Dissertations / Theses on the topic 'Rischi cardiovascolari'

L'endotelio è il più grande organo del corpo umano e ricopre tutti i vasi del sistema cardiovascolare (cuore, arterie, vene, capillari e sistema linfatico). Considerato in passato come semplice tessuto, svolge invece un ruolo di primaria importanza nella modulazione del tono vasale e del flusso ematico, oltre ad altre numerose funzioni come la regolazione dei processi infiammatori ed immunitari e la permeabilità vascolare. Un'alterazione dell'endotelio comporta una condizione patologica caratterizzata da una ridotta vasodilatazione, contribuendo a diverse alterazioni cardiovascolari come l'aterosclerosi, l'ipertensione e la trombosi. Tale condizione, prende il nome di disfunzione endoteliale ed è e alla base di numerosi fattori di rischio cardiovascolare come il fumo, la dislipidemia, il diabete, l'obesità, il sedentarismo, oltre ad essere presente in alcune patologie cardiovascolari come la cardiopatia ischemica e lo scompenso cardiaco. La diagnosi precoce della disfunzione endoteliale, può giocare un ruolo fondamentale nella prevenzione di eventi cardiovascolari. Ad oggi la metodica gold standard, oltre ad essere costosa ed altamente operatore dipendente, richiede l'impiego di personale specializzato, limiti che la rendono molto lontana dall'essere considerata una metodica di screening. Partendo da questa premessa, questa tesi mira a sviluppare un nuovo dispositivo di screening per valutare la funzione endoteliale. L'ambizione finale è quella di rivolgere l'utilizzo del dispositivo a tutta la popolazione, così da agevolare le azioni di prevenzione nel ridurre gli eventi cardiovascolari, rendendo quindi l'esame più accessibile alla pratica clinica. L'attenzione è stata rivolta allo sviluppo del dispositivo con tecnologia affidabile e riproducibile e allo sviluppo di algoritmi sofisticati per valutare la funzione endoteliale. Questo lavoro intende fornire uno strumento medicale da poter testare e validare in un ambiente ospedaliero, anche in campi ad oggi sconosciuti. Proprio rispetto a quest'ultimo punto, un'applicazione altamente innovativa è l'utilizzo del nuovo dispositivo sui pazienti oncologici per monitorare l'effetto dei farmaci chemioterapici. Questo aspetto è stato affrontato nel contesto di un progetto regionale chiamato Intelligent Oncology Telecare (IOT), dove il dispositivo in questione svolge un ruolo centrale del sistema di monitoraggio del paziente oncologico. Per la progettazione del dispositivo medicale sono stati eseguiti i seguenti passaggi: (a) studio delle tecnologie normalmente adoperate per lo studio della disfunzione endoteliale, (b) scelta della tecnologia, (c) definizione di tutte le specifiche a livello hardware, software e di design, (d) sviluppo di un sistema di supporto alle decisioni con applicazione basate su tecniche di "Machine Learning" (f) sviluppo degli algoritmi per rilevare dal segnale pletismografico biomedico la disfunzione endoteliale. Contestualmente, è stata seguita tutta l'attività di ricerca relativa al dispositivo nel contesto del progetto IOT, che ha permesso lo sviluppo del primo prototipo che verrà testato e validato presso l'ospedale di Fabriano. Parte dell'attività di ricerca presentata in questa tesi è stata svolta presso il Dipartimento di Ingegneria Biomedica dell'Università di Lund. I due contributi scientifici prodotti da questo lavoro sono stati presentati uno a conferenza internazionale ed uno è in revisione in una rivista internazionale. Altri risultati saranno presentati una volta tutelata la proprietà intellettuale di questo progetto, a questo scopo il progetto è patent pending. Per questo motivo è stato richiesto, per un periodo di 18 mesi, la non divulgazione di questo lavoro. Tutto il lavoro descritto in questa tesi è stato supervisionato dalla Strumedical s.r.l. che ha cofinanziato questo progetto di ricerca.
The endothelium is the largest organ in the human body and covers all the vessels in the cardiovascular system (heart, arteries, veins, capillaries and lymphatic system). It plays a role of primary importance in the modulation of vessel tone and blood flow, as well as other numerous functions such as the regulation of inflammatory and immune processes and vascular permeability. The alteration of this organ leads to and endothelial dysfunction is known to be implicated in the pathogenesis and clinical course of all known cardiovascular diseases (CVDs). CVDs refer to several disorders of the heart and blood vessels and include coronary, cerebrovascular, rheumatic-heart diseases and other conditions that could lead to heart attacks and strokes, with consequent premature death. A possible strategy to prevent premature deaths is identifying the individuals at highest risk of Cardiovascular Diseases (preventive healthcare) to ensure that they receive appropriate treatment. The aim of this thesis it is develop a new medical screening device to detect the endothelial dysfunction. • The main contributions of this Thesis can be summarised as follows: • Design and development of a new medical device for ED screening; • Design and development of data-driven approaches for the analysis of signals acquired with the new device; • Design and development of a new Clinical Trial Study and Protocol for the ED device in the oncology context (IOT project). • The new Clinical Decision Support Systems for ED clinical evaluation The device design and development has been a complex process rife with regulations, specifications, application requirements, and end user needs and all of which are balanced and adhered to for a successful product. Results prove the correctness of the design intuition trough the real device implementation, the effectiveness of the biomedical data processing technique and of the Clinical Decision Support System applied to a real dataset and real patients, using the proposed device. The application to Oncology Telecare is suitable and the use of the overall approach on real clinical trials will apply the proposed device and methodology to the oncological care follow-up. Part of the research presented in this thesis was carried out at the Department of Biomedical Engineering of the University of Lund. The scientific contributions of this work have been presented at an international conference and one is being reviewed in an international journal. Other results are not presented because has been protected the intellectual property of this project, indeed the project is patent pending. For this reason, the non-disclosure of this work was requested for a period of 18 months. All the work described in this thesis was supervised by Strumedical s.r.l. who co-founded of this research project.

