JP2009186474A - System and method for diagnosing and managing patients having risk of cardiovascular disease - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for supporting the evaluation and management of the risk of lipids and metabolism concerning cardiovascular diseases. <P>SOLUTION: The method includes the steps of: determining a fasting triglyceride (TG) level of an individual from a first sample derived from the individual; when the TG level of the individual is greater than 70 mg/dl and less than 200 mg/dl, testing, for small-particle low-density lipoprotein (LDL), a second sample derived from the individual; and determining a low-density lipoprotein-cholesterol (LDL-C) level of the individual from a third sample derived from the individual. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

(Refer to related applications)
This application claims priority based on US Provisional Patent Application No. 60 / 888,415 (February 6, 2007), which is hereby incorporated by reference in its entirety.

(Field of Invention)
The present invention relates to systems and methods for diagnosing and managing patients at risk for cardiovascular disease. The method assists in managing the patient's disease risk by assessing the lipid and metabolic risks associated with cardiovascular disease and then recommending various treatment options based on the patient's test results To do many advanced tests to do. The system and method of the present invention translates the latest clinical studies into available treatment options based on patient test results.

(Background of the Invention)
Nearly 5 million people suffer from congestive heart failure in the United States, and about 550,000 new cases are shown each year. Many do not develop symptoms such as due to left ventricular dysfunction, and as a result, those diseases remain undiagnosed.

  The main cause of morbidity and mortality in the United States is coronary artery disease. Determining the risk of heart attacks and strokes using a single criterion, such as total cholesterol levels in different population groups, has achieved some success. In fact, it has been found that many cases of coronary artery disease occur in those with normal levels of cholesterol.

  Currently, there are no systems, methods, or tools that apply the latest clinical research and comprehensive studies with scientifically referenced clinical pathways to determine and manage patients at risk for cardiovascular disease. Thus, there is a need for a system and method that combines advanced lipid and metabolic testing to assess the risk of cardiovascular disease and assist in managing that risk.

(Summary of Invention)
The present invention relates to systems and methods for diagnosing and managing patients at risk for cardiovascular disease. The systems and methods manage the risk of a patient's disease by assessing lipid and metabolic risks associated with cardiovascular disease and then recommending various treatment options based on the patient's test results. Includes many advanced tests to help.

  Advanced studies include brain natriuretic peptide (BNP), C-reactive protein, total cholesterol, high density lipoprotein cholesterol (HDL-C), ratio of cholesterol to HDL-C, triglycerides, calculated low density lipoprotein Cholesterol (LDL-C), fibrinogen, homocysteine, low density lipoprotein (LDL) subfraction (including LDL 1, LDL 2, LDL 3, LDL 4, LDL 5, LDL 6, LDL 7), calculated LDL , Calculated average LDL particle size, lipoprotein (a), Apo E genotype, plasminogen activator inhibitor 1 (PAI-1), insulin, and pro-BNP, but are not limited to these. Various treatment options may include, but are not limited to, dietary recommendations, exercise recommendations, drug application, and further testing.

  Test results and recommendations are for information and recommendations. It can be provided in the form of a report that facilitates presentation and summary. The systems and methods of the present invention are intended to be performed by computer software and hardware.

  Therefore, the present invention provides the following items.

(Item 1) A method for supporting assessment and management of lipid and metabolic risks related to cardiovascular diseases,
Determining an individual's fasting triglyceride (TG) level from a first sample from said individual;
Testing a second sample from the individual for small particle low density lipoprotein (LDL) when the individual has a TG level greater than 70 mg / dl and less than 200 mg / dl, comprising:
The presence of small particle LDL is presumed to be present in the individual when the TG level of the individual is 200 mg / dl or higher,
If small particle LDL is present in the individual, the following disease management recommendations: loss of excess body fat due to exercise and caloric restriction, avoidance of simple carbohydrates in the diet, selective and non-selective beta blockers Avoidance of possible cases, confirmation of normal thyroid function, introduction of one or more of niacin, fibrate, and fish oil, high density lipoprotein when normal high density lipoprotein cholesterol (HDL-C) ( HDL) subclass testing, as well as one or more of testing first-degree relatives for cardiovascular disease can be brought about in the report;
Determining the low density lipoprotein cholesterol (LDL-C) level of the individual from a third sample from the individual,
When the LDL-C level is in the range of 70 mg / dl to 130 mg / dl and small particle LDL is present, the following disease management recommendations: body avoidance of simple carbohydrates, exercise and calorie restriction in the diet Reduction of fat, introduction of one or more of nicotinic acid, fibrates, statins and fish oils, and testing of apolipoprotein B (Apo B) levels as a measure of LDL particle number can be provided in the report,
When the LDL-C level is 130 mg / dl or higher and small particle LDL is not present, the following disease management recommendations: avoiding simple carbohydrates in the diet, reducing body fat by exercise and caloric restriction, as a diagnosis A study of familial complex hyperlipidemia (FCH), introduction of one or more of nicotinic acid, fibrate, statins and fish oil, testing of apolipoprotein B (Apo B) levels as a measure of LDL particle number, As well as one or more of the screens for cardiovascular disease in first-degree relatives can be provided in the report,
When the LDL-C level is in the range of 70 mg / dl to 130 mg / dl and small particle LDL is not present, the following disease management recommendations are: American Heart Association Phase X diet, medium dose statins At least one of a dose of ezetimibe and a dose of bile acid-binding resin and one or more of apolipoprotein B (Apo B) level tests as a measure of LDL particle counts are also reported If the LDL-C level is greater than 130 mg / dl and no small particle LDL is present, the following disease management recommendations are: low fat diet, statins, ezetimibe, resin, and nicotinic acid As well as apolipotampas as a measure of the number of LDL particles One or more of the test quality B (Apo B) levels, may result in the reporting step;
Including the method.

  (Item 2) If the individual initially has a result indicating that LDL-C is in the range of 70 mg / dl to 130 mg / dl and small particle LDL is present, a fourth sample from the individual The method of item 1, further comprising the step of performing a standard lipid profile test from

  (Item 3) If the individual initially has a result indicating that LDL-C is in the range of 70 mg / dl to 130 mg / dl and small particle LDL is present, The method of item 1, wherein risk management is achieved when the individual has an LDL-C level of less than 70 mg / dl and the individual has a TG level of less than 70 mg / dl.

  (Item 4) When the LDL-C level of the individual is less than 70 mg / dl and the TG level of the individual is 70 mg / dl or more, the LDL subclass test is performed on the fifth sample derived from the individual. Item 3. The method according to Item 2, further comprising a step.

  (Item 5) The method according to item 4, wherein the risk management of the individual for cardiovascular disease is achieved when the result of the LDL subclass test indicates the absence of small particle LDL in the individual.

  (Item 6) If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, supplementing the individual with fibrates, and Item 5. The method of item 4, wherein at least one of the steps of replenishing fish oil is effected in the form of a report.

  (Item 7) If the LDL-C level of the individual is 70 mg / dl or greater and the TG level of the individual is greater than 70 mg / dl, the following disease management recommendations: increasing the statin dose for the individual and The method of item 2, wherein at least one of the steps of adding a dose of resin or ezetimibe to the individual is effected in a reported form.

  (Item 8) If the result from the fourth sample indicates that the LDL-C level of the individual is greater than 70 mg / dl and the TG level of the individual is 70 mg / dl or more, The method of item 2, further comprising the step of performing an LDL subclass test on the fifth sample.

  (Item 9) If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, increasing the statin dose for the individual, 9. The method of item 8, wherein at least one of adding a dose of resin or ezetimibe to the individual and supplementing the individual with fibrate is provided in a reported form.

  (Item 10) If the results of the LDL subclass test indicate the absence of small particle LDL in the individual, the following disease management recommendations: increasing the statin dose for the individual and a dose of resin or ezetimibe to the individual 9. The method of item 8, wherein at least one of the steps of adding to is effected in a report form.

  (Item 11) If the individual initially has a result indicating that LDL-C is greater than or equal to 130 mg / dl and small particle LDL is not present, a standard lipid profile from a fourth sample from the individual Item 2. The method according to Item 1, further comprising a step of performing a test.

  (Item 12) If the individual initially has a result indicating that LDL-C is 130 mg / dl or greater and small particle LDL is not present, managing the risk of the individual for cardiovascular disease is: 2. The method of item 1, wherein the method is achieved when the individual has an LDL-C level of less than 70 mg / dl and the individual has a TG level of less than 100 mg / dl.

  (Item 13) When the LDL-C level of the individual is less than 70 mg / dl and the TG level of the individual is 100 mg / dl or more, an LDL subclass test is performed on the fifth sample derived from the individual. Item 12. The method according to Item 11, further comprising a step.

  14. The method of claim 13, wherein managing the risk for cardiovascular disease in the individual is achieved when the results of the LDL subclass test indicate the absence of small particle LDL in the individual.

  (Item 15) If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, then the following disease management recommendations: increasing nicotinic acid for the individual, supplementing the individual with fibrates, and 14. A method according to item 13, wherein at least one of the steps of replenishing fish oil is effected in the form of a report.

  (Item 16) If the LDL-C level of the individual is 70 mg / dl or greater and the TG level of the individual is greater than 100 mg / dl, the following disease management recommendations: increasing the statin dose for the individual and 12. The method of item 11, wherein at least one of the steps of adding a dose of resin or ezetimibe to the individual is effected in a reported form.

  (Item 17) When the result from the fourth sample indicates that the LDL-C level of the individual is 70 mg / dl or more and the TG level of the individual is 100 mg / dl or more, 12. The method according to item 11, further comprising the step of performing an LDL subclass test on the fifth sample.

  (Item 18) If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, increasing the statin dose for the individual, 18. The method of item 17, wherein at least one of adding a dose of resin or ezetimibe to the individual and supplementing the individual with fibrate is provided in a reported form.

  (Item 19) If the results of the LDL subclass test indicate the absence of small particle LDL in the individual, the following disease management recommendations: increasing the statin dose for the individual and a dose of resin or ezetimibe to the individual 19. The method of item 18, wherein at least one of the steps of adding to is effected in a report form.

  (Item 20) If the individual initially has a result indicating that LDL-C is in the range of 70 mg / dl to 130 mg / dl and no small particle LDL is present, a fourth sample from the individual The method of item 1, further comprising the step of performing a standard lipid profile test from

  (Item 21) If the individual initially has a result indicating that LDL-C is in the range of 70 mg / dl to 130 mg / dl and no small particle LDL is present, then the individual's cardiovascular disease The method of item 1, wherein risk management is achieved when the individual's LDL-C level is less than 70 mg / dl and the individual's TG level has not increased.

  (Item 22) When the LDL-C level of the individual is less than 70 mg / dl and the TG level of the individual is increased, a step of performing an LDL subclass test on a fifth sample derived from the individual 21. The method of item 20, further comprising.

  23. The method of claim 22, wherein managing the risk for cardiovascular disease in the individual is achieved when the results of the LDL subclass test indicate the absence of small particle LDL in the individual.

  (Item 24) If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, supplementing the individual with fibrates, fish oil 23. The method of item 22, wherein at least one of the steps of supplementing the individual with and changing the lifestyle of the individual is effected in the form of a report.

  (Item 25) If the individual's LDL-C level is 70 mg / dl or higher and the individual's TG level has not increased, the following disease management recommendations: increasing the statin dose for the individual and 21. The method of item 20, wherein at least one of the steps of adding a dose of resin or ezetimibe to the individual is effected in a reported form.

  (Item 26) When the result from the fourth sample indicates that the LDL-C level of the individual is 70 mg / dl or more and the TG level of the individual is increased, 21. The method of item 20, further comprising performing an LDL subclass test on 5 samples.

  (Item 27) If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, supplementing the individual with fibrates, fish oil 27. The method of item 26, wherein at least one of the steps of: supplementing the individual and changing the lifestyle of the individual is effected in the form of a report.

  28. If the results of the LDL subclass test indicate the absence of small particle LDL in the individual, the following disease management recommendations: increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual 27. The method of item 26, wherein at least one of the steps of adding to is effected in report form.

  (Item 29) If the individual initially has a result indicating that LDL-C is greater than 130 mg / dl and that small particle LDL is not present, managing the risk of the individual for cardiovascular disease is: The method according to item 1, wherein the method is achieved when the individual has an LDL-C level of less than 70 mg / dl and the TG level of the individual has not changed.

  (Item 30) When the LDL-C level of the individual is less than 70 mg / dl and the TG level of the individual is increased, a step of performing an LDL subclass test on a fifth sample derived from the individual 30. The method of item 29, further comprising.

  31. The method of claim 30, wherein the risk management of the individual for cardiovascular disease is achieved when the results of the LDL subclass test indicate the absence of small particle LDL in the individual.

  32. If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, supplementing the individual with fibrates, and 32. The method of item 30, wherein at least one of the steps of supplementing the individual with fish oil is effected in a reported form.

  (Item 33) If the individual initially has a result indicating that LDL-C is greater than 130 mg / dl and no small particle LDL is present, the LDL-C level of the individual is 70 mg / dl or greater And when the individual's TG level has not changed, at least one of the following disease management recommendations: increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual The method according to item 1, provided in the form of a report.

