Showing papers by "Francisco Marín published in 2003"

Soluble E-selectin in cardiovascular disease and its risk factors A review of the literature

Abstract: The initial steps in the pathogenesis of atherosclerosis involve changes to the vascular endothelium, which produces numer-ous substances involved in the regulation and maintenance of vascular integrity and the homeostasis of the coagulation/fibri-nolysis system. A further change in endothelial physiology is an increase in the surface expression of cell adhesion molecules, such as E-selectin, which regulate adhesive interactions between certain blood cells and endothelium. As E-selectin is only expressed on activated endothelium, it therefore provides an opportunity to study pathophysiological aspects of this cell in cardiovascular and other disease. However, a soluble form of E selectin (i.e. sE-selectin) can be found in the plasma. This review will focus on sE-selectin, and its potential role in the pathogenesis of cardiovascular disease as raised levels have been found in hypertension, diabetes and hyperlipidemia, although its association in established atherosclerosis disease and its value as a prognostic factor is more controversial.

Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation.

Abstract: Background A prothrombotic or hypercoagulable state has been described in AF, which could increase the risk of thromboembolism. As inflammation has been related to thrombogenesis and endothelial activation, we hypothesised that the prothrombotic state in AF (as assessed by an index of thrombogenesis, prothrombin fragment 1+2 [F1+2]) and endothelial activation (soluble E-selectin (sEsel)) could be related to an index of inflammation (interleukin-6 (IL-6)). Patients and methods We studied 191 consecutive patients (98 male; mean age 72.3±9.2years) with chronic non-rheumatic AF who were not on anticoagulant therapy. Plasma IL-6, sEsel and F1+2 were measured by ELISA. Research indices were compared to 74 controls in sinus rhythm matched for age and sex. In 43 patients with AF, the effects of introducing anticoagulation (INR 2.0–3.0) were also studied. Results Patients with AF had elevated levels of F1+2 (p<0.001) and IL-6 (p=0.045), but not sEsel. There was no significant correlation between F1+2 and IL-6. In multivariate analysis, only F1+2 levels were independently associated with the presence of AF (p=0.001). After oral anticoagulation, plasma levels of F1+2 and sEsel were significantly decreased (both p <0.01). Conclusion High levels of IL-6 in AF suggest an inflammatory state, which appears to be more related to clinical variables of the patients, rather than to the presence of AF per se. There was no association of inflammation with endothelial activation (sEsel) or the presence of abnormal thrombogenesis (high F1+2 levels) in AF. Moreover, no changes in IL-6 levels were found despite the reduction of the other markers by oral anticoagulant therapy.

Is Thrombogenesis in Atrial Fibrillation Related to Matrix Metalloproteinase-1 and Its Inhibitor, TIMP-1?

Abstract: Background and Purpose— Decreased matrix metalloproteinase-1 (MMP-1) and increased levels of its inhibitor, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), reflect impaired matrix degradation with an increase in fibrosis. A prothrombotic state has been described in atrial fibrillation (AF), increasing the risk of stroke and thromboembolism. Because structural abnormalities and remodeling of atria have been observed in AF, we hypothesized that the prothrombotic state in AF may be related to abnormal indexes of matrix degradation. Methods— We studied 48 consecutive patients (30 men; age, 70.5±9.0 years) with chronic nonrheumatic AF who were not on anticoagulation. Plasma levels of MMP-1, TIMP-1, and prothrombin fragment 1+2 (F1+2, an index of thrombogenesis) were measured by enzyme-linked immunosorbent assay. M-mode, 2-dimensional, and Doppler echocardiographic studies were performed in all patients. Research indexes were compared with data from 32 control subjects in sinus rhythm who were of simil...

Valor pronóstico de los niveles séricos del factor de necrosis tumoral alfa en pacientes con insuficiencia cardíaca

