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Is very low LDL-C harmful?

[ Vol. 24 , Issue. 31 ]


Charles Faselis*, Konstantinos Imprialos, Haris Grassos, Andreas Pittaras, Manolis Kallistratos and Athanasios Manolis   Pages 3658 - 3664 ( 7 )


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.


Low-density lipoprotein cholesterol, safety, statins, PCSK9 inhibitors, cardiovascular disease, cancer.


VA Medical Center and George Washington University, Washington, DC, Second Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Cardiology Department, KAT Hospital, Athens, Cardiology Department, Asklepeion Hospital, Athens, Cardiology Department, Asklepeion Hospital, Athens, Cardiology Department, Asklepeion Hospital, Athens

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