Metabolic Profiling of Cardiovascular Disease

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Advances in Metabolomics".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 37603

Special Issue Editors

Dept. of Medical Science and Public Health – University of Cagliari, 09124 Cagliari, Italy
Interests: cardiovascula disease; heart failure; cardiovascular metabolism; drug cardiotoxicity; non-invasive cardiovascular imaging
Special Issues, Collections and Topics in MDPI journals
Dept of Surgical Sciences–University of Cagliari, Neonatal Intensive Care Unit AOU Cagliari, Cagliari, Italy
Interests: neonatology; nephrology; pharmacology; infections; microbiomics; metabolomics
Special Issues, Collections and Topics in MDPI journals
Dept. of Medical Science and Public Health–University of Cagliari, Cagliari, Italy
Interests: autopsy; bioethics; forensic medicine; forensic pathology; DNA profiling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The first cause of morbidity and mortality in industrialised countries is represented nowadays by cardiovascular diseases. During the last decade, both animal and human studies have facilitated the rapid development of metabolomics, and a combination of targeted and untargeted approaches has been applied for cardiovascular research. Specific metabolic profiles have been identified for several cardiovascular risk factors and diseases. In this Special Issue, our aim is to provide an in-depth view of metabolomics, addressing the current rationale for its application to cardiology and describing relevant data available from animal and human studies. This Special Issue show the importance of metabolomic application in understanding the mechanisms underlying diseases from a systems biology perspective and as a non-invasive approach to diagnosis, grading, and treatment of cardiovascular diseases.

Prof. Dr. Christian Cadeddu Dessalvi
Prof. Dr. Vassilios Fanos
Prof. Dr. Ernesto d’Aloja
Guest Editors

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Keywords

  • metabolomics
  • cardiovascular diseases
  • diagnosis
  • personalized medicine
  • biomarkers
  • cardiac function
  • cardiovascular metabolism

Published Papers (9 papers)