  (Item 34) If the results from the fourth sample indicate that the LDL-C level of the individual is greater than 70 mg / dl and the TG level of the individual is increased, the fifth from the individual 30. The method of item 29, further comprising the step of performing an LDL subclass test on the sample.

  35. If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: adding nicotinic acid to the individual, increasing the statin dose for the individual 35. The method of item 34, wherein at least one of the steps of supplementing the individual with at least one resin and ezetimibe, and supplementing the individual with fibrate is effected in a reported form.

  36. If the results of the LDL subclass test indicate the absence of small particle LDL in the individual, the following disease management recommendations: increasing the statin dose for the individual and a dose of resin or ezetimibe to the individual 35. The method of item 34, wherein at least one of the steps of adding to is effected in a report form.

  The present invention further provides the following items.

(Item 1a) A method for diagnosing and managing an individual at risk for cardiovascular disease comprising:
Determining an individual's fasting triglyceride (TG) level;
Testing the individual for small particle low density lipoprotein (LDL) depending on the TG level of the individual;
Providing disease management options based on the presence or absence of small particle LDL;
Determining low density lipoprotein cholesterol (LDL-C) levels in the individual; and providing disease management options based on the LDL-C levels in the individual and the presence or absence of small particle LDL in the individual;
Including the method.

  (Item 2a) The individual is tested for small particle LDL when the individual's TG level is greater than 70 mg / dl and less than 200 mg / dl, and the presence of the small particle LDL is determined by the TG of the individual. The method according to item 1a, wherein the method is presumed to be present in the individual when the level is 200 mg / dl or more.

(Item 3a) The following:
Loss of excess body fat due to exercise and caloric restriction, avoidance of simple carbohydrates in the diet, avoidance of selective and non-selective beta-blockers where possible, confirmation of normal thyroid function, niacin, fibrate, And introduction of one or more of fish oil, high density lipoprotein cholesterol (HDL-C) when high density lipoprotein cholesterol (HDL-C) is normal, and first-degree relatives with cardiovascular disease Testing for;
The method of item 2a, wherein one or more of the disease management options is performed when small particle LDL is present in the individual.

(Item 4a) The following:
Avoidance of simple carbohydrates in the diet, reduction of body fat by exercise and caloric restriction, introduction of one or more of nicotinic acid, fibrate, statin and fish oil, and apolipoprotein B (Apo B) as a measure of LDL particle count Level testing;
The method of item 2a, wherein one or more of the disease management options is performed when LDL-C is in the range of 70 mg / dl to 130 mg / dl and small particle LDL is present.

  (Item 5a) The method according to item 4a, further comprising performing a standard lipid profile test.

  (Item 6a) Managing the risk of cardiovascular disease in the individual is achieved when the individual's LDL-C is less than 70 mg / dl and the individual's TG is less than 70 mg / dl. The method according to item 4a.

  (Item 7a) The method according to item 5a, further comprising a step of performing an LDL subclass test when LDL-C of the individual is less than 70 mg / dl and the TG of the individual is 70 mg / dl or more.

  (Item 8a) The method according to item 7a, wherein the risk management of the individual for cardiovascular disease is achieved when the result of the LDL subclass test indicates the absence of small particle LDL in the individual.

  (Item 9a) At least one of a step of increasing nicotinic acid for the individual, a step of supplementing the individual with fibrate, and a step of supplementing fish oil is performed, and the result of the LDL subclass test indicates that the small particle LDL in the individual The method according to item 7a, which further includes a case of indicating the presence of

  (Item 10a) At least one of increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual, the individual having an LDL-C of 70 mg / dl or more, and The method according to item 5a, further comprising a case where the TG of the individual is greater than 70 mg / dl.

  (Item 11a) The method according to item 5a, further comprising the step of performing an LDL subclass test when LDL-C of the individual is greater than 70 mg / dl and the TG of the individual is 70 mg / dl or more.

  (Item 12a) Among the steps of increasing nicotinic acid for the individual, increasing the statin dose for the individual, adding a dose of resin or ezetimibe to the individual, and supplementing the individual with fibrates The method of item 11a, further comprising at least one if the result of the LDL subclass test indicates the presence of small particle LDL in the individual.

  (Item 13a) At least one of increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual, the results of the LDL subclass test indicate that the non-particulate LDL in the individual The method according to item 11a, further including a case of indicating presence.

(Item 14a) The following:
Avoiding simple carbohydrates in the diet, reducing body fat through exercise and caloric restriction, examining familial complex hyperlipidemia (FCH) as a diagnosis, nicotinic acid, fibrate, statins and one or more of fish oil Introduction, testing of apolipoprotein B (Apo B) levels as a measure of LDL particle count, and screening for cardiovascular disease in first-degree relatives;
The method of item 2a, wherein one or more of the disease management options is performed when LDL-C is 130 mg / dl or greater and no small particle LDL is present.

  (Item 15a) The method of item 14a, further comprising performing a standard lipid profile test.

  (Item 16a) Management of risk for cardiovascular disease in the individual is achieved when the LDL-C of the individual is less than 70 mg / dl and the TG of the individual is less than 100 mg / dl. The method according to item 14a.

  (Item 17a) The method according to item 15a, further comprising a step of performing an LDL subclass test when LDL-C of the individual is less than 70 mg / dl and the TG of the individual is 100 mg / dl or more.

  (Item 18a) The method according to item 17a, wherein the risk management of the individual for cardiovascular disease is achieved when the result of the LDL subclass test indicates the absence of small particle LDL in the individual.

  (Item 19a) At least one of a step of increasing nicotinic acid for the individual, a step of supplementing the individual with fibrate, and a step of supplementing fish oil, the result of the LDL subclass test indicates that the small particle LDL in the individual The method according to item 17a, which is further included when indicating the presence of.

  (Item 20a) At least one of increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual, the individual having an LDL-C of 70 mg / dl or more, and The method according to item 15a, further comprising the case where the TG of the individual is greater than 100 mg / dl.

  (Item 21a) The method according to item 15a, further comprising a step of performing an LDL subclass test when LDL-C of the individual is 70 mg / dl or more and TG of the individual is 100 mg / dl or more.

  (Item 22a) Among the steps of increasing nicotinic acid for the individual, increasing the statin dose for the individual, adding a dose of resin or ezetimibe to the individual, and supplementing the individual with fibrates The method of item 21a, further comprising at least one if the result of the LDL subclass test indicates the presence of small particle LDL in the individual.

  (Item 23a) At least one of increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual, the result of the LDL subclass test indicates that the non-particulate LDL in the individual The method according to item 21a, further including a case of indicating presence.

(Item 24a) The following:
American Heart Association Phase X diet, medium dose statin and at least one dose of ezetimibe and a dose of bile acid binding resin, and apolipoprotein B (Apo B) level test as a measure of LDL particle count;
The method of item 2a, wherein one or more of the disease management options is performed when LDL-C is in the range of 70 mg / dl to 130 mg / dl and no small particle LDL is present.

  (Item 25a) The method of item 24a, further comprising performing a standard lipid profile test.

  (Item 26a) Managing the risk of cardiovascular disease in the individual is achieved when the individual's LDL-C is less than 70 mg / dl and the TG of the individual has not increased. The method described in 1.

  (Item 27a) The method according to item 25a, further comprising a step of performing an LDL subclass test when LDL-C of the individual is less than 70 mg / dl and TG of the individual is increased.

  (Item 28a) The method of item 27a, wherein the risk management of the individual for cardiovascular disease is achieved when the results of the LDL subclass test indicate the absence of small particle LDL in the individual.

  (Item 29a) At least one of a step of increasing nicotinic acid for the individual, a step of supplementing the individual with fibrate, a step of supplementing the individual with fish oil, and a step of changing the lifestyle of the individual, The method according to item 27a, further comprising when the result of the LDL subclass test indicates the presence of small particle LDL in said individual.

  (Item 30a) At least one of increasing a statin dose for the individual and adding a dose of resin or ezetimibe to the individual, the individual having an LDL-C of 70 mg / dl or more, and The method according to item 25a, further including the case where the TG of the individual has not increased.

  (Item 31a) The method according to item 25a, further comprising a step of performing an LDL subclass test when LDL-C of the individual is 70 mg / dl or more and TG of the individual is increased.

  (Item 32a) At least one of the step of increasing nicotinic acid for the individual, the step of supplementing the individual with fibrate, the step of supplementing the individual with fish oil, and the step of changing the lifestyle of the individual, The method according to item 31a, further comprising the case where the result of the LDL subclass test indicates the presence of small particle LDL in said individual.

  (Item 33a) At least one of increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual, the result of the LDL subclass test indicates that the small particle LDL in the individual The method according to item 31a, further including a case of indicating presence.

(Item 34a) The following:
Introduction of one or more of a low fat diet, statins, ezetimibe, resin, and nicotinic acid, and testing of apolipoprotein B (Apo B) levels as a measure of LDL particle number;
The method of item 2a, wherein one or more of the disease management options is performed when LDL-C is greater than 130 mg / dl and no small particle LDL is present.

  (Item 35a) Management of risk for cardiovascular disease in the individual is achieved when the individual's LDL-C is less than 70 mg / dl and the TG of the individual has not changed. The method described in 1.

  (Item 36a) The method according to item 35a, further comprising a step of performing an LDL subclass test when LDL-C of the individual is less than 70 mg / dl and TG of the individual is increased.

  (Item 37a) The method according to item 36a, wherein the risk management of the individual for cardiovascular disease is achieved when the result of the LDL subclass test indicates the absence of small particle LDL in the individual.

  (Item 38a) At least one of a step of increasing nicotinic acid for the individual, a step of supplementing the individual with fibrates, and a step of supplementing the individual with fish oil, the result of the LDL subclass test being determined in the individual The method of item 36a, further comprising when indicating the presence of small particle LDL.

  (Item 39a) At least one of increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual, the individual having an LDL-C of 70 mg / dl or more, and The method according to item 34a, further including the case where the TG of the individual has not changed.

  (Item 40a) The method according to item 35a, further comprising the step of performing an LDL subclass test when LDL-C of the individual is greater than 70 mg / dl and TG of the individual is increased.

  (Item 41a) Among the steps of adding nicotinic acid to the individual, increasing the dose of statin to the individual, supplementing the individual with at least one resin and ezetimibe, and supplementing the individual with fibrate 40. The method of item 40a, further comprising at least one of: wherein the results of the LDL subclass test indicate the presence of small particle LDL in the individual.

  (Item 42a) At least one of increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual, the result of the LDL subclass test indicates that the small particle LDL in the individual 40. The method of item 40a, further including when indicating presence.

FIG. 1 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing a patient at risk for cardiovascular disease. FIG. 2 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 3 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 4 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing a patient at risk for cardiovascular disease. FIG. 5 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 6 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 7 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing a patient at risk for cardiovascular disease. FIG. 8 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 9 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 10 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing a patient at risk for cardiovascular disease. FIG. 11 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing a patient at risk for cardiovascular disease. FIG. 12 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 13 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 14 illustrates a flowchart of an exemplary embodiment of the system and method of the present invention for diagnosing and managing a patient at risk for cardiovascular disease. FIG. 15 shows an exemplary patient report made in accordance with the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 16 shows an exemplary patient report generated according to the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 17 shows another exemplary patient report made in accordance with the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 18 shows another exemplary patient report generated according to the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 19 shows another exemplary patient report made in accordance with the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. FIG. 20 shows a scatter plot between fasting TG and LDL PPD in patients with established CHD. FIG. 21 shows HDL-C and HDL2 in men without coronary artery calcification (n = 176, r = 0.82.p <0.0001, mean HDLC = 45.5 + 12.9 mg / dl, HDL2b = 16.0 + 7.5%). FIG. 22 shows HDL-C and HDL2b in men with + CAC (n = 173, r = 0.74, p <0.0001, mean HDLC = 44.0 + 12.0, HDL2b = 14.7% + 6. 4%). Note that low HDL2b in the group of patients with HDLC greater than 55 mg / dl is still low (<20%). FIG. 23 shows HDL-C and HDL2b in women (n = 1523, r = 0.73, p <0.0001, mean HDLC =). FIG. 24 shows HDL-C and HDL2b in males (n = 3,408, r = 0.86, p <0.0001, mean HDLC =).

(Detailed explanation)
The detailed description of the exemplary embodiments refers herein to the accompanying drawings and schematics that illustrate the exemplary embodiment by way of illustration and its best mode. These exemplary embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, but other embodiments may be recognized and logical and mechanical changes may occur. It should be understood that this can be done without departing from the spirit and scope of the invention. Accordingly, the detailed description is provided herein for illustrative purposes only and is not intended to be limiting. For example, the steps described in the description of any method or process can be performed in any order and are not limited to the order provided. Further, any function or process may be outsourced to one or more third parties or performed by one or more third parties. Moreover, any reference to the singular includes the multiple embodiments, and any reference to more than one component can include the singular.

