LDL Cholesterol

LDL Cholesterol

These tests are used to assess risk for coronary heart disease (CHD; primary or secondary) and lipid-lowering therapy.

See also 9 related tests 6 related guides Test Guide List

LDL Cholesterol

Test Summary

 

LDL Cholesterol

Test codes: 7600, 91716, 92053, 92052, 14852, 92061, 19543, 8293, 91723

 

Clinical use

  • Assess risk for coronary heart disease (CHD; primary or secondary)
  • Monitor lipid-lowering therapy

Clinical background

Low-density lipoprotein cholesterol (LDL-C) testing is an important part of a CHD prevention strategy. Test results are used to assess the risk of CHD and also to monitor patients who have an increased risk of CHD due to diabetes, prior CHD, other atherosclerotic disease(s), 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 do not sufficiently lower LDL-C.2,3

LDL-C is recommended as a primary target of lipid-lowering therapy for CHD prevention.2,3 However, approaches to LDL-C monitoring during therapy vary. Some guidelines recommend targeting percent reductions in LDL-C from baseline,2 while other guidelines recommend targeting absolute LDL-C values.3 Regardless of the guidelines followed, LDL-C targets depend on a patient’s atherosclerotic cardiovascular disease (ASCVD) risk, and absolute LDL-C values are used as thresholds for therapy intensification.2,3 Thus, 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 equation, which incorporates the results of 3 separate measurements (all units are in mg/dL): (1) Total cholesterol (the sum of all forms of cholesterol, including very low-density lipoprotein cholesterol [VLDL-C]), (2) high-density lipoprotein cholesterol (HDL-C), and (3) triglycerides (TG):

LDL-C = total cholesterol – HDL-C – TG/5

“TG/5” is an estimate of VLDL-C. The fixed factor of 5 represents a presumed “constant” ratio of TG to VLDL-C cholesterol. However, for patients with high TG and/or low LDL-C levels, the equation may yield artificially high VLDL-C and artificially low or nonreportable LDL-C values. Therefore, Quest Diagnostics calculates LDL-C using an alternative method that allows greater personalization to a patient’s specific TG and non-HDL-C levels: the Martin-Hopkins calculation.4

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.4 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-C (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-C (≥220 mg/dL), and highest (11.9) for those with very high levels of TG (≥400 mg/dL) and low levels of non-HDL-C (<100 mg/dL).

Compared with the Friedewald equation, the Martin-Hopkins calculation provides many advantages, including better correlation with direct LDL-C measurements,4-8 better concordance with guidelines-based risk classification, especially at high TG and low LDL-C,4-8 and tracking more closely with total atherogenic burden, assessed by apolipoprotein B and non-HDL-C levels.9 The ability of the Martin-Hopkins calculation to adjust for high TG levels may also make LDL-C estimates more reliable in nonfasting patients.10 This can be convenient for risk assessment, especially for patients who have difficulty fasting (eg, young children and people with diabetes).10 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.

Compared with other LDL-C equations, the Martin-Hopkins calculation provides the most accurate estimate. Large-scale studies have shown that it provides better correlation with LDL-C reference values determined by a “gold standard” beta-quantitation isotope dilution mass spectrometry method, which has traceability to the International System of Units.11 The Martin-Hopkins calculation also has better concordance with guideline-based LDL-C categorization determined using methods validated against beta-quantitation.12

Assays using 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 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/dL) and calculation is less accurate.7

Individuals suitable for testing

  • Individuals undergoing cardiovascular disease (CVD) risk assessment
  • Individuals at intermediate CVD risk who are being considered for pharmacotherapy
  • Individuals undergoing lipid-lowering therapy

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-C4
  • Direct LDL-C
    • 2-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

Patients should discuss with their provider whether their LDL is normal or abnormal based on their overall risk profile. Target LDL-C levels vary by guideline. The American Association of Clinical Endocrinologists and the American College of Endocrinology guideline recommends the following LDL-C goals for patients: <55 mg/dL for those with extreme risk (eg, premature ASCVD); <70 mg/dL for those with very high risk (eg, ASCVD or diabetes); <100 mg/dL for those with high or moderate risk; and <130 mg/dL for those with low risk.3 A different multi-organization guideline recommends reductions from baseline of ≥30% to ≥50%, depending on patient characteristics, risk assessment, and therapy.2 Once lipid goals have been achieved, guidelines recommend follow-up testing every 3 to 12 months.2,3

Patients with very high LDL-C (≥190 mg/dL) are at increased likelihood of having familial hypercholesterolemia.3 Testing of the patient and potentially family members should be discussed with their provider. See Familial Hypercholesterolemia | Test Summary | Quest Diagnostics for more information.

