Method to predict the risk of a cardiovascular event in a patient

Abstract

The inventors have identified new peptide biomarkers related to methylglyoxal (MGO)-induced glycation of plasma albumin, as well as the most abundant plasma apolipoproteins. Plasma concentrations of MGH-APOB1003184-3194, MGH-ALB219-225, CEL-APOA229-39 were higher in patients with type 2 diabetes (T2D). After follow-up, cases of major adverse cardiovascular events (MACE), cases of severe coronary artery disease (CAD) events, cases of cardiovascular (CV) deaths and cases of all-cause deaths were reported in The SURDIAGENE study (n = 1425). Increased plasma concentrations of MGH-APOB1003184-3194,MGH-ALB219- 225, CEL-APOA229-39 were significantly associated with an increased risk of developing MACE, CAD, CV death, and / or CV death. Thus the present invention refers to a method of predicting the risk of having or developing a cardiovascular event in a patient.

Description

[0001] METHOD TO PREDICT THE RISK OF A CARDIOVASCULAR EVENT IN A PATIENT FIELD OF THE INVENTION: The present invention relates to a method of determining whether a patient with a type 2 diabetes (TD2) is at a risk of developing a cardiovascular event. BACKGROUND OF THE INVENTION: Nowadays, 463 million people are living with diabetes worldwide1, and recent predictions estimate that the number of affected people may rise up to 578 million by the year 20302, with type 2 diabetes (T2D) as the predominant form of the disease (~90%). Compared to the general population, cardiovascular diseases (CVD) are 2–4 times more prevalent in patients living with T2D, and CVD constitute one of the leading causes of T2D-associated mortality3. Because traditional clinical markers do not fully capture this increased risk, novel early biomarkers of T2D-associated CVD and mortality are urgently needed to improve the clinical management of T2D. Proteins are reliable biomarkers for the early detection of diseases4, and their post- translational modifications (PTMs) have emerged as essential for understanding the mechanisms involved in organ failure5. PTMs are covalent modifications of proteins following their biosynthesis4, and combine various chemical reactions allowing the addition of functional groups to an amino acid6–8. PTMs also depend on the metabolic environment, and specific protein PTMs are closely involved in the pathogenesis of diabetes complications9. However, protein PTMs are diverse and present at low concentration levels. Several studies evidenced that chronic hyperglycemia and insulin resistance alter lipoprotein homeostasis17. Lipoproteins are biochemical assemblies between proteins(apolipoproteins) and lipids (triglycerides, cholesterol) whose primary function is to ensureblood transport and distribution of lipids to tissues. The main abnormalities reported in T2D are elevated triglyceride concentrations, attributed to an overproduction and a reduced clearance of triglyceride-rich lipoproteins18, and a reduction of high-density lipoprotein (HDL) cholesterol, attributed to an increased HDL catabolism and a reduction of their cholesterol efflux capacity17. T2D patients also displays elevated very-low-density lipoproteins (VLDLs), increased small / dense low-density lipoproteins (LDLs), prone to oxidation and exhibiting higher plasma residence time, and an overexposure of lipoproteins to glycation, among other PTMs17. Apolipoproteins function as structural components of lipoprotein particles, cofactors for enzymes and ligands for cell-surface receptors4,16. They are abundant in the plasma and play a central role in lipoprotein metabolism and atherosclerotic processes10. It has been reported that plasma apolipoproteins can predict CVD better than plasma lipids10. Apolipoproteins also exhibit proteoforms arising from both single nucleotide polymorphisms (SNPs) and PTMs4, which can affect their turnover and functions. A few studies have unraveled the presence of PTMs for some major apolipoproteins in T2D and CVD11–15. Therefore, the identification of relevant new biomarker candidates related to apolipoprotein PTMs is highly promising to refine the early detection of CVD in patients living with T2D. Mendelian randomization studies indicated a causal association between CV events and genetic variants related to glycated hemoglobin (HbA1c)19, supporting that glycation is strongly associated with CVD. Glycation is a nonenzymatic and irreversible PTM initiated by theaddition of a reducing sugar (e.g. glucose) onto the free amine of a protein to form a Schiffbase, which are then transformed into irreversible Amadori products by rearrangements. Amadori products can form either glycation intermediates, such as methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) by cleavage and oxidation, or directly advanced glycation end-products (AGE) in a few weeks20. Glycation intermediates, and especially MGO, are highly reactive and can bind in turn to free amines of proteins to form AGEs in a few days21. Hence, glycation mediated by such dicarbonyl intermediates seems of interest for the study of apolipoprotein glycation as apolipoproteins display turnover rates of a few days. Glycation intermediates or related by-products could be also promising biomarkers of T2D-associated CVD and mortality. In that respect, a recent epidemiological study reported that higher plasma levels of MGO were associated with total and fatal CVD and with all-cause mortality, myocardial infarction, and amputations in patients living with T2D22. In this study, plasma MGO levels were not apparently associated with stroke, and higher GO levels were significantly associated with fatal CVD but not with other outcomes. Then, in this study, 3-DG was not significantly associated with any of the outcomes. However, MGO, GO and 3-DG are not stable over time and their quantification requires immediate and specific sample preparation at the time of collection to obtain reliable concentrations23. Such requirements remain difficult to translate into clinical practice and make the analysis and result interpretation complex for existing cohorts. For the last decade, numerous studies have shown that mass spectrometry (MS)-based assays allows the simultaneous and specific quantification of multiple proteins in a single run10,24. Such protocols often involve the analysis of peptide mixtures resulting from the enzymatic proteolysis of proteins. By selecting appropriate proteotypic peptides, MS can also provide further information by targeting specific polymorphisms24–26, including those related to PTM4,27. Here we hypothesized that proteotypic peptides related to MGO-induced glycation of plasma proteins could be promising and stable biomarkers associated with CVD and related mortality in persons living with T2D. However, since protein PTM are various and present atlow concentration levels, their study remains a huge challenge. Hence, our aims were to identifyand validate peptide biomarkers related to MGO-induced glycation of plasma albumin, the mostabundant protein in plasma, as well as the most abundant plasma apolipoproteins (i.e. apoA-Iand apoA-II for HDL metabolism, apoB100 for VLDL / LDL metabolism) and then to assess their association with the risk of major adverse cardiovascular events (MACE) in patients living with T2D. SUMMARY OF THE INVENTION: The invention refers to an ex vivo method for determining whether a subject is at a riskof having or developing a cardiovascular event comprising the steps of: i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine amino acid residue (R) at position 3185 in SEQ IDNO:4 (ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the arginine amino acid residue (R) at position 222 in SEQ IDNO:5 (Albumin) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the lysine amino acid residue (K) at position 30 in SEQ ID NO:6(ApoA-II) into a carboxyethyl-lysine (K+72) ii) and positively correlating said level of glycation with the risk of developing acardiovascular event in said subject. The invention also refers to an ex vivo method for assessing a subject’s risk of havinga poor prognostic of survival, an in particular CV mortality, comprising the steps of: i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine amino acid residue (R) at position 3185 in SEQ IDNO:4 (ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the arginine amino acid residue (R) at position 222 in SEQ IDNO:5 (Albumin) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the lysine amino acid residue (K) at position 30 in SEQ ID NO:6(ApoA-II) into a carboxyethyl-lysine (K+72), ii) comparing each level of glycation determined at step i) with a reference value,and iii) concluding that the that the subject is at high risk of having a poor prognostic ofsurvival when the level(s) of glycation(s) determined at step i) are higher than the reference value. Particularly, the invention is defined by its claims. DETAILED DESCRIPTION OF THE INVENTION: The inventors have identified new peptide biomarkers related to MGO-induced glycation of plasma albumin, the most abundant protein in plasma, as well as the most abundantplasma apolipoproteins (i.e. apoA-I and apoA-II for HDL metabolism, apoB100 forVLDL / LDL metabolism). All peptide identified displayed a change in their arginine residue toa carboxyethyl-arginine (CEA (+72 Da)), a methylglyoxal-derived hydroimidazolone (MG-H(+54 Da)) or both, except for apoA-II for which a change in a lysine residue to a carboxyethyl-lysine (CEL (+72 Da)) was observed.After a new screening of trypsin-digested plasma samples with the optimized LC- MS / MS method, only measurements of NR+54NNALDFVTK (named MGH-ApoB1003184-3194, SEQ ID NO:1), LSQR+54FPK (named MGH-Alb219-225, SEQ ID NO:2), VK+72SPELQAEAK (named CEL-ApoA229-39,SEQ ID NO:3), and VEPLR+54AELQEGAR (named MGH-ApoA1143-155, SEQ ID NO:4), were repeatable. Plasma concentrations of MGH-ALB219-225,CEL-APOA229-39 and MGH-APOB1003184-3194 were significantly higher in patients with T2Dcompared to non-diabetic controls. During follow-up, cases of MACE, cases of severe CADevents, CV deaths and all-cause deaths were reported in The SURDIAGENE study. Plasmaconcentrations of MGH-APOB1003184-3194, MGH-ALB219-225, CEL-APOA229-39 weresignificantly associated with the risk of developing severe CAD events, and / or MACE and / orCV mortality. Definition As used herein the term “apolipoproteins” has its general meaning in the art, and refers to serum proteins that mediate carriage of cholesterol and other lipids in the serum. As such, they form the protein components of lipoprotein particles such as high-density lipoproteins(HDL) and low-density lipoproteins (LDL) in serum. There are multiple classes ofapolipoproteins and several sub-classes such as apolipoprotein A (ApoA-I, ApoA-II, ApoA-IVand ApoA-V), apolipoprotein B (ApoB48 and ApoB100), apolipoprotein C (ApoC-I, ApoC-II,ApoC-III and ApoC-IV), apolipoprotein D, apolipoprotein E, apolipoprotein F, apolipoproteinH, apolipoprotein L, and apolipoprotein M. Apolipoprotein B are the primary apolipoproteins of chylomicrons (ApoB48), very-low-density lipoprotein (VLDL, ApoB100), lipoprotein (a) [Lp(a), ApoB100], intermediate-density lipoprotein (IDL, ApoB100), and LDL (ApoB100) particles, which are responsible forcarrying lipids, including triglyceride and cholesterol, from their sites of synthesis or absorptionto their sites of use and storage through the bloodstream. The protein occurs in the plasma in 2main isoforms, ApoB48 and ApoB100. The first is synthesized exclusively by the smallintestine, the second by the liver. ApoB100 is the largest of the ApoB group of proteins,consisting of 4563 amino acids. Its Uniprot reference is P04114.The human ApoB100 (without peptide signal) has the following amino acid sequence SEQ ID NO:4: SEQ ID NO:4 > P04114_HUMAN Apolipoprotein B-100 OS=Homo sapiensEEEMLENVSLVCPKDATRFKHLRKYTYNYEAESSSGVPGTADSRSATRINCKVELEVPQLCSFILKTSQ CTLKEVYGFNPEGKALLKKTKNSEEFAAAMSRYELKLAIPEGKQVFLYPEKDEPTYILNIKRGIISALLVPPETE EAKQVLFLDTVYGNCSTHFTVKTRKGNVATEISTERDLGQCDRFKPIRTGISPLALIKGMTRPLSTLISSSQSCQ YTLDAKRKHVAEAICKEQHLFLPFSYKNKYGMVAQVTQTLKLEDTPKINSRFFGEGTKKMGLAFESTKSTSPPKQ AEAVLKTLQELKKLTISEQNIQRANLFNKLVTELRGLSDEAVTSLLPQLIEVSSPITLQALVQCGQPQCSTHILQ WLKRVHANPLLIDVVTYLVALIPEPSAQQLREIFNMARDQRSRATLYALSHAVNNYHKTNPTGTQELLDIANYLM EQIQDDCTGDEDYTYLILRVIGNMGQTMEQLTPELKSSILKCVQSTKPSLMIQKAAIQALRKMEPKDKDQEVLLQ TFLDDASPGDKRLAAYLMLMRSPSQADINKIVQILPWEQNEQVKNFVASHIANILNSEELDIQDLKKLVKEALKE SQLPTVMDFRKFSRNYQLYKSVSLPSLDPASAKIEGNLIFDPNNYLPKESMLKTTLTAFGFASADLIEIGLEGKG FEPTLEALFGKQGFFPDSVNKALYWVNGQVPDGVSKVLVDHFGYTKDDKHEQDMVNGIMLSVEKLIKDLKSKEVP EARAYLRILGEELGFASLHDLQLLGKLLLMGARTLQGIPQMIGEVIRKGSKNDFFLHYIFMENAFELPTGAGLQL QISSSGVIAPGAKAGVKLEVANMQAELVAKPSVSVEFVTNMGIIIPDFARSGVQMNTNFFHESGLEAHVALKAGK LKFIIPSPKRPVKLLSGGNTLHLVSTTKTEVIPPLIENRQSWSVCKQVFPGLNYCTSGAYSNASSTDSASYYPLT GDTRLELELRPTGEIEQYSVSATYELQREDRALVDTLKFVTQAEGAKQTEATMTFKYNRQSMTLSSEVQIPDFDV DLGTILRVNDESTEGKTSYRLTLDIQNKKITEVALMGHLSCDTKEERKIKGVISIPRLQAEARSEILAHWSPAKL LLQMDSSATAYGSTVSKRVAWHYDEEKIEFEWNTGTNVDTKKMTSNFPVDLSDYPKSLHMYANRLLDHRVPQTDM TFRHVGSKLIVAMSSWLQKASGSLPYTQTLQDHLNSLKEFNLQNMGLPDFHIPENLFLKSDGRVKYTLNKNSLKI EIPLPFGGKSSRDLKMLETVRTPALHFKSVGFHLPSREFQVPTFTIPKLYQLQVPLLGVLDLSTNVYSNLYNWSA SYSGGNTSTDHFSLRARYHMKADSVVDLLSYNVQGSGETTYDHKNTFTLSCDGSLRHKFLDSNIKFSHVEKLGNN PVSKGLLIFDASSSWGPQMSASVHLDSKKKQHLFVKEVKIDGQFRVSSFYAKGTYGLSCQRDPNTGRLNGESNLR FNSSYLQGTNQITGRYEDGTLSLTSTSDLQSGIIKNTASLKYENYELTLKSDTNGKYKNFATSNKMDMTFSKQNA LLRSEYQADYESLRFFSLLSGSLNSHGLELNADILGTDKINSGAHKATLRIGQDGISTSATTNLKCSLLVLENEL Ķ