  For the sake of brevity, conventional data network construction, application development, and other functional aspects of the system (and the individual components that drive the components of the system) cannot be described in detail herein. Further, the associated lines shown in the various figures contained herein are intended to illustrate exemplary functional relationships and / or physical connections between various elements. It should be described that many alternative functional relationships or additional functional relationships or physical connections may exist in a practical system.

  Various system components disclosed herein may include one or more of the following: a host server or other computer system with a processor for processing digital data; a processor for storing digital data An input digitizer coupled to a processor for inputting digital data; an application program stored in memory and accessible by the processor for instructing the processing of the digital data by the processor; A display coupled to the processor and memory for displaying information obtained from the digital data; and a plurality of databases. The various databases used herein may include: patient data such as family history, demographics and environmental data, biological sample data, pretreatment and protocol data, patient clinical data, trials Data (brain natriuretic peptide (BNP), C-reactive protein, total cholesterol, high density lipoprotein cholesterol (HDL-C), ratio of cholesterol to HDL-C, triglycerides, calculated low density lipoprotein cholesterol (LDL- C), fibrinogen, homocysteine, low density lipoprotein (LDL) subfraction (including LDL 1, LDL 2, LDL 3, LDL 4, LDL 5, LDL 6, LDL 7), calculated LDL, calculated Average LDL particle size, lipoprotein (a , Apo E genotype, plasminogen activator inhibitor 1 (PAI-1), insulin, and patient-individual data in pro-BNP), disease management options, patient tracking data , File management data, financial management data, billing data and / or data useful for system operation. Those skilled in the art will recognize that the user computer is associated with an operating system (eg, Windows® NT, 95/98/2000, OS2, UNIX®, Linux, Solaris, MacOS, etc.) as well as various computers Recognize that conventional support software and drivers can be provided. The computer can include any suitable personal computer, network computer, workstation, minicomputer, mainframe, and the like. The user computer may be in a home environment or medical / work environment with access to a network. In the exemplary embodiment, the access is via a network or Internet via a commercially available web browser software package.

  As used herein, the term “network” includes any telecommunications means that incorporates both such hardware and software components. Communication between parties can be, for example, devices, keyboards, mice and / or telephone networks, extranets, intranets, the Internet, points of interaction devices (mobile information connected to or connected to any suitable communication or data entry mode) Terminal (eg, Palm Pilot (registered trademark), Blackberry (registered trademark)), mobile phone, kiosk, etc., online communication, satellite communication, offline communication, wireless communication, transponder communication, local area network (LAN), wide area network ( It can be achieved by any suitable communication channel such as WAN). Furthermore, although the system is frequently described herein as being implemented by a TCP / IP communication protocol, the system can also be IPX, Appletalk, IP-6, NetBIOS, OSI or a number of existing or future. Can be implemented using the following protocols: If the network is in the nature of a public network such as the Internet, it may be advantageous to assume that the network is anxious and open to eavesdroppers. Certain information regarding protocols, standards, and application software utilized in communication over the Internet is generally known to those skilled in the art and need not be detailed herein. For example, DILIP NAIK, INTERNET STANDARDS AND PROTOCOLS (1998); JAVA 2 COMPLETE, various authors (Sybex 1999); DEBORAH RAY AND ERIC RAY, MASTERING HTML 4.0 (HIN 1997); and SLO; See TCP / IP CLEARLY EXPLAINED (1997) and DAVID GOURLEY AND BRIAN TOTY, HTTP, THE DEFINITIVE GUIDE (2002), the contents of which are incorporated herein by reference.

  The various system components may be suitably coupled to the network independently, individually or collectively via a data link, which typically includes, for example, standard modem communications, cable modems, dish networks, ISDN, digital subscriptions Used in connection with a subscriber line (DSL) or various wireless communication methods (eg, GILBERT HELD, UNDERSTANDING DATA COMMUNICATIONS (1996), which is incorporated herein by reference) Connection to an Internet Service Provider (ISP) on such a local loop. It is shown that the network can be implemented as other types of networks (eg, interactive television (ITV) networks). Further, the system contemplates the use, sale or distribution of any goods, services or information on any network having similar functionality described herein.

  As used herein, “transmitting” can include transmitting electronic data from one system component to another via network communication. Further, as used herein, “data” may include including information in digital or any other form (eg, instructions, queries, files, data for storage, etc.).

  The systems include web services, utility computing, pervasive and personalized computing, security and identity solutions, autonomous computing, commodities computing, mobility and wireless solutions, open source, bio Contemplates applications related to metrics, grid computing and / or mesh computing.

  Any database disclosed herein may include a relational structure, a hierarchical structure, a graphical structure, or an object-oriented structure and / or any other database configuration. Common database products that can be used to run the database are DB2 by IBM (White Plains, NY), various database products available from Oracle Corporation (Redwood Shores, CA), Microsoft by Microsoft Corporation (Redmond, Washington). Includes Access or Microsoft SQL Server, or any other suitable database product. Further, the database can be organized in a suitable manner, such as a data table or a lookup table. Each record can be a single file, a series of files, a concatenated series of data fields, or any other data structure. The particular data association may be achieved by any desired data association technique (eg, those known or implemented in the art). For example, the association can be accomplished either manually or automatically. Automatic federation techniques, for example, use key fields in tables for database search, database join, GREP, AGREP, SQL, fast search, sequential search by all tables and files, well-known to simplify the search Sorting records in a file according to the above order may be included. The federation process may be accomplished by a database join function (eg, using a “key field” in a preselected database or data sector).

  More specifically, the “key field” divides the database according to the high level class of objects defined by the key field. For example, a particular type of data can be specified as a key field in multiple related data tables, and the data table can be concatenated based on the type of data in the key field. The data corresponding to the key field in each of the concatenated data tables is preferably the same or of the same type. However, data tables with similar but not identical data in the key field can also be concatenated, for example, by using AGREP. In accordance with one embodiment, any suitable data storage technique can be utilized to store data regardless of a standard format. The data set may be stored using any suitable technique, including storing individual files using, for example, the ISO / IEC 7816-4 file structure; To select a dedicated file that exposes one or more basic files containing one or more datasets; to use datasets stored in individual files using a hierarchical filing system; in a single file Data set stored as a record (compressed, SQL accessible, hashed with one or more keys, numeric, alphabetic with first tuple, etc.); Binary Large Object (BLOB); using ISO / IEC 7816-6 data elements As an ungrouped data element encoded as Stored as ungrouped data elements encoded using ISO / IEC Abstract Syntax Notation (ASN.1) as in ISO / IEC 8824 and 8825; and / or a fractal compression method; Other proprietary technologies that can include image compression methods.

  In one exemplary embodiment, the ability to store a wide variety of information in different formats is facilitated by storing the information as a BLOB. Thus, any binary information can be stored in a storage area associated with the data set. The BLOB method described above uses two components with fixed storage offset using either fixed storage allocation, circular queue techniques, or memory management best practices (eg, least recently used paged memory). Data sets may be stored as ungrouped data elements formatted as blocks. By using BLOB, the ability to store various data sets having different formats facilitates the storage of data by multiple and unrelated owners of the data set. For example, a first data set that can be stored can be provided by a first party, and a second data set that can be stored can be provided by an unrelated second party and can be stored third. The data set may be provided by a third party that is not related to the first party and the second party. Each of these three exemplary data sets may include different information stored using different data storage formats and / or techniques. Further, each data set may include a subset of data that may differ from other subsets.

  As described above, in various embodiments, the data can be stored regardless of a common format. However, in one exemplary embodiment, the data set (eg, BLOB) can be annotated in a standard fashion when provided to manipulate the data. Annotations may include a short header, trailer, or other suitable indicator associated with each data set configured to convey information useful for managing the various data sets. For example, an annotation may be referred to herein as a “condition header”, “header”, “trailer”, or “status” and may include an indication of the status of the dataset, or It may include an identifier associated with a particular publisher or owner of the data. The next byte of data can be used, for example, to indicate the identity or publisher of the data, the user, the transaction / member account identifier, etc. Each of these condition annotations is further disclosed herein.

  The data set annotation may also be used for other types of status information and various other purposes. For example, the data set annotation may include security information that establishes an access level. The above access levels are based on, for example, only specific individuals, employee levels, companies, or other entities have access to the dataset, or are based on transactions, data publishers or owners, users, etc. Can be configured to allow access to a particular data set. Further, the security information may limit / permit only certain operations such as accessing the data set, modifying the data set, and / or deleting the data set. In one example, the data set annotation allows only the data set owner or user to be allowed to delete the data set, and various verified users access the data set for reading. It can be permitted to do so and that others are completely excluded from accessing the data set. However, other access restriction parameters may also be used, allowing different entities to access the data set with different permission levels as needed. Data including the header or trailer may be received by a stand-alone interaction device configured to add, delete, modify, or expand data according to the header or trailer.

  Those skilled in the art also recognize that for security purposes, any database, system, device, server, or other component of the system may consist of a single location or any combination thereof in multiple locations, The system exhibits any of a variety of suitable security functions (eg, firewall, access code, encryption, decryption, compression, decompression, etc.).

  The web client computing unit may further comprise an internet browser connected to the internet or intranet using standard dialup, cable, DSL or any other internet protocol known in the art. . Transactions originating from the web client can pass through the firewall to prevent unauthorized access from other network users. Furthermore, additional firewalls can be deployed between the changing components of the CMS to further enhance security.

  A firewall may include any hardware and / or software suitably configured to protect CMS components and / or enterprise computing resources from users of other networks. In addition, the firewall may be configured to limit or restrict access to various systems and components behind the firewall of web clients connecting through a web server. The firewall can exist in a variety of configurations, including Stateful Inspection, Proxy-based and Packet Filtering, among others. The firewall may be integrated within the web server or any other CMS component, or may exist as a separate entity.

  The computers disclosed herein may provide a suitable website or other internet-based graphical user interface that is accessible by the user. In one embodiment, Microsoft Internet Information Server (IIS), Microsoft Transaction Server (MTS), and Microsoft SQL Server, Microsoft SQL Server, Microsoft Software Server (IIS), Microsoft Transaction Server (IIS), Microsoft Transaction Server (IIS) and Microsoft SQL Server. used. In addition, components (eg, Access or Microsoft SQL Server, Oracle, Sybase, Inform MySQL, Interbase, etc.) can be used to provide an Active Data Object (ADO) compliant database management system.

  Any communication, input, storage, database or display disclosed herein may be facilitated by a website having web pages. The term “web page” as used herein is not meant to limit the types of documents and applications that can be used to interact with the user. For example, typical websites include various forms, Java applets, Java scripts, active server pages (ASP), common gateway interface scripts (CGI) in addition to standard HTML documents. , Extensible markup language (XML), dynamic HTML, cascading style sheets (CSS), helper applications, plug-ins, and the like. The server may include web services that accept requests from web servers, requests including URLs and IP addresses. The web server retrieves the appropriate web page and sends the web page data or application to the IP address. A web service may interact with other applications over a communication means (eg, the Internet). Web services are typically based on standards or protocols such as XML, XSLT, SOAP, WSDL and UDDI. Web service methods are well known in the art and are covered in many standard textbooks. See, for example, ALEX NGHIEM, IT WEB SERVICES: A ROAMAP FOR THE ENTERPRISE (2003), which is incorporated herein by reference.

  A clinical database (which may be web-based) for the systems and methods of the present invention preferably has the ability to upload and store clinical data files in a native format and is searchable for any clinical parameter It is. The database can also utilize the EAV data model (metadata) to enter clinical annotations from any study that is searchable and easy to integrate with other studies. Further, web-based clinical databases can be XML and XSLT that are flexible and allow users to add customized questions alike. Further, the database has an export capability to CDISC ODM.

  The practitioner also recognizes that there are many ways to display data in browser-based documents. The data may be presented as standard text or in a fixed list, scrollable list, drop-down list, editable text area, fixed text area, popup window, and the like. Similarly, there are many methods (eg, free text entry using the keyboard, menu item selection, check boxes, option boxes, etc.) that can be used to modify data in a web page.

  The above systems and methods may be described herein with respect to functional block components, flowcharts, screenshots, option selections, and various processing steps. It should be appreciated that such functional blocks can be implemented by a number of hardware and / or software components configured to perform a particular function. For example, the system may include various integrated circuit components (eg, memory elements, processing elements, logic elements, lookup tables, etc.) that perform various functions under the control of one or more microprocessors or other control devices. ) Can be used. Similarly, the software elements of the system can be any programming language or scripting language (eg, C, C ++, Macromedia Cold Fusion, Microsoft Active Server Pages, Java, COBOL, Assembler, PERL, Visual Basic, ed SQL, Procedures, Extensible Markup Language (XML)), and various algorithms may be performed by any combination of data structures, objects, processes, routines or other programming elements. Furthermore, it should be described that the system can use a number of conventional techniques for data transmission, signaling, data processing, network control, and the like. Still further, the system can be used to detect or prevent security issues with a client-side scripting language (eg, Java® Script, VBScript, etc.). For an introduction to the basics of encryption and network security, see one of the following references: (1) “Applied Cryptography: Protocols, Algorithms, And Source Code In C” by Bruce Schneier, John Wiley & S (2nd edition, 1995); (2) “Java® Cryptography” by Jonathan Knudson, published by O'Reilly & Associates (1998); (3) “CryptogramStry Writership: "Principles & Practice", Pren Published by ice Hall; all of which are incorporated herein by reference.

