A long time ago, the Framingham Heart Study found that high blood cholesterol — especially high levels of low density lipoprotien (LDL – bad) cholesterol — was associated with more atherosclerosis and heart attacks: cardiovascular disease (CVD). Further evidence that cholesterol was the culprit came from drugs, especially the statins, that reduced LDL cholesterol and decreased CVD with a tightly linear correlation — more LDL more CVD, less LDL proportionally less CVD. Statins have saved a lot of lives operating on this evidence. This can predispose you to the notoriously bad habit of thinking that close correlation means causation. It turns out that the cholesterol part of low density lipoprotien cholesterol doesn’t matter. It’s really the protein part that matters.
LDL cholesterol floats in your blood attached to a big molecule of apolipoprotein B (apoB). So the number of these particles determines your blood levels of LDL cholesterol … pretty much. The protein part and the cholesterol part are tightly correlated for the most part.
New drugs that can lower LDL cholesterol levels a lot have been found to not lower risk of CVD when added to statin treatment. A new study report in The Journal of the American Medical Association using mendelian randomization has helped us understand that these new drugs may have different effects on the cholesterol parts and the protein parts of these particles.1
Remember mendelian randomization is a nifty way of using the random hodgepodge of peoples’ genetic make up to study things such as the target of effects of drugs. Some people naturally have low LDL cholesterol without taking statins, for example. We can look at natural variations in the intended targets of these drugs among people to understand better how they might work without the expense and time of giving drugs to people. Also you can avoid possible side effects — all drugs do lots of other things besides what you mean to do.2
It turns out that LDL cholesterol particles can have different amounts of cholesterol attached. It’s the apoB that binds to liver recepters and also recepters in your arteries that grow athersclerotic plaques, that are the real villians in this story. Mouse studies have shown you can’t live without any apoB, but we would be better off with a lot less. This can guide new drug development.
Should we eat less protein?
1. Ference BA et al. Association of genetic variants related to CETP inhibitors and statins with lipoprotein levels and cardiovascular risk. JAMA. 2017;318(10):947-56.
2. Sniderman AD, Peterson ED. Genetic studies help clarify the complexities of lipid biology and treatment. JAMA. 2017;318(10):915-7.
John DiTraglia, M.D., is a pediatrician in Portsmouth. He can be reached by email at email@example.com or call 740-354-6605.
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