Treatment and prevention of cardiovascular disease and thrombosis

Abstract

Provided herein are compositions for the treatment and/or prevention of cardiovascular disease (CVD), and methods of application and use thereof. In particular, the present invention provides treatment and/or prevention of cardiovascular disease with compounds that inhibit the production of TMA in the gut, such as 3,3-dimethyl-1-butanol (DMB) or other compounds represented by Formula I or as shown in FIGS. 20 - 23.

We claim: 
     
         1 . A method for the treatment and/or prevention of cardiovascular disease and/or thrombosis comprising:
 a) identifying a subject as having increased platelet aggregation and/or elevated TMAO levels, and   b) administering to said subject: i) a composition comprising a compound selected from the group consisting of: N,N-dimethylethanolamine (DMEA), N-methylethanolamine (MEA), ethanolamine (EA), trimethylsilyl ethanol, and P,P,P-trimethyl ethanolphosphine; and/or ii) a composition comprising a compound represented by Formula I:   
       
         
           
           
               
               
           
         
         wherein n is an integer, or n is 0, indicating that CH 2  is not present; 
         wherein Y is C, Si, P, S, Ge, Sn, Pb, P, As, Sb, or Bi; 
         wherein X is O or S and the corresponding bond is either present or absent or double, wherein R is H, an alkyl group, alkenyl group, alkynyl group, phenyl group, or a benzyl group; 
         wherein Z is C, CH 2 , CH, O or S, 
         wherein XR is an ester, thioester, or thionester; glycerol, or one of the following three formulas: 
       
       
         
           
           
               
               
           
         
         wherein R′ is H, an alkyl group, alkenyl group, alkynyl group, phenyl group, or a benzyl group; and 
         wherein X′ is O, or S. 
       
     
     
         2 . The method of  claim 1 , further comprising administering a prebiotic, probiotic, and/or fiber to said subject. 
     
     
         3 . The method of  claim 1 , wherein said identifying comprises viewing results of a platelet aggregation assay performed on a sample from said subject which shows increased platelet aggregation. 
     
     
         4 . The method of  claim 1 , wherein said identifying comprises viewing results of a TMA or TMAO assay performed on a sample or exhaled breath from said subject which show elevated TMA or TMAO levels. 
     
     
         5 . The method of  claim 1 , wherein said Formula I has a formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 1 , wherein said Formula I has a formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The method of  claim 1 , wherein said Formula I has a formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 1 , wherein said Formula I induces one or more of the following when administered to a subject: reduced trimethyl amine level, reduced TMAO level, reduced total cholesterol level, reduced LDL level, increased HDL level, reduced triglyceride level, reduced glucose level, and reduced hemoglobin A1C level. 
     
     
         9 . The method of  claim 1 , wherein said dimethylbutanol, and/or derivatives thereof reduce the risk of cardiovascular disease and/or thrombosis when administered to a subject. 
     
     
         10 . The method of  claim 1 , wherein said Formula I has a formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 1 , wherein said Formula I has a formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         12 . A method of treating and/or preventing cardiovascular disease and/or thrombosis comprising administering to a subject: i) a composition comprising a compound selected from the group consisting of: N,N-dimethylethanolamine (DMEA), N-methylethanolamine (MEA), ethanolamine (EA), trimethylsilyl ethanol, and P,P,P-trimethyl ethanolphosphine; and/or ii) a composition comprising a compound represented by Formula I: 
       
         
           
           
               
               
           
         
         wherein n is an integer, or n is 0, indicating that CH 2  is not present; 
         wherein Y is C, Si, P, S, Ge, Sn, Pb, P, As, Sb, or Bi; 
         wherein X is O or S and the corresponding bond is either present or absent or double, wherein R is H, an alkyl group, alkenyl group, alkynyl group, phenyl group, or a benzyl group; 
         wherein Z is C, CH 2 , CH, O or S, 
         wherein XR is an ester, thioester, or thionester; glycerol, or one of the following three formulas: 
       
       
         
           
           
               
               
           
         
         wherein R′ is H, an alkyl group, alkenyl group, alkynyl group, phenyl group, or a benzyl group; and 
         wherein X′ is O, or S. 
       
     
     
         13 . The method of  claim 11 , wherein said subject has been determined to have increased platelet aggregation. 
     
     
         14 . The method of  claim 11 , wherein said subject has been determined to have an elevated TMAO level or an elevated TMA level as indicated by a breath test. 
     
     
         15 . The method of  claim 13 , wherein said administering is under such conditions that at least one symptom of said cardiovascular disease and/or said thrombosis is reduced or eliminated. 
     
     
         16 . The method of  claim 11 , further comprising administering a probiotic, a prebiotic, and/or fiber to said subject. 
     
     
         17 . The method of  claim 11 , wherein said composition comprises dimethylbutanol. 
     
     
         18 . The method of  claim 11 , wherein said composition is co-administered with one or more agents which provide therapy for cardiovascular disease. 
     
     
         19 . The method of  claim 17 , wherein said one or more agents comprises one or more antibiotics that target gut flora. 
     
     
         20 . A food or beverage comprising: i) a compound selected from the group consisting of: N,N-dimethylethanolamine (DMEA), N-methylethanolamine (MEA), ethanolamine (EA), trimethylsilyl ethanol, and P,P,P-trimethyl ethanolphosphine; and/or ii) a compound represented by Formula I: 
       
         
           
           
               
               
           
         
         wherein n is an integer, or n is 0, indicating that CH 2  is not present; 
         wherein Y is C, Si, P, S, Ge, Sn, Pb, P, As, Sb, or Bi; 
         wherein X is O or S and the corresponding bond is either present or absent or double, wherein R is H, an alkyl group, alkenyl group, alkynyl group, phenyl group, or a benzyl group; 
         wherein Z is C, CH 2 , CH, O or S, 
         wherein XR is an ester, thioester, or thionester; glycerol, or one of the following three formulas: 
       
       
         
           
           
               
               
           
         
         wherein R′ is H, an alkyl group, alkenyl group, alkynyl group, phenyl group, or a benzyl group; and 
         wherein X′ is O, or S.