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Research

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10 pages, 825 KiB  
Article
Why Do High-Risk Patients Develop or Not Develop Coronary Artery Disease? Metabolic Insights from the CAPIRE Study
by Martino Deidda, Antonio Noto, Christian Cadeddu Dessalvi, Daniele Andreini, Felicita Andreotti, Eleuterio Ferrannini, Roberto Latini, Aldo P. Maggioni, Marco Magnoni, Giuseppe Mercuro and on behalf of the CAPIRE Investigators
Metabolites 2022, 12(2), 123; https://doi.org/10.3390/metabo12020123 - 27 Jan 2022
Cited by 4 | Viewed by 2372
Abstract
Traditional cardiovascular (CV) risk factors (RFs) and coronary artery disease (CAD) do not always show a direct correlation. We investigated the metabolic differences in a cohort of patients with a high CV risk profile who developed, or did not develop, among those enrolled [...] Read more.
Traditional cardiovascular (CV) risk factors (RFs) and coronary artery disease (CAD) do not always show a direct correlation. We investigated the metabolic differences in a cohort of patients with a high CV risk profile who developed, or did not develop, among those enrolled in the Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation (CAPIRE) study. We studied 112 subjects with a high CV risk profile, subdividing them according to the presence (CAD/High-RFs) or absence of CAD (No-CAD/High-RFs), assessed by computed tomography angiography. The metabolic differences between the two groups were identified by gas chromatography-mass spectrometry. Characteristic patterns and specific metabolites emerged for each of the two phenotypic groups: high concentrations of pyruvic acid, pipecolic acid, p-cresol, 3-aminoisobutyric acid, isoleucine, glyceric acid, lactic acid, sucrose, phosphoric acid, trimethylamine-N-oxide, 3-hydroxy-3-methylglutaric acid, erythritol, 3-hydroxybutyric acid, glucose, leucine, and glutamic acid; and low concentrations of cholesterol, hypoxanthine, glycerol-3-P, and cysteine in the CAD/High-RFs group vs the No-CAD/High-RFs group. Our results show the existence of different metabolic profiles between patients who develop CAD and those who do not, despite comparable high CV risk profiles. A specific cluster of metabolites, rather than a single marker, appears to be able to identify novel predisposing or protective mechanisms towards CAD beyond classic CVRFs. Full article
(This article belongs to the Special Issue Metabolic Profiling of Cardiovascular Disease)
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12 pages, 1414 KiB  
Article
The Echocardiographic Parameters of Systolic Function Are Associated with Specific Metabolomic Fingerprints in Obstructive and Non-Obstructive Hypertrophic Cardiomyopathy
by Martino Deidda, Antonio Noto, Daniele Pasqualucci, Claudia Fattuoni, Luigi Barberini, Cristina Piras, Pier Paolo Bassareo, Maurizio Porcu, Giuseppe Mercuro and Christian Cadeddu Dessalvi
Metabolites 2021, 11(11), 787; https://doi.org/10.3390/metabo11110787 - 18 Nov 2021
Cited by 3 | Viewed by 1555
Abstract
The purpose of this study was to assess whether metabolomics, associated with echocardiography, was able to highlight pathophysiological differences between obstructive (OHCM) or non-obstructive (NOHCM) hypertrophic cardiomyopathy. Thirty-one HCM patients underwent standard and advanced echocardiography; a plasma sample was collected for metabolomic analysis. [...] Read more.
The purpose of this study was to assess whether metabolomics, associated with echocardiography, was able to highlight pathophysiological differences between obstructive (OHCM) or non-obstructive (NOHCM) hypertrophic cardiomyopathy. Thirty-one HCM patients underwent standard and advanced echocardiography; a plasma sample was collected for metabolomic analysis. Results. Patients with OHCM compared with subjects with NOHCM had higher values of 2DLVEF (66.5 ± 3.3% vs. 60.6 ± 1.8%, p < 0.01), S wave (7.6 ± 1.1 vs. 6.3 ± 0.7 cm/s, p < 0.01) and 3D global longitudinal strain (17.2 ± 4.2%, vs. 13.4 ± 1.3%, p < 0.05). A 2-group PLS-Discriminant Analysis was performed to verify whether the two HCM groups differed also based on the metabolic fingerprint. A clear clustering was shown (ANOVA p = 0.014). The most discriminating metabolites resulted as follows: in the NOHCM Group, there were higher levels of threitol, aminomalonic acid, and sucrose, while the OHCM Group presented higher levels of amino acids, in particular those branched chains, of intermediates of glycolysis (lactate) and the Krebs cycle (fumarate, succinate, citrate), of fatty acids (arachidonic acid, palmitoleic acid), of ketone bodies (2-OH-butyrate). Our data point out a different systolic function related to a specific metabolic activity in the two HCM phenotypic forms, with specific metabolites associated with better contractility in OHCM. Full article
(This article belongs to the Special Issue Metabolic Profiling of Cardiovascular Disease)
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12 pages, 306 KiB  
Article
Pattern of Adiponectin, Osteocalcin, Irisin, FGF-21, and MCP-1 According to the Body Size Phenotype: Could They Be Markers of Metabolic Health in Mexican-Mestizo Middle-Aged Women?
by Lourdes Balcázar-Hernandez, Lourdes Basurto, Leticia Manuel-Apolinar, Sara Vega-García, Norma Basurto-Acevedo, Carlos Martínez-Murillo and Rosalinda Sánchez-Arenas
Metabolites 2021, 11(11), 771; https://doi.org/10.3390/metabo11110771 - 11 Nov 2021
Viewed by 1856
Abstract
Variations in levels of some adipokines, myokines, osteokines, hepatokines and inflammatory cytokines contribute to abnormal glucose and lipid metabolism. The aim of this study was to determine the pattern of adiponectin, osteocalcin (OCN), irisin, FGF-21, and MCP-1 according to the body size phenotype [...] Read more.
