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Article: Insulin resistance/hyperinsulinemia: an important cardiovascular risk factor that has long been underestimated.

Fazio, Serafino / Mercurio, Valentina / Tibullo, Loredana / Fazio, Valeria / Affuso, Flora

2024 Volume 11, Page(s) 1380506

Abstract: Cardiovascular mortality is still excessively high, despite the considerable progress made in the prevention and treatment of cardiovascular diseases. Although many cardiovascular risk factors (such as arterial hypertension, hypercholesterolemia, ... ...

Abstract	Cardiovascular mortality is still excessively high, despite the considerable progress made in the prevention and treatment of cardiovascular diseases. Although many cardiovascular risk factors (such as arterial hypertension, hypercholesterolemia, diabetes, etc.), identified in the general population, are being promptly treated, to date little consideration is given to a cardiovascular risk factor which we believe has largely demonstrated in the scientific literature of the last three decades that, if neglected, can produce a series of relevant negative effects on the cardiovascular system: insulin resistance (IR)/hyperinsulinemia (Hyperins). This risk factor is still not sufficently sought in the general population and, consequently, is not treated promptly, as it should be, to avoid its negative impact on the cardiovascular system. IR's prevalence is constantly growing worldwide, and it is estimated to have reached a prevalence of 51% of the general population in developed and developing countries, and Hyperins is a constant and strong feature of IR. This article aims to stimulate the scientific community towards IR/Hyperins as relevant cardiovascular risk factor, since it is still neglected. The scientific literature analyzed and used to for this article was found on PubMed, Scopus, Science Direct, etc, using the following keywords: insulin, insulin signaling, insulin resistance, hyperinsulinemia, cardiovascular risk factors, cardiovascular system, cardiovascular diseases. We selected studies that explored the association between IR/Hyperins and the cardiovascular system, and those that discussed the possibilities of screening and treatment of IR/Hyperins.
Language	English
Publishing date	2024-03-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2024.1380506
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Insulin Resistance/Hyperinsulinemia, Neglected Risk Factor for the Development and Worsening of Heart Failure with Preserved Ejection Fraction.

Fazio, Serafino / Mercurio, Valentina / Fazio, Valeria / Ruvolo, Antonio / Affuso, Flora

Biomedicines

2024 Volume 12, Issue 4

Abstract: Heart failure (HF) has become a subject of continuous interest since it was declared a new pandemic in 1997 because of the exponential increase in hospitalizations for HF in the latest years. HF is the final state to which all heart diseases of different ...

Abstract	Heart failure (HF) has become a subject of continuous interest since it was declared a new pandemic in 1997 because of the exponential increase in hospitalizations for HF in the latest years. HF is the final state to which all heart diseases of different etiologies lead if not adequately treated. It is highly prevalent worldwide, with a progressive increase with age, reaching a prevalence of 10% in subjects over the age of 65 years. During the last two decades, it was possible to see that the prevalence of heart failure with preserved ejection fraction (HFpEF) was increasing while that of heart failure with reduced ejection fraction (HFrEF) was decreasing. HFpEF is typically characterized by concentric remodeling of the left ventricle (LV) with impaired diastolic function and increased filling pressures. Over the years, also the prevalence of insulin resistance (IR)/hyperinsulinemia (Hyperins) in the general adult population has progressively increased, primarily due to lifestyle changes, particularly in developed and developing countries, with a range that globally ranges between 15.5% and 46.5%. Notably, over 50% of patients with HF also have IR/Hyperins, and the percentage is even higher in those with HFpEF. In the scientific literature, it has been well highlighted that the increased circulating levels of insulin, associated with conditions of insulin resistance, are responsible for progressive cardiovascular alterations over the years that could stimulate the development and/or the worsening of HFpEF. The aim of this manuscript was to review the scientific literature that supports a pathophysiologic connection between IR/Hyperins and HFpEF to stimulate the scientific community toward the identification of hyperinsulinemia associated with insulin resistance as an independent cardiovascular risk factor in the development and worsening of HF, believing that its adequate screening in the general population and an appropriate treatment could reduce the prevalence of HFpEF and improve its progression.
Language	English
Publishing date	2024-04-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines12040806
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Article ; Online: A Descriptive Review of the Action Mechanisms of Berberine, Quercetin and Silymarin on Insulin Resistance/Hyperinsulinemia and Cardiovascular Prevention.

Bellavite, Paolo / Fazio, Serafino / Affuso, Flora

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 11

Abstract: Insulin resistance (IR) and the associated hyperinsulinemia are early pathophysiological changes which, if not well treated, can lead to type 2 diabetes, endothelial dysfunction and cardiovascular disease. While diabetes care is fairly well standardized, ...