References

  1. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678
  2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285-e350. doi:10.1016/j.jacc.2018.11.003
  3. Handelsman Y, Jellinger P, Guerin C, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the management of dyslipidemia and prevention of cardiovascular disease algorithm – 2020 executive summary. Endocr Pract. 2020;26(10):1196-1224. doi:10.4158/CS-2020-0490
  4. 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(19):2061-2068. doi:10.1001/jama.2013.280532
  5. 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(12):1355-1364. doi:10.5551/jat.35972
  6. 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(1):e0148147. doi:10.1371/journal.pone.0148147
  7. Quispe R, Hendrani A, Elshazly MB, et al. Accuracy of low-density lipoprotein cholesterol estimation at very low levels. BMC Med. 2017;15(1):83. doi:10.1186/s12916-017-0852-2
  8. Meeusen JW, Lueke AJ, Jaffe AS, et al. Validation of a proposed novel equation for estimating LDL cholesterol. Clin Chem. 2014;60(12):1519-1523. doi:10.1373/clinchem.2014.227710
  9. 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;11(4):1065-1072. doi:10.1016/j.jacl.2017.05.005
  10. 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(7):930-946.doi:10.1373/clinchem.2016.258897
  11. Tan HT, Yong S, Liu H, et al. Evaluation of low-density lipoprotein cholesterol equations by cross-platform assessment of accuracy-based EQA data against SI-traceable reference value. Clin Chem Lab Med. 2023;61(10):1808-1819. doi:10.1515/cclm-2022-1301
  12. Samuel C, Park J, Sajja A, et al. Accuracy of 23 equations for estimating LDL cholesterol in a clinical laboratory database of 5,051,467 patients. Glob Heart. 2023;18(1):36. doi:10.5334/gh.121

Content reviewed 04/2024

top of page

These tests are used to assess risk for coronary heart disease (CHD; primary or secondary) and lipid-lowering therapy.

Test Guide List

LDL Cholesterol

Test Summary

 

LDL Cholesterol

Test codes: 7600, 91716, 92053, 92052, 14852, 92061, 19543, 8293, 91723

 

Clinical use

  • Assess risk for coronary heart disease (CHD; primary or secondary)
  • Monitor lipid-lowering therapy

Clinical background

Low-density lipoprotein cholesterol (LDL-C) testing is an important part of a CHD prevention strategy. Test results are used to assess the risk of CHD and also to monitor patients who have an increased risk of CHD due to diabetes, prior CHD, other atherosclerotic disease(s), 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 do not sufficiently lower LDL-C.2,3

LDL-C is recommended as a primary target of lipid-lowering therapy for CHD prevention.2,3 However, approaches to LDL-C monitoring during therapy vary. Some guidelines recommend targeting percent reductions in LDL-C from baseline,2 while other guidelines recommend targeting absolute LDL-C values.3 Regardless of the guidelines followed, LDL-C targets depend on a patient’s atherosclerotic cardiovascular disease (ASCVD) risk, and absolute LDL-C values are used as thresholds for therapy intensification.2,3 Thus, 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 equation, which incorporates the results of 3 separate measurements (all units are in mg/dL): (1) Total cholesterol (the sum of all forms of cholesterol, including very low-density lipoprotein cholesterol [VLDL-C]), (2) high-density lipoprotein cholesterol (HDL-C), and (3) triglycerides (TG):

LDL-C = total cholesterol – HDL-C – TG/5

“TG/5” is an estimate of VLDL-C. The fixed factor of 5 represents a presumed “constant” ratio of TG to VLDL-C cholesterol. However, for patients with high TG and/or low LDL-C levels, the equation may yield artificially high VLDL-C and artificially low or nonreportable LDL-C values. Therefore, Quest Diagnostics calculates LDL-C using an alternative method that allows greater personalization to a patient’s specific TG and non-HDL-C levels: the Martin-Hopkins calculation.4

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.4 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-C (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-C (≥220 mg/dL), and highest (11.9) for those with very high levels of TG (≥400 mg/dL) and low levels of non-HDL-C (<100 mg/dL).