Variations in levels of some adipokines, myokines, osteokines, hepatokines and inflammatory cytokines contribute to abnormal glucose and lipid metabolism. The aim of this study was to determine the pattern of adiponectin, osteocalcin (OCN), irisin, FGF-21, and MCP-1 according to the body size phenotype of middle-aged women, and their associations with BMI, visceral adipose tissue (VAT), and HOMA-IR. A cross-sectional study in 265 women aged from 40 to 65 years was performed. The biochemical characteristics were evaluated in metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy obese, and metabolically unhealthy obese women. There was an association of OCN with BMI (r = −0.107; p = 0.047); adiponectin with BMI (r = −0.217; p = 0.001), insulin (r = −0.415; p = 0.0001), HOMA-IR (r = −0.429; p = 0.0001), and VAT (r = −0.134; p = 0.025); irisin with BMI (r = 0.604; p = 0.001), insulin (r = 0.446; p = 0.0001), HOMA-IR (r = 0.452; p = 0.0001), and VAT (r = 0.645; p = 0.0001); FGF−21 with insulin (r = −0.337; p= 0.030) and HOMA-IR (r = −0.341; p = 0.03); and MCP-1 with BMI (r = 0.481; p = 0.0001), VAT (r = 0.497; p = 0.001), insulin (r = 0.298; p= 0.001), and HOMA-IR (r = 0.255; p = 0.004). A multivariate analysis showed that an elevation of OCN (OR 1.4 (95%CI 1.06–1.81)) and a reduction of adiponectin (OR 0.9 (0.84–0.96)) were associated factors for a metabolic unhealthy phenotype in normal weight participants. Likewise, higher irisin (OR 1.007 (1.003–1.011)) and MCP-1 (1.044 (1.008–1.083)) were risk factors for a metabolic unhealthy phenotype in woman with obesity. OCN, adiponectin, irisin, FGF-21, and MCP-1 are associated with some metabolic parameters such as BMI, HOMA-IR, and VAT, and could be possible biomarkers of an unhealthy metabolic phenotype in middle-aged women. Full article
(This article belongs to the Special Issue Metabolic Profiling of Cardiovascular Disease)
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19 pages, 560 KiB  
Article
Risk Factors of Metabolic Syndrome among Polish Nurses
by Anna Bartosiewicz, Edyta Łuszczki, Małgorzata Nagórska, Łukasz Oleksy, Artur Stolarczyk and Katarzyna Dereń
Metabolites 2021, 11(5), 267; https://doi.org/10.3390/metabo11050267 - 23 Apr 2021
Cited by 6 | Viewed by 2533
Abstract
The metabolic syndrome, also known as syndrome X or the insulin resistance, is defined by the World Health Organization as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Both all over the world and in Poland, there is a [...] Read more.
The metabolic syndrome, also known as syndrome X or the insulin resistance, is defined by the World Health Organization as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Both all over the world and in Poland, there is a shortage of nurses; most of those employed are in the pre-retirement age. However, the requirements in this profession and the patient’s right to care at the highest level remain unchanged and do not take into account the poor condition or age of working nurses, so special attention should be paid to the state of health in this professional group. There is an emphasis on the importance of the adopted attitude toward health and the resulting behaviors, such as regular weight control, following dietary recommendations, regular physical activity and participation in preventive examinations. The aim of the study was to assess the frequency of the occurrence of the metabolic syndrome, its individual components and determining the factors influencing its development in Polish nurses. The research conducted among the nurses in question included DXA (Dual Energy X-ray Absorptiometry) measurements, assessment of glucose concentration, lipid profile, blood pressure and a questionnaire survey. Almost half of the surveyed nurses have metabolic syndrome, which significantly increases the risk of developing cardiovascular diseases or diabetes. After multivariate analysis, it was found that being overweight and obesity were significant factors influenced the MS (metabolic syndrome) occurrence among Polish nurses. Being overweight increases the chances of MS occurrence 8.58 times in relation to BMI (Body Mass Index) <25, obesity increases the chances of MS occurrence 8.085 times in relation to BMI <25, and obesity class II/III increases the chances of MS occurrence 16.505 times in relation to BMI <25. Preventive and supportive measures for this professional group are needed. Full article
(This article belongs to the Special Issue Metabolic Profiling of Cardiovascular Disease)
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11 pages, 634 KiB  
Article
Comparing Levels of Metabolic Predictors of Coronary Heart Disease between Healthy Lean and Overweight Females
by Rasha Abu-El-Ruz, Manar E. Abdel-Rahman, Stephen L. Atkin and Mohamed A. Elrayess
Metabolites 2021, 11(3), 169; https://doi.org/10.3390/metabo11030169 - 15 Mar 2021
Cited by 2 | Viewed by 1939
Abstract
Screening for the metabolomic signature of coronary heart disease (CHD) before disease onset could help in early diagnosis and potentially disease prevention. In this study, the levels of 17 CHD metabolic biomarkers in apparently healthy overweight females were compared to lean counterparts, and [...] Read more.
Screening for the metabolomic signature of coronary heart disease (CHD) before disease onset could help in early diagnosis and potentially disease prevention. In this study, the levels of 17 CHD metabolic biomarkers in apparently healthy overweight females were compared to lean counterparts, and their associations with conventional clinical risk factors were determined. Clinical and metabolic data from 200 apparently healthy non-obese Qatari females were collected from Qatar Biobank (discovery cohort). Logistic regression was used to assess the association between body mass index (BMI) groups and 17 CHD metabolic biomarkers, and receiver operating characteristic (ROC) analysis was used to evaluate the prognostic value of CHD metabolic biomarkers in overweight. Stepwise linear regression was performed to identify the classical risk factors associated with CHD metabolites differentiating the two BMI groups. Validation of the association of CHD metabolic biomarkers with BMI groups was performed in 107 subjects (replication cohort). Out of the tested CHD metabolic biomarkers, five were significantly different between lean and overweight females in the discovery cohort (AUC = 0.73). Among these, the association of mannose, asparagine, and linoleate with BMI groups was confirmed in the replication cohort (AUC = 0.97). Significant correlations between predictors of CHD in overweight healthy women and classical risk factors were observed, including serum levels of cholesterol, testosterone, triiodothyronine, thyroxine, creatinine, albumin, bilirubin, glucose, c-peptide, uric acid, calcium and chloride. Apparently, healthy overweight females exhibit significantly different levels of specific CHD metabolites compared to their lean counterparts, offering a prognostic potential with preventative value. Full article
(This article belongs to the Special Issue Metabolic Profiling of Cardiovascular Disease)
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Review

