Abstract 19593: The Association of Circulating Cytokines, Chemokines and Growth Factors With Major Cardiovascular Risk Factor in Subjects With Clinical Manifestations of Atherosclerosis
Introduction: Different cardiovascular risk factors affect different size arteries in atherosclerotic peripheral artery disease. The molecular mechanisms behind this phenomenon remain unknown.
Hypothesis: We hypothesize that to some extent major cardiovascular risk factors act through differing immunological pathways in the development of atherosclerosis.
Methods: The levels of 48 circulating cytokines were analyzed and correlated with major cardiovascular risk factors in two separate patient cohorts with prevalent symptomatic atherosclerosis from the PURE ASO and FINRISK studies. In addition, the same analyses were performed using a matched patient cohort of incident atherosclerosis and an age-matched cohort of subjects without clinical manifestation of cardiovascular risk factors and atherosclerosis during ten year follow up from the FINRISK-02 Study.
Results: Multivariate modeling revealed that aging independently associated with MIG, CTACK and IP-10 (P <0.001 for all). Up-regulation of these IFN-γ inducible factors suggests that aging and atherosclerosis is associated with Th1 immune responses. Chronic kidney disease also associated with Th1 mediated mechanisms: IL-2Rα (P = 0.033), IL-16 (P < 0.001), IL-18 (P = 0.035), MIF (P = 0.001), MIG (P = 0.014), SCF (P <0.001), but also M-CSF (P = 0.019), which is known to be associated with Th17 activity. Smoking and hypertension were associated with IL-17 (P = 0.037 and 0.015, respectively). In addition, smoking was associated with growth factors known to induce myeloid progenitor cell proliferation: GM-CSF (P = 0.035), PDGF (P = 0.004), FGF (P = 0.026), and HGF (P = 0.030). Dyslipidemia associated with myeloproliferative factors: MIB-1α (P = 0.005) and PDGF (P = 0.007). Diabetes had a negative association with IFN-γ induced mechanisms (IP-10 and CTACK, P = 0.03 and P =0.02, respectively), but otherwise a positive association with Th1 and Th2 mediated inflammation: IL-13 (P = 0.009), IL-16 (P = 0.003) and IL-18 (P = 0.027).
Conclusions: Cardiovascular risk factors are associated with different immunological pathology in patients with clinically symptomatic prevalent and incident atherosclerosis.
Author Disclosures: J. Jalkanen: None. M. Hollmén: None. S. Jalkanen: None. H. Hakovirta: None. V. Salomaa: None.
- © 2016 by American Heart Association, Inc.