Guido Iaccarino

• Md, PhD; FESC
• Professor (Full) at University of Naples Federico II

The circadian clock is an endogenous timekeeping system that regulates various physiological and behavioral processes. Recently, it has been shown that the timing of physical activity and food intake can significantly influence metabolic muscle health. Some recent clinical evidence has shown that physical activity practiced in the late afternoon ca...

Background Insulin resistance (IR) and serum uric acid (SUA) are closely interconnected: SUA contributes to adversely affects the insulin signaling pathway and contributes to IR, while IR is a known predictor for the development of hyperuricemia. The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proposed as an eas...

The delayed or missed diagnosis of secondary hypertension contributes to the poor blood pressure control worldwide. This study aimed to assess the diagnostic approach to primary aldosteronism (PA) and pheochromocytoma (PHEO) among Italian centers associated to European and Italian Societies of Hypertension. Between July and December 2023, a 10-item...

In patients with type II diabetes, the development of diabetic cardiomyopathy (DC) is associated with a high risk of mortality. Left ventricular hypertrophy, diastolic dysfunction, and exercise intolerance are the first signs of DC. The underlying mechanisms are not fully elucidated, and there is an urgent need for specific biomarkers and molecular...

Background Insulin resistance (IR) and serum uric acid (SUA) are closely interconnected: SUA contributes to adversely affects the insulin signaling pathway and contributing to IR, while IR is a known predictor for the development of hyperuricemia. The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proposed as an ea...

Renovascular hypertension (RVH) remains underdiagnosed despite its significant cardiovascular and renal morbidity. This survey investigated screening and management practices for RVH among hypertensive patients in Italian hypertension centres in a real-life setting. Secondary, we analysed the current spread of renal denervation (RDN) and the criter...

Anderson–Fabry disease (AFD) is a lysosomal storage disorder, depending on defects in alpha galactosidase A activity, due to a mutation in the galactosidase alpha gene. Cardiovascular involvement represents the leading cause of death in AFD. Cardiac imaging plays a key role in the evaluation and management of AFD patients. Echocardiography is the f...

Background: Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which increases the risk of prefrailty and frailty among older individuals. Methods: We screened older adults with prefrailty and hypertension from March 2021 to January 2023. We assessed the correlation linking...

Ischemia with non-obstructive coronary artery (INOCA) is a common cause of hospital admissions, leading to negative outcomes and reduced quality of life. Central to its pathophysiology is endothelial dysfunction, which contributes to myocardial ischemia despite the absence of significant coronary artery blockage. Addressing endothelial dysfunction...

BACKGROUND Insufficient physical activity is one of the leading risk factors for death worldwide. Regular exercise can improve physical performance and quality of life, reduce the risks of falls and depressive symptoms, and reduce the likelihood of cognitive decline in older adults. Immersive virtual reality (VR) and serious games (SG) are promisin...

The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic statu...

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound a...

Fabry disease (FD), also known as Anderson-Fabry disease, is a hereditary disorder of glycosphingolipid metabolism, caused by a deficiency of the lysosomal alpha-galactosidase A enzyme. This causes a progressive accumulation of glycosphingolipids in tissues and organs which represents the main pathogenetic mechanism of FD. The disease is progressiv...

Objective Left ventricular hypertrophy (LVH) and dysfunction are the main causes of death in patients with Fabry Disease (FD). Identification of clinical predictors of FD evolution is crucially important for the correct timing of therapeutic intervention. On this ground, we aim to evaluate the impact of hypertension (H) as a predictor of (LVH) prog...

INTRODUCTION: Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of pre-frailty and frailty among older individuals. METHODS: We screened pre-frail hypertensive elders from March 2021 to January 2023. We assessed the correlation linking cognitive dy...

Fabry disease (FD) is caused by mutations in the galactosidase alpha (GLA) gene which lead to the accumulation of globotriaosylceramide (Gb-3). Enzyme replacement therapy (ERT) and oral chaperone therapy are the current pharmacological treatments for this condition. However, in the literature, there is a growing emphasis on exploring non-pharmacolo...

Purpose Recently, a novel index [the triglyceride-glucose (TyG) index]) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. There...

