The relationship of circulating neuregulin 4 and irisin, and traditional and novel cardiometabolic risk factors with the risk and severity of coronary artery disease.

BACKGROUND AND AIMS:Neuregulin 4 (NRG4) and irisin are adipokines that have been suggested to be associated with cardiometabolic risk factors and coronary artery disease (CAD), but the data are inconclusive. This study aimed to investigate the relationship between circulating NRG4 and irisin and cardiometabolic risk factors with CAD risk and severity. METHODS AND RESULTS:In this cross-sectional study, the presence of CAD and the severity of stenosis (gensini score) were documented based on coronary angiography in 166 adults. Circulating NRG4 and irisin, glucose homeostasis markers, hs-CRP, lipid profiles, blood pressure, and anthropometric measurements were assessed as well. Age (p = 0.005), sex (p = 0.008), SBP (p = 0.033), DBP (p = 0.04), MAP (p = 0.018), FBG (p = 0.012), insulin (p = 0.039) and HOMA-IR (p = 0.01) were significantly associated with odds of having CAD. The final logistic regression model showed that age, sex, HOMA-IR, and MAP were the most important determinants of having CAD. There were no significant associations between circulating irisin and NRG4 with odds of having CAD. The final general linear model showed that being men (β = 17.303, 95% CI: 7.086-27.52, P = 0.001), age (Aβ = 0.712, 95% CI: 0.21-1.214, P = 0.006), HOMA-IR (Aβ = 2.168, 95% CI: 0.256 to 4.079, P = 0.027), and NRG4 level (β = 1.836, 95% CI: 0.119-3.553, P = 0.036) were directly associated with higher gensini score. Participants with the three-vessel disease had a mean increase of about 5 units in circulating irisin compared to those with no clinical CAD (β = 5.221, 95% CI: 0.454-9.987, p = 0.032). CONCLUSIONS:This study showed that the adipokines NRG4 and Irisin might be associated with the severity of coronary stenosis.