[0002] NAELGLSGASMKLTTNGRFREHNAKFSLDGKAALTELSLGSAYQAMILGVDSKNIFNFKVSQEGLKLSNDMMGSY AEMKFDHTNSLNIAGLSLDFSSKLDNIYSSDKFYKQTVNLQLQPYSLVTTLNSDLKYNALDLTNNGKLRLEPLKL HVAGNLKGAYQNNEIKHIYAISSAALSASYKADTVAKVQGVEFSHRLNTDIAGLASAIDMSTNYNSDSLHFSNVF RSVMAPFTMTIDAHTNGNGKLALWGEHTGQLYSKFLLKAEPLAFTFSHDYKGSTSHHLVSRKSISAALEHKVSAL LTPAEQTGTWKLKTQFNNNEYSQDLDAYNTKDKIGVELTGRTLADLTLLDSPIKVPLLLSEPINIIDALEMRDAV EKPQEFTIVAFVKYDKNQDVHSINLPFFETLQEYFERNRQTIIVVLENVQRNLKHINIDQFVRKYRAALGKLPQQ ANDYLNSFNWERQVSHAKEKLTALTKKYRITENDIQIALDDAKINFNEKLSQLQTYMIQFDQYIKDSYDLHDLKI AIANIIDEIIEKLKSLDEHYHIRVNLVKTIHDLHLFIENIDFNKSGSSTASWIQNVDTKYQIRIQIQEKLQQLKR HIQNIDIQHLAGKLKQHIEAIDVRVLLDQLGTTISFERINDILEHVKHFVINLIGDFEVAEKINAFRAKVHELIE RYEVDQQIQVLMDKLVELAHQYKLKETIQKLSNVLQQVKIKDYFEKLVGFIDDAVKKLNELSFKTFIEDVNKFLD MLIKKLKSFDYHQFVDETNDKIREVTQRLNGEIQALELPQKAEALKLFLEETKATVAVYLESLQDTKITLIINWL QEALSSASLAHMKAKFRETLEDTRDRMYQMDIQQELQRYLSLVGQVYSTLVTYISDWWTLAAKNLTDFAEQYSIQ DWAKRMKALVEQGFTVPEIKTILGTMPAFEVSLQALQKATFQTPDFIVPLTDLRIPSVQINFKDLKNIKIPSRFS TPEFTILNTFHIPSFTIDFVEMKVKIIRTIDQMLNSELQWPVPDIYLRDLKVEDIPLARITLPDFRLPEIAIPEF IIPTLNLNDFQVPDLHIPEFQLPHISHTIEVPTFGKLYSILKIQSPLFTLDANADIGNGTTSANEAGIAASITAK GESKLEVLNFDFQANAQLSNPKINPLALKESVKFSSKYLRTEHGSEMLFFGNAIEGKSNTVASLHTEKNTLELSN GVIVKINNQLTLDSNTKYFHKLNIPKLDFSSQADLRNEIKTLLKAGHIAWTSSGKGSWKWACPRFSDEGTHESQI SFTIEGPLTSFGLSNKINSKHLRVNQNLVYESGSLNFSKLEIQSQVDSQHVGHSVLTAKGMALFGEGKAEFTGRH DAHLNGKVIGTLKNSLFFSAQPFEITASTNNEGNLKVRFPLRLTGKIDFLNNYALFLSPSAQQASWQVSARFNQY KYNQNFSAGNNENIMEAHVGINGEANLDFLNIPLTIPEMRLPYTIITTPPLKDFSLWEKTGLKEFLKTTKQSFDL SVKAQYKKNKHRHSITNPLAVLCEFISQSIKSFDRHFEKNRNNALDFVTKSYNETKIKFDKYKAEKSHDELPRTF QIPGYTVPVVNVEVSPFTIEMSAFGYVFPKAVSMPSFSILGSDVRVPSYTLILPSLELPVLHVPRNLKLSLPDFK ELCTISHIFIPAMGNITYDFSFKSSVITLNTNAELFNQSDIVAHLLSSSSSVIDALQYKLEGTTRLTRKRGLKLA TALSLSNKFVEGSHNSTVSLTTKNMEVSVATTTKAQIPILRMNFKQELNGNTKSKPTVSSSMEFKYDFNSSMLYS TAKGAVDHKLSLESLTSYFSIESSTKGDVKGSVLSREYSGTIASEANTYLNSKSTRSSVKLQGTSKIDDIWNLEV KENFAGEATLQRIYSLWEHSTKNHLQLEGLFFTNGEHTSKATLELSPWQMSALVQVHASQPSSFHDFPDLGQEVA LNANTKNQKIRWKNEVRIHSGSFQSQVELSNDQEKAHLDIAGSLEGHLRFLKNIILPVYDKSLWDFLKLDVTTSI GRRQHLRVSTAFVYTKNPNGYSFSIPVKVLADKFIIPGLKLNDLNSVLVMPTFHVPFTDLQVPSCKLDFREIQIY KKLRTSSFALNLPTLPEVKFPEVDVLTKYSQPEDSLIPFFEITVPESQLTVSQFTLPKSVSDGIAALDLNAVANK IADFELPTIIVPEQTIEIPSIKFSVPAGIVIPSFQALTARFEVDSPVYNATWSASLKNKADYVETVLDSTCSSTV QFLEYELNVLGTHKIEDGTLASKTKGTFAHRDFSAEYEEDGKYEGLQEWEGKAHLNIKSPAFTDLHLRYQKDKKG ISTSAASPAVGTVGMDMDEDDDFSKWNFYYSPQSSPDKKLTIFKTELRVRESDEETQIKVNWEEEAASGLLTSLK DNVPKATGVLYDYVNKYHWEHTGLTLREVSSKLRRNLQNNAEWVYQGAIRQIDDIDVRFQKAASGTTGTYQEWKD KAQNLYQELLTQEGQASFQGLKDNVFDGLVRVTQEFHMKVKHLIDSLIDFLNFPRFQFPGKPGIYTREELCTMFI REVGTVLSQVYSKVHNGSEILFSYFQDLVITLPFELRKHKLIDVISMYRELLKDLSKEAQEVFKAIQSLKTTEVL RNLQDLLQFIFQLIEDNIKQLKEMKFTYLINYIQDEINTIFSDYIPYVFKLLKENLCLNLHKFNEFIQNELQEAS QELQQIHQYIMALREEYFDPSIVGWTVKYYELEEKIVSLIKNLLVALKDFHSEYIVSASNFTSQLSSQVEQFLHR NIQEYLSILTDPDGKGKEKIAELSATAQEIIKSQAIATKKIISDYHQQFRYKLQDFSDQLSDYYEKFIAESKRLI DLSIQNYHTFLIYITELLKKLQSTTVMNPYMKLAPGELTIIL As used herein, the term “albumin” has its general meaning in the art and refers to a transport protein that bind to various ligands and carry them around. The human albumin (without peptide signal) has the following amino acid sequence in the art SEQ ID NO:5. SEQ ID NO:5 > P02652_HUMAN HSA OS=Homo sapiensDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTL FGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIAR RHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARL SQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVE NDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHEC YAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAK RMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEK ERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL Apolipoprotein A-II (ApoA-II) is the second most abundant apolipoprotein in HDLparticles after ApoA-I, playing important and contrasted roles in lipid metabolism. The proteinis found in plasma as a monomer, homodimer, or heterodimer with ApoD. ApoA-II regulates many steps in HDL metabolism, and its role in coronary heart disease is unclear. Its Uniprot reference is P02652. The human ApoA-II (without peptide signal) has the following amino acid sequence inSEQ ID NO:6: SEQ ID NO:6 > P02652_HUMAN Apolipoprotein A-2 OS=Homo sapiensQAKEPCVESLVSQYFQTVTDYGKDLMEKVKSPELQAEAKSYFEKSKEQLTPLIKKAGTELVNFLSYFVE LGTQPATQ Apolipoproteins (such as apoA-I, apoA-II, and apoB100) and Albumin can be glycated via a non-enzymatic reaction (Amadori reaction) that is affected by the plasmatic concentrationof glucose. Amadori compounds are produced from reducing sugars, such as glucose, and a freeamine. Amadori products can form either glycation intermediates, such as methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) by cleavage and oxidation, or directlyadvanced glycation end-products (AGE) in a few weeks20. AGEs are therefore a family ofcompounds of diverse chemical nature. Some typical AGEs resulting from MGO reactionsinclude carboxyethyl-arginine (CEA (+72 Da)), methylglyoxal-derived hydroimidazolone(MG-H (+54 Da)) and carboxyethyl-lysine (CEL (+72 Da)). As used herein, the term “glycated-protein”, such as glycated-apolipoprotein orglycated-albumin, is a form of protein that results from a non-enzymatic reaction (i.e Amadorireaction). Apolipoprotein (such as apoA-I, apoA-II and ApoB100) as well as Albumin can bechemically glycated by different glucose metabolites, and this reaction can be affected by theplasmatic concentration of glucose. Amadori compounds are produced from reducing sugars, such as glucose, and an amine. Amadori products can form either glycation intermediates, such as methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) by cleavage andoxidation, or directly advanced glycation end-products (AGE) in a few weeks20. AGEs are afamily of compounds of diverse chemical nature that are the products of non-enzymatic reactions between reducing sugars and proteins, lipids, or nucleic acids. Some typical AGEsresulting from MGO reactions include carboxyethyl-arginine (CEA (+72 Da)), methylglyoxal-derived hydroimidazolone (MG-H (+54 Da)) and carboxyethyl-lysine (CEL (+72 Da)).As used herein the term “comprise” or a variant thereof (e.g., “comprises”, “comprising”) also encompasses narrower expression “substantially consist of”, further narrower expression “consist of” and any variants thereof (e.g., “consists of”, “consisting of”), unless otherwise stated. As used herein, the term “patient” or “subject” denotes a mammal, such as a rodent, afeline, a canine, and a primate. Particularly, the subject according to the invention is a human. In some embodiments, the patient is a human having a personal history of coronary artery disease (CAD). In some embodiments, the patient is a human with diabetes, and more particularly a type2 diabetes (T2D). In some embodiments, the subject suffers from type 2 diabetes and has a personal history of coronary artery disease (CAD). As used herein, the term “sample” refers to any sample obtained from the subject forthe purpose of performing the method of the present invention. In some embodiments, thesample is a bodily fluid (e.g. a blood sample) or a tissue. In some embodiments, the sample isa blood sample. As used herein, the term “blood sample” means any blood sample derivedfrom the subject. Collections of blood samples can be performed by methods well known tothose skilled in the art. In some embodiments, the blood sample is a serum or plasma sample.Typically the plasma sample may be obtained using methods well known in the art. Plasma may then be obtained from the plasma sample following standard procedures of thefield including, but not limited to, centrifuging the whole blood sample containing ananticoagulant, followed by pipetting of the plasma layer. More preferably, the plasma sample obtained from the patient is a ethylene diamine tetra-acetic acid (EDTA) plasma. In a particular embodiment, the sample has been previously obtained from the subject.As used herein, the term “level of glycated-peptide(s)” refers to the concentration ofthe glycated-peptide of the invention. Typically, the level or concentration of the glycated-peptide may be determined by any technology known by a person skilled in the art.As used herein, the term “diabetes” or “diabetes mellitus” refers to chronic diseasesthat occurs either when the pancreas does not produce enough insulin or when the body cannoteffectively use the insulin it produces. The major types of diabetes are type 1 (~10%)and type2 diabetes (~90%).As used herein, the term “type 1 diabetes”, “insulin-dependent diabetes mellitus," "IDDM", "type 1 diabetes mellitus," and "T1DM," refer to diseases characterized by the autoimmune destruction of the β cells in the pancreatic islets of Langerhans. Such diseases can be diagnosed during their clinical phase characterized by the onset of dysglycemia or hyperglycemia (a dysregulated glucose metabolism) or during their preclinical phase characterized by the presence of active β-cell autoimmunity with positivity for islet autoantibodies, such as those targeting insulin, glutamic acid decarboxylase (GAD), islet- associated antigen (IA)-2 and zinc transporter (ZnT)8. As used herein, the term "type 2 diabetes" or “non-insulin dependent diabetes mellitus (NIDDM)” has its general meaning in the art. Type 2 diabetes often occurs when levels of insulin are normal or even elevated and appears to result from the inability of tissues to respond appropriately to insulin. Most of the type 2 diabetics are obese. As used herein the term "obesity" refers to a condition characterized by an excess of body fat. The operational definition of obesity is based on the Body Mass Index (BMI), which is calculated as body weight per height in meter squared (kg / m²). Obesity refers to a condition of increased fat mass whereby an otherwise healthy subject has a BMI greater than or equal to 30 kg / m², or a condition whereby a subject with at least one co-morbidity has a BMI greater than or equal to 27 kg / m². An "obese subject" is an otherwise healthy subject with a BMI greater than or equal to 30 kg / m² or a subject with at least one co-morbidity with a BMI greater than or equal 27 kg / m². A "subject at risk of obesity" is an otherwise healthy subject with a BMI of 25 kg / m² to less than 30 kg / m² or a subject with at least one co-morbidity with a BMI of 25 kg / m² to less than 27 kg / m². The increased risks associated with obesity may occur at a lower BMI in people of Asian descent. In Asian and Asian-Pacific countries, including Japan, "obesity" refers to a condition whereby a subject with at least one obesity-induced or obesity-related co-morbidity that requires weight reduction or that would be improved by weight reduction, has a BMI greater than or equal to 25 kg / m². An "obese subject" in these countries refers to a subject with at least one obesity-induced or obesity-related co-morbidity that requires weight reduction or that would be improved by weight reduction, with a BMI greater than or equal to 25 kg / m². In these countries, a "subject at risk of obesity" is a person with a BMI of greater than 23 kg / m2to less than 25 kg / m². As used herein, the term “cardiovascular event” denotes all disease characterised with a cardiac and / or vascular problem. A cardiovascular event included but is not limited toischemic heart disease, atherosclerotic cardiovascular disease such as coronary artery disease(CAD), peripheral arterial disease, cerebro-vascular disease and / or heart failure.As used herein, the term “coronary artery disease” or “CAD” refers to a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis, and acutecoronary syndrome such as angina pectoris and myocardial infarction. CAD remains thenumber one cause of death in industrialized society. Revascularization is the restoration ofblood supply to ischemic myocardium in an effort to limit ongoing damage, reduce ventricular irritability, and improve short-term and long-term outcomes in patients with acute coronary syndromes. According to the invention severe CAD refers to fatal or non-fatal myocardial infarction and / or coronary artery revascularization. As used herein, the term “personal history of CAD” or “CAD personal history” refersthat the subject has previously developed coronary artery disease. According to the invention,personal history of coronary artery disease was defined as history of angina pectoris and / or coronary revascularization and / or myocardial infarction. As used herein, the term “major adverse cardiovascular events” or “MACE” refersto a composite of cardiovascular mortality and non-fatal myocardial infarction, non-fatal stroke.As used herein, the term “glycated hemoglobin” also known as “GHb" is a form of hemoglobin that results from a non-enzymatic reaction (i.e Amadori reaction) covalent addition of a sugar molecule to the hemoglobin. Glycated hemoglobin includes several forms of glycation: HbA1a corresponds to the link of a fructose-1,6-diphosphate (HbA1a1) or a glucose-6-phosphate (HbA1a2); HbA1b corresponds to the link of a pyruvate; and HbA1c, the mostabundant glycated Hb found in red blood cells, contributing for more than 80% of glycated hemoglobin, corresponds to the link of a glucose and is affected by the plasmatic concentrationof glucose and the time red blood cells last in the circulationAs used herein, the term “glomerular filtration rate” or “”GFR” has its general meaning in the art and refers to important aspect of kidney function. The estimated glomerularfiltration rate (eGFR) is a test that measures your level of kidney function and determinesyour stage of kidney disease. There are several methods to test GFR. Most often, the GFR is estimated by measuring another substance. The estimated glomerular filtration rate (eGFR) test typically uses a formula based on the levels of creatinine. In particular embodiment, theestimated glomerular filtration rate (eGFR) is calculated with the CKD-EPI 2009-formula35As used herein, the term “LDL cholesterol” has its general meaning in the art and refersto the cholesterol content of low-density lipoproteins. It is sometimes called “bad” cholesterol,because it can contributes to fatty buildups in arteries (atherosclerosis). High levels of LDLcholesterol increase risk for ischemic heart disease and stroke. According to the invention, LDLcholesterol can be calculated using the Friedewald equation with some limitations like highplasma triglyceride concentrations. As used herein, the term “HDL cholesterol” has its general meaning in the art and refersto the cholesterol content of high-density lipoproteins. It is sometimes called “goodcholesterol”, it carries excess cholesterol away from arteries and back to the liver. Accordingto the invention, non-HDL cholesterol can be calculated as total cholesterol minus HDLcholesterol. As used herein, the term “creatinine” has its general meaning in the art and refers to abreakdown product of creatine phosphate from muscle and protein metabolism. Serumcreatinine (a blood measurement) is an important indicator of kidney health, because it is an easily measured byproduct of muscle metabolism that is excreted unchanged by the kidneys. “Urine albumin-creatinine ratio” (or uACR) an important test for identifying kidneydamage, in addition to the eGFR test. Different test can be used to determine uACR such asquantitative uACR, urine dipstick test, 24-hour urine collection As used herein, the term "Risk" in the context of the present invention, relates to the probability (i.e. at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,99% of risk) that an event will occur over a specific time period (e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, or10 years), as in the conversion to cardiovascular event, and can mean a subject's "absolute" risk or "relative" risk. Absolute risk can be measured with reference to either actual observation post-measurement for the relevant time cohort, or with reference to index values developed from statistically valid historical cohorts that have been followed for the relevant time period. Relative risk or hazard ratio refers to the ratio of absolute risks of a subject compared either to the absolute risks of low risk cohorts or an average population risk, which can vary by how clinical risk factors are assessed. A hazard ratio (HR) is the probability of positive event in a group relative to the control group probability over a unit of time. This ratio is an effect sizemeasure for time-to-event data. Relative risk asses risk at one point, often at the end of a studyIn contrast, hazard ratios originate from survival analysis studies that record time-to-event data. Odds ratios, the proportion of positive events to negative events for a given test result, are also commonly used (odds are according to the formula p / (l-p) where p is the probability ofevent and (1- p) is the probability of no event) to no- conversion."Risk evaluation," or "evaluation of risk" in the context of the present invention encompasses making a prediction of the probability, odds, or likelihood that an event or disease state may occur, the rate of occurrence of the event or conversion from one disease state to another, i.e., from a normal condition to loss of renal function or to one at risk of developing loss of renal function. Risk evaluation can also comprise prediction of future clinicalparameters, traditional laboratory risk factor values, or other indices of loss of renal function,either in absolute or relative terms in reference to a previously measured population. The methods of the present invention may be used to make continuous or categorical measurementsof the risk of conversion to loss of renal function, thus diagnosing and defining the risk spectrumof a category of subjects defined as being at risk of having loss of renal function. In the categorical scenario, the invention can be used to discriminate between normal and other subject cohorts at higher risk of having loss of renal function. Thus, the