Compared with the Friedewald equation, the Martin-Hopkins calculation provides many advantages, including better correlation with direct LDL-C measurements,4-8 better concordance with guidelines-based risk classification, especially at high TG and low LDL-C,4-8 and tracking more closely with total atherogenic burden, assessed by apolipoprotein B and non-HDL-C levels.9 The ability of the Martin-Hopkins calculation to adjust for high TG levels may also make LDL-C estimates more reliable in nonfasting patients.10 This can be convenient for risk assessment, especially for patients who have difficulty fasting (eg, young children and people with diabetes).10 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.

Compared with other LDL-C equations, the Martin-Hopkins calculation provides the most accurate estimate. Large-scale studies have shown that it provides better correlation with LDL-C reference values determined by a “gold standard” beta-quantitation isotope dilution mass spectrometry method, which has traceability to the International System of Units.11 The Martin-Hopkins calculation also has better concordance with guideline-based LDL-C categorization determined using methods validated against beta-quantitation.12

Assays using 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 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/dL) and calculation is less accurate.7

Individuals suitable for testing

  • Individuals undergoing cardiovascular disease (CVD) risk assessment
  • Individuals at intermediate CVD risk who are being considered for pharmacotherapy
  • Individuals undergoing lipid-lowering therapy

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-C4
  • Direct LDL-C
    • 2-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

Patients should discuss with their provider whether their LDL is normal or abnormal based on their overall risk profile. Target LDL-C levels vary by guideline. The American Association of Clinical Endocrinologists and the American College of Endocrinology guideline recommends the following LDL-C goals for patients: <55 mg/dL for those with extreme risk (eg, premature ASCVD); <70 mg/dL for those with very high risk (eg, ASCVD or diabetes); <100 mg/dL for those with high or moderate risk; and <130 mg/dL for those with low risk.3 A different multi-organization guideline recommends reductions from baseline of ≥30% to ≥50%, depending on patient characteristics, risk assessment, and therapy.2 Once lipid goals have been achieved, guidelines recommend follow-up testing every 3 to 12 months.2,3

Patients with very high LDL-C (≥190 mg/dL) are at increased likelihood of having familial hypercholesterolemia.3 Testing of the patient and potentially family members should be discussed with their provider. See Familial Hypercholesterolemia | Test Summary | Quest Diagnostics for more information.

References

  1. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678
  2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285-e350. doi:10.1016/j.jacc.2018.11.003
  3. Handelsman Y, Jellinger P, Guerin C, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the management of dyslipidemia and prevention of cardiovascular disease algorithm – 2020 executive summary. Endocr Pract. 2020;26(10):1196-1224. doi:10.4158/CS-2020-0490
  4. 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(19):2061-2068. doi:10.1001/jama.2013.280532
  5. 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(12):1355-1364. doi:10.5551/jat.35972
  6. 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(1):e0148147. doi:10.1371/journal.pone.0148147
  7. Quispe R, Hendrani A, Elshazly MB, et al. Accuracy of low-density lipoprotein cholesterol estimation at very low levels. BMC Med. 2017;15(1):83. doi:10.1186/s12916-017-0852-2
  8. Meeusen JW, Lueke AJ, Jaffe AS, et al. Validation of a proposed novel equation for estimating LDL cholesterol. Clin Chem. 2014;60(12):1519-1523. doi:10.1373/clinchem.2014.227710
  9. 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;11(4):1065-1072. doi:10.1016/j.jacl.2017.05.005
  10. 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(7):930-946.doi:10.1373/clinchem.2016.258897
  11. Tan HT, Yong S, Liu H, et al. Evaluation of low-density lipoprotein cholesterol equations by cross-platform assessment of accuracy-based EQA data against SI-traceable reference value. Clin Chem Lab Med. 2023;61(10):1808-1819. doi:10.1515/cclm-2022-1301
  12. Samuel C, Park J, Sajja A, et al. Accuracy of 23 equations for estimating LDL cholesterol in a clinical laboratory database of 5,051,467 patients. Glob Heart. 2023;18(1):36. doi:10.5334/gh.121

Content reviewed 04/2024

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Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

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