  As used herein, the terms “end user”, “consumer”, “customer”, “client”, “treating physician”, “hospital”, or “business” are used interchangeably. And each means any person, entity, machine, hardware, software or business. Each participant is equipped with a computing device to interact with the system and facilitate online data access and data entry. The customer has a computing device in the form of a personal computer, but other types of computing devices such as laptop computers, notebook computers, portable computers, set-top boxes, cell phones, push phones can be used. The owner / operator of the system and method of the present invention has a computing unit that is executed in the form of a computer server, but other executions are the same as a computing center, minicomputer, PC server, shown as the main computer Or contemplated by the above system comprising a network of computers located at different geographical locations. Further, the system contemplates the use, sale or distribution of any goods, services or information on any network having similar functionality described herein.

  In one exemplary embodiment, each client customer may be issued an “account” or “account number”. As used herein, the account or account number is stably configured to allow consumers to access, interact with, or communicate with the system. Any device, code, number, letter, symbol, digital certificate, smart chip, digital signal, analog signal, biometric or other identifier / indicia (eg authorization / access code, One or more of a personal identification number (PIN), internet code, other identification code, etc.). The above account number can be charged card (charge card), credit card, debit card, prepaid card, embossed card, smart card, magnetic stripe card, barcode card, transponder, radio frequency card (if necessary) radio frequency card) or associated accounts, or may be associated with them. The system may comprise or work with any of the aforementioned cards or devices, or a fob having a transponder and RFID reader in RF communication with a fob. Although the system may include a fob embodiment, the invention is not so limited. Indeed, the system may comprise any device having a transponder configured to communicate with an RFID reader via RF communication. Exemplary devices may include, for example, keychains, tags, cards, cell phones, watches, or any such form that can be provided for inquiries. Further, the systems, computing devices or devices disclosed herein may include “pervasive computing devices” that may comprise traditionally non-computerized devices that are incorporated into computing devices. The account number may be distributed and stored in any form of plastic device, electronic device, magnetic device, radio frequency device, wireless device, acoustic device and / or optical device, the device being a second from itself. Data can be transmitted or downloaded to the device.

  As will be appreciated by those skilled in the art, the above systems include existing system customizations, add-on products, upgraded software, standalone systems, distributed systems, methods, data processing systems, devices for data processing, And / or may be embodied as a computer program product. Thus, the system may take the form of an entirely software embodiment, an entirely hardware embodiment, or an embodiment that combines aspects of both software and hardware. Further, the system can take the form of a computer program product for a computer readable storage medium having computer readable program code, the program code means being embodied in the storage medium. Any suitable computer readable storage medium may be utilized including hard disks, CD-ROMs, optical storage devices, magnetic storage devices, and the like.

  The above systems and methods are described herein with reference to screen shots, block diagrams, and flowchart diagrams of methods, apparatus (eg, systems), and computer program products according to various embodiments. It is understood that each functional block and flowchart diagram in the block diagram, and combinations of functional blocks in the block diagram and flowchart diagram, respectively, can be implemented by computer program instructions.

  Guidelines 1 to 14 shown in FIGS. 1-14 illustrate the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease. The 14 guidelines are listed on the following pages of the specification, along with the related tests performed by the guidelines, the background of the tests, and the results of those tests. Testing, editing of test results, decisions and recommendations for further testing, and recommendations for disease management options can all be automated utilizing computer hardware and computer software (including web-based applications). Patient reports reflecting trials, test results, and recommendations can also be provided, and these reports can also be automated.

(Guideline number 1. Fasting triglyceride levels and small particle LDL test in CHD patients)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Trial fasting triglyceride (TG)
Background A statistically significant inverse correlation exists between fasting triglycerides and the peak particle diameter (PPD) of LDL (r ˜0.55, p <0.001). In general, the higher the TG value, the smaller the LDL size. However, there is considerable overlap within the physical range of 70-200 mg / dl. FIG. 20 shows a scatter plot between fasting TG and LDL PPD in patients with established CHD.

  Blood TG levels can vary in significant amounts in any one patient on a daily basis. For this reason, a few TG values obtained on different days may be promising if the patient's TG value is in the boundary range for medical judgment. Check that the TG value shows a true 12-hour fasting value.

  FIG. 1 shows a flow chart for implementing the first guidelines in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. TG ≦ 70mg / dl
• It is very unlikely that the LDL particles are predominantly small and dense, indicating that the atherogenic lipoprotein profile (ALP) is probably not expressed.
The small LDL is probably not informative.
• Assume that small particle LDL does not prevail for treatment purposes unless there is other clinical suspicion.
Monitor triglyceride (TG) levels. Consider small particle LDL test when TG ≧ 150 mg / dl. Changes in medical conditions and lifestyle (eg, diet, body fat, exercise) can affect fasting TG levels. Some drug applications and OTC drugs can affect TG levels.
Investigate other metabolic disorders contributing to the risk of CHD as small particle LDL does not appear to be a contributing factor in time in this study.

Result number 2. TG> 70 <200 mg / dl
-Indicates that the LDL particles may or may not be predominantly small and low density.
• Testing for small particle LDL traits may provide information in this group.
If small particle LDL traits contribute to risk determination, test for small particle LDL traits.
If small particle LDL traits contribute to treatment decisions, test for small particle LDL traits.
Test for small particle LDL traits when useful as a baseline to assess the effects of lifestyle or drug application.
If small particle LDL traits contribute to family counseling, test for small particle LDL traits.
・ Monitor TG level. An increase in TG often thrives on the presence of increased small particle LDL, and a decrease in TG often reflects a decreased small particle LDL.
HDL subclass distribution not reflected by HDL-C values for HDL-C greater than 40 mg / dl in men and HDL-C greater than 50 mg / dl in premenopausal women (or postmenopausal women in HRT) Consider the determination of HDL subclasses to detect abnormalities in

Result number 3. TG ≧ 200mg / dl
• It is very likely that LDL particles are predominantly small and dense, and that an atherogenic lipoprotein profile (ALP) is probably expressed.
The small particle LDL test is probably not informative.
• Assume that small particle LDL predominates for the purpose of treatment decisions unless there is other clinical suspicion.
Monitor triglyceride (TG) levels. Since the LDL subclass phenotype may have changed, if TG <200 mg / dl, consider a small particle LDL test.

  (Related readings incorporated herein by reference)

(Guideline number 2. LDL subclass distribution in CHD patients (basic meaning))
Testing LDL Subclass Pattern Testing Background LDL is not a homogenous classification of lipoproteins, but consists of a set of distinct subspecies with different molecular properties. In normal subjects, 4-7 major LDL subspecies can be identified that are distinguished by size and density. Often, but not always, a dense LDL subclass pattern (LDL pattern B), a genetic property determined by a single major dominant gene (ALP locus), is associated with increased plasma triglycerides To do. The gene has been named ATHS (for atherosclerosis susceptibility) and is located on the short arm of chromosome 19 (0.5 CM from the LDL receptor). Based on Hardy-Weinberg equilibrium, 30-35% are heterozygous for ALP and another 5% are homozygous. High density LDL variants increase the risk of CAD by a factor of three, and if small particle LDL traits are present in combination with other risk factors (eg, high Apo B and high insulin), the risk is substantial Increase.

  FIG. 2 shows a flow chart for implementing the second guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. LDL pattern A
• Indicates that LDL particles are not predominantly small and dense and that no atherogenic lipoprotein profile (ALP) is expressed.
If LDL-C is increasing: Diet: AHA Step II low-fat diet reduces LDL-C to about 70 mg / dl, and Drug: Statin + ezetimibe or + bile acid binding resin consider. Nicotinic acid (NA) can also help reduce LDLC. Monitor and titrate safety tests as needed and dose • Monitor triglyceride (TG) levels. If the TG is 50 mg / dl, repeat the small particle LDL test. Increases in fasting TG levels may reflect the expression of small particle LDL traits and are affected by body fat, dietary carbohydrates, exercise levels, some drug applications, and some medical conditions.
• Small particle LDL is not a contributing factor at the time of this study, so investigate other metabolic disorders that contribute to the risk of CHD.

Result number 2. LDL pattern B
• LDL particles are predominantly small and dense and reflect the presence of ALP. This indicates a 3-fold increased risk of CHD in the asymptomatic and CHD populations, a 2-fold increased rate of arteriographic progression compared to patients predominating with large LDL particles. ALP is associated with insulin resistance and reflects the high risk of further development of type 2 diabetes. ALP has many of the characteristics of what is referred to herein as “metabolic syndrome”.
• Small, high density LDL and LDL-C • Lifestyle: loss of excess body fat, optimization of exercise, • Diet: simple carbohydrates, avoidance of alcohol, • Drug: when medically appropriate Reduction to about 70 mg / dl by avoidance of selective and non-selective beta blockers. Consider treatment with NA, fibrate, NA + fibrate, or NA + statin. Fish oil nutrients can be beneficial. Monitor and dose therapy as needed.
・ Monitor TG level. An increase in TG often reflects the presence of increased small particle LDL, and a decrease in TG often reflects a decreased small particle LDL.
Consider the measurement of LDL Apo B as a determination of LDL particle number.
HDL subclass distribution not reflected by HDL-C values when HDL-C> 40 <65 mg / dl in men and HDL-C ≧ 50 ≦ 75 mg / dl in premenopausal women (or postmenopausal women in HRT) Consider the determination of HDL subclasses to detect abnormalities in
• Consider family screening. Small particle LDL traits are genetic, and screening a close relative for fasting triglycerides and small particle LDL traits can be informative where appropriate.

  (Related readings incorporated herein by reference)

(Guideline number 3: 70-130 mg / dl of LDL-C and LDL pattern A)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Test * LDL subclass test Background If small particle LDL traits are not present in patients with CHD, investigations into LDL-C depletion and other metabolic disorders may be productive. Safely achieving LDL-C close to 70 mg / dl appears to reduce the risk of CHD.

  Since LDL-C does not increase dramatically, studies for Lp (a), HDL subclass abnormalities, homocysteine, and hyperfibrinogenemia are considered.

If triglyceride (TG) levels increase, consider retesting small LDL to confirm adverse effects on LDL subclass distribution.
Consider AHA low-fat diet or Mediterranean cuisine to help reduce LDL-C.
Consider moderately potent statins to help reduce LDL-C.
Consider ezetimibe ± statin to help reduce LDL-C.
Consider low dose bile acid binding resins to help reduce LDL-C.
Measure baseline apo B for subsequent assessment of LDL particle number and screening for hyperapobetalipoproteinemia.
Repeat the standard lipid profile (TG, TC, LDL-C, HDL-C).

  FIG. 3 shows a flow chart for implementing the third guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. LDL-C <70 mg / dl, TG is not increased.
Achievement of purpose.
Monitor standard lipid profiles and safety studies.

Result number 2. LDL-C <70 mg / dl, TG is increasing.
Repeat the LDL subclass test:
In the case of LDL pattern A, the objective has been achieved.
-For LDL pattern B:
Avoid simple carbohydrates in the diet.
Achieve optimal weight.
Consider increasing physical activity.
Consider using NA, fibrate, or fish oil.

Result number 3. LDL-C ≧ 70 mg / dl, TG is not increased.
Consider increasing statin doses to reduce LDL-C to <70 mg / dl, switching to more powerful statins, or adding ezetimibe or BABR.
Monitor standard lipid profiles and safety studies.

Result number 4. LDL-C ≧ 70 mg / dl, TG is increasing.
Repeat the LDL subclass test:
* For LDL pattern A, consider increasing the statin dose to switch LDL-C to <70 mg / dl, switching to a more powerful statin, or adding ezetimibe or BABR.
-For LDL pattern B:
Avoid simple carbohydrates in the diet.
Achieve optimal weight.
Consider increasing physical activity.
Consider using NA, fibrate, or fish oil.

  (Related readings incorporated herein by reference)

(Guideline number 4: 70 to 130 mg / dl of LDL-C and LDL pattern B)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Test * LDL Subclass Test Background Small particle LDL traits exist in combination with moderately increased LDL-C. In patients with CHD, this combination often requires concomitant medications in addition to lifestyle changes. Achieving LDL-C close to 70 mg / dl appears to reduce the risk (X) of CHD. The presence of small particle LDL implies an increased rate of progression on arteriography and an increased risk of CHD events (x, x). Disturbed reverse cholesterol transport is often also present in these patients. The presence of small particle LDL amplifies the risk of other risk factors such as high Apo B and high insulin (x).
• Avoid simple carbohydrates in the diet and consider Mediterranean cuisine.
Reduce excess body fat (x).
Consider moderately potent statins to help reduce LDL-C.
Consider NA to help reduce small particle LDL and Apo B.
Consider fibrate if NA is unacceptable or contraindicated.
• Consider fish oil nutrients.
Consider ezetimibe + statin to help reduce LDL-C.
Consider low dose bile acid binding resins to help reduce LDL-C.
Measure baseline apo B for subsequent assessment of changes in LDL particle number.
The standard lipid profile (TG, TC, LDL-C, HDL-C) is repeated.