terms "high risk", "intermediate risk" and "low risk" refers to differences in the individual predisposition for developing a disease, disorder, complication or susceptibility therefor, preferably after a subject has been treated by one of the therapies referred to below, such as high-dose chemotherapy. Said high, intermediate or low risk can be statistically analyzed. Preferably, the differences between asubject or a group of subjects having a high, intermediate or low risk are statistically significant.This can be evaluated by well-known statistic techniques including Student's t-Test, Chi2-Test, Wilcoxon-Mann-Whitney Test, Kurskal-Wallis Test or Fisher's exact Test, log-rank test, logistic regression analysis, or Cox models. Most preferably, the risk groups are analyzed as described in the accompanied Examples whereby explorative data analysis is carried out and the risk groups are formed with respect to the median, the 25% and the 75% percentiles. Differences in continuous variables of the groups are tested by Wilcoxon-Mann-Whitney Test or Kurskal-Wallis Test depending on the number of groups to be compared. For nominal orordered categories, Fisher's exact or Chi2-Test for trend are applied. Without further ado, theperson skilled in the art can carry out multivariant analysis with stratified versions of the aforementioned tests or Cox models in order to examine the independent impact of predictive factors and to establish the different risk groups. As used herein, the term “high” refers to a measure that is significantly greater thannormal, greater than a standard, such as a predetermined reference value or a subgroup measure,or that is relatively greater than another subgroup measure. As used herein, the term “low”refers to a level that is less than normal or less than a standard, such as a predetermined referencevalue or a subgroup measure that is relatively less than another subgroup level. In some embodiments, the “predetermined reference value” is relative to a number orvalue derived from population studies, including without limitation, patients of the same or similar age range, patients in the same or similar ethnic group, and patients having the same severity of cancer. Such predetermined reference values can be derived from statistical analyses and / or risk prediction data of populations obtained from mathematical algorithms and computed indices of the disease. Typically, the predetermined reference value is a threshold or cutoffvalue. Typically, a "threshold value" or "cutoff value" can be determined experimentally,empirically, or theoretically. A threshold value can also be arbitrarily selected based on theexisting experimental and / or clinical conditions, as would be recognized by a person of ordinaryskill in the art. For example, retrospective measurement in properly banked historical subjectsamples may be used in establishing the predetermined reference value. The threshold valuehas to be determined to obtain the optimal sensitivity and specificity according to the functionof the test and the benefit / risk balance (clinical consequences of false positive and falsenegative). Typically, the optimal sensitivity and specificity (and the threshold value) can bedetermined using a Receiver Operating Characteristic (ROC) curve based on experimental data.For example, after determining the level of glycated-peptide in a group of reference, one canuse algorithmic analysis to statistically treat the levels determined in samples to be tested andthus obtain a classification standard having significance for sample classification. The full nameof the ROC curve is the receiver operator characteristic curve, also known as the receiveroperation characteristic curve. It is mainly used for clinical and biochemical diagnostic tests.The ROC curve is a comprehensive indicator that reflects the continuous variables of truepositive rate (sensitivity) and false positive rate (1-specificity). It reveals the relationshipbetween sensitivity and specificity with the image composition method. A series of differentcutoff values (thresholds or critical values, boundary values between normal and abnormaldiagnostic test results) are set as continuous variables to calculate a series of sensitivity andspecificity values. Then sensitivity is used as the vertical coordinate, and specificity is used asthe horizontal coordinate to draw a curve. The higher the area under the curve (AUC), the higherthe accuracy of diagnosis. On the ROC curve, the point closest to the far upper left of thecoordinate diagram is a critical point with high sensitivity and specificity values. The AUCvalue of the ROC curve is between 1.0 and 0.5. When AUC>0.5, the diagnostic result improvesas AUC approaches 1. When AUC is between 0.5 and 0.7, the accuracy is low. When AUC isbetween 0.7 and 0.9, the accuracy is moderate. When AUC is higher than 0.9, the accuracy ishigh. This algorithmic method is preferably done with a computer. Existing software or systemsin the art may be used to draw the ROC curve, such as MedCalc 9.2.0.1 medical statisticalsoftware, SPSS 9.0, ROCPOWER.SAS, DESIGNROC.FOR, MULTIREADER POWER.SAS, CREATE-ROC.SAS, GB STAT VI0.0 (Dynamic Microsystems, Inc. Silver Spring, Md., USA), etc. In some embodiments, the predetermined reference value is typically determined by carrying out a method comprising the steps of: a) providing a collection of samples from patients, in particular patients suffering fromT2D; b) providing, for each sample provided at step a), information relating to the actualclinical outcome for the corresponding patient (i.e. the occurring of cardiovascular event, the overall survival (OS), and the cardiovascular mortality); c) providing a serial of arbitrary quantification values; d) determining the level of the marker of interest (i.e. the glycated peptide of theinvention) for each sample contained in the collection provided at step a); e) classifying said samples in two groups for one specific arbitrary quantification value provided at step c), respectively: (i) a first group comprising samples that exhibit a quantification value for level that is lower than the said arbitrary quantification value containedin the said serial of quantification values; (ii) a second group comprising samples that exhibit aquantification value for said level that is higher than the said arbitrary quantification value contained in the said serial of quantification values; whereby two groups of samples are obtained for the said specific quantification value, wherein the samples of each group are separately enumerated; f) calculating the statistical significance between (i) the quantification value obtained at step e) and (ii) the actual clinical outcome of the patients from which samples contained in the first and second groups defined at step f) derive; g) reiterating steps f) and g) until every arbitrary quantification value provided at step d) is tested; h) setting the said predetermined reference value as consisting of the arbitrary quantification value for which the highest statistical significance (most significant) has been calculated at step g). As used herein, the term "treatment" or "treat" refer to both prophylactic or preventive treatment as well as curative or disease modifying treatment, including treatment of patient at risk of contracting the disease or suspected to have contracted the disease as well as patients who are ill or have been diagnosed as suffering from a disease or medical condition, and includes suppression of clinical relapse. The treatment may be administered to a patient havinga medical disorder or who ultimately may acquire the disorder, in order to prevent, cure, delaythe onset of, reduce the severity of, or ameliorate one or more symptoms of a disorder or recurring disorder, or in order to prolong the survival of a patient beyond that expected in the absence of such treatment. By "therapeutic regimen" is meant the pattern of treatment of an illness, e.g., the pattern of dosing used during therapy. A therapeutic regimen may include an induction regimen and a maintenance regimen. The phrase "induction regimen" or "induction period" refers to a therapeutic regimen (or the portion of a therapeutic regimen) that is used for the initial treatment of a disease. The general goal of an induction regimen is to provide a high level of drug to a patient during the initial period of a treatment regimen. An induction regimen may employ (in part or in whole) a "loading regimen", which may include administering a greater dose of the drug than a physician would employ during a maintenance regimen, administering a drug more frequently than a physician would administer the drug during a maintenance regimen, or both. The phrase "maintenance regimen" or "maintenance period" refers to a therapeutic regimen (or the portion of a therapeutic regimen) that is used for the maintenance of a patient during treatment of an illness, e.g., to keep the patient in remission for long periods of time (months or years). A maintenance regimen may employ continuous therapy (e.g., administering a drug at regular intervals, e.g., weekly, monthly, yearly, etc.) or intermittent therapy (e.g., interrupted treatment, intermittent treatment, treatment at relapse, or treatment upon achievement of a particular predetermined criteria [e.g., disease manifestation, etc.]). As used herein the terms "administering" or "administration" refer to the act ofinjecting or otherwise physically delivering a substance as it exists outside the body (e.g. ananti-cardiovascular disease treatment) into the subject, such as by mucosal, intradermal, intravenous, subcutaneous, intramuscular delivery and / or any other method of physical delivery described herein or known in the art. When a disease, or a symptom thereof, is being treated,administration of the substance typically occurs after the onset of the disease or symptomsthereof. In the context of the invention, the subject is administered with the polypeptide of the invention by topical administration. The topical administration is performed by a patch application. In a further embodiment, the subject is administered with the polypeptide of the invention by subcutaneous, nebulization or sublingual administration. In another embodiment, the subject is administered with the polypeptide of the invention by oral administration. The oral administration is performed by tablets, gel capsules, powders, granules and oral suspensions or solutions, sublingual and buccal administration forms. A “therapeutically effective amount” is intended for a minimal amount of active agent which is necessary to impart therapeutic benefit to a subject. For example, a "therapeutically effective amount" to a subject is such an amount which induces, ameliorates or otherwise causes an improvement in the pathological symptoms, disease progression or physiological conditions associated with or resistance to succumbing to a disorder. It will be understood that the total daily usage of the compounds of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific compound employed; the specific composition employed, the age, body weight, general health, sex and diet of the subject; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidential with the specific compound employed; and like factors well known in the medical arts. For example, it is well within the skill of the art to start doses of the compound at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. However, the daily dosage of the products may be varied over a wide range from 0.01 to 1,000 mg per adult per day. Typically, the compositions contain 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 15.0, 25.0, 50.0, 100, 250 and 500 mg of the active ingredient for the symptomatic adjustment of the dosage to the subject to be treated. A medicament typically contains from about 0.01 mg to about 500 mg of the active ingredient, preferably from 1 mg to about 100 mg of the active ingredient. An effective amount of the drug is ordinarily supplied at a dosage level from 0.0002 mg / kg to about 20 mg / kg of body weight per day, especially from about 0.001 mg / kg to 7 mg / kg of body weight per day. Peptides biomarkers of the invention Thus, the present invention relates to an isolated glycated-peptide comprising the amino acid sequence selected from the group consisting in : NR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194), LSQR+54FPK (SEQ ID NO:2, MGH-Alb219-225), and VK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39), and, wherein R+54is a methylglyoxal-derived hydroimidazolone and K+72 is a carboxyethyl-lysine.In particular embodiments, the invention relates to a peptide derived from glycated-apolipoprotein B100 (ApoB100) comprising or consisting of the amino acid sequence set forthas NR+54NNALDFVTK (SEQ ID NO:1), wherein R+54is a methylglyoxal-derivedhydroimidazolone (MGH-ApoB1003184-3194).In particular embodiments, the invention relates to an isolated peptide derived fromglycated-albumin (Alb) comprising or consisting of the amino acid sequence set forth as LSQR+54FPK (SEQ ID NO:2), wherein R+54is a methylglyoxal-derived hydroimidazolone (MGH-Alb219-225). In particular embodiments, the invention relates to an isolated peptide derived fromglycated-apolipoprotein A-II (ApoA-II) comprising or consisting of the amino acid sequenceset forth as VK+72SPELQAEAK (SEQ ID NO:3), wherein K+72 is a carboxyethyl-lysine (CEL-ApoA229-39). The peptides of the invention may be produced by any technique known per se in the art, such as, without limitation, any chemical, biological, genetic or enzymatic technique, either alone or in combination. For instance, knowing the amino acid sequence of the desired sequence, one skilled in the art can readily produce said peptides, by standard techniques for production of amino acid sequences. For instance, they can be synthesized using well-known solid phase method, preferably using a commercially available peptide synthesis apparatus (such as that made by Applied Biosystems, Foster City, California) and following the manufacturer's instructions. Alternatively, the peptides of the invention can be synthesized by recombinant DNA techniques as is now well-known in the art. For example, these fragments can be obtained as DNA expression products after incorporation of DNA sequences encoding the desired (poly)peptide into expression vectors and introduction of such vectors into suitable eukaryotic or prokaryotic hosts that will express the desired peptide, from which they can be later isolated using well-known techniques. The peptide of the invention can be produced by generated isolated peptide derived fromthe recombinant protein of interest (such as ApoB100, Albumin, ApoA-II) and by glycated saidobtained-peptide by using methylglyoxal (MGO). Method of prognosis diabetes type 2 In another aspect, the invention relates to method for diagnosis of diabetes type 2comprising in subject.Thus, in another aspect, the present invention relates to an ex vivo method for diagnosingand / or prognosing type 2 diabetes (TD2) in a subject, comprising the steps of: i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine amino acid residue (R) at position 3185 in SEQ IDNO:4 (ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the arginine amino acid residue (R) at position 222 in SEQ IDNO:5 (Albumin) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the lysine amino acid residue (K) at position 30 in SEQ ID NO:6(ApoA-II) into a carboxyethyl-lysine (K+72) ii) and positively correlating said level of glycation with the prognosis and / or thediagnosis of a type 2 diabetes in said subject. In other words, the invention relates to an ex vivo method for diagnosing and / orprognosing type 2 diabetes (TD2) in a subject, comprising the steps of: i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine amino acid residue (R) at position 3185 in SEQ IDNO:4 (ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the arginine amino acid residue (R) at position 222 in SEQ IDNO:5 (Albumin) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the lysine amino acid residue (K) at position 30 in SEQ ID NO:6(ApoA-II) into a carboxyethyl-lysine (K+72), ii) comparing each level of glycation determined at step i) with a reference value,and iii) concluding that the subject has type 2 diabetes when the concentration ofglycated-peptide determined at step i) are higher than the reference value. In some embodiment, regarding all the methods of the invention, the level of theglycation of the arginine amino acid residue (R) at position 3185 in SEQ ID NO:5 (ApoB100)into a methylglyoxal-derived hydroimidazolone (R+54) is determined by the level of a glycated-peptide derived from ApoB100 comprising 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 amino acid residuesfrom amino acid residues 3184 to 3194 of SEQ ID NO: 4, wherein the arginine amino acidresidue (R) at position 3185 is glycated in a methylglyoxal-derived hydroimidazolone (R+54). In some embodiment, regarding all the methods of the invention, the glycated-peptidederived from ApoB100 comprises the amino acid of NR+54NNALDFVTK (SEQ ID NO:1,MGH-ApoB1003184-3194), wherein R+54is a methylglyoxal-derived hydroimidazolone. In some embodiment, regarding all the methods of the invention, the glycation of thearginine amino acid residue (R) at position 222 in SEQ ID NO:5 (Albumin) into amethylglyoxal-derived hydroimidazolone (R+54) is determined by the level of a glycated- peptide derived from Albumin comprising 4, 5, 6, or 7 amino acid residues from amino acidresidues 219 to 225 of SEQ ID NO: 5, wherein the arginine acid residue (R) at position 222 isglycated in a a methylglyoxal-derived hydroimidazolone (R+54) In some embodiment, regarding all the methods of the invention, the glycated-peptidederived from Albumin comprises the amino acid of LSQR+54FPK (SEQ ID NO:2, MGH-Alb219-225), wherein R+54is a methylglyoxal-derived hydroimidazolone. In some