Abstract: Introduccion y objetivos El factor de necrosis tumoral alfa es una citocina inflamatoria que se eleva en la insuficiencia cardiaca, con valor pronostico en casos graves, aunque menos establecido en casos moderados. Pretendemos conocer su valor pronostico en los casos de un hospital secundario. Pacientes Se estudian 50 pacientes de 59,5 ± 12,3 anos, con miocardiopatia dilatada (72% no isquemica), con insuficiencia cardiaca moderada (clase funcional II, 59%). Metodos Se realizo un ecocardiograma y una ergoespirometria (Naughton), y se determinaron la fuerza muscular (dinamometro de mano) y los valores plasmaticos del factor de necrosis tumoral; se efectuo un seguimiento de 17,5 ± 9 meses (intervalo, 1–29), en el que se recogieron la mortalidad total, el trasplante cardiaco y el reingreso por insuficiencia cardiaca. Resultados Tuvieron episodios 23 pacientes, que tenian mayor edad (63 ± 12,7 frente a 55,7 ± 11,4 anos; p = 0,042), un VO2 pico (pVO2) mas bajo (13,7 ± 3,9 frente a 16 ± 3,3 ml/kg/min; p = 0,035), y una relacion pVE/VCO2 y valores del factor mas elevados (41,9 ± 10,6 frente a 33,2 ± 5,7; p = 0,001 y 4,3 [3,1–7,9] frente a 3,3 [2,4–4,3] pg/ml; p = 0,021, respectivamente). En el analisis de Cox, la unica variable con valor pronostico independiente fue la relacion pVE/VCO2 (RR = 1,13 [1,07–1,19]; p Conclusiones Nuestros pacientes con episodios tienen mayor edad, un pVO2 menor y la relacion pVE/VCO2 y los valores sericos del factor de necrosis tumoral mas elevados, aunque solo el pVE/VCO2 tiene valor pronostico independiente.

NT-proBNP y desplazamiento del plano auriculoventricular. Relación e implicaciones diagnósticas

Abstract: Introduction and objectives. NT-proBNP is useful in the diagnosis of heart failure and ventricular dysfunction. Left atrioventricular plane displacement (AVPD) is a consolidated index of ventricular function. Our objective was to carry out a multicenter population-based study to establish the relationship between plasma NT-proBNP levels with AVPD values. Patients and method. We studied 215 subjects (age 66 ± 9 years; 57.7% women) chosen from a random sample of 432 people from the Community of Valencia, who previously reported suffering from some degree of dyspnea. Doppler echocardiography was done, AVPD was calculated and plasma NT-proBNP concentrations were determined. All studies were completed in 194 patients. Results. For the whole population NT-proBNP was 88 (02,586) pg/ml and AVPD was 11.9 ± 1.6 mm. NT-proBNP concentration correlated well with AVPD (r = 0.44; p < 0.00001), and higher peptide levels were obtained in AVPD quartiles that indicated less displacement (p < 0.05). When NT-proBNP values were grouped according to their association with AVPD lower or higher than the 50th percentile AVPD, the difference was significant at p < 0.01. When AVPD values lower and higher than 10 mm were compared, NT-proBNP values were higher in persons with AVPD lower than 10 mm (p < 0.05). Conclusions. This population study found higher NTproBNP concentrations in subjects with lower AVPD, and illustrates the potential diagnostic usefulness of NTproBNP in clinical practice.

[Angiogenesis and statins, the highest the dose the best? ].

Abstract: We read with great interest the excellent review article by Llevadot and Asahara on the effect of statins in angiogenesis.1 Although it was suggested that angiongenesis might be involved in the progression of coronary lesions,2 as its name indicates, this is a complex process that leads to the formation of new vessels from preexisting ones.3 Thus, induction of angiogenesis by this group of drugs may be just another of their various nonlipidic properties,4 such as improved endothelial function, reduced inflammatory response and attenuated plaque thrombogenicity. These effects may be involved in the clinically observed benefits in both primary and secondary prevention in clinical trials that have tested statins. In recent years proof of the benefits of greater reductions in lipid levels as a result of increased doses of statins5 has raised the following questions: do the benefits increase with decreasing lipid levels? Do they increase with higher doses of statins? Hypercholesterolemia has been seen to lead to worsening angiogenesis.6 In their review, Llevadot and Asahara1 show how statins reverse this condition. How-ever, the considerable antiinflammatory effect of statins7 may have important consequences, which are not always favorable. When attacked, the endothelium undergoes functional and structural changes. In principle the inflammatory response is beneficial in protecting the individual against noxious agents. Ischemia and inflammation are among the main angiogenesisstimulating agents.8 Thus, in patients with coronary arteriosclerosis, suppressing the «adaptive» inflammatory mechanism might delay the development of collateral circulation in response to episodes of ischemia. Expe-rimental studies recently showed that statins can have a biphasic effect on angiogenesis.9,10 At low doses they increased angiogensis, whereas this effect was significantly reduced at higher doses. These findings confirm the need for further studies to analyze the effect of high doses of statins in humans, and to evaluate their long-term clinical benefits.