  FIG. 4 shows a flow chart for implementing the fourth guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. LDL-C <70 mg / dl, TG <70 mg / dl.
Achievement of purpose.
Monitor standard lipid profiles and safety studies.

Result number 2. LDL-C <70 mg / dl, TG> 70 mg / dl.
Repeat the LDL subclass test.
* In the case of LDL pattern A, the objective is achieved.
* For LDL pattern B:
Optimize lifestyle.
Consider setting the NA dose to a higher level.
Consider adding fibrate if medically acceptable.
Consider adding fish oil nutrients.
Monitor potential drug interactions.

Result number 3. LDL-C ≧ 70 mg / dl and TG <70 mg / d1.
Consider increasing the statin dose or switching to a more powerful statin.
Consider ezetimibe ± statin to help reduce LDL-C.
Consider low dose bile acid binding resins to help reduce LDL-C.

Result number 4. LDL-C ≧ 70 mg / dl and TG ≧ 70 mg / d1.
Repeat the LDL subclass test.
* For LDL pattern A:
Consider increasing the statin dose or switching to a more powerful statin.
Consider ezetimibe + statin to help reduce LDL-C.
Consider low-dose bile acid-binding resins to help reduce LDL-C.
* For LDL pattern B:
Optimize lifestyle.
Consider setting the NA dose to a higher level.
Consider adding fibrate if medically acceptable.
Consider increasing the statin dose or switching to a more powerful statin.
Consider ezetimibe + statin to help reduce LDL-C.
Consider low-dose bile acid-binding resins to help reduce LDL-C.
Consider adding fish oil nutrients.
Monitor potential drug interactions.

  (Related readings incorporated herein by reference)

(Guideline number 5: LDL-C ≧ 130 mg / dl and LDL pattern A)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Test / LDL-C
LDL subclass test Background If small particle LDL traits are not present in patients with CHD, investigations for concentration and other metabolic disorders for LDL-C reduction may be productive. High LDL-C levels appear to play an atherogenic role in this type of patient. Safely achieving LDL-C close to 70 mg / dl appears to reduce the risk of CHD.

Since LDL-C does not increase dramatically, studies for Lp (a), HDL subclass abnormalities, homocysteine, and hyperfibrinogenemia are considered. This is because the risk of these failures is exacerbated by high LDL-C levels. If triglyceride (TG) levels increase in a clinically significant amount, consider retesting small particle LDL to confirm adverse effects on LDL subclass distribution.
Consider AHA low-fat diet or Mediterranean cuisine to help reduce LDL-C.
Consider moderately potent statins to help reduce LDL-C.
Consider ezetimibe ± statin to help reduce LDL-C.
Consider low dose bile acid binding resin + statins to help reduce LDL-C.
The combination of statin + nicotinic acid has been successfully used in patients with familial heterozygous hyperlipidemia.
Measure baseline apo B for subsequent assessment of changes in LDL particle number.
The standard lipid profile (TG, TC, LDL-C, HDL-C) is repeated.

  FIG. 5 shows a flow chart for implementing the fifth guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. LDL-C <70 mg / dl and TG did not increase.
Achievement of purpose.
Monitor standard lipid profiles and safety studies.

Result number 2. LDL-C <70 mg / dl and TG increased in amounts that were considered clinically significant.
Repeat the LDL subclass test:
In the case of LDL pattern A, the objective is achieved.
-For LDL pattern B:
Avoid simple carbohydrates in the diet.
Achieve optimal weight.
Consider increasing physical activity.
Consider using NA, fibrate, or fish oil.
Note the effects of beta blockers (selective and non-selective) on TG, small particle LDL, and HDL2.

Result number 3. LDL-C ≧ 70 mg / dl and TG did not increase.
Consider increasing the statin dose, switching to a more powerful statin, or adding ezetimibe or BABR to reduce LDL-C to <70 mg / dl.
Monitor standard lipid profiles and safety studies.

Result number 4. LDL-C ≧ 70 mg / dl and TG increased.
Repeat the LDL subclass test:
For LDL pattern A, increase the statin dose, switch to a more powerful statin, or add ezetimibe, or BABR, or nicotinic acid to reduce LDL-C to <70 mg / dl consider.
-For LDL pattern B:
Avoid simple carbohydrates in the diet.
Achieve optimal weight.
Consider increasing physical activity.
Consider using NA, fibrate, or fish oil.
Note the effects of beta blockers (selective and non-selective) on TG, small particle LDL, and HDL2.

  (Related readings incorporated herein by reference)

(Guideline number 6: LDL-C> 130 mg / dl and LDL pattern B)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Test / LDL-C
LDL subclass test Background Small particle LDL traits exist in combination with significantly higher LDL-C. Consider the diagnosis of familial combined hyperlipidemia (FCH). The diagnostic criteria for FCH have recently been modified to include fasting TG> 133 mg / dl and apo B> 120 mg / dl. Diagnosis of FCH implies a 4-fold increased risk of CHD associated with genetic contributors and family relationships. In patients with CHD, this combination often requires combination drug therapy in addition to lifestyle changes. Safely achieving LDL-C close to 70 mg / dl appears to reduce the risk of CHD. The presence of small particle LDL implies an increased rate of progression on arteriography and the risk of increased CHD events. Disturbed reverse cholesterol transport is often present in these patients and is identified by reduced HDL-C and low HDL2. The presence of small particle LDL amplifies the risk of other risk factors (eg, high Apo B and high insulin). CHD patients with this disorder can benefit greatly from treatment with the nicotinic acid + statin or nicotinic acid + bile acid binding resin combination.
• Eliminate major and minor causes of hyperlipidemia.
• Avoid simple carbohydrates in the diet and consider Mediterranean cuisine.
・ Reduce excess body fat.
Consider moderately potent statins to help reduce LDL-C.
Consider nicotinic acid to help reduce small particle LDL and Apo B.
Consider fibrate if nicotinic acid is unacceptable or contraindicated.
• Consider fish oil nutrients.
Consider ezetimibe ± statin to help reduce LDL-C.
• Consider bile acid binding resins + statins to help reduce LDL-C.
Measure baseline apo B for subsequent assessment of changes in LDL particle number and to assist in the diagnosis of FCH.
• Consider screening for first-degree relatives.
The standard lipid profile (TG, TC, LDL-C, HDL-C) is repeated.

  FIG. 6 shows a flow chart for implementing the sixth guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. LDL-C <70 mg / dl and TG <100 mg / dl.
Achievement of purpose.
Monitor standard lipid profiles and safety studies.

Result number 2. LDL-C <70 mg / dl and TG> 100 mg / dl.
Repeat the LDL subclass test.
* In the case of LDL pattern A, the objective is achieved.
* For LDL pattern B:
Optimize lifestyle.
Consider setting the nicotinic acid dose to a higher level.
Consider adding fibrate if medically acceptable.
Consider adding fish oil nutrients.
Monitor potential drug interactions.

Result number 3. LDL-C ≧ 70 mg / dl and TG <100 mg / dl.
Consider increasing the statin dose or switching to a more powerful statin.
Consider ezetimibe ± statin to help reduce LDL-C.
Consider low dose bile acid binding resins to help reduce LDL-C.

Result number 4. LDL-C ≧ 70 mg / dl and TG ≧ 100 mg / dl.
Repeat the LDL subclass test.
* For LDL pattern A:
Consider increasing the statin dose or switching to a more powerful statin.
Consider ezetimibe + statin to help reduce LDL-C.
Consider low-dose bile acid-binding resins to help reduce LDL-C.
* For LDL pattern B:
Optimize lifestyle.
Consider setting the nicotinic acid dose to a higher level.
Consider adding fibrate if medically acceptable.
Consider increasing the statin dose or switching to a more powerful statin.
Consider ezetimibe + statin to help reduce LDL-C.
Consider low-dose bile acid-binding resins to help reduce LDL-C.
Consider the combination of nicotinic acid + statin + bile acid binding resin.
Consider adding fish oil nutrients.
Monitor potential drug interactions.

  (Related readings incorporated herein by reference)

(Guideline 7: Determination of HDL subclass in patients with CHD or PVD)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Test HDL Subclass Distribution Background The HDL subclass test determines the HDL subclass distribution and is reported as the amount (mg / dl) and% (% of total HDL) of HDL2 and HDL3. The HDL2 subclass is associated with a reduced risk of CHD when high and with an increased risk of CHD when low. Low HDL2 levels are associated with arteriographic severity and CHD progression. Increased HDL2 is associated with improved arteriographic results. Low HDL2 is more commonly found in patients with CHD, patients with early CHD, patients with a family history of CHD, patients with type 2 diabetes, patients with high triglycerides, patients with obesity, and some It is found in patients of a racial population (eg, individuals from the Indian subcontinent). This can be particularly important in patients with type 2 diabetes.

  The amount and percentage distributions have been suggested to reflect the efficiency of reverse cholesterol transport (RCT). Very high or very low HDL-C levels predict HDL2 distribution, but HDL-C is about 40-55 mg / dl in men (FIGS. 21, 22, and 24) and women In the case of about 50-65 mg / dl at (Figure 23), there is a low correlation.

In patients with CHD, the approximate mean HDL2 distribution is xxmg / dl (xx%) for males and xxmg / dl (xx%) for females. In men with no evidence of CAD, the above approximate mean is xxmg / dl (xx%) among those with small particle LDL traits and xxmg / dl between those with large particle LDL traits ( xx%) and xxmg / dl (xx%) among middle-aged people who exercise regularly. In women who are premenopausal or in postmenopausal hormone replacement therapy (HRT) and have no evidence of CAD, the approximate mean value is xxmg / mg among those with small particle LDL traits dl (xx%) and xx mg / dl (xx%) among those with large particle LDL traits.
If the HDL-C is greater than 55 mg / dl in men or greater than 65 mg / dl in women who are premenopausal or in HRT, the basic treatment objective is achieved. However, in rare cases, HDL2 may be a low event when HDL-C is above these levels.
Enhance reverse cholesterol transport as reflected by HDL2 values to assist in the treatment of atherosclerosis.
• Consider further increases in HDL2 if evidence of disease progression is evident.

  FIG. 7 shows a flow chart for implementing the seventh guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Standard HDL-C measurement.
Note that HDL-C measurements can vary considerably in any patient due to physiological variability and laboratory method variability.

Result number 1. HDL-C <40 mg / dl in men and HDL-C <50 mg / dl in premenopausal women or women in HRT.
HDL-C is low, and HDL2 appears to be low as well.
FIG. 21 shows HDL-C and HDL2 in men without coronary artery calcification (n = 176, r = 0.82.p <0.0001, mean HDLC = 45.5 + 12.9 mg / dl, HDL2b = 16.0 + 7.5%).
FIG. 22 shows HDL-C and HDL2b in men with + CAC (n = 173, r = 0.74, p <0.0001, mean HDLC = 44.0 + 12.0, HDL2b = 14.7% + 6. 4%). Note that low HDL2b in the group of patients with HDLC greater than 55 mg / dl is still low (<20%).
FIG. 23 shows HDL-C and HDL2b in women (n = 1523, r = 0.73, p <0.0001, mean HDLC =).
FIG. 24 shows HDL-C and HDL2b in males (n = 3,408, r = 0.86, p <0.0001, mean HDLC =).

Result number 1. Low HDL-C (<40 mg / dl in M, <50 mg / dl in W)
If HDL-C is low, HDL2 appears to be low.
Consider HDL subclass test to confirm low HDL2 diagnosis.
• Consider HDL subclass studies as a baseline to compare with future values.

Result 1a. Low HDL2 levels (<xx mg / dl, <xx%).
This supports impaired impaired reverse cholesterol transport as suggested by low HDL-C.
Optimize lifestyle factors that can contribute to low HDL2 and avoid meals high in simple carbohydrates, avoid drug application of non-selective beta-blockers, control excess body fat and optimize exercise , And optimize blood glucose control (insulin resistance).

Identify lack of other medical conditions, including hypertriglyceridemia, hypothyroidism, renal failure, diabetes, and immune disorders.
1) Nicotinic acid (NA) can increase HDL2 by slowing the degradation of HDL2 and increasing the action of ABCA1. NA can be dosed over a wide range to achieve the desired effect.
2) When triglycerides are elevated, fibrates can reduce TG and increase HDL, but the effect can be greater and beneficial for HDL3.
3) Consider a combination of NA (1,000-2,000 mg / d) in combination with a fibric acid derivative (fibrate) reported to achieve a 35% increase in HDL2. Warn about drug-drug interactions.
4) Fish oil (EPA) has been reported to increase HDL2.
5) Consider maintaining LDL-C in the range of 50-70 mg / dl in addition to attempts to increase HDL2 in high-risk patients with low HDL2.
6) Different effects of thiozolodinedione may exist and troglitazone has been reported to increase HDL3 while pioglitazone increases HDL2.
7) Avoid male hormones.
8) Avoid cyclosporine when possible.
9) Avoid selective and non-selective beta blockers where medically appropriate.
10) Consider testing first-degree relatives.

