Is very low LDL-C harmful?

Abstract

Background: Low-density Lipoprotein Cholesterol (LDL-C) is a major Cardiovascular (CV) risk factor. Accumulating evidence supports a linear association between LDL-C levels and CV risk. However, the lower limit of LDL-C that might offer CV benefits without any safety concerns is still a topic of debate. Objective: The purpose of this review is to present the safety of reducing LDL-C to low levels as it comes from major lipid-lowering drug studies, and to discuss data on several safety events that have been associated with low LDL-C levels. Methods: A comprehensive literature search was performed to identify available data from clinical studies evaluating the association of low LDL-C with safety outcomes. Results: Several large trials have evaluated the safety or reducing LDL-C to levels lower than 50 mg/dl or even lower than 25 mg/dl, more commonly with the use of a combination of statins with ezetimibe or proprotein convertase subtilisin kexin 9 inhibitors. In almost all trials, CV benefits were observed with LDL-C levels of 50 mg/dl or less compared with higher levels. In terms of safety, reduction of LDL-C to such levels was not associated with any significant adverse event. Of importance, cancer and hemorrhagic stroke incidences were not increased in patients attaining LDL-C lower than 40-50 mg/dl. Data regarding the impact of lowering LDL-C with neurocognitive disorders are contradictory; nevertheless, most studies stand in favor of neurocognitive safety with LDL-C reductions to low levels. Conclusion: Achieving an LDL-C of 40-50 mg/dl seems to be safe, and importantly might offer CV beneficial effects. Data for attaining levels below 25 mg/dl is limited, however in favor of such reductions.

Possible mechanisms of cholesterol elevation aggravating COVID-19

“…It is worth noting that most of the lipid-lowering goals set the upper limit of LDL-C without mentioning the lower limit, mainly because the lipid-lowering ability of lipid-lowering drugs before cannot reduce the absolute value of LDL-C to a very low level, and the safety of very low cholesterol has not been evaluated 114 . It is currently believed that LDL-C reaching 40-50 mg/dL seems to be safe, while the data below 25 mg/dL is limited, and more in-depth research and post-mortem analysis are needed in the future 115 .…”

Genetic determinants of circulating metabolites and the risk of stroke and its subtypes

“…Small LDL particles, especially cholesterol in small LDL, have been consistently featured for their deleterious effects on the pathogenesis of stroke, where the atherogenic potential caused by higher LDL cholesterol (LDL-C) levels has been viewed as a main aetiological contributor [34,35]. Our results have provided evidence for a destructive role of small LDL particles, especially cholesterol in small LDL, on the occurrence of stroke.…”

Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels

“…The dysregulation of cholesterol homeostasis contributes to the pathogenesis of several alimentary-dependent diseases [28]. The concentration of cholesterol in the blood is an important metabolic biomarker not only for of 15 atherosclerosis and its reduction can be found in certain disorders, such as hyperthyroidism, during the damage of the central nervous and immune systems, and some other multiple organ dysfunctions [29][30][31]. It is also known that endogenous and exogenous cholesterol is metabolically involved in cell membrane production [32].…”