Surrogate markers never provide the whole picture. What to do about cholesterol and statins…

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For the last two decades, Americans have been taking statins, among the most widely used drugs in the world, with the aim of getting their cholesterol numbers down to target levels. Right now, some 24 million Americans are prescribed statins at a cost of some $ 14 billion annually.  Statins are considered useful therapy because they block liver enzymes that produce cholesterol; there may be ancillary actions from taking statins, as well.

Those chosen to take the drug have been diagnosed with problems with LDL [low density lipoprotein]  (“bad”) cholesterol.  This test became prevalent in the early 70’s about the time the first statins were being developed. (The test itself was developed in 1949.)  In a fashion similar to how we prescribe Coumadin, we tweak the doses (and sometimes the specific version of the statin) until a specific goal is achieved.

The normal target level for LDL is 100mg/dl (or less); but there are some patients whose LDL needs to be controlled to below 70.  If the physician feels the patients is not high risk (and  exercise regularly with some diet modifications),  they may not prescribe statins until the LDL reaches 160 or so.

Britain’s NICE (National Institute for Health and Clinical Excellence) believes that statins should be prescribed when the patient has a 20% (or greater) risk of developing heart disease.  This group, which provides health guidelines for Britain, does not stipulate a target cholesterol level.

The problem is that the data would indicate a better reduction in heart problems than we have achieved.  For example, we now know that patients that have variable blood pressure are six times more likely to have a stroke (when compared to those with conventional hypertension.)  A set of doctors want a more honed approach- including diabetes, hypertension, and family medical history, not just the LDL levels.  The lead researchers are Dr. Rodney Hayward at the VA in Ann Arbor and Harlan Krumholz, a Yale cardiologist.  Their group published their results in the Annals of Internal Medicine in January, which suggested 40 mg doses of simvastatin for people with a 5% to 15% risk of coronary artery disease over five years; 40 mg of Lipitor is recommended for those with higher risk. However, they found no target level of LDL was indicated.

But, these may still be misguided efforts.  The problem is the LDL cholesterol is just a surrogate marker.  Dr. Robert Krauss (Children’s Hospital, Oakland Research Institute) has developed an analyzer based upon ion mobility analysis.  His testing shows that LDL is a poor surrogate- since there are four major types of LDL (“scientifically” appelated large, medium, small, and very small), some of which may be benign. And, a diet high in saturated fats boosts the large LDL particles, a low-fat high carb diet propogates the smaller forms.  (It is the smaller, denser versions that are problematic.)

The most predictive of cardiac disease are those patients with low HDL (high density lipoprotein levels) and those with small/medium LDL with low HDL levels.  You will notice that high LDL cholesterol is NOT an accurate predictor. A 1977 NIH study  [“a small (early) portion of the Framingham Heart Study”] confirmed that high HDL is associated with a reduced risk of heart disease. It also confirmed that LDL and “total cholesterol” tells us little about the risk of having a heart attack (something that seems to have been forgotten lately). We do know that eating fewer carbohydrates, losing weight, and becoming active all reduce LDL- with weight loss being the most instrumental.

Perhaps the better approach would be altering our diets and the exercise regime mentioned above.  Then, if we find that the LDL levels are high (somewhere around 100), we should employ the new more discriminatory test to determine which LDL’s prevail. And, then, based upon that testing, should we find the LDL’s to be of the more dense variety, begin titrating with statins.

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