TWI708945B - Method of aiding judgment of risk of circulatory diseases or the like - Google Patents

Abstract

Disclosed are a method of aiding judgment of risk of circulatory diseases, coronary heart diseases, or stroke; and a method of aiding diagnosis of stroke. The method of aiding judgment of risk of circulatory diseases, coronary heart diseases, or stroke includes measuring LDL-TG value in blood separated from the body, and a high LDL-TG value is indicative of high risk of circulatory diseases, coronary heart diseases, or stroke. The method of aiding diagnosis of stroke includes measuring LDL-TG value in blood separated from the body, and a high LDL-TG value is indicative of onset of stroke.

Description

Method to assist in judging the risk of circulatory organ diseases

The present invention relates to a method for assisting in judging the risk of circulatory organ diseases, coronary heart disease or cerebral stroke, and a method for assisting the diagnosis of cerebral apoplexy.

The main components of lipids in serum and plasma are cholesterol, triglycerides, phospholipids, etc. These lipids in the blood combine with prosthetic group-deficient proteins and circulate in the blood as lipoproteins. These lipoproteins are classified into chylomicrons (CM), ultra-low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (hereinafter, sometimes referred to as LDL), and high density lipoproteins due to the difference in density. Lipoprotein (hereinafter, sometimes referred to as HDL) and the like. Among these lipoproteins, LDL is the main transporter of cholesterol from the liver to various tissues. It is believed that the increase of LDL cholesterol (hereinafter, sometimes referred to as LDL-C) is closely related to the production of arteriosclerosis. Therefore, it is believed that LDL-C is a risk factor for arteriosclerosis, ischemic heart disease (coronary artery disease), etc. Knowing the content of LDL-C is an important indicator in the diagnosis, treatment and prevention of these diseases. On the other hand, a large number of cases of ischemic heart disease occurred even if the LDL-C in the blood is within the normal range. Recently, the qualitative change of LDL particles has also begun to be noticed.

A large amount of LDL containing triglycerides (hereinafter, sometimes referred to as TG-rich LDL) is a lipoprotein that differs from normal LDL with higher cholesterol content. It is more common in the blood of patients with liver diseases. Progression of liver disease, its concentration in blood It increases in fluid, and at the end of liver disease, it accounts for most of the lipoproteins present in the blood. In addition, it is reported that TG-rich LDL foamed macrophages, but the foaming rate of macrophages caused by TG-rich LDL is directly proportional to the serum concentration of malondialdehyde-modified LDL, which is a type of oxidized LDL; There is almost no detection of triglyceride peroxide in the blood of healthy people. Compared with patients with liver disease, a significant increase of triglyceride peroxide can be seen in the blood of patients with liver disease. According to these reports, it is believed that triglycerides and oxidized LDL in LDL The relationship is also deep. When comparing the triglycerides in LDL (hereinafter, sometimes referred to as LDL-TG) in patients with coronary heart disease (CHD) and healthy people, the coronary heart disease The LDL-TG in the blood of the patient increases (Non-Patent Document 1). However, there is no evidence that the higher LDL-TG among healthy people with no coronary artery disease at present will have a higher risk of coronary heart disease in the future.

On the other hand, regarding stroke, there is no evidence showing the association with LDL-TG, and it is not clear whether it can be used to diagnose stroke patients or subjects with high LDL-TG values in the future. Whether the risk becomes higher.

As a quantification method of LDL-TG, there is a method of combining two steps of separation and quantification of triglycerides. Differentiating and separating operations include methods such as ultracentrifugation, electrophoresis, and high-performance liquid chromatography. As a quantitative method, for example, an automatic analyzer used in clinical examinations is used for quantification using reagents for triglyceride measurement. Methods etc. The combination of these two can be used to quantify LDL-TG, but these are performed in two stages of the pretreatment step to completely separate LDL and lipoproteins other than LDL and the measurement step, so the operation is complicated and time-consuming . In addition, depending on the separation method, the separated sample itself is difficult to recover, or it is difficult to recover quantitatively, or even if it is a method that can be recovered quantitatively, it requires proficiency or special requirements for the operation. Other machines. These costs are also relatively expensive and are methods that are not easy to popularize in terms of simplicity or economy.

