Procalcitonin for the prognosis of adverse events

Abstract

The present invention relates to an in vitro method for the prognosis of an adverse event in asymptomatic subjects comprising the determination of the level of Procalcitonin (PCT) or a fragment thereof or a precursor or fragment thereof having at least 12 amino acid residues in a sample of a bodily fluid from said subject and the correlation of the determined level to a potential risk of sustaining an adverse event.

1 - 17 . (canceled) 
     
     
         18 . A method for determining an increased risk of an apparently healthy subject, preferably a human, for suffering from an adverse event, comprising:
 providing a sample from said subject;   determining the level of procalcitonin (PCT) or of a fragment thereof in said sample; and   determining whether said subject has an increased risk for suffering from an adverse event based on said PCT level,   
       wherein said adverse event is not an event caused by an acute exogene induced adverse event and/or exogene induced trauma and wherein the following subjects are excluded from the group of apparently healthy subjects:
 neonates between 1 day to 3 days
 and 
 
 patients after surgery wherein the surgery has been conducted within the last 7 days
 and 
 
 post-trauma patients and persons which experienced said trauma within the last 7 days. 
 
     
     
         19 . The method of  claim 18 , wherein PCT has the amino acid sequence shown as SEQ ID NO. 1. 
     
     
         20 . The method of  claim 18 , wherein said PCT fragment comprises (contains)
 at least 12 amino acids, preferably more than 50 amino acids, most preferably more than 100 amino acids, or   the amino acids 2 to 116 or 3 to 116 of the amino acid sequence shown as SEQ ID NO. 1.   
     
     
         21 . The method of  claim 18 , wherein said level determination is performed using a diagnostic assay, preferably an immunoassay. 
     
     
         22 . The method of  claim 18 , wherein the adverse event is chosen from the group consisting of cardiac events, cardiovascular events, cerebrovascular events, cardiovascular mortality, diabetes, cancer mortality, and death. 
     
     
         23 . The method of  claim 18 , wherein the risk determination is performed by
 comparing the determined PCT or PCT fragment level with the median of the level of PCT or fragments thereof in an ensemble of predetermined samples from a population of apparently healthy subjects, or   comparing the determined PCT or PCT fragment level with a quantile of the level of PCT or fragments thereof in an ensemble of predetermined samples from a population of apparently healthy subjects, or   performing calculations based on Cox Proportional Hazards analysis or on risk index calculations such as the Net Reclassification Index (NRI) or the Integrated Discrimination Index (IDI).   
     
     
         24 . The method of  claim 18 , wherein the subject is free of symptomatic infections. (PCT level not increased above normal range) 
     
     
         25 . The method of  claim 18 , wherein the sample is a bodily fluid, in particular blood, serum, plasma, cerebrospinal fluid, urine, saliva, sputum, or a pleural effusion. 
     
     
         26 . The method of  claim 18 , wherein said subject is determined of being at risk for suffering from an adverse event when said PCT level in a serum or plasma sample is at least 0.015 ng/ml, preferably at least 0.02 ng/ml. 
     
     
         27 . The method of  claim 18 , wherein said subject is determined of being at an increased risk for suffering from a cardiac event or a cardiovascular event when said PCT level in a serum sample is at least 0.0155 ng/ml. 
     
     
         28 . The method of  claim 18 , wherein said subject is determined of being at an increased risk for suffering from a cerebrovascular event or from dying due to a cardiovascular cause when said PCT level in a serum sample is at least 0.0215 ng/ml. 
     
     
         29 . The method of  claim 18 , wherein said subject is determined of being at an increased risk for dying from cancer when said PCT level in a serum sample is at least 0.0155 ng/ml. 
     
     
         30 . The method of  claim 18 , wherein said subject is determined of being at an increased risk for dying when said PCT level in a serum sample is at least 0.0205 ng/ml. 
     
     
         31 . The method of  claim 18 , wherein said subject is determined of being at an increased risk for suffering from diabetes when said PCT level in a serum sample is at least 0.0185 ng/ml. 
     
     
         32 . The method of  claim 18 , further comprising determining
 a clinical parameter that is selected from the group consisting of gender, age, systolic blood pressure, systolic blood pressure, diastolic blood pressure, body mass index, waist circumference, waist-hip ratio, and smoking habit; or   a laboratory parameter that is selected from the group consisting of fasting blood or plasma glucose concentration, triglycerides, cholesterol concentration, and HDL cholesterol concentration and subfractions thereof, LDL cholesterol concentration and subfractions thereof, cystatin C, insulin, CRP, natriuretic peptides of the A- and B-type as well as their precursors and fragments thereof including ANP, proANP, NT-proANP, MR-proANP, BNP, proBNP, NT-proBNP, GDF15, ST2, procalcitonin and fragments thereof, pro-adrenomedullin and fragments thereof including ADM, PAMP, MR-proADM, CT-proADM, pro-Endothelin-1 and fragments thereof including CT-proET-1, NT-proET-1, big-Endothelin-1, and Endothelin-1; or   a genetic parameter that is selected from the group consisting of single nucleotide polymorphisms (SNP), and mutations, in particular related to diabetes heredity.   
     
     
         33 . The method of  claim 18 , further comprising taking at least one preventive measure for avoiding said adverse event from occurring in said subject. 
     
     
         34 . Use of a method of  claim 18  for determining an increased risk of an apparently healthy subject for suffering from an adverse event.