The Correlation Between Whole Blood Copper (Cu), Zinc (Zn) Levels and Cu/Zn Ratio and Sepsis-Induced Left Ventricular Systolic Dysfunction (SILVSD) in Patients with Septic Shock: A Single-Center Prospective Observational Study

PURPOSE: This study aimed to explore relationships between whole blood copper (Cu), zinc (Zn) and Cu/Zn ratio and cardiac dysfunction in patients with septic shock. SUBJECTS AND METHODS: Between April 2018 and March 2020, septic shock patients with sepsis-induced left ventricular systolic dysfunction (SILVSD, left ventricular ejection fraction, LVEF<50%) and with no sepsis-induced myocardial dysfunction (non-SIMD, septic shock alone and LVEF>50%) and controls were prospectively enrolled. Whole blood Cu and Zn levels were measured using flame atomic absorption spectrophotometry. RESULTS: Eighty-six patients with septic shock including both 41 SILVSD and 45 non-SIMD and 25 controls were studied. Whole blood Cu levels and Cu/Zn ratio were significantly higher and Zn levels were lower in SILVSD compared with non-SIMD and controls (Cu, p=0.009, <0.001; Zn, p=0.029, <0.001; Cu/Zn ratio, p=0.003, <0.001). Both increased whole blood Cu and Cu/Zn ratio and reduced Zn were associated with lower LVEF (all p<0.001) and higher amino-terminal pro-B-type natriuretic peptide (NT-proBNP) (Cu, p=0.002; Zn, p<0.001; Cu/Zn ratio, p<0.001) and had predictive values for SILVSD (Cu, AUC=0.666, p=0.005; Zn, AUC=0.625, p=0.039; Cu/Zn ratio, AUC=0.674, p=0.029). Whole blood Cu levels and Cu/Zn ratio were increased but Zn levels were reduced in non-survivors compared with survivors (Cu, p<0.001; Zn, p<0.001; Cu/Zn ratio, p<0.001). Whole blood Cu and Zn displayed the value of predicting 28-day mortality (Cu, AUC = 0.802, p<0.001; Zn, AUC=0.869, p<0.001; Cu/Zn ratio, AUC=0.902, p<0.001). CONCLUSION: Findings of the study suggest that whole blood Cu levels and Cu/Zn ratio are increased in SILVSD patients and positively correlated with cardiac dysfunction, while whole blood Zn levels are reduced and negatively associated with cardiac dysfunction. Moreover, both whole blood Cu, Zn and Cu/Zn ratio might distinguish between SILVSD and non-SIMD in septic shock patients and predict 28-day mortality. TRIAL REGISTRATION: Registered at http://www.chictr.org.cn/ChiCTR1800015709.