Metabolic marker for distinguishing hypertrophic cardiomyopathy and left ventricular hypertrophy and application thereof

Abstract

The invention belongs to the technical field of molecular biology, and particularly relates to a metabolic marker for distinguishing hypertrophic cardiomyopathy and left ventricular hypertrophy and application. According to the application disclosed by the invention, metabonomics of hypertrophic cardiomyopathy (HCM) patients, left ventricular hypertrophy (LVH) patients caused by non-hypertrophic cardiomyopathy and healthy people are analyzed, and the results show that carnitine C16: 2, carnitine C14: 0, carnitine C16: 0, carnitine C18: 0 and carnitine C18: 1 are differentially expressed in the HCM patients and the LVH patients; the pyridoxine phosphate, the itolic acid, the adenosine monophosphate, the adenosine diphosphate and the adenosine triphosphate are all differentially expressed in HCM patients and healthy people, the lysine group, the methylglutamic acid, the acetylproline, the malate semialdehyde and the citrinine are all differentially expressed in LVH patients and healthy people, ROC curve analysis shows an excellent prediction effect, the specificity is high, and the accuracy is high. The sensitivity is high.

Description

Technical Field

[0001] The present invention belongs to the technical field of molecular biology, and particularly relates to metabolic markers for distinguishing hypertrophic cardiomyopathy and left ventricular hypertrophy and their applications. Background Art

[0002] Left ventricular hypertrophy (LVH), also known as left ventricular enlargement, is caused by various reasons such as hypertension, heart disease, etc., resulting in the thickening of the left ventricular wall, which in turn causes a series of conditions that lead to reduced cardiac function, or diseases such as myocardial infarction and pulmonary hypertension. Once left ventricular hypertrophy occurs, active treatment is required. For example, hypertension and coronary heart disease require antihypertensive treatment and treatment to improve myocardial blood supply. In addition, anticoagulant and antiplatelet drugs such as aspirin and clopidogrel need to be taken to cure the primary disease and gradually restore left ventricular hypertrophy to the normal level.

[0003] Hypertrophic cardiomyopathy (HCM) is clinically characterized by left ventricular hypertrophy, and pathologically manifested as enlarged and disordered myocardial cells, interstitial fibrosis and inflammatory cell infiltration. Patients with HCM may develop some complications, including left ventricular outflow tract obstruction, arrhythmia, heart failure, and particularly prominent sudden cardiac death in adolescents. Therefore, it may impose a huge economic, social and medical burden on the healthcare system. Currently, the screening and diagnosis of HCM mainly rely on imaging methods. However, there are many factors causing left ventricular hypertrophy, and it is impossible to distinguish between hypertrophic cardiomyopathy and left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy only based on imaging methods. Therefore, it is particularly important for this field to screen and distinguish markers for left ventricular hypertrophy caused by hypertrophic cardiomyopathy and non-hypertrophic cardiomyopathy, and accurately judge hypertrophic cardiomyopathy. Summary of the Invention

[0004] The purpose of the present invention is to accurately judge left ventricular hypertrophy caused by hypertrophic cardiomyopathy and non-hypertrophic cardiomyopathy, and accurately distinguish left ventricular hypertrophy caused by hypertrophic cardiomyopathy and non-hypertrophic cardiomyopathy.

[0005] The present invention provides markers for distinguishing hypertrophic cardiomyopathy and left ventricular hypertrophy, including one or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1;

[0006] The left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0007] The present invention also provides the application of the markers in the above technical solution in the preparation of products for distinguishing hypertrophic cardiomyopathy and left ventricular hypertrophy;

[0008] The left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0009] The present invention also provides markers related to hypertrophic cardiomyopathy, including one or more of pyridoxal phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate.

[0010] The present invention also provides the use of the markers described in the above technical solution in the preparation of products for diagnosing hypertrophic cardiomyopathy.

[0011] The present invention also provides markers related to left ventricular hypertrophy, including one or more of lysyl group, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline;

[0012] The left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0013] The present invention also provides the use of the markers described in the above technical solution in the preparation of products for diagnosing left ventricular hypertrophy; the left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0014] Preferably, the product includes a kit.