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study...

The actual effects of empagliflozin on cognitive impairment in elderly patients remain to be fully determined; specifically, there are no studies exploring this aspect in frail older adults with T2D and CKD. In order to fill this knowledge gap, we enrolled consecutive frail older adults with confirmed diagnoses of T2D and CKD presenting at the Loca...

Background Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic c...

Fabry disease (FD) is a lysosomal storage disorder due to the impaired activity of the α-galactosidase A (GLA) enzyme which induces Gb3 deposition and multiorgan dysfunction. Exercise intolerance and fatigue are frequent and early findings in FD patients, representing a self-standing clinical phenotype with a significant impact on the patient's qua...

Background The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, in the setup of heart failure in response to doxorubicin (Dox) is recently becoming of growing interest. Objectives The study aims to evaluate the role of macrophages in cardiac damage elicited by Dox treatment. Methods C57BL/6 mice were treated with...

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and...

High blood pressure is the leading cause of death and disability globally and an important treatable risk factor for cardiovascular, cerebrovascular and chronic kidney diseases. Digital technology, including mobile health solutions and digital therapy, is expanding rapidly in clinical medicine and has the potential to improve the quality of care an...

Background Self-management of Type 2 diabetes mellitus (T2D) is challenging. Regular self-monitoring of blood glucose and healthy lifestyles are required to improve glycometabolic control, thus delaying diabetes complications, and reducing hospitalizations. Digital technologies can empower patients in their disease management promoting self-managem...

In the quest for sustainable systems for the deployment of healthcare, Integrated care represents a pillar for the de-hospitalization of care, the management of chronic conditions, and the prevention of frailty. This model, though, implies a multilevel complexity and many challenges that have often led to its underutilization in the past. Modern IC...

Background: Despite longstanding epidemiologic data on the association between increased serum triglycerides (TG) and cardiovascular (CV) events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the p...

Objective The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, in the setup of heart failure in response to doxorubicin (Dox) is recently becoming of growing interest. Objective: The study aims to evaluate the role of macrophages in cardiac damage elicited by Dox treatment. Design and method C57BL/6 mice were treat...

Objective Skeletal muscle (SM) pain and fatigue are common in Fabry disease (FD), and strongly impact the patient's quality of life. Still, the SM in FD is poorly investigated. Although energetic alterations are reported in cells from FD patients, they have never been related to fatigue and pain. Given the pivotal relevance of energetics for SM hea...

Objective High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular risk phenotypes, including subclinical atherosclerosis. An interaction between plaques Xanthine Oxidase (XO) expression, SUA, and HDL-C has been recently postulated Design and method N = 6211 patients from the URic acid Right for heArt Health (U...

Objective The aim of this study is to evaluate the associations of serum 25-OHD and PTH concentrations with blood pressure and hypertension mediated target organ damage including left ventricular hypertrophy (LVH) and carotid intima-media thickness (IMT). Design and method This observational retrospective study included 98 patients admitted at Hyp...

Objective We showed that the endothelium can synthesize and release catecholamines in response to hypoxia. However, the pathophysiological implications of such findings are still unknown since no mouse model is available to achieve this goal. The aim of the study is the generation and characterization of a transgenic mouse model in which the tyrosi...

Current therapies for Fabry disease are based on reversing intra-cellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization of the defective enzyme, thereby alleviating lysosome dysfunction. However, their effect in the reversal of end-organ damage, like kidney injury and chronic kid...

Unlabelled: A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study. Aim: of this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV d...

Skeletal muscle (SM) pain and fatigue are common in Fabry disease (FD). Here, we undertook the investigation of the energetic mechanisms related to FD-SM phenotype. A reduced tolerance to aerobic activity and lactate accumulation occurred in FD-mice and patients. Accordingly, in murine FD-SM we detected an increase in fast/glycolytic fibers, mirror...

In 2016, a systematic review and a meta-analysis of existing data on the effects of switch from agalsidase beta to alfa in patients with Fabry disease showed that the switch was well tolerated and associated with stable disease progression. However, additional evidence that supports the need for an update of the review on the long-term effects of s...

