Mercedes Cladellas

High oxidative stress in patients with stable coronary heart disease

Oxidized low density lipoprotein (oxLDL) plays a pivotal role in the development of atherosclerosis. The aim of the study was to investigate the relationship between oxLDL and other oxidative stress biomarkers with stable coronary heart disease (CHD). We compared the degree of oxidative stress in patients with CHD and sex-matched healthy control subjects in a case-control study. The study included 64 male subjects: