535 research outputs found
The International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC): 2010–2015
No full textBackground Central and East European (CEE) patients with acute coronary syndromes (ACS) have worse outcomes than US and West European patients, including higher mortality rates. The aim of the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) was to define patient and treatment characteristics in order to examine whether differences in clinical and ethnic factors or healthcare organization may mediate the observed disparities in outcomes. Methods and results Between October 2010 and December 2015, 14,326 patients with ACS were prospectively enrolled. Of these patients 8650 (60%) had ST-segment elevation myocardial infarction (STEMI). Patients were enrolled from 41 centers in 12 countries in Europe. Standardized electronic case report forms were completed by trained study coordinators, and included fields relating to demographic factors, medical history and processes of inpatient care, supplemented with a detailed baseline interview on time delays to hospital admission. Blood sampling for genetic data were obtained at hospital discharge. Prospective individual patient follow-up was carried out with a focus on patient health (symptoms) and vital status. Thirty day follow-up was 100% complete. Difficulties were found for recruitment of patients at 6 months. Publications are available at ClinicalTrials.gov: NCT01218776. Conclusions ISACS-TC is a novel ACS registry with detailed information on CEE patients' clinical, demographic, treatment, and metabolic characteristics and health status. The concurrent enrollment of patients from some European Union founding members provides greater generalizability of the data. ISACS-TC may help to make an additional improvement in clinical outcomes of countries with economy in transition
Pathophysiology of acute coronary syndromes in the elderly
No full textElderly patients represent an important proportion of the acute coronary syndrome (ACS) population. Furthermore, this group of ACS patients is continuously growing because of the progressive ageing of the population. The ageing process implies marked changes in patient physiology that directly impact in their risk. However, there is a differential distribution in the risk of elderly patients, revealing the existence of a discrepancy between the chronological and the "biological age". This discrepancy has highlighted the need of performing individual risk assessment in order to identify those patients at higher risk. In addition, the lack of representation of elderly patients in clinical trials leads to the underutilization of evidence-based therapies in this group of patients. All these factors influence not only the high prevalence of ACS presentation in the elderly but also their worse prognosis after suffering an ischaemic event. Herein we will explore the pathophysiological mechanisms behind the age-related changes at the vascular and the cardiac level that explain the high risk of elderly subjects of suffering ACS and their worse prognosis
Up-regulation of reverse cholesterol transport key players and rescue from global inflammation by ApoA-I Milano
No full textBioinformatic platforms for clinical stratification of natural history of atherosclerotic cardiovascular diseases
No full textAlthough bioinformatic methods gained a lot of attention in the latest years, their use in real-world studies for primary and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD) is still lacking. Bioinformatic resources have been applied to thousands of individuals from the Framingham Heart Study as well as health care-associated biobanks such as the UK Biobank, the Million Veteran Program, and the CARDIoGRAMplusC4D Consortium and randomized controlled trials (i.e. ODYSSEY, FOURIER, ASPREE, and PREDIMED). These studies contributed to the development of polygenic risk scores (PRS), which emerged as novel potent genetic-oriented tools, able to calculate the individual risk of ASCVD and to predict the individual response to therapies such as statins and proprotein convertase subtilisin/kexin type 9 inhibitor. ASCVD are the first cause of death around the world including coronary heart disease (CHD), peripheral artery disease, and stroke. To achieve the goal of precision medicine and personalized therapy, advanced bioinformatic platforms are set to link clinically useful indices to heterogeneous molecular data, mainly epigenomics, transcriptomics, metabolomics, and proteomics. The DIANA study found that differential methylation of ABCA1, TCF7, PDGFA, and PRKCZ significantly discriminated patients with acute coronary syndrome from healthy subjects and their expression levels positively associated with CK-MB serum concentrations. The ARIC Study revealed several plasma proteins, acting or not in lipid metabolism, with a potential role in determining the different pleiotropic effects of statins in each subject. The implementation of molecular high-throughput studies and bioinformatic techniques into traditional cardiovascular risk prediction scores is emerging as a more accurate practice to stratify patients earlier in life and to favour timely and tailored risk reduction strategies. Of note, radiogenomics aims to combine imaging features extracted for instance by coronary computed tomography angiography and molecular biomarkers to create CHD diagnostic algorithms useful to characterize atherosclerotic lesions and myocardial abnormalities. The current view is that such platforms could be of clinical value for prevention, risk stratification, and treatment of ASCVD
The cardioprotection granted by metoprolol is restricted to its administration prior to coronary reperfusion
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Recombinant HDL Milano exerts greater anti-inflammatory and plaque stabilizing properties than HDL wild-type
No full textObjective: To verify the existence of association between plasma levels of pro- or anti-inflammatory mediators and atherosclerotic burden at coronary and carotid arteries in individuals aged of 80 or more years old.
