Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile
In clinical and research settings worldwide, low-density lipoprotein cholesterol (LDL-C) is typically estimated using the Friedewald equation. This equation assumes a fixed factor of 5 for the ratio of triglycerides to very low-density lipoprotein cholesterol (TG:VLDL-C); however, the actual TG:VLDL...
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| Vydané v: | JAMA : the journal of the American Medical Association Ročník 310; číslo 19; s. 2061 |
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| Hlavní autori: | , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
United States
20.11.2013
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| ISSN: | 1538-3598, 1538-3598 |
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| Abstract | In clinical and research settings worldwide, low-density lipoprotein cholesterol (LDL-C) is typically estimated using the Friedewald equation. This equation assumes a fixed factor of 5 for the ratio of triglycerides to very low-density lipoprotein cholesterol (TG:VLDL-C); however, the actual TG:VLDL-C ratio varies significantly across the range of triglyceride and cholesterol levels.
To derive and validate a more accurate method for LDL-C estimation from the standard lipid profile using an adjustable factor for the TG:VLDL-C ratio.
We used a convenience sample of consecutive clinical lipid profiles obtained from 2009 through 2011 from 1,350,908 children, adolescents, and adults in the United States. Cholesterol concentrations were directly measured after vertical spin density-gradient ultracentrifugation, and triglycerides were directly measured. Lipid distributions closely matched the population-based National Health and Nutrition Examination Survey (NHANES). Samples were randomly assigned to derivation (n = 900,605) and validation (n = 450,303) data sets.
Individual patient-level concordance in clinical practice guideline LDL-C risk classification using estimated vs directly measured LDL-C (LDL-CD).
In the derivation data set, the median TG:VLDL-C was 5.2 (IQR, 4.5-6.0). The triglyceride and non-high-density lipoprotein cholesterol (HDL-C) levels explained 65% of the variance in the TG:VLDL-C ratio. Based on strata of triglyceride and non-HDL-C values, a 180-cell table of median TG:VLDL-C values was derived and applied in the validation data set to estimate the novel LDL-C (LDL-CN). For patients with triglycerides lower than 400 mg/dL, overall concordance in guideline risk classification with LDL-CD was 91.7% (95% CI, 91.6%-91.8%) for LDL-CN vs 85.4% (95% CI, 85.3%-85.5%) for Friedewald LDL-C (LDL-CF) (P < .001). The greatest improvement in concordance occurred in classifying LDL-C lower than 70 mg/dL, especially in patients with high triglyceride levels. In patients with an estimated LDL-C lower than 70 mg/dL, LDL-CD was also lower than 70 mg/dL in 94.3% (95% CI, 93.9%-94.7%) for LDL-CN vs 79.9% (95% CI, 79.3%-80.4%) for LDL-CF in samples with triglyceride levels of 100 to 149 mg/dL; 92.4% (95% CI, 91.7%-93.1%) for LDL-CN vs 61.3% (95% CI, 60.3%-62.3%) for LDL-CF in samples with triglyceride levels of 150 to 199 mg/dL; and 84.0% (95% CI, 82.9%-85.1%) for LDL-CN vs 40.3% (95% CI, 39.4%-41.3%) for LDL-CF in samples with triglyceride levels of 200 to 399 mg/dL (P < .001 for each comparison).
A novel method to estimate LDL-C using an adjustable factor for the TG:VLDL-C ratio provided more accurate guideline risk classification than the Friedewald equation. These findings require external validation, as well as assessment of their clinical importance. The implementation of these findings into clinical practice would be straightforward and at virtually no cost.
