This study showed that Lp-PLA2 activity in adolescence is associated with many cardimetabolic parameters. The factors that had an impact in the activity of the enzyme, from the most to the least important, were the Apo B/Apo AI ratio, waist circumference, glucose and HDL size.
Our results demonstrated the negative effect of obesity on Lp-PLA2 activity, which were reinforced by waist circumference and fat mass percentage. Among the anthropometric variables the waist circumference was the most important factor explaining the variation in the Lp-PLA2 activity. This fact confirms the relevance of the body fat location. Interestingly, analysis of correlations in individual groups did not show association with healthy weight and overweight adolescents, except for fat mass percentage and Lp-PLA2 activity. In this sense, Taylor and Hergenroeder demonstrated that elevated waist circumference in male adolescents was associated with an increased risk of cardiometabolic disease and overweight females with elevated waist circumference were likely to have elevated blood pressure .
In addition, we demonstrated for the first time the strong impact of Apo B/Apo AI ratio on changes in Lp-PLA2 activity; more specifically, the changes in these apolipoproteins were associated with a 73.5 times higher risk of elevated Lp-PLA2 activity. Recently, Hatoum et al., studying patients between 50 and 60 years old, observed that the enzyme was modestly associated with total cholesterol, LDL-C, Apo B and BMI; however, the lipid adjustment attenuates the relation between BMI and Lp-PLA2. The atherogenic role of Lp-PLA2 was widely associated to LDL-C [16, 35]. On the contrary, Okamura et al. suggested that Lp-PLA2 in HDL plays an antiaterogenic action. This observation was reinforced by a high LDL-Lp-PLA2 to HDL-Lp-PLA2 ratio verified in patients with atrial fibrillation. In the same way, Rizos et al. and Lagos et al. observed a high total Lp-PLA2 activity in patients with metabolic syndrome, however, HDL-Lp-PLA2 showed low activity. Accordingly, our results confirm the impact of HDL and LDL on Lp-PLA2 activity given the strong association of this enzyme with Apo B/Apo AI ratio, that was the most important parameter related to the risk of increasing of Lp-PLA2 activity in adolescents.
The negative association of Lp-PLA2 with HDL-size signals a possible scenario where the functionality of HDL particles is impaired. Accordingly, Pascot et al.,  showed that the small HDL particle has been associated with atherogenic dyslipidemic profile and hyperinsulinemia. More recently, Medina-Urrutia et al. demonstrated that adolescents with small HDL have reduced HDL-C, high triglycerides and HOMA-IR. Rizos et al. verified that patients with metabolic syndrome have higher Lp-PLA2 than the control group, but the enzyme linked to HDL-Lp-PLA2 was lower in this group and negatively associated with HOMA-IR.
Tsimikas et al., analyzing patients with or without cardiovascular events, observed that Lp-PLA2 was positively correlated with HOMA-IR in the two groups; nonetheless, the correlation was higher in the cardiovascular event group. In this fashion, our study demonstrated that this enzyme was positively correlated with glucose, reinforcing the notion of the negative impact of obesity on glucose metabolism.
Previous studies have shown that Lp-PLA2 is a good marker for cardiovascular risk in adults [10, 15, 40]. For instance, the Lp-PLA2 Studies Collaboration showed that the enzyme activity was positively correlated with non-HDL-C, LDL-C, Apo B and negatively correlated with HDL-C and Apo AI . In the same way, Sabatine et al. emphasized that Lp-PLA2 is an important predictor of coronary revascularization and unstable angina, and can also be treated as a new risk factor.
In contrast to many investigations related to negative impact of obesity on lipids, few studies including children and adolescents that linked obesity, lipid profile and Lp-PLA2. At the moment, there are only four studies evaluating Lp-PLA2 in children and adolescents. First, Okada et al. showed that the Lp-PLA2 concentration of 17 obese children (11.9 ± 0.7 years old) was positively correlated with weight, waist/height ratio, subscapular/triceps ratio and LDL-C level. Castro et al. compared diabetic young adults and adolescents (24.9 ± 7.8 years old) with controls (24.3 ± 9.6 years old), observing higher Lp-PLA2 activity and elevated susceptibility for oxidized LDL in diabetic patients. Subsequently, Nagel et al., studying children with 10 years old, observed that overweight was positively associated with cardiometabolic markers, including Lp-PLA2 concentration. In 2011, Motykova et al. , examining a group of non-diabetic obese/overweight children, verified that body weight reduction determined a drop of Lp-PLA2 levels, but even after this alteration the concentrations remain elevated. Our study confirms the negative impact of Lp-PLA2 and amplifies these results in function of sample size, number cardiometabolic markers and the age of the adolescents included.
In addition, many studies have shown that Lp-PLA2 activity is elevated in hypercholesterolemic, diabetic and metabolic syndrome patients [12, 46]. Nambi et al. associated C-reactive protein and Lp-PLA2 to traditional risk factors for cardiovascular disease and proposed that these variables can be especially useful in individuals that are in intermediate risk according to these evaluations. Hence, Lp-PLA2 appears to be an important link between oxidation, inflammation, and altered lipid profile and insulin resistance on cardiovascular diseases. This action maybe involves the formation of lysophosphatidylcholine and isoprostanes that are the bioactive lipids released by Lp-PLA2.
In spite of the important results obtained, we believe that this study shows limitations directly related to the design (cross-sectional) that limits the establishment of the causal impact of our results on prevalence of clinical events.
Finally, we conclude that in adolescence, Lp-PLA2 changes in function of obesity, and that it shows important associations with markers of cardiovascular risk, in particular with waist circumference, glucose, HDL size and Apo B/Apo AI ratio. This supports the hypothesis that Lp-PLA2 can be a biomarker of cardiovascular risk in adolescence, however for confirm this; new prospective cohorts will be required.