on the ASTEROID Trial provides commentary on the results.

Though I remain skeptical that a statin-only treatment strategy can reverse coronary plaque in the majority of people, I do believe that the AstraZeneca-sponsored ASTEROID Trial does add to the wisdom on heart disease management. More importantly, it has served to raise awareness among both the public and my physician colleagues that atherosclerosis is indeed a potentially reversible condition.

Specifically, the ASTEROID results confirm that, either directly or indirectly, LDL cholesterol reduction achieved with statin agents does correspond to increasing degrees of plaque reversal. The mean (calculated) LDL cholesterol achieved in ASTEROID was 60 mg/dl, the same as the Track Your Plaque suggested LDL target.

Though the ASTEROID Trial is not news, I stumbled on a chart posted on the ASTEROID Trial website that clearly highlights how a number of other studies beyond ASTEROID have fallen into this pattern:

The graph reveals a linear relationship: The greater the reduction in LDL cholesterol with statin drugs, the greater the plaque regression ("change in percent atheroma volume"). (Several other studies not included in the graph also cluster into the same linear relationship.)

I am no supporter of drug companies, nor a defender of their policies and practices. But I do believe that their data can serve to teach us a few lessons. For instance, here is an (cherry-picked, to be sure) example of intracoronary ultrasound cross-sectional images before and after two years of rosuvastatin, 40 mg daily:

The color-coded/outlined atherosclerotic coronary plaque is shown shrinking, while the "lumen," or the path for blood to flow, enlarges. The reduction in coronary plaque is irrefutable. (The small circle within the lumen with the white halo surrounding it is the ultrasound catheter.)

If you and I were to choose a single treatment approach to coronary disease reversal, then 40 mg of rosuvastatin is probably at the top of the list. However, in the Track Your Plaque program, we do not advocate a single treatment strategy. While the Crestor-only approach is relatively straightforward--one pill a day--few people, in my experience, can tolerate this dose for any length of time. Patients invariably have to stop the drug or reduce the dose severely due to muscle aches when I've had patients try it. Contrary to the ASTEROID results, in my experience the majority of people, perhaps all, eventually give up with this improbable "one-size-fits-all" scheme.

The Track Your Plaque approach, while more complicated and involves several nutritional supplements and strategies, in my view addresses more causes of coronary plaque, is better tolerated, and provides health benefits outside of just LDL cholesterol reduction. It also minimizes or eliminates the need for prescription medication.

Studies cited in graph:

1.Nissen S et al. N Engl J Med 2006;354:1253-1263.
2 Tardif J et al. Circulation 2004;110:3372-3377.
3 Nissen S et al. JAMA 2006;295 (13):1556-1565
4 Nissen S et al. JAMA 2004;292: 2217–2225.
5 Nissen S et al. JAMA 2004; 291:1071–1080

Comments (12) -

  • J Michael Nicholls

    4/13/2008 6:49:00 AM |

    Dear Dr. Davis,
    I have read your blog for some time now, and I consider it to be the no 1 in the nutrition-health-cardiology field. A couple of years ago I became interested in the “cholesterol theory” and I have studied the development of the statins in detail. Having a background in the “hard sciences” I am appalled at the lack of sound science in this field in particular, as well as in some other areas of medical research.

    To my knowledge there is zero evidence that the lowering of any of the cholesterol levels has anything to do with preventing heart disease or reversing plack. On the contrary, an anti-inflammatory mechanism is probably the reason for the little protective effect there is, while the lowering of the cholesterol levels probably causes more harm then good (as can be suspected from the extensive list of side effects).

    Reading this post and the statement, “LDL cholesterol reduction achieved with statin agents does correspond to increasing degrees of plaque reversal”, I couldn’t help feeling that some readers would get it all wrong, especially since “cholesterol lowering” is the healing mantra that is being communicated to the market (and even most doctors seem to advocate).

  • Anonymous

    4/13/2008 11:50:00 PM |

    "Having a background in the hard sciences"? In the "hard siences" they call plaque "plak" ? That was a dead give away that you have no idea what your talking about even before you made the ridiculus statement"to my knowledge there is zero eveidence that the lowering of any of the cholesterol has anything to do with preveting heart disease or lowering plak(sic)" You should read some of the studies, they're easily found on the internet or in journals. By the way did you look at the pictures Dr. davis put up in the article? As Dr. davis always says I don't work for the drug companies and statins certainly aren't miracle drugs but they do have a place. Ever hear of the Framingham Study, just a small study thats been going on for over 60 years now and has studied over 10,000 people( now in its third generation) and they have NEVER had a recorded heart attack in ANYBODY with a cholesterol level under 150. So much for "your knowledge"

  • Anonymous

    4/14/2008 4:40:00 AM |

    Dear Dr. Davis,

    In reading this and about vitamin D, if you have a plaque problem, but your HDL is high and your Vitamin D level in normal, would it still be helpful to take the suppliment?

