Abstract 11150: The Effect of Eicosapentaenoic Acid and Docosahexaenoic Acid on Neutrophil/Lymphocyte Ratio, a Marker of Inflammation, in Subjects With Coronary Artery Disease: Results of a Randomized Trial

Abstract

Background: The neutrophil/lymphocyte (N/L) ratio increases with the systemic inflammatory response due to an increase in neutrophils and decrease in lymphocytes with systemic inflammation. An elevated N/L ratio has been associated with an increased risk of cardiovascular disease (CVD), cancer and mortality. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease levels of high sensitivity C-reactive protein (hs-CRP), the gold standard inflammatory marker, when levels of hs-CRP are elevated. Randomized trials have also reported a decrease in CVD events with EPA. The mechanism for this benefit is unclear. Objective: To examine the effect of high-dose EPA and DHA supplementation on inflammation as measured by the N/L ratio in the setting of low levels of hs-CRP. Methods: A total of 242 subjects with stable coronary artery disease on statin treatment were randomized to 3.36 g EPA+DHA daily or none. N/L ratio and the monocyte to lymphocyte (M/L) ratio were measured at baseline and 1 year. Results: Mean (SD) age was 63.1 years (7.7); mean (SD) LDL-C: 77.8 mg/dL (27.3); median [IQR] TG: 117.5 mg/dL [81.3,166.8] and median [IQR] hs-CRP: 0.75 mg/L [0.40,2.5]. Those on EPA+DHA had a 2.2% reduction in N/L ratio (P=0.014) at 1 year compared to those not on EPA+DHA who had a 12.2% increase (Figure) (between group P= 0.007). There was a trend toward benefit with the M/L ratio (P=0.078). Conclusion: High-dose EPA+DHA decreases systemic inflammation as reflected in the N/L ratio even with low hs-CRP levels. This is a new finding which suggests that under conditions of generally low levels of inflammation in terms of hs-CRP levels, the N/L ratio may be a more sensitive measure of underlying inflammation than hs-CRP and should be considered as an additional marker in future studies of omega-3 fatty acids. If a decrease in inflammation by N/L ratio were accompanied by a clinical decrease in CVD events, this would assist in determining a plausible mechanism of action.