Abstract

Background: Inflammation has been implicated in the pathogenesis of acute coronary syndrome (ACS). The comparative performance of blood cell-based inflammatory markers in mortality prediction among ACS patients remains unclear. Methods: In this multinational, double-blind, phase 2 trial, patients with recent ACS were randomized to receive rivaroxaban or a placebo. The relationship of inflammatory markers (including neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], systemic immune-inflammation index [SII], and C-reactive protein [CRP]) with 6-month all-cause mortality was assessed using logistic regression, and the optimal cut points were determined by the Youden index. The discriminative performance of the combinations of inflammatory markers was compared by the c statistic. Results: A total of 2918 patients were analyzed. A higher risk of mortality was observed in patients with elevated NLR (≥3.691; OR=3.732; 95% CI=1.930 to 7.217; p<0.0001), elevated PLR (≥14.18; OR=2.915; 95% CI=1.447 to 5.873; p=0.0028), decreased LMR (<3.125; OR=3.179; 95% CI=1.643 to 6.152; p=0.0006), elevated SII (≥875.7; OR=2.494; 95% CI=1.285 to 4.840; p=0.0069), or elevated CRP (≥26 mg/L; OR=3.435; 95% CI=1.771 to 6.662; p=0.0003). The discriminative capacity of CRP plus NLR (c statistic=0.7326) was greater than CRP or NLR alone (c statistic=0.6444 and 0.6443) but not significantly affected by further inclusion of PLR, PLR plus SII, or PLR plus SII plus LMR into the model (c statistic=0.7430, 0.7412, and 0.7406) (Figure 1). Conclusion: NLR calculated from differential white blood cell count provides incremental prognostic value to CRP in predicting mortality among ACS patients. Future studies may consider NLR and CRP conjunctively in constructing mortality risk assessment models.

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