[0015] The present invention also provides a kit for differentiating hypertrophic cardiomyopathy and left ventricular hypertrophy, and the kit includes reagents for detecting the levels of the markers described in the above technical solution;

[0016] The left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0017] The present invention also provides a kit for diagnosing hypertrophic cardiomyopathy, and the kit includes reagents for detecting the levels of the markers described in the above technical solution.

[0018] The present invention also provides a kit for diagnosing left ventricular hypertrophy, and the kit includes reagents for detecting the levels of the markers described in the above technical solution;

[0019] The left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0020] Advantageous effects:

[0021] By analyzing the metabolomes of patients with hypertrophic cardiomyopathy (HCM), patients with left ventricular hypertrophy (LVH) caused by non - hypertrophic cardiomyopathy, and healthy individuals, it was found that carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 were all differentially expressed in patients with HCM and patients with LVH. ROC curve analysis showed excellent predictive effects, with strong specificity and high sensitivity. Markers for differentiating hypertrophic cardiomyopathy and left ventricular hypertrophy, pyridoxal phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate were all differentially expressed in patients with HCM and healthy individuals. ROC curve analysis showed excellent predictive effects, with strong specificity and high sensitivity. Markers for differentiating hypertrophic cardiomyopathy and left ventricular hypertrophy, lysyl group, methylglutamic acid, acetylproline, malic semialdehyde, and citric acid were all differentially expressed in patients with LVH and healthy individuals. ROC curve analysis showed excellent predictive effects, with strong specificity and high sensitivity. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the embodiments.

[0023] Figure 1 ROC curves for differential metabolites between HCM and LVH in the derivation cohort;

[0024] Figure 2 Box plots of differential metabolites between HCM and LVH in the derivation cohort; where NS indicates no significant difference; * indicates a significant difference, P < 0.05; ** indicates a significant difference, P < 0.01; *** indicates a significant difference, P < 0.001;

[0025] Figure 3 ROC curves for differential metabolites between HCM and the NC group in the derivation cohort;

[0026] Figure 4 Box plots of differential metabolites between HCM and the NC group in the derivation cohort; where NS indicates no significant difference; * indicates a significant difference, P < 0.05; ** indicates a significant difference, P < 0.01; *** indicates a significant difference, P < 0.001;

[0027] Figure 5 ROC curves for differential metabolites between LVH and the NC group in the derivation cohort;

[0028] Figure 6Box plot of differential metabolites between the LVH and NC groups in the derivation cohort; where NS indicates no significant difference; * indicates significant difference, P < 0.05; ** indicates significant difference, P < 0.01; *** indicates significant difference, P < 0.001;

[0029] Figure 7 ROC curves of differential metabolites between the HCM, LVH and NC groups in the validation cohort;

[0030] Figure 8 Box plot of differential metabolites between the HCM, LVH and NC groups in the validation cohort; where NS indicates no significant difference; * indicates significant difference, P < 0.05; ** indicates significant difference, P < 0.01; *** indicates significant difference, P < 0.001. Detailed implementation manner

[0031] The present invention provides markers for differentiating hypertrophic cardiomyopathy and left ventricular hypertrophy, including one or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1; the left ventricular hypertrophy is left ventricular hypertrophy caused by non - hypertrophic cardiomyopathy.

[0032] As an implementation manner, the carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1 are respectively carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1 in plasma.

[0033] As an implementation manner, the marker can be a combination of two or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1; as another implementation manner, the marker can be a combination of three or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1; as another implementation manner, the marker can be a combination of four or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1; as another implementation manner, the marker can be carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1.

[0034] In the present invention, by analyzing the metabolomes of patients with hypertrophic cardiomyopathy and patients with left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy in the derivation cohort, it was found that carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 were all differentially expressed in the plasma of patients with hypertrophic cardiomyopathy and patients with left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy. Through receiver operating characteristic (ROC) curve analysis for evaluation, carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 showed excellent predictive effects, and the areas under the curve (AUC) reached 0.94, 0.94, 0.91, 0.82, and 0.79 respectively. Moreover, the present invention used a validation cohort for verification. When carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 were used as markers, the areas under the curve (AUC) reached 0.88, 1.00, 0.91, 0.97, and 0.83 respectively. Therefore, it can be determined that one or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 can accurately distinguish hypertrophic cardiomyopathy from left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy, with strong specificity and high sensitivity.