Notre travail de recherche de ces dernières années a été caractérisé par deux thématiques principales : l’étude de la mécanique vasculaire et des problématiques associées à la mesure des paramètres hémodynamiques centraux ; l’intérêt de l’hémodynamique pour les maladies métaboliques. Le système cardiovasculaire est caractérisé, d’une part, par les ondes de pression et de flux qui représentent la propagation de l’énergie pulsatile du coeur aux tissus ; et d’autre part par la relation complexe entre les deux (pression et flux), qui est le dialogue permanent entre le ventricule gauche et les vaisseaux. Les ondes de pression peuvent être mesurées par différentes techniques, mais la calibration des ondes, permettant d’obtenir les valeurs précises de pression artérielle, comporte des approximations et des contraintes qui ne sont pas encore résolues. Notamment, des calibrations différentes peuvent aboutir à des valeurs de pression très différentes. Notre travail montre que l’étude de l’amplification de la pression pulsée permet de dépasser les problèmes liés à la calibration, et aurait une importance non négligeable en matière de stratégies d’évaluation et de réduction du risque cardiovasculaire. Nos résultats suggèrent que l’hémodynamique centrale est un outil permettant d’étudier les modifications physiopathologiques artérielles occasionnées par les maladies cardiovasculaires et métaboliques. Chez les patients porteurs de ces maladies, la mesure de la rigidité aortique semble être capable de quantifier le degré de l’atteinte artérielle et donc le sur-risque cardiovasculaire, indépendamment et au-delà de l’hypertension artérielle.

Le attuali linee guida stratificano il rischio dei pazienti con ipertensione arteriosa polmonare (IAP) in basso, intermedio e alto (rispettivamente con mortalità a 1 anno <5%, 5-10% e >10%). La maggior parte dei pazienti è però classificata nella categoria intermedia. Per stratificare ulteriormente questi pazienti, abbiamo valutato il ruolo prognostico dello stroke volume index (SVI) misurato al cateterismo cardiaco destro (CCDx) in 725 pazienti naïve da terapia con IAP idiopatica/ereditaria, associata a malattie del tessuto connettivo o cardiopatie congenite. I pazienti sono stati valutati al basale e 3-4 mesi dopo l'inizio della terapia (1° F-UP) con CCDx, livelli plasmatici di peptide natriuretico cerebrale (BNP), test dei 6 minuti (T6M) e classe funzionale OMS. Abbiamo applicato una tabella di rischio semplificata utilizzando i criteri: classe funzionale OMS, T6M, pressione atriale destra o livelli plasmatici di BNP e indice cardiaco (IC) o saturazione di ossigeno venoso misto (SvO2). Le classi di rischio sono state definite come: basso= almeno 3 criteri a basso rischio e nessun criterio ad alto rischio; alto= almeno 2 criteri ad alto rischio inclusi IC o SvO2; intermedio= tutti gli altri casi. Lo SVI, mediante la regressione di Cox, stratifica la prognosi dei pazienti a rischio intermedio al 1° F-UP [p=0.008] ma non al basale [p=0.085]. Considerandone l’ottimale cut-off predittivo (38 ml/m2) i pazienti a rischio intermedio sono ulteriormente classificabili in intermedio-basso e intermedio-alto. Considerando l'effetto dei 3 principali farmaci che agiscono sulla via della prostaciclina in aggiunta alla duplice terapia di combinazione con inibitori della fosfodiesterasi-5 e antagonisti dell'endotelina, i pazienti trattati con epoprostenolo e.v. hanno ottenuto un maggiore miglioramento rispetto ai pazienti trattati con selexipag; col treprostinil s.c. vi è stata una risposta intermedia. Abbiamo quindi proposto un algoritmo di terapia con selexipag in pazienti a rischio intermedio-basso e con prostanoidi parenterali in pazienti a rischio intermedio-alto.
Current guidelines stratify the risk of patients with pulmonary arterial hypertension (PAH) in low, intermediate and high-risk categories (respectively 1-year mortality <5%, 5-10% and >10%). Most patients anyway are classified in the intermediate risk category. In order to further stratify this group of patients we evaluate the prognostic role of stroke volume index (SVI) measured during right heart catheterization (RHC) in 725 treatment naïve patients with idiopathic/heritable PAH and PAH associated with connective tissue disease and congenital heart disease. All patients were assessed at baseline and 3-4 months after starting PAH-specific therapy (1st F-UP) with RHC, brain natriuretic peptide (BNP) plasma levels, 6-min walking distance (6MWD) and WHO functional class. We applied a simplified risk assessment strategy using the following criteria: WHO functional class, 6MWD, right atrial pressure or BNP plasma levels and cardiac index (CI) or mixed venous oxygen saturation (SvO2). Risk strata were defined as: Low risk= at least 3 low risk and no high-risk criteria; High risk= at least 2 high risk criteria including CI or SvO2; Intermediate risk= definitions of low or high risk not fulfilled. SVI, according to Cox regression analysis, can stratify the prognosis of intermediate-risk patients at 1st F-UP [p=0.008] but not at baseline [p=0.085]. According to the best predictive cut-off value (38 ml/m2) intermediate risk patients were further stratified in intermediate-low and intermediate-high. Considering the effect of the 3 main drugs acting on the prostacyclin pathway on top of the dual combination therapy with phosphodiesterase-5 inhibitors and endothelin receptor antagonists patients treated with i.v. Epoprostenol obtained a higher improvement than the patients treated with Selexipag while the patients treated with s.c. Treprostinil presented an intermediate response. According to these results we propose a therapeutic approach with Selexipag in intermediate-low risk patients and with parenteral prostanoids in intermediate-high risk patients.

