The State of the Problem of Achieving Extremely Low LDL Levels

Abstract

Abstract.: Patients who have achieved very low low-density lipoprotein cholesterol (LDL-C) levels in clinical trials have the lowest cardio-vascular risk. The current clinical guidelines set such concentration for LDL-C as < 1.4 mmol/L. However, the question of minimum permissible target values of the lipids remains unresolved. A number of experimental and clinical studies showed some unfavorable consequences of low LDL-C levels, at the same time, the modern arsenal of lipid lowering drugs allows reducing LDL-C levels to extremely low values.

The Multifaceted Biology of PCSK9

“…Even though a strong body of evidence indicates that cholesterol plays a role in cancer development, the evaluation of the impact of extremely low cholesterol levels (LDLc < 25 mg/dL) on human tumorigenesis, cancer progression and/or metastasis should be addressed. Namely, the combination of cholesterol lowering drugs (PCSK9i, statins, ezetimibe) that drastically reduce LDLc ( 282 ) and enhance surface LDLR levels may reduce tumor growth and/or metastasis via cholesterol depletion and increased TCR and MHC-I activities. Pairing this approach with chemotherapy/immunotherapy has been proposed ( 268 ).…”

The PCSK9 discovery, an inactive protease with varied functions in hypercholesterolemia, viral infections, and cancer

“…Altogether, the use of a safe PCSK9 inhibitor strategy (mAb or siRNA) in combination with statins and possibly ezetimibe should drastically reduce circulating LDL-C levels ( 137 ), while enhancing the levels of cell surface LDLR and MHC-I to possibly provide some protection against tumor growth and/or metastasis. Pairing this approach with chemotherapy/immunotherapy has been proposed ( 138 ).…”