This article reports the study protocol of a nationwide multicentric study in seven Italian regions aimed at assessing the effectiveness of a digitally supported approach for the early screening of frailty risk factors in community-dwelling older adults. SUNFRAIL+ is a prospective observational cohort study aimed at carrying out a multidimensional...

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were follo...

Background Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits . The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction. Methods A detailed search related to...

Introduction Calcific aortic valve stenosis (CAVS) is a clinically relevant issue due to the lack of drugs for prevention or treatment. CAVS is driven by endothelial dysfunction and inflammation. A novel therapeutic strategy should target specific molecules involved in the regulation of both endothelial function and immune responses. G protein-coup...

Background and Aims Whether the association between very high HDL-cholesterol levels and cardiovascular mortality (CVM) is modulated by some facilitating factors is unclear. Aim of the study was to investigate whether the risk of CVM associated with very high HDL-cholesterol is increased in subjects with hyperuricemia. Methods and Results Multivar...

Frailty is a complex interplay between several factors, including physiological changes in ageing, multimorbidities, malnutrition, living environment, genetics, and lifestyle. Early screening for frailty risk factors in community-dwelling older people allows for preventive interventions on the clinical and social determinants of frailty, which allo...

This Research Topic focuses on both strengths and weaknesses of social innovation, technological innovation, and health innovation that are increasingly recognized as crucial concepts related to the formulation of responses to the social, health, and environmental challenges. Goals of this Research Topic: (1) to identify and share the best recent p...

Introduction: Anderson-Fabry disease (AFD) is a systemic disorder caused by impaired alpha-galactosidase (GLA) activity, leading to a progressive cardiomyopathy, with hypertrophy and diastolic dysfunction. However, the molecular mechanisms underlying these features are unknown. Aim: To explore the role of mitochondria as a pathogenic mechanism of c...

Objective: In the frame of the Uric Acid Right for Heart Health (URRAH) study, a nationwide multicenter study involving adult participants recruited on a regional community basis from all the territory of Italy under the patronage of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, we searched for the...

The empirical evidence from different countries point out many of those who die from coronavirus would have died anyway in the relatively near future due to their existing frailties or co-morbidities. The acceleration of the mortality conceives the underlying insight according to deaths are "accelerated" ahead of schedule due to COVID-19. Starting...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to be a global challenge due to resulting morbidity and mortality. Cardiovascular (CV) involvement is a crucial complication in COVID-19, and no strategies are available to prevent or specifically address CV events in COVID patients. The identification of molecular...

Objective: A relationship between serum uric acid(UA)and CV events has been documented in the URRAH study.The association between UA and left ventricular mass index(LVMI)has been investigated with heterogeneous results.Aim of this study was to investigate the association between UA and LVMI and whether UA and LVMI or they combination may predict t...

Objective: Searching for a prognostic cut-off value of triglycerides (TG) in predicting cardiovascular (CV) outcome in a large regional-based Italian database of men and women. Design and method: A nationwide multicentre database collects data on subjects aged 18 to 95 years recruited on a regional community basis from all the territory of Italy...

Fabry disease (FD) is a lysosomal storage disorder caused by mutations in the gene for alpha-galactosidase A (GAL) inducing a progressive accumulation of globotriaosylceramide (Gb3) and its metabolites in different organs and tissues. GB3 deposition does not fully explain the clinical manifestations of FD, and other pathogenetic mechanisms have bee...

[This corrects the article DOI: 10.1371/journal.pone.0237297.].

The article describes some of the achievements of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), after eight years in operation. These results were achieved thanks to the collaborative work of the action groups (AGs) and reference sites (RSs). RS regional ecosystems include key organisations committed to investing in...

Introduction: Hypertension is the biggest contributor to the global burden of cardiovascular diseases and related death, but the rates of hypertension awareness, treatment, and control remain largely perfectible. Methods: During the XVII World Hypertension Day (May 17th, 2021), a nationwide cross-sectional opportunistic study endorsed by the Ita...

Objective The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes. Methods The URRAH subpopulation of people with diabetes was studied. Al...

