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.

  • buy jeans

    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:

Idiot farm

Idiot farm

The notion of genetic modification of foods and livestock is a contentious issue. The purposeful insertion or deletion of a gene into a plant or animal's genome to yield specific traits, such as herbicide resistance, nutritional composition, or size, prompted the Codex Alimentarius Commission, an international effort to regulate the safety of foods, to issue guidelines concerning genetically-modified foods.

The committee is aware of the concept of unintended effects, i.e., effects that were not part of the original gene insertion or deletion design. In their report, last updated in 2009, they state that:

Unintended effects can result from the random insertion of DNA sequences into the plant genome, which may cause disruption or silencing of existing genes, activation of silent genes, or modifications in the expression of existing genes. Unintended effects may also result in the formation of new or changed patterns of metabolites. For example, the expression of enzymes at high levels may give rise to secondary biochemical effects or changes in the regulation of metabolic pathways and/or altered levels of metabolites.

They make the point that food crops generated using techniques without genetic modification are released into the food supply without safety testing:

New varieties of corn, soybean, potatoes and other common food plants are evaluated by breeders for agronomic and phenotypic characteristics, but generally, foods derived from such new plant varieties are not subjected to the rigorous and extensive food safety testing procedures, including studies in animals, that are typical of chemicals, such as food additives or pesticide residues, that may be present in food.

In other words, conventional plant breeding techniques, such as hybridization, backcrossing, and introgression, practices that include crossing parental plants with their progeny over and over again or crossing a plant with an unrelated plant, yield unique plants that are not subject to any regulation. This means that unintended effects that arise are often not identified or tested. Plant geneticists know that, when one plant is crossed with another, approximately 5% of the genes in the offspring are unique to that plant and not present in either parent. It means that offspring may express new characteristics, such as unique gliadin or gluten proteins in wheat, not expressed in either parent and with new immunological potential in consuming humans.

Dr. James Maryanski, the FDA's Biotechnology Coordinator, stated during Congressional testimony in 1999 that:

The new gene splicing techniques are being used to achieve many of the same goals and improvements that plant breeders have sought through conventional methods. Today's techniques are different from their predecessors in two significant ways. First, they can be used with greater precision and allow for more complete characterization and, therefore, greater predictability about the qualities of the new variety. These techniques give scientists the ability to isolate genes and to introduce new traits into foods without simultaneously introducing many other undesirable traits, as may occur with traditional breeding. [Emphasis mine.]

Efforts by the Codex Alimentarius and FDA are meant to control the introduction and specify safety testing procedures for genetically modified foods. But both organizations have publicly stated that there is another larger problem that has not been addressed that predates genetic modification. In other words, conventional methods like hybridization techniques, the crossing of different strains of a crop or crossing two dissimilar plants (e.g., wheat with a wild grass) have been practiced for decades before genetic modification became possible. And it is still going on.

In other words, the potential hazards of hybridization, often taken to extremes, have essentially been ignored. Hybridized plants are introduced into the food supply with no question of human safety. While hybridization can yield what appear to be benign foods, such as the tangelo, a hybrid of tangerines and grapefruit, it can also yield plants containing extensive unintended effects. It means that unique immunological sequences can be generated. It might be a unique gliadin sequence in wheat or a unique lectin sequence in beans. None are tested prior to selling to humans. So the world frets over the potential dangers of genetic modification while, all along, the much larger hazard of hybridization techniques have been--and still are--going on.

Imagine we applied the hybridization techniques applied by plant geneticists to humans, mating an uncle with his niece, then having the uncle mate again with the offspring, repeating it over and over until some trait was fully expressed. Such extensive inbreeding was practiced in the 19th century German village of Dilsberg, what Mark Twain described as "a thriving and diligent idiot factory."

Comments (10) -

  • Jayzee

    6/12/2011 2:26:37 AM |

    Google Hinze Hogendoorn http://tinyurl.com/3t48zhf
    17-year-old Dutch undergraduate student Hinze Hogendoorn  has created scientific history with his simple experiments.

    is there ever any good news from the food science arena?

  • Might-o'chondri-AL

    6/12/2011 5:20:15 AM |

    Metabolite screening should be done to compare with old standard and apparently is being done to some extent; there will always be someone who reacts adversely to what is innocuous to most people.  Since field agriculture is not free of  problems there will always be need for adaptations.

    Japanese daikon root pickle made today has a different degree of physiological benefit  than when made with a traditional old cultivar of smaller sized daikon.  Hinze's rats might have found old fashioned fare more appetizing but they don't have to struggle to produce it like hungry people worldwide must try to do.

    *  2006 article "Transgenes has less impact on the transcriptome of wheat grain than conventional breeding"
    Plant Biotechnology Journal 4, 369 - 380

    * 2006 article "Effect of transgenes on global gene expression in soybean is within the natural range of variation of conventional cultivars"
    Journal Agricultural Food Chemistry 56, 3057 - 3067

    * 2008 article " Microarray analyses reveal that plant mutagenesis may induce more transcriptomic changes than transgene insertion"
    Proceedings National Academy Science USA 105, 3640 - 3645

  • Jim Anderson

    6/13/2011 7:31:13 PM |

    It's astounding that tests are not done -- are not mandated by law and international treaty -- on hybridized plants prior to the plants being sold for human consumption! One doesn't need to be a bio-chemist to see the danger there.  Of course, I have to wonder what kind of tests should be required.  Some dangers may not be readily apparent.  It could take a human generation or two for the problems to be recognized.  We are lab rats!

