Prognostic impact of the controlling nutritional status score in Chinese patients undergoing cardiac surgery.

To the Editor: The overall survival rate among patients undergoing cardiac surgery has significantly increased, and reducing mortality and post-operative complications remain vital. Malnutrition is a common condition in hospitalized patients. There are several methods to evaluate nutritional status; however, some elements of malnutrition are difficult to measure. The controlling nutritional status (CONUT) score is an objective nutritional indicator and easy-to-perform practical screening tool that uses the serum albumin, peripheral lymphocyte count, and total cholesterol. Specifically, the combination of these three components can evaluate protein reserves, immune defenses, and calorie depletion.[1] Recently, the predictive value of the CONUT score has been validated in surgical patients with peripheral arterial disease, malignant tumors, and heart disease.[2] Several studies found high CONUT score was associated with high mortality in patients undergoing transcatheter aortic valve implantation (TAVI), percutaneous coronary intervention, or coronary artery bypass grafting.[2,3] However, the prognostic impact of the CONUT score has not been fully investigated in Chinese patients undergoing cardiac surgery. Therefore, this study aimed to determine the prognostic impact of malnutrition, as assessed by the CONUT score, in patients undergoing cardiac surgery. We conducted a single-center retrospective observational study in patients undergoing cardiac surgery who were admitted to the cardiothoracic surgery department of the First People's Hospital of Changzhou between February 2011 and December 2015. This study was conducted following the principles of the Declaration of Helsinki and with the approval of the Ethics Committee at the Third Affiliated Hospital of Soochow University, China (No. 24/2014). The exclusion criteria were: (1) age <18 years; (2) emergency or redo surgery; and (3) malignant tumor or end-stage renal disease. Written informed consent was obtained from all patients. Laboratory data were obtained from the clinical chemistry department, including hemoglobin, lymphocyte count, serum creatinine, albumin, cystatin-C, uric acid, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac troponinI (cTnI) before surgery. Peri-operative data were obtained from Electronic Medical Record System. Demographic data, including gender, age, and comorbidities, were collected upon admission. Left ventricular ejection fraction (LVEF), surgical duration, and cardiopulmonary bypass (CBP) time were also recorded. The CONUT score was calculated based on lymphocyte count, serum albumin, and total cholesterol [Supplementary Table 1, https://links.lww.com/%20CM9/A993]. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. To diagnose shrunken pore syndrome (SPS), the equation pair Caucasian Asian Pediatric Adult and Lund Malmo Revised, which were based upon cystatin-C and creatinine (according to www. egfr.se), were used. The tentative value of eGFRcystatin-C/eGFRcreatinine ratio was 0.7. Mean arterial pressure (MAP) was calculated from diastolic blood pressure plus one-third of the pulse pressure. The primary outcome was all-cause mortality during or after cardiac surgery. The secondary outcomes were postoperative complications, including acute kidney injury (AKI), transient ischemic attack or stroke, and reoperation for bleeding. The procedural complications were collected from the medical records. AKI was defined as an increase in serum creatinine ≥0.3 mg/dL within 48 h or ≥50% within 7 days. Clinical follow-up was performed via a review of medical charts and telephone interviews. The occurrence of any adverse clinical events was also assessed. Normally distributed continuous variables were compared using an unpaired t-test, and the results are presented as mean ± standard deviation. Non-normally distributed variables were compared using Mann–Whitney U test, and the results are presented as median (interquartile range). Categorical variables were compared using Pearson Chi-squared test and the results are presented as frequency (percentage). Based on the receiver operating characteristic curve analysis, the optimal cutoff CONUT score was 3. The Kaplan–Meier curve and log-rank test were conducted to estimate patient survival. To identify independent risk factors, we performed univariate and multivariate Cox regression analyses. Hazard ratios (HRs) and 95% confidence intervals (CIs) were also calculated. Furthermore, we analyzed the area under the curve (AUC) to compare the models containing only the CONUT score with the joint models in predicting outcomes. All statistical analyses were conducted using SPSS 24.0 software (IBM, NY, USA). A two-sided P value of <0.05 was considered to be statistically significant. A total of 631 patients underwent cardiac surgery at our hospital. During follow-up, 178 patients withdrew from the study. Finally, 408 patients were enrolled according to the exclusion criteria. Only 12 patients (2.9%) were diagnosed with SPS. Ninety-nine patients had a high CONUT score (>3). Supplementary Table 2, https://links.lww.com/CM9/A993 shows baseline clinical characteristics. The majority of patients was male and there was a significant difference in gender between the two groups. Compared with the low CONUT score group, patients in the high CONUT score group were older. A total of 196 (48.0%) and 70 (17.2%) patients had comorbid hypertension and diabetes mellitus, respectively, and the proportion of patients with these conditions was higher in the high CONUT score group. Patients in the high CONUT score group had lower hemoglobin, lower serum albumin, higher serum creatinine, lower triglyceride, lower cholesterol, lower HDL-C, lower LDL-C, higher CRP, and lower LVEF (P < 0.05). There were no significant differences in MAP, current smoking status, alcohol consumption, NT-proBNP, cTnI, surgical duration, and CBP time between the two groups. The median follow-up period was 72.12 months (58.19, 88.87) and 28 (6.9%) patients fulfilled the primary outcomes. The total 5-year survival rate according to the Kaplan–Meier analysis was 94.9%. Thirteen patients (13.1%) reached the primary endpoint in the high CONUT score group. As shown in [Figure 1A], the 5-year survival rate was 90.9% in the high CONUT score group compared with 96.1% in the low CONUT score group (P = 0.002). No patients diagnosed with SPS died during