Associations of inflammatory biomarkers with morbidity and mortality after noncardiac surgery: A systematic review and meta-analysis

Background: Noncardiac surgery is associated with an inflammatory response. Whether increased inflammation in the perioperative period is associated with subsequent morbidity and mortality is unknown. Methods: MEDLINE, EMBASE, and CENTRAL were systematically searched from date of inception until May 2023. Longitudinal studies were included if they reported multivariable adjusted associations of biomarkers measured preoperatively and/or within 10 days after surgery with at least one prespecified adverse outcome in noncardiac surgery patients. Data were extracted independently and in duplicate. Risk estimates were pooled using DerSimonian-Laird random-effects models and reported as summary odds ratios (ORs) with 95% CIs. The outcomes were all-cause mortality and major adverse cardiovascular events. Results: Fifty-two studies with a total of 121,849 patients were included. The median follow-up was 56 [IQR, 28-63] months and the average age was 57 (+/- 3) years. Elevated preoperative C-reactive protein (CRP) levels were associated with a higher risk of mortality (OR 1.57, 95% CI 1.29-1.90, I2 = 93%, 28 studies). This association was stronger in non-cancer surgery populations (OR 2.10, 95% CI 1.92-2.31, I2 = 0%, 4 studies) when compared to cancer surgery populations (OR 1.51, 95% CI 1.26-1.81, I2 = 83%, 24 studies) (p for subgroup difference = 0.001). Similarly, higher postoperative CRP levels were associated with all-cause mortality (OR 1.61, 95% CI 1.17-2.20, I2 = 90%, 7 studies). Higher preoperative CRP levels were associated with major cardiovascular events (OR 2.11, 95% CI 1.51-2.94, I2 = 0%, 2 studies). Other preoperatively measured biomarkers associated with all-cause mortality were fibrinogen (OR 1.48, 95% CI 1.05-2.09, I2 = 52%, 5 studies), interleukin-6 (OR 1.17, 95% CI 1.07-1.28, I2 = 27%, 3 studies), and tumour necrosis factor-alpha (OR 1.37, 95% CI 1.16-1.61, I2 = 0%, 2 studies). Conclusion and relevance: Inflammatory biomarker levels in the perioperative period were associated with allcause mortality and adverse cardiovascular events in patients undergoing noncardiac surgery.