Association of plasma homocysteine with the atherogenic index of plasma and modification by body mass index: a cross-sectional study.

OBJECTIVE: Hyperhomocysteinemia is generally considered an independent risk factor for cardiovascular disease; nevertheless, the independent connection between plasma homocysteine (HCY) and the atherogenic index of plasma (AIP), which integrates the risk of atherogenic lipids, has not been completely elucidated. The potential biological mechanisms relating HCY to AIP also need to be clarified further. This investigation investigates the relation between plasma HCY and AIP in a general adult group, examines whether inflammation and liver function statistically influence this relation, and evaluates the effect of body mass index (BMI) on the relationship. In this cross-sectional study, 887 adults were analyzed in the final stage. Outliers were excluded based on a lenient threefold interquartile range criterion to maintain biologically reasonable variations. The relationship between HCY and continuous AIP was analyzed by multiple linear regression, while the relation with high AIP risk was studied by logistic regression. Mediation analysis was performed using the bootstrap method, with white blood cell count (WBC) and alanine aminotransferase (ALT) as putative mediators. Subgroup analysis and formal interaction tests were conducted to investigate if the association between HCY and AIP varied among different clinical groups.

RESULTS: Plasma HCY was positively correlated with AIP (r = 0.294, P < 0.001). In multivariable linear regression, each 1 μmol/L increase in HCY was associated with a 0.0113-unit increase in AIP after adjustment for potential confounders (P < 0.001). Logistic regression showed that each 1 μmol/L increase in HCY was associated with a higher likelihood of high AIP risk (OR = 1.282, 95% CI: 1.186-1.387). Bootstrap mediation analyses did not identify significant indirect effects through either WBC or ALT. Subgroup analyses further showed that the positive association between HCY and AIP was stronger in participants with BMI ≥ 24 kg/m (=0.014) than in those with BMI < 24 kg/m (=0.008), with significant effect modification by BMI (P for interaction = 0.006).

CONCLUSION: Plasma HCY was independently and positively associated with AIP, and this relationship was more pronounced among overweight or obese participants. The association appeared to be driven mainly by a direct pathway, with no statistically significant mediation through the selected markers of inflammation or liver function. These findings suggest that BMI should be considered when evaluating the lipid-related atherogenic risk associated with elevated HCY.