TW201942578A - 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

Methods to assist in judging the risk of circulatory diseases, etc.

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

The main components of lipids in serum and plasma are cholesterol, triglycerides, phospholipids, etc. These blood lipids bind to apoproteins and circulate in the blood as lipoproteins. These lipoproteins are classified into chylomicrons (CM), ultra-low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (hereinafter sometimes referred to as LDL), and high density due to differences in density. Lipoprotein (hereinafter, sometimes referred to as HDL) and the like. Among these lipoproteins, LDL is a major carrier of cholesterol from the liver to various tissues, and it is believed that an increase in LDL cholesterol (hereinafter, sometimes referred to as LDL-C) is closely related to the occurrence of arteriosclerosis. Therefore, it is considered that LDL-C is a risk factor for arteriosclerosis, ischemic heart disease (coronary artery disease), and knowing that the content of LDL-C is an important indicator in the diagnosis, treatment and prevention of these diseases. On the other hand, it has also been found that a large number of cases in which ischemic heart disease occurs even if LDL-C in the blood is within a normal range. Recently, the quality of LDL particles has also been noticed.

A large amount of triglyceride-containing LDL (hereinafter, sometimes referred to as TG-rich LDL) is a lipoprotein whose traits are different from normal LDL with a high cholesterol content, which is more common in the blood of patients with liver disease. Progression of liver disease, its concentration in blood Increased in fluid, and at the end of liver disease, it accounts for most of the lipoproteins present in the blood. Also, it is reported that TG-rich LDL foams macrophages, but the foaming rate of macrophages caused by TG-rich LDL is directly proportional to the concentration of malondialdehyde-modified LDL in serum as a kind of oxidized LDL; Relatively few triglycerides were detected in the blood of healthy people. A significant increase in triglycerides was seen in the blood of patients with liver disease. According to these reports, triglycerides and LDL in LDL The relationship is also deeper. Coronary heart disease was reported when comparing triglycerides (hereinafter sometimes referred to as LDL-TG) in LDL in patients with coronary heart disease (CHD) and healthy people. LDL-TG is increased in the blood of the sick patient (Non-Patent Document 1). However, there is no evidence that the risk of coronary heart disease in the future will be higher for those with higher LDL-TG in healthy normals who do not currently have coronary artery disease.

On the other hand, with regard to stroke, there is no evidence showing its association with LDL-TG, and it is unclear whether it can be used to diagnose patients with stroke, or subjects with high LDL-TG values in the future. Whether the risk becomes higher.

As a method for quantifying LDL-TG, there is a method of combining two steps of separation and separation and triglyceride quantification. Differentiating and separating operations include methods such as ultracentrifugation, electrophoresis, and high-performance liquid chromatography. As a quantitative method, for example, an automatic analysis device used in clinical examination is used, and the amount of triglyceride is determined by a reagent. Method, etc. The combination of the two can be used to quantify LDL-TG, but these are performed in two stages: the pretreatment step of completely separating LDL from lipoproteins other than LDL and the measurement step, so the operation is complicated and time-consuming. . Also, 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 skilled operation or requires special Other machines. These costs are also relatively expensive, and are not easy to spread in terms of simplicity or economy.

As a method for eliminating such problems, it is possible to perform the measurement by using an automatic analysis device without performing a discrimination operation. It is known that in the first step, triglyceride in all lipoproteins except LDL is removed, and then in the second step Method for measuring triglyceride in the remaining LDL (Patent Documents 1 and 2); or after removing (free glycerol and) triglyceride in HDL in the first step, only the LDL is measured in the second step 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 object of the present invention is to provide a method for assisting in judging the risk of circulatory organ disease, coronary heart disease or stroke. Furthermore, an object of the present invention is to provide a method for assisting the diagnosis of stroke.

The inventors of the present case conducted intensive research and found that healthy normal people who did not develop circulatory organ disease, coronary heart disease or stroke had been in the blood. When the LDL-TG value is high, the possibility of circulatory organ disease, coronary heart disease or stroke in the future will increase. In addition, it was found that among patients with stroke, the LDL-TG value in the blood Higher, thus completing the present invention.

That is, the present invention provides the following.

(1) A method for judging the risk of circulatory organ disease, coronary heart disease or stroke, which comprises measuring the LDL-TG value in blood isolated from a living body, and a higher LDL-TG value indicates a circulatory organ The risk of disease, coronary heart disease or stroke is higher.

(2) A method for assisting the diagnosis of stroke, which includes measuring the LDL-TG value in blood isolated from a living body. A higher LDL-TG value indicates that a stroke is more likely to develop.

According to the present invention, for the first time, a method is provided for accurately judging the risk of the onset of such diseases in the stage when the circulatory organ disease, coronary heart disease or stroke does not develop. When judging the high-risk situation, we can try to reduce the risk by changing living habits or taking drugs, etc., and prevent the onset of these diseases.

