Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease

Topic Information

Dear Colleagues,

There is a growing burden of cardiometabolic disease in many parts of the world. Despite some progress in its prevention and management, more should be done to tackle the risks of its development and treatment in the community and in different specialties of clinical medicine. Currently, the identification and management of those at elevated risk of developing cardiovascular diseases (CVDs) or diabetes remains fragmented and is not linked to constructive managements. Inflammation plays an important role in the development and progression of cardiovascular diseases and diabetes. Hypertension and hyperlipidemia are the key risk factors of CVDs and induce inflammation in the heart and vessels. Unhealthy diet and infection coupled with genetic factors lead to the development of CVDs and diabetes as well as induce inflammation. Obesity-related sub-acute chronic inflammation has been associated with incident type 2 diabetes and atherosclerotic cardiovascular disease. Inflammation is increasingly considered to be a pathologic mediator of these commonly co-occurring diseases. Pharmacologic approaches to the management of CVDs and diabetes may have direct or indirect anti-inflammatory effects. Conversely, some anti-inflammatory approaches may affect glucose metabolism and cardiovascular health. Clinical trials suggest that targeting the inflammatory cascade may be promising for the prevention and management of cardiometabolic disease. In this series, we will discuss a more collaborative approach by researchers of epidemiology, infectious diseases, cardiovascular medicine, endocrinology, and metabolism with encouragement for novel attempts to improve the management of cardiometabolic disease. The topics to be discussed by worldwide experts include the role of inflammation in the pathogenesis, prevention, diagnosis, and treatment of cardiometabolic disease such as cardiovascular diseases and diabetes, new inflammatory biomarkers, and anti-inflammatory interventions of lifestyle, diet, and drug therapy.

Dr. Akira Matsumori
Dr. DeLisa Fairweather
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	3.9	5.2	2013	15.3 Days	CHF 2600
Hearts hearts	-	-	2020	18.5 Days	CHF 1000
Journal of Cardiovascular Development and Disease jcdd	2.4	2.6	2014	22.9 Days	CHF 2700
Journal of Clinical Medicine jcm	3.0	5.7	2012	17.3 Days	CHF 2600
Medicines medicines	-	-	2014	24.5 Days	CHF 1400

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Published Papers (9 papers)

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33 pages, 6057 KiB  

Open AccessReview

Innate Immunity in Cardiovascular Diseases—Identification of Novel Molecular Players and Targets

by Wolfgang Poller, Bettina Heidecker, Enrico Ammirati, Andreas W. Kuss, Ana Tzvetkova, Wolfram C. Poller, Carsten Skurk and Arash Haghikia

J. Clin. Med. 2023, 12(1), 335; https://doi.org/10.3390/jcm12010335 - 1 Jan 2023

Cited by 2 | Viewed by 3379

Abstract

During the past few years, unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into [...] Read more.

During the past few years, unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking advantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss the emerging clinical relevance of advanced diagnostics for cardiovascular diseases, including those associated with COVID-19—with a focus on the role of inflammation in cardiomyopathies and arrhythmias. Second, we consider newly identified immunological interactions at organ and system levels which affect cardiovascular pathogenesis. Thus, studies into immune influences arising from the intestinal system are moving towards therapeutic exploitation. Further, powerful new research tools have enabled novel insight into brain–immune system interactions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress—acting through defined brain regions—upon viral and cardiovascular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena. Full article

(This article belongs to the Topic Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease)

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22 pages, 7426 KiB  

Open AccessArticle

Combination of Spirulina platensis, Ganoderma lucidum and Moringa oleifera Improves Cardiac Functions and Reduces Pro-Inflammatory Biomarkers in Preclinical Models of Short-Term Doxorubicin-Mediated Cardiotoxicity: New Frontiers in Cardioncology?