Abstract	Insulin resistance (IR) and the associated hyperinsulinemia are early pathophysiological changes which, if not well treated, can lead to type 2 diabetes, endothelial dysfunction and cardiovascular disease. While diabetes care is fairly well standardized, the prevention and treatment of IR lacks a single pharmaceutical approach and many lifestyle and dietary interventions have been proposed, including a wide range of food supplements. Among the most interesting and well-known natural remedies, alkaloid berberine and the flavonol quercetin have particular relevance in the literature, while silymarin-the active principle of the
MeSH term(s)	Animals ; Humans ; Silymarin/pharmacology ; Silymarin/therapeutic use ; Silymarin/chemistry ; Quercetin/pharmacology ; Quercetin/therapeutic use ; Insulin Resistance ; Berberine/pharmacology ; Berberine/therapeutic use ; Diabetes Mellitus, Type 2 ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/prevention & control ; Silybum marianum/chemistry
Chemical Substances	Silymarin ; Quercetin (9IKM0I5T1E) ; Berberine (0I8Y3P32UF)
Language	English
Publishing date	2023-06-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28114491
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Article: The Negative Impact of Insulin Resistance/Hyperinsulinemia on Chronic Heart Failure and the Potential Benefits of Its Screening and Treatment.

Fazio, Serafino / Mercurio, Valentina / Affuso, Flora / Bellavite, Paolo

Biomedicines

2023 Volume 11, Issue 11

Abstract: This opinion article highlights the potential alterations caused by insulin resistance and hyperinsulinemia on the cardiovascular system and their negative impact on heart failure (HF), and describes the potential benefits of an early screening with ... ...

Abstract	This opinion article highlights the potential alterations caused by insulin resistance and hyperinsulinemia on the cardiovascular system and their negative impact on heart failure (HF), and describes the potential benefits of an early screening with consequent prompt treatment. HF is the final event of several different cardiovascular diseases. Its incidence has been increasing over the last decades because of increased survival from ischemic heart disease thanks to improvements in its treatment (including myocardial revascularization interventions) and the increase in life span. In particular, incidence of HF with preserved ejection fraction (HFpEF) is significantly increasing, and patients with HFpEF often are also affected by diabetes mellitus and insulin resistance (IR), with a prevalence > 45%. Concentric left ventricular (LV) remodeling and diastolic dysfunction are the main structural abnormalities that characterize HFpEF. It is well documented in the literature that IR with chronic hyperinsulinemia, besides causing type 2 diabetes mellitus, can cause numerous cardiovascular alterations, including endothelial dysfunction and increased wall thicknesses of the left ventricle with concentric remodeling and diastolic dysfunction. Therefore, it is conceivable that IR might play a major role in the pathophysiology and the progressive worsening of HF. To date, several substances have been shown to reduce IR/hyperinsulinemia and have beneficial clinical effects in patients with HF, including SGLT2 inhibitors, metformin, and berberine. For this reason, an early screening of IR could be advisable in subjects at risk and in patients with heart failure, to promptly intervene with appropriate therapy. Future studies aimed at comparing the efficacy of the substances used both alone and in association are needed.
Language	English
Publishing date	2023-10-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11112928
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Article ; Online: A Descriptive Review of the Action Mechanisms of Berberine, Quercetin and Silymarin on Insulin Resistance/Hyperinsulinemia and Cardiovascular Prevention

Paolo Bellavite / Serafino Fazio / Flora Affuso

Molecules, Vol 28, Iss 4491, p

2023 Volume 4491

Abstract	Insulin resistance (IR) and the associated hyperinsulinemia are early pathophysiological changes which, if not well treated, can lead to type 2 diabetes, endothelial dysfunction and cardiovascular disease. While diabetes care is fairly well standardized, the prevention and treatment of IR lacks a single pharmaceutical approach and many lifestyle and dietary interventions have been proposed, including a wide range of food supplements. Among the most interesting and well-known natural remedies, alkaloid berberine and the flavonol quercetin have particular relevance in the literature, while silymarin—the active principle of the Silybum marianum thistle—was traditionally used for lipid metabolism disorders and to sustain liver function. This review describes the major defects of insulin signaling leading to IR and the main properties of the three mentioned natural substances, their molecular targets and synergistic action mechanisms. The actions of berberine, quercetin and silymarin are partially superimposable as remedies against reactive oxygen intermediates generated by a high-lipid diet and by NADPH oxidase, which is triggered by phagocyte activation. Furthermore, these compounds inhibit the secretion of a battery of pro-inflammatory cytokines, modulate intestinal microbiota and are especially able to control the various disorders of the insulin receptor and post-receptor signaling systems. Although most of the evidence on the effects of berberine, quercetin and silymarin in modulating insulin resistance and preventing cardiovascular disease derive from experimental studies on animals, the amount of pre-clinical knowledge strongly suggests the need to investigate the therapeutic potential of these substances in human pathology.
Keywords	insulin resistance ; diabetes ; food supplements ; flavonoids ; oxidative stress ; insulin signaling ; Organic chemistry ; QD241-441
Subject code	571
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Management of Mild-to-Moderate Symptomatic COVID-19.

