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

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 tri...

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Published inAtherosclerosis Vol. 249; pp. 59 - 64
Main Authors Lupton, Joshua R., Quispe, Renato, Kulkarni, Krishnaji, Martin, Seth S., Jones, Steven R.
Format Journal Article
LanguageEnglish
Published Ireland Elsevier Ireland Ltd 01.06.2016
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ISSN0021-9150
1879-1484
1879-1484
DOI10.1016/j.atherosclerosis.2016.03.031

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Abstract 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. 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. 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. 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. [Display omitted] •We examine the association between homocysteine (tHcy) and an extended lipid panel.•We compare lipid distributions between the highest and lowest quartile of tHcy.•We adjust for age, sex, HbA1c, insulin, creatinine, and blood urea nitrogen.•After adjustment, higher tHcy was not associated with any lipid differences.
AbstractList 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. 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. 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. 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. [Display omitted] •We examine the association between homocysteine (tHcy) and an extended lipid panel.•We compare lipid distributions between the highest and lowest quartile of tHcy.•We adjust for age, sex, HbA1c, insulin, creatinine, and blood urea nitrogen.•After adjustment, higher tHcy was not associated with any lipid differences.
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.
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. 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. 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. 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.
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.BACKGROUND AND AIMSHyperhomocysteinemia 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.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.METHODSOur 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.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.RESULTSIn 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.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.CONCLUSIONSAlthough 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.
Author Kulkarni, Krishnaji
Lupton, Joshua R.
Martin, Seth S.
Quispe, Renato
Jones, Steven R.
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Keywords Lipoprotein
Homocysteine
Kidney function
Glycemic status
Lipid
Atherosclerosis
Language English
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Snippet Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, but the mechanism for this risk remains unclear. While reducing serum total...
Abstract Background and aims Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, but the mechanism for this risk remains unclear....
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crossref
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StartPage 59
SubjectTerms Aged
Atherosclerosis
Atherosclerosis - blood
Blood Urea Nitrogen
Cardiovascular
Creatinine - blood
Databases, Factual
Female
Glycated Hemoglobin A - metabolism
Glycemic status
Homocysteine
Homocysteine - blood
Humans
Insulin - blood
Kidney - physiology
Kidney function
Lipid
Lipids - blood
Lipoprotein
Lipoproteins - blood
Male
Middle Aged
Title Serum homocysteine is not independently associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-21) study
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https://dx.doi.org/10.1016/j.atherosclerosis.2016.03.031
https://www.ncbi.nlm.nih.gov/pubmed/27065242
https://www.proquest.com/docview/1791321806
Volume 249
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