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LDL Cholesterol

LDL Cholesterol

Test Summary

LDL Cholesterol

  

Clinical Use

  • Assess risk for coronary heart disease (CHD; primary or secondary)

  • Monitor nondrug or drug therapy

Clinical Background

Low-density lipoprotein-cholesterol (LDL-C) testing is an important part of a CHD prevention strategy. It is used to assess the risk of CHD and also to monitor patients who have an increased risk of CHD due to prior CHD, other atherosclerotic disease(s), diabetes mellitus, or other risk factors. The risk of CHD can be reduced through lifestyle changes and medical therapy.1-3 Alternative pharmacotherapy may be recommended if statins are not tolerated or insufficiently lower LDL-C.1-3

The precise role of treating to LDL-C targets in prevention strategies is controversial, however. LDL-C is recommended as the primary target of therapy by some organizations2 or as a secondary target by others.1 The American College of Cardiology (ACC) and the American Heart Association (AHA) 2013 guidelines de-emphasize LDL-C targets. Instead they favor a "statin benefit group" approach.3 See Atherosclerotic Cardiovascular Disease Risk: Assessment and Management for more information. Regardless of the guidelines followed, the accurate measurement of LDL-C is important for patient management.

Because of the complexity of direct measurement, LDL-C levels have traditionally been calculated using the Friedewald equation4:

LDL-C (mg/dL) = total cholesterol – HDL-C – TG/5

This equation is based on 3 separate measurements: total cholesterol (the sum of all forms of cholesterol, including very low density lipoprotein-cholesterol [VLDL-C]), high-density lipoprotein-cholesterol (HDL-C), and triglycerides (TG). "TG/5" is an estimate of VLDL-C. The fixed factor of 5 represents a presumed "constant" ratio of TG to VLDL-C cholesterol, which was originally derived from a sample of 448 people in the early 1970s.4 This approach has some limitations. Specifically, for patients with high TG and/or low LDL-C levels, the equation may yield artificially high VLDL-C and artificially low or non-reportable LDL-C values.

Therefore, Quest Diagnostics calculates LDL-C using an alternative method that allows greater personalization to a patient's specific TG level: the Martin-Hopkins calculation.5 The Martin-Hopkins calculation uses an adjustable factor to estimate VLDL-C instead of a fixed factor of 5, but is otherwise similar to the Friedewald equation. This adjustable factor was derived from an analysis of TG to VLDL-C ratios in nearly 1.4 million people.5 The factor is chosen from a matrix table of 180 possible factors, which range from 3.1 to 11.9, corresponding to an individual's TG and non-HDL-cholesterol (total cholesterol – HDL-C) levels. It is lowest (3.1) for patients with very low levels of TG (7 to 49 mg/dL) and high levels of non-HDL-cholesterol (≥220 mg/dL), and highest (11.9) for those with very high levels of TG (≥400 mg/dL) and low levels of non-HDL-cholesterol (<100 mg/dL).

Compared with the Friedewald equation, the Martin-Hopkins calculation provides better correlation with direct LDL-C measurements.5-9 Concordance with guidelines-based risk classification, especially at high TG and low LDL-C, is also superior using the Martin-Hopkins calculation.5-9 Importantly, total atherogenic burden, assessed by apolipoprotein B and non-HDL-C levels, tracks more closely with LDL-C using the Martin-Hopkins calculation.10 The ability of the Martin-Hopkins calculation to adjust for high TG levels may also make LDL-C estimation more reliable in nonfasting patients.11 This can be convenient for risk assessment, especially for patients who have difficulty fasting (eg, young children and people with diabetes).11 The improved accuracy at lower LDL-C (≤70 mg/dL) allows more accurate categorization of patients in very high-risk categories undergoing aggressive treatment with low LDL-C goals.

