Background:

The Berlin Longterm Observation of Vascular Events (BeLOVE) study is a prospective, multicenter, cohort study aiming to improve the short- and long-term prediction of cardiovascular events in preselected patients with high cardiovascular burden including patients with acute coronary syndrome (ACS) and acute ischemic stroke (AIS). By a combination of clinical characteristics and laboratory measurements in a time-dependent course after the index event, the BeLOVE study provides fundamental understanding of disease-overarching mechanisms. The current sub-analysis focuses on the dynamic changes in the main immune cells populations ninety days after in comparison to immediately after the index event of ACS or AIS and examines clinical risk factors (hsCRP, LDL or Lp(a)) as markers of distinct immunological signatures.

Methods:

In the current analysis ninety (n=90) patients with ACS and seventy six (n=76) patients with AIS with serial immunophenotyping at visit 1 (0-7 days after index event) and follow-up-visit 3 (app. 90 days) were included. Both groups were further stratified by common risk factors like hsCRP, LDL and Lp(a) at visit 3 into following groups: residual inflammatory risk (RIR) with hsCRP >2mg/l, residual lipid risk with LDL cholesterol >70mg/dl or lipoprotein (a) >70nmol/l. Patients with relevant inflammatory or malignant comorbidities have been excluded. Immune cell populations of interest were leucocytes, CD4+ T cells, CD8+ T cells, B cells, CD16 ^hi neutrophils, classical, non-classical and intermediate monocytes. Linear regression models were used to evaluate the difference in the dynamic changes of the immune cell counts between patients with and without the above-mentioned risk factors and between the entities. Models were adjusted for age, sex, diabetes, time from index event to acute visit (0-7d), cell count at acute visit and time to follow up visit. Estimated marginal means were calculated with 95% confidence interval.

Results:

In the current analysis, a significant increase of classical monocytes at visit 3 was observed in the ACS cohort in contrast to the AIS- cohort (ACS: +0.20;95%CI:+0.02 to +0.38; AIS: -0.17; 95%CI: -0.37 to 0.02). ACS-patients show stable CD16^hi neutrophil (-0.02;95%CI: -0.14 to 0.09) and non-classical monocytes counts (-0.00;95%CI: -0.16 to +0.16). This is again in sharp contrast to the effect observed for AIS patients, who are characterized by a decreasing counts of CD16^hi neutrophils (-0.28;95%CI: -0.40 to -0.15) and non-classical monocytes (-0.28;95%CI: -0.45 to -0.10). There were no differences in the cells of the adaptive immune system. Interestingly, RLR in AIS patients implied lower decrease in the intermediate monocyte count (-0.52;95%CI -0.77 to -0.26) than AIS patients without RLR (-0.89;95%CI -1.20 to -0.57). This effect was opposite in ACS-patients with RLR, where intermediate monocyte show a more pronounced decrease (-0.71;95%CI -0.93 to -0.48) than in ACS patients without RLR (-0.50;95%CI -0.80 to -0.21).

Conclusion:

For the first time, divergent immunological signatures were observed for ACS and AIS patients. These findings highlight the pathophysiological role of the innate immune system in the subsequent disease progression. RLR 3 months after AIS was associated with higher monocyte counts, suggesting an interaction between elevated LDL and activated atherosclerosis in AIS patients. BeLOVE will investigate the relevance of these findings for future recurrent events.