by Vincenzo Quagliariello, Manuela Giovanna Basilicata, Giacomo Pepe, Raffaele De Anseris, Annabella Di Mauro, Giosuè Scognamiglio, Giuseppe Palma, Vincenzo Vestuto, Simona Buccolo, Antonio Luciano, Massimiliano Barbieri, Francesca Bruzzese, Carlo Maurea, Rossella Pumpo, Carmine Ostacolo, Pietro Campiglia, Massimiliano Berretta and Nicola Maurea

J. Cardiovasc. Dev. Dis. 2022, 9(12), 423; https://doi.org/10.3390/jcdd9120423 - 28 Nov 2022

Cited by 13 | Viewed by 3220

Abstract

Anthracyclines are essential adjuvant therapies for a variety of cancers, particularly breast, gastric and esophageal cancers. Whilst prolonging cancer-related survival, these agents can induce drug-related cardiotoxicity. Spirulina, Reishi (Ganoderma lucidum) and Moringa are three nutraceuticals with anti-inflammatory effects that are currently [...] Read more.

Anthracyclines are essential adjuvant therapies for a variety of cancers, particularly breast, gastric and esophageal cancers. Whilst prolonging cancer-related survival, these agents can induce drug-related cardiotoxicity. Spirulina, Reishi (Ganoderma lucidum) and Moringa are three nutraceuticals with anti-inflammatory effects that are currently used in cancer patients as complementary and alternative medicines to improve quality of life and fatigue. We hypothesize that the nutraceutical combination of Spirulina, Reishi and Moringa (Singo) could reduce inflammation and cardiotoxicity induced by anthracyclines. Female C57Bl/6 mice were untreated (Sham, n = 6) or treated for 7 days with short-term doxorubicin (DOXO, n = 6) or Singo (Singo, n = 6), or pre-treated with Singo for 3 days and associated with DOXO for remaining 7 days (DOXO–Singo, n = 6). The ejection fraction and radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100, Fujifilm, Tokyo, Japan). The myocardial expressions of NLRP3, DAMPs (galectin-3 and calgranulin S100) and 13 cytokines were quantified through selective mouse ELISA methods. Myocardial fibrosis, necrosis and hypertrophy were analyzed through immunohistochemistry (IHC). Human cardiomyocytes were exposed to DOXO (200 nM) alone or in combination with Singo (at 10, 25 and 50 µg/mL) for 24 and 48 h. Cell viability and inflammation studies were also performed. In preclinical models, Singo significantly improved ejection fraction and fractional shortening. Reduced expressions of myocardial NLRP3 and NF-kB levels in cardiac tissues were seen in DOXO–Singo mice vs. DOXO (p < 0.05). The myocardial levels of calgranulin S100 and galectin-3 were strongly reduced in DOXO–Singo mice vs. DOXO (p < 0.05). Immunohistochemistry analysis indicates that Singo reduces fibrosis and hypertrophy in the myocardial tissues of mice during exposure to DOXO. In conclusion, in the preclinical model of DOXO-induced cardiotoxicity, Singo is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. Full article

(This article belongs to the Topic Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease)

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12 pages, 2357 KiB  

Open AccessArticle

Dynamic of Circulating DNAM-1+ Monocytes and NK Cells in Patients with STEMI Following Primary Percutaneous Coronary Intervention

by Marko Kumric, Hrvoje Urlic, Admira Bilalic, Nikolina Rezic-Muzinic, Angela Mastelic, Anita Markotic, Doris Rusic, Josip A. Borovac, Darko Duplancic, Marina Luetic, Ivan Covic, Tina Ticinovic Kurir and Josko Bozic

J. Cardiovasc. Dev. Dis. 2022, 9(11), 395; https://doi.org/10.3390/jcdd9110395 - 15 Nov 2022

Cited by 1 | Viewed by 1860

Abstract

Although the role of inflammation and adverse cardiac remodeling in myocardial infarction (MI) have been extensively explored, gaps in knowledge on the complex interaction between these processes still exist. Data suggest that DNAX accessory molecule-1 (DNAM-1), an activating receptor implicated in NK cell [...] Read more.

