Pressione arteriosa brachiale e centrale nel giovane adulto: associazione con fattori di rischio tradizionali ed emergenti

Scopo dello studio L’obiettivo dello studio è quello di valutare gli effetti dell’esposizione a fattori di rischio cardiovascolari sia tradizionali (sesso, BMI, fumo, alcol, attività fisica, familiarità per Ipertensione arteriosa ed eventi cardiovascolari precoci) che emergenti (depressione, ansia, stress, disturbi del sonno, tipo di alimentazione) sui valori di pressione arteriosa nei giovani adulti. Si valuta inoltre la relazione tra parametri vascolari e valori di pressione arteriosa. Metodi Sono stati reclutati 52 soggetti di età compresa tra 18 e 35 anni afferenti agli ambulatori di alcuni medici di Medicina Generale che esercitano nella città di Pisa. I volontari sono stati invitati a presentarsi al Centro Ipertensione dell’Ospedale Santa Chiara di Pisa. Il giorno dello studio i pazienti sono stati sottoposti alla compilazione di un questionario di valutazione dello stile di vita, alla raccolta dell’anamnesi, ad un esame obiettivo generale, alla rilevazione di alcuni parametri antropometrici, alla misurazione della pressione arteriosa e a studi non invasivi vascolari con metodica tonometrica ad applanazione: pulse wave velocity carotido-femorale (PWV), pressioni centrali e parametri di riflessione d’onda. I risultati sono presentati come media ± Deviazione Standard (DS). Eventuali differenze tra gruppi sono state valutate utilizzando ANOVA test e test T di Student. Le correlazioni univariate sono state valutate utilizzando l’indice di correlazione di Pearson. L’analisi di regressione multipla è stata condotta per identificare correlazioni indipendenti tra le variabili considerate. Risultati L’età media risulta di 28.5 ± 4.4 anni e si nota una lieve predominanza del sesso maschile (56%). I valori di PA sistolica e diastolica sono distribuiti nella popolazione secondo una curva di tipo gaussiano e risultano in media di 119.0 ± 13.1 e 68.6 ± 8.8 mmHg rispettivamente. Solo 3 volontari riferivano di soffrire attualmente di ipertensione arteriosa, pur avendo valori normali in assenza di trattamento, mentre è stata posta diagnosi di ipertensione arteriosa in ulteriori 3 volontari. I valori di pressione arteriosa sistolica (PAS) brachiale più elevati si sono riscontrati nel sesso maschile piuttosto che in quello femminile (126.0 ± 10.7 vs 110.2 ± 10.2 mmHg, p<0.0001). Inoltre le seguenti condizioni erano associate a valori di PAS brachiale significativamente più elevate: familiarità per infarto miocardico acuto (IMA), consumare più di 3 fette di pane al giorno, consumare snack fuori pasto almeno una volta a settimana (p < 0.05). E’ stata inoltre rilevata una correlazione inversa tra lo score di ansia e depressione e la PAS brachiale (r = -0.34, p < 0.02 e r = -0.30, p = 0.03 rispettivamente). Nessuna associazione statisticamente significativa è stata osservata tra PAS brachiale e familiarità per ipertensione arteriosa, età, BMI, fumo di sigaretta, alcol, droghe, introito di sale riferito, insonnia, aderenza alla dieta mediterranea. I valori di PAS brachiale erano correlati in modo diretto alla frequenza cardiaca (r=0.30, p=0.03) e in modo inverso al numero di ore settimanali di attività fisica (r=0.46, p=0.002). L’analisi di regressione multipla conferma che sono associati in maniera indipendente ai valori di PAS brachiale: il sesso maschile (β = 0.31, p = 0.03), le ore di attività fisica (β = 0.36, p = 0.01), e i livelli di ansia (β = - 0.28, p = 0.03). Al contrario, nel modello di regressione multipla i valori di PAS centrale sono risultati associati in maniera indipendente ai seguenti parametri: l’età (β=0.30, p=0.03), i livelli di ansia (β= -0.35, p=0.01), il consumo elevato di pane (β= 0.39, p=0.003) e snack fuori pasto (β= 0.33, p=0.01), ma non al sesso maschile o al livello di attività fisica. I parametri vascolari ottenuti mediante tonometria (pressione sistolica centrale, pressione di pulsazione centrale e PWV) hanno una stretta correlazione con i valori di PAS. Conclusioni La PAS centrale, ma non quella brachiale, è associata in maniera indipendente al consumo elevato di cibi ad alto contenuto di sale come il pane e gli snack fuori pasto. Questo fenomeno non è evidente considerando la sola PAS brachiale, probabilmente a causa del fenomeno di amplificazione dell’onda pressoria dal centro alla periferia. La pressione centrale e la PWV sono correlate positivamente con la PAS. Nel giovane adulto la misurazione della pressione centrale potrebbe fornire informazioni più accurate rispetto a quella brachiale

Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors

Resistant Hypertension: An Incurable Disease or Just a Challenge For Our Medical Skill?