As a method to eliminate these problems, which can be measured by an automatic analyzer without distinguishing operations, it is known that after removing triglycerides in all lipoproteins except LDL in the first step, in the second step Method for measuring triglycerides in the remaining LDL (Patent Documents 1 and 2); or after removing (free glycerol and) triglycerides in HDL in the first step, only LDL is measured in the second step The method of triglyceride (Patent Document 3).

[Prior Technical Literature] [Patent Literature]

Patent Document 1: JP 2006-180707 A

Patent Document 2: US2005/042703 A1

Patent Document 3: US2015/132834 A1

[Non-Patent Literature]

Non-Patent Document 1: Circulation 2004; 109, 2844-2849

The purpose of the present invention is to provide a method to assist in judging the risk of circulatory organ diseases, coronary heart disease or stroke. Furthermore, the object of the present invention is to provide a method for assisting the diagnosis of stroke.

The inventors of this case and others have conducted intensive research and found that healthy people with circulatory organ disease, coronary heart disease or cerebral stroke are in the blood. When the LDL-TG value is high, the possibility of circulatory organ disease, coronary heart disease or cerebral stroke is increasing in the future. In addition, it was found that among patients with stroke, the blood LDL-TG value Higher, thus completing the present invention.

That is, the present invention provides the following.

(1) A method to assist in judging the risk of circulatory organ diseases, coronary heart disease or cerebral stroke, which includes measuring the LDL-TG value in blood separated from a living body, the higher the measured LDL-TG value indicates the circulatory organ The risk of disease, coronary heart disease or stroke is higher.

(2) A method for assisting the diagnosis of cerebral apoplexy, which includes measuring the value of LDL-TG in blood separated from a living body. The higher the value of LDL-TG measured indicates that the possibility of the onset of cerebral apoplexy is higher.

According to the present invention, a method is provided for the first time to accurately determine the risk of developing circulatory organ diseases, coronary heart disease, or cerebral stroke before the onset of these diseases. When judging the higher-risk situations, by changing your lifestyle or taking drugs, you can try to reduce the risk and prevent the onset of these diseases.

Furthermore, according to the present invention, it is possible to assist the diagnosis of stroke quickly and accurately. Therefore, rapid treatment can be carried out at the initial stage of stroke, and death caused by stroke can be prevented.

In the method of the present invention, the LDL-TG value in blood is measured. by It is preferable to use serum or plasma as a blood sample system for easy measurement.

The method for measuring the LDL-TG value in blood is well known (for example, the above-mentioned Patent Documents 1 to 3), and the reagents used for the above-mentioned measurement are also commercially available. Therefore, it is possible to easily quantify LDL-TG in the blood using commercially available reagents. To briefly explain, the LDL-TG value can be measured by the following method: (1) Use surfactants that act on lipoproteins other than LDL (for example, polyalkylene oxide derivatives with HLB values above 13 and below 14) Etc.) The specimen is processed, and then, in the presence of a surfactant (polyalkylene oxide derivatives with an HLB value of 11 or more and less than 13) that acts on LDL, lipoprotein lipase, glycerol kinase, and glycerol- 3-phosphate oxidase acts on the sample to quantify the hydrogen peroxide produced; or (2) the surfactant that acts on lipoproteins other than LDL (for example, polyepoxy with an HLB value of 13 or more and 15 or less) In the presence of alkane derivatives, etc.), lipoprotein lipase, cholesterol esterase, glycerol kinase and glycerol-3-phosphate oxidase are allowed to act on the sample to remove the hydrogen peroxide produced, and then act on the interface activity of LDL In the presence of an agent (polyalkylene oxide derivatives with an HLB value of 11 or more and less than 13, etc.), lipoprotein lipase, glycerol kinase, and glycerol-3-phosphate oxidase are applied to the sample, and the produced Hydrogen peroxide method, etc. In the following examples, a commercially available LDL-TG quantitative kit (LDL-TG "Seiken" (manufactured by DENKA SEIKEN Co., Ltd.)) was used for quantification.