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17 pages, 1372 KiB  
Review
Metabolic Profiling and Metabolites Fingerprints in Human Hypertension: Discovery and Potential
by John Oloche Onuh and Hongyu Qiu
Metabolites 2021, 11(10), 687; https://doi.org/10.3390/metabo11100687 - 07 Oct 2021
Cited by 13 | Viewed by 2755
Abstract
Early detection of pathogenesis through biomarkers holds the key to controlling hypertension and preventing cardiovascular complications. Metabolomics profiling acts as a potent and high throughput tool offering new insights on disease pathogenesis and potential in the early diagnosis of clinical hypertension with a [...] Read more.
Early detection of pathogenesis through biomarkers holds the key to controlling hypertension and preventing cardiovascular complications. Metabolomics profiling acts as a potent and high throughput tool offering new insights on disease pathogenesis and potential in the early diagnosis of clinical hypertension with a tremendous translational promise. This review summarizes the latest progress of metabolomics and metabolites fingerprints and mainly discusses the current trends in the application in clinical hypertension. We also discussed the associated mechanisms and pathways involved in hypertension’s pathogenesis and explored related research challenges and future perspectives. The information will improve our understanding of the development of hypertension and inspire the clinical application of metabolomics in hypertension and its associated cardiovascular complications. Full article
(This article belongs to the Special Issue Metabolic Profiling of Cardiovascular Disease)
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31 pages, 3385 KiB  
Review
Defining Acute Coronary Syndrome through Metabolomics
by Arun Surendran, Negar Atefi, Hannah Zhang, Michel Aliani and Amir Ravandi
Metabolites 2021, 11(10), 685; https://doi.org/10.3390/metabo11100685 - 06 Oct 2021
Cited by 8 | Viewed by 16599
Abstract
As an emerging platform technology, metabolomics offers new insights into the pathomechanisms associated with complex disease conditions, including cardiovascular diseases. It also facilitates assessing the risk of developing the disease before its clinical manifestation. For this reason, metabolomics is of growing interest for [...] Read more.
As an emerging platform technology, metabolomics offers new insights into the pathomechanisms associated with complex disease conditions, including cardiovascular diseases. It also facilitates assessing the risk of developing the disease before its clinical manifestation. For this reason, metabolomics is of growing interest for understanding the pathogenesis of acute coronary syndromes (ACS), finding new biomarkers of ACS, and its associated risk management. Metabolomics-based studies in ACS have already demonstrated immense potential for biomarker discovery and mechanistic insights by identifying metabolomic signatures (e.g., branched-chain amino acids, acylcarnitines, lysophosphatidylcholines) associated with disease progression. Herein, we discuss the various metabolomics approaches and the challenges involved in metabolic profiling, focusing on ACS. Special attention has been paid to the clinical studies of metabolomics and lipidomics in ACS, with an emphasis on ischemia/reperfusion injury. Full article
(This article belongs to the Special Issue Metabolic Profiling of Cardiovascular Disease)
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18 pages, 1065 KiB  
Review
Cardiovascular Risk Factors in Children with Obesity, Preventive Diagnostics and Possible Interventions
by Mirjam Močnik and Nataša Marčun Varda
Metabolites 2021, 11(8), 551; https://doi.org/10.3390/metabo11080551 - 20 Aug 2021
Cited by 10 | Viewed by 2862
Abstract
The increasing burden of obesity plays an essential role in increased cardiovascular morbidity and mortality. The effects of obesity on the cardiovascular system have also been demonstrated in childhood, where prevention is even more important. Obesity is associated with hormonal changes and vascular [...] Read more.
The increasing burden of obesity plays an essential role in increased cardiovascular morbidity and mortality. The effects of obesity on the cardiovascular system have also been demonstrated in childhood, where prevention is even more important. Obesity is associated with hormonal changes and vascular dysfunction, which eventually lead to hypertension, hyperinsulinemia, chronic kidney disease, dyslipidemia and cardiac dysfunction—all associated with increased cardiovascular risk, leading to potential cardiovascular events in early adulthood. Several preventive strategies are being implemented to reduce the cardiovascular burden in children. This paper presents a comprehensive review of obesity-associated cardiovascular morbidity with the preventive diagnostic workup at our hospital and possible interventions in children. Full article
(This article belongs to the Special Issue Metabolic Profiling of Cardiovascular Disease)
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Other