Fazio, Serafino / Affuso, Flora / Bellavite, Paolo

Medical science monitor : international medical journal of experimental and clinical research

2022 Volume 28, Page(s) e936292

Abstract: In the past 2 years, the coronavirus disease 2019 (COVID-19) pandemic has driven investigational studies and controlled clinical trials on antiviral treatments and vaccines that have undergone regulatory approval. Now that the severe acute respiratory ... ...

Abstract	In the past 2 years, the coronavirus disease 2019 (COVID-19) pandemic has driven investigational studies and controlled clinical trials on antiviral treatments and vaccines that have undergone regulatory approval. Now that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants may become endemic over time, there remains a need to identify drugs that treat the symptoms of COVID-19 and prevent progression toward severe cases, hospitalization, and death. Understanding the molecular mechanisms of SARS-CoV-2 infection is extremely important for the development of effective therapies against COVID-19. This review outlines the key pathways involved in the host response to SARS-CoV-2 infection and discusses the potential role of antioxidant and anti-inflammatory pharmacological approaches for the management of early mild-to-moderate COVID-19, using the examples of combined indomethacin, low-dose aspirin, omeprazole, hesperidin, quercetin, and vitamin C. The pharmacological targets of these substances are described here for their possible synergism in counteracting SARS-CoV-2 replication and progression of the infection from the upper respiratory airways to the blood, avoiding vascular complications and cytokine and bradykinin storms.
MeSH term(s)	Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Endemic Diseases ; Host Microbial Interactions/drug effects ; Host Microbial Interactions/physiology ; Humans ; Pharmacological Phenomena/physiology ; SARS-CoV-2/drug effects ; SARS-CoV-2/pathogenicity
Chemical Substances	Anti-Inflammatory Agents ; Antioxidants ; Antiviral Agents
Language	English
Publishing date	2022-03-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1439041-3
ISSN	1643-3750 ; 1234-1010
ISSN (online)	1643-3750
ISSN	1234-1010
DOI	10.12659/MSM.936292
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis of Early COVID-19 and Treated at Home Within 3 Days or After 3 Days of Symptom Onset with Prescribed and Non-Prescribed Treatments Between November 2020 and August 2021.

Fazio, Serafino / Bellavite, Paolo / Zanolin, Elisabetta / McCullough, Peter A / Pandolfi, Sergio / Affuso, Flora

Medical science monitor : international medical journal of experimental and clinical research

2021 Volume 27, Page(s) e935379

Abstract: BACKGROUND This retrospective study aimed to investigate outcomes and hospitalization rates in patients with a confirmed diagnosis of early COVID-19 treated at home with prescribed and non-prescribed treatments. MATERIAL AND METHODS The medical records ... ...

