Is very low LDL-C harmful?

作者：Charles J. Faselis, Konstantinos P. Imprialos, Haris Grassos, Andreas E. Pittaras, Manolis S. Kallistratos, Athanasios J. Manolis · 发表于：Current Pharmaceutical Design · 年份：2018 · DOI：10.2174/1381612824666181008110643 · 被引用次数：27 · 研究领域：Lipoproteins and Cardiovascular Health、Diabetes, Cardiovascular Risks, and Lipoproteins、Atherosclerosis and Cardiovascular Diseases

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 reduc...