Updates on very low LDL cholesterol

LDL cholesterol is a major factor for developing atherosclerosis. On the basis of our current knowledge 80% of human body cholesterol requirement is made endogenously particularly in the liver. This material is definitely necessary for our cells metabolism, particularly in nervous system and endocrine glands. It has been said excess cholesterol particularly LDL part causes atherosclerosis. It is clear that decrease of circulatory LDL usually with the drugs decreases atherosclerotic cardiovascular events.The ideal efficacy accompany with safety of lowering LDL is an issue of controversy. Blood level of cholesterol like many other materials such as glucose, electrolytes, and etc. automatically controlled in the body, so called homeostasis. Blood glucose level is regulated by insulin, glucagon, epinephrine and etc. to maintain it around 100 mg/ml. significant hypo or hyperglycemia can cause severe symptoms and sometimes is fatal. However, changes of cholesterol level which is also regulated by liver enzymes, LDL receptors, bile excretion, intestinal reabsorption and etc., do not show acute symptoms. But chronic hypercholesterolemia causes atherosclerosis, on the other hand hypocholesterolemia has been claimed to cause cancer, depression, anxiety, nervous and immune systems dysfunction, hemorrhagic stroke, preterm birth and cataract. Effect of statins, (the best current anti-cholesterol drug) is limited by homeostatic compensatory mechanism, and LDL cannot fall in a very low level. Adding other drugs such as ezetimibe and particularly anti PCSK9, such as Evolocumab can decrease LDL to a very low level. Fourier study results, presented in the European Society of Cardiology Congress 2017 in Barcelona, Spain by several expert speakers. Achieving ultra-low LDL levels down to <10 mg/dl safely results in additional lowering of risk of cardiovascular events in high risk patients. Atherosclerosis won’t be eradicated completely if blood LDL kept in ultra-low level. It should be noted that 3 major disturbances in lipoprotein metabolism contributing in CV risk. These 3 lines are: 1- Apo B/ non-HDL/LDL 2- TG- reach lipoprotein and remnant cholesterol 3- LP (a)We have drugs such as statin and PCSK9i to lower the 1st. line hyperlipoproteinemia. But there no approved effective drugs for the 2nd. and 3th. lines. However new RNA based drugs are in investigational process for remnant cholesterol and LP(a)with an optimistic initial results . Would it be completely safe to eradicate all atherogenic LPs from blood stream in long term too Further studies are needed to answer this question. So we have to follow the guidelines to treat our patients at the present time.