embodiment, regarding all the methods of the invention, the level of the glycation of the lysine amino acid residue (K) at position 30 in SEQ ID NO:6 (ApoA-II) into acarboxyethyl-lysine (K+72) is determined by the level of a glycated-peptide derived from ApoA-II comprising 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 amino acid residues from amino acid residues29 to 39 of SEQ ID NO: 6, wherein the arginine acid residue (R) at position 3185 is glycatedin a a methylglyoxal-derived hydroimidazolone (R+54) In some embodiment, regarding all the methods of the invention, the glycated-peptidederived from ApoA-II comprises the amino acid of VK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39), wherein K+72is a carboxyethyl-lysine. In particular embodiment, the reference value is determined from the level ofglycation(s) of the invention from one or more healthy subject (i.e that has not been diagnosedfor T2D). As used herein, the term “level of glycation” or “level of glycated-peptide(s)” refersto the concentration of the glycated-peptide of the invention. Typically, the level orconcentration of the glycated-peptide may be determined by any technology known by a person skilled in the art. The level of the glycated-peptide of the invention may be determined by using standardelectrophoretic, immunoassays and mass-spectrometry techniques, including immuno-electrophoresis; electrophoresis, capillary electrophoresis-mass spectroscopy technique (CE-MS), liquid chromatography coupled to tandem mass spectrometry (LC-MS / MS). Such immunoassays include, but are not limited to, Western blots; agglutination tests; enzyme-labelled and mediated immunoassays, such as ELISAs; biotin / avidin type assays; radioimmunoassays; immunoelectrophoresis; immunoprecipitation, capillary electrophoresis-mass spectroscopy technique (CE-MS) etc. The reactions generally include revealing labelssuch as fluorescent, chemioluminescent, radioactive, enzymatic labels or dye molecules, or other methods for detecting the formation of a complex between the antigen and the antibody or antibodies reacted therewith. Electrophoresis assays are well known in the art and includes gel electrophoresis, alsoknown as slab-gel electrophoresis (SGE), and capillary electrophoresis (CE), which includes capillary zone electrophoresis (CZE) and capillary gel electrophoresis (CGE), among others. In some embodiments, the level of glycated-peptide of the invention present in thesample is detected by mass spectrometry. Particularly, a mass spectrometry-based quantification methods may be used. Mass spectrometry-based quantification methods may be performed using either labelled orunlabelled approaches. Mass spectrometry-based quantification methods may be performedusing chemical labelling, metabolic labelling or proteolytic labelling. Mass spectrometry-based quantification methods may be performed using mass spectrometry label free quantification, a quantification based on extracted ion chromatogram (EIC) and then profile alignment todetermine differential level of polypeptides. Particularly, a mass spectrometry-basedquantification method particularly useful can be the use of targeted mass spectrometry methods as selected reaction monitoring (SRM), multiple reaction monitoring (MRM), parallel reaction monitoring (PRM), data independent acquisition (DIA) and sequential window acquisition of all theoretical mass spectra (SWATH). In some embodiments, the level of glycated-peptide of the invention present in thesample is detected by liquid chromatography coupled to tandem mass spectrometry (LC-MS / MS). LC-MS / MS is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography (LC) with the mass analysis capabilities of massspectrometry (MS). The advantages of using MS / MS in the selected reaction monitoring (SRM)mode are mainly the increased specificity, sensitivity and throughput. The quantifying ofapolipoproteins using LC-MS / MS technology is well knows and described10,24. Such protocols often involve the analysis of peptide mixtures resulting from the enzymatic proteolysis of proteins. Method for determining whether a subject is at a risk of having or developing a cardiovascular event In another aspect, the invention relates to method for predicting the risk of having ordeveloping cardiovascular diseases in subject in need thereof by determining the level of glycation described above. Thus, in another aspect, the present invention relates to an ex vivo method fordetermining whether a subject is at a risk of having or developing a cardiovascular eventcomprising the steps of: iii) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the arginine acid residue (R) at position 222 in SEQ ID NO:5(Albumin) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72) iv) and positively correlating said level of glycation with the risk of developing acardiovascular event in said subject. In other words, the invention relates to an ex vivo method for determining whether asubject is at a risk of having or developing a cardiovascular event comprising the steps of:i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine amino acid residue (R) at position 3185 in SEQ IDNO:4 (ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the arginine amino acid residue (R) at position 222 in SEQ IDNO:5 (Albumin) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the lysine amino acid residue (K) at position 30 in SEQ ID NO:6(ApoA-II) into a carboxyethyl-lysine (K+72),ii) comparing each level of glycation determined at step i) with a reference value,and iii) concluding that the that the subject is at high risk of having or developing acardiovascular event when the level(s) of glycation(s) determined at step i) are higher than the reference value. In particular embodiment, it is concluded that the subject is at low risk of having or developing a cardiovascular event when the level(s) of glycation(s)) determined at step i) are lower than the reference value. In particular embodiment, the subject suffers from diabetes.In particular embodiment, the subject suffers from type 2 diabetes.In particular embodiment, the reference value is determined from the level ofglycation(s) of the invention from one or more subject that have not having or developing acardiovascular event. In some embodiment, the level of at least one glycation is determined by the level of atleast one glycated peptide selected from the group consisting of :- a glycated-peptide derived from ApoB100 comprising 2, 3, 4, 5, 6, 7, 8, 9, 10 or11 amino acid residues from amino acid residues 3184 to 3194 of SEQ ID NO: 4, wherein the arginine amino acid residue (R) at position 3185 is glycated in a amethylglyoxal-derived hydroimidazolone (R+54) -a glycated-peptide derived from Albumin comprising 4, 5, 6, or 7 amino acidresidues from amino acid residues 219 to 225 of SEQ ID NO: 5, wherein the arginineacid residue (R) at position 222 is glycated in a methylglyoxal-derivedhydroimidazolone (R+54) -a glycated-peptide derived from ApoA-II comprising 2, 3, 4, 5, 6, 7, 8, 9, 10, 11or 12 amino acid residues from amino acid residues 29 to 39 of SEQ ID NO: 6, whereinthe arginine acid residue (R) at position 3185 is glycated in a carboxyethyl-lysine (K+72).In some embodiment, the level of at least one glycation is determined by the level of atleast one glycated peptide selected from the group consisting of :- a glycated-peptide comprising the amino acid of NR+54NNALDFVTK (SEQ IDNO:1, MGH-ApoB1003184-3194), wherein R+54 is a methylglyoxal-derivedhydroimidazolone- a glycated-peptide comprising the amino acid of LSQR+54FPK (SEQ ID NO:2,MGH-Alb219-225), wherein R+54is a methylglyoxal-derived hydroimidazolone -VK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39), wherein K+72 is acarboxyethyl-lysine. Thus, in particular embodiment, the invention relates to an ex vivo method fordetermining whether a subject is at a risk of having or developing a cardiovascular event comprising the steps of: i) determining in a sample obtained from the patient the level of 1, 2or 3 glycated-peptide comprising the amino acid selected from the group consisting ofNR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194), LSQR+54FPK (SEQ ID NO:2, MGH-Alb219-225), and VK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39), wherein R+54isa methylglyoxal-derived hydroimidazolone and K+72 is a carboxyethyl-lysine, and, ii)comparing each level of glycated-peptide determined at step i) with a reference value, and iii)concluding that the subject is at high risk of having or developing a cardiovascular event whenthe level(s) of glycated-peptide(s) determined at step i) are higher than the reference value.In some embodiments, the at least one peptide glycated is the amino acid comprisingNR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194). In a particular embodiment, 1, 2, 3, 4, 5, 6, 7 biomarkers selected from the groupconsisting of the amino acid subject’s age, subject’s sex, level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), level of non-HDLcholesterol and level of HDL cholesterol can further be determined.In a particular embodiment, the level of glycation (such as the level of the glycated-peptide) can be adjusted with 1, 2, 3, 4, 5, 6, 7 or 8 biomarkers selected from the groupconsisting of the glycated-peptide comprising or consisting of the amino acid subject’s age,subject’s sex, subject’s personal history of CAD level of eGFR, urine albumin / creatinine ratio(uACR), level of glycated haemoglobin (HbA1c), level of non-HDL cholesterol and level ofHDL cholesterol to determine the risk of having or developing a cardiovascular events.As used herein, the term “adjusted” refers to statistic model where a supervised analysis of the level of glycated-peptide of the invention and the biomarkers described above is performed, and the calculation of the optimal threshold can be done to determine the subject’srisk of having or developing a cardiovascular events or to determine the subject’s risk of all-mortality or cardiovascular mortality. The score of the model (M) is then defined as the result of the logistic regression orproportional hazard function that describes the probability function of the subject risk of havingor developing cardiovascular events or the subject’s risk of all-mortality or cardiovascularmortality as a function of the expression levels of the selected markers and follow-up time.In particular, the glycation or glycated-peptide(s) of the invention is adjusted with thefollowing biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level ofeGFR, and urine albumin / creatinine ratio (uACR) (“Model 2”) In particular, the glycation or glycated-peptide(s) of the invention is adjusted with thefollowing biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level ofeGFR, urine albumin / creatinine ratio (uACR), and level of glycated haemoglobin (HbA1c)(“Model 3”) In particular, the glycation or glycated-peptide(s) of the invention is adjusted with thefollowing biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level ofeGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), levelof non- HDL cholesterol ( “Model 4”)In particular, the glycation or glycated-peptide(s) of the invention is adjusted with thefollowing biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level ofeGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), levelof total HDL cholesterol (“Model 5”). According to the invention, the supervised analysis can be performed for example byusing Cox hazard model, Random Forest algorithm, Adaboost algorithm, or CART algorithm.In a particular embodiment, the supervised analysis is using cox hazard model.- Method for determining whether a subject is at a risk of having or developingCAD The inventors found that increased concentration of plasma MGH-APOB1003184-3194 orplasma MGH-ALB219-225 was associated with severe CAD events.In a particular embodiment, the cardiovascular event is severe coronary artery disease.Thus, in particular embodiments, the invention relates to an ex vivo method ofdetermining whether a subject is at a risk of having or developing a severe CAD comprisingthe steps of:i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine amino acid residue (R) at position 3185 in SEQ IDNO:4 (ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the arginine amino acid residue (R) at position 222 in SEQ IDNO:5 (Albumin) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the lysine amino acid residue (K) at position 30 in SEQ ID NO:6(ApoA-II) into a carboxyethyl-lysine (K+72), ii) comparing each level of glycation determined at step i) with a reference value,and iii) concluding that the subject is at high risk of having or developing a severe CADwhen the level(s) of glycation(s) determined at step i) are higher than the reference value. In particular embodiment, it is concluded that the subject is at low risk of having ordeveloping severe CAD when the level(s) of glycation(s)) determined at step i) are lower thanthe reference value. In particular embodiment, the subject suffers from diabetes.In particular embodiment, the subject suffers from type 2 diabetes.In particular embodiment, the reference value is determined from the level ofglycation(s) of the invention from one or more subject that have not having or developing severeCAD. In some embodiment, the level of at least one glycation is determined by the level of at least one peptide selected from the group consisting of: -a glycated-peptide derived from ApoB100 comprising the amino acid ofNR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194) -a glycated-peptide derived from Albumin comprising the amino acid ofLSQR+54FPK (SEQ ID NO:2, MGH-Alb219-225), wherein R+54is a methylglyoxal- derived hydroimidazolone -a glycated-peptide derived from ApoA-II comprising the amino acid ofVK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39), wherein K+72is a carboxyethyl-lysine. In some embodiment, the at least one glycation is the glycation of the arginine amino acid residue (R) at position 3185 in SEQ ID NO:4 (ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54). In some embodiments, the at least one glycated-peptide are the glycated-peptide derivedfrom ApoB100 comprising the amino acid NR+54NNALDFVTK (SEQ ID NO:1 MGH-ApoB1003184-3194) and / or the glycated peptide derived from ApoA-II comprising the aminoacid LSQR+54FPK (SEQ ID NO:2, MGH-Alb219-225).In some embodiments, the glycated-peptide is the peptide derived from ApoB100comprising the amino acid sequence set forth as NR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194) wherein R+54 is a methylglyoxal-derived hydroimidazolone.In some embodiments, the glycated-peptide is the peptide derived from ApoB100comprising the amino acid sequence set forth as NR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194) wherein R+54 is a methylglyoxal-derived hydroimidazolone, and the subjecthas a personal history of CAD. In a particular embodiment, the level of at least one glycation (such as glycated-peptide)can be adjusted with 1, 2, 3, 4, 5, 6, 7 or 8 biomarkers selected from the group consisting ofthe glycated-peptide comprising or consisting of the amino acid subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), level of non-HDL cholesterol and level of total HDLcholesterol to determine the risk of having or developing a severe CAD.In particular, the inventors discover that a high level of glycated VK+72SPELQAEAK(SEQ ID NO:3, CEL-ApoA229-39), when adjusted with at least the following biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urinealbumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c) and level of totalHDL cholesterol indicates a subject’s risk of having or developing severe CAD. Thus, in some embodiment, when the at least one glycation is the glycation of the lysineamino acid residue (K) at position 30 in SEQ ID NO:6 (ApoA-II) into a carboxyethyl-lysine(K+72), said level is adjusted with at least the following biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urine albumin / creatinine ratio (uACR),level of glycated haemoglobin (HbA1c) and level of total HDL cholesterol.Thus, the invention also refers to an ex vivo method of determining whether a subject isat a risk of having or developing a severe CAD comprising the steps of: i) determining in asample obtained from the patient the level of the glycation of the lysine amino acid residue (K)at position 30 in SEQ ID NO:6 (ApoA-II) into a carboxyethyl-lysine (K+72), ii) adjusting thelevel of said glycated-peptide with the level of eGFR, urine albumin / creatinine ratio (uACR),level of glycated haemoglobin (HbA1c) and level of total HDL cholesterol, the subject’s age,the subject’s sex, and the subject’s personal history of CAD to obtained a score M5 as explainedabove and iii) concluding that the subject is at high risk of having or developing a severe CADwhen the score M5 determined at step ii) are higher than a reference value.In other words, when the level of glycated-peptide comprising the amino acid VK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39) is determined, said level is adjusted with at least the following biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin(HbA1c) and level of total HDL cholesterol.