Lies, damned lies, and statistics

In the last Heart Scan Blog post, I discussed the question of whether statin drugs provide incremental benefit when excellent lipid values are already achieved without drugs.

But I admit that I was guilty of oversimplification.

One peculiar phenomenon is that, when plaque-causing small LDL particles are reduced or eliminated and leave relatively benign large LDL particles in their place, conventional calculated LDL overestimates true LDL.

In other words, eliminate wheat from your diet, lose 25 lbs. Small LDL is reduced as a result, leaving large LDL. Now the LDL cholesterol from your doctor's office overestimates the true value.

Anne raised this issue in her comment on the discussion:

I eliminated wheat - and all grains - from my diet nearly three years ago (I eat low carb Paleo). My fish oils give me a total of 1680 mg EPA and DHA per day, and my vitamin D levels since last year have varied between 50 ng/ml and 80 ng/ml. However, my lipid profile is not like either John's or Sam's:

LDL cholesterol 154 mg/dl
HDL cholesterol 93 mg/dl
Triglycerides 36 mg/dl
Total cholesterol 255 mg/dl

My cardiologist and endocrinologist are happy with my profile because they say the ratios are good, no one is asking me to take a statin. My calcium score is 0.

However, if we were to measure LDL, not just calculate it from the miserably inaccurate Friedewald equation, we would likely discover that her true LDL is far lower, certainly <100 mg/dl. (My preferred method is the bull's eye accurate NMR LDL particle number; alternatives include apoprotein B, the main apoprotein on LDL.)

So Anne, don't despair. You are yet another victim of the misleading inaccuracy of standard LDL cholesterol determination, a number that I believe should no longer be used at all, but eliminated. Unfortunately, it would further confuse your poor primary care doctor or cardiologist, who--still believe in the sanctity of LDL cholesterol.

By the way, the so-called "ratios" (i.e., total cholesterol to HDL and the like) are absurd notions of risk. Take weak statistical predictors, manipulate them, and try to squeeze better predictive value out of them. This is no better than suggesting that, since you've installed new brakes on your car, you no longer are at risk for a car accident. It may reduce risk, but there are too many other variables that have nothing to do with your new brakes. Likewise cholesterol ratios.

Comments (8) -

  • Jeff

    4/18/2009 12:02:00 PM |

    I am in a similar boat.  I eliminated wheat, added cod liver oil(1-1.5 TBS or so per day), and take vitamin D supplements(gel caps around 4-5K IU per day).  Here were my results:

    TOTAL: 272
    HDL: 76
    LDL(calculated): 184
    Triglycerides: 62

    I strongly suspect the LDL is BS due to large particle size.  I will only be able to tell with the NMR, which I will do sometime this year.  I am not worried so I am in no rush.

  • arnoud

    4/18/2009 1:26:00 PM |

    Dr. Davis, thank you for providing such eye-opening insights in the interpretation of lipid testing results, and for explaining the limits of the usefulness of these measurements.

    However, in the typical doctor's office, the high (calculated) LDL prompts the doctor to push for treatment (including statins).  My doctor tells me that I need not avoid statins, as he is taking those himself, and he wouldn't if he'd think they were a problem.

    I can take my NMR Liposcience LDL particle count result to my doctor, and tell him that my real LDL number is 1/10th of the LDL particle count.  This actual number looks great!  How can I show my doctor that this calculation is correct (LDL particle count divided by 10), and that the standard Framingham calculated LDL should be ignored.   Is there a reference paper I can show my doctor, which explains the science behind the "LDL particle count divided by 10" rule?

  • john elfrank

    4/18/2009 1:35:00 PM |

    I had a coronary calcium scan a  few years ago. My score was about 350 with most of the calcium in the LAD.

    My Manhattan cardiologist responded by putting me on the treadmill and doing an eco stress test. I passed it with flying colors.

    I went to my internist who said  I should be concerned about that calcium score. I said my cardio won't give me any other tests. He said to go back and tell him I have chest pains. I did, got the angiogram and a stent for the 80% blockage in my "widow-maker" LAD.

    Now my lipid profile (I have dyslipidemia) is LDL 23, HDL 23, triglycerides 350 (1000 w/o meds). I had thyroidectomy in 1991 and take synthroid 200 mg.

    My combo thereapy is:
    2000 Niaspan, 40 Simvastatin, 200 Co-enzyme Q10, 1200 fish oil. It'a about as aggressive as my body can stand. Tricor and other fibrates interfere with synthroid absorption (I bet you didn't know that).

    My questions are:
    1. Would it be better for me to take the new combo Simvastatin/Niaspan drug rather than take them separately?

    2. Just passed a nuclear stress test. Should I insist on another angiogram soon?

    3. Would another calcium scan be useful?



  • sk

    4/18/2009 3:38:00 PM |

    this is absolutely spot on!  My numbers prior to NMR showed a total cholesterol of 150, HDL of 41, and TRG of 53.  Because of family history, my internist had me take NMR study and results showed that my particle number for LDL was 1795 and all small particles.  Since eliminating wheat and being on a statin my particle number is down to 1305,but still all small. Not sure that size can be changed, probably genetic.  
    Sadly, many out there think they have a fine profile from indirect measurement, and reality is that many probably do not.

  • Kiwi

    4/18/2009 10:05:00 PM |

    What is the recommended range for the ApoB test?
    My lab gives this:

    Male reference range 0.52 - 1.09 g/L
    Female reference range 0.49 - 1.03 g/L

    Using the Immunoturbidimetric method.
    VAP and NMR tests not available here.

  • Dr. B G

    4/20/2009 9:42:00 PM |


    Those are FANTASTIC, phenomenal labs !!!

    You go GIRL!


  • Dr. B G

    4/20/2009 9:42:00 PM |


    Those are FANTASTIC, phenomenal labs !!!

    You go GIRL!


  • Ravi

    4/23/2009 9:42:00 AM |

    I strongly suspect the LDL is BS due to large particle size. I will only be able to tell with the NMR, which I will do sometime this year. I am not worried so I am in no rush.