Abstract	BACKGROUND This retrospective study aimed to investigate outcomes and hospitalization rates in patients with a confirmed diagnosis of early COVID-19 treated at home with prescribed and non-prescribed treatments. MATERIAL AND METHODS The medical records of a cohort of 158 Italian patients with early COVID-19 treated at home were analyzed. Treatments consisted of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed. The association of treatment timeliness and of clinical variables with the duration of symptoms and with the risk of hospitalization was evaluated by logistic regression. RESULTS Patients were divided into 2 groups: group 1 (n=85) was treated at the earliest possible time (<72 h from onset of symptoms), and group 2 (n=73) was treated >72 h after the onset of symptoms. Clinical severity at the beginning of treatment was similar in the 2 groups. In group 1, symptom duration was shorter than in group 2 (median 6.0 days vs 13.0 days, P<0.001) and no hospitalizations occurred, compared with 19.18% hospitalizations in group 2. One patient in group 1 developed chest X-ray alterations and 2 patients experienced an increase in D-dimer levels, compared with 30 and 22 patients, respectively, in group 2. The main factor determining the duration of symptoms and the risk of hospitalization was the delay in starting therapy (P<0.001). CONCLUSIONS This real-world study of patients in the community showed that early diagnosis and early supportive patient management reduced the severity of COVID-19 and reduced the rate of hospitalization.
MeSH term(s)	Aged ; Aged, 80 and over ; Aspirin/therapeutic use ; Betamethasone/therapeutic use ; COVID-19/diagnosis ; Cohort Studies ; Dietary Supplements ; Early Diagnosis ; Female ; Flavonoids/therapeutic use ; Follow-Up Studies ; Heparin, Low-Molecular-Weight/therapeutic use ; Hospitalization/statistics & numerical data ; Humans ; Indomethacin/therapeutic use ; Italy ; Male ; Middle Aged ; Omeprazole/therapeutic use ; Patient Acuity ; Retrospective Studies ; Risk Assessment ; SARS-CoV-2 ; Time ; Time-to-Treatment/statistics & numerical data ; Treatment Outcome ; COVID-19 Drug Treatment
Chemical Substances	Flavonoids ; Heparin, Low-Molecular-Weight ; Betamethasone (9842X06Q6M) ; Omeprazole (KG60484QX9) ; Aspirin (R16CO5Y76E) ; Indomethacin (XXE1CET956)
Language	English
Publishing date	2021-12-30
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	1439041-3
ISSN	1643-3750 ; 1234-1010
ISSN (online)	1643-3750
ISSN	1234-1010
DOI	10.12659/MSM.935379
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Article ; Online: Cardiovascular and metabolic effects of Berberine.

Affuso, Flora / Mercurio, Valentina / Fazio, Valeria / Fazio, Serafino

World journal of cardiology

2010 Volume 2, Issue 4, Page(s) 71–77

Abstract: Berberine (BBR) is a natural alkaloid isolated from the Coptis Chinensis. While this plant has been used in Ayurvedic and Chinese medicine for more than 2500 years, interest in its effects in metabolic and cardiovascular disease has been growing in the ... ...

Abstract	Berberine (BBR) is a natural alkaloid isolated from the Coptis Chinensis. While this plant has been used in Ayurvedic and Chinese medicine for more than 2500 years, interest in its effects in metabolic and cardiovascular disease has been growing in the Western world in the last decade. Many papers have been published in these years reporting beneficial effects in carbohydrate and lipid metabolism, endothelial function and the cardiovascular system. In this review, we report a detailed analysis of the scientific literature regarding this topic, describing the effects and the underlying mechanisms of BBR on carbohydrate and lipid metabolism, endothelial function and the cardiovascular system.
Language	English
Publishing date	2010-11-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2573665-6
ISSN	1949-8462 ; 1949-8462
ISSN (online)	1949-8462
ISSN	1949-8462
DOI	10.4330/wjc.v2.i4.71
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Article ; Online: Long term combination treatment for severe idiopathic pulmonary arterial hypertension.

Affuso, Flora / Cirillo, Plinio / Ruvolo, Antonio / Carlomagno, Guido / Fazio, Serafino

World journal of cardiology

2010 Volume 2, Issue 3, Page(s) 68–70

Abstract: We report the long-term follow-up of 3 cases of severe idiopathic pulmonary arterial hypertension, in whom tadalafil plus sitaxentan combination therapy improved the clinical condition and exercise performance without any relevant adverse event. ...

Abstract	We report the long-term follow-up of 3 cases of severe idiopathic pulmonary arterial hypertension, in whom tadalafil plus sitaxentan combination therapy improved the clinical condition and exercise performance without any relevant adverse event.
Language	English
Publishing date	2010-12-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2573665-6
ISSN	1949-8462 ; 1949-8462
ISSN (online)	1949-8462
ISSN	1949-8462
DOI	10.4330/wjc.v2.i3.68
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Article ; Online: Prehypertension and elevated risk of cardiovascular disease: physiopathologic mechanisms.

Affuso, Flora / Ruvolo, Antonio / Fazio, Serafino

The American journal of medicine

2007 Volume 120, Issue 4, Page(s) e11

MeSH term(s)	Blood Pressure ; Cardiovascular Diseases/physiopathology ; Exercise Test ; Humans ; Vascular Resistance ; Ventricular Function, Left
Language	English
Publishing date	2007-04
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	80015-6
ISSN	1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
ISSN (online)	1555-7162 ; 1873-2178
ISSN	0002-9343 ; 1548-2766
DOI	10.1016/j.amjmed.2006.02.032
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