The higher the LDL-TG value in the blood of healthy people with circulatory organ disease, coronary heart disease or cerebral stroke without onset, the higher the possibility of these diseases in the future. Therefore, it is possible to assist in judging the risk of the onset of these diseases in the future based on the measured LDL-TG value in the blood. Since the higher the LDL-TG value in the blood, the higher the possibility of the onset of these diseases in the future, so specific criteria can be set appropriately. For example, in the following example, based on the LDL-TG value in the blood, the subjects were roughly divided into four equal parts, and the incidence rate of each group within 15.6 years was investigated. As a result, if the LDL-TG value is the lowest in the fourth Of quantile The incidence rate is benchmarked, and the incidence rates of the second quartile, the third quartile and the fourth quartile have statistically high statistically significant variation and increase significantly. Since the lower limit of the second quartile at this time is 17.1 mg/dL, for example, if the threshold is set to 17 mg/dL, when it exceeds 17 mg/dL, it can be judged as high risk. Or, when a higher risk is regarded as a high risk, for example, 22.7 mg/dL or more, which is an intermediate value, may be judged as high risk. As described above, the threshold can be arbitrarily set in consideration of the balance with the height of the risk to be detected. For example, any value in the range of 17mg/dL~40mg/dL, especially any value in the range of 25mg/dL~35mg/dL can be set as the threshold value. Furthermore, the LDL-TG value may vary with ethnic groups and other groups. Therefore, the median or average value within the group, the boundary value of the first quartile and the second quartile, etc. can be used as the threshold. Or judge the value near the value (for example, any value within ±20%, etc.) as the threshold value. Furthermore, since the higher the threshold value is, the higher the risk is. Therefore, the risk can be determined based on the specific measurement value, and the probability can be expressed as a numerical value by associating the measurement value with the frequency of event occurrence.

Similarly, based on the LDL-TG value in the blood, it is possible to assist in the diagnosis of stroke in the onset, and furthermore, it is possible to evaluate/determine whether the stroke is severe. For example, when the quantitative value of LDL-TG is 20-40 mg/dL, preferably more than 30 mg/dL, it is judged that the risk of CVD (cardiovascular disease) or CHD or stroke will increase in the future. However, since it is considered that the baseline value of FCHL (familial combined hyperlipidemia) diagnosis varies depending on the ethnic group, it is not limited to this. In addition, among people diagnosed with a higher risk of CHD or stroke, it can be judged that the risk of the disease is higher based on the LDL-TG value of 40 mg/dL and 50 mg/dL.

Hereinafter, the present invention will be specifically explained based on examples. However, the present invention is not limited to the following examples.

[Example 1]

Using the preserved specimen (serum) of the American Generation Test, the concentration of LDL-TG was determined. Specifically, 9,334 cases of CHD or stroke were not onset at baseline blood sampling, and LDL-TG concentration was measured. In addition, based on the 15.6-year results of the subjects of the follow-up study, investigate the incidence of CHD and stroke (and CVD with these) during the period to verify the correlation with the measurement items.

The measurement of LDL-TG uses LDL-TG "Seiken" (manufactured by DENKA SEIKEN Co., Ltd.).

The LDL-TG value was divided into quartiles, and the COX proportional regression model was used to compare the risk ratio relative to the first quartile.

The results are shown in Table 1.

As shown in Table 1, relative to the LDL-TG value of the first quartile, the second The risk ratios of CHD, stroke and CVD in the quartile, the 3rd quartile, and the 4th quartile increased, and the increased risk was confirmed. The above results indicate that by calculating the LDL-TG value, the risk of CHD, stroke (and CVD with both) can be judged in the future.

Claims (2)

A method to assist in judging the risk of circulatory organ disease, coronary heart disease or cerebral stroke, which includes measuring the LDL-TG value in blood separated from a living body. The higher the measured LDL-TG value, the higher the circulatory organ disease, The higher the risk of coronary heart disease or stroke. A method for assisting the diagnosis of cerebral apoplexy, which includes measuring the LDL-TG value in blood separated from a living body. The higher the LDL-TG value measured, the higher the possibility that the stroke is occurring.