[0035] Therefore, the application of the marker described in the above technical solution in the preparation of a product for distinguishing hypertrophic cardiomyopathy from left ventricular hypertrophy also belongs to the protection scope of the present invention; the left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy. As an implementation manner, the product includes a kit.

[0036] The present invention also provides a kit for distinguishing hypertrophic cardiomyopathy from left ventricular hypertrophy, and the kit includes reagents for detecting the levels of the markers described in the above technical solution; the left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

[0037] The present invention does not have strict requirements for the types of other components in the kit, and conventional selection can be made. Using the kit of the present invention, it is only necessary to detect the levels of one or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0, and carnitine C18:1 in the plasma of the subject to accurately distinguish hypertrophic cardiomyopathy from left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy, without the need for gene detection.

[0038] The present invention also provides markers related to hypertrophic cardiomyopathy, including one or more of pyridoxal phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate.

[0039] As an embodiment, the pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate are respectively pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate in plasma.

[0040] As an embodiment, the biomarker can be a combination of two or more of pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate; as another embodiment, the biomarker can be a combination of three or more of pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate; as another embodiment, the biomarker can be a combination of four or more of pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate; as another embodiment, the biomarker can be pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate.

[0041] In the present invention, by analyzing the metabolomes of patients with hypertrophic cardiomyopathy and healthy individuals in the derivation cohort, it is found that pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate are all differentially expressed in patients with hypertrophic cardiomyopathy and healthy individuals. Through receiver operating characteristic (ROC) curve analysis for evaluation, pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate show excellent predictive effects. Moreover, the present invention uses the validation cohort for testing, and one or more of pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate can accurately distinguish patients with hypertrophic cardiomyopathy from healthy individuals, diagnose patients with hypertrophic cardiomyopathy, with strong specificity and high sensitivity.

[0042] Therefore, the application of the biomarker described in the above technical solution in the preparation of a product for diagnosing hypertrophic cardiomyopathy also belongs to the protection scope of the present invention. As an embodiment, the product includes a kit.

[0043] The present invention also provides a kit for diagnosing hypertrophic cardiomyopathy, and the kit includes reagents for detecting the level of the biomarker described in the above technical solution.

[0044] The present invention has no strict requirements for the types of other components in the kit, and conventional selection can be made. Using the kit of the present invention, only by detecting the level of one or more of pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate in the plasma of the subject, patients with hypertrophic cardiomyopathy can be accurately distinguished from healthy individuals, and patients with hypertrophic cardiomyopathy can be diagnosed, without gene detection, with strong specificity and high sensitivity.

[0045] The present invention also provides a biomarker related to left ventricular hypertrophy, including one or more of lysyl, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline; the left ventricular hypertrophy is left ventricular hypertrophy caused by non - hypertrophic cardiomyopathy.

[0046] As an embodiment, the lysyl, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline are respectively lysyl, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline in plasma.

[0047] As an embodiment, the biomarker can be a combination of two or more of lysyl, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline; as another embodiment, the biomarker can be a combination of three or more of lysyl, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline; as another embodiment, the biomarker can be a combination of four or more of lysyl, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline; as another embodiment, the biomarker can be lysyl, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline.

[0048] The present invention analyzed the metabolomes of patients with left ventricular hypertrophy caused by non - hypertrophic cardiomyopathy and healthy populations in the derivation cohort, and found that lysyl, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline were all differentially expressed in patients with left ventricular hypertrophy caused by non - hypertrophic cardiomyopathy and healthy populations. Through receiver operating characteristic (ROC) curve analysis for evaluation, lysyl, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline showed excellent predictive effects. Moreover, the present invention used the validation cohort for verification. When one or more of lysyl, methylglutamic acid, acetylproline, malic semialdehyde, and citrulline were used as biomarkers, they could accurately distinguish patients with left ventricular hypertrophy caused by non - hypertrophic cardiomyopathy from healthy populations and diagnose patients with left ventricular hypertrophy caused by non - hypertrophic cardiomyopathy, with strong specificity and high sensitivity.