follow-up. Forty-three patients (10.5%) presented with post-operative complications. The high CONUT group had a significantly higher rate of secondary outcomes than the low CONUT score group (Figure 1B, P = 0.02).Figure 1: Kaplan–Meier curves for outcomes in patients undergoing cardiac surgery. (A) All-cause mortality; (B) Post-operative complications. CONUT: Controlling nutritional status.The correlations between baseline characteristics and all-cause mortality were analyzed by Cox regression analysis. In the univariate analysis, age (HR = 1.084, 95% CI = 1.033–1.138, P = 0.001), hypertension (HR = 2.975, 95% CI = 1.308–6.767, P = 0.009), and a high CONUT score (HR = 3.179, 95% CI = 1.489–6.788, P = 0.003) were significantly associated with an increased risk of mortality [Supplementary Table 3, https://links.lww.com/CM9/A993]. A high CONUT score (HR = 5.973, 95% CI = 1.537–23.213, P = 0.010; Supplementary Table 4, https://links.lww.com/CM9/A993) remained a significant predictor of mortality in the multivariate Cox regression model. The AUC of the joint probability of CONUT score, age, and hypertension in predicting all-cause mortality was 0.744 (95% CI = 0.687–0.775; Supplementary Figure 1, https://links.lww.com/CM9/A993). With respect to the secondary outcomes, a high CONUT score was an independent risk factor (HR = 16.619, 95% CI = 1.484–86.120, P = 0.023; Supplementary Table 5, https://links.lww.com/CM9/A993) after adjusting for con-foundingfactors, includingage, hypertension, and surgical duration. The CONUT score is a well-known immune-nutritional index. To our knowledge, the relationship between CONUT score and mortality has been rarely investigated previously in Chinese patients undergoing cardiac surgery. The major finding of our study is that a high CONUT score (>3) is an independent predictor of all-cause mortality and post-operative complications in patients undergoing cardiac surgery. Recently, malnutrition has been recognized as an independent predictor of mortality in patients with coronary artery disease (CAD).[3] De Ulibarri et al[1] used the CONUT score to identify malnutrition in an inhospital population for the first time. In the present study, the high CONUT score before surgery was associated with a higher risk of mortality and post-operative complications. Approximately 24.3% of patients had a high CONUT score, and the survival rate of patients in this group was significantly lower than the low CONUT group. In addition, the AUC of the joint probability of CONUT score, age, and hypertension was the largest. According with a previous study, the CONUT score is associated with an increased incidence of death in asymptomatic patients with cardiac disease.[4] Moreover, poor nutritional status, as assessed by the CONUT score, is associated with a poor prognosis in patients with acute heart failure. Wada et al[3] followed 1987 patients with stable CAD who underwent percutaneous coronary intervention for 7.4 years and found that a high CONUT score was related to major adverse cardiac events. To date, numerous studies have evaluated the prognostic value of nutrition indicators in patients undergoing cardiac surgery. Standard scoring systems, such as the Mini-Nutritional Assessment, the Subjective Global Assessment, and the Malnutrition Universal Screening Tool, have been regarded as significant predictors of prognosis in patients undergoing cardiac surgery. However, these nutritional screening tools are based on cognitive assessments evaluated by clinicians, which may cause bias. The Geriatric Nutritional Risk Index (GNRI) is calculated based on serum albumin and body weight. Previous study found that the CONUT score had a better prognostic value than the GNRI in predicting 1-year all-cause mortality in patients undergoing TAVI.[2] The CONUT score assesses different aspects of malnutrition using inexpensive objective markers determined from laboratory data. Albumin is recognized as the major protein in human plasma and it is also the most plentiful protein in the extracellular component. Nutrient intake plays an important role in albumin synthesis. Therefore, malnutrition, inflammation, and cachexia can lead to hypoalbuminemia. Several studies have shown that hypoalbuminemia is associated with mortality after TAVI. Cardiac surgery results in an anticipated increase in inflammatory mediators. Albumin, inflammatory, and nutritional factors have been reported to be correlated with the progression of atherosclerosis and cardiovascular disease.[5] Lymphocytopenia can reflect a poorly regulated immune response because of corticosteroid release. Marcula et al[6] reported that low lymphocyte counts predicted poor outcomes in patients with CAD. Horwich et al[7] showed that hypocholesterolemia was associated with a marked increase in mortality in patients with heart failure, although it is common knowledge that hypercholesterolemia is a risk factor for CAD in the general population. Based on these observations, the CONUT score is appropriate to evaluate nutritional status and to predict clinical outcomes in patients undergoing cardiac surgery. Several studies have shown that patients with chronic heart failure may benefit from nutritional intake. Thus, researchers should conduct follow-up studies to evaluate whether nutritional interventions could improve clinical outcomes in patients undergoing cardiac surgery. Our study has several limitations that should be considered. First, it was a retrospective single-center study of the Chinese population with small sample size, so the study may suffer from selection bias and a center-specific effect. In addition, incomplete data and loss to follow-up cannot be ignored. The applicability of our findings to other ethnic groups also needs further validation in future studies. Second, we only evaluated the CONUT score before surgery, we did not record changes over time. Third, we did not confirm whether perioperative nutritional support improved clinical outcomes. Finally, information on cardiovascular drug use was unavailable, and poor compliance might have affected the clinical outcomes. In summary, nutritional status evaluated by the CONUT score was independently associated with all-cause mortality and post-operative complications in patients undergoing cardiac surgery in this study. Thus, a preoperative assessment of the CONUT score may have useful prognostic value in clinical practice. Funding This study was supported by a grant from Jiangsu Provincial Medical Youth Talent (No. KY2017142).