- Method of determining whether a subject is at a risk of having or developing aMACE The inventors found that increased concentration of plasma MGH-APOB1003184-3194was associated with major adverse cardiovascular event (MACE).In a particular embodiment, the cardiovascular event is a major adverse cardiovascular event (MACE). In particular embodiments, the invention relates to an ex vivo method of determiningwhether a subject is at a risk of having or developing a MACE comprising the steps of:i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54), and- the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72), ii) comparing each level of glycation determined at step i) with a reference value,and iii) concluding that the that the subject is at high risk of having or developing aMACE when the level(s) of glycation(s) determined at step i) are higher than the reference value. In particular embodiment, it is concluded that the subject is at low risk of having ordeveloping a MACE when the level(s) of glycation(s)) determined at step i) are lower than thereference value. In particular embodiment, the subject suffers from diabetes.In particular embodiment, the subject suffers from type 2 diabetes.In particular embodiment, the reference value is determined from the level ofglycation(s) of the invention from one or more subject that have not having or developing aMACE. In some embodiment, the at least one glycation is the glycation of the arginine amino acid residue (R) at position 3185 in SEQ ID NO:4 (ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54). In some embodiment, the level of at least one glycation is determined by the level of aglycated-peptide derived from ApoB100 comprising the amino acid of NR+54NNALDFVTK(SEQ ID NO:1, MGH-ApoB1003184-3194), and / or the level of a glycated peptide derived fromApoA-II comprising the amino acid of VK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39),wherein K+72 is a carboxyethyl-lysine and R+54 is a methylglyoxal-derived hydroimidazolone.In some embodiments, the at least one glycated-peptide is the peptide derived fromApoB100 comprising of the amino acid sequence set forth as NR+54NNALDFVTK (SEQ IDNO:1, MGH-ApoB1003184-3194) wherein R+54 is a methylglyoxal-derived hydroimidazolone.In a particular embodiment, the level of glycation (such as glycated-peptide) can beadjusted with 1, 2, 3, 4, 5, 6, 7 or 8 biomarkers selected from the group consisting of theglycated-peptide comprising or consisting of the amino acid subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), level of non-HDL cholesterol and level of total HDLcholesterol to determine the risk of having or developing MACE.In particular, the inventors discover that a high level of glycated VK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39), when adjusted with at least the following biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urinealbumin / creatinine ratio (uACR), and level of glycated haemoglobin (HbA1c) indicates asubject’s risk of having or developing MACE. Thus, in a particular embodiment, when the at least one glycation is the glycation of thelysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II) into a carboxyethyl-lysine (K+72),said level is adjusted with at least the following biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urine albumin / creatinine ratio (uACR), andlevel of glycated haemoglobin (HbA1c) (“Model 3”).In a particular embodiment, when the at least one glycation is the glycation of the lysineresidue (K) at position 30 in SEQ ID NO:6 (ApoA-II) into a carboxyethyl-lysine (K+72), saidlevel is adjusted with subject’s age, subject’s sex, subject’s personal history of CAD, level ofeGFR, urine albumin / creatinine ratio (uACR), and level of glycated haemoglobin (HbA1c) andlevel of non-HDL cholesterol (“Model 4”).In a particular embodiment, when the at least one glycation is the glycation of the lysineresidue (K) at position 30 in SEQ ID NO:6 (ApoA-II) into a carboxyethyl-lysine (K+72), saidlevel is adjusted with subject’s age, subject’s sex, subject’s personal history of CAD, level ofeGFR, urine albumin / creatinine ratio (uACR), and level of glycated haemoglobin (HbA1c) andlevel of total HDL cholesterol (“Model 5”).Thus, the invention also refers to an ex vivo method of determining whether a subject isat a risk of having or developing a MACE comprising the steps of: i) determining in a sampleobtained from the patient the level of the glycation of the lysine amino acid residue (K) atposition 30 in SEQ ID NO:6 (ApoA-II) into a carboxyethyl-lysine (K+72), ii) adjusting the levelof said glycated-peptide with the level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), the subject’s age, the subject’s sex, and the subject’spersonal history of CAD to obtained a score M3 as explained above and iii) concluding that thesubject is at high risk of having or developing MACE when the score M3 determined at step ii)are higher than a reference value.In a particular embodiment, the glycation of the lysine residue (K) at position 30 in SEQID NO:6 (ApoA-II) into a carboxyethyl-lysine (K+72)can further be adjusted with level of non-HDL cholesterol (“Model 4”) or level of total HDL cholesterol (“Model 5”).Methods for assessing a subject’s risk of having a poor prognostic of survival The glycation of the present invention (such as the glycated-peptide of the of the presentinvention) is particularly suitable for predicting the duration of the overall survival (OS) of thetype 2 diabetes patient. Those of skill in the art will recognize that OS survival time is generallybased on and expressed as the percentage of people who survive a certain cardiovascular eventand / or diabetes type 2 for a specific amount of time.- Method for assessing a subject’s risk of having a poor prognostic of survivalAccordingly, the invention relates to an ex vivo method for assessing a subject’s risk ofhaving a poor prognostic of survival comprising the steps of: i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the arginine acid residue (R) at position 222 in SEQ ID NO:5(Albumin) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72), ii) comparing each level of glycation determined at step i) with a reference value,and iii) concluding that the that the subject is at high risk of having a poor prognostic ofsurvival when the level(s) of glycation(s) determined at step i) are higher than the reference value. In particular embodiment, it is concluded that the subject is at low risk of having a poorprognostic when the level(s) of glycation(s)) determined at step i) are lower than the referencevalue. In particular embodiment, the subject suffers from diabetes.In particular embodiment, the subject suffers from type 2 diabetes.In some embodiment, the level of at least one glycation is determined by the level of at least one glycated-peptide selected from the group consisting of: -a glycated-peptide derived from ApoB100 comprising the amino acid ofNR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194), wherein R+54 is amethylglyoxal-derived hydroimidazolone -a glycated-peptide derived from Albumin comprising the amino acid ofLSQR+54FPK (SEQ ID NO:2, MGH-Alb219-225), wherein R+54is a methylglyoxal- derived hydroimidazolone -a glycated-peptide derived from ApoA-II comprising the amino acid ofVK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39), wherein K+72is a carboxyethyl-lysine. In some embodiment, the at least one glycation is the glycation of the arginine amino acid residue (R) at position 3185 in SEQ ID NO:4 (ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54). In some embodiments, the level of 1 or 2 glycated-peptide selected from the groupconsisting of a glycated-peptide derived from ApoB100 comprising the amino acid ofNR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194) and a glycated-peptide derivedfrom Albumin comprising the amino acid of LSQR+54FPK (SEQ ID NO:2, MGH-Alb219-225), wherein R+54is a methylglyoxal-derived is determined in step i). Typically, a high level of NR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194)and / or LSQR+54FPK (SEQ ID NO:2, MGH-Alb219-225) indicates that the subject is at high riskof having a poor prognostic of survival (all-mortality). In some embodiments, the level of glycated-peptide comprising the amino acidNR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194) is determined in step i).In some embodiments, the level of glycated-peptide comprising the amino acidNR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194) is determined in step i) and thesubject has a personal history of CAD. In a particular embodiment, the level of glycation (such as glycated-peptide) can beadjusted with 1, 2, 3, 4, 5, 6, 7 or 8 biomarkers selected from the group consisting of theglycated-peptide comprising or consisting of the amino acid subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), level of non-HDL cholesterol and level of total HDLcholesterol to determine the subject’s risk of having a poor prognostic of survival.In particular, the inventors discovers that a high level of glycated VK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39), when adjusted with at least the following biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urinealbumin / creatinine ratio (uACR), and level of glycated haemoglobin (HbA1c) indicates asubject’s risk of having a poor prognostic of survival (“Model 3”).Thus, in some embodiment, when the at least one glycation is the glycation of the lysineamino acid residue (K) at position 30 in SEQ ID NO:6 (ApoA-II) into a carboxyethyl-lysine(K+72), said level is adjusted with at least the following biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urine albumin / creatinine ratio(uACR),and level of glycated haemoglobin (HbA1c) (“Model 3”)Thus, the invention also refers to an ex vivo method for assessing a subject’s risk ofhaving a poor prognostic of survival comprising the steps of: i) determining in a sampleobtained from the patient the level of the glycation of the lysine residue (K) at position 30 inSEQ ID NO:6 (ApoA-II) into a carboxyethyl-lysine (K+72), ii) adjusting the level of saidglycated-peptide with the level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), the subject’s age, the subject’s sex, and the subject’s personalhistory of CAD to obtained a score M3 as explained above and iii) concluding that the subjectis at high risk of having cardiovascular mortality when the score M3 determined at step ii) arehigher than a reference value.In a particular embodiment, the glycation of the lysine residue (K) at position 30 in SEQID NO:6 (ApoA-II) into a carboxyethyl-lysine (K+72)can further be adjusted with level of non-HDL cholesterol (“Model 4”) or level of total HDL cholesterol (“Model 5”).- Method for for assessing a subject’s cardiovascular mortality riskThe glycated-peptide of the present invention is particularly suitable for predicting therisk of cardiovascular mortality in subject. As used herein, the term “cardiovascular mortality” has its general meaning in the art and refers to the death caused by a cardiovascular disease, such as coronary artery disease, sudden cardiac death or stroke. Accordingly, the invention relates to an ex vivo method for assessing a subject’scardiovascular mortality risk comprising the steps of:i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the arginine acid residue (R) at position 222 in SEQ ID NO:5(Albumin) into a methylglyoxal-derived hydroimidazolone (R+54)- the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72), ii) comparing each level of glycation determined at step i) with a reference value,andiii) concluding that the that the subject is at high risk of having a poor prognostic ofsurvival when the level(s) of glycation(s) determined at step i) are higher than the reference value. In particular embodiment, it is concluded that the subject is at low risk of having a poorprognostic when the level(s) of glycation(s)) determined at step i) are lower than the referencevalue. In particular embodiment, the subject suffers from diabetes.In particular embodiment, the subject suffers from type 2 diabetes.In some embodiment, the at least one glycation is the glycation of the arginine amino acid residue (R) at position 3185 in SEQ ID NO:4 (ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54). In some embodiment, the level of at least one glycation is determined by the level of at least one glycated-peptide selected from the group consisting of: -a glycated-peptide derived from ApoB100 comprising the amino acid ofNR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194), wherein R+54is a methylglyoxal-derived hydroimidazolone -a glycated-peptide derived from Albumin comprising the amino acid ofLSQR+54FPK (SEQ ID NO:2, MGH-Alb219-225), wherein R+54is a methylglyoxal- derived hydroimidazolone -a glycated-peptide derived from ApoA-II comprising the amino acid ofVK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39), wherein K+72is a carboxyethyl-lysine. Typically, a high level of NR+54NNALDFVTK (SEQ ID NO:1) and / or LSQR+54FPK(SEQ ID NO:2, MGH-Alb219-225) indicates that the subject is at high risk of cardiovascularmortality, and a low level NR+54NNALDFVTK (SEQ ID NO:1) and / or LSQR+54FPK (SEQ IDNO:2, MGH-Alb219-225) indicates that the subject is at low risk of cardiovascular mortality.In some embodiment, the glycated peptide determined at step i) is a glycated-peptide derived from ApoB100 comprising the amino acid of NR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194). In a particular embodiment, the level of glycation (such as glycated-peptide) can beadjusted with 1, 2, 3, 4, 5, 6, 7 or 8 biomarkers selected from the group consisting of theglycated-peptide comprising or consisting of the amino acid subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), level of non-HDL cholesterol and level of total HDLcholesterol to determine the subject’s risk of having cardiovascular mortality.In particular, the inventors discover that a high level of glycated VK+72SPELQAEAK (SEQ ID NO:3, CEL-ApoA229-39), when adjusted with at least the following biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urinealbumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), and level of totalHDL cholesterol of indicates a subject’s risk of having cardiovascular mortality (“Model 5”).Thus, in some embodiment, when the at least one glycation is the glycation of the lysineamino acid residue (K) at position 30 in SEQ ID NO:6 (ApoA-II) into a carboxyethyl-lysine(K+72), said level is adjusted with at least the following biomarkers : subject’s age, subject’s sex, subject’s personal history of CAD, level of eGFR, urine albumin / creatinine ratio (uACR),level of glycated haemoglobin (HbA1c) and level of total HDL cholesterol (“Model 5”)Thus, the invention also refers to an ex vivo method assessing a subject’s cardiovascularmortality risk comprising the steps of: i) determining in a sample obtained from the patient the level of the glycation of the lysine amino acid residue (K) at position 30 in SEQ ID NO:6 (ApoA-II) into a carboxyethyl-lysine (K+72), ii) adjusting the level of said glycated-peptide with the level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), level of total HDL cholesterol, the subject’s age, the subject’s sex, and the subject’spersonal history of CAD to obtained a score M5 as explained above and iii) concluding that thesubject is at high risk of having cardiovascular mortality when the score M5 determined at stepii) are higher than a reference value.Therapeutics applications and Methods for monitoring anti-cardiovasculartreatment Once it is concluded that the subject is at risk of having cardiovascular event such asCAD and / or MACE, treatment options may be prescribed. In a further aspect, the invention also relates to a method for treating a cardiovascularevent in a subject determined a risk of cardiovascular event according to the inventioncomprising the administration to said patient of an anti-cardiovascular disease treatment. In a further aspect, the invention also relates to a method for treating a cardiovascularevent in a subject determined a risk of having or developing a cardiovascular event accordingto the invention comprising the administration to said patient of an anti-cardiovascular disease treatment. As used herein, the term “anti-cardiovascular disease treatment” relates to any treatment of a cardiovascular event as described above like revascularization, erythropoietin stimulatingagents, statins, niacin, fibrates and bile acid sequestrants, anticoagulants, anti-platelet druts(aspirin, clopidogrel, …), Ranolazine, nitroglycerin, anti-hypertensive drugs includingangiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs),GLP1 analogs and SGLT2 inhibitor. The glycated-peptide of the invention can also be used to monitor the anti-cardiovascular disease treatment administered to a patient on cardiovascular mortality risk.Thus, the invention also refers to a method for monitoring the anti-cardiovasculardisease treatment administered to a patient on cardiovascular mortality risk according to theinvention, comprising determining in a sample obtained from the patient the level of at least one glycation of apolipoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the arginine acid residue (R) at position 222 in SEQ ID NO:5(Albumin) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72). In particular embodiment, the level(s) of the glycation (such as the level(s) of theglycated-peptide) are determined at a first specific time (i.e before or at the beginning of saidtreatment) and at a second later specific time and it is concluding that said treatment is efficientwhen the level(s) of the glycation (such as the glycated-peptide) determined at the second timeis lower than the level(s) determined at the second time. In other words, the invention also refers to an ex vivo method for monitoring the anti-cardiovascular disease treatment administered to a patient on cardiovascular mortality risk according to the invention, comprising the steps: i) determining in a sample obtained from the patient the level of at least one glycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the arginine acid residue (R) at position 222 in SEQ ID NO:5(Albumin) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72), ii) determining level of said glycation at a second specific time, and iii) concluding thatsaid treatment is efficient when the level determined at step ii) is lower than the level determinedat step i). Such a method may thus help the physician to make a choice on a therapeutic treatment. Costs of the treatments may therefore be adapted to risk of