Serum homocysteine is not independently associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-21) study

Joshua R. Lupton, Renato Quispe, Krishnaji Kulkarni, Seth Martin, Steven Jones

Research output: Contribution to journalArticle

Abstract

Background and aims: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, but the mechanism for this risk remains unclear. While reducing serum total homocysteine (tHcy) has been shown to decrease strokes, there is no evidence for an effect on myocardial infarctions in randomized controlled trials. This study aims to examine the relationship between tHcy and several lipid measures. Methods: Our analyses included 18,297 U.S. adults from the Very Large Database of Lipids who had an extended lipid panel including direct measurement of triglycerides (TG), and the cholesterol concentration of low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), non-HDL-C, very low-density lipoprotein (VLDL-C), and remnant-lipoprotein cholesterol (RLP-C: IDL-C + VLDL3-C). Additional measurements were tHcy, hemoglobin A1c (HbA1c), insulin, creatinine, and blood urea nitrogen (BUN). Subjects were categorized into tHcy quartiles. Linear regression models were performed using lipids and tHcy as dependent and independent variables respectively, and further adjusted with age, sex, HbA1c, insulin, creatinine, and BUN levels in multivariable regression. Results: In unadjusted analysis, levels of LDL-C (p <0.001), non-HDL-C (p <0.001) and HDL-C (p <0.001) were 7-10% lower whereas levels of TG (p <0.001), VLDL-C (p = 0.016) and RLP-C (p <0.001) were 2-6% higher in the highest tHcy quartile. These associations between tHcy levels and lipids were eliminated (p-value range: 0.101-0.750) when controlling for age, sex, HbA1c, insulin, creatinine, and BUN. Conclusions: Although high levels of tHcy were associated with 2-6% higher TG-rich lipoproteins in unadjusted analysis, after adjustment for confounders our findings do not support the hypothesis that hyperhomocysteinemia is associated with an atherogenic lipid profile.

Original languageEnglish (US)
Pages (from-to)59-64
Number of pages6
JournalAtherosclerosis
Volume249
DOIs
StatePublished - Jun 1 2016

Fingerprint

Homocysteine
Databases
Lipids
Serum
Blood Urea Nitrogen
Creatinine
Hyperhomocysteinemia
Hemoglobins
Triglycerides
Insulin
Linear Models
VLDL Lipoproteins
HDL Lipoproteins
LDL Cholesterol
Lipoproteins
Cardiovascular Diseases
Randomized Controlled Trials
Stroke
Myocardial Infarction

Keywords

  • Atherosclerosis
  • Glycemic status
  • Homocysteine
  • Kidney function
  • Lipid
  • Lipoprotein

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Serum homocysteine is not independently associated with an atherogenic lipid profile : The Very Large Database of Lipids (VLDL-21) study. / Lupton, Joshua R.; Quispe, Renato; Kulkarni, Krishnaji; Martin, Seth; Jones, Steven.

In: Atherosclerosis, Vol. 249, 01.06.2016, p. 59-64.

Research output: Contribution to journalArticle

@article{55bb24ad2a0d4af2b1bd164009fcd8ac,
title = "Serum homocysteine is not independently associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-21) study",
abstract = "Background and aims: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, but the mechanism for this risk remains unclear. While reducing serum total homocysteine (tHcy) has been shown to decrease strokes, there is no evidence for an effect on myocardial infarctions in randomized controlled trials. This study aims to examine the relationship between tHcy and several lipid measures. Methods: Our analyses included 18,297 U.S. adults from the Very Large Database of Lipids who had an extended lipid panel including direct measurement of triglycerides (TG), and the cholesterol concentration of low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), non-HDL-C, very low-density lipoprotein (VLDL-C), and remnant-lipoprotein cholesterol (RLP-C: IDL-C + VLDL3-C). Additional measurements were tHcy, hemoglobin A1c (HbA1c), insulin, creatinine, and blood urea nitrogen (BUN). Subjects were categorized into tHcy quartiles. Linear regression models were performed using lipids and tHcy as dependent and independent variables respectively, and further adjusted with age, sex, HbA1c, insulin, creatinine, and BUN levels in multivariable regression. Results: In unadjusted analysis, levels of LDL-C (p <0.001), non-HDL-C (p <0.001) and HDL-C (p <0.001) were 7-10{\%} lower whereas levels of TG (p <0.001), VLDL-C (p = 0.016) and RLP-C (p <0.001) were 2-6{\%} higher in the highest tHcy quartile. These associations between tHcy levels and lipids were eliminated (p-value range: 0.101-0.750) when controlling for age, sex, HbA1c, insulin, creatinine, and BUN. Conclusions: Although high levels of tHcy were associated with 2-6{\%} higher TG-rich lipoproteins in unadjusted analysis, after adjustment for confounders our findings do not support the hypothesis that hyperhomocysteinemia is associated with an atherogenic lipid profile.",
keywords = "Atherosclerosis, Glycemic status, Homocysteine, Kidney function, Lipid, Lipoprotein",
author = "Lupton, {Joshua R.} and Renato Quispe and Krishnaji Kulkarni and Seth Martin and Steven Jones",
year = "2016",
month = "6",
day = "1",
doi = "10.1016/j.atherosclerosis.2016.03.031",
language = "English (US)",
volume = "249",
pages = "59--64",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Serum homocysteine is not independently associated with an atherogenic lipid profile

