Association between CRP rs1800947 genotypes, dexamethasone use, postoperative CRP level and morbidity in adult cardiac surgical patients in post-hoc analysis of the observational INFLACOR cohort trial.

UNLABELLED: Postoperative inflammation contributes to organ dysfunction and complications after cardiac surgery. C-reactive protein (CRP) is a common marker of systemic inflammation. In this study, we assessed how postoperative CRP levels and their trajectories are associated with the CRP rs1800947 gene variant and perioperative dexamethasone use, and how these factors relate to postoperative morbidity. We analysed CRP levels in 484 adults who underwent cardiac surgery with cardiopulmonary bypass (CPB). CRP levels on postoperative day 1 (CRP1) were compared across the rs1800947 genotype and intraoperative dexamethasone dose: (1) none, (2) low (median 0.4 mg/kg), or (3) high (median 1.0 mg/kg). The 4-day CRP trajectories were evaluated in a subgroup of 174 patients with serial CRP measurements. The composite outcome of 30-day morbidity and mortality was analysed to reveal the association with CRP trajectories.

RESULTS

Adjusted analysis revealed an association between the GC genotype and a 15% reduction in CRP1 levels. Dexamethasone, regardless of dose, reduced CRP1 levels by ~ 30%. Morning surgery increased CRP1 levels by 27%. Elevated preoperative CRP levels increased postoperative CRP1 levels by 19%. CRP trajectories varied by genotype and dexamethasone exposure. Patients were grouped into four trajectory types, whose associations with postoperative complications differed significantly.

CONCLUSIONS

Postoperative CRP levels and trends were associated with genetic and clinical factors. Low-dose dexamethasone is as effective as high-dose dexamethasone in limiting increases in CRP1 level. The CRP patterns associated with CRP genotypes and dexamethasone use potentially represent inflammatory endotypes linked to different morbidity risks.

TRIAL REGISTRATION: This study was registered in the US National Clinical Trial under the code NCT01020409 https://clinicaltrials.gov/ct2/show/study/NCT01020409. Registered on November 24, 2009.