the patients. Kit of the invention Another aspect of the present invention relates to a kit or device for performing the method of the present invention, comprising means for determining the level of the glycated peptide(s) of the invention in a biological sample. In other words the present invention relates to the use of a kit or device for performing the method of the present invention, wherein said kit or device comprising means for determining the level of the glycated peptide(s) of the invention in a biological sample. In particular embodiments, the kits further comprises means for determining the level of level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), level of non-HDL cholesterol and level of total HDL cholesterol. In some embodiments, the kit or device of the present invention further comprises software to implement model 1, 2, 3, 4 or 5 as defined above. In some embodiments, the kit or device of the present invention further comprises a microprocessor to implement an algorithm on data comprising the level of glycated-peptide(s) in the sample so as to determine the risk of having or developing cardiovascular event in T2D subjects. In some embodiments, the kit or device of the present invention further comprises avisual display and / or audible signal that indicates the risk determined by the microprocessor.In some embodiments, the kit or device of the present invention comprises: -a mass spectrometer;- a receptacle into which the biological sample is placed, and which is connectableto the mass spectrometer so that the mass spectrometer can quantify the level of glycated- peptide(s) of the invention in the sample; -a microprocessor to implement an algorithm on data comprising the levels of theglycated-peptide in the sample so as to determine the risk of having or developingcardiovascular event or to determine the all-mortality or cardiovascular mortality. -a visual display and / or audible signal that indicates the probability determinedby the microprocessor. In some embodiments, the kit of the present invention comprise reagents employed in the various methods. The kit may also comprise various buffer mediums. The kits can furtherinclude a software package for calculating the determine the risk of having or developingcardiovascular event or to determine the all-mortality or cardiovascular mortality. In addition to the above components, the subject kits will further include instructions for practicing the subject methods. FIGURES: Figure 1. In-vitro glycation of plasma albumin, apoA-I, apoA-II and apoB100 by methylglyoxal (MGO). Untargeted proteomic analysis highlighting the reactivity of MGO for in-vitro glycation of recombinant proteins. Only specific peptides amenable to targeted mass spectrometry (MS)-based assay are represented. The identification of the main MGO-induced modifications within protein sequences was performed by MS-based proteomics. CEL, carboxyethyl-lysine; CEA, carboxyethyl-arginine; MGH, methylglyoxal-derived hydroimidazolone. Figure 2. Characterization and validation of the proteotypic peptides suitable for targeted high-throughput mass spectrometry analysis. A) In-vitro production of the methylglyoxal (MGO)-glycated peptides after incubation of a pool of plasma (healthy donors, n = 8) with MGO at different concentrations. B) Quantification of selected peptides in the plasma of healthy subjects (CTL) and patients with type 2 diabetes (T2D) with no renal failure. Patients were matched for sex and age (n = 20 per group). C) Long-term stability of selected peptides over 6 months at -80 °C. Bland-Altman plot was generated to test the similarity of two assays performed at 6 months interval period for the same set of samples (n = 40). The difference of values (y axis) obtained from the two assays was plotted according to the average value obtained by the two assays. The mean difference and the limits of agreement grey area), corresponding to the 95% confidence level (i.e., mean ± 1.96 × SD), are represented.Figure 3: Associations between plasma levels of peptide biomarkers at baseline andthe incidence of coronary artery disease (CAD) during follow-up in the SURDIAGENEstudy. Cox models based on the proportional hazards assumption. Hazard ratios (HRs) arecalculated per 1 standard deviation (SD) without natural-log transformation except for triglycerides and MGH-APOB1003184-3194. Model 1: not adjusted (univariate). Model 2: adjusted for baseline values of age, sex, estimated glomerular filtration rate, urine albumin- creatinine ratio and personal history of coronary artery disease. Model 3: model 2 withadditional adjustment for the HbA1c. Model 4: model 3 adjusted for non-HDL cholesterol.Model 5: model 3 adjusted for HDL cholesterol CI, confidence interval; HbA1c, glycated hemoglobin (A1c fraction); LDL, low-density lipoprotein; HDL, high-density lipoprotein; MGH-ALB219-225, methylglyoxal-glycated albumin. Figure 4: Associations between plasma levels of peptide biomarkers at baseline and the incidence of major adverse cardiovascular events (MACE) during follow-up in theSURDIAGENE study. Cox models based on the proportional hazards assumption. Hazardratios (HRs) are calculated per 1 standard deviation (SD) without natural-log transformation except for triglycerides and MGH-APOB1003184-3194. Model 1: not adjusted (univariate). Model 2: adjusted for baseline values of age, sex, estimated glomerular filtration rate, urine albumin- creatinine ratio and personal history of coronary artery disease. Model 3: model 2 with additional adjustment for the HbA1c. Model 4: model 3 adjusted for non-HDL cholesterol.Model 5: model 3 adjusted for HDL cholesterol CI, confidence interval; HbA1c, glycatedhemoglobin (A1c fraction); LDL, low-density lipoprotein; HDL, high-density lipoprotein; MGH-ALB219-225, methylglyoxal-glycated albumin. Figure 5: Associations between plasma levels of peptide biomarkers at baseline andthe incidence of all-cause mortality during follow-up in the SURDIAGENE study. Coxmodels based on the proportional hazards assumption. Hazard ratios (HRs) are calculated per 1 standard deviation (SD) without natural-log transformation except for triglycerides and MGH- APOB1003184-3194. Model 1: not adjusted (univariate). Model 2: adjusted for baseline values of age, sex, estimated glomerular filtration rate, urine albumin-creatinine ratio and personal history of coronary artery disease. Model 3: model 2 with additional adjustment for the HbA1c. Model 4: model 3 adjusted for non-HDL cholesterol. Model 5: model 3 adjusted for HDL cholesterol CI, confidence interval; HbA1c, glycated hemoglobin (A1c fraction); LDL, low-density lipoprotein; HDL, high-density lipoprotein; MGH-ALB219-225, methylglyoxal-glycated albumin. Figure 6: Associations between plasma levels of peptide biomarkers at baseline andthe incidence of CV mortality during follow-up in the SURDIAGENE study. Cox modelsbased on the proportional hazards assumption. Hazard ratios (HRs) are calculated per 1 standard deviation (SD) without natural-log transformation except for triglycerides and MGH- APOB1003184-3194. Model 1: not adjusted (univariate). Model 2: adjusted for baseline values ofage, sex, estimated glomerular filtration rate, urine albumin-creatinine ratio and personal historyof coronary artery disease. Model 3: model 2 with additional adjustment for the HbA1c. Model 4: model 3 adjusted for non-HDL cholesterol. Model 5: model 3 adjusted for HDL cholesterol CI, confidence interval; HbA1c, glycated hemoglobin (A1c fraction); LDL, low-density lipoprotein; HDL, high-density lipoprotein; MGH-ALB219-225, methylglyoxal-glycated albumin. EXAMPLE: Material & Methods Biological samples Pooled EDTA plasma from healthy donors was provided by the French Blood Donors Bank (Nantes, France). Individual EDTA plasma samples from healthy donors (n = 20) and people living with T2D (n = 20) were provided by the Centre de Ressources Biologiques of Poitiers (Collections Endocrinologie-, France https: / / www.chu-poitiers.fr / specialites / centre- ressources-biologiques / le-catalogue / #endocrino) (CRB Poitiers). Subjects with and without diabetes were matched for sex and age and had estimated glomerular filtration rate (eGFR)higher than 60 mL / min / 1.73 m² (data not shown). Ethics committee (CPP Ouest III) approvedthe biocollection and written informed consent was obtained from each participant. The biocollection was designed in accordance with the principles of the Declaration of Helsinki. In-vitro glycationMGO and recombinant plasma proteins (albumin, apoA-I, apoA-II and apoB100) were obtained from Sigma-Aldrich (Saint-Quentin Fallavier, France). Working solutions of MGO were prepared in ultrapure water (Biosolve, Valkenswaard, Netherlands). Then, the glycation reaction was induced in-vitro in recombinant proteins (200 µg / mL, dPBS, pH 7.4) and pooled EDTA plasma (French Blood Bank). MGO solutions or water (10 µL) were added to samples (90 µL) and incubated at 37 °C at different time points. Samples were analyzed by MS as described hereafter. Untargeted mass spectrometry-based proteomics Proteomic analyses were performed by online nano-LC-MS / MS using a 50 min elution method. Recombinant protein samples were solubilized in Laemmli buffer and stacked in the top of a 4-12% NuPAGE gel (Invitrogen). After staining with R-250 Coomassie Blue (Bio- Rad), proteins were digested in-gel using modified sequencing grade trypsin (Promega, Charbonnières-les-Bains, France) as described previously28. The resulting peptides were analyzed on a Q-Exactive HF mass spectrometer with an electrospray (ESI) interface and an UltimateTM 3000 RSLCnano device (Thermo Fisher Scientific). Peptides were sampled on a pre-column (300 μm × 5 mm PepMap C18, Thermo Fisher Scientific) and separated in a 75 μm× 250 mm C18 column (Reprosil-Pur 120 C18-AQ, 1.9 μm, Dr. Maisch). Data were acquiredusing Xcalibur (version 2.9, Thermo Fisher Scientific). Peptides were identified by Mascot (version 2.8.0, Matrix Science) through concomitant searches in the Human sequence of albumin, apoA-I, apoA-II and apoB100 as well as a homemade database containing the sequences of classical contaminant proteins. Trypsin / P was chosen as the enzyme and two missed cleavages were allowed. Precursor and fragment mass error tolerances were set at ± 10 and ± 20 ppm, respectively. Peptide modifications allowed during the search were: carbamidomethyl (cysteine [C]: +57.0214 Da, fixed), acetyl (N-term: +42.0105 Da, variable), oxidation (methionine [M]: +15.9949 Da, variable), carboxyethyl (lysine [K], histidine [H], arginine [R]: +72.0211 Da, variable), and methylglyoxal-derived hydroimidazolone (MG-H) (arginine [R]: +54.0106 Da, variable). The Proline software (version 2.2.0)29was used for the compilation, grouping, and filtering of the results30. Proline was used to perform a MS1 label- free quantification of the identified peptides. Selection of peptide biomarker candidates Peptide candidates were searched among the list of peptides that was generated by proteomic analyses (peptide length > 7 amino acids). Peptides were selected to maximizesensitivity, specificity, and stability of further targeted analyses. In this respect, peptidescarrying methionine (M) and cysteine (C) residues were not considered due to potential oxidation, and those carrying amino acids (i.e. histidine [H] and tryptophan [W]) that wereidentified as unstable during the glycation process were discarded. Peptides leading to theformation of precursor ions with more than 3 charges were also excluded. Only candidates displaying one specific glycation-related modification and less than two missed cleavages were selected for further investigations. Absolute quantification of selected peptide biomarkers by mass spectrometry Total albumin, apoA-I, apoA-II, apoB100 and selected proteotypic peptide biomarkers of glycated albumin, apoA-I, apoA-II and apoB100 were quantified in plasma by LC-MS / MS. All solvents used were LC-MS grade and purchased from Biosolve. A mixed solution of synthetic unlabeled peptides (Thermo Fisher Scientific) was constituted and serially diluted in ultrapure water to obtain seven standard solutions ranging from 0.01 to 10 µmol / L for peptide biomarkers of glycated proteins, and from 5 to 100 µmol / L for total albumin, from 0.5 to 50 µmol / L for total apoA-I and apoA-II, and from 0.25 to 25 µmol / L for total apoB100. The labeled peptides were used as internal standards and added to the digestion buffer prior to sample preparation. Standard solutions and EDTA plasma samples were then prepared with theProteinWorks™ eXpress kit (Waters Corporation, Milford, MA, USA) as describedpreviously31. Briefly, samples (40 µL) were reduced, alkylated and trypsin digested overnight, and the resulting peptides were cleaned on 30 mg Oasis HLB cartridges (Waters Corporation). The eluates were dried under nitrogen, reconstituted with 5% acetonitrile containing 0.1% formic acid (100 µL), and injected into the LC-MS / MS system. Analyses were performed on an Absolute® triple quadrupole mass spectrometer with an ESI interface and an AcquityPremier® UPLC™ device (Waters Corporation). Peptides were separated on an Acquity®Premier BEH C18 column (2.1 × 100 mm, 1.7 µm VanGuardTM FIT, Waters Corporation) kept at 60 °C with a linear gradient of mobile phase B (acetonitrile containing 0.1% formic acid) in mobile phase A (5% acetonitrile in water containing 0.1% formic acid) as described previously31. Peptides were then detected by the mass spectrometer with the ESI interface operating in the positive ion mode (capillary voltage, 3 kV; desolvation gas (N2) flow and temperature, 650 L / h and 450 °C; source temperature, 120 °C). The multiple reaction monitoring (MRM) mode was applied for MS / MS detection, and the parameters were optimized for each peptide from synthetic peptide solutions. Data acquisition and analyses were performed with MassLynx® and TargetLynx® software, respectively (version 4.1; Waters Corporation). Chromatographic peak area ratios between unlabeled / labeled peptides constituted the detector responses. Standard solutions were used to plot the calibration curves for quantification. Method validation The targeted LC-MS / MS method was first applied to individual plasma samples (CRB Poitiers). Peptides that were not or partially detected were excluded from further investigations. The specificity of the remaining candidates was evaluated by incubating pooled plasma (FrenchBlood Bank) with solutions of MGO as described before. To assess the intra- and inter-assay variability of the LC-MS / MS method, three other pooled EDTA plasma samples were prepared by mixing samples from six subjects (CRB Poitiers) who were selected to get three concentration levels of targeted peptide biomarkers: low, middle and high. Each pool was divided into 24 equal fractions of 40 µL and treated as described above. Six fractions per levelwere analyzed, and the analyses were repeated on four consecutive days. The intra- and inter-assay variability was expressed by the coefficient of variation (CV, %) with a maximum tolerance of 15%32. The linearity was illustrated by R² coefficients calculated from calibration curves by linear regression analysis (1 / x weighting, origin excluded). Additional pooled plasmafractions were prepared to test the stability of peptides after three freeze / thaw cycles at -80 °C.The stability was expressed by the mean recovery (%) calculated between freshly prepared samples and those stored at -80 °C. Long-term stability and repeatability was assessed by re- analyzing the individual plasmas (n = 40) 6 months later. A Bland-Altman plot was generated to test the similarity of both assays33. The SURDIAGENE cohort The design of the SURDIAGENE cohort has already been extensively described elsewhere34. Briefly, SURDIAGENE is a large, prospective, monocentric cohort study with the consecutive inclusion of 1468 patients with T2D taken care at the Poitiers University Hospital (France) between 2001 and 2012. Clinical and biological data were collected at inclusion and blood / urine samples were drawn. Standard biological analyses included C-reactive protein (CRP), HbA1c, urinary creatinine / albumin, serum concentrations of soluble tumor necrosis factor receptor 1 (TNFR1), fasting plasma glucose, total and HDL cholesterol, plasma triglycerides and plasma MGO23. LDL cholesterol was calculated using the Friedewald equation, and non-HDL cholesterol was calculated as total cholesterol minus HDL cholesterol. Renal function was assessed using estimated glomerular filtration rate (eGFR) calculated withthe CKD-EPI 2009-formula35. Patients with baseline eGFR < 15 mL / min / 1.73 m² or renalreplacement therapy were excluded. History of coronary artery disease was defined as history of angina pectoris and / or coronary revascularization and / or myocardial infarction. Patient living status were determined from patients’ hospital records and inquiry to the French National Death Registry. Participants were followed from baseline until death or December 31, 2015, whichever came first. The co-primary endpoints were 1) severe coronary artery disease (CAD) outcome, a composite of fatal and non-fatal myocardial infarction and coronary artery revascularization, 2) MACE, a composite of CV death, non-fatal myocardial infraction, non- fatal stroke, 3) CV morality and 4) all-cause mortality. Each event was reviewed by an adjudication committee according to the international definitions of clinical outcomes. The adjudication committee was blinded with regard to plasma concentrations of biomarkers and other risk factors. Statistical analysis For the validation of the LC-MS / MS assay, statistical analyses were performed with GraphPad Prism software (version 8.0, GraphPad Software Inc., La Jolla, CA). Values are expressed as means ± standard deviations (SD) if normally distributed (D’Agostino–Pearson test); otherwise, they are expressed as medians (range). Unpaired