[Low and very low cholesterol levels: what we need to know]

Due to the growing evidence of clinical benefits conferred by the reduction of low-density lipoprotein cholesterol (LDL-C) levels, the availability of multiple effective lipid-lowering agents, and guideline recommendations, clinicians not infrequently have to manage patients with low or very low LDL-C levels. In clinical practice it is essential to consider that, when LDL-C plasma concentrations are low, the Friedewald formula commonly used for LDL-C level calculation is less accurate, hence risk assessment should be integrated by using different methods for LDL-C level quantification and other parameters, such as non-high-density lipoprotein cholesterol and, where possible, apolipoprotein B, should be measured. As regards the clinical impact of low LDL-C levels, genetically determined hypocholesterolemia forms provide reassuring data on the effects of this condition in the long term, except for the forms with extremely low or undetectable LDL-C levels. Evidence from clinical studies that used highly effective lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 inhibitors, goes in the same direction. In these studies, the incidence of non-cardiovascular adverse events in patients who reached very low LDL-C levels was similar to that in the placebo arm. Overall, the fear of adverse effects should not deter intensive lipid-lowering treatment when indicated to reduce the risk of cardiovascular events.