Genetic predisposition in patients undergoing cardiopulmonary bypass surgery is associated with an increase of inflammatory cytokines

Objective: Cardiopulmonary bypass (CPB) surgery induces a transient rise in pro-inflammatory cytokines typically released by activated monocytes. The E4 variant of apolipoprotein E is a recognized risk factor for atherosclero sis. It has recently been shown that apolipoprotein E affects monocyte func tions in vitro and leads to higher levels of median lipoprotein (a) in huma ns. The aim of the study is to investigate if the E4 genetic variant of apo lipoprotein E affects cytokine release after CPB surgery. Methods: 22 patie nts were operated on with standard coronary artery bypass grafting. Concent rations of interleukin 8 (IL-8) and tumor necrosis factor (TNF-alpha) were measured by automated Immulite immunoassay at regular intervals within 48 h after surgery. Total apparent cytokine outputs were calculated as area und er the curve. Results are expressed as mean +/- standard deviation and comp ared by unpaired t-test. Results: In the presented patient population 6 (27 %) carried the E4 allele. Sixteen (63%) showed no E4 allele. Mean cross cla mp time (CCT) was 56.2 +/- 13.5 min versus 55.7 +/- 12.1 min and CPB time w as 91.8 +/- 17.5 versus 93.5 +/- 15.7 min. No statistical difference betwee n E4-carriers and E4 non-carriers regarding CCT and CPB was observed. The t otal amount of IL-8 and TNF-alpha was higher in patients carrying the E4 ge netic variant of apolipoprotein E in comparison to E4 non-carriers (P < 0.0 8, P < 0.039). Conclusion: The presence of the E4 allele is associated with increased release of IL-8 and TNF-alpha after CBP surgery. The preoperativ e determination of E4 in patients undergoing cardiac surgery may lead to ad ditional perioperative measures for the treatment of an increased systemic inflammatory response. (C) 2001 Elsevier Science B.V. All rights reserved.