[0049] The present invention also provides the application of the biomarker described in the above technical solution in the preparation of a product for diagnosing left ventricular hypertrophy; the left ventricular hypertrophy is left ventricular hypertrophy caused by non - hypertrophic cardiomyopathy. As an embodiment, the product includes a kit.

[0050] The present invention also provides a kit for diagnosing left ventricular hypertrophy, and the kit includes a reagent for detecting the level of the biomarker described in the above technical solution; the left ventricular hypertrophy is left ventricular hypertrophy caused by non - hypertrophic cardiomyopathy.

[0051] The present invention has no strict requirements on the types of other components in the kit, and conventional selection is sufficient. By using the kit of the present invention, only the level of one or more of lysine, methylglutamic acid, acetylproline, malic semialdehyde and citrate in the plasma of the subject needs to be detected to accurately distinguish patients with hypertrophic cardiomyopathy from healthy people, and diagnose patients with hypertrophic cardiomyopathy without genetic testing, with high specificity and sensitivity.

[0052] To further illustrate the present invention, the metabolic markers for distinguishing hypertrophic cardiomyopathy from left ventricular hypertrophy and their applications provided by the present invention are described in detail below in conjunction with the accompanying drawings and examples, but they should not be construed as limiting the scope of protection of the present invention.

[0053] Example 1

[0054] Sample collection

[0055] The inventor team collected 720 individuals from the Fuwai Hospital of the Chinese Academy of Medical Sciences, including 441 patients with hypertrophic obstructive cardiomyopathy (HCM), 160 patients with left ventricular hypertrophy (LVH) not caused by HCM, and 119 normal controls (NC). The diagnostic criteria for obstructive HCM are based on the 2024 ACC / AHA Guidelines for Primary Prevention of Cardiovascular Disease and the 2023 ESC Guidelines, as follows: echocardiography shows that the maximum left ventricular wall thickness is ≥15 mm. Patients who have previously undergone septal myectomy and alcohol septal ablation were excluded. Clinical examination and echocardiography showed that all normal controls had no heart disease. To minimize metabolite degradation, fasting blood samples were processed into frozen plasma within 1 hour. Whole blood was centrifuged at 4000 rpm for 10 minutes at 4°C, and the plasma supernatant was collected and dispensed into 0.2mL Eppendorf tubes (70μL plasma per tube). Plasma was immediately quenched in liquid nitrogen and stored at -80°C until analysis. This study was approved by the Ethics Committee of Fuwai Hospital and was conducted in accordance with the 1964 Declaration of Helsinki. Individuals participating in this study provided written informed consent. The clinical characteristics of the subjects are shown in Table 1.

[0056] Table 1 Clinical characteristics of the patients

[0057]

[0058]

[0059] Note: Continuous variables are expressed as median (25th-75th percentile).

[0060] Example 2

[0061] Metabolomic analysis of plasma samples

[0062] 1. The plasma samples of each subject patient in the derivation cohort of Example 1 were mixed in equal volumes, and after extraction, centrifugation, drying, and re-dissolution, LC-MS analysis was performed. The specific steps are as follows: A targeted metabolomics method was used with a Vanquish ultra-high performance liquid chromatography system coupled with a Q-Exactive HF mass spectrometer (Thermo Fisher Scientific). Gradient separation was carried out using an ACQUITY BEH Amide chromatographic column (150×2.1 mm, 1.7 μm, Waters). Solvent A: 95% water + 5% acetonitrile, Solvent B: 5% water + 95% acetonitrile. The gradient settings were as follows: 0 - 1.5 min, 5% A; 1.5 - 10 min, 5 - 35% A; 10 - 19 min, 35 - 70% A; 19 - 23.5 min, 70% A; 23.5 - 25 min, 70 - 5% A; 25 - 30 min, 5% A. Data was acquired in the fullMS-ddMS2 mode (top five negative ions) and processed using Compound Discoverer version 3.3 software (Thermo Fisher Scientific). The process included deconvolution, peak alignment, extraction, and annotation. The following mass spectrometry parameters were set: scan mode, MS / MS; resolution 30000, normalized collision energies 20, 40, 60 eV. The source ionization parameters were: spray voltage 3.5 kV for electrospray positive ions (ESI+), capillary temperature 320 °C, sheath gas 40 °C, auxiliary gas 15 °C. A total of 406 metabolites were identified by LC-MS analysis, including amino acids, organic acids, nucleotides, acylcarnitines, and carbohydrates, demonstrating a comprehensive metabolic profile.

