CRP and Jupiter

What is C-reactive protein (CRP)?

It is a blood-borne protein that originates in the liver and serves as an index of the body's inflammatory state. It is triggered by yet another inflammatory signal molecule, interleukin-6.

What triggers this cascade of inflammatory markers? Any inflammatory stimulus, such as being overweight, lack of exercise, vitamin D deficiency, viral illness no matter how trivial, any inflammatory disease like arthritis, small LDL, high triglycerides, poor diet rich in processed foods, resistance to insulin, any injury, incipient diabetes, hidden cancer, lack of education (no kidding), etc.

In other words, many, many conditions, from trivial to serious, trigger increased inflammatory markers like CRP.

A recent analysis (Genetically elevated C-reactive protein and ischemic vascular disease of persons with genetically elevated levels of CRP) suggests that CRP does not, by itself, cause atherosclerotic disease. CRP is therefore simply a marker for conditions that heighten inflammatory responses.

The AstraZeneca people sponsored the enormous JUPITER study of the statin drug, Crestor, that has been causing a stir, mostly glowing pronouncements of how the world would be a better place if everyone took Crestor.

In JUPITER, nealry 18,000 people (men 50 years and over, women 60 years and over) took 20 mg per day Crestor for two years. Participants all had starting LDL cholesterols in the "normal" range of no higher than 130 mg/dl and elevated CRP of 2 mg/dl or greater.

Crestor treatment resulted in 44% reduction in nonfatal heart attack, nonfatal stroke, hospitalization for unstable angina, revascularization (bypass surgery, stents) and death from cardiovascular causes. The reduction in nonfatal heart attack was most marked at 55%.

Admittedly, these are impressive results. Benefits held true for both males and females. At the very least, JUPITER should put to rest some of the fringe arguments that statins do not reduce cardiovascular events. They do. There is no sense in arguing against that. While we might argue about the value of statins in various subsets of people, there is no doubt that they do indeed exert a significant effect.

However, contrary to the hype and broad pronouncements of my colleagues, my concerns are:

1) Rather than shotgun the inflammatory response with a statin drug regardless of cause, doesn't it make more sense to ask why a specific individual has an increased CRP in the first place? For instance, if the answer is vitamin D deficiency, doesn't correction of the deficiency make more sense? (Vitamin D by itself reduces CRP around 60%--more than statin drugs.) Not to mention you obtain all the extraordinary benefits of vitamin D restoration, such as reduced cancer risk, increased bone density, relief from winter "blues," rise in HDL, etc. How about junk foods, obesity, and unrelated inflammatory conditions? Would we therefore indirectly be treating obesity with Crestor?

2) Crestor 20 mg per day, contrary to the study and to many statin studies, will not be tolerated for long by the majority. Muscles aches are not common--they are inevitable, sometimes incapacitating. While JUPITER showed 15% of both treatment and placebo groups experienced muscle effects--no different--this is wildly contrary to real life.

3) While there was a 55% reduction in the number of heart attacks, there continued to be a substantial number of heart attacks in the Crestor treatment arm. Clearly, reduction of CRP with Crestor, while helpful, is not a cure.

I view studies like JUPITER as simply an interesting piece of semi-scientific evidence, tainted to an unknown degree by commercial interests (including those of Dr. Paul Ridker, one of the principal investigators). It is not a mandate to use Crestor carte blanche in people with elevations of CRP.

My interpretation of these data in a practical sense is that Crestor 20 mg per day as sole therapy is useful in a disinterested, non-compliant patient who is unwilling to make substantial changes in lifestyle and nutrition. Helpful? Yes, but hardly an invitation for the world to take Crestor.

I believe that doesn't include any of the readers of this blog.

Comments (15) -

  • e4e

    11/11/2008 9:28:00 PM |

    Typo alert. You said, "3) 45% of the people on the Crestor treatment arm of the trial did experience heart attack. Clearly, reduction of CRP with Crestor, while helpful, is not a cure."

    That does not seem correct.

  • Anonymous

    11/11/2008 11:05:00 PM |

    Dr. Davis,
    This is interesting that you mention that vitamin D can reduce CRP.
    Statin researcher Dr.Beatrice Golomb,MD said that statins BLOCK the formation of vitamin D. (her comment can be heard on her
    YouTube video) Is it possible that blocking of vitamin D could be responsible for the statin side effects?

  • Dr. William Davis

    11/12/2008 1:03:00 AM |


    Thanks for catching that.

    Now corrected.

  • Anonymous

    11/12/2008 1:50:00 AM |

    I'm glad you did a post concerning the JUPITER study, Dr. Davis.

    I saw this news story on NBC Nightly News last night extolling Crestor even for people with low CV risk factors. And, I said to myself, I bet Dr. Davis will soon have something to say about this study.

    The next time I see my GP, I can pretty much count on him pushing Crestor on me.  He is very, very pro-statin drug and dislikes that I don't take "something" as a 48 y.o. M.  This, even though I only have a 104LDL/51HDL/54TG lipid profile.

    I keep telling him I do take something, 1g Niacin, 4gs EPA/DHA's, 5000IU vitamin D3, and 90mcgs vitamin K2 daily.  His answer is always; Zocor is much more effective in reducing CV risk than just taking vitamin pills.