Although the role of inflammation and adverse cardiac remodeling in myocardial infarction (MI) have been extensively explored, gaps in knowledge on the complex interaction between these processes still exist. Data suggest that DNAX accessory molecule-1 (DNAM-1), an activating receptor implicated in NK cell education, may be involved in cardiac remodeling following coronary artery occlusion. In the present study, we aimed to explore the dynamic of DNAM-1+ monocytes and NK cells in peripheral blood in the early phase following reperfusion in patients with ST-elevation MI (STEMI). The study enrolled 49 patients older than 18 years of age diagnosed with STEMI, referred to primary percutaneous coronary intervention (pPCI). Blood samples were obtained at three distinct points (at admission, 3 h, and 24 h after pPCI) and analyzed using flow cytometry. The number of circulating DNAM-1+ monocytes (CD16++ and CD14++) and CD56dimCD16++NK cells was significantly reduced 3 h after pPCI and subsequently returned to initial levels 24 h after procedure (p = 0.003, p < 0.001, and p = 0.002, respectively). Notably, such dynamic was dependent on age of patients. A positive correlation between high sensitivity troponin I levels and number of CD16++DNAM-1+ monocytes in peripheral blood 3 h after pPCI was observed (r = 0.431, p = 0.003). In conclusion, in the present study we delineated the post-reperfusion dynamic of DNAM-1-expresing leukocytes. Additionally, we demonstrated that the number of CD16++ DNAM-1+ monocytes correlate with the extent of myocardial injury. Full article

(This article belongs to the Topic Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease)

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14 pages, 2397 KiB  

Open AccessArticle

Cardioprotective Role for Paraoxonase-1 in Chronic Kidney Disease

by Prabhatchandra Dube, Fatimah K. Khalaf, Armelle DeRiso, Chrysan J. Mohammed, Jacob A. Connolly, Dhanushya Battepati, Apurva Lad, Joshua D. Breidenbach, Andrew L. Kleinhenz, Bella Khatib-Shahidi, Mitra Patel, Iman Tassavvor, Amira F. Gohara, Deepak Malhotra, Eric E. Morgan, Steven T. Haller and David J. Kennedy

Biomedicines 2022, 10(9), 2301; https://doi.org/10.3390/biomedicines10092301 - 16 Sep 2022

Cited by 7 | Viewed by 2012

Abstract

Paraoxonase-1 (PON-1) is a hydrolytic enzyme associated with HDL, contributing to its anti-inflammatory, antioxidant, and anti-atherogenic properties. Deficiencies in PON-1 activity result in oxidative stress and detrimental clinical outcomes in the context of chronic kidney disease (CKD). However, it is unclear if a [...] Read more.

Paraoxonase-1 (PON-1) is a hydrolytic enzyme associated with HDL, contributing to its anti-inflammatory, antioxidant, and anti-atherogenic properties. Deficiencies in PON-1 activity result in oxidative stress and detrimental clinical outcomes in the context of chronic kidney disease (CKD). However, it is unclear if a decrease in PON-1 activity is mechanistically linked to adverse cardiovascular events in CKD. We investigated the hypothesis that PON-1 is cardioprotective in a Dahl salt-sensitive model of hypertensive renal disease. Experiments were performed on control Dahl salt-sensitive rats (SS^Mcwi, hereafter designated SS-WT rats) and mutant PON-1 rats (SS-Pon1^em1Mcwi, hereafter designated SS-PON-1 KO rats) generated using CRISPR gene editing technology. Age-matched 10-week-old SS and SS-PON-1 KO male rats were maintained on high-salt diets (8% NaCl) for five weeks to induce hypertensive renal disease. Echocardiography showed that SS-PON-1 KO rats but not SS-WT rats developed compensated left ventricular hypertrophy after only 4 weeks on the high-salt diet. RT-PCR analysis demonstrated a significant increase in the expression of genes linked to cardiac hypertrophy, inflammation, and fibrosis, as well as a significant decrease in genes essential to left ventricular function in SS-PON-1 KO rats compared to SS-WT rats. A histological examination also revealed a significant increase in cardiac fibrosis and immune cell infiltration in SS-PON-1 KO rats, consistent with their cardiac hypertrophy phenotype. Our data suggest that a loss of PON-1 in the salt-sensitive hypertensive model of CKD leads to increased cardiac inflammation and fibrosis as well as a molecular and functional cardiac phenotype consistent with compensated left ventricular hypertrophy. Full article