Methods: Healthy individuals aged between 80 and 102 years old (n = 178) underwent evaluation of plasma cytokines and acute phase proteins, intima-media thickness (IMT) and presence of plaques in carotid arteries by ultrasound and coronary artery calcification (CAC) by cardiac computed tomography.
Results: There was no association between CAC and carotid plaques (p = 0.8), maximum (p = 0.06) or mean IMT (p = 0.2). No association was found between the presence of carotid plaques and CRP (p = 0.4), TNF-α (p = 0.8) or IL-10 (p = 0.2). Likewise, individuals in the first three quartiles for CRP, TNF-α or IL-10 had similar values of CAC, mean and maximum IMT. In contrast, individuals above the 75th percentile for CRP or for TNF-α had enhanced maximum IMT (p = 0.017 and p < 0.0001) and CAC (p = 0.026 and p = 0.01) and subjects with IL-10 levels above the 75th percentile had lower maximum IMT (p = 0.027) and CAC (p = 0.006) as compared with those below this percentile. There was no difference in mean IMT for individuals above or below the 75th percentile for CRP, TNF-α or IL-10.
Conclusion: In very old individuals, CAC and maximum IMT were positively associated with systemic inflammatory activity only in those above the 75th percentile. The markers of atherosclerotic burden at coronary and carotid arteries were not related to each other and were distinctly associated with pro- and anti-inflammatory mediators, suggesting that atherosclerosis development is different in these vascular beds
Prevención de la arterioesclerosis : efectos celulares y moleculares de intervenciones dietéticas y farmacológicas
No full textConsultable des del TDXTítol obtingut de la portada digitalitzadaLas enfermedades cardiovasculares son la primera causa de morbi/mortalidad en los países industrializados y también en los países en vías de desarrollo. El sustrato patológico más importante en la etiología de estas enfermedades es la formación de la placa ateromatosa y la subsiguiente trombosis, potenciados ambos por la presencia de factores de riesgo como la dislipemia, el tabaquismo y la hipertensión. Uno de los principales objetivos en la prevención de las enfermedades cardiovasculares es el tratamiento de la hiperlipemia. Esta tesis analiza las dos principales estrategias de prevención de las enfermedades cardiovasculares en la reducción de las concentraciones séricas de colesterol: la modificación de la dieta, centrándonos en un único componente de la dieta Mediterránea (el vino tinto), y el tratamiento con fármacos hipolipemiantes (pravastatina). El objetivo de esta tesis es investigar los mecanismos moleculares de acción de ambas estrategias preventivas en la inhibición del riesgo trombótico en el modelo experimental porcino de hipercolesterolemia inducida con dieta. Para evaluar el efecto antitrombótico del vino tinto y de la pravastatina se ha estudiado la deposición plaquetaria, desencadenada tras perfundir sustratos vasculares homólogos en una cámara de perfusión cilíndrica o reactor de flujo (Badimon L, 1987). Los animales se alimentaron durante 100 días con pienso hipercolesterolémico que simula la dieta de los países industrializados (2% de colesterol y 20% de grasas saturadas). Se estudiaron tres dosis de vino tinto (20, 30 y 40g alcohol/día), administradas junto a la ración diaria de pienso, en tres grupos diferentes de animales y se compararon con el grupo control (solamente pienso hipercolesterolémico sin ingesta de vino). Al finalizar el período experimental y tras realizar análisis bioquímicos y hematológicos los animales se sometieron al estudio de trombosis desencadenada por sustratos vasculares moderada y severamente lesionados. Se emplearon dos tipos de cámaras de perfusión para obtener las velocidades de flujo deseadas, 212 s-1 (velocidad baja, típica de arterias coronarias ligeramente estenosadas) y 1690 s-1 (velocidad alta, modelo de arterias coronarias estenosadas). También se analizaron los cambios en la traslocación de RhoA en las plaquetas y la expresión de factor tisular (FT) en monocitos. La deposición plaquetaria