L’iperaldosteronismo primario (PA) è una patologia caratterizzata da ipertensione arteriosa e da una serie di complicanze che coinvolgono cuore, vasi, rene e metabolismo. I meccanismi patogenetici che sottendono la relazione tra PA e lo sviluppo delle sue complicanze non sono ancora noti e il tessuto adiposo potrebbe avere un ruolo chiave. Lo scopo del lavoro è stato: 1) valutare il rischio cardiovascolare (CVR) secondo le Linee Guida ESH-ESC su 102 pazienti affetti da PA alla diagnosi e dopo terapia, confrontandolo con 132 ipertesi essenziali (EH) di pari età, sesso e durata di malattia; 2) studiare l’espressione di geni coinvolti nel metabolismo glico-lipidico e nell’infiammazione nel tessuto adiposo omentale di pazienti con adenoma aldosterone secernente (APA) sottoposti a surrenectomia. Per lo studio clinico, oltre al grado di ipertensione, abbiamo valutato l’assetto lipidico, la glicemia a digiuno e dopo carico, la circonferenza vita, la funzionalità renale, la familiarità, il fumo, le comordità ed eseguito ecocardiogramma e ecodoppler vasi epiaortici. Per lo studio molecolare abbiamo effettuato un'analisi microarray seguita poi da real time-PCR su adipe di 16 pazienti con APA e di 10 pazienti con adenoma surrenalico noniperfunzionante, per quantificare l’espressione di alcuni geni selezionati (esochinasi 1, IL-1R1, IL- 6, colesterolo-25-idrossilasi, lipoprotein lipasi, omentina, visfatina). Il CVR è risultato essere più elevato nei PA rispetto agli EH per la presenza di più elevati valori pressori, maggiore prevalenza di iperglicemia, sindrome metabolica, abitudine tabagica e ipertrofia ventricolare sinistra. Dopo terapia, il CVR si è ridotto in entrambe le popolazioni ed è diventato sovrapponibile tra PA ed EH, nonostante i PA presentassero valori di pressione arteriosa più alti, grazie ad una riduzione di alcuni fattori di rischio ed una parziale regressione del danno d’organo. E’ stata inoltre rilevata un’aumentata espressione del gene dell’interleuchina 6, una citochina proinfiammatoria coinvolta nello sviluppo di insulino-resistenza e di patologie vascolari, a livello del tessuto adiposo omentale di pazienti con APA, che potrebbe, almeno in parte, contribuire alla patogenesi della sindrome cardiometabolica e all’elevato rischio cardiovascolare che caratterizza questi soggetti.
Primary aldosteronism is an endocrine disease characterized by hypertension and several cardiovascular, renal and metabolic complications. The pathogenetic mechanisms that explain the relationship between PA and the development of such complications are still unknown but adipose tissue could play a key role. The aims of this study were: 1) to evaluate the cardiovascular risk (CVR) according to the ESH-ESC Guidelines in 102 patients with PA at diagnosis and after treatment, and compare it with the CVR of 132 patients with essential hypertension (EH) matched for age, sex and duration of hypertension, 2) to study the expression of genes involved in glucolipid metabolism and inflammation in adipose tissue of patients with aldosterone- producing adenoma (APA) who underwent adrenalectomy. For the clinical study, in addition to the grading of hypertension, we evaluated the lipid profile, fasting glucose and glucose tolerance test, waist circumference, renal function, family history, smoking habit, comorbidities and we performed echocardiographic and carotid ultrasound studies. For the molecular study we performed microarray analysis followed by real-time PCR on adipose tissue samples of 16 patients with APA and 10 patients with non-functioning adrenal adenoma, to quantify the expression of selected genes (hexokinase 1, IL- 1R1, IL-6-25-hydroxylase cholesterol, lipoprotein lipase, omentin, visfatin). The CVR was higher in PA patients than in EH for the presence of higher blood pressure values, higher prevalence of hyperglycemia, metabolic syndrome, smoking habit and left ventricular hypertrophy. After treatment, the CVR was reduced in both populations and became comparable between PA and EH, although the PA group presented higher blood pressure levels, due to the reduction of several risk factors and a partial regression of organ damage . We also found an increased gene expression of interleukin 6, a proinflammatory cytokine involved in the development of insulin resistance and vascular disease, in omental adipose tissue of patients with APA, which can be likely claimed, at least in part, as contributor to the pathogenesis of the cardiometabolic syndrome frequently observed in these subjects.

Abstract Restless legs syndrome (RLS) is a sensori-motor neurological disorder characterzed by paraesthesia, dysaesthesia and irresistibile urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. In our study we investigated the association between RLS and cardiovascular events risk and laboratory parameters in End-stage kidney disease (ESKD) patients on dialysis. We studied 100 ESKD patients undergoing hemodialysis that were enrolled in an 18-months prospective observational study. The main outcomes were the association of RLS with new cardiovascular events and cardiovascular mortality. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual dieresis, lower albumin (P=0.039) and inflammation, but not the dialysis parameters spKt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P=0.019). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P=0.04). This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality. Abstract Restless legs syndrome (RLS) is a sensori-motor neurological disorder characterzed by paraesthesia, dysaesthesia and irresistibile urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. In our study we investigated the association between RLS and cardiovascular events risk and laboratory parameters in End-stage kidney disease (ESKD) patients on dialysis. We studied 100 ESKD patients undergoing hemodialysis that were enrolled in an 18-months prospective observational study. The main outcomes were the association of RLS with new cardiovascular events and cardiovascular mortality. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual dieresis, lower albumin (P=0.039) and inflammation, but not the dialysis parameters spKt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P=0.019). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P=0.04). This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.