(This article belongs to the Topic Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease)

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13 pages, 649 KiB  

Open AccessArticle

Effects of Butyrate Supplementation on Inflammation and Kidney Parameters in Type 1 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

by Ninna H. Tougaard, Marie Frimodt-Møller, Hanne Salmenkari, Elisabeth B. Stougaard, Andressa D. Zawadzki, Ismo M. Mattila, Tine W. Hansen, Cristina Legido-Quigley, Sohvi Hörkkö, Carol Forsblom, Per-Henrik Groop, Markku Lehto and Peter Rossing

J. Clin. Med. 2022, 11(13), 3573; https://doi.org/10.3390/jcm11133573 - 21 Jun 2022

Cited by 16 | Viewed by 3246

Abstract

Type 1 diabetes is associated with increased intestinal inflammation and decreased abundance of butyrate-producing bacteria. We investigated the effect of butyrate on inflammation, kidney parameters, HbA1c, serum metabolites and gastrointestinal symptoms in persons with type 1 diabetes, albuminuria and intestinal inflammation. We conducted [...] Read more.

Type 1 diabetes is associated with increased intestinal inflammation and decreased abundance of butyrate-producing bacteria. We investigated the effect of butyrate on inflammation, kidney parameters, HbA1c, serum metabolites and gastrointestinal symptoms in persons with type 1 diabetes, albuminuria and intestinal inflammation. We conducted a randomized placebo-controlled, double-blind, parallel clinical study involving 53 participants randomized to 3.6 g sodium butyrate daily or placebo for 12 weeks. The primary endpoint was the change in fecal calprotectin. Additional endpoints were the change in fecal short chain fatty acids, intestinal alkaline phosphatase activity and immunoglobulins, serum lipopolysaccharide, CRP, albuminuria, kidney function, HbA1c, metabolites and gastrointestinal symptoms. The mean age was 54 ± 13 years, and the median [Q1:Q3] urinary albumin excretion was 46 [14:121] mg/g. The median fecal calprotectin in the butyrate group was 48 [26:100] μg/g at baseline, and the change was −1.0 [−20:10] μg/g; the median in the placebo group was 61 [25:139] μg/g at baseline, and the change was −12 [−95:1] μg/g. The difference between the groups was not significant (p = 0.24); neither did we find an effect of butyrate compared to placebo on the other inflammatory markers, kidney parameters, HbA1c, metabolites nor gastrointestinal symptoms. Twelve weeks of butyrate supplementation did not reduce intestinal inflammation in persons with type 1 diabetes, albuminuria and intestinal inflammation. Full article

(This article belongs to the Topic Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease)

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8 pages, 454 KiB  

Open AccessBrief Report

A Cease in Shift Work Reverses Arterial Stiffness but Increases Weight and Glycosylated Hemoglobin A 5-Month Follow-Up in Industry

by Marit Skogstad, Hans Christian D. Aass, Lars-Kristian Lunde, Øivind Skare, Per Anton Sirnes and Dagfinn Matre

J. Cardiovasc. Dev. Dis. 2022, 9(6), 190; https://doi.org/10.3390/jcdd9060190 - 12 Jun 2022

Cited by 2 | Viewed by 2229

Abstract

Background: Literature suggests an association between shift work and cardiovascular disease (CVD). Limited evidence is available on how a cessation of shift work affects CVD risk factors. Aim: We investigated whether a five-month plant shutdown affected CVD risk factors in 30 industrial shift [...] Read more.

