Background: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, but the mechanism for this risk remains unclear. Complicating this association, reducing serum homocysteine (Hcy) has not been shown to decrease cardiovascular disease events in randomized controlled trials. This study aims to examine the relationship between Hcy and several lipid measures.
Methods: Our analyses included a subset of 18,297 U.S. adults from the Very Large Database of Lipids, who had an extended lipid panel by density gradient ultracentrifugation, which included 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 levels of Hcy, hemoglobin A1c (HbA1c), insulin, creatinine, and blood urea nitrogen (BUN). Subjects were categorized into Hcy quartiles. Linear regression models were performed using lipid measures and Hcy as dependent and independent variables respectively, and further adjusted with potential confounders (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 Hcy quartile. These associations between Hcy 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 Hcy 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.