clinicaltrials.gov Identifier: NCT01698489. |
|---|---|
| AbstractList | In clinical and research settings worldwide, low-density lipoprotein cholesterol (LDL-C) is typically estimated using the Friedewald equation. This equation assumes a fixed factor of 5 for the ratio of triglycerides to very low-density lipoprotein cholesterol (TG:VLDL-C); however, the actual TG:VLDL-C ratio varies significantly across the range of triglyceride and cholesterol levels.IMPORTANCEIn clinical and research settings worldwide, low-density lipoprotein cholesterol (LDL-C) is typically estimated using the Friedewald equation. This equation assumes a fixed factor of 5 for the ratio of triglycerides to very low-density lipoprotein cholesterol (TG:VLDL-C); however, the actual TG:VLDL-C ratio varies significantly across the range of triglyceride and cholesterol levels.To derive and validate a more accurate method for LDL-C estimation from the standard lipid profile using an adjustable factor for the TG:VLDL-C ratio.OBJECTIVETo derive and validate a more accurate method for LDL-C estimation from the standard lipid profile using an adjustable factor for the TG:VLDL-C ratio.We used a convenience sample of consecutive clinical lipid profiles obtained from 2009 through 2011 from 1,350,908 children, adolescents, and adults in the United States. Cholesterol concentrations were directly measured after vertical spin density-gradient ultracentrifugation, and triglycerides were directly measured. Lipid distributions closely matched the population-based National Health and Nutrition Examination Survey (NHANES). Samples were randomly assigned to derivation (n = 900,605) and validation (n = 450,303) data sets.DESIGN, SETTING, AND PARTICIPANTSWe used a convenience sample of consecutive clinical lipid profiles obtained from 2009 through 2011 from 1,350,908 children, adolescents, and adults in the United States. Cholesterol concentrations were directly measured after vertical spin density-gradient ultracentrifugation, and triglycerides were directly measured. Lipid distributions closely matched the population-based National Health and Nutrition Examination Survey (NHANES). Samples were randomly assigned to derivation (n = 900,605) and validation (n = 450,303) data sets.Individual patient-level concordance in clinical practice guideline LDL-C risk classification using estimated vs directly measured LDL-C (LDL-CD).MAIN OUTCOMES AND MEASURESIndividual patient-level concordance in clinical practice guideline LDL-C risk classification using estimated vs directly measured LDL-C (LDL-CD).In the derivation data set, the median TG:VLDL-C was 5.2 (IQR, 4.5-6.0). The triglyceride and non-high-density lipoprotein cholesterol (HDL-C) levels explained 65% of the variance in the TG:VLDL-C ratio. Based on strata of triglyceride and non-HDL-C values, a 180-cell table of median TG:VLDL-C values was derived and applied in the validation data set to estimate the novel LDL-C (LDL-CN). For patients with triglycerides lower than 400 mg/dL, overall concordance in guideline risk classification with LDL-CD was 91.7% (95% CI, 91.6%-91.8%) for LDL-CN vs 85.4% (95% CI, 85.3%-85.5%) for Friedewald LDL-C (LDL-CF) (P < .001). The greatest improvement in concordance occurred in classifying LDL-C lower than 70 mg/dL, especially in patients with high triglyceride levels. In patients with an estimated LDL-C lower than 70 mg/dL, LDL-CD was also lower than 70 mg/dL in 94.3% (95% CI, 93.9%-94.7%) for LDL-CN vs 79.9% (95% CI, 79.3%-80.4%) for LDL-CF in samples with triglyceride levels of 100 to 149 mg/dL; 92.4% (95% CI, 91.7%-93.1%) for LDL-CN vs 61.3% (95% CI, 60.3%-62.3%) for LDL-CF in samples with triglyceride levels of 150 to 199 mg/dL; and 84.0% (95% CI, 82.9%-85.1%) for LDL-CN vs 40.3% (95% CI, 39.4%-41.3%) for LDL-CF in samples with triglyceride levels of 200 to 399 mg/dL (P < .001 for each comparison).RESULTSIn the derivation data set, the median TG:VLDL-C was 5.2 (IQR, 4.5-6.0). The triglyceride and non-high-density lipoprotein cholesterol (HDL-C) levels explained 65% of the variance in the TG:VLDL-C ratio. Based on strata of triglyceride and non-HDL-C values, a 180-cell table of median TG:VLDL-C values was derived and applied in the validation data set to estimate the novel LDL-C (LDL-CN). For patients with triglycerides lower than 400 