Dynamic changes of monocytes subsets predict major adverse cardiovascular events and left ventricular function after STEMI

We explored how dynamic changes in monocyte subset counts (as opposed to static values to specific time points), and their phagocytic and NF kappa B activity relate to major adverse cardiovascular events (MACE) and left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI). Changes in counts, phagocytic activity and intracellular levels of inhibitory kappa B kinase beta (IKK beta) (a marker of NF kappa B activity) of monocyte subsets (CD14(++)CD16(-)CCR2(+) [Mon1], CD14(++)CD16(+)CCR2(+) [Mon2] and CD14(+)CD16(++)CCR2(-) [Mon3]) were measured by flow cytometry in patients with STEMI at baseline, and again after one week, two weeks, and one month. LVEF was measured by echocardiography at baseline and six months after STEMI. Baseline data included 245 patients (mean +/- SD age 60 +/- 12 years; 22% female), who were followed for a median of 46 (19-61) months. Multivariate Cox regression demonstrated that more prominent dynamic reduction in Mon2 by week 1 (n = 37) was independently associated with fewer MACE (HR 0.06, 95% CI 0.01-0.55, p = 0.01). Also, less prominent reduction in Mon2 at month 1 (n = 24) was independently predictive of 6-month LVEF. None of the other dynamic changes in monocyte subsets were associated with changes in survival from MACE. Neither phagocytic activity nor IKK beta were associated with survival for each monocyte subset. We showed how distinct pattern of dynamic changes in Mon2 are related to both MACE risk and recovery of cardiac contractility. Further research is needed to understand the mechanism of the monocyte effect and possibilities of their pharmacological manipulation.

Automated summary

We investigated the association between dynamic changes in monocyte subset counts, phagocytic activity, and NF kappa B activity with major adverse cardiovascular events (MACE) and left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI). Multivariate Cox regression analysis revealed that a more significant reduction in Mon2 by week 1 was independently associated with fewer MACE events. Additionally, a less prominent reduction in Mon2 at 1 month was predictive of better 6-month LVEF. This study highlights the importance of dynamic changes in Mon2 and their potential significance for MACE risk and cardiac recovery.