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Targeting LDL: is lower better and is it safe?

Evan A Stein1, Frederick J Raal2

  • 1Department of Pathology & Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45215, USA.

Best Practice & Research. Clinical Endocrinology & Metabolism
|May 21, 2014
PubMed

Insights

Reducing low-density lipoprotein cholesterol (LDL-C) significantly lowers cardiovascular disease (CVD) risk. New research explores the safety and efficacy of achieving very low LDL-C levels, particularly with PCSK9 inhibitors.

Area of Science:

  • Cardiology
  • Clinical Medicine
  • Pharmacology

Background:

  • Low-density lipoprotein cholesterol (LDL-C) is a primary target for cardiovascular disease (CVD) risk reduction.
  • Established outcome trials confirm LDL-C reduction benefits, even at levels below 1.8 mmol/L.

Purpose of the Study:

  • To evaluate the benefits of achieving even lower LDL-C levels than currently targeted.
  • To address the accuracy of LDL-C measurement methods at very low concentrations.
  • To examine the potential harms associated with very low LDL-C levels.

Main Methods:

  • Review of large randomized outcome trials.
  • Analysis of LDL-C measurement methodologies, including the Friedewald calculation.
  • Assessment of safety data regarding potential adverse events at low LDL-C levels.

Main Results:

  • Cardiovascular disease risk reduction is linked to the absolute reduction in LDL-C.
  • The Friedewald calculation can underestimate LDL-C values below 1.8 mmol/L, impacting risk assessment.
  • Current evidence does not strongly support a link between very low LDL-C and increased risks of cancer, hemorrhagic stroke, or violent death.

Conclusions:

  • Achieving very low LDL-C levels, potentially below 1.3 mmol/L, warrants further investigation for CVD risk reduction.
  • Accurate LDL-C measurement is crucial for precise risk assessment and treatment guidance.
  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are expected to provide key insights into the efficacy and safety of extremely low LDL-C levels.

Keywords:
Friedewald formulaLDL cholesterolPCSK9 inhibitorsstatins

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