Resistant hypertension is classically defined as a clinical condition in which target blood pressure values of 140/90 mmHg are not achieved despite an optimal pharmacological therapy of at least three antihypertensive drugs, including a diuretic. The aim of this review is to give an outline of the nosography of this disorder, highlighting the differences between true and apparent resistant hypertension. Since the proportions of patients who can be defined as resistant to antihypertensive treatment is elevated, this distinction is mandatory in order to identify only those who need special clinical attention and, possibly, newer non-traditional techniques. While at first glance resistant hypertension may appear as an insuperable problem, an accurate clinical work-up of these patients, aimed at excluding reversible causes and optimizing pharmacological treatment, represents an effective solution in most cases

Gender differences in the relationships between psychosocial factors and hypertension

Gender differences in the epidemiology, pathophysiology, clinical manifestations and outcomes of cardiovascular disease are well established but there is still a lack of awareness of this both in the general population and among healthcare providers. In addition to the traditionally recognized cardiovascular risk factors, more recently psychosocial risk factors such as stress, mood disorders, low socioeconomic status and sleep disorders have been linked to cardiovascular diseases and hypertension. Psychosocial factors may have different cardiovascular consequences in men and women; thus further efforts are required to explore pathophysiological mechanisms, to obtain gender-specific data from clinical trials and to translate this knowledge into everyday clinical practice

Acute limb ischemia in a patient with pre-fibrotic myelofibrosis complicated by heparin-induced thrombocytopenia and thrombosis - case report and systematic review of dabigatran use

A 49-year-old man was diagnosed with pre-fibrotic myelofibrosis after acute left lower-limb ischemia requiring amputation and portal vein thrombosis. After surgery he developed heparin-induced thrombocytopenia (HIT) with venous thromboembolism, successfully treated with argatroban followed by dabigatran. Our systematic review of the literature supports the use of dabigatran for suspected HIT

Eventos precoces condicionantes de doenças neurodegenerativas

Estudios clínicos sugieren que las complicaciones obstétricas están relacionadas con el desarrollo de alteraciones funcionales en el sistema nervioso central del individuo adulto. Una hipótesis establecida indica que las enfermedades neurodegenerativas estarían asociadas a un proceso iniciado por un estrés oxidativo temprano, y mediante distintos modelos experimentales tratamos de identificar cambios que pueden producirse durante la preñez, o al momento del nacimiento, relacionados con trastornos conductuales o cognitivos descriptos en enfermedades neurodegenerativas. De esta manera mediante una asfixia perinatal global que no afecta la sobrevida del individuo, hemos descripto alteraciones en las sinapsis de neoestriado e hipocampo, observando agregación proteica y ubiquitinación aumentada así como cambios en el contenido de actina, mientras que en retina describimos alteraciones en la actividad de la oxido nítrico sin-tasa. Resultados similares fueron reproducidos in vitro usando cultivos organotípicos, donde las estructuras del cerebro y las conexiones entre los diferentes núcleos se conservan. En un tercer modelo donde se induce una diabetes gestacional (DG) hemos evidenciado alteraciones importantes en las vías de señalización intracelular en cerebro embrionario involucradas en el proceso de muerte celular programada. En este mismo modelo estamos evaluando los efectos de la DG sobre la expresión de receptores hepáticos X y su relación con la expresión de la enfermedad de Alzheimer.Clinical studies suggest that obstetric complications are related to the development of functional alterations in the central nervous system of an adult. An established hypothesis suggests that neurodegenerative diseases would be associated to a process initiated by early oxidative stress. Then, using different experimental models, early changes that may occur during pregnancy or at the perinatal period related to behavioral or cognitive disorders described in neurodegenera-tive diseases are identified. Using the model of perinatal asphyxia without affecting the survival of the individual, changes in neostriatum and hippocampus synapses, such as increased protein aggregation and ubiquitination as well as changes in the actin content have been described. On the other hand, in the retina, alterations of nitric oxide synthase were also observed. Similar results were reproduced in vitro using organotypic cultures where the brain structures and connections between different nuclei are preserved. In a third model, induction of gestational diabetes (GD) has shown significant alterations in the intracellular signaling pathways involved in the embryonic brain related to programmed cell death. In this model, we are currently evaluating the effects of GD on the levels of liver X receptors and their possible relationship with the expression of Alzheimer disease.Estudos clínicos sugerem que as complicações obstétricas estão relacionadas com o desenvolvimento de alterações funcionais no sistema nervoso central do indivíduo adulto. Una hipótese estabelecida indica que as doenças neurodegenerativas estariam associadas a um processo iniciado por um estresse oxidativo precoce, e através de diferentes modelos experimentais procuramos identificar alterações que podem ser produzidas durante a prenhez, ou no momento do nascimento, relacionados com transtornos de conduta ou cognitivos descritos em doenças neurodegenerativas. Deste modo, mediante uma asfixia perinatal global que não afeta a sobrevida do indivíduo, temos descrito alterações nas si-napses de neoestriado e hipocampo observando agregação proteica e ubiquitinação aumentada bem como alterações no conteúdo de actina, ao passo que em retina descrevemos al-terações na atividade da óxido nítrico sintase. Resultados similares foram reproduzidos in vitro usando culturas organo-típicas, onde as estruturas do cérebro e as conexões entre os diferentes núcleos se conservam. Num terceiro modelo onde se induz uma diabetes gestacional (DG) temos evidenciado alterações importantes nas vias de sinalização intracelular em cérebro embrionário envolvidas no processo de morte celular programada. Neste mesmo modelo estamos avaliando os efeitos da DG sobre a expressão de receptores hepáticos X e sua relação com a expressão da doença de Alzheimer.Fil: Coirini, Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Kruse, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Rey, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Di Pilla, Marina Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Vega, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin

Impact of seasonality and air pollutants on carotid-femoral pulse wave velocity and wave reflection in hypertensive patients

The effects of seasonality on blood pressure (BP) and cardiovascular (CV) events are well established, while the influence of seasonality and other environmental factors on arterial stiffness and wave reflection has never been analyzed. This study evaluated whether seasonality (daily number of hours of light) and acute variations in outdoor temperature and air pollutants may affect carotid-femoral pulse wave velocity (PWV) and pressure augmentation

Molecular and Immune Biomarkers for Cutaneous Melanoma: Current Status and Future Prospects

Advances in the genomic, molecular and immunological make-up of melanoma allowed the development of novel targeted therapy and of immunotherapy, leading to changes in the paradigm of therapeutic interventions and improvement of patients&rsquo; overall survival. Nevertheless, the mechanisms regulating either the responsiveness or the resistance of melanoma patients to therapies are still mostly unknown. The development of either the combinations or of the sequential treatment of different agents has been investigated but without a strongly molecularly motivated rationale. The need for robust biomarkers to predict patients&rsquo; responsiveness to defined therapies and for their stratification is still unmet. Progress in immunological assays and genomic techniques as long as improvement in designing and performing studies monitoring the expression of these markers along with the evolution of the disease allowed to identify candidate biomarkers. However, none of them achieved a definitive role in predicting patients&rsquo; clinical outcomes. Along this line, the cross-talk of melanoma cells with tumor microenvironment plays an important role in the evolution of the disease and needs to be considered in light of the role of predictive biomarkers. The overview of the relationship between the molecular basis of melanoma and targeted therapies is provided in this review, highlighting the benefit for clinical responses and the limitations. Moreover, the role of different candidate biomarkers is described together with the technical approaches for their identification. The provided evidence shows that progress has been achieved in understanding the molecular basis of melanoma and in designing advanced therapeutic strategies. Nevertheless, the molecular determinants of melanoma and their role as biomarkers predicting patients&rsquo; responsiveness to therapies warrant further investigation with the vision of developing more effective precision medicine

Regression coefficients (95% CL) for daily O₃ concentrations in multiple regression analysis considering PWV as dependent variable according to BP-lowering treatment (a) and gender (b).

<p>Multiple regression models included sex, IFG / DM, hyperTG, CKD, BP-lowering treatment as discrete variables, and age, BMI, Mean T°C, Central SBP, DBP, heart rate, CO, Ozone, NO2 as continuous variables. In panel a), Black squares represent treated patients and gray squares untreated patients. In panel b), Black squares represent men and gray squares represent women.</p