[0063] 2. General metabolic characteristics of plasma from HCM patients, LVH patients, and normal controls

[0064] Using the plasma samples of each subject patient in the derivation cohort of Example 1 as test samples, the following tests were performed:

[0065] (1) Using version 15.0 software (Umetrics, Sweden) to perform orthogonal partial least squares discriminant analysis (OPLS-DA). Unit variance (UV) scaling was performed before multivariate analysis to establish an OPLS-DA model. The results showed significant metabolite differences between HCM and LVH, HCM and NC, and LVH and NC.

[0066] (2) The R2Y and Q2 intercepts were used to evaluate the performance of the OPLS-DA model, and cross-validated analysis of variance (CV-ANOVA) was used to evaluate the goodness of fit. The results showed that all the predicted variances (HCM vs. LVH, R2Y = 0.972; HCM vs. NC, R2Y = 0.974; LVH vs. NC, R2Y = 0.951), predictive abilities (HCM vs. LVH, Q2 = 0.952; HCM vs. NC, Q2 = 0.954; LVH vs. NC, Q2 = 0.914) and CV-ANOVA (HCM vs. LVH, P < 0.001; HCM vs. NC, P < 0.001; LVH vs. NC, P < 0.001) values indicated that the OPLS-DA model was robust and reliable.

[0067] (3) To prevent overfitting, a permutation test (n = 200) was performed, and the results showed that the OPLS-DA model was not overfitted.

[0068] (4) Kyoto Encyclopedia of Genes and Genomes database (KEGG) was used for enrichment analysis and unsupervised hierarchical clustering analysis was performed. The results showed that 83 differential metabolites were identified in the comparison between HCM and LVH, 103 in the comparison between HCM and NC, and 79 in the comparison between LVH and NC (Mann-Whitney U test, FDR < 0.05 and |FC| > 2). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential metabolites between HCM and LVH, HCM and NC, and LVH and NC were enriched in arginine and proline metabolism, cysteine and methionine metabolism, and histidine metabolism, respectively. The results of unsupervised hierarchical clustering analysis showed that the metabolic profiles of HCM were significantly different from the other two groups. Overall, metabolomics provided valuable insights into the etiological heterogeneity of HCM, LVH, and NC.

[0069] (5) Pairwise comparisons (HCM vs. LVH, HCM vs. NC, and LVH vs. NC) were performed, and biomarkers were screened through the following steps: (1) False discovery rate (FDR)-adjusted P value < 0.05: In the comparisons between HCM and LVH, HCM and NC, and LVH and NC, 309, 321, and 335 metabolites met this criterion, respectively. (2) |FC| > 2: After this step, 83, 103, and 79 metabolites remained in the comparisons between HCM and LVH, HCM and NC, and LVH and NC, respectively. (3) OPLS-DA VIP value > 1.5: Finally, 27, 39, and 16 metabolites were considered as potential biomarkers in the comparisons between HCM and LVH, HCM and NC, and LVH and NC, respectively.

[0070] 3. Identification of Biomarkers for Differentiating HCM and LVH Patients

[0071] The diagnostic performance of potential biomarkers in Step 2 was evaluated by receiver operating characteristic (ROC) curve and box plot analysis. The results showed that long-chain acylcarnitines exhibited particularly strong and consistent diagnostic performance in differentiating HCM and LVH. Specifically, C16:2 carnitine, C14:0 carnitine, C16:0 carnitine, C18:0 carnitine, and C18:1 carnitine showed excellent predictive effects, with the area under the curve (AUC) reaching 0.94, 0.94, 0.91, 0.82, and 0.79 respectively ( Figure 1 and Figure 2 ). Compared with NC, pyridoxine phosphate, itaconic acid, adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) in HCM patients showed excellent predictive effects, with the area under the curve (AUC) reaching 0.89, 0.90, 0.93, 0.95, and 0.99 respectively ( Figure 3 and Figure 4 ). This indicates that even in the absence of systolic dysfunction, HCM is characterized by abnormal energy metabolism. The metabolic differences between LVH and NC mainly focus on the impact on amino acid metabolism. Lysidine, methylglutamate, acetylproline, succinate semialdehyde, and citrulline showed excellent predictive effects, with the area under the curve (AUC) reaching 0.91, 0.97, 0.94, 0.91, and 0.94 respectively ( Figure 5 and Figure 6 ). Therefore, plasma metabolomics can be used to differentiate HCM and LVH patients caused by non-HCM, improving the accuracy of HCM differential diagnosis.