Assays with calculated LDL-C include Lipid Panel (Test Codes 7600 and 91716), ASCVD Risk Panel with Score (Test Codes 92053 and 92052), Lipid Panel with Reflex to Direct LDL (Test Codes 14852[X] and 92061), and Lipid Panel with Ratios (Test Code 19543). Panel components can be ordered separately (total cholesterol [Test Codes 334 and 91717], HDL-C [Test Codes 608 and 91719], and TG [Test Codes 896 and 91718]).

The direct LDL-C assay (Test Codes 8293 and 91723) provides an alternative to calculated LDL-C. Direct measurement provides a reliable result even when TG levels are up to 1,290 mg/dL, or LDL-C values are low (10 to 40 mg/mL) and calculation is less accurate.6 Further, the direct LDL-C assay has been correlated with the CDC-accepted reference method ("the gold standard"). Thus, results can be related to the epidemiologic data that have been generated for the assessment of CHD risk and the monitoring of therapy to reduce that risk.

Individuals Suitable for Testing

  • Individuals undergoing cardiovascular disease (CVD) risk assessment

  • Individuals at intermediate CVD risk who are being considered for pharmacotherapy

  • Individuals undergoing LDL-C-lowering pharmacotherapy

Method

  • Calculated LDL-C

    –  Enzymatic assays for total cholesterol, HDL-C, and TG

    –  Adjustable factors read from a 180-cell table based on TG and non-HDL-C are used for calculating VLDL-C, and subsequently LDL-C5

  • Direct LDL-C

    –  Two-phase enzymatic: enzymatic assay for LDL-C after selectively solubilizing and enzymatically digesting non-LDL-lipoproteins

    –  Analytical measurement range: 10 to 400 mg/dL

Interpretive Information

Target LDL-C levels vary according to the atherosclerotic cardiovascular disease risk profile of the patient. The National Lipid Association recommends the following LDL-C goals for patients: <70 mg/dL (very high risk, eg, patients with diabetes and known heart disease), <100 mg/dL (high, moderate, and low risk). Once goals have been achieved for LDL-C and non-HDL-C, the NLA recommends follow-up testing within 4 to 12 months.

Patients with very high LDL-C (≥190 mg/mL) are at risk for familial hypercholesterolemia.

 

References

  1. Jacobson TA, Ito MK, Maki KC, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report. J Clin Lipidol. 2015;9:129-169.

  2. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of atherosclerosis. Endocr Pract. 2017;23(Suppl 2):1-85.

  3. Goff DC, Jr., Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2935-2959.

  4. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502.

  5. Martin SS, Blaha MJ, Elshazly MB, et al. Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. JAMA. 2013;310:2061-2068.

  6. Quispe R, Hendrani A, Elshazly MB, et al. Accuracy of low-density lipoprotein cholesterol estimation at very low levels. BMC Med. 2017;15:83. doi:10.1186/s12916-017-0852-2

  7. Meeusen JW, Lueke AJ, Jaffe AS, et al. Validation of a proposed novel equation for estimating LDL cholesterol. Clin Chem. 2014;60:1519-1523.

  8. Lee J, Jang S, Son H. Validation of the Martin method for estimating low-density lipoprotein cholesterol levels in Korean adults: findings from the Korea National Health and Nutrition Examination Survey, 2009-2011. PLoS One. 2016;11:e0148147.

  9. Chaen H, Kinchiku S, Miyata M, et al. Validity of a novel method for estimation of low-density lipoprotein cholesterol levels in diabetic patients. J Atheroscler Thromb. 2016;23:1355-1364.

  10. Whelton SP, Meeusen JW, Donato LJ, et al. Evaluating the atherogenic burden of individuals with a Friedewald-estimated low-density lipoprotein cholesterol <70 mg/dL compared with a novel low-density lipoprotein estimation method. J Clin Lipidol. 2017; Published Online June 1, 2017 (doi:10.1016/j.jacl.2017.05.005).

  11. Nordestgaard BG, Langsted A, Mora S, et al. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cutpoints-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem. 2016;62:930-946.
     

Content reviewed 07/2017

 
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