Abstract Restless legs syndrome (RLS) is a sensori-motor neurological disorder characterzed by paraesthesia, dysaesthesia and irresistibile urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. In our study we investigated the association between RLS and cardiovascular events risk and laboratory parameters in End-stage kidney disease (ESKD) patients on dialysis. We studied 100 ESKD patients undergoing hemodialysis that were enrolled in an 18-months prospective observational study. The main outcomes were the association of RLS with new cardiovascular events and cardiovascular mortality. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual dieresis, lower albumin (P=0.039) and inflammation, but not the dialysis parameters spKt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P=0.019). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P=0.04). This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality. Abstract Restless legs syndrome (RLS) is a sensori-motor neurological disorder characterzed by paraesthesia, dysaesthesia and irresistibile urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. In our study we investigated the association between RLS and cardiovascular events risk and laboratory parameters in End-stage kidney disease (ESKD) patients on dialysis. We studied 100 ESKD patients undergoing hemodialysis that were enrolled in an 18-months prospective observational study. The main outcomes were the association of RLS with new cardiovascular events and cardiovascular mortality. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual dieresis, lower albumin (P=0.039) and inflammation, but not the dialysis parameters spKt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P=0.019). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P=0.04). This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.

Introduzione. La morte cardiaca improvvisa (MCI) è una delle principali cause di morte in servizio tra i lavoratori dei servizi di emergenza statunitensi. Il nostro progetto di ricerca mirava a : 1) valutare l’incidenza della MCI; 2) identificare i trigger occupazionali di MCI; 3) descrivere la prevalenza dei fattori di rischio cardiovascolari personali tra i lavoratori dei servizi di emergenza statunitensi. Metodi. Sono stati condotti studi indipendenti tra i vigili del fuoco e gli agenti di polizia. Abbiamo consultato delle banche dati gestite da agenzie federali statunitensi e condotto ad hoc sondaggi nazionali (USA). Risultati principali. Tra il 1998 ed il 2012, il tasso di incidenza di MCI tra i vigili del fuoco in carriera è stato pari a 18.1 eventi per 100.000 anni-persona. La causa sottostante di morte più comune è stata la malattia coronarica. Tra i giovani vigili del fuoco (≤ 45 anni), il 63% delle MCI è stato osservato tra soggetti obesi. Questo dato è in linea con lo studio della dieta dei vigili del fuoco, che ha rivelato la necessità di condurre interventi per migliorare le abitudini alimentari in questa popolazione per diminuire la prevalenza dei comuni fattori di rischio cardiovascolare. Due studi hanno dimostrato che l’esecuzione di compiti fisicamente ed emotivamente intensi (ad esempio, lo spegnimento di incendi e le colluttazioni con sospetti) sono trigger importanti (rischi relativi superiori a 30) di MCI tra i vigili del fuoco e gli agenti di polizia. Conclusioni. La riduzione dell’incidenza di MCI tra i lavoratori dei servizi di emergenza rappresenta una priorità assoluta. L’alto carico di malattia è imputabile alla prevalenza dei fattori di rischio cardiovascolare tradizionali superiore a quanto comunemente pensato e all’esposizione a fattori di rischio professionali. Sono necessarie strategie di prevenzione primaria (es. variazioni delle abitudini alimentari) e secondarie (valutazione dell’idoneità alla mansione).
Background. Sudden cardiac death (SCD) is a major cause of on-duty death among US emergency workers. We conducted a research project aimed to: 1) assessing the incidence of cardiovascular diseases; 2) identifying occupational triggers of SCD; 3) describing the prevalence of personal cardiovascular risk factors among US emergency workers. Methods. We performed separate investigations among firefighters and law enforcement officers. We obtained data on cardiovascular deaths from national databases maintained by federal agencies and we conducted a series of nationwide surveys. Main results. Between 1998 and 2012, the incidence rate of SCD among US career firefighters was 18.1 per 100,000 person-years. Coronary heart disease was the leading underlying cause of death. Among young firefighters (≤ 45 years), 63% of deaths were observed among obese subjects. This observation is in line with our study on firefighters’ diet, which highlighted the need for dietary intervention in order to decrease the extremely high prevalence of traditional cardiovascular risk factors in a cohort of active firefighters. Two independent studies showed that stressful duties (e.g. fire suppression or restraints and physical altercation) are important trigger of SCD (relative risks>30) among firefighters and law enforcement officers. Conclusions. The burden of sudden cardiac death among emergency workers is a major concern. On the one hand, emergency workers showed an unacceptably high prevalence of traditional risk factors, which were the main contributors of the observed incidence of coronary artery disease. On the other hand, law enforcement and firefighting involve extremely strenuous duties with may trigger cardiovascular events among susceptible individuals. The primary prevention of cardiovascular diseases in these populations must be considered a priority. In particular, dietary intervention might be particularly effective in decreasing the burden of SCD among emergency workers. As a secondary prevention strategy, emergency workers should receive sufficient evaluation to exclude underlying heart disease.