mg/dL, overall concordance in guideline risk classification with LDL-CD was 91.7% (95% CI, 91.6%-91.8%) for LDL-CN vs 85.4% (95% CI, 85.3%-85.5%) for Friedewald LDL-C (LDL-CF) (P < .001). The greatest improvement in concordance occurred in classifying LDL-C lower than 70 mg/dL, especially in patients with high triglyceride levels. In patients with an estimated LDL-C lower than 70 mg/dL, LDL-CD was also lower than 70 mg/dL in 94.3% (95% CI, 93.9%-94.7%) for LDL-CN vs 79.9% (95% CI, 79.3%-80.4%) for LDL-CF in samples with triglyceride levels of 100 to 149 mg/dL; 92.4% (95% CI, 91.7%-93.1%) for LDL-CN vs 61.3% (95% CI, 60.3%-62.3%) for LDL-CF in samples with triglyceride levels of 150 to 199 mg/dL; and 84.0% (95% CI, 82.9%-85.1%) for LDL-CN vs 40.3% (95% CI, 39.4%-41.3%) for LDL-CF in samples with triglyceride levels of 200 to 399 mg/dL (P < .001 for each comparison).A novel method to estimate LDL-C using an adjustable factor for the TG:VLDL-C ratio provided more accurate guideline risk classification than the Friedewald equation. These findings require external validation, as well as assessment of their clinical importance. The implementation of these findings into clinical practice would be straightforward and at virtually no cost.CONCLUSIONS AND RELEVANCEA novel method to estimate LDL-C using an adjustable factor for the TG:VLDL-C ratio provided more accurate guideline risk classification than the Friedewald equation. These findings require external validation, as well as assessment of their clinical importance. The implementation of these findings into clinical practice would be straightforward and at virtually no cost.clinicaltrials.gov Identifier: NCT01698489.TRIAL REGISTRATIONclinicaltrials.gov Identifier: NCT01698489. In clinical and research settings worldwide, low-density lipoprotein cholesterol (LDL-C) is typically estimated using the Friedewald equation. This equation assumes a fixed factor of 5 for the ratio of triglycerides to very low-density lipoprotein cholesterol (TG:VLDL-C); however, the actual TG:VLDL-C ratio varies significantly across the range of triglyceride and cholesterol levels. To derive and validate a more accurate method for LDL-C estimation from the standard lipid profile using an adjustable factor for the TG:VLDL-C ratio. We used a convenience sample of consecutive clinical lipid profiles obtained from 2009 through 2011 from 1,350,908 children, adolescents, and adults in the United States. Cholesterol concentrations were directly measured after vertical spin density-gradient ultracentrifugation, and triglycerides were directly measured. Lipid distributions closely matched the population-based National Health and Nutrition Examination Survey (NHANES). Samples were randomly assigned to derivation (n = 900,605) and validation (n = 450,303) data sets. Individual patient-level concordance in clinical practice guideline LDL-C risk classification using estimated vs directly measured LDL-C (LDL-CD). In the derivation data set, the median TG:VLDL-C was 5.2 (IQR, 4.5-6.0). The triglyceride and non-high-density lipoprotein cholesterol (HDL-C) levels explained 65% of the variance in the TG:VLDL-C ratio. Based on strata of triglyceride and non-HDL-C values, a 180-cell table of median TG:VLDL-C values was derived and applied in the validation data set to estimate the novel LDL-C (LDL-CN). For patients with triglycerides lower than 400 mg/dL, overall concordance in guideline risk classification with LDL-CD was 91.7% (95% CI, 91.6%-91.8%) for LDL-CN vs 85.4% (95% CI, 85.3%-85.5%) for Friedewald LDL-C (LDL-CF) (P < .001). The greatest improvement in concordance occurred in classifying LDL-C lower than 70 mg/dL, especially in patients with high triglyceride levels. In patients with an estimated LDL-C lower than 70 mg/dL, LDL-CD was also lower than 70 mg/dL in 94.3% (95% CI, 93.9%-94.7%) for LDL-CN vs 79.9% (95% CI, 79.3%-80.4%) for LDL-CF in samples with triglyceride levels of 100 to 149 mg/dL; 92.4% (95% CI, 91.7%-93.1%) for LDL-CN vs 61.3% (95% CI, 60.3%-62.3%) for LDL-CF in samples with triglyceride levels of 150 to 199 mg/dL; and 84.0% (95% CI, 82.9%-85.1%) for LDL-CN vs 40.3% (95% CI, 39.4%-41.3%) for LDL-CF in samples with triglyceride levels of 200 to 399 mg/dL (P < .001 for each comparison). A novel method to estimate LDL-C using an adjustable factor for the TG:VLDL-C ratio provided more accurate guideline risk classification than the Friedewald equation. These findings require external validation, as well as assessment of their clinical importance. The implementation of these findings into clinical practice would be straightforward and at virtually no cost. clinicaltrials.gov Identifier: NCT01698489. |