  • MK Davis

    6/14/2011 2:59:29 AM |

    Our number one forage crop is in danger of infecting the nation's livestock with an organism that is causing infertility in a large percentage of food animals.

    Don Huber Interview - Roundup Ready GMOs - PATHOGEN NEW TO SCIENCE.flv

  • MK Davis

    6/14/2011 3:09:49 AM |

    The URL to the Don Huber video is:  http://bit.ly/k25NpH

  • Dr. William Davis

    6/14/2011 1:01:36 PM |

    Thanks, MK.

    Anyone with even a passing interest in food and food safety absolutely need to view the video link posted by MK Davis (no relationship).

    Dr. Huber brings an incredible depth of insight into the glyphosate GMO crop question.

  • jpatti

    6/14/2011 1:40:02 PM |

    I'm surprised to see stuff about hybrid and GMO plants here.  

    I was an avid gardener before I became disabled and very gung-ho about using open-pollinated seeds, mostly heirlooms.   Even though I didn't save seed, I only bought open-pollinated seeds and plants in order to encourage their preservation by seed companies.  No F1 seeds for me, and DEFINITELY no GMO.  

    When you look into the history even a little bit, you realize even the so-called heirlooms are all pretty new plants.  

    It's been a very short period of time that sweet corn has even existed - corn was always a grain, not a vegetable.  

    Similarly, tomatoes used to be much more acidic than modern varieties are.  It used to be safe to can tomatoes in a hot-water bath.  But new tomatoes need to be canned in a pressure canner... or you have to add acid to the recipe to safely do the water-bath thing and avoid botulism.

    Also, most people have no idea how much yummier heirlooms are.  Vegetables for factory farming have been bred for things like uniform harvest by machinery, ability to keep in storage, not bruising when shipped across country, etc.  Not for TASTE.  

    A Brandywine tomato (my favorite heirloom) tastes NOTHING like what you can buy in a grocery store - because when individuals were doing the breeding, taste was a factor as opposed to  ease of machine harvest and transport and long-term storage.

    You can get good seeds from companies that have taken the No-GMO pledge... such as Baker's Creek Heirloom Seeds, Bountiful Gardens, Southern Exposure Seed Exchange, Pinetree Garden Seeds and Seed Savers Exchange.

    The largest problem is with corn.  Monsanto corn has a gene that makes the plant resistant to Round-up, their primary pesticide.  Even farmers who intend to raise heirlooms have found their fields pollinated by neighbor's Monsanto corn - and been sued since the gene is patented.  

    Farmers that raise heirloom seeds have to raise corn in very isolated spots, and good seed companies test each batch of seed to make sure it's not been infected by the GMO gene.

    Almost ALL corn available today is not only not open-pollinated, but not even normal hybrid corn; rather most of it is GMO.  There's a very few sources of things like non-GMO cornmeal and almost no sweet corn.  

    Same with soybeans - it's all pretty much GMO.  

    IMO, very good reasons to avoid these products in the diet.  I keep a small batch of non-GMO  cornstarch and non-GMO tamari for cooking purposes, but we eat very little corn or soy - and absolutely none of their oils.  Even the non-GMO stuff, corn is very carby, soy causes thyroid issues, and their oils are full of PUFAs. But the small amounts we use in our diet are absolutely non-GMO.

    I forget if it's been released yet or not, but there's a GMO alfalfa coming down the pike.  If the gene is as invasive as the corn gene is, soon it'll be hard to find pasture-raised meat and dairy that hasn't been raised on GMO feed.  

    The largest problem worldwide is in poor countries, where farmers traditionally saved seed to plant again the next year.  These folks literally cannot afford to buy seeds every year.  When all that is available is patented seed or hybrid seed, they are screwed in terms of being able to raise their own food.  People literally starve due to the geopolitics of GMO seed.

    Read up on Monsanto.  They're pretty damned evil.  Probably responsible for more infant deaths than even Nestle.  I personally won't buy products from any company that sells Monsanto products; it's really THAT bad.

    Well, I shall stop my rant now.  I've been ranting about this since back when I was in grad school doing recombinant DNA work myself... I'm getting bored with myself.  ;)

    I actually stopped by to drop off this link for you, Dr. D: http://www.diabetesincontrol.com/articles/diabetes-news/10953-common-test-predicts-early-death-in-diabetes-

  • Dr. William Davis

    6/15/2011 12:11:28 PM |

    Thanks for the detailed commentary, jpatti. Exceptionally well said.

    A return to the simplest forms of farming and plant selection are, I agree, are about the only ways to dodge all the genetic shenanigans provided by agribusiness. Scary stuff.

  • Lois

    7/11/2011 3:23:15 PM |

    Now we know who the snesible one is here. Great post!

  • Peter Defty

    7/21/2011 3:05:27 PM |

    Thank you! for stating a musing I have expressed for years! Plant breeding starting with Mendel has probably done a whole lot more than soem obscure snippet of gene insertion....not being a proponet here but I agree that a much larger point is missed......but this theme seems to run in a lot of directions in the health world like worrying about "SmartMeters" and their radiation when that cell phone, cordless phone and wireless signals are right there in their face......or how African-American kids in urban environments are asthmatic and all the potential causes make the news  EXCEPT that the notion that that high carb diet they most likely are eating is the main trigger......ditto for all the suffering this population group has later in life.....

    thanks for reviving this Mark Twain quote... to book end it  perhaps reviving Parkinson's Law would be appropriate.