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16 pages, 1158 KiB  
Systematic Review
Contribution of Metabolomics to the Understanding of NAFLD and NASH Syndromes: A Systematic Review
by Cristina Piras, Antonio Noto, Luciano Ibba, Martino Deidda, Vassilios Fanos, Sandro Muntoni, Vera Piera Leoni and Luigi Atzori
Metabolites 2021, 11(10), 694; https://doi.org/10.3390/metabo11100694 - 11 Oct 2021
Cited by 20 | Viewed by 3728
Abstract
Several differential panels of metabolites have been associated with the presence of metabolic syndrome and its related conditions, namely non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). This study aimed to perform a systematic review to summarize the most recent finding in [...] Read more.
Several differential panels of metabolites have been associated with the presence of metabolic syndrome and its related conditions, namely non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). This study aimed to perform a systematic review to summarize the most recent finding in terms of circulating biomarkers following NAFLD/NASH syndromes. Hence, the research was focused on NAFLD/NASH studies analysed by metabolomics approaches. Following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, a systematic search was conducted on the PubMed database. The inclusion criteria were (i) publication date between 2010 and 2021, (ii) presence of the combination of terms: metabolomics and NAFLD/NASH, and (iii) published in a scholarly peer-reviewed journal. Studies were excluded from the review if they were (i) single-case studies, (ii) unpublished thesis and dissertation studies, and (iii) not published in a peer-reviewed journal. Following these procedures, 10 eligible studies among 93 were taken into consideration. The metabolisms of amino acids, fatty acid, and vitamins were significantly different in patients affected by NAFLD and NASH compared to healthy controls. These findings suggest that low weight metabolites are an important indicator for NAFLD/NASH syndrome and there is a strong overlap between NAFLD/NASH and the metabolic syndrome. These findings may lead to new perspectives in early diagnosis, identification of novel biomarkers, and providing novel targets for pharmacological interventions. Full article
(This article belongs to the Special Issue Metabolic Profiling of Cardiovascular Disease)
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