In addition, according to the present invention, it is possible to assist the diagnosis of stroke quickly and accurately. Therefore, rapid treatment can be performed at the early stage of the onset of stroke, which can prevent death caused by stroke.

In the method of the present invention, the LDL-TG value in blood is measured. by Since it is easy to measure using serum or plasma as a blood sample, it is preferable.

A method for measuring the LDL-TG value in blood is well known (for example, the above-mentioned Patent Documents 1 to 3), and reagents for the above-mentioned measurement are also commercially available. Therefore, it is possible to easily quantify LDL-TG in blood using commercially available reagents. If it is simply explained, the LDL-TG value can be measured by the following methods: (1) using a surfactant acting on lipoproteins other than LDL (for example, a polyalkylene oxide derivative having an HLB value of 13 or more and 14 or less) Etc.) The specimen is processed, and then lipoprotein lipase, glycerin kinase, and glycerol are made in the presence of a surfactant acting on LDL (polyalkylene oxide derivatives having an HLB value of 11 or more and less than 13). A method in which 3-phosphate oxidase acts on a specimen and quantifies the amount of hydrogen peroxide produced; or (2) a surfactant that acts on lipoproteins other than LDL (for example, a polyepoxide with an HLB value of 13 or more and 15 or less) In the presence of alkane derivatives, etc., the lipoprotein lipase, cholesterol esterase, glycerol kinase, and glycerol-3-phosphate oxidase are allowed to act on the specimen, remove the generated hydrogen peroxide, and then act on the interface activity of LDL Agents (polyalkylene oxide derivatives with an HLB value of 11 or more and less than 13) to cause lipoprotein lipase, glycerol kinase, and glycerol-3-phosphate oxidase to act on the specimen and quantify the amount of Method of hydrogen peroxide and so on. 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 normal people who do not have circulatory disease, coronary heart disease or stroke, the higher the possibility of the disease in the future. Therefore, based on the measured blood LDL-TG value, it can assist in judging the risk of the onset of these diseases in the future. Since the higher the LDL-TG value in the blood, the higher the possibility of the onset of these diseases in the future, it is possible to appropriately set specific judgment criteria. For example, in the following examples, based on the blood LDL-TG value, the subjects were roughly divided into four equal parts, and the incidence of each group within 15.6 years was investigated. As a result, if the LDL-TG value was the fourth lowest Quantile The incidence rate is benchmarked, and the incidence rates of the 2nd, 3rd, and 4th quartiles are statistically significantly higher and statistically significant. Since the lower limit value of the second quartile at this time is 17.1 mg / dL, for example, the threshold value is set to 17 mg / dL, and when it exceeds 17 mg / dL, it can be determined as high risk. Alternatively, when a higher risk is considered as a high risk, for example, a high risk may be determined as a median value of 22.7 mg / dL or more. As described above, the threshold value 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 17 mg / dL to 40 mg / dL, particularly any value in the range of 25 mg / dL to 35 mg / dL can be set as the threshold value. In addition, the LDL-TG value may be different for groups such as ethnic groups. Therefore, the median or average value within the group, the boundary value between the first quartile and the second quartile can be used as threshold values. Or use the values in the vicinity (such as any value within ± 20%) as the threshold. Furthermore, since the higher the risk is, the higher the threshold is, the higher the risk, the risk can be determined based on the specific measured value, and the probability can also be expressed numerically by associating the measured 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 a stroke in the onset, and further, it is possible to evaluate / determine whether a stroke is severe. For example, when the quantitative value of LDL-TG is 20 to 40 mg / dL, preferably more than 30 mg / dL, it is judged that the risk of CVD (cardiovascular disease), CHD, or stroke will increase in the future. However, it is considered that the reference value for the diagnosis of familial combined hyperlipidemia (FCHL) differs depending on the ethnic group, so it is not limited to this. In addition, among those who are diagnosed with a higher risk of CHD or stroke, they can also be judged to have a higher LDL-TG value of 40 mg / dL and 50 mg / dL.

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

[Example 1]

LDL-TG concentrations were measured using preserved specimens (serum) from the American generation test. Specifically, the LDL-TG concentration was measured in 9,334 patients who did not develop CHD or stroke during baseline blood collection. In addition, based on the results of the follow-up studies of the subjects for 15.6 years, the incidence of CHD and stroke (and both of them with CVD) was investigated during the period to verify the correlation with the measurement items.

The measurement of LDL-TG was performed using LDL-TG "Seiken" (manufactured by Denka Seiken Co., Ltd.).

The LDL-TG values were divided into quartiles, and the COX proportional regression model was used to compare the hazard ratios relative to the first quartile group.

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 hazard ratios of CHD, stroke, and CVD in the quartile, third quartile, and fourth quartile increased, and increased risk was confirmed. The above results indicate that by determining the LDL-TG value, the degree of risk of CHD and stroke (and CVD with both) can be judged in the future.

Claims (2)

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