USE OF sCD14 OR ITS FRAGMENTS OR DERIVATIVES FOR RISK STRATIFICATION, DIAGNOSIS AND PROGNOSIS

Abstract

The present invention relates to a method for diagnosis of a cardiovascular disease or condition or atherosclerosis and for a method for evaluating the risk of a subject of developing the same. Methods are further provided for evaluating a subject's risk of mortality, for evaluating whether a subject will benefit from a certain treatment or whether a subject needs to be hospitalized or whether a subject may be discharged. The present invention provides sCD14 or a fragment or derivative thereof (including in particular sCD14-ST) as a novel marker for cardiovascular risk in general, more specifically as a marker for cardiovascular disease or condition, or atherosclerosis.

1 . A method for evaluating a subject's risk of developing a cardiovascular disease or condition or atherosclerosis, comprising the steps of
 a) determining the amount of a compound selected from sCD14, sCD14-ST, or a fragment or derivative of sCD14 other than sCD14-ST, in a sample of said subject,   b) comparing the amount determined in step a) to at least one reference amount, and   c) evaluating the subject's individual risk of developing a cardiovascular disease or condition or atherosclerosis based on the result obtained in step b).   
     
     
         2 . A method for diagnosing a cardiovascular disease or condition or atherosclerosis in a subject, comprising
 a) determining of the amount of a compound selected from sCD14, sCD14-ST, or a fragment or derivative of sCD14 other than sCD14-ST, in a sample of said subject,   b) comparing the amount determined in step a) to at least one reference amount, and   c) determining the presence or absence of the cardiovascular disease or condition or atherosclerosis based on the result obtained in step b).   
     
     
         3 . A method for evaluating the risk of mortality in a subject with a cardiovascular disease or condition or atherosclerosis, comprising
 a) determining the amount of a compound selected from sCD14, sCD14-ST, or a fragment or derivative of sCD14 other than sCD14-ST, in a sample of said subject,   b) comparing the amount determined in step a) to at least one reference amount, and   c) determining the subject's risk of mortality based on the result obtained in step b).   
     
     
         4 . A method for evaluating whether a subject with a cardiovascular disease or condition or atherosclerosis will benefit from the treatment with substance selected from the group consisting of antibiotics, probiotics and lactulose, comprising the steps of
 a) determining of the amount of a compound selected from sCD14, sCD14-ST, or a fragment or derivative of sCD14 other than sCD14-ST, in a sample of said subject,   b) comparing the amount determined in step a) to at least one reference amount, and   c) evaluating said likelihood based on the result obtained in step b).   
     
     
         5 . A method for determining whether a subject needs to be hospitalized due to a cardiovascular disease or condition or atherosclerosis, the method comprising
 a) determining the amount of a compound selected from sCD14, sCD14-ST, or a fragment or derivative of sCD14 other than sCD14-ST, in a sample of said subject,   b) comparing the amount determined in step a) to at least one reference amount, and   c) determining whether the subject needs to be hospitalized on the result obtained in step b).   
     
     
         6 . The method according to  claim 1 , further comprising the steps of
 a′) determining in the same or different sample of the same individual at least one additional marker,   b′) comparing the amount of the at least one additional marker determined in step a′) to at least one reference amount of said additional marker, and   c′) performing the respective step c) by combining the result obtained for said compound in step b) and the result obtained in step b′) for the at least one additional marker.   
     
     
         7 . The method according to  claim 6 , wherein the at least one additional marker is selected from the group consisting of neurohormonal markers, regulators of water balance, ischemic cardiac markers, cytokines, inflammatory markers and cellular adhesion molecules, preferably wherein the at least one additional marker is selected from the group consisting of procalcitonin, C-reactive protein and markers of the transforming growth factor-β cytokine superfamily, and/or the group consisting of a neurohormonal marker, an ischemic cardiac marker; an inflammatory marker and optionally a marker of the interleukin-1 receptor family. 
     
     
         8 . The method according to  claim 1 , wherein the subject shows symptoms of one or more cardiovascular diseases or conditions selected from the group consisting of acute coronary syndrome, acute heart failure, chronic heart failure, coronary artery disease, angina pectoris, myocardial infarction, ischemic stroke, hemorrhagic stroke, transient ischemic attacks. 
     
     
         9 . The method according to  claim 8 , wherein the cardiovascular disease or condition is any one of:
 (i) chronic heart failure, preferably wherein the amount of the compound is 115 pg/ml or higher, more preferably 150 pg/ml or higher, even more preferably 260 pg/ml or higher;   (ii) angina pectoris, preferably wherein the amount of the compound is 214 pg/ml or higher, more preferably 216 pg/ml or higher, even more preferably 222 pg/ml or higher;   (iii) acute heart failure, preferably wherein the amount of the compound is 295 pg/ml or higher, more preferably 354 pg/ml or higher, even more preferably 455 pg/ml or higher;   (iv) myocardial infarction, preferably wherein the amount of the compound is 260 pg/ml or higher, more preferably 276 pg/ml or higher, even more preferably 295 pg/ml or higher.   
     
     
         10 . The method according to  claim 1 , wherein the method is for identifying a subject having a cardiovascular disease or condition or atherosclerosis that has an elevated risk of mortality, wherein the amount of the compound is preferably 500 pg/ml or higher, more preferably 800 pg/ml or higher, even more preferably 1300 pg/ml. 
     
     
         11 . The method according to  claim 1 , wherein the method is for evaluating the risk of a subject free from clinical signs of cardiovascular diseases or conditions or atherosclerosis to develop a cardiovascular disease or condition or atherosclerosis. 
     
     
         12 - 14 . (canceled) 
     
     
         15 . A kit for diagnosis of a cardiovascular disease or condition or atherosclerosis, for evaluating a subject's risk of developing a cardiovascular disease or condition or atherosclerosis, for evaluating a risk of mortality in a subject with a cardiovascular disease or condition or atherosclerosis, for evaluating the likelihood that a subject with a cardiovascular disease or condition or atherosclerosis will benefit from the treatment with a substance selected from the group consisting of antibiotics, probiotics and lactulose and/or for evaluating whether a subject needs to be hospitalized due to a cardiovascular disease or condition or atherosclerosis, the kit comprising
 a) means for determining the amount of a compound selected from sCD14, sCD14-ST, or a fragment or derivative of sCD14 other than sCD14-ST, in a sample from a subject;   b) instructions for the diagnosis and/or risk evaluation based on the amount determined by a); and optionally   c) means for determining the amount of at least one additional marker and instructions for the diagnosis and/or risk evaluation based on the determined amount of said at least one additional marker.   
     
     
         16 . A method according to  claim 3 , wherein said risk of mortality is the risk of mortality after cardiac surgery or the subject has undergone cardiac surgery. 
     
     
         17 . (canceled) 
     
     
         18 . A method for differentiating between cardiac and non-cardiac chest pain in a subject presenting with chest pain, comprising the steps of
 a) determining the amount of a compound selected from sCD14, sCD14-ST, or a fragment or derivative of sCD14 other than sCD14-ST, in a sample of said subject,   b) comparing the amount determined in step a) to at least one reference amount, and   c) determining the presence or absence of cardiac chest pain based upon the result obtained in step (b).   
     
     
         19 . (canceled) 
     
     
         20 . A method according to  claim 1 , wherein the compound is sCD14-ST.