Introduzione. La morte cardiaca improvvisa (MCI) è una delle principali cause di morte in servizio tra i lavoratori dei servizi di emergenza statunitensi. Il nostro progetto di ricerca mirava a : 1) valutare l’incidenza della MCI; 2) identificare i trigger occupazionali di MCI; 3) descrivere la prevalenza dei fattori di rischio cardiovascolari personali tra i lavoratori dei servizi di emergenza statunitensi. Metodi. Sono stati condotti studi indipendenti tra i vigili del fuoco e gli agenti di polizia. Abbiamo consultato delle banche dati gestite da agenzie federali statunitensi e condotto ad hoc sondaggi nazionali (USA). Risultati principali. Tra il 1998 ed il 2012, il tasso di incidenza di MCI tra i vigili del fuoco in carriera è stato pari a 18.1 eventi per 100.000 anni-persona. La causa sottostante di morte più comune è stata la malattia coronarica. Tra i giovani vigili del fuoco (≤ 45 anni), il 63% delle MCI è stato osservato tra soggetti obesi. Questo dato è in linea con lo studio della dieta dei vigili del fuoco, che ha rivelato la necessità di condurre interventi per migliorare le abitudini alimentari in questa popolazione per diminuire la prevalenza dei comuni fattori di rischio cardiovascolare. Due studi hanno dimostrato che l’esecuzione di compiti fisicamente ed emotivamente intensi (ad esempio, lo spegnimento di incendi e le colluttazioni con sospetti) sono trigger importanti (rischi relativi superiori a 30) di MCI tra i vigili del fuoco e gli agenti di polizia. Conclusioni. La riduzione dell’incidenza di MCI tra i lavoratori dei servizi di emergenza rappresenta una priorità assoluta. L’alto carico di malattia è imputabile alla prevalenza dei fattori di rischio cardiovascolare tradizionali superiore a quanto comunemente pensato e all’esposizione a fattori di rischio professionali. Sono necessarie strategie di prevenzione primaria (es. variazioni delle abitudini alimentari) e secondarie (valutazione dell’idoneità alla mansione).
Background. Sudden cardiac death (SCD) is a major cause of on-duty death among US emergency workers. We conducted a research project aimed to: 1) assessing the incidence of cardiovascular diseases; 2) identifying occupational triggers of SCD; 3) describing the prevalence of personal cardiovascular risk factors among US emergency workers. Methods. We performed separate investigations among firefighters and law enforcement officers. We obtained data on cardiovascular deaths from national databases maintained by federal agencies and we conducted a series of nationwide surveys. Main results. Between 1998 and 2012, the incidence rate of SCD among US career firefighters was 18.1 per 100,000 person-years. Coronary heart disease was the leading underlying cause of death. Among young firefighters (≤ 45 years), 63% of deaths were observed among obese subjects. This observation is in line with our study on firefighters’ diet, which highlighted the need for dietary intervention in order to decrease the extremely high prevalence of traditional cardiovascular risk factors in a cohort of active firefighters. Two independent studies showed that stressful duties (e.g. fire suppression or restraints and physical altercation) are important trigger of SCD (relative risks>30) among firefighters and law enforcement officers. Conclusions. The burden of sudden cardiac death among emergency workers is a major concern. On the one hand, emergency workers showed an unacceptably high prevalence of traditional risk factors, which were the main contributors of the observed incidence of coronary artery disease. On the other hand, law enforcement and firefighting involve extremely strenuous duties with may trigger cardiovascular events among susceptible individuals. The primary prevention of cardiovascular diseases in these populations must be considered a priority. In particular, dietary intervention might be particularly effective in decreasing the burden of SCD among emergency workers. As a secondary prevention strategy, emergency workers should receive sufficient evaluation to exclude underlying heart disease.

Evaluation of carotid artery intima-media thickness in patients affected by psoriasis Psoriasis is associated with an increased risk of atherosclerosis. This study compared subclinical atherosclerosis, evaluating intima-media thickness the of the carotid in psoriasis vulgaris patients and healthy controls using high-resolution ultrasonography and the correlation of this parameter with other cardiovascular risk factors, like insulin resistance and dyslipidemia, METHODS: We will study 40 psoriasis patients, asymptomatic for cardiovascular diseases, and 40 healthy controls matched for age and sex. Intima-media thickness of the common carotid arteries will be measured ultrasonographically. Diabetes mellitus, hypertension, renal failure, a history of cardiovascular or cerebrovascular disease will be exclusion criteria. Subjects who are receiving lipid-lowering therapy, antihypertensive or anti-aggregant drugs, nitrates or long-term systemic steroids will be also excluded. Objective of this study is the evaluation of carotid artery intima-media thickness and its correlation with other blood cardiovascular risk factors in patients affected by psoriasis but asinptomatic for coronary comparing this data with the healthy control subjects. Considering that the presence of psoriasis is an independent risk factor for subclinical atherosclerosis, we want to consider this method of evaluation of cardiovascular risk and to control this risk to prevent IMA.

Evaluation of carotid artery intima-media thickness in patients affected by psoriasis Psoriasis is associated with an increased risk of atherosclerosis. This study compared subclinical atherosclerosis, evaluating intima-media thickness the of the carotid in psoriasis vulgaris patients and healthy controls using high-resolution ultrasonography and the correlation of this parameter with other cardiovascular risk factors, like insulin resistance and dyslipidemia, METHODS: We will study 40 psoriasis patients, asymptomatic for cardiovascular diseases, and 40 healthy controls matched for age and sex. Intima-media thickness of the common carotid arteries will be measured ultrasonographically. Diabetes mellitus, hypertension, renal failure, a history of cardiovascular or cerebrovascular disease will be exclusion criteria. Subjects who are receiving lipid-lowering therapy, antihypertensive or anti-aggregant drugs, nitrates or long-term systemic steroids will be also excluded. Objective of this study is the evaluation of carotid artery intima-media thickness and its correlation with other blood cardiovascular risk factors in patients affected by psoriasis but asinptomatic for coronary comparing this data with the healthy control subjects. Considering that the presence of psoriasis is an independent risk factor for subclinical atherosclerosis, we want to consider this method of evaluation of cardiovascular risk and to control this risk to prevent IMA.

Introduction. Cardiovascular disease (CVD) represents the main cause of morbidity and mortality in kidney recipients. This study was undertaken to assess the impact of functional polymorphisms located in cytokine and apoptosis genes on CVD after kidney transplantation. Cytokine polymorphisms, generally located in gene regulatory regions, are associated with high and low cytokine production and are likely to modulate the magnitude of inflammatory responses following transplantation, depending on the balance between the levels of pro-inflammatory and antiinflammatory cytokines. The role of apoptosis in atherosclerosis has not been completely elucidated, and here we explored the hypothesis that the heterogeneity in cardiovascular risk in kidney recipients may also be linked to functional polymorphisms involved in apoptosis induction. Purpose. In the search for relevant genetic markers of predisposition to CVD after renal transplant, the present investigation was undertaken to identify the clinical impact of polymorphisms of cytokines TNF-α, TGF-β, IL-10, IL-6, IFN-γ and IL-8 and of apoptosis genes Fas and Caspase 9 in a population of kidney transplant recipients. Materials and methods. The study involved 167 patients who received cadaveric kidney transplantation at our centre between 1997 and 2005 (minimum follow-up of 12 months); 35 of them had experienced cardiovascular events (CVD group) and 132 had no cardiovascular complications (non-CVD group). Genotyping was performed using RFLP (Restriction Fragment Length Polymorphism) for RFLP per IL-8/T-251A, Fas/G-670A e Casp9/R221Q polymorphism and SSP (Sequence Specific Primer) for TNF-α/G-308A, TGF-β/L10P, TGF-β/R25P, IL-10/G-1082A, IL- 10/C-819T, IL-10/C-592A, IL-6/G-174C, IFN-γ/T+874A polymorphisms.Results. We found a significant difference in TNF-α and IL-10 genotype frequencies between the patients who had suffered cardiovascular events and those with no CVD history. The high producer genotype for proflogistic cytokine TNF-α appeared to have a significantly superior prevalence in the CVD group compared to the non-CVD group (40.0% vs 21.2%) and it resulted in a 2.4-fold increased cardiovascular risk (OR=2.361; p=0.0289). On the other hand, the high producer genotype for the antiinflammatory cytokine IL-10 was found in 2.8% of the CVD group and in 16.7% of non-CVD group; logistic regression showed a 0.3-fold reduced risk of CVD associated with genetically determined high IL-10 production (OR=0.278; p<0.0001). The other polymorphisms did not prove to have any impact on CVD. Conclusions. TNF-α and IL-10 gene polymorphisms might represent cardiovascular risk markers in renal transplant recipients.

Introduction. Cardiovascular disease (CVD) represents the main cause of morbidity and mortality in kidney recipients. This study was undertaken to assess the impact of functional polymorphisms located in cytokine and apoptosis genes on CVD after kidney transplantation. Cytokine polymorphisms, generally located in gene regulatory regions, are associated with high and low cytokine production and are likely to modulate the magnitude of inflammatory responses following transplantation, depending on the balance between the levels of pro-inflammatory and antiinflammatory cytokines. The role of apoptosis in atherosclerosis has not been completely elucidated, and here we explored the hypothesis that the heterogeneity in cardiovascular risk in kidney recipients may also be linked to functional polymorphisms involved in apoptosis induction. Purpose. In the search for relevant genetic markers of predisposition to CVD after renal transplant, the present investigation was undertaken to identify the clinical impact of polymorphisms of cytokines TNF-α, TGF-β, IL-10, IL-6, IFN-γ and IL-8 and of apoptosis genes Fas and Caspase 9 in a population of kidney transplant recipients. Materials and methods. The study involved 167 patients who received cadaveric kidney transplantation at our centre between 1997 and 2005 (minimum follow-up of 12 months); 35 of them had experienced cardiovascular events (CVD group) and 132 had no cardiovascular complications (non-CVD group). Genotyping was performed using RFLP (Restriction Fragment Length Polymorphism) for RFLP per IL-8/T-251A, Fas/G-670A e Casp9/R221Q polymorphism and SSP (Sequence Specific Primer) for TNF-α/G-308A, TGF-β/L10P, TGF-β/R25P, IL-10/G-1082A, IL- 10/C-819T, IL-10/C-592A, IL-6/G-174C, IFN-γ/T+874A polymorphisms.Results. We found a significant difference in TNF-α and IL-10 genotype frequencies between the patients who had suffered cardiovascular events and those with no CVD history. The high producer genotype for proflogistic cytokine TNF-α appeared to have a significantly superior prevalence in the CVD group compared to the non-CVD group (40.0% vs 21.2%) and it resulted in a 2.4-fold increased cardiovascular risk (OR=2.361; p=0.0289). On the other hand, the high producer genotype for the antiinflammatory cytokine IL-10 was found in 2.8% of the CVD group and in 16.7% of non-CVD group; logistic regression showed a 0.3-fold reduced risk of CVD associated with genetically determined high IL-10 production (OR=0.278; p<0.0001). The other polymorphisms did not prove to have any impact on CVD. Conclusions. TNF-α and IL-10 gene polymorphisms might represent cardiovascular risk markers in renal transplant recipients.

La maggior parte dei fattori di rischio cardiovascolari si traduce in un'aumentata produzione di specie reattive dell'ossigeno (ROS), che a loro volta causano disfunzione endoteliale riducendo la biodisponibilità del mediatore vasodilatante ossido nitrico (NO). È noto che la supplementazione con Coenzima Q10 (CoQ10) migliora la performance cardiaca nello scompenso congestizio e nella cardiopatia ischemica, ed inoltre diminuisce significativamente la pressione arteriosa. Un trial clinico in doppio-cieco, randomizzato, a gruppi paralleli, è stato condotto su 51 soggetti con rischio cardiovascolare moderato e disfunzione endoteliale per comprendere gli effetti della supplementazione con ubichinolo sulla funzione endoteliale, misurata attraverso la determinazione ecografica non invasiva della flow-mediated dilation (FMD). I soggetti sono stati randomizzati in due gruppi di trattamento (ubichinolo, 100 mg o 200 mg/die) e un gruppo placebo. Durante ciascuna visita (T0, 4 e 8 settimane), sono stati misurati pressione arteriosa e FMD, parametri sieroematici (compreso il profilo lipidico), livelli plasmatici di CoQ10 ossidato/ridotto, NO e perossinitrito. La somministrazione di ubichinolo ha aumentato fortemente i livelli plasmatici di CoQ10 totale e ridotto. I soggetti assegnati ad entrambi i gruppi di trattamento hanno mostrato un incremento nella FMD, senza differenze significative tra i due dosaggi. Tuttavia, in seguito all'analisi di biodisponibilità plasmatica di CoQ10, è stata dimostrata una relazione positiva tra l'incremento di FMD e il miglioramento dello stato ossidativo del CoQ10. Nessuna variazione significativa del profilo lipidico è stata riscontrata nei soggetti trattati. Un aumento dose-dipendente dei livelli plasmatici di NO è stato osservato nei soggetti trattati dopo 8 settimane. Esiste una correlazione positiva tra FMD e livelli di NO e, dunque, tra questi ultimi e la funzione endoteliale. La FMD e lo stato ossidativo plasmatico migliorano significativamente dopo somministrazione di ubichinolo. La biodisponibilità dell'ubichinolo si correla positivamente ai miglioramenti della FMD. Inoltre, l'influenza positiva della supplementazione con CoQ10 è indipendente dal profilo lipidico plasmatico, suggerendo un possibile effetto diretto dell'ubichinolo sulle cellule endoteliali.
Most of the major cardiovascular risk factors are characterized by an increased production of reactive oxygen species (ROS), leading to endothelial dysfunction through breakdown of the vasodilating compound nitric oxide (NO). Supplementation with Coenzyme Q10 (CoQ10) positively affects heart performance in congestive heart failure and ischemic heart disease, along with a significant blood pressure lowering effect. To understand the effects of ubiquinol supplementation on endothelial function, measured through non-invasive ultrasonographic assessment of flow-mediated dilation (FMD), a double-blind, randomized, parallel-groups clinical trial was carried out on 51 subjects with moderate cardiovascular risk and endothelial dysfunction. Subjects were randomized to receive ubiquinol, 100 or 200 mg daily, or placebo. During each visit (T0, 4-weeks, 8-weeks) blood pressure, FMD, hematologic parameters (including lipid profile), reduced/oxidized CoQ10 levels, NO and peroxynitrite plasma levels were evaluated. Ubiquinol administration strongly improved total and reduced CoQ10 plasma levels. Subjects assigned to both treatment groups showed an increased FMD compared with subjects in placebo group, with no significant difference between the two dosages. However, after CoQ10 plasma bioavailability analysis, a positive relationship between FMD increases and CoQ10 oxidative status improvements was demonstrated. No significant change in lipid profile was observed in treated subjects. A significant dose-dependent increase in NO plasma levels was observed in treated subjects after T2. NO plasma levels are positively related to FMD and, thus, to endothelial function. FMD and plasma oxidative status are significantly improved following administration of ubiquinol. Bioavailability of ubiquinol is positively correlated with FMD improvements. Positive influence of CoQ10 supplementation is independent from plasma lipid profile, suggesting a direct effect of ubiquinol on endothelial cells.

