Discovering Biomarkers in Coronary Heart Disease Comorbidities with GC–MS

Coronary heart disease (CHD), hypertension (HTN), depression (Dep), and Type 2 diabetes mellitus (T2DM) are often comorbid, resulting in an exacerbated patient condition and worsened prognosis. There is a lack of systematic metabolomic studies on comorbidities of CHD and comprehensive metabolomic-based evaluation of comorbidities of CHD is necessary. To that end, a joint team of researchers from Nankai University (Tianjin, China), Central South University (Changsha, China), Shandong First Medical University (Jining, China) and Tengzhou Central People's Hospital (Tengzhou, China) employed a gas chromatography-mass spectrometry (GC–MS)-based metabolomic approach to conduct this evaluation. A paper based on this work was recently published in the Journal of Diabetic Research (1).

Although there has been a decline in CHD incidence in most countries, the disease state remains the leading cause of worldwide mortality. Furthermore, HTN, Dep, and T2DM are often comorbid with CHD, which may induce or worsen the development of CHD and affect prognosis (2-5). There have been previous studies done on CHD, HTN-comorbid CHD, Dep-comorbid CHD, and T2DM-comorbid CHD, and many risk factors (including genetic and environmental factors) have been proposed (3,6-11). However, these comorbidities cannot be fully explained by these risk factors. Therefore, the researchers involved with the study said that a novel approach to assess the comprehensive metabolic status in comorbidities of CHD is needed (1).

Patients for the study were recruited at the outpatient clinic of Jining First People’s Hospital in Jining, China, with diagnoses of CHD made by at least two experienced cardiologists and confirmed using coronary angiography results (significant coronary artery stenosis ≥ 50% in at least one of the three major coronary arteries or major branches). Among all the patients, 149 had CHD with no HTN, Dep, or T2DM; 107 had CHD comorbid with HTN defined as systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg, a history of HTN, or current antihypertensive treatment; and 126 had CHD comorbid with Dep assessed by at least two experienced psychiatrists according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders criteria for major depressive disorder, which is characterized by significantly depressed mood and anhedonia. Blood samples from all subjects were collected during a fasting period to accurately reflect the metabolic profile. The represented total ion chromatograms of serum samples presented a strong signal response, with 114 metabolites identified in each serum sample and then used in the subsequent multivariate analysis. In addition, the relative standard deviation (RSD) in intra- and interday of the peak area and RT of the IS were less than 15%, indicating that the analytical instrument operated within acceptable standard variations (1).

This research provides a systematic view of metabolic alterations in CHD comorbidity that correlate with amino acid, lipid, and energy metabolism, providing predictive information for CHD comorbidity and enhancing our understanding, the authors wrote. However, they acknowledge several limitations. First, a single GC–MS-based metabolomic method was used in their study, which could be improved by also using nuclear magnetic resonance and liquid chromatography-mass spectrometry (LC–MS) or combined with proteomics, genomics, and other multiple omics methods to further validate their findings. Also, a larger sample size (especially those classified as CHD comorbid with HTN group, CHD comorbid with Dep group, and CHD comorbid with T2DM group) should be collected. Finally, the diagnostic value of the potential biomarkers should be validated with setting up internal and external validation sets and multicenter in clinical practice (1).

3d rendered illustration of heart disease. © appledesign - stock.adobe.com

References

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