Results lb. “Normal” HDL2 levels (> xxmg / dl (xx%) <xxmg / dl (xx%))
The “normal” range for risk prediction is not necessarily the optimal level for lipoprotein manipulation intended to improve atherosclerosis.

  Consider increasing HDL2 to support the treatment of atherosclerosis.

  Consider optimizing exercise, weight management, and carbohydrate loss in the diet.

When TG increases, the decrease in TG is often associated with an increase in HDL2.
1) Nicotinic acid (NA) can increase HDL2 by slowing the degradation of HDL2 and increasing the action of ABCA1. NA can be dosed over a wide range to achieve the desired effect.
2) If TG rises, consider fibric acid derivatives.
3) Fish oil (EPA) has been reported to increase HDL2.
4) Consider maintaining LDL-C in the range of 50-70 mg / dl in addition to attempts to increase HDL2 in high-risk patients with low HDL2.
5) Avoid male hormones.
6) Test first-degree relatives for low HDL-C.

Result 1c. High HDL2 level> xxmg / dl, xx%.
• It is unlikely that impaired HDL subclass distribution contributes to the risk of atherosclerosis.
Consider optimizing exercise, weight management, and carbohydrate reduction in the diet to increase HDL-C.
Consider NA increasing HDL-C or NA combined with fibrate.
・ Avoid male hormones.
Test for other metabolic disorders that contribute to atherosclerosis.

Result number 2. HDL-C is considered to be in the “normal” range (≧ 40 <65 in M, ≧ 50 <75 in W).
Within this range, it is very difficult to predict the probability of low HDL2 or high HDL2.
• Patients within this HDL-C range can benefit from the HDL subclass test if the results of the HDL subclass test are utilized for:
Make a diagnosis.

  Assist in determining risk predictions.

  Use as a baseline.

  Assist in the choice of lipid therapy.

  To examine the effect of β-blockers on HDL subclass distribution.

Result 2a. Low HDL2 level (<xxmg / dl, <xx%)
This suggests impaired impaired reverse cholesterol transport.
Optimize lifestyle factors that can contribute to low HDL2 and avoid meals high in simple carbohydrates, avoid drug application of non-selective beta-blockers, control excess body fat and optimize exercise , And optimize blood glucose control (insulin resistance).

Identify lack of other medical conditions, including hypertriglyceridemia, hypothyroidism, renal failure, diabetes, and immune disorders.
1) Nicotinic acid (NA) can increase HDL2 by slowing the degradation of HDL2 and increasing the action of ABCA1. NA can be dosed over a wide range to achieve the desired effect.
2) When triglycerides are elevated, fibrates can reduce TG and increase HDL, but the effect can be greater and beneficial for HDL3.
3) Consider a combination of NA (1,000-2,000 mg / d) in combination with a fibric acid derivative (fibrate) reported to achieve an xx% increase in HDL2 (16). Warn about drug-drug interactions.
4) Fish oil (EPA) has been reported to increase HDL2.
5) Consider maintaining LDL-C in the range of 50-70 mg / dl in addition to attempts to increase HDL2 in high-risk patients with low HDL2.
6) Different effects of thiozolozinedione may exist and troglitazone has been reported to increase HDL3, while pioglitazone increases HDL2.
7) Avoid male hormones.
8) Avoid cyclosporine when possible.
9) Avoid selective and non-selective beta blockers where medically appropriate.
10) Consider testing first-degree relatives.

Result 2b. “Normal” HDL2 levels (> xxmg / dl (xx%) <xxmg / dl (xx%))
The “normal” range for risk prediction is not necessarily the optimal level for lipoprotein manipulation intended to improve atherosclerosis.

  Consider increasing HDL2 to support the treatment of atherosclerosis.

  Consider optimizing exercise, weight management, and carbohydrate loss in the diet.

  When TG increases, the decrease in TG is often associated with an increase in HDL2.

Consider the following:
1) Nicotinic acid (NA) can increase HDL2 by slowing the degradation of HDL2 and increasing the action of ABCA1. NA can be dosed over a wide range to achieve the desired effect.

  2) Fish oil (EPA) has been reported to increase HDL2.

  3) Avoid male hormones.

Result 2c. High HDL2 level> xxmg / dl, xx%.
• It is unlikely that impaired reverse cholesterol transport contributes to the risk of atherosclerosis.

  Test for other metabolic disorders that contribute to atherosclerosis.

Result number 3. High HDL-C (> 65 mg / dl in men,> 75 mg / dl in women)
• Does not reflect major dysfunction in RCT, but optimization of RCT may provide some protection against CHD progression.
-The possibility that HDL2 is low is low.
Consider HDL subclass studies for the presence of clinical suspicion such as early CHD or ethnicity reported to have low HDL2 in the presence of normal HDL-C.
Study other metabolic causes of atherosclerosis.
A low dose of NA (1,000 mg / d) may be more effective in delaying the progression of atherosclerosis than statin alone.

Result 3a. Low HDL2 level (<xxmg / dl, <xx%)
• The meaning of low HDL2 in high HDL-C settings is unclear.
Investigate and treat other disorders associated with CHD.
• In the absence of other disorders, attempts to increase HDL2 may be useful, but clinical trial data is limited.
Optimize lifestyle factors that can contribute to low HDL2 and avoid meals high in simple carbohydrates, avoid drug application of non-selective beta-blockers, control excess body fat and optimize exercise , And optimize blood glucose control (insulin resistance).
1. Nicotinic acid (NA) can increase HDL2 by slowing the degradation of HDL2 and increasing the action of ABCA1. NA can be dosed over a wide range to achieve the desired effect.
2. Avoid male hormones.
3. Avoid selective and non-selective β-blockers where medically appropriate.

Result 3b. “Normal” HDL2 levels (> xxmg / dl (xx%) <xxmg / dl (xx%))
“Normal” HDL2 in a high HDL-C setting suggests that there are other obstacles contributing to CHD.
Investigate other metabolic causes of atherosclerosis.
1) Nicotinic acid (NA) can increase HDL2 by slowing the degradation of HDL2 and increasing the action of ABCA1. NA can be dosed over a wide range to achieve the desired effect.
2) Fish oil (EPA) has been reported to increase HDL2.
3) Avoid male hormones.

Result 3c. High HDL2 level> xxmg / d1, xx%.
• It is unlikely that impaired reverse cholesterol transport contributes to the risk of atherosclerosis.
1) Test for other metabolic disorders that contribute to atherosclerosis.

  (Incorporated references)

(Guideline 8: Fasting triglycerides from 400 mg / dl to 1,000 mg / dl)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

test:
Fasting triglycerides Background Fasting triglyceride values> 400 mg / dl and <1,000 mg / dl are often the result of polygenic environmental interactions. The risk of CHD can vary considerably depending on the underlying cause of hypertriglyceridemia. Normal lipoprotein lipase (LPL) function is essential for normal triglyceride hydrolysis, and apolipoprotein C-II is a cofactor for LPL action. Over 26 mutations in the LPL gene have been identified that can result in a range of mild to complete LPL activity deficiency (3). Apolipoprotein C-II is a cofactor for LPL action. A substantial increase in kilomicrons and VLDL is seen in patients lacking this apoprotein (4). A heterozygous state is present in about 12% of Americans with African ancestry (8).

High triglycerides can be exacerbated by several factors including thyroid function, kidney function, diabetes, beta-blockers and the use of some steroids, diets rich in simple carbohydrates, overweight status, and alcohol consumption.
Eliminate thyroid dysfunction, kidney disease, diabetes, excess calorie consumption, overweight status, and any alcohol consumption.
• Avoid simple carbohydrates in the diet and consider Mediterranean cuisine.
・ Reduce excess body fat.
・ Reduce dietary calories.
・ Optimize physical activity.
• Consider fish oil nutrients.
• Consider nicotinic acid (NA).
Consider fibrate if NA is unacceptable or contraindicated.
• Consider screening for first-degree relatives.
Repeat fasting triglycerides.

  FIG. 8 shows a flow chart for implementing the eighth guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. TG <400, LDLC ≦ 100 mg / d1.
Consider guideline number x.
Repeat the LDL subclass test.
-For LDL pattern A:
Consider increasing the statin dose or switching to a more powerful statin.
Consider ezetimibe ± statin to help reduce LDL-C.
Consider low-dose bile acid-binding resins to help reduce LDL-C.
-For LDL pattern B:
Optimize lifestyle.
Consider setting the NA dose to a higher level.
Consider adding fibrate if medically acceptable.
Consider increasing the statin dose or switching to a more powerful statin.
Consider ezetimibe ± statin to help reduce LDL-C.
Consider low-dose bile acid-binding resins to help reduce LDL-C.
Consider adding fish oil nutrients.
Monitor potential drug interactions.

Result number 2. LDL-C <70 mg / dl, TG ≧ 100 mg / d1.
Repeat the LDL subclass test.
In the case of LDL pattern A, the objective is achieved.
-For LDL pattern B:
Optimize lifestyle.
Consider setting the NA dose to a higher level.
Consider adding fibrate if medically acceptable.
Consider adding fish oil nutrients.
Monitor potential drug interactions.

Result number 3. LDL-C ≧ 70 mg / dl and TG <100 mg / d1.
Consider increasing the statin dose or switching to a more powerful statin.
Consider ezetimibe ± statin to help reduce LDL-C.
Consider low dose bile acid binding resins to help reduce LDL-C.

  (Incorporated references)

(Guideline number 9: Triglyceride> 1,000 mg / dl)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Tests Fasting Triglycerides Background Fasting triglyceride values> 1,000 mg / dl greatly increase the risk of pancreatitis. At this level, laboratory accuracy is problematic and changes in triglycerides of about 100 mg / dl probably do not reflect significant physiological or actual changes. High triglycerides are several factors including thyroid function, kidney function, diabetes, beta-blockers and some steroid use, simple carbohydrate-rich and fat-rich diets, overweight status, and alcohol consumption Can be exacerbated by.

While mild to moderate increases in plasma triglycerides are often polygenic environmental interactions, dramatic increases in fasting triglycerides are usually greater than 1,000 mg / dl, often triglyceride metabolism Associated with genetic defects in Normal lipoprotein lipase (LPL) function is essential for normal triglyceride hydrolysis, and apolipoprotein C-II is a cofactor for LPL action. LPL deficiency is the most common cause of familial chylomicronemia and is an autosome often presented in early childhood with severely high plasma triglycerides, pancreatitis and abdominal pain, rash xanthomas, and retinolipidemia It is a recessive inheritance. It occurs in about 1: 5,000 individuals, and heterozygous conditions are more common than traditional hereditary cholesterol disorders, familial heterozygous hypercholesterolemia, and several populations Can be found in 1 of 40 individuals. Over 26 mutations in the LPL gene have been identified that can cause a range of mild to complete LPL activity deficiency. Apolipoprotein C-II is a cofactor for LPL action. A substantial increase in kilomicrons and VLDL is seen in patients lacking this apoprotein. Homozygous patients lacking apoprotein C-II have significantly reduced LDL and HDL values, which is apoprotein C-II as a cofactor in the conversion of kilomicrons and VLDL to high density lipoprotein Support the role of Apo C-II deficiency is a rare disorder inherited in an autosomal recessive manner and presents clinically in a manner similar to LPL deficiency. However, unlike LPL deficiency, normal plasma infusion temporarily reduces plasma triglycerides. Heterozygote conditions are present in about 12% of African ancestry Americans.
• Consider endocrinology visits to help eliminate major causes of severe hypertriglyceridemia.
Eliminate thyroid dysfunction, kidney disease, diabetes, excessive calorie consumption, and any alcohol consumption.
Reduce triglycerides rapidly to <1,000 mg / dl to help prevent pancreatitis.
• Avoid simple carbohydrates in the diet and consider Mediterranean cuisine.
・ Reduce excess body fat.
・ Reduce dietary calories.
・ Optimize physical activity.
• Consider fish oil nutrients.
• Consider nicotinic acid (NA).
Consider fibrate if NA is unacceptable or contraindicated.
Consider NA + statin.
• Consider screening for first-degree relatives.
Repeat fasting triglycerides.

  FIG. 9 shows a flowchart for implementing the ninth guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. TG <100, LDLC <70 mg / d1.
Achievement of purpose.
Monitor standard lipid profiles and safety studies.

Result number 2. TG ≧ 100 mg / dl, LDL-C <70 mg / dl.
Repeat the LDL subclass test.
In the case of LDL pattern A, the objective is achieved.
-For LDL pattern B:
Optimize lifestyle.
Consider setting the NA dose to a higher level.
Consider adding fibrate if medically acceptable.
Consider adding fish oil nutrients.
Monitor potential drug interactions.

Result number 3. TG <100 mg / dl and LDL-C ≧ 70 mg / dl.
Consider increasing the statin dose or switching to a more powerful statin.
Consider ezetimibe ± statin to help reduce LDL-C.
Consider low dose bile acid binding resins to help reduce LDL-C.

