Ceramide is upregulated and associated with mortality in patients with chronic heart failure.
BACKGROUND
Ceramide is involved in apoptosis, inflammation, and stress responses, which are among the pathogenic components of chronic heart failure (CHF). However, no one has documented the levels of ceramide itself in CHF or determined its potential prognostic value.


METHODS
In this study we recruited patients with heart failure consecutively from the hospital, of whom 423 stable patients were eventually selected to participate in this study after an observation period of at least 3 months after hospital discharge. All patents were followed up for all-cause death to December 31, 2013.


RESULTS
Plasma ceramide levels were increased stepwise with New York Heart Association functional class (I, 5.32 ± 1.98; II, 5.81 ± 1.63; III, 6.14 ± 2.14; IV, 6.66 ± 2.61 ng/mL). During a mean follow-up of 4.4 years (interquartile range: 3.5-5.3 years), a total of 200 CHF patients died. The optimal threshold value of ceramide was 6.05 ng/mL. Ceramide levels as continuous and as dichotomous variables are risk factors for mortality in CHF (adjusted hazard ratio, 1.31; 95% confidence interval, 1.16-1.47; P < 0.001 and adjusted hazard ratio, 2.07, 95% confidence interval, 1.53-2.81; P < 0.001, respectively). When ceramide levels were combined with conventional CHF risk factors, the area under the curve increased from 0.68 (0.63-0.72) to 0.72 (0.68-0.76); P = 0.047. The continuous net reclassification index and integrated discrimination improvement index were 17.2% (5.0-29.9%; P = 0.027) and 0.04 (0.01-0.08; P = 0.020), respectively.


CONCLUSIONS
Plasma ceramide levels were increased and correlated with the severity of CHF, and were an independent risk factor of mortality in patients with CHF and reduced left ventricular systolic function. Ceramide levels might provide additional predictive value after conventional risk assessment.
The State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, Changsha, Hunan, China.
Jingjia
J
Yu
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
Wei
W
Pan
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
Ruizheng
R
Shi
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
Tianlun
T
Yang
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
Yuanjian
Y
Li
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
Guolong
G
Yu
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
Yongping
Y
Bai
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Edward H
EH
Schuchman
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: xingxuan.he@mssm.edu.
Xingxuan
X
He
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China. Electronic address: xyzgg2006@sina.com.
Guogang
G
Zhang
D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002518:Ceramides / Q000097:blood*; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D015415:Biomarkers; D002518:Ceramides