Objectives: In older individuals, the role of serum uric acid (SUA) as risk factor for mortality is debated. This study investigated the association of SUA with all-cause and cardiovascular (CV) mortality in older adults participating in the large multicentre observational uric acid right for heart health (URRAH) study. Methods: Eight thousand U...

Aims Hypertension is a known risk factor for stroke and vascular dementia. Recent studies have also shown that arterial hypertension represents a clear risk factor for mild cognitive decline and its evolution into Alzheimer’s disease. Really, mild cognitive decline significantly compromises the patient’s quality of life, reducing compliance with th...

Aims Left ventricular global longitudinal strain (GLS) detects subtle systolic abnormalities in various cardiovascular conditions, which represent significant risk factors for cognitive impairment and stroke. Specifically, GLS has emerged as a more precise myocardial function measure than left ventricular ejection fraction (LVEF). This study invest...

This article describes a user-centred approach taken by a group of five procurers to set specifications for the procurement of value-based research and development services for IT-supported integrated hypertension management. The approach considered the unmet needs of patients and health systems of the involved regions. The procurers established a...

The biological mechanisms linking nutrition and antioxidants content of the diet with cardiovascular protection are subject of intense investigation. It has been demonstrated that dietary supplementation with cow, donkey or human milk, characterized by distinct nutritional properties, triggers significant differences in the metabolic and inflammato...

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is...

[This corrects the article DOI: 10.1371/journal.pone.0237297.].

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality....

Introduction Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. Aim We assessed the prognostic role of SUA in patients with and without MS. Methods We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular...

Objective: Altered coagulation parameters in COVID-19 patients is associated with a poor prognosis. We tested whether COVID-19 patients on chronic oral anticoagulants (cOACs) for thromboembolism prophylaxis could receive protection from developing more severe phenotypes of the disease. Approach and Results: We searched the database of the SARS-RAS...

This article describes how innovations are exploited in Campania (Italy) to improve health outcomes, quality of life, and sustainability of social and healthcare services. Campania's strategy for digitalization of health and care and for healthy aging is based on a person-centered, life-course, “One Health” approach, where demographic change is con...

The growing digitalization of health and care calls for the development of ICT tools and mHealth solutions to monitor and control the patient's health parameters and lifestyles. ProEmpower is a Pre Commercial Procurement project aimed at procuring research and development services to develop innovative solutions for patient empowerment and self-man...

Mitochondrial dysfunction is a crucial contributor to heart diseases. Alterations in energetic metabolism affect crucial homeostatic processes, such asATP production, the generation of reactive oxygen species, and the release of pro-apoptotic factors, associated with metabolic abnormalities. In response to energetic deficiency, the cardiomyocytes a...

The beneficial effects of physical activity on the cardiovascular system nowadays have achieved the relevance of clinical evidence. In fact, several studies have documented the benefits of exercise training in the prevention of the cardiovascular risk. Abnormalities of insulin signaling transduction account for the impairment of insulin sensitivity...

Objective Vitamin D deficiency contributes to cardiovascular risk (CVR), with hyperparathyroidism advocated as a putative mechanism. Indeed, mounting evidence supports the hypothesis that parathyroid hormone (PTH) impairs endothelial function, even though mechanisms are not fully elucidated. The present study was designed to verify in vitro the abi...

Objective Hyperuricemia can be both determined by overproduction (due to xanthine oxidase hyperactivity) or renal hypoexcretion. In this latter case, also diuretic use (particularly hydrochlorotiazhide) can be involved. While the relationship between hyperuricemia and CardioVascular (CV) events has been definitively linked in many studies, data on...

Background Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease...

Background: Ergogenic nutritional supplementation is sought by professional athletes for improving physical performance; nevertheless, scientific evidence to support the chronic use of L-Arginine among water polo players is missing. Methods: Seventeen male professional water polo players were randomly assigned to assume 5 grams per day of L-Argi...

In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role o...

Aims Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results Multivariable Cox...

Background: Demographic changes have forced communities and people themselves to reshape ageing concepts and approaches and try to develop actions towards active and healthy ageing. In this context, the European Commission launched different private-public partnerships to develop new solutions and answers on questions related to this topic. The Eu...

In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment senso...