T2 - The Very Large Database of Lipids (VLDL-21) study

AU - Lupton, Joshua R.

AU - Quispe, Renato

AU - Kulkarni, Krishnaji

AU - Martin, Seth

AU - Jones, Steven

PY - 2016/6/1

Y1 - 2016/6/1

N2 - Background and aims: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, but the mechanism for this risk remains unclear. While reducing serum total homocysteine (tHcy) has been shown to decrease strokes, there is no evidence for an effect on myocardial infarctions in randomized controlled trials. This study aims to examine the relationship between tHcy and several lipid measures. Methods: Our analyses included 18,297 U.S. adults from the Very Large Database of Lipids who had an extended lipid panel including direct measurement of triglycerides (TG), and the cholesterol concentration of low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), non-HDL-C, very low-density lipoprotein (VLDL-C), and remnant-lipoprotein cholesterol (RLP-C: IDL-C + VLDL3-C). Additional measurements were tHcy, hemoglobin A1c (HbA1c), insulin, creatinine, and blood urea nitrogen (BUN). Subjects were categorized into tHcy quartiles. Linear regression models were performed using lipids and tHcy as dependent and independent variables respectively, and further adjusted with age, sex, HbA1c, insulin, creatinine, and BUN levels in multivariable regression. Results: In unadjusted analysis, levels of LDL-C (p <0.001), non-HDL-C (p <0.001) and HDL-C (p <0.001) were 7-10% lower whereas levels of TG (p <0.001), VLDL-C (p = 0.016) and RLP-C (p <0.001) were 2-6% higher in the highest tHcy quartile. These associations between tHcy levels and lipids were eliminated (p-value range: 0.101-0.750) when controlling for age, sex, HbA1c, insulin, creatinine, and BUN. Conclusions: Although high levels of tHcy were associated with 2-6% higher TG-rich lipoproteins in unadjusted analysis, after adjustment for confounders our findings do not support the hypothesis that hyperhomocysteinemia is associated with an atherogenic lipid profile.

AB - Background and aims: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, but the mechanism for this risk remains unclear. While reducing serum total homocysteine (tHcy) has been shown to decrease strokes, there is no evidence for an effect on myocardial infarctions in randomized controlled trials. This study aims to examine the relationship between tHcy and several lipid measures. Methods: Our analyses included 18,297 U.S. adults from the Very Large Database of Lipids who had an extended lipid panel including direct measurement of triglycerides (TG), and the cholesterol concentration of low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), non-HDL-C, very low-density lipoprotein (VLDL-C), and remnant-lipoprotein cholesterol (RLP-C: IDL-C + VLDL3-C). Additional measurements were tHcy, hemoglobin A1c (HbA1c), insulin, creatinine, and blood urea nitrogen (BUN). Subjects were categorized into tHcy quartiles. Linear regression models were performed using lipids and tHcy as dependent and independent variables respectively, and further adjusted with age, sex, HbA1c, insulin, creatinine, and BUN levels in multivariable regression. Results: In unadjusted analysis, levels of LDL-C (p <0.001), non-HDL-C (p <0.001) and HDL-C (p <0.001) were 7-10% lower whereas levels of TG (p <0.001), VLDL-C (p = 0.016) and RLP-C (p <0.001) were 2-6% higher in the highest tHcy quartile. These associations between tHcy levels and lipids were eliminated (p-value range: 0.101-0.750) when controlling for age, sex, HbA1c, insulin, creatinine, and BUN. Conclusions: Although high levels of tHcy were associated with 2-6% higher TG-rich lipoproteins in unadjusted analysis, after adjustment for confounders our findings do not support the hypothesis that hyperhomocysteinemia is associated with an atherogenic lipid profile.

KW - Atherosclerosis

KW - Glycemic status

KW - Homocysteine

KW - Kidney function

KW - Lipid

KW - Lipoprotein

UR - http://www.scopus.com/inward/record.url?scp=84962757718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962757718&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2016.03.031

DO - 10.1016/j.atherosclerosis.2016.03.031

M3 - Article

C2 - 27065242

AN - SCOPUS:84962757718

VL - 249

SP - 59

EP - 64

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

ER -