[LDL-cholesterol hypothesis:the lower is trully better]

LDL-cholesterol hypothesis : the lower is trully better. LDL-cholesterol (LDL-C) hypothesis is the concept that elevated LDL-C is a main risk factor in the development of atherosclerosis and consequently in cardiovascular diseases. By extension, the LDL-hypothesis also states that reducing LDL-C levels by nutritional and/or pharmacological approaches is an efficient strategy to reduce cardiovascular events. Concordant evidence supports the LDL-hypothesis, including epidemiologic and genetic studies. Importantly, randomized clinical trials with lipid-lowering drugs, mainly statins, have clearly demonstrated that the reduction of LDL-C levels is associated to a reduction of cardiovascular events. The results from recent clinical trials with ezetemibe (a non-statin hypolipidemic drug) further reinforce the LDL-hypothesis instead of the statin hypothesis. Thus, it seems more logical to define a LDL-target, which is tailored to the cardiovascular risk of each subject, rather than emphasize a therapeutic strategy with statins only. The oncoming results from cardiovascular outcomes studies with PCSK9 inhibitors will help to precise the optimal LDL-C target as well as the safety of achieving very-low LDL-C concentrations.