Cardiovascular disease risk assessment

Abstract

The invention provides improved methods for analyzing cardiovascular disease risk. According to the invention, an algorithm that considers LDL and HDL subfractions, along with Lp(a) provides significant improvement in predicting CVD versus standard assays that include standard risk factors. Methods of the invention comprise measuring LDL and HDL subfractions in addition to Lp(a) without reference to standard risk factor measurements, such as CRP, total cholesterol, body mass index, weight, triglycerides, and the like. It is unexpected that an algorithm focusing only on LDL and HDL subfractions and Lp(a) would be more informative as to CVD risk than measurements that are much more comprehensive in terms of the markers that are reviewed. In particular, the sdLDL-C subfraction of LDL and the ApoA-1 in large alpha-1 HDL are most informative in conjunction with Lp(a).

What is claimed is: 
     
         1 . A method for assessing cardiovascular risk, the method comprising the steps of:
 obtaining a sample from a patient;   conducting an assay on the sample to determine blood levels of an LDL subfraction, an HDL subfraction, and Lp(a);   entering said levels into a multivariate model to produce a probability of the individual developing cardiovascular disease.   
     
     
         2 . The method of  claim 1 , further comprising:
 obtaining information about one or more of the patient's age, history of blood pressure treatment, smoking, and diabetes; and   entering the obtained information into the multivariate model.   
     
     
         3 . The method of  claim 1 , wherein the multivariate model does not include a C-Reactive protein level. 
     
     
         4 . The method of  claim 1 , wherein the multivariate model does not include triglycerides, total cholesterol, body mass index, waist circumference, patient use of cholesterol lowering medication, and patient use of glucose lowering medication. 
     
     
         5 . The method of  claim 1 , wherein the assay comprises one selected from a group consisting of an enzymatic assay, high-performance liquid chromatography, affinity chromatography, an immunoassay, a radioassay, an enzyme-linked immunosorbent assay, colorimetry, and an electrochemical assay. 
     
     
         6 . The method of  claim 1 , further comprising administering a therapy to the patient based on the assessed cardiovascular risk. 
     
     
         7 . The method of  claim 6 , wherein administering the therapy comprises administering a statin drug. 
     
     
         8 . The method of  claim 1 , further comprising producing a report describing the cardiovascular risk for the patient. 
     
     
         9 . A method of predicting the risk of a patient developing cardiovascular disease, the method comprising:
 obtaining a sample from the patient who presents as negative for cardiovascular disease;   conducting an assay on the sample to determine a level of small, dense low-density lipoprotein cholesterol (sdLDL-C) in the sample;   conducting an assay on the sample to determine a level of lipoprotein(a) (Lp(a)) in the sample;   conducting an assay on the sample to determine a level of apolipoprotein A-I (apoA-I) in the sample; and   entering said levels into a multivariate model to predict a risk of the patient developing cardiovascular disease.   
     
     
         10 . The method of  claim 9 , wherein the conducting an assay to determine a level of apoA-I in the sample comprises determining a level of apoA-I in large α-1 high-density lipoprotein cholesterol in the sample. 
     
     
         11 . The method of  claim 9 , wherein the assay is selected from a group consisting of an enzymatic assay, high-performance liquid chromatography, affinity chromatography, an immunoassay, a radioassay, an enzyme-linked immunosorbent assay, colorimetry, an electrochemical assay, and a combination thereof. 
     
     
         12 . A system for analyzing cardiovascular disease (CVD) hazards, the system comprising:
 a processor coupled to a memory subsystem having instructions stored therein that when executed by the processor cause the system to:
 create a record for a subject; 
 obtain for the subject and store in the record a set of subject levels that include an SdLDL-C level (mg/dL), a level of ApoA-1 in α-1 HDL (mg/dL), and a Lipoprotein(a) level (mg/dL); 
 append, to the record, information for the subject for age (years), smoker status (y/n), use of blood pressure medication (y/n); 
 retrieve a pre-determined coefficient set from the memory subsystem; 
 apply the predetermined coefficient set to the set of subject levels to determine an a CVD hazard factor (x); and 
 operate an output device operably connected to the processor to provide a report indicating a level of future CVD hazard for the subject. 
   
     
     
         13 . The system of  claim 12 , wherein the processor operates to send the report from the output device to a medical facility. 
     
     
         14 . The system of  claim 13 , wherein the predetermined coefficient set consists of numerical coefficients A, B, C, D, E, F, and G, wherein the CVD hazard factor (x) is determined according to:
     x=A+B *(the age)+ C *(the smoker status)+ D *(the SdLDL-C level)+ E *(the level of ApoA-1 in a-1 HDL)+ F *(log(Lipoprotein(a)) level)+ G *(the use of blood pressure medication).   
     
     
         15 . The system of  claim 14 , the memory subsystem having instructions stored therein that when executed by the processor cause the system to further:
 determine from the CVD hazard factor, a probability (p) of the subject developing CVD wherein p=1/(1+ê(−x).   
     
     
         16 . The system of  claim 14 , wherein A is within 25% of -6.4752, B is within 25% of +0.0655, C is within 25% of +0.5816, D is within 25% of +0.0144, E is within 25% of -0.0235, F is within 25% of +0.257, and G is within 25% of +0.6254. 
     
     
         17 . The system of  claim 16 , wherein A is -6.4752, B is +0.0655, C is +0.5816, D is +0.0144, E is -0.0235, F is +0.257, and G is +0.6254. 
     
     
         18 . The system of  claim 15 , wherein the report indicates a high risk of CVD for the subject when p >0.5. 
     
     
         19 . The system of  claim 12 , wherein the output device comprises a network interface card (nic) and the report comprises a file provided to the medical facility using the nic.