Decreased CTRP3 Plasma Concentrations Are Associated with Sepsis and Predict Mortality in Critically Ill Patients

Abstract

C1q/ tumor necrosis factor (TNF)-like protein 3 (CTRP3) represents a novel member of the adipokine family that exerts favorable metabolic actions in humans. However, the role of CTRP3 in critical illness and sepsis is currently unknown. Upon admission to the medical intensive care unit (ICU), we investigated CTRP3 plasma concentrations in 218 critically ill patients (145 with sepsis, 73 without sepsis). Results were compared with 66 healthy controls. CTRP3 plasma levels were significantly decreased in critically ill patients, when compared to healthy controls. In particular, low CTRP3 levels were highly associated with the presence of sepsis. CTRP3 levels were neither associated with obesity nor diabetes. In critically ill patients, CTRP3 plasma concentrations were inversely correlated with inflammatory cytokines and classical sepsis markers. Among a wide group of adipokines, CTRP3 only correlated with circulating resistin. Low CTRP3 plasma levels were associated with the overall mortality, and CTRP3 levels below 620.6 ng/mL indicated a particularly increased mortality risk in ICU patients. Our study demonstrates for the first time the role of circulating CTRP3 as a biomarker in critically ill patients that might facilitate diagnosis of sepsis as well as prognosis prediction. The association between low CTRP3 and increased inflammation warrants further pathophysiological investigations.

The Role of Adipokines as Circulating Biomarkers in Critical Illness and Sepsis

“…In human critical illness, circulating CTRP3 levels were found to be reduced. In a cohort of n = 218 patients, both critically ill patients with ( n = 145) or without ( n = 73) sepsis had significantly decreased plasma CTRP3 levels compared with healthy controls [38]. Moreover, low CTRP3 levels were directly associated with the presence of sepsis among ICU patients.…”

“…In line, CTRP3 plasma concentrations were inversely correlated with inflammatory cytokines and standard markers of sepsis such as CRP and PCT. Importantly, the authors described a direct association between low CTRP3 levels (<620.6 ng/mL) and an increased overall mortality [38]. Although these data need to be confirmed in further trials, it suggests a clinically relevant role of CTRP3 as a potential new diagnostic and prognostic biomarker in patients with critical illness and sepsis.…”

Decreased Epicardial CTRP3 mRNA Levels in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease Undergoing Elective Cardiac Surgery: A Possible Association with Coronary Atherosclerosis

“…Interestingly, other studies reported that CTRP3 is the only adipokine in septic patients that decreases significantly compared to such proteins as ghrelin, resistin, leptin, and CTRP1 [ 36 , 37 , 38 , 39 ]. Another study showed that metabolic comorbidities did not affect the CTRP3 dynamic in the setting of critical illness [ 40 ].…”

Níveis Reduzidos de CTRP3 em Pacientes com Doença Arterial Coronariana Estável Relacionados à Presença de Fibrilação Atrial Paroxística

“…Nos estudos sobre os efeitos da CTRP3 no sistema cardiovascular mostra-se que: i) reduz o estresse oxidativo, ii) inibe a apoptose, iii) tem efeitos anti-inflamatórios e antiaterogênicos, iv) reduz o desenvolvimento de fibrose, v) inibe a gliconeogênese e, como resultado de todos esses efeitos, a CTRP3 reduz as chances de desenvolver doenças cardiovasculares (CV). [2][3][4][5][6][7][8][9]15,16 Considerando seus efeitos atuais, observou-se que a CTRP3 pode, em termos fisiopatológicos, proteger e melhorar os aspectos clínicos de pacientes com DAC. Níveis séricos de CTRP3 foram avaliados em pacientes com insuficiência cardíaca com fração de ejeção reduzida (ICFEr), SCA, angina estável e dissecção aórtica aguda; e os níveis sérios de CTRP3 foram significativamente menores.…”