  • Sue

    11/12/2008 10:28:00 AM |

    There is a lot of blogging about the Jupiter study:

  • Anonymous

    11/13/2008 2:05:00 PM |

    What are we to believe when experts so often disagree with each other?
    I remain curious about the statement statin researcher, Dr.Beatrice Golomb made about statins blocking the formation of vitamin D.  
    A web search of "statins and Vitamin D" show results of other medical studies. They indicate that statins actually INCREASE vitamin D.
    What is the reality here?

  • Anonymous

    11/14/2008 7:41:00 PM |

    Dr Davis,

    Generally I think your blog is very informative and interesting.
    On this occasion I think you ahve been more than a little generous to Astra Zenaca in particular and to statins in general.

    Others have coevered this in more detail elsewhere so I'll just list a few facts that I feel are relevant:

    (i)  The selection criteria for the study is highly selective, an far from normal. I gather that the presence of high CRP and low or normal cholesterol is very rare.

    (ii) Those taking crestor had a developed diabetes at a high er rate than those in the placebo group.

    (iii)  Whereas there were in fact a higher proportion of people with metabolic syndrome in the placebo group.  Quite a big turnaround equally deserving of headlines.  "statins cause diabetes, even in nealthy people..."  There were also a higher proportion of people with a family history of CVD in the placebo group.

    (iv)  One of the lead people on the reseach panelhas recently patented a test for measuring CRP levels - "coincidence"

    (v)  More fatal attacks in the crestor group than in the placebo group.

    (vi)  Absoute number not having (non fatal) heart attacks very small.

    (vii)  Number to treat very high.

    (viii)  Maybe the test was ended early because of the fear of the small trend of benefits reversing and greater levels of cancer, etc showing up.  Presumably if you believe all the hype continuing the trial would have benefitted those in the crestor group whilst no harm came to the placebo group.  

    (ix)  1 in 4 stop taking crestor yet side effects were the same in the placebo and crestor taking groups.

    (x) 28% more deaths from non CVD causes in the Crestor group.  It quite reasoneble to assume that deaths arising as a side effect of taking these drugs would increase over time.

    I could go on, but I think the above makes my point.

    Of course another interpretation of the data is that high cholesterol doesn't cause heart disease, someting else does - inflamation?  

    - in the same way that high blood sugar doesn't cause type 1 diabetes - its a consequence of a failing pancreas.

    Paul Anderson.

  • Anna

    11/15/2008 2:56:00 PM |

    Anonymous said:  What are we to believe when experts so often disagree with each other?

    We don't want experts to agree, for the most part.  When they agree too much, that means little is begin done to push the bounderies of knowledge.  

    I think too many non-experts want to be told what to think, and abdicate their own responsibility to at least try to understand the factors involved and be part of the decision.  

    I realize life is (too) complicated today and we can't know how to do everything ourselves, so we farm out a lot of the "improve and repair" work to experts (car mechanics, electricians, plumbers, and yes, physicians).  But we still need to know enough to know if the proposed work is good or not.  It's not much different with health and/or medicine, in fact it's more important.  Cars or electrical wiring can be replaced after shoddy work; health is more challenging.

    Dr. Davis, I hope you don't take offense to my comparison of physicians and medical experts to trade jobs (nor do I mean any offense to tradesmen).  I merely mean to say we rely all the time on people who have more specialized knowledge and skills than we do.  We still need to understand what's going on.

  • Anonymous

    11/17/2008 4:07:00 AM |

    Anna said, "We don't want experts to agree, for the most part. When they agree too much, that means little is begin done to push the bounderies of knowledge."

    You make a good point, Anna.  
    Regarding the question about disagreement among medical professionals,I would expect that well done unbiased studies would result in clear irrefutable facts. The question was does a statin block vitamin D production or does it enhance it? Doctors disagree on this issue. Why?  There is no way we can know this on our own.
    Regardless of how self-reliant we are, we can only make intelligent health care decisions when we have clear and accurate information.
    When the pharmaceutical industry has so much control of medical education, we definitely have a challenge.

  • Weight Loss

    4/10/2009 2:33:00 AM |

    your article is great. Also CRP does not cause atherosclerotic disease, I too find this after a long study. Thanks for your suggestions.

  • Anonymous

    5/5/2009 8:17:00 PM |

    Another probable typo, and a common one throughout the medical literature, is the use of mg/dL units rather than mg/L.  The correct cutoff value for eligibity in the Jupiter study was 10 times lower at 2 mg/L.

  • Anonymous

    11/12/2009 4:53:53 AM |

    >>>>> Vitamin D by itself reduces CRP around 60%--more than statin drugs <<<<

    Could I have a good source for this statement.  I find it fascinating.

    /a family doc in Canada.
    Thanks !

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    6/30/2010 5:36:08 PM |

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    11/2/2010 8:14:13 PM |

    You make a good point, Anna.
    Regarding the question about disagreement among medical professionals,I would expect that well done unbiased studies would result in clear irrefutable facts. The question was does a statin block vitamin D production or does it enhance it? Doctors disagree on this issue