[0072] Example 3

[0073] Using the plasma samples of each subject patient in the validation cohort of Example 1 as test samples, the receiver operating characteristic (ROC) curve analysis and box plot analysis were carried out with reference to the steps of Example 4. The results showed that C16:2 carnitine, C14:0 carnitine, C16:0 carnitine, C18:0 carnitine and C18:1 carnitine showed excellent prediction effects, and the area under the curve (AUC) reached 0.88, 1.00, 0.91, 0.97 and 0.83 respectively( Figure 7 and Figure 8 ). It was determined that carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1 could all be used as markers to distinguish LVH caused by HCM and non-HCM.

[0074] Pyridoxine phosphate, Itaconic acid, adenosine monophosphate (AMP), adenosine diphosphate (ADP) and adenosine triphosphate (ATP) showed excellent prediction effects, and the area under the curve (AUC) reached 0.89, 0.91, 0.95, 0.97 and 0.99 respectively( Figure 7 and Figure 8 ). It was determined that pyridoxine phosphate, itaconic acid, adenosine monophosphate, adenosine diphosphate and adenosine triphosphate could all be used as markers to distinguish HCM from healthy people and diagnose HCM.

[0075] Lysidine, Methylglutamate, Acetylproline, Succinate semialdehyde and Citrulline showed excellent prediction effects, and the area under the curve (AUC) reached 0.86, 1.00, 1.00, 1.00 and 0.60 respectively( Figure 7 and Figure 8 ). It was determined that lysidine, methylglutamate, acetylproline, succinate semialdehyde and citrulline could all be used as markers to distinguish LVH from healthy people and diagnose LVH.

[0076] Although the above embodiments have described the present invention in detail, they are only a part of the embodiments of the present invention, not all of them. People can also obtain other embodiments without creative efforts based on this embodiment, and these embodiments all belong to the protection scope of the present invention.

Claims

1. A marker for distinguishing hypertrophic cardiomyopathy from left ventricular hypertrophy, characterized in that: Including one or more of carnitine C16:2, carnitine C14:0, carnitine C16:0, carnitine C18:0 and carnitine C18:1; The left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

2. Use of the marker according to claim 1 in the preparation of a product for distinguishing hypertrophic cardiomyopathy from left ventricular hypertrophy; The left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

3. A marker associated with hypertrophic cardiomyopathy, characterized in that: It includes one or more of pyridoxine phosphate, etopoic acid, adenosine monophosphate, adenosine diphosphate and adenosine triphosphate.

4. Use of the marker according to claim 3 in the preparation of a product for diagnosing hypertrophic cardiomyopathy.

5. A marker associated with left ventricular hypertrophy, characterized in that: including one or more of lysine, methylglutamic acid, acetylproline, malic semialdehyde and citric acid; The left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

6. Use of the marker according to claim 5 in the preparation of a product for diagnosing left ventricular hypertrophy; the left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

7. The use according to claim 2, 4 or 6, characterized in that: The products include kits.

8. A kit for distinguishing hypertrophic cardiomyopathy from left ventricular hypertrophy, characterized in that: The kit comprises a reagent for detecting the level of the marker of claim 1; The left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

9. A kit for diagnosing hypertrophic cardiomyopathy, characterized in that: The kit comprises a reagent for detecting the level of the marker according to claim 3.

10. A kit for diagnosing left ventricular hypertrophy, characterized in that: The kit comprises a reagent for detecting the level of the marker of claim 5; The left ventricular hypertrophy is left ventricular hypertrophy caused by non-hypertrophic cardiomyopathy.

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