en la pared disminuyó significativamente en los animales que habían ingerido vino junto con el pienso comparados con los animales controles. La expresión de RhoA en el citoplasma plaquetario (forma inactiva) aumentó en los grupos con ingesta de vino, mientras que la expresión en la membrana plaquetaria (forma activa) disminuyó. La expresión de FT en los monocitos estimulados con LPS (lipopolisacárido) disminuyó en los animales que habían ingerido vino. Los niveles de colesterol no fueron significativamente diferentes entre los grupos de estudio. En el siguiente estudio los animales se alimentaron durante 100 días con pienso hipercolesterolémico, pero durante los 50 últimos días un grupo se trató con una dosis de 5mg/kg de pravastatina y el otro con placebo. Ambos grupos fueron comparados con el grupo control (animales que durante 100 días se alimentaron con pienso normocolesterólemico). Al finalizar el período experimental se evaluó el riesgo trombótico empleando un reactor de flujo (cámara) de segunda generación; una cámara de perfusión que permite una velocidad de cizalladura de 212s-1 con estenosis del 70% en la zona central (Badimon L, 1991). También se evaluó la expresión de RhoA en la membrana plaquetaria y la del FT en la pared vascular. El tratamiento con pravastatina inhibe significativamente la deposición plaquetaria sobre pared vascular lesionada (ligera y severamente) sin que se observe una diferencia significativa en los niveles plasmáticos de colesterol entre los dos grupos hipercolesterolémicos. Además la pravastatina redujo la expresión de RhoA en la membrana plaquetaria y la expresión de FT en la pared vascular de los animales tratados. Podemos concluir que el consumo moderado de vino y el tratamiento con pravastatina son capaces de disminuir el riesgo trombótico en condiciones de hipercolesterolemia sostenida, es decir, sin disminuir el aporte externo de colesterol y grasas saturadas. Esto significa que ambos actúan también por mecanismos independientes a la disminución de los lípidos plasmáticos, sugiriendo un efecto directo sobre la actividad de la plaqueta y la interacción plaqueta-pared vascular.Cardiovascular diseases cause more than 16 millions deaths every year. The main pathologic substrate for these diseases is the atherothrombotic process, a multifactorial and silent process that starts in the childhood and progresses through life. Clinical manifestation develops at the 3 or 4th decade of life. The velocity of progression and the severity of clinical manifestations depends on the presence of risk factors such as elevated plasmatic cholesterol, tobacco and hypertension. The main objective in preventing cardiovascular diseases is the management and treatment of hypercholesterolemia. In this Ph.D two principal strategies in prevention of cardiovascular diseases by reducing plasmatic cholesterol levels have been analyzed: diet modifications (focused in red wine as a component of Mediterranean diet) and treatment with lipid-lowering drugs (studies with pravastatin). The objective of this Ph.D is to investigate the molecular mechanisms of action of both preventive strategies in the inhibition of thrombotic risk in the porcine experimental model of cholesterol-clamp induced by diet. The antithrombotic effects of red wine and pravastatin in platelet deposition triggered by homologous vascular tissues have been analyzed in a ex vivo perfusion chamber (Badimon L, 1987). Animals were fed for 100 days with cholesterol rich diet similar to that ingested in western countries (20% saturated fats, 1% cholic acid and 2% cholesterol). Three doses of wine (20, 30 y 40g wine ethanol/day) were given to three different groups of animals and compared to the hypercholesterolemic control group. At the end of the experimental period and after biochemical and haematological controls, thrombotic risk was assessed by exposure of blood from studied animals to a thrombogenic damaged arterial vessel wall in the previously validated and standardized Badimon flow chamber. Two different perfusion chamber were used to