Abstract
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.
OBJECTIVES: The authors aimed to evaluate whether interleukin-6 (IL-6), a biomarker associated with inflammation and cardiovascular disease, helps risk-stratify individuals with elevated Lp(a).
METHODS: Data from participants in the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 6,514) and the UK Biobank (UKB) (n = 26,574) were 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 hazard models adjusted for traditional cardiovascular risk factors and high-sensitivity C-reactive protein (hsCRP). HRs were presented per standard deviation. Participants were also grouped by Lp(a) level (≤50 or >50 mg/dL [125 nmol/L]) and IL-6 level (≤ median 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).
CONCLUSIONS: In 2 independent primary prevention cohorts, Lp(a) and IL-6 were independent predictors of ASCVD risk, and their combination identified individuals at highest risk.