Abstract 13352: Higher Plasma CXCL12 Levels Predict Incident Cardiovascular Disease Events: Findings from the Chronic Renal Insufficiency Cohort Study
Background: Genome wide association studies have repeatedly shown an association between myocardial infarction (MI) and common variation at locus 10q11 downstream from CXCL12, an inflammatory cytokine. The risk allele for MI at 10q11 is also related to increased plasma levels of CXCL12. However, the relationship among plasma CXCL12 cardiovascular (CV) risk factors, prevalent CV disease (CVD), incident MI and death is unknown.
Methods: We measured plasma CXCL12 levels at baseline in 3,869 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective cohort study of heart disease and kidney outcomes in patients with chronic kidney disease (CKD). At baseline, prevalent CVD was defined as history of MI, stroke, revascularization. Participants were followed for 5 years for incident MI or death. Cross-sectional associations with plasma CXCL12 were assessed by chi-square, Spearman correlation, Kruskal-Wallis testing or by multivariable logistic regression. Cox proportional hazard modeling was used to assess the relationship between CXCL12 levels and incident MI as well as death, adjusting for traditional CV risk factors and CKD measures (eGFR and cystatin C).
Results: Plasma CXCL12 levels were positively associated with CV risk factors including age, hypertension, diabetes, hypercholesterolemia, smoking, lower eGFR and higher levels of inflammatory markers including IL-6, TNF-alpha and hs-CRP (p<0.001 for all). In fully adjusted models, higher baseline CXCL12 levels were associated with an increased odds of prevalent CVD (OR 1.26 for increase in 1 SD of CXCL12; p<0.001). Similarly, a 1 SD higher plasma level of CXCL12 was associated with increased risk of both incident MI (hazard ratio (HR) 1.34; p<0.001) and death (HR 1.33; p<0.001) in models fully adjusted for CV risk factors and measures of CKD.
Conclusions: In CKD, baseline plasma levels of CXCL12 were associated with known CV risk factors, prevalent CV disease as well as incident MI/death after adjustment for traditional CV risk factors and measures of CKD. While these findings suggest that plasma CXCL12 levels may be atherogenic, further mechanistic studies are required to establish if plasma CXCL12 levels reflect causal actions at the vessel wall.
- © 2012 by American Heart Association, Inc.