Abstract Body (Do not enter title and authors here): Background
Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease (ASCVD) risk, and vascular inflammation is one mechanism through which Lp(a) causes ASCVD. Biomarkers associated with inflammation and cardiovascular disease, such as interleukin-6 (IL-6), may help risk stratify individuals with elevated Lp(a).

Research Questions
We aimed to evaluate whether the association between Lp(a) and ASCVD risk is modified by IL-6.

Methods
Data from participants in the Multi-Ethnic Study of Atherosclerosis (MESA, n=6,514) and the UK Biobank (UKB, n=26,574) was used for this analysis. The associations between Lp(a) and IL-6 with coronary heart disease (CHD, defined as myocardial infarction or resuscitated cardiac arrest), ASCVD (CHD and ischemic stroke) and peripheral vascular disease (PVD) were evaluated separately and with mutual adjustment in Cox proportional hazards models adjusted for traditional cardiovascular risk factors and high-sensitivity c-reactive protein (hsCRP). Hazard ratios (HR) were presented per SD. Participants were also grouped by Lp(a) level (≤ or >50 mg/dL or 125 nmol/L) and IL-6 level (≤ or >median) in similar models.

Results
Participants with higher IL-6 levels were more likely to have higher body mass index, systolic blood pressure, triglycerides and hsCRP with lower high-density lipoprotein-cholesterol. Lp(a) (HR 1.13, 95% CI 1.04-1.23 in MESA; HR 1.11, 95% CI 1.09-1.13 in UKB) and IL-6 (HR 1.22, 95% CI 1.10-1.35 in MESA; HR 1.19, 95% CI 1.15-1.24 in UKB) were both independently associated with CHD events when evaluated separately. When evaluated together, no significant change was noted, and interaction testing was not significant. Similar results were seen for ASCVD and PVD. When participants were categorized by both Lp(a) and IL-6 levels, the strongest association for each outcome was noted when both levels were high (for CHD: HR 1.72, 95% CI 1.25-2.36 in MESA; HR 1.39, 95% CI 1.12-1.72 in UKB, Figure).

Conclusions
In two independent primary prevention cohorts, Lp(a) and IL-6 are independent predictors of ASCVD risk, and their combination identifies individuals at highest risk