  • J Michael Nicholls

    4/14/2008 1:56:00 PM |

    Dear Anonymous, there is no need to be so sarcastic, and I apologize for spelling plaque plack. Do you mean to say that all of medical science is of high quality, and that it shouldn’t be questioned? Most of the serious critique against the cholesterol hypothesis comes from medical researchers by the way. I am waiting to be enlightened, please show me the evidence that the LOWERING of cholesterol by it self (per se) is the protective mechanism of statins.

    From your writing it appears that you still believe in the old dogma of high cholesterol CAUSING atherosclerosis. Only a few of the fiercest statinators in the research community still maintain that, and probably so for financial reasons (most statin-advertising is doing its best to communicate just that). Most GPs seem to believe that cholesterol causes atherosclerosis too. It is trivial that in any academic context “correspond to”, “linear relationship” or “associated with” do not mean “direct effect of” or “directly caused by”. With this simple understanding we would have better doctors and better scientist in the medical field, and consequently less treatment of SYMPTOMS such as high cholesterol, high blood pressure and high blood sugar. By the way, is there any proof that atherosclerosis is not causing the higher cholesterol levels instead of the other way around?

    The problem with many defenders of the cholesterol dogma is that they don’t read the scientific literature in a scientific way. I personally don’t know of anyone still believing in the cholesterol hypothesis after having studied it in depth from strictly scientific principles. There is simply no evidence to motivate all the “lowering” of “levels”. It is nothing more than a highly profitable market concept ($30 billion in 2007).

  • Anonymous

    4/14/2008 2:25:00 PM |

    Great write up.

    As  a diabetic, with all of my numbers under very good control, I have been on statins for 8 years and my last two heart scans (5 years apart) had a score of 0 plague.  My question is the following:

    Are you saying that statins are good and should be part of a comprehensive approach?

    Many websites that push your blog are against the use of statins in any approach.  How do you respond to that type of thinking?

    Should you continue taking drugs to reduce your plague if your score is zero?

    Thanks for your time

  • Anonymous

    4/14/2008 6:23:00 PM |

    Playing devil's advocate, I'm not sure if science has proved cholesterol to be a cause of heart disease. What if it's a marker and not a cause?

    Those in the Framingham study with low cholesterol values might not get heart attacks due to lifestyle/genetics, and their low cholesterol is a reflection of their overall good health?

    Those who take high dose statins obtain benefit from less inflammation, but not because of cholesterol reduction?

    I'm not saying the above two statements are true, but it could be possible. It could also explain why statins, as a single treatment, usually don't work for most people, and why the Vytorin/Zetia/Torcetrapib trials failed so miserably.

    Or it could be that the reduction in LDL wasn't enough to matter, or that particle sizes for LDL/HDL wasn't taken into account, or some other factor? It appears that  right now, there isn't hard data that proves what causes heart disease exactly, but simply a lot of risk factors and disease markers instead.

  • Anonymous

    4/15/2008 1:52:00 AM |

    I never suggested that Cholesterol by itself caused heart disease. Clearly many things do, inflamation, CRP, Lp(a)... On the other hand to suppose that cholesterol has NOTHING to do with heart disease is foolish. Show me a cardiologist that believes cholesterol has nothing to do with heart disease and I'll show you a quack. It may not even be the main cause of heart disease in most people but the fact of the matter is reducing LDL lowers the the chance for heart attack in a good number of people. Have you ever heard of Dr. Agagston ? He of the South Beach Diet fame, a cardiologist in South Florida, who by the way the way of scoring calcium scans is named after. See what he thinks of statins and reducing cholesterol levels. and as Im sure you know it gets much more complicated than that when you get into particle size. Take a person who's scans keep going up because he has small LDL and nothing in Dr. Davis program has worked for him 9I am such a patient of the good Dr.s) The best you can do for such a person is lower his LDL as far as you can since its all going to be small particle anyway. I would also refer you to Dr. Greg Browns HATS Study for examples of lowering cholesterol and lowering heart disease or Dr. Davis' example that started this discussion. I apologise if I came off a bit sarcastic in my earlier comments I think this is an important issue to get all points of view on.

