Postoperative elevated cardiac troponin levels predict all-cause mortality and major adverse cardiovascular events following noncardiac surgery: A dose-response meta-analysis of prospective studies.

STUDY OBJECTIVE

To perform a dose-response meta-analysis for the association between postoperative myocardial injury (PMI) in noncardiac surgery and the risk of all-cause mortality or major adverse cardiovascular event (MACE).

DESIGN

Dose-response meta-analysis of prospective studies with weighted (WL) or generalized (GL) linear and restricted cubic spline (RCS) regression.

SETTING

Teaching hospitals.

PATIENTS

Adult patients undergoing noncardiac surgery.

INTERVENTIONS

No.

MEASUREMENTS

The primary outcome was all-cause mortality. The secondary outcome was MACE.

MAIN RESULTS

29 studies (53,518 patients) were included. The overall incidence of PMI was 26.0% (95% CI 21.0% to 32.0%). Compared to those without PMI, patients with PMI had an increased risk of all-cause mortality at short- (<12 months) (cardiac troponin[cTn]I: unadj OR 1.71,95%CI 1.22 to 2.41, P < 0.001; cTnT: unadj OR 2.33,95%CI 2.07 to 2.63, P < 0.001), and long-term (≥ 12 months) (cTnI: unadj OR 1.80, 95%CI 1.63 to 1.99; cTnT: unadj OR 1.47,95%CI 1.33 to 1.62) (All P < 0.001) follow-up. For MACE, the group with elevated values was associated with an increased risk (cTnI: unadj OR 1.98, 95% CI 1.13 to 3.47, P = 0.018; cTnT: unadj OR 2.29, 95% CI 1.88 to 2.79, P < 0.001). Dose-response analysis showed positive associations between PMI (per 1× upper reference limit[URL] increment) and all-cause mortality both at short- (unadj OR) (WL, OR 1.09, 95% CI 1.09 to 1.10; GL, OR 1.06, 95% CI 1.06 to 1.07; RCS in the range of 1-2× URL, OR = 2.43, 95%CI 2.25 to 2.62) and long-term follow-up (unadj HR) (WL, OR 1.16, 95% CI 1.14 to 1.17; GL, OR 1.15, 95% CI 1.13 to 1.16; RCS in the range of 1-2.75× URL, OR = 1.23, 95%CI 1.13 to 1.33), and MACE at longest follow-up (unadj OR) (WL: OR 1.53, 95% CI 1.49 to 1.57; GL: OR 1.46, 95% CI 1.42 to 1.50; RCS in the range of 1-2 x URL, OR = 3.10, 95%CI 2.51 to 3.81) (All P < 0.001). For mild cTn increase below URL, the risk of mortality increased with every increment of 0.25xURL (WL, OR 1.03, 95% CI 1.02 to 1.03; GL, OR 1.05, 95% CI 1.03 to 1.07; RCS in the range of 0-0.5 URL, OR = 9.41, 95% CI 7.41 to 11.95) (All P < 0.001).

CONCLUSIONS

This study shows positive WL or GL and RCS dose-response relationships between PMI and all-cause mortality at short (< 12 mons)- and long-term (≥ 12 mons) follow-up, and MACE at longest follow-up. For mild cTn increase below URL, the risk of mortality also increases even with every increment of 0.25× URL.