Lexicon
LDL Cholesterol
Also known as LDL-C, Low-density lipoprotein cholesterol
Definition
Low-density lipoprotein cholesterol (LDL-C) plays a causal role in the development and progression of atherosclerosis and cardiovascular disease. [1] A high level of LDL-C has long been considered a major cause of atherosclerosis and cardiovascular disease and is one of the well-known risk factors for coronary heart disease. [2] Mendelian randomization studies and randomized trials have conclusively demonstrated that lower LDL cholesterol results in fewer cardiovascular events. [3]
How it works
Statins lower serum cholesterol by inhibiting hepatic cholesterol biosynthesis, which upregulates hepatic LDL receptors and increases the clearance of LDL-cholesterol from the blood. [4] The association between LDL-C reduction and cardiovascular benefit is consistent across therapies that act by upregulating LDL receptor expression, including statins, diet, bile acid sequestrants, ileal bypass, and ezetimibe. [5] Abnormally elevated LDL cholesterol in familial hypercholesterolaemia is most often caused by LDL receptor mutations, but mutations in ApoB, a gene encoding a protein involved in cholesterol metabolism and LDL receptor function, can also be causative [6]
Connected concepts
How it's measured
LDL-C is reported in molar units (mmol/L) and mass units (mg/dL), where 1 mmol/L corresponds to 38.7 mg/dL. [3] After starting or adjusting statin therapy, adherence and the percentage response should be assessed with a repeat lipid measurement 4 to 12 weeks later, then repeated every 3 to 12 months as needed. [7] European consensus recommendations place LDL cholesterol within the primary lipid panel alongside total cholesterol, triglycerides, HDL cholesterol, and calculated non-HDL cholesterol, noting these can be measured in the nonfasting state for atherosclerotic cardiovascular risk estimation [8]
What levels mean
Severe primary hypercholesterolemia is defined by an LDL-C level of 190 mg/dL (4.9 mmol/L) or higher, for which high-intensity statin therapy is recommended without calculating 10-year risk. [7] A persistently elevated LDL-C level of 160 mg/dL (4.1 mmol/L) or higher is a risk-enhancing factor that favors initiation of statin therapy in adults at intermediate risk. [7]
Community knowledge
## Overview
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- 1.Nelson AJ, Nicholls SJ. Managing hypercholesterolaemia. Aust Prescr · 2024
- 2.Jokinen E. Obesity and cardiovascular disease. Minerva Pediatr · 2015
- 3.Preiss D, Tobert JA, Hovingh GK, Reith C. Lipid-Modifying Agents, From Statins to PCSK9 Inhibitors: JACC Focus Seminar. J Am Coll Cardiol · 2020
- 4.Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res · 2017
- 5.Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, Braunwald E, Sabatine MS. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA · 2016
- 6.Defesche JC, Gidding SS, Harada-Shiba M, Hegele RA, Santos RD, Wierzbicki AS.
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