Association of chronic low-grade inflammation with adverse outcomes after gastrointestinal surgery: observational and Mendelian randomization study.

Although overt systemic inflammation immediately before gastrointestinal surgery has been associated with postoperative complications and mortality, it remains unclear whether baseline low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) in a non-surgery-related state is associated with the same outcomes. This study included a subset of individuals from the Copenhagen General Population Study (CGPS) who underwent any type of gastrointestinal surgery between 2003 and 2015 after enrolment in the CGPS. Exposures were baseline hs-CRP levels (used in observational analyses) and two genetic variants that affect hs-CRP levels, namely interleukin 6 receptor (IL6R) rs4537545 and CRP rs1130864 (used in Mendelian randomization analyses), all of which were tested routinely at CGPS enrolment. Primary outcomes were 30-day complications and 90-day and 5-year mortality after the index surgery. Associations between exposures and outcomes were assessed using multivariable Cox regression models. Of the 107 536 individuals in the CGPS, 12 803 were included in the present study. Of these individuals, 1236 (9.7%) experienced 30-day complications, 865 (6.8%) died within 90 days, and 2789 (21.8%) died within 5 years. Adjusted hazard ratios for the highest hs-CRP quartile (hs-CRP ≥ 2.73 mg/l) versus the lowest quartile (hs-CRP < 1.04 mg/l) were 1.19 (95% confidence interval (c.i.) 1.02 to 1.40; P = 0.029) for 30-day complications, 1.29 (95% c.i. 1.07 to 1.57; P = 0.009) for 90-day mortality, and 1.17 (95% c.i. 1.06 to 1.31; P = 0.003) for 5-year mortality. Sensitivity analyses restricted to those with hs-CRP measurements within 1 year before surgery had larger point estimates. Genetically predicted elevations in hs-CRP were not associated with any outcomes. Baseline hs-CRP levels ≥ 2.73 mg/l, consistent with chronic low-grade systemic inflammation, were associated with higher risk of 30-day complications, 90-day mortality, and 5-year mortality after gastrointestinal surgery.