Ratio of dense to buoyant LDL subclass is associated with LDL density phenotype (VLDL-5)

Haitham M. Ahmed, Mohamed B. Elshazly, Seth Martin, Michael Blaha, Krishnaji R. Kulkarni, Steven Jones

Research output: Contribution to journalArticle

Abstract

Background: Dense LDL phenotypes are associated with increased atherogenicity, and are commonly evaluated for the purposes of atherosclerosis research and cardiovascular risk discrimination. Objective: To examine the ability of LDL subclasses, expressed as a ratio of dense-to-buoyant subclass, to predict LDL density phenotype. Methods: LDL subclasses and density phenotypes were measured with vertical auto profile ultracentrifugation in 1,339,898 consecutive lipid profiles between 2009 and 2011 from a clinical sample of US adults. Logarithmic LDL density ratio (LLDR) was calculated as ratio of dense-to-buoyant LDL subclasses, ln[(LDL3-C + LDL4-C)/(LDL1-C +LDL2-C)]; normally distributed after log-transformation. LLDR was compared to density phenotype using ROC C-statistic with optimum sensitivity and specificity cutpoints determined. Results: There was a strong, highly significant, monotonic increase in LLDR across progressively higher density phenotypes (p-4, optimum cutpoint -4 optimum cutpoint >0.905, sensitivity 81%, specificity 86%. There was also a positive correlation between LLDR and LDL Max Time (R2=0.802). Conclusion: LLDR is a convenient, easily calculated, and continuous variable that is strongly associated with LDL density phenotype and LDL Max Time. Further research is needed to investigate the relationship between lipoprotein density and size, and whether LLDR provides more cardiovascular risk discrimination than LDL density phenotype.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalOpen Chemical and Biomedical Methods Journal
Volume6
Issue number1
StatePublished - 2013

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Phenotype
Lipoproteins
Lipids
Statistics
oxidized low density lipoprotein
LDL Lipoproteins
Sensitivity and Specificity
Ultracentrifugation
Research
Atherosclerosis

Keywords

  • Atherosclerosis
  • Hyperlipidemia
  • LDL cholesterol
  • Lipids
  • Ultracentrifugation

ASJC Scopus subject areas

  • Biochemistry
  • Biomedical Engineering

Cite this

Ratio of dense to buoyant LDL subclass is associated with LDL density phenotype (VLDL-5). / Ahmed, Haitham M.; Elshazly, Mohamed B.; Martin, Seth; Blaha, Michael; Kulkarni, Krishnaji R.; Jones, Steven.

In: Open Chemical and Biomedical Methods Journal, Vol. 6, No. 1, 2013, p. 1-5.

Research output: Contribution to journalArticle

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AU - Elshazly, Mohamed B.

AU - Martin, Seth

AU - Blaha, Michael

AU - Kulkarni, Krishnaji R.

AU - Jones, Steven

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N2 - Background: Dense LDL phenotypes are associated with increased atherogenicity, and are commonly evaluated for the purposes of atherosclerosis research and cardiovascular risk discrimination. Objective: To examine the ability of LDL subclasses, expressed as a ratio of dense-to-buoyant subclass, to predict LDL density phenotype. Methods: LDL subclasses and density phenotypes were measured with vertical auto profile ultracentrifugation in 1,339,898 consecutive lipid profiles between 2009 and 2011 from a clinical sample of US adults. Logarithmic LDL density ratio (LLDR) was calculated as ratio of dense-to-buoyant LDL subclasses, ln[(LDL3-C + LDL4-C)/(LDL1-C +LDL2-C)]; normally distributed after log-transformation. LLDR was compared to density phenotype using ROC C-statistic with optimum sensitivity and specificity cutpoints determined. Results: There was a strong, highly significant, monotonic increase in LLDR across progressively higher density phenotypes (p-4, optimum cutpoint -4 optimum cutpoint >0.905, sensitivity 81%, specificity 86%. There was also a positive correlation between LLDR and LDL Max Time (R2=0.802). Conclusion: LLDR is a convenient, easily calculated, and continuous variable that is strongly associated with LDL density phenotype and LDL Max Time. Further research is needed to investigate the relationship between lipoprotein density and size, and whether LLDR provides more cardiovascular risk discrimination than LDL density phenotype.

AB - Background: Dense LDL phenotypes are associated with increased atherogenicity, and are commonly evaluated for the purposes of atherosclerosis research and cardiovascular risk discrimination. Objective: To examine the ability of LDL subclasses, expressed as a ratio of dense-to-buoyant subclass, to predict LDL density phenotype. Methods: LDL subclasses and density phenotypes were measured with vertical auto profile ultracentrifugation in 1,339,898 consecutive lipid profiles between 2009 and 2011 from a clinical sample of US adults. Logarithmic LDL density ratio (LLDR) was calculated as ratio of dense-to-buoyant LDL subclasses, ln[(LDL3-C + LDL4-C)/(LDL1-C +LDL2-C)]; normally distributed after log-transformation. LLDR was compared to density phenotype using ROC C-statistic with optimum sensitivity and specificity cutpoints determined. Results: There was a strong, highly significant, monotonic increase in LLDR across progressively higher density phenotypes (p-4, optimum cutpoint -4 optimum cutpoint >0.905, sensitivity 81%, specificity 86%. There was also a positive correlation between LLDR and LDL Max Time (R2=0.802). Conclusion: LLDR is a convenient, easily calculated, and continuous variable that is strongly associated with LDL density phenotype and LDL Max Time. Further research is needed to investigate the relationship between lipoprotein density and size, and whether LLDR provides more cardiovascular risk discrimination than LDL density phenotype.

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