data (i.e., healthy vs. patients with T2D) were compared with the nonparametric Mann–Whitney test. The results were considered to be significant at p < 0.05. For the analysis of the SURDIAGENE study, categorical parameters were described using population size (%) and quantitative parameterswere described with means ± SD or medians (25th – 75th percentiles), according to thedistribution. The independence between two categorical parameters was tested using Fisher’s exact test. The difference between two quantitative variables was tested using unpaired Student t-test or Wilcoxon ranksum test. Correlations between quantitative parameters were summarized using correlation plot, with Pearson method on pairwise complete observations. Time-to-event analyses studying the association between the different biomarkers and the events were performed using multivariable Cox models based on proportional hazardhypothesis, considering five main different models (M): M1, without adjustment; M2, adjustedfor age, sex, eGFR, urine albumin / creatinine ratio (uACR) and CAD history; M3, M2 adjusted for HbA1c; M4, M3 adjusted for non-HDL cholesterol; and M5: M3 adjusted for total HDL cholesterol. The hazard ratios (HR) were calculated after standardization, with or without (log+1) transformation for non-normal distribution. Two-sided p < 0.05 were deemed statistically significant, without accounting for multiple testings. Calculations were performed on available data, without imputation. All statistical analyses were performed using R, version 4.3.2. RESULTS: Identification and selection of proteotypic peptide biomarkers of MGO-glycated proteins Untargeted MS-based proteomic analysis showed that the incubation of recombinant proteins with MGO for 48h (0.3 mmol / L) led to the formation of 88, 54, 3 and 287 proteotypic peptides, for albumin, apoA-I, apoA-II and apoB100, respectively .To increase the specificity of the assay, peptide candidates presenting more than one missed cleavage and / or modification were excluded. In this respect, MGO led to the formation of 32, 22, 3 and 171 specific and simple proteotypic peptides for albumin, apoA-I, apoA-II and apoB100, respectively. Untargeted MS-based proteomic analysis also showed that MGO primarily targets protein- bound arginine to form CEA and MG-H glycation by-products, except for apoA-II. MGO alsoreacted with protein-bound lysine to form CEL glycation by-products (Figure 1). The selectionof proteotypic peptides is critical to accurately quantify MGO-glycated proteins by LC-MS / MS. They must be stable, sensitive, efficiently released from proteolysis, and not interfere with nontargeted proteins. Therefore, peptide candidates carrying methionine (M), cysteine (C), histidine (H) and tryptophan (W) residues were not considered due to potential oxidation and / or cross-reactions as their related by-products were not clearly identified. Thus, 13, 8, 3 and 96 possible biomarkers of MGO-glycated albumin, apoA-I, apoA-II and apoB100 were selected, respectively. Peptide candidates were then searched in trypsin-digested plasma samples to determine those actually produced in-vivo. Only 5, 2, 1 and 6 peptides over all the candidates were specifically detected for albumin, apoA-I, apoA-II and apoB100, respectively. All displayed a change in their arginine residue to a CEA (+72 Da), a MG-H (+54 Da) or both, except for apoA- II for which a change in a lysine residue to a CEL (+72 Da) was observed. All peptides presented a missed cleavage in their modified arginine due to a loss of proteolysis efficiency, the trypsin also targeting arginine and lysine. Each peptide was primarily detected as doubly or triplycharged precursor ion (data not shown). After MS / MS fragmentation, each precursor ionyielded to specific and singly or doubly charged “y” or “b” product ions, ascertaining thereby the peptide sequences and the modified arginine (R) or lysine (K) residue (data not shown). Validation of the LC-MS / MS method for peptide biomarker quantification in humanplasma The LC-MS / MS method developed for the absolute quantification of total plasma albumin and apolipoproteins has already been validated27,31. To test the linearity of the method for the absolute quantification of selected peptide biomarkers, a regression model was used. After analysis of the 8 calibration curves (2 calibration curves per experiment, 4 experiments), the mean R² values were of 0.997 ± 0.002, 0.995 ± 0.004, 0.996 ± 0.005, and 0.998 ± 0.002 for MGH-ALB219-225 (SEQ ID NO:2), MGH-APOA1143-155, CEL-APOA229-39 (SEQ ID NO:3) and MGH-APOB1003184-3194 (SEQ ID NO:1), respectively, and the CVs never exceeded 14.2% over the concentration range tested (7 concentrations ranging 0.01-10 µmol / L). At the lower limit of quantification, the signal-to-noise ratios were higher than 27, which was within the usualcriteria (> 10). Intra- and inter-assay precisions were then assessed using calibration curves andthe 3 pooled plasma samples. Intra- and inter-assay CVs did not exceed 11.7% for all peptidesover the 3 concentration levels (data not shown)). Besides, all peptides were found to remainstable after 3 freeze / thaw cycles (-80 °C) in human EDTA plasma and digested samples were found stable for 48h in the refrigerated autosampler (10 °C) and 6 months at -20 °C (not shown). The specificity of the assay was then evaluated by incubating pooled plasma with MGO solutions. As shown in Figure 2A, the production of MGH-ALB219-225, MGH-APOA1143-155,CEL-APOA229-39 and MGH-APOB1003184-3194 was time- and dose-dependent of the MGOconcentrations. Selected peptides were then assayed in plasma samples from healthy donors and patients with T2D. As shown in Figure 2B, plasma concentrations of MGH-ALB219-225, CEL-APOA229-39 and MGH-APOB1003184-3194 were significantly higher in patients with T2D(p < 0.05), but not MGH-APOA1143-155. To test the long-term stability of peptides and therepeatability of the assay, all of these samples were assayed again 6 months later after a storage at -80 °C. The means of both concentrations were calculated and plotted against the differences between both measurements in the Bland-Altman test. The mean difference and limits of similarity, corresponding to the 95% confidence interval, were drawn and it was demonstrated that all values were within these limits for MGH-ALB219-22,and only 1 or 2 outliers were foundfor MGH-APOA1143-155, CEL-APOA229-39 and MGH-APOB1003184-3194 (Figure 2C). Besides,the mean deviations between both assays were of 3.8 ± 2.3%, 2.8 ± 0.1%, 3.0 ± 0.1% and 4.9 ± 0.1% for MGH-ALB219-225, MGH-APOA1143-155, CEL-APOA229-39and MGH-APOB1003184-3194, respectively, which was within our acceptance criteria. Thus, the LC-MS / MS method allowing the absolute quantification of MGH-ALB219-225, MGH-APOA1143-155, CEL-APOA229-39and MGH-APOB1003184-3194was considered robust and applicable to epidemiological studies. Baseline characteristics of participants of the SURDIAGENE study The SURDIAGENE study included 1468 patients with T2D, of whom 42 patients (2.9%) were excluded because of eGFR < 15 mL / min / 1.73 m² and / or renal replacement therapy at baseline, and one patient was not considered due to a missing determination. The median follow-up duration was 85 months (interquartile range: 75 months). After follow-up, 380 cases of MACE (37.8 / 1000 patient-year), 223 cases of severe CAD events (22.8 / 1000 patient-year), 285 CV deaths (27.1 / 1000 patient-year), and 505 all-cause deaths (35.1 / 100 patient-year) were reported. Total albumin, apoA-I, apoA-II, apoB100 and MGH-ALB219-225, MGH-APOA1143-155, CEL-APOA229-39and MGH-APOB1003184-3194concentrations were successfully measured in the plasma of patients at baseline (data not shown). As expected, all events were significantly associated with age, diabetes duration, personal history of CAD, inflammatory biomarkers and renal function. Besides, CAD and MACE were also associated with chronic hyperglycemia and some lipid disorders such as reduced HDL cholesterol and plasma apoA-I concentrations (CAD) or increased total cholesterol and non-HDL cholesterol concentrations in addition to reduced apoA-I and apoA- II plasma concentrations (MACE). Plasma MGH-ALB219-225was significantly higher in patients who died during follow-up, while total albumin levels were not different. Like apoA-I, plasma MGH-APOA1143-155 was lower in patient who died from all-causes during follow-up. Plasma CEL-APOA229-39was significantly higher in patients who developed CAD during follow-up, while total apoA-II levels were not different. Finally, plasma MGH-APOB1003184-3194 was significantly higher in patients who developed all selected events, while total apoB100 levels were not different. Pearson’s rank correlation coefficients were also calculated between the plasma levelsof peptide biomarkers and the baseline parameters of participants (data not shown). Whereasno major significant correlations were found for total albumin, baseline concentrations of plasma MGH-ALB219-225were positively correlated with CRP and TNFR1. Like apoA-I, plasma concentrations of MGH-APOA1143-155 were primarily and positively correlated with HDL cholesterol. In contrast, while plasma levels of apoA-II were slightly and positively correlated with HDL cholesterol, plasma levels of CEL-APOA229-39were positively correlated with total and LDL cholesterol. Interestingly, while plasma levels of apoB100 were positively correlated with total and LDL cholesterol, no significant correlations were found for plasma levels of MGH-APOB1003184-3194. Of note, none of plasma concentrations of the peptide biomarkers were significantly correlated with HbA1c, plasma glucose nor plasma MGO. Plasma concentrations of peptide biomarkers and risk of cardiovascular events duringfollow‑up Coronary artery disease events (severe CAD events): Figure 3 The baseline levels of HbA1c, plasma albumin, MGO, total cholesterol, non-HDL cholesterol, triglycerides, and MGH-APOA1143-155were not significantly associated with severeCAD events during follow-up, both before (model 1) and after multiple adjustments (models 2-3). Whereas reduced concentration of HDL cholesterol was not associated with severe CADevents before adjustments (model 1), it became significantly associated after adjustment for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD and HbA1c(models 2- 3). In line with this observation, reduced concentrations of plasma apoA-I and apoA-II wereassociated with severe CAD events both before (model 1) and after multiple adjustments(models 2-3). Whereas increased concentration of plasma apoB100 was not associated withsevere CAD events before adjustments (model 1), it became significantly associated afteradjustment for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD, HbA1c, and non-HDL cholesterol (models 2-4). Whereas increased concentration of plasma MGH-ALB219-225was associated with CADbefore adjustments (model 1; HR per 1 SD [95% CI] = 1.11 [1.01; 1.22]; p = 0.027), it was notsignificantly associated after adjustment (models 2-3). Increased concentration of plasma MGH-APOB1003184-3194was associated with severeCAD events both before (model 1; HRM1 = 1.27 [1.14; 1.41]; p < 0.001) and after multipleadjustments for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD, HbA1c, and non-HDL cholesterol (models 2-4; HRM4= 1.27 [1.14; 1.41]; p < 0.001). Of note, this association remained significant after further adjustment for plasma apoB100. Increased concentration of plasma CEL-APOA229-39 was not associated with severeCAD events before adjustments (model 1). However, it became significantly associated afteradjustment for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD, HbA1c, and HDL cholesterol (models 5; HRM5 = 1.13 [1.01; 1.26]; p = 0.030). Of note, this association remained significant after further adjustment for plasma apoA-II. Major adverse cardiovascular events (MACE): Figure 4 The baseline levels of plasma albumin, apoA-II, apoB100, MGO, total cholesterol, non- HDL cholesterol, triglycerides, MGH-ALB219-225and MGH-APOA1143-155were not significantly associated with MACE during follow-up, both before (model 1) and after multiple adjustments (models 2-3). Whereas reduced concentration of HDL cholesterol was associated with MACE before adjustments (model 1), it was not significantly associated after adjustment for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD and HbA1c(models 2-3). In contrast, reduced concentration of plasma apoA-I was associated with MACE both before (model 1) and after multiple adjustments (models 2-3). Whereas increased concentration of plasma apoB100 was not associated with MACE before adjustments (model 1), it became significantly associated after adjustment for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD, and HbA1c (models 2-3), but this association did not survive to further adjustment for non-HDL cholesterol (model 4). Increased concentration of plasma MGH-APOB1003184-3194was associated with MACE both before (model 1; HRM1 = 1.28 [1.11; 1.47]; p < 0.001) and after multiple adjustments for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD, HbA1c, and non-HDL cholesterol (models 2-4; HRM4= 1.25 [1.08; 1.44]; p = 0.002). Of note, this association remained significant after further adjustment for plasma apoB100. Increased concentration of plasma CEL-APOA229-39 was slightly associated with MACE before adjustments (model 1). However, it became significantly associated after adjustment for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD, HbA1c, and HDL cholesterol (models 5; HRM5 = 1.21 [1.06; 1.38]; p = 0.006). Of note, this association remained significant after further adjustment for plasma apoA-II. All-cause mortality: Figure 5 The baseline levels of HbA1c, plasma albumin, apoB100, MGO, total cholesterol, non- HDL cholesterol, and triglycerides were not significantly associated with all-cause mortality during follow-up, both before (model 1) and after multiple adjustments (models 2-3). Whereas reduced concentration of HDL cholesterol was not associated with all-cause mortality before adjustments (model 1), it was significantly associated after adjustment for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD and HbA1c (models 2-3). In line with this observation, reduced concentrations of plasma apoA-I and apoA-II were associated with all- cause mortality both before (model 1) and after multiple adjustments (models 2-3). Surprisingly and like plasma apoA-I, reduced concentration of plasma MGH- APOA1143-155was associated with all-cause mortality both before (model 1; HRM1= 0.85 [0.77; 0.94]; p < 0.001) and after multiple adjustments for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD and HbA1c (models 2-3; HRM3 = 0.86 [0.78; 0.94]; p = 0.001). Increased concentration of plasma MGH-APOB1003184-3194was associated with all- cause mortality both before (model 1; HRM1= 1.13 [1.03; 1.24]; p = 0.007) and after multiple adjustments for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD, HbA1c, and non-HDL cholesterol (models 2-4; HRM4 = 1.14 [1.04; 1.24]; p = 0.006). Of note, this association remained significant after further adjustment for plasma apoB100. Increased concentration of plasma CEL-APOA229-39 was not associated with all-cause mortality before adjustments (model 1). However, it became significantly associated after adjustment for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD, HbA1c, and HDL cholesterol (models 5; HRM5 = 1.12 [1.02; 1.24]; p = 0.020). Of note, this association remained significant after further adjustment for plasma apoA-II. Increased concentration of plasma MGH-ALB219-225was associated with all-cause mortality both before (model 1; HRM1 = 1.14 [1.05; 1.23]; p = 0.001) and after multiple adjustments for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD and HbA1c (models 2-3; HRM3= 1.10 [1.02; 1.19]; p = 0.018). Cardiovascular mortality: Figure 6 The baseline levels of HbA1c, plasma albumin, apoB100, total cholesterol, HDL cholesterol, non-HDL cholesterol, triglycerides, and MGH-APOA1143-155 were not significantly associated with CV mortality during follow-up, both before (model 1) and after multiple adjustments (models 2-3). Reduced concentrations of plasma apoA-I and apoA-II were associated with CV mortality both before (model 1) and after multiple adjustments (models 2- 3). Surprisingly, reduced plasma concentration of MGO was significantly associated with CV mortality during follow-up, both before (model 1) and after multiple adjustments (models 2-3). Increased concentration of plasma MGH-APOB1003184-3194 was associated with CV mortality both before (model 1; HRM1= 1.22 [1.08; 1.39]; p = 0.001) and after multiple adjustments for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD, HbA1c, and non-HDL cholesterol (models 2-4; HRM4 = 1.23 [1.08; 1.39]; p = 0.001). Of note, this association remained significant after further adjustment for plasma apoB100. Increased concentration of plasma CEL-APOA229-39was not associated with CV mortality before adjustments (model 1). However, it became significantly associated after adjustment for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD, HbA1c, and HDL cholesterol (models 5; HRM5= 1.16 [1.02; 1.32]; p = 0.026). Of note, this association remained significant after further adjustment for plasma apoA-II. Increased concentration of plasma MGH-ALB219-225 was associated with CV mortality both before (model 1; HRM1= 1.20 [1.08; 1.33]; p = 0.001) and after multiple adjustments for age, sex, eGFR, urine albumin / creatinine ratio, personal history of CAD and HbA1c(models 2-3; HRM3 = 1.14 [1.03; 1.26]; p = 0.011).REFERENCES: Throughout this application, various references describe the state of the art to which this invention pertains. The disclosures of these references are hereby incorporated by reference into the present disclosure. 1. Saeedi, P. et al. 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Claims

