Association of Lp-PLA ₂ activity and LDL size with interleukin-6, an inflammatory cytokine and oxidized LDL, a marker of oxidative stress, in women with metabolic syndrome

Objective: We investigated an association between lipoprotein-associated phospholipase A ₂ (Lp-PLA ₂) activity, inflammation, and oxidative stress in women with metabolic syndrome (MS). Methods: We performed a case-control study in MS women (n=368) and non-MS women (n=854). Lp-PLA ₂ activity LDL particle size; leukocyte number; ox-LDL, LDL-cholesterol, TNF-α, IL-6, and CRP levels were measured. Results: MS women had smaller LDL particle size; higher plasma ox-LDL levels and Lp-PLA ₂ activity; and higher serum TNF-α, IL-6, and CRP, than non-MS women. In controls, Lp-PLA ₂ activity weakly but significantly correlated with LDL-cholesterol; in MS women, Lp-PLA ₂ activity positively correlated with LDL-cholesterol, ox-LDL, TNF-α, and IL-6 after adjusting for age and BMI. The relationship between Lp-PLA ₂ activity and ox-LDL still maintained after further adjustment for LDL-cholesterol. Additionally, Lp-PLA ₂ activity together with LDL particle size were significant independent predictors of MS (multivariate analysis), and ox-LDL was a major contributor to the increase in Lp-PLA ₂ activity in MS women (multiple stepwise regression). In a subgroup analysis, Lp-PLA ₂ activity was negatively associated with IL-6 levels in non-MS postmenopausal women, but positively with IL-6 in both postmenopausal and premenopausal women with MS. Postmenopausal women with MS had significantly higher Lp-PLA ₂ activity, ox-LDL and IL-6 than those without MS, and premenopausal women with or without MS, after the adjustment. Conclusions: Elevated plasma Lp-PLA ₂ activity was associated with an increase in inflammatory cytokines, particularly IL-6 and ox-LDL in MS women. This association was also affected by menopause status, suggesting that Lp-PLA ₂ may represent a novel marker for oxidation and inflammation in MS.