Targeting LDL: is lower better and is it safe?
Low density lipoprotein cholesterol (LDL-C) is one of the most validated targets in clinical medicine. Large randomized, outcome trials have demonstrated a clear relationship between reducing LDL-C and cardiovascular disease (CVD) risk, which has been maintained to LDL-C levels of <1.8 mmol/L. To assess the benefit of even lower LDL-C it is important to recognize that CVD risk reduction is related to absolute reduction in LDL-C, not to percent change. Furthermore measurement of LDL-C is also critical as recent studies show the Friedewald calculation significantly underestimates true LDL-C values <1.8 mmol/L, distorting the relationship with CVD risk reduction. Discussion of potential harm from low, or lower, LDL-C has centered on cancer, hemorrhagic stroke, and violent death, but there is little evidence from outcome trials to show a relationship with low LDL-C. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors which will reduce LDL-C well below 1.3 mmol/L, will likely provide the clearest answer to both the question of efficacy and safety of low LDL-C within the next few years.
Department of Pathology & Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45215, USA. Electronic address: esteinmrl@aol.com.
Evan A
EA
Stein
Division of Endocrinology and Metabolism, Department of Medicine, Carbohydrate & Lipid Metabolism Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
Frederick J
FJ
Raal
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors* / Q000097:blood*; D002986:Clinical Trials as Topic; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects* / Q000379:methods*; D012307:Risk Factors
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL
Friedewald formula; LDL cholesterol; PCSK9 inhibitors; statins