  • Anonymous

    4/16/2008 3:32:00 AM |

    Great thead.

    So what are you really saying about statins?  Is there value taking statins in combination with other treatments for men and women?

    How do you address the comments that states statins don't work?

    Thanks for your time.  Your comments are really appreciated.

  • Anonymous

    4/16/2008 6:14:00 PM |

    There is NO DOUBT that statins reduce the chances of a person having a heart attack, NONE. There is question as to what about the statins does that, is it lowering LDL, is it stablising plaque, is it reducing inflamation . . .? Or is it all of these ? And there is no doubt statins have side effects, some serious, but the fact that they reduce heart attacks, that argument has been settled.

  • J Michael Nicholls

    4/16/2008 7:26:00 PM |

    I will not go deeper into the science of atherosclerosis except to say that it has been known for several years now that cholesterol per se does not initiate atheroma, or plaque. You find cholesterol in the lesions but you also find calcium. We find cholesterol and calcium because it is available in the bloodstream. Cholesterol does not have a mind of its own, and it doesn’t one day decide to develop plaque by raising “the level”. Neither does calcium.

    We need cholesterol for many important processes in the body, and it is a part of almost all of our cell membranes. Mother’s milk is packed with it because the baby needs it. Eggs are full of the stuff “because it takes a hell of a lot of cholesterol to make a chicken”. The body has the level it needs at all times, and a higher level could indicate that something is wrong, i e, it is a marker, like someone said. Lowering of levels makes no sense at all.

    It is just dumb luck that the cholesterol lowering statins happen to be anti-inflammatory and therefore have some preventive effect, and may reverse plaque in some cases. The higher the dose the more anti-inflammatory effect, and reversal of atheroma. The higher the dose the bigger the lowering of the cholesterol level, because that is exactly how statins are designed to work. However, there is NO evidence in the scientific literature that the lowering of the cholesterol level has a protective effect, and I am very sorry if this upsets anyone’s religious beliefs. Dumb luck, as I said, the rest is coincidence and correspondence. Big Pharma will do its best to uphold the “religion” though, since it is so profitable. Levels will always be too high, and everybody should be statinated. Statins should be distributed in the drinking water, no less.

    So, why bother, the statins seems to work in a few cases? Well, statins are really poisonous substances, and there are many indications that they cause harm to the human body, particularly by the lowering of cholesterol levels. Side effects are plentiful and it is probable that we will witness statin induced cancers in large numbers in the near future.

    The point to be made here is that there are other and better methods to avoid atherosclerosis and to reverse plaque. Dr Davis is one of the leading proponents of such methods. I personally think it is interesting to se the results of the statin study presented here; I just wanted to stress the point of what statins really do. By all means, we should keep an eye our cholesterol levels. But many people having a hearth attack do not have high cholesterol. But did you know that 90% of them have diabetes or in some other way a pathological sugar metabolism? So what level is the more important?

    About the quacks, who don’t buy the cholesterol dogma, there are thousands of them. Some of them can be found at www.thincs.org. If you are interested in how the cholesterol religion was developed and how science was corrupted to that end, I can recommend Gary Taubes latest book Good Calories – Bad Calories.

    By the way, CRP is just another marker for hearth disease, but I wouldn’t be surprised if there will soon be talk about lowering the level Smile

  • Anonymous

    4/18/2008 1:13:00 AM |

    Well by your klogic there is no scientific proof the lowering inflamation is what cause stsatins to lower your risk of a herat attack, the only thing we do know is that ststins DO infact lower your risk, we just all keep guessing as to why. Well heres another piece to the puzzle: double blind study releasesed this week follow groups of people on statins or placebos and by a slight BUT significant margin the statin takers blood oressure was lowered ! So besides all the other things we think statins do we now KNOW they lower blood pressure. 2 ver5y interesting points for all of our paranoid readers 1. Not one of the study members recieving the statins in the 2 year period had to leave bececause of side effects and 2. this study was NOT paid for by the big bad scarry Drug companies, so there goes your default response.

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    11/3/2010 4:55:07 PM |

    I am no supporter of drug companies, nor a defender of their policies and practices. But I do believe that their data can serve to teach us a few lessons. For instance, here is an (cherry-picked, to be sure) example of intracoronary ultrasound cross-sectional images before and after two years of rosuvastatin, 40 mg daily: