Apolipoprotein(a) production and clearance are associated with plasma IL-6 and IL-18 levels, dependent on ethnicity

Background and aimsHigh lipoprotein (a) [Lp(a)] plasma levels are associated with increased atherosclerotic cardiovascular disease (ASCVD), in part attributed to elevated inflammation. High plasma Lp(a) levels inversely correlate with apolipoprotein (a) [(APO(a)] isoform size. APO(a) isoform size is negatively associated with APO(a) production rate (PR) and positively associated with APO(a) fractional catabolic rate (FCR). We asked whether APO(a) PR and FCR (kinetics) are associated with plasma levels of interleukin (IL)-6 and IL-18, pro-inflammatory interleukins that promote ASCVD.MethodsWe used samples from existing data of APO(a) kinetic studies from an ethnically diverse cohort (n = 25: 10 Black, 9 Hispanic, and 6 White subjects) and assessed IL-6 and IL-18 plasma levels. We performed multivariate linear regression analyses to examine the relationships between predictors APO(a) PR or APO(a) FCR, and outcome variables IL-6 or IL-18. In these analyses, we adjusted for parameters known to affect Lp(a) levels and APO(a) PR and FCR, including race/ethnicity and APO(a) isoform size.ResultsAPO(a) PR and FCR were positively associated with plasma IL-6, which was independent of isoform size, and dependent on race/ethnicity. APO(a) PR was positively associated with plasma IL-18, independent of isoform size and race/ethnicity. APO(a) FCR was not associated with plasma IL-18.ConclusionsOur studies demonstrate a relationship between APO(a) PR and FCR and plasma IL-6 or IL-18, interleukins that promote ASCVD. These studies provide new insights into Lp(a)'s pro-inflammatory properties and are especially relevant in view of therapies targeting APO(a) to decrease cardiovascular risk.