Background: Literature suggests an association between shift work and cardiovascular disease (CVD). Limited evidence is available on how a cessation of shift work affects CVD risk factors. Aim: We investigated whether a five-month plant shutdown affected CVD risk factors in 30 industrial shift workers. Methods: We collected demographic data, self-reported data on physical activity (PA) and medical history by questionnaire. Pre- and post-plant shutdown, we measured blood pressure (BP), heart rate, lipids, glycosylated hemoglobin (HbA1c) and C-reactive protein (CRP). Additionally, we collected markers of inflammation, Matrix metalloproteinase-9 (MMP-9), Interleukin-6 (IL-6), Monocyte chemoattractant protein-1 (MCP-1), Tumor necrosis factor-alpha (TNF-α), P-selectin, Interleukin-1 beta (IL-1β), and Interleukin-23 (IL-23). We also examined arterial stiffness (central blood pressure, augmentation pressure, and pulse wave velocity) by means of SphygmoCor^® (AtCor Medical Pty Ltd., Sydney, Australia). We monitored sleep by actigraphy prior to and after plant shutdown, with additional registration of sleep quality and assessment of insomnia symptoms. Results: After five months of plant shutdown, we found that HbA1c increased by 1.9 mmol/mol, weight by 1 kg and MCP-1 by 27.3 pg/mL, all unexpectedly. The other markers of inflammation did not change during shutdown, but CRP decreased close to significant levels. There were no changes in lipids during follow-up. Pulse-wave velocity (PWV) was reduced from 8.1 m/s (SD = 1.5) to 7.6 m/s (SD = 1.5), p = 0.03. The workers reported fewer signs of insomnia after shutdown. Conclusions: Our findings suggest that a five-month cessation in shift work increases weight and HbA1c, but also improves insomnia symptoms and reverses arterial stiffening. Full article

(This article belongs to the Topic Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease)

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13 pages, 1012 KiB  

Open AccessArticle

Association between Body Mass Index and Renal Outcomes Modified by Chronic Kidney Disease and Anemia: The Obesity Paradox for Renal Outcomes

by Chi-Chih Hung, Pei-Hua Yu, Sheng-Wen Niu, I-Ching Kuo, Jia-Jung Lee, Feng-Ching Shen, Jer-Ming Chang and Shang-Jyh Hwang

J. Clin. Med. 2022, 11(10), 2787; https://doi.org/10.3390/jcm11102787 - 15 May 2022

Cited by 5 | Viewed by 2924

Abstract

Obesity-related nephropathy is associated with renal function progression. However, some studies have associated a high body mass index (BMI) with improved renal outcomes—this is referred to as the obesity paradox for renal outcomes, especially in relation to advanced chronic kidney disease (CKD). Central [...] Read more.

Obesity-related nephropathy is associated with renal function progression. However, some studies have associated a high body mass index (BMI) with improved renal outcomes—this is referred to as the obesity paradox for renal outcomes, especially in relation to advanced chronic kidney disease (CKD). Central obesity can explain the obesity paradox in all-cause mortality. However, whether obesity or central obesity is associated with renal outcomes (renal replacement therapy or a 50% decline in the estimated glomerular filtration rate) in patients with advanced CKD remains unclear. Our study included 3605 Asian patients with CKD stages 1–5 divided into six groups according to their BMI (between 15 and 35 kg/m²). Through linear regression, BMI was positively associated with hemoglobin and albumin at CKD stages 4 and 5. In the competing risk Cox regression model, a high BMI (27.5–35 kg/m²) was associated with renal outcomes at CKD stages 1–3, but not stages 4 and 5. A high BMI was associated with renal outcomes in patients with hemoglobin ≥11 g/dL, but not <11 g/dL. A high waist-to-hip ratio was not associated with renal outcomes. We conclude that the CKD stage and anemia may explain the obesity paradox in renal outcomes in patients with CKD. Full article

(This article belongs to the Topic Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease)

