Low-density lipoprotein cholesterol (LDL-C) is a well-established major cardiovascular
(CV) risk factor supported by clinical evidence showing decreased atherosclerotic disease events when
LDL-C is therapeutically lowered. A reasonable approach is to tailor each patient’s LDL-C target level
depending on the initial LDL-C level and the perceived risk. Multiple clinical entities such as the newborn,
hypobetalipoproteinemia, proprotein convertase subtilisin/kexin type 9 (PCSK9) missense mutations,
and an unexpected excess response to a statin or other medications, are associated with very low
LDL-C levels in otherwise healthy individuals. Therefore, an issue of major interest to clinicians who
buy into “lower is better” for LDL-C in the high-risk CV patient is how low can and should the LDL-C
be taken? Available information is discussed and placed into context. A definite safe lowest LDL-C
level cannot be specified but there appears to be support that a level as low as 20 mg/dL (0.52 mmol/l)
can be justified in the highest CV risk patients with extensive atherosclerosis where plaque stabilization
and regression are necessary.
Keywords: Coronary artery disease, low-density lipoprotein cholesterol, peripheral arterial disease, proprotein convertase subtilisin/
kexin type 9, statins.
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