achieve shear rates of 212/s (low shear, model of patent coronary arteries) and 1690/s (high shear rate, model of mildly stenotic coronary arteries). Perfusions were run over homologous porcine vessel wall with two types of damage: mild (aortic subendothelium, model of erosion) and severe, mechanically ruptured vessel wall (tunica media, model of severe injury). Platelet aggregation and changes in RhoA translocation, tissue factor (TF) gene-expression in not/induced monocytes, lipid plasma composition and LDL oxidazability (MCD, Maximal Conjugated Diene formation) were analyzed as possible targets of red wine activity. Blood thrombogenicity, measured as platelet deposition rate (Total Platelet Deposition /min of perfusion), was statistically reduced (P<0.05) in animals ingesting red wine compared with control hypercholesterolemic animals. Expression of RhoA in the platelet cytoplasm (inactive form) was increased for animals ingesting red wine, while RhoA membrane expression (active form) was reduced in wine-fed animals. TF expression was reduced in LPS-stimulated monocytes in animals ingesting red wine. Plasma cholesterol levels were not different among groups of study, but groups ingesting red wine showed beneficial improvement of oxidation parameters. In the second study, animals were fed a cholesterol-rich diet (2% cholesterol; 1% cholic acid; 20% beef tallow) for 100 days (hypercholesterolemic group). The hypercholesterolemic diet was administered during the first 50 days to induce sustained hyperlipemia derived from cholesterol absorption and, thus, diminishing cholesterol synthesis. Then, pigs started an oral daily treatment with pravastatin (5mg/kg) or placebo for the last 50 days of the hypercholesterolemic diet. A group of four animals was fed, for the same period of time, a commercial chow (normocholesterolemic group). At the end of the experimental period and after biochemical and haematological controls, thrombotic risk was assessed by exposure of blood from studied animals to a thrombogenic damaged arterial vessel wall in the previously validated and standardized Badimon flow chamber. Deposition of radio-labelled platelets was evaluated using a second generation flow chamber that allows a shear rate of 212/s with a 70% of stenosis in the central segment (Badimon L, 1991). RhoA expression in the platelet membrane and TF in the vascular wall were also evaluated. Pravastatin treatment significantly inhibits mural thrombosis triggered by both eroded and disrupted vessel wall without reducing plasma lipid levels in the hypercholesterolemic animals. The expression of RhoA in platelet membrane and TF expression in arterial wall were significantly reduced in animals treated with pravastatin. We can conclude that moderate wine intake and pravastatin treatment reduce thrombotic risk in cholesterol-clamp conditions, therefore mechanisms of action operate through pathways both dependent and independent from plasma cholesterol lowering effects suggesting a direct effect over platelet activity and platelet-vessel wal interaction
Management of no-reflow
No full textDespite considerable progress in percutaneous coronary interventions, the phenomenon of coronary no-reflow (NR) still represents a serious problem. It occurs when cardiac tissue fails to perfuse normally despite opening of the occluded vessel. The consequences of NR include infarct expansion, early congestive heart failure, ventricular arrhythmias and adverse left ventricular remodeling. All the actions that improve myocardial tissue perfusion should convert into a better prognosis and a better clinical outcome. The pathophysiology of NR is still not fully elucidated, and several mechanisms are proposed, with microvascular obstruction as the leading one. Despite considerable progress in the identification of the risks to NR development, no specific therapies have been developed so far. In this review, pharmacological and nonpharmacological interventions that might improve coronary blood flow are discussed
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