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Low-density lipoprotein cholesterol (LDL-C) is widely recognized as an established cardiovascular risk marker predicated on results from numerous clinical trials that demonstrate the ability of LDL-C to independently predict development and progression of coronary heart disease. In the United States, LDL-C remains the primary focus for cardiovascular risk assessment and evaluation of pharmacologic effectiveness. There have been considerable educational efforts invested and directed towards physicians, laboratorians, allied health staff, and the general public regarding LDL-C and strategies to lower LDL-C for reduction of cardiovascular risk.
Low-density lipoproteins are a heterogeneous population of lipid particles classically defined as having a density of 1.006 to 1.063 kg/L obtained by preparative ultracentrifugation. The gold standard beta-quantification (beta-quant or BQ) method combines ultracentrifugation with precipitation and yields a collective quantitative measurement of LDL-C, intermediate-density lipoprotein cholesterol (IDL-C), and lipoprotein(a) (Lp[a]) cholesterol. In practice, LDL-C is most commonly reported using the Friedewald equation (LDL-C=TC-HDL-TG/5).
Importantly, there are significant shortcomings and limitations to the Friedewald equation. Calculated LDL-C is not accurate in patients who are nonfasting, have triglycerides greater than 400 mg/dL, or have type III hyperlipoproteinemia. The equation is particularly inaccurate once the triglycerides are above 200 mg/dL or when LDL-C is <70 mg/dL.
Extremely low concentrations of LDL-C are associated with 2 genetic disorders; abetalipoproteinemia and hypobetalipoproteinemia. In both cases individuals will have very low total cholesterol and diminished or absent LDL-C, apolipoprotein B (apoB) (APLB / Apolipoprotein B, Plasma) and very low-density lipoprotein cholesterol (VLDL-C). Patients may exhibit clinical signs and symptoms of polyneuropathy, intestinal fat malabsorption, hepatosteatosis, and fat soluble vitamin deficiencies (VAE / Vitamin A and Vitamin E, Serum).
Evaluation of cardiovascular risk
Assessment of low-density lipoprotein C (LDL-C) in patients with hypertriglyceridemia, type III hyperlipoproteinemia/dysbetalipoproteinemia, or when an accurate gold standard determination of LDL-C is required
Diagnosis of familial hypobetalipoproteinemia and abetalipoproteinemia
The optimal concentration for LDL cholesterol in primary prevention depends on individual patient risk. Risk factors include: family history of coronary heart disease (CHD), hypertension, cigarette smoking, obesity, diabetes mellitus, and low HDL cholesterol, among others. Consideration of drug treatment is recommended for patients with LDL cholesterol >190 mg/dL.
Values <80 mg/dL indicate hypobetalipoproteinemia. Complications due to fat malabsorption may be present in affected individuals.
Undetectable LDL-C is highly suggestive of abetalipoproteinemia. Related polyneuropathy may exist in affected individuals.
It is preferable but not required that the patients fast for 12 to 14 hours before the blood is drawn. The patient can take water and prescription drugs if necessary. Alcohol should be avoided for at least 24 hours before specimen draw.
Result can be falsely decreased in patients with elevated levels of N-acetyl-p-benzoquinone imine (NAPQI)-a metabolite of acetaminophen), N-acetylcysteine (NAC), and metamizole.
The National Lipid Association and the National Cholesterol Education Program (NCEP) have set the following guidelines for LDL-C in adults (ages 18 years and up):
Desirable: <100 mg/dL
Above Desirable: 100-129 mg/dL
Borderline high: 130-159 mg/dL
High: 160-189 mg/dL
Very high: > or =190 mg/dL
The Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents has set the following guidelines for LDL-C in children and adolescents (ages 2-17 years):
Acceptable: <110 mg/dL
Borderline high: 110-129 mg/dL
High: > or =130 mg/dL
1. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), JAMA 2001;285:2486-2497
2. Jacobson TA, Ito MK, Maki KC, et al: National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 - executive summary. J Clin Lipidol 2014 Sep-Oct;8(5):473-488
3. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011 Dec;128 Suppl 5:S213-S256