Result number 4. TG> 100 mg / d1 and> 70 mg / d1.
・ Consider guideline X (related readings incorporated herein by reference)

(Guideline number 10. Possible CAD patients with type III hyperlipidemia: Apo E2 / E2 + TG ≧ A60 mg / dl)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Trial Fasting Triglycerides Apo E Genotype Background Disorder (type III hyperlipoproteinemia) is another cause of significant accumulation of apoE2 homozygous state and triglyceride rich lipoprotein remnants and atherosclerosis acceleration Examples of interactions with genetic and environmental factors. About 1: 5,000 individuals develop this disorder. More than 90% of individuals with type III hyperlipoproteinemia are apoE2 homozygotes; however, the disease is caused by the interaction of apoE2 / E2 status with other genetic and environmental factors It is. Because about 1% of the population expresses E2 / 2 isoforms, only 2% of these develop type III hyperlipidemia and large E2 / E2 This is because some individuals do not show an abnormal lipid profile. Expression is suggested by combining the presence of ≧ 160 mg / dl triglyceride (TG) level with the apo E2 / E2 genotype.

Two established alternative indicators of type III hyperlipidemia are the following:
The ratio of VLDL-C to fasting TG above 0.3 (measured directly by ultracentrifugation rather than calculated as TG / 5).
-Demonstration of "flowing data" in agarose gel electrophoresis (old laboratory method).

  Individuals with type III HLP have an increased risk of CHD events.

  Nodular xanthoma and tendon xanthoma can be found in patients with type III HLP.

  FIG. 10 shows a flow chart for implementing the tenth guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. Apo E genotype 2/3, 3/3, 3/4, 4/4.
Since the Apo E 2/2 genotype does not appear to be present, the likelihood that a type III HLP may be present is very low.

Result number 2. Apo E genotype 2/2.
Type III HLP can occur.
• If VLDL-C / TG is> 0.3 or TG is> 160 mg / dl, a putative diagnosis of type III HLP can be made.
The presence of “flowing data” in agarose gel electrophoresis has been a traditional diagnostic criterion in the past.
This condition can be greatly exacerbated by calories in the diet (including those derived from alcohol). It is important to reduce excess body fat and optimize daily physical activity.
• Consider gemfibrozil or fenofibrate as a drug application. Clofibrate has been successfully used in type III hyperlipidemia. Note that fibric acid treatment can cause an increase in LDL-C as TG decreases.
• Consider combinations of fibrate and nicotinic acid.
Consider screening fasting TG and apo E genotypes for first-degree relatives where appropriate.
Repeat laboratory test.

Result number 1. TG <160 mg / dl, LDL-C <100 mg / d1.
Achievement of objectives for type III expression.
Consider the presence of other obstacles that contribute to the risk of CHD.

Result number 2. TG <160 mg / dl, LDL-C ≧ 100 mg / d1.
Refer to guideline number 6.

Result number 3. TG> 160 mg / d1, LDL-C <100 mg / d1.
• A high TG suggests that type III hyperlipidemia continues to develop.
• Consider replacing gemfibrozil or fenofibrate with clofibrate, balancing the potential for reduced cardiovascular events with the reported association of clofibrate with adverse side effects.
If clofibrate is unacceptable, consider adding nicotinic acid (NA) to gemfibrozil or fenofibrate.
・ Continue to promote treatment based on lifestyle.
• Consider fish oil nutrients.
・ Avoid all alcohol consumption.

Result number 4. TG> 160 mg / dl, LDL-C ≧ 100 mg / d1.
• A high TG suggests that type III hyperlipidemia continues to develop.
• Consider replacing gemfibrozil or fenofibrate with clofibrate, balancing the potential for reduced cardiovascular events with the reported association of clofibrate with adverse side effects.
If clofibrate is unacceptable, consider adding nicotinic acid (NA) to gemfibrozil or fenofibrate.
• Consider adding statins with appropriate attention to potential drug interactions.
・ Continue to promote treatment based on lifestyle.
• Consider fish oil nutrients.
・ Avoid all alcohol consumption.

  (Related readings incorporated herein by reference)

(Guideline number 11. Lipoprotein (a) level in CHD patients)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Test / Lp (a)
Background Lipoprotein little (a) (Lp (a)) is an LDL particle with protein apo (a) linked by disulfide bridges. [A] is a protein having structural similarity to plasminogen. High Lp (a) has a strong association with CHD and carotid atherosclerosis and can be elevated in 20-40% of individuals with CHD. Rapid progression of CHD as quantified by arteriography is significantly more common in subjects with high Lp (a), and high Lp (a) may be an independent risk factor for myocardial infarction in adolescents It has been reported and is independently associated with coronary artery disease as defined by arteriography, and more closely related to coronary atherosclerosis than other lipid parameters. The risk of CHD associated with Lp (a) is amplified by other risk factors such as high LDL-C or low HDL-C. The risk is transmitted in a dominant manner, and approximately 50% of first-degree relatives of patients with high Lp (a) also develop this disorder.

  While the evidence that Lp (a) has a strong association with CHD and PVD is abundant, there is little clinical evidence that reducing Lp (a) is beneficial to patients. The high Lp (a) reduction after apheresis is associated with a significant reduction in restenosis after PTCA. A high Lp (a) decrease in postmenopausal women undergoing HRT is associated with a statistically significant decrease in CV events. Retrospective evidence from the FATS trial shows that a significant decrease in LDL-C in patients with high Lp (a) is associated with the rate of progression of arteriography, even though Lp (a) levels are not significantly decreased. obtain.

  The high Lp (a) risk associated with a particular blood level is associated with different Lp (a) isoforms and genotypes. The (a) protein can vary in size and, in general, the smaller (a), greater CHD risk and impaired vascular flow mediated dilation. The racial difference has been explained by the fact that American black men have a larger (a) size compared to white men, and this represents a given Lp ( a) may help explain the relatively low risk of CHD associated with the level. Similar differences have also been described in different native Mexican populations.

  In general, nicotinic acid (NA), or estrogen in postmenopausal women, can reduce high Lp (a). A NA dose of 2000-5000 mg / d is often required for efficacy and can reduce Lp (a) by about 50%. Estrogens can reduce Lp (a) by about 20-30%. A 20 mg / dl Lp (a) is about the 90th percentile in a healthy population, and a threshold for increased CHD risk is generally observed at 20-30 mg / dl. Laboratory methods can vary and result in different values that are considered at risk for cardiovascular events.

Initial treatment Start NA 1500 mg / d or postmenopausal estrogen treatment if clinically appropriate.
• Assess other risk factors and treat them appropriately.

  FIG. 11 shows a flow chart for implementing the eleventh guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. Lp (a) <20 mg / dl.
Lp (a) is probably less than the 90th percentile and within an acceptable range. However, the ultimate goal for each patient should be individualized based on medical history and other risk factors.

Result number 2. Lp (a) ≧ 20 mg / dl.
Consider an additional but acceptable increase in NA to reduce Lp (a).
Consider optimizing other risk factors if Lp (a) is not likely to decrease. It may be beneficial to use statins, ± ezetimibe, ± bile acid binding resins to reduce LDL-C to 50-70 mg / dl.
Neomycin therapy has been shown to reduce Lp (a), but warnings have been issued due to reports of the association of this drug with hearing loss.
Antioxidant treatment with vitamin E and vitamin C provides some protection, as oxidation of Lp (a) increases macrophage uptake of Lp (a) particles. The benefits of this treatment in humans have not been shown and can adversely affect the ability to increase HDL2 and reduce CHD events and their progression.

  (Related readings incorporated herein by reference)

(Guideline number 12: homocysteine> 14 μmol / l)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Tests / Fasting Homocysteine Background High plasma homocysteine (Hcy) may reflect underlying disorders including renal failure, thyroid dysfunction, and pernicious anemia. High Hcy is also associated with an increased risk of CAD, and in patients with established CAD, plasma homocysteine levels greater than 10 μmol / l are associated with a significant increase in mortality. . High homocysteine levels are also associated with impaired vascular reactivity. High blood Hcy levels reflect an increased risk of CHD.

  High homocysteine levels are associated with increased restenosis after PCI, and small studies have shown that homocysteine reduction by folate, B12, and B6 after PCI (baseline 11.4 μmo1 / 1 > 7.5 μmo1 / L) indicate that restenosis is associated with a significant (p <0.03) reduction of 33%.

  High Hcy treatment includes the use of folic acid, vitamin B6, vitamin B12, and betaine. However, recent studies suspect the efficacy of treating Hcy, and even some potential harm. Studies of treatment with folate, B6 and B12 in patients receiving metal stents with reduced blood Hcy levels from 12.2 μmol / l to 9.0 μmol / l have no benefit and revascularization in the vitamin-treated group The higher% required (15.8% vs. 10.6%, p = 0.05). The HOPE-2 study explained the effect of folate, B6 and B12 supplementation on placebo in 5522 subjects over a 5-year period. Patients in the treatment suffered fewer strokes compared to placebo, but patients in the treatment group were hospitalized for unstable angina compared to placebo. No subject benefit was reported at higher Hcy distributions. The VISP study studied “low” or “high” doses of vitamin B nutrients in 3,680 subjects with 13.4 μmol / l Hcy at baseline, and the vascular outcome over two years It was reported that there was no effect on it. However, a 10% reduction in stroke and coronary events was reported in the subset with Hcy> 14 μmol / l at baseline. In a recent NORVIT study, 3,749 post-MI patients were randomized to a combination of 0.8 mg folate, 0.4 mg B12, 40 mg B6 or placebo. Baseline Hcy was about 13 μmol / l, and about 9.5 μmol / l (about −27%) at the active arm. Cardiovascular benefits were not reported in the group receiving folate + B12 + B6, and a trend to increase risk (RR 1.22) was reported. Subjects with a baseline of Hcy> 13 μmo1 / 1 had an increased risk when treated with combined vitamin B therapy compared to subjects with a lower baseline Hcy.

Fasting Homocysteine FIG. 12 shows a flow chart for implementing the twelfth guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. Hcy <10 μmol / l
• Hcy is not associated with an increased risk of CHD.

Result number 2. Hcy ≧ 10 and <14 μmol / l
Hcy is associated with an increased risk of the CHD population.

Result number 3. Hcy ≧ 14 μmol / l
• High Hcy is associated with an increased risk of CHD and may reflect other metabolic disorders.
• Consider screening for renal and thyroid dysfunction.
• Consider screening for pernicious anemia.

  (Related readings incorporated herein by reference)

(Guideline number 13. PAI-I)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Test plasminogen activator inhibitor-1 (PAI-I)
Background The decrease in endogenous fibrinolysis following an increase in PAI-1 appears to exacerbate atherogenesis and is associated with an increased risk of CHD. This is also associated with high insulin levels. The PAI-1 4G / 4G genotype is associated with an increased risk of MI due to increased PAI-1 blood levels. In the Caerphilly Study (13 years study of 2,398 men), multivariate analysis with conventional risk factors (PAI-1, fibrinogen, and D-dimer) was significantly associated with increased risk of CVD . Recent AHA / ACC guidelines recommended PAI-1 as a potential clinically useful marker.

  Niacin may reduce PAI-mRNA and PAI-1 synthesis by 72%. Niacin has been shown to reduce the induced elevation of TNF-α by 66% -89% in tissue culture at ICAM-1 levels (p <0.0001). Gemfibrozil has been reported to attenuate the insulin-induced increase of PAI-1 by 61% in tissue culture (p <0.01). Cerivastatin and simvastatin have been reported to reduce PAI-1 production in tissue culture. The effect of directly targeting high PAI-1 for treatment purposes has not been addressed as a major hypothesis in clinical trials. High PAI-1 can be viewed as a component of the increased thrombosis potentially associated with metabolic syndrome.

  FIG. 13 shows a flow chart for implementing the thirteenth guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. PAI-1 ≦ xx
PAI-1 does not rise. Achievement of purpose.

Result number 2. PAI-1> xx ≦ xx
• PAI-1 rises moderately and reflects a moderate increase in CHD risk.
Consider testing for other factors (including fibrinogen, factor VII, tissue-type plasminogen activator, insulin, and von Willebrand factor) that amplify the risk of CHD associated with high PAI-1 .
Consider appropriate treatment with statin, niacin, fibrate, or TZD (if clinically appropriate) if other factors reflect an increased risk of CHD.

Result number 3. PAI-1> xx
-PAI-1 rises. The risk of CHD increases.
Consider repeating the PAI-1 blood test to confirm the elevated value. Consider treatment with statins, niacin, fibrate, or TZD (when clinically appropriate).
Consider PAI-1 genotyping for counseling of relatives.

  (Incorporated references)

(Guideline Number 14: Fasting Insulin> xxmg / dl)
Descriptions about diagnosis and management are merely suggestions and medical judgment must be personalized for the patient.

Test / Fasting Insulin Background The term “insulin resistance” is used to describe a metabolic state in which insulin action in peripheral tissues is less efficient than normal, which maintains normal blood glucose levels To produce increased insulin secretion. A moderate rise in fasting insulin suggests the presence of insulin resistance and insulin resistance syndrome.