La valutazione del profilo steroideo mediante cromatografia liquida abbinata alla spettrometria di massa (LC-MS/MS è di grande utilità nella diagnosi e tipizzazione delle masse del surrene. Abbiamo analizzato il profilo steroideo basale e post test di soppressione al desametasone, in 302 pazienti con incidentaloma surrenalico, mediante un metodo LC-MS/MS per la quantificazione di 11 steroidi. Abbiamo poi valutato le associazioni con la salute cardiovascolare durante il periodo di follow-up. Lo scopo secondario prevedeva lo studio della steroidogenesi intra-tumore ed il confronto con il tessuto surrenalico normale corrispondente, mediante lo sviluppo di un nuovo metodo LC-MS/MS per la caratterizzazione di un pannello di 22 steroidi surrenalici. Da tale studio è emerso che i soggetti con adenoma unilaterale e secrezione disregolata di cortisolo avevano valori basali più elevati di cortisolo, 11-desossicortisolo e corticosterone e livelli ridotti di DHEA rispetto ai pazienti con adenoma non funzionante. I pazienti con secrezione disregolata hanno mostrato la mancata soppressione di cortisolo, 11-desossicortisolo e corticosterone post test al desametasone indipendentemente dalla morfologia della lesione. I livelli di cortisolo e corticosterone post test al desametasone erano inoltre associati con una prevalenza più elevata del peggioramento dell’ipertensione. Pazienti con adenoma unilaterale e secrezione disregolata avevano un’incidenza più elevata del peggioramento dell’ipertensione e per l’insorgenza di nuovi eventi cardiovascolari rispetto ai non secernenti, con il cortisolo post desametasone (Hazard Ratio 1.02, 95% CI 1.01-1.03, P<0.001) ed il corticosterone basale (Hazard Ratio 1.06, 95% CI 1.01-1.12, P<0.031) come maggiori predittori. Dallo studio della sterodogenesi tissutale è emerso il potenziale valore informativo di alcuni steroidi non tradizionali, le cui variazioni erano frequentemente riscontrate nel tessuto tumorale rispetto al tessuto surrenalico normale. I pazienti con incidentaloma surrenalico hanno mostrato un profilo steroideo differente in relazione allo status funzionale ed alla morfologia dei surreni che si associava a differenti livelli di rischio cardiovascolare.
The assessment of steroid profile by liquid-chromatography tandem mass spectrometry has proved to be of great usefulness in the diagnosis and characterization of the adrenal masses. We analyzed the circulating steroid profile in 302 patients with adrenal incidentaloma, by an LC-MS/MS method for the quantification of 11 steroids. We then assessed the associations with cardiovascular health during the follow-up period (median 39 months). The secondary aim was the exploratory study of intra-tumor steroidogenesis and the comparison with the corresponding normal tissue, through the development of a new LC-MS/MS method for the characterization of a panel of 22 adrenal steroids. We found that subjects with unilateral adenoma and dysregulated cortisol secretion had higher basal values of cortisol, 11-deoxychortisol and corticosterone and reduced DHEA levels compared to patients with non-functioning adenoma. Moreover, subjects with hyperplasia and dysregulated cortisol secretion had high cortisol and reduced androgen levels compared to non-functioning hyperplasia. Patients with dysregulated secretion showed no suppression of cortisol, 11-deoxycortisol and corticosterone post dexamethasone-test regardless of lesion morphology. After suppression-test, cortisol and corticosterone levels were also associated with higher prevalence of worsening hypertension. Patients with unilateral adenoma and dysregulated secretion had higher incidence of worsening hypertension and of onset of new cardiovascular events than non-secreting, with post-dexamethasone cortisol (Hazard Ratio 1.02, 95%CI 1.01-1.03, P<0.001) and basal corticosterone (Hazard Ratio 1.06, 95%CI 1.01-1.12, P<0.031) as major predictors. The study of tissue sterodogenesis revealed the usefulness of non-classical steroids, such as the metabolites of cortisol, progesterone, 16-hydroxyprogesterone and some 11-oxidized C19-androgens such as 11-hydroxydrostenedione, 11-ketoadrostenedione and 11-hydroxytestosterone whose variations were frequently found in adrenal lesions compared to normal adrenal tissue. We concluded that patients with adrenal incidentaloma showed a different steroid profile in relation to the functional status and morphology of the adrenals, which was associated with different levels of cardiovascular risk.

Il presente lavoro di tesi è stato condotto in ambito psicocardiologico, e riguarda l’indagine delle determinanti psicosociali potenzialmente coinvolte nell’eziopatogenesi, digressione e prognosi delle malattie cardiache. Più studi preliminari sono stati condotti a fini esplorativi, e solo le varabili risultate caratteristiche del campione mantenute in indagini successive. Dopo aver indagato il ruolo del benessere psicologico nell’influenzare la Capacità Funzionale dei pazienti, uno degli indicatori di esito di maggiore importanza in Riabilitazione Cardiologica (RC) (studio 1), si è proceduto a verificare quali tra le variabili cognitive e psicologiche tradizionalmente associate alle malattie cardiache caratterizzasse lo specifico campione, condizionandone Qualità della Vita (QdV) e benessere psicologico (studio 2). Esclusa l’influenza delle variabili cognitive sullo stato emotivo dei soggetti, si è, poi, approfondito il ruolo delle variabili psicologiche nel determinarne la QdV percepita dei degenti (studio 3). Obiettivo del quarto studio è, infine, valutare efficacia ed efficienza dell’aggiunta di tecniche e principi propri del Colloquio Motivazionale (CM) al trattamento psicologico standard (Terapia Breve Strategica, TBS), al di la del solo trattamento breve strategico, nell’incrementare autoefficacia percepita, disponibilità al cambiamento ed aderenza al trattamento riabilitativo nel malati di cuore. Un esempio dell’uso di tale stile comunicativo viene, inoltre, proposto mediante caso clinico (studio 5).
The general aim of this thesis is to seek evidence on how to achieve long-term maintenance of lifestyle changes in a sample of obese inpatients with heart diseases referred to Cardiac Rehabilitation by investigating the influence of selected variables on their physical and psychological status, as well as by examining the efficacy and effectiveness of a motivational-based intervention. Study 1 is aimed at evaluating whether psychological well-being represents an independent predictor of Exercise Capacity. Study 2 focuses on investigating the influence of cognitive abilities and established psychosocial risk factors on the sample’s subjective Quality of life (QoL) and well-being. Since no effect of different levels of cognitive impairments on the expression of psychological distress among the study participants has been identified, in study 3 the effect of emotional impairments on QoL has been further explored. To conclude, the MOTIV-HEART study (study 4) is aimed at testing the incremental efficacy of a brief strategic treatment including motivational components (BST + MI) in improving physical and psychological outcomes over and beyond the stand-alone brief strategic treatment (BST) and whether results will be maintained/increased at 3-month follow-up. An example of this style of communication is also presented through a case study (study 5).