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15 pages, 1541 KiB  

Open AccessSystematic Review

Significance of Serum-Plasma Leptin Profile during Pregnancy in Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

by María del Mar Roca-Rodríguez, Pablo Ramos-García, Cristina López-Tinoco and Manuel Aguilar-Diosdado

J. Clin. Med. 2022, 11(9), 2433; https://doi.org/10.3390/jcm11092433 - 26 Apr 2022

Cited by 14 | Viewed by 2272

Abstract

Gestational diabetes mellitus (GDM) represents a stage of subclinical inflammation and a risk factor for subsequent future type 2 diabetes and cardiovascular disease development. Leptin has been related with vascular and metabolic changes in GDM with heterogeneous and contradictory results with respect to [...] Read more.

Gestational diabetes mellitus (GDM) represents a stage of subclinical inflammation and a risk factor for subsequent future type 2 diabetes and cardiovascular disease development. Leptin has been related with vascular and metabolic changes in GDM with heterogeneous and contradictory results with respect to their possible involvement in maternal, perinatal, and future complications. Our objective is to evaluate current evidence on the role of leptin in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies’ quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Thirty-nine relevant studies were finally included, recruiting 2255 GDM and 3846 control pregnant women. Leptin levels were significantly higher in GDM participants than in controls (SMD = 0.57, 95%CI = 0.19 to 0.94; p < 0.001). Subgroup meta-analysis did not evidence significant differences in leptin in the different trimesters of pregnancy. Meta-regression showed a positive significant relationship for HOMA in the GDM group (p = 0.05). According to these results, it seems that high levels of leptin can be used as predictive markers in GDM. Full article

(This article belongs to the Topic Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease)

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12 pages, 1902 KiB  

Open AccessEditor’s ChoiceArticle

Combining Stress Speckle Tracking with High-Sensitivity C-Reactive Protein in Diagnosis of Coronary Artery Disease

by Ahmed M. Saleh, Konstantin Zintl and Johannes Brachmann

J. Cardiovasc. Dev. Dis. 2022, 9(5), 123; https://doi.org/10.3390/jcdd9050123 - 20 Apr 2022

Cited by 2 | Viewed by 2354

Abstract

Introduction: CAD (coronary artery disease) is a leading cause of death and disability in developed nations. Exercise testing is recommended as a first-line diagnostic test for patients with stable angina pectoris. In addition to myocardial strain, high-sensitivity CRP (hs-CRP) can predict the presence [...] Read more.

Introduction: CAD (coronary artery disease) is a leading cause of death and disability in developed nations. Exercise testing is recommended as a first-line diagnostic test for patients with stable angina pectoris. In addition to myocardial strain, high-sensitivity CRP (hs-CRP) can predict the presence of significant coronary artery disease. Aim of work: The purpose of this study was to demonstrate the utility of 2D-speckle tracking at rest and under stress along with hs-CRP for detection of CAD in patients who were referred to the chest pain unit with stable or low risk unstable angina pectoris. Methods: A total of 108 individuals met the inclusion criteria and gave their written consent to participate in this study. Coronary angiography was performed within 48 h after admission to the chest pain unit. Myocardial strain was recorded at rest and during dobutamine administration. Results: Global longitudinal strain at stress appeared to be moderately correlated with the presence of significant coronary artery disease (CAD); r = 0.41, p < 0.0001. A moderate correlation was also found between global longitudinal strain at stress and the severity of coronary occlusion; r = 0.62, p < 0.0001. With a cut-off value of −19.1, global longitudinal strain under stress had a sensitivity of 74.1% and a specificity of 76.7% for detecting significant CAD. Hs-CRP was significantly higher in patients with manifested CAD. Conclusion: Evaluation of longitudinal strain parameters at rest and under stress may predict coronary artery disease in patients with stable angina pectoris. A measurable Hs-CRP is a potential marker of coronary stenosis. Strain data could assist in diagnosing CAD severity. Full article

(This article belongs to the Topic Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease)

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