| Author | Blumenthal, Roger S Elshazly, Mohamed B Kwiterovich, Peter O Jones, Steven R Martin, Seth S Blaha, Michael J Toth, Peter P |
| Author_xml | – sequence: 1 givenname: Seth S surname: Martin fullname: Martin, Seth S organization: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland – sequence: 2 givenname: Michael J surname: Blaha fullname: Blaha, Michael J – sequence: 3 givenname: Mohamed B surname: Elshazly fullname: Elshazly, Mohamed B – sequence: 4 givenname: Peter P surname: Toth fullname: Toth, Peter P – sequence: 5 givenname: Peter O surname: Kwiterovich fullname: Kwiterovich, Peter O – sequence: 6 givenname: Roger S surname: Blumenthal fullname: Blumenthal, Roger S – sequence: 7 givenname: Steven R surname: Jones fullname: Jones, Steven R |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24240933$$D View this record in MEDLINE/PubMed |
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| References_xml | – reference: 16214597 - Lancet. 2005 Oct 8;366(9493):1267-78 – reference: 15939107 - Int J Cardiol. 2005 Jun 22;102(1):117-20 – reference: 24122913 - Clin Cardiol. 2013 Nov;36(11):641-8 – reference: 23524048 - J Am Coll Cardiol. 2013 Aug 20;62(8):732-9 – reference: 3306674 - Proc Natl Acad Sci U S A. 1987 Sep;84(17):6259-61 – reference: 21067804 - Lancet. 2010 Nov 13;376(9753):1670-81 – reference: 5333081 - N Engl J Med. 1967 Jan 5;276(1):34-42 contd – reference: 5332928 - N Engl J Med. 1967 Jan 12;276(2):94-103 contd – reference: 23147400 - Arch Intern Med. 2012 Dec 10;172(22):1707-10 – reference: 19920234 - JAMA. 2009 Nov 18;302(19):2104-10 – reference: 18426324 - Arch Iran Med. 2008 May;11(3):318-21 – reference: 19812802 - Can J Cardiol. 2009 Oct;25(10):567-79 – reference: 20487572 - Lipids Health Dis. 2010;9:52 – reference: 24240929 - JAMA. 2013 Nov 20;310(19):2043-4 – reference: 9690912 - Atherosclerosis. 1998 Jun;138(2):289-99 – reference: 11368702 - JAMA. 2001 May 16;285(19):2486-97 – reference: 5333808 - N Engl J Med. 1967 Jan 26;276(4):215-25 contd – reference: 3464768 - JAMA. 1986 Nov 7;256(17):2372-7 – reference: 5334266 - N Engl J Med. 1967 Jan 19;276(3):148-56 contd – reference: 10545069 - Clin Chem. 1999 Nov;45(11):1981-7 – reference: 24449350 - Dtsch Med Wochenschr. 2014 Jan;139(5):180 – reference: 23401886 - Arch Intern Med. 2012 Dec 10;172(22):1705-6 – reference: 15249516 - Circulation. 2004 Jul 13;110(2):227-39 – reference: 4337382 - Clin Chem. 1972 Jun;18(6):499-502 – reference: 21712404 - Eur Heart J. 2011 Jul;32(14):1769-818 – reference: 22871867 - JAMA. 2012 Aug 8;308(6):575-6 – reference: 22910761 - JAMA. 2012 Aug 22;308(8):816-7 – reference: 7586510 - Clin Chem. 1995 Oct;41(10):1414-20 – reference: 22052934 - Circulation. 2011 Nov 29;124(22):2458-73 – reference: 18402913 - J Am Coll Cardiol. 2008 Apr 15;51(15):1512-24 – reference: 18711012 - Circulation. 2008 Sep 2;118(10):993-1001 – reference: 22910753 - JAMA. 2012 Aug 22;308(8):773-4 – reference: 3197296 - Clin Chem. 1988 Dec;34(12):2532-4 – reference: 12485966 - Circulation. 2002 Dec 17;106(25):3143-421 – reference: 5334042 - N Engl J Med. 1967 Feb 2;276(5):273-81 concl – reference: 17110240 - Clin Lab Med. 2006 Dec;26(4):787-802 – reference: 21600530 - J Clin Lipidol. 2011 Jun;5(3 Suppl):S9-17 – reference: 23108766 - Ann Clin Biochem. 2013 Jan;50(Pt 1):13-9 |
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| Snippet | In clinical and research settings worldwide, low-density lipoprotein cholesterol (LDL-C) is typically estimated using the Friedewald equation. This equation... |
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| SubjectTerms | Adolescent Adult Child Cholesterol, LDL - analysis Cholesterol, VLDL - analysis Female Humans Hypercholesterolemia - diagnosis Male Models, Theoretical Practice Guidelines as Topic Random Allocation Reference Values Risk Assessment Triglycerides - analysis |
| Title | Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile |
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