CLAIMS 1. An ex vivo method for diagnosing and / or prognosing type 2 diabetes (TD2) in asubject, comprising the steps of: i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the arginine acid residue (R) at position 222 in SEQ ID NO:5(Albumin) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72) ii) and positively correlating said level of glycation with the prognosis and / or thediagnosis of a type 2 diabetes in said subject.

2. An ex vivo method for determining whether a subject is at a risk of having ordeveloping a cardiovascular event comprising the steps of: i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the arginine acid residue (R) at position 222 in SEQ ID NO:5(Albumin) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72) ii) and positively correlating said level of glycation with the risk of developing acardiovascular event in said subject.

3. The method of claim 2, wherein the cardiovascular event is severe coronaryartery disease (CAD).

4. The method of claim 2, wherein the cardiovascular event is a major adversecardiovascular event (MACE).

5. An ex vivo method for assessing a subject’s risk of having a poor prognostic ofsurvival comprising the steps of: i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the arginine acid residue (R) at position 222 in SEQ ID NO:5(Albumin) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72), ii) comparing each level of glycation determined at step i) with a reference value,and iii) concluding that the that the subject is at high risk of having a poor prognostic ofsurvival when the level(s) of glycation(s) determined at step i) are higher than the reference value.

6. An ex vivo method for assessing a subject’s cardiovascular mortality riskcomprising the steps of: i) determining in a sample obtained from the patient the level of at least oneglycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the arginine acid residue (R) at position 222 in SEQ ID NO:5(Albumin) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72), ii) comparing each level of glycation determined at step i) with a reference value,and iii) concluding that the that the subject is at high risk of having a poor prognostic ofsurvival when the level(s) of glycation(s) determined at step i) are higher than the reference value.

7. An ex vivo method for monitoring the anti-cardiovascular disease treatmentadministered to a patient on cardiovascular mortality risk according to the invention, comprising the steps: i) determining in a sample obtained from the patient the level of at least one glycation of apoprotein and / or albumin selected from the group consisting of : -the glycation of the arginine acid residue (R) at position 3185 in SEQ ID NO:4(ApoB100) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the arginine acid residue (R) at position 222 in SEQ ID NO:5(Albumin) into a methylglyoxal-derived hydroimidazolone (R+54) -the glycation of the lysine residue (K) at position 30 in SEQ ID NO:6 (ApoA-II)into a carboxyethyl-lysine (K+72), ii) determining level of said glycation at a second specific time, and iii) concluding that said treatment is efficient when the level determined at step ii) is lower than the level determined at step i).

8. The method of claim 1 to 7, wherein the the level of at least one glycation isdetermined by the level of at least one glycated peptide selected from the group consisting of :- a glycated-peptide derived from ApoB100 comprising 2, 3, 4, 5, 6, 7, 8, 9, 10 or11 amino acid residues from amino acid residues 3184 to 3194 of SEQ ID NO: 4, wherein thearginine acid residue (R) at position 3185 is glycated in a a methylglyoxal-derivedhydroimidazolone (R+54) -a glycated-peptide derived from Albumin comprising 4, 5, 6, or 7 amino acidresidues from amino acid residues 219 to 225 of SEQ ID NO: 5, wherein the arginine acidresidue (R) at position 222 is glycated in a a methylglyoxal-derived hydroimidazolone (R+54)- a glycated-peptide derived from ApoA-II comprising 2, 3, 4, 5, 6, 7, 8, 9, 10, 11or 12 amino acid residues from amino acid residues 29 to 39 of SEQ ID NO: 6, wherein thearginine acid residue (R) at position 3185 is glycated in a methylglyoxal-derivedhydroimidazolone (R+54).

9. The method of claim 8, wherein the level of a glycated-peptide comprising theamino acid of NR+54NNALDFVTK (SEQ ID NO:1, MGH-ApoB1003184-3194) is determined in step i).

10. The method according to claim 1 to 9, wherein the the level of glycation orglycated-peptide present in the sample is detected by mass spectrometry.

11. The method according to claim 1 to 10, wherein the sample is plasma sample.

12. The method according to claim 11, wherein the subject suffers from type 2diabetes.

13. The method according to claim 1 to 12, wherein the level of glycation orglycated-peptide can be adjusted with 1, 2, 3, 4, 5, 6, 7 or 8 biomarkers selected from the group consisting of the glycated-peptide comprising or consisting of the amino acid subject’s age, subject’s sex, subject’s personal history of CAD level of eGFR, urine albumin / creatinine ratio (uACR), level of glycated haemoglobin (HbA1c), level of non-HDL cholesterol and level of HDL cholesterol.

14. A method for treating a cardiovascular event in a subject determined a risk ofhaving or developing a cardiovascular events according to claim 2 to 4 comprising theadministration to said patient of an anti-cardiovascular disease treatment.

15. Use of a kit or device for performing the method of claim 1 to 14, wherein saidkit or device comprising means for determining the level of the glycated peptide(s) of the invention in a biological sample.