RESUMEN
BACKGROUND: Complement activation has been associated with atherosclerosis, atherosclerotic plaque destabilization and increased risk of cardiovascular events. Complement component 7 (CC7) binds to the C5bC6 complex which is part of the terminal complement complex (TCC/C5b-9). High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of systemic inflammation and may reflect the increased inflammatory state associated with cardiovascular disease. AIM: To evaluate the associations between CC7 and total- and cardiac mortality in patients hospitalized with chest-pain of suspected coronary origin, and whether combining CC7 with hsCRP adds prognostic information. METHODS: Baseline levels of CC7 were related to 60-months survival in a prospective, observational study of 982 patients hospitalized with a suspected acute coronary syndrome (ACS) at 9 hospitals in Salta, Argentina. A cox regression model, adjusting for conventional cardiovascular risk factors, was fitted with all-cause mortality, cardiac death and sudden cardiac death (SCD) as the dependent variables. A similar Norwegian population of 871 patients was applied to test the reproducibility of results in relation to total death. RESULTS: At follow-up, 173 patients (17.7%) in the Argentinean cohort had died, of these 92 (9.4%) were classified as cardiac death and 59 (6.0%) as SCD. In the Norwegian population, a total of 254 patients (30%) died. In multivariable analysis, CC7 was significantly associated with 60-months all-cause mortality [hazard ratio (HR) 1.26 (95% confidence interval (CI), 1.07-1.47) and cardiac death [HR 1.28 (95% CI 1.02-1.60)], but not with SCD. CC7 was only weakly correlated with hsCRP (r = 0.10, p = 0.002), and there was no statistically significant interaction between the two biomarkers in relation to outcome. The significant association of CC7 with total death was reproduced in the Norwegian population. CONCLUSIONS: CC7 was significantly associated with all-cause mortality and cardiac death at 60-months follow-up in chest-pain patients with suspected ACS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01377402, NCT00521976.
Asunto(s)
Síndrome Coronario Agudo/sangre , Angina de Pecho/sangre , Complemento C7/análisis , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/mortalidad , Anciano , Anciano de 80 o más Años , Angina de Pecho/diagnóstico , Angina de Pecho/mortalidad , Argentina , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Causas de Muerte , Femenino , Hospitalización , Humanos , Mediadores de Inflamación/sangre , Masculino , Persona de Mediana Edad , Noruega , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
INTRODUCTION: Naturally occurring antibodies are linked to inflammation, tissue injury and apoptosis, processes also linked to heart failure. Associations between antibodies, inflammation and myocardial damage, have not been elucidated in heart failure. OBJECTIVE: We investigated if 25 antibodies to receptors expressed in the cardiovascular system were associated with troponin-T, biomarkers of inflammation and clinical measures of disease severity, in patients with heart failure. METHODS: Antibodies in sera from patients (n=191) with ischemic (n=155) or non-ischemic (n=36) heart failure were measured with full-receptor sandwich enzyme-linked immunosorbent assays. All patients underwent coronary angiography with determination of left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP). Measured biomarkers included troponin-T, C-reactive protein, erythrocyte sedimentation rate, fibrinogen and neopterin. RESULTS: Stabilin-1-antibodies correlated with troponin-T (ß 0.23 p=0.008), soluble endoglin-antibodies with erythrocyte sedimentation rate (ß 0.19, p=0.007) and fibrinogen (ß 0.28, p<0.001). Platelet-derived growth factor subunit ß-antibodies were associated with neopterin (ß 0.17, p=0.002). All antibodies were correlated (R 0.26 to 0.91) and formed 4 principal components (PCs). Patients with high CRP and high PC2 had higher NYHA class and patients with high troponin-T and high PC1 had lower LVEDP (interactions, all p<0.05). CONCLUSION: Antibodies to receptors are correlated and are associated with biomarkers of inflammation and myocardial damage, which further modifies their association with disease severity in heart failure. Their functional activity and immunological function, remain undecided.
Asunto(s)
Autoanticuerpos/sangre , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Mediadores de Inflamación/sangre , Miocardio/patología , Anciano , Animales , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Células CHO , Moléculas de Adhesión Celular Neuronal/sangre , Estudios de Cohortes , Cricetinae , Cricetulus , Femenino , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Mapas de Interacción de Proteínas/fisiología , Receptores Sensibles al Calcio/sangre , Receptores Mensajeros de Linfocitos/sangre , Receptores de Factores de Crecimiento Endotelial Vascular/sangre , Troponina T/sangreRESUMEN
This paper reviews the current evidence regarding long-chained marine omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD), their possible mechanisms of action, and results of clinical trials. Also, primary and secondary prevention trials as studies on antiarrhythmic effects and meta-analyses are summarized. However, the individual bioavailability of n-3 PUFAs along with the highly different study designs and estimations of FAs intake or supplementation dosages in patient populations with different background intake of n-3 PUFAs might be some of the reasons for the inconsistent findings of the studies evaluating the impact of n-3 PUFAs on CVD. The question of an optimum dose of n-3 PUFAs or whether there exists a dose-response relation for n-3 PUFA supplementation is widely discussed. Moreover, the difficulties in interpreting meta-analyses are clearly demonstrated by two recently published meta-analyses (Rizos et al. and Delgado Lista et al.), evaluating the efficacy of n-3 PUFAs on CVD, including 12 common studies, but drawing opposite conclusions. We definitely need more large-scale, randomized clinical trials of long duration, also reporting harmful effects of n-3 PUFAs.
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BACKGROUND: Haptocorrin (HC) carries the major part of circulating cobalamin, but whether HC is altered on treatment with vitamin B12 remains unknown. METHODS: Our study included 3 populations: a population of vegan men (n = 174; vegan population), of whom 63 were treated daily with 5 mg of oral vitamin B12 for 3 months; a group of patients with a previous methylmalonic acid (MMA) concentration >0.4 micromol/L (n = 140; population with suspected deficiency), of which 69 were treated with weekly vitamin B12 injections (1 mg) for 4 weeks; and a subgroup of participants in a vitamin B intervention study (n = 88; nondeficient population), of whom 45 were treated daily with 0.4 mg of oral vitamin B12 for 3 months. Total HC and holoHC were measured by ELISA. Cobalamin was measured by an intrinsic factor (IF)-based assay. Samples were collected at baseline and 3 months after start of treatment. RESULTS: Compared with baseline results for the 3 study populations, total HC and holoHC increased 30 pmol/L for every 100 pmol/L increase in cobalamin. After treatment with vitamin B12, holoHC (P <0.0001) and total HC (P <0.0001) increased significantly in the vegan population. Only holoHC increased in the population with suspected deficiency (P <0.0001), whereas no alteration was observed in the nondeficient population. CONCLUSIONS: The HC concentration is decreased in severely cobalamin-deficient individuals and increases on treatment. The concentration of cobalamin also relates significantly to the HC concentration in nondeficient individuals.