  The second definition of “metabolic syndrome” is indicated by World Health Organization (WHO) based on the European Group for the Study of Insulin Resistance, and hyperinsulinemia or high fasting blood glucose and two of the following: Includes more: abdominal obesity, dyslipidemia, or hypertension (8). This alternative definition is useful because the ATP-III definition does not predict CVD and all-cause mortality very consistently (9). An individual may be insulin resistant without meeting the ATP criteria for “metabolic syndrome”.

  This can be shown by the findings of the Quebec Cardiovascular Study, where the presence of small particle LDL as a metabolic anomaly increases the risk of CV by a factor of 3, while small particle LDL and high apo B The combination of increased the risk of CV 6-fold, and the combination of the presence of small particle LDL and the presence of high apo B and high fasting insulin levels increased the risk of CV 20-fold (25) . The Malmo Heart Disease Prevention Project reported that fasting and post glucose loading insulin levels were highly predictive of CV events in 5,484 healthy men who were followed over the next 19 years. In this plan, the average fasting insulin of the group not affected by the CV event was 10.3 pU / L compared to 12.1 pU / L for the group affected by the CV event.

Insulin levels (not glucose levels) after high glucose load in patients with established CHD are associated with PTCA and stent restenosis. In the “healthy” adult population, the median fasting insulin is 10 pU / ml and the upper 1/3 starts at 12 pU / ml.
・ Examine endocrinology department and eliminate the cause of hyperinsulinemia.
• Consider the diagnosis of metabolic syndrome.
• Avoid simple carbohydrates in the diet and consider Mediterranean cuisine.
・ Reduce excess body fat.
・ Optimize physical activity.
Repeat fasting triglycerides.

  FIG. 14 shows a flow chart for implementing the 14th guideline in the system and method of the present invention for diagnosing and managing patients at risk for cardiovascular disease.

Result number 1. Fasting insulin <10 pU / ml
・ Fasting insulin does not rise.
• Consider insulin testing after glucose load if clinical doubt exists.

Result number 2, fasting insulin ≧ 10 <12 pU / m1
Fasting insulin is moderately elevated.
Consider the following:
-Glucose tolerance test-Reduce simple carbohydrates in the diet-Optimize exercise-Optimize body weight-Repeat fasting insulin after lifestyle adjustment Result number 3. Fasting insulin ≧ 12 pU / m1
Fasting insulin rises.
Consider the following:
・ Endocrinology consultation ・ Glucose tolerance test ・ Reducing simple carbohydrates in meal ・ High fiber diet (50 g / d)
• Optimize exercise • Optimize body weight • Repeat fasting insulin after lifestyle adjustments • Screen for thiazorodindione, metformin, and other components of metabolic syndrome (incorporated herein by reference) Related reading)

SUMMARY Systems and methods for diagnosing and managing patients at risk for cardiovascular disease. The systems and methods provide for automating the sequencing of many advanced tests, editing and evaluating test results, and generating automated reports that include recommended disease management options.

Claims (36)

A method for assisting in the assessment and management of lipid and metabolic risks associated with cardiovascular disease comprising:
Determining an individual's fasting triglyceride (TG) level from a first sample from the individual;
Testing a second sample from the individual for small particle low density lipoprotein (LDL) when the TG level of the individual is greater than 70 mg / dl and less than 200 mg / dl,
The presence of small particle LDL is presumed to be present in the individual when the TG level of the individual is 200 mg / dl or higher,
When small particles LDL are present in the individual, the following disease management recommendations: loss of excess body fat due to exercise and caloric restriction, avoidance of simple carbohydrates in the diet, selective beta blockers and non-selective beta blockers Avoidance of possible cases, confirmation of normal thyroid function, introduction of one or more of niacin, fibrate, and fish oil, high density lipoprotein when normal high density lipoprotein cholesterol (HDL-C) ( HDL) subclass testing, as well as one or more of testing first-degree relatives for cardiovascular disease can be brought about in the report;
Determining the low density lipoprotein cholesterol (LDL-C) level of the individual from a third sample from the individual, comprising:
When the LDL-C level is in the range of 70 mg / dl to 130 mg / dl and small particle LDL is present, the following disease management recommendations: body by avoiding simple carbohydrates in the diet, exercise and caloric restriction Reduction of fat, introduction of one or more of nicotinic acid, fibrates, statins and fish oils, and testing of apolipoprotein B (Apo B) levels as a measure of LDL particle number can be provided in the report,
When the LDL-C level is 130 mg / dl or higher and small particle LDL is not present, the following disease management recommendations: avoiding simple carbohydrates in the diet, reducing body fat by exercise and caloric restriction, as a diagnosis Study of familial complex hyperlipidemia (FCH), introduction of one or more of nicotinic acid, fibrate, statin and fish oil, testing of apolipoprotein B (Apo B) levels as a measure of LDL particle number, As well as one or more of the screens for cardiovascular disease in first-degree relatives can be provided in the report,
When the LDL-C level is in the range of 70 mg / dl to 130 mg / dl and small particle LDL is not present, the following disease management recommendations: American Heart Association Phase X diet, medium dose statins At least one of a dose of ezetimibe and a dose of bile acid binding resin and one or more of apolipoprotein B (Apo B) level tests as a measure of LDL particle counts are also reported When the LDL-C level is greater than 130 mg / dl and no small particle LDL is present, the following disease management recommendations are: low fat diet, statins, ezetimibe, resin, and nicotinic acid As well as apolipoprotein as a measure of LDL particle number One or more of the test (Apo B) levels, may result in the reporting step;
Including the method. If the individual initially has a result indicating that LDL-C is in the range of 70 mg / dl to 130 mg / dl and small particle LDL is present, a standard from a fourth sample from the individual is used. The method of claim 1, further comprising performing a lipid profile test. If the individual initially has a result indicating that LDL-C is in the range of 70 mg / dl to 130 mg / dl and small particle LDL is present, managing the risk of the individual for cardiovascular disease The method of claim 1, wherein the method is achieved when the individual has an LDL-C level of less than 70 mg / dl and the individual has a TG level of less than 70 mg / dl. Further comprising performing an LDL subclass test on a fifth sample from the individual when the individual has an LDL-C level of less than 70 mg / dl and the individual has a TG level of 70 mg / dl or greater. The method according to claim 2. 5. The method of claim 4, wherein risk management for the individual's cardiovascular disease is achieved when the results of the LDL subclass test indicate the absence of small particle LDL in the individual. If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, supplementing the individual with fibrates, and supplementing fish oil The method of claim 4, wherein at least one of the steps is effected in the form of a report. If the individual's LDL-C level is 70 mg / dl or greater and the individual's TG level is greater than 70 mg / dl, the following disease management recommendations: increasing the statin dose for the individual and a dose of resin 3. The method of claim 2, wherein at least one of the steps of adding ezetimibe to the individual is effected in a reported form. If the result from the fourth sample indicates that the individual has an LDL-C level greater than 70 mg / dl and the individual has a TG level of 70 mg / dl or greater, a fifth sample from the individual The method of claim 2, further comprising performing an LDL subclass test on. If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, increasing the statin dose for the individual, a dose of resin 9. The method of claim 8, wherein at least one of adding ezetimibe to the individual and supplementing the individual with fibrate is effected in a reported form. If the results of the LDL subclass test indicate the absence of small particle LDL in the individual, the following disease management recommendations: increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual 9. A method according to claim 8, wherein at least one of said is provided in the form of a report. If the individual initially has a result indicating that LDL-C is greater than or equal to 130 mg / dl and no small particle LDL is present, performing a standard lipid profile test from a fourth sample from the individual The method of claim 1, further comprising: If the individual initially has a result indicating that LDL-C is greater than or equal to 130 mg / dl and that there is no small particle LDL, the risk management for the individual's cardiovascular disease is The method of claim 1, wherein the method is achieved when the C level is less than 70 mg / dl and the TG level of the individual is less than 100 mg / dl. When the LDL-C level of the individual is less than 70 mg / dl and the TG level of the individual is 100 mg / dl or more, the method further includes a step of performing an LDL subclass test on a fifth sample derived from the individual. The method according to claim 11. 14. The method of claim 13, wherein managing the risk for cardiovascular disease in the individual is achieved when the results of the LDL subclass test indicate the absence of small particle LDL in the individual. If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, supplementing the individual with fibrates, and supplementing fish oil 14. The method of claim 13, wherein at least one of the steps is effected in a report form. If the individual's LDL-C level is 70 mg / dl or greater and the individual's TG level is greater than 100 mg / dl, the following disease management recommendations: increasing the statin dose for the individual and a dose of resin 12. The method of claim 11, wherein at least one of the steps of adding ezetimibe to the individual is effected in a reported form. If the result from the fourth sample indicates that the individual has an LDL-C level of 70 mg / dl or greater and the individual has a TG level of 100 mg / dl or greater, the fifth from the individual The method of claim 11, further comprising performing an LDL subclass test on the sample. If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, increasing the statin dose for the individual, a dose of resin 18. The method of claim 17, wherein at least one of adding ezetimibe to the individual and supplementing the individual with fibrate is effected in a reported form. If the results of the LDL subclass test indicate the absence of small particle LDL in the individual, the following disease management recommendations: increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual The method of claim 18, wherein at least one of the results is provided in the form of a report. If the individual initially has a result indicating that LDL-C is in the range of 70 mg / dl to 130 mg / dl and no small particle LDL is present, a standard from a fourth sample from the individual is used. The method of claim 1, further comprising performing a lipid profile test. If the individual initially has a result indicating that LDL-C is in the range of 70 mg / dl to 130 mg / dl and no small particle LDL is present, managing the risk of the individual for cardiovascular disease The method of claim 1, wherein the method is achieved when the individual's LDL-C level is less than 70 mg / dl and the individual's TG level has not increased. When the individual's LDL-C level is less than 70 mg / dl and the individual's TG level is increased, further comprising performing an LDL subclass test on a fifth sample from the individual; The method of claim 20. 23. The method of claim 22, wherein managing the risk for cardiovascular disease in the individual is achieved if the results of the LDL subclass test indicate the absence of small particle LDL in the individual. If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, supplementing the individual with fibrates, fish oil to the individual 23. The method of claim 22, wherein at least one of the step of supplementing and changing the lifestyle of the individual is effected in a report form. If the individual's LDL-C level is 70 mg / dl or higher and the individual's TG level has not increased, the following disease management recommendations: increasing the statin dose for the individual and a dose of resin or 21. The method of claim 20, wherein at least one of the steps of adding ezetimibe to the individual is effected in a reported form. If the result from the fourth sample indicates that the LDL-C level of the individual is 70 mg / dl or higher and the TG level of the individual is increased, the fifth sample from the individual 21. The method of claim 20, further comprising performing an LDL subclass test on the subject. If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, supplementing the individual with fibrates, fish oil to the individual 27. The method of claim 26, wherein at least one of the step of supplementing and changing the lifestyle of the individual is effected in the form of a report. If the results of the LDL subclass test indicate the absence of small particle LDL in the individual, the following disease management recommendations: increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual 27. The method of claim 26, wherein at least one of the results is provided in a report form. If the individual initially has a result indicating that LDL-C is greater than 130 mg / dl and that there is no small particle LDL, the risk management for the individual's cardiovascular disease is The method of claim 1, wherein the method is achieved when the C level is less than 70 mg / dl and the TG level of the individual has not changed. When the individual's LDL-C level is less than 70 mg / dl and the individual's TG level is increased, further comprising performing an LDL subclass test on a fifth sample from the individual; 30. The method of claim 29. 32. The method of claim 30, wherein the risk management for the individual's cardiovascular disease is achieved when the results of the LDL subclass test indicate the absence of small particle LDL in the individual. If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: increasing nicotinic acid for the individual, supplementing the individual with fibrates, and adding fish oil to the individual 32. The method of claim 30, wherein at least one of the steps of supplementing is effected in a report form. If the individual initially has a result indicating that LDL-C is greater than 130 mg / dl and no small particle LDL is present, the individual has an LDL-C level of 70 mg / dl or greater, and the individual The following disease management recommendations when the TG level of the subject has not changed: at least one of increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual is in the form of a report The method of claim 1, wherein If the result from the fourth sample indicates that the individual's LDL-C level is greater than 70 mg / dl and the individual's TG level is increased, then for the fifth sample from the individual 30. The method of claim 29, further comprising performing an LDL subclass test. If the results of the LDL subclass test indicate the presence of small particle LDL in the individual, the following disease management recommendations: adding nicotinic acid to the individual, increasing the statin dose for the individual, 35. The method of claim 34, wherein at least one of the steps of supplementing at least one resin and ezetimibe and supplementing the individual with fibrate is effected in a reported form. If the results of the LDL subclass test indicate the absence of small particle LDL in the individual, the following disease management recommendations: increasing the statin dose for the individual and adding a dose of resin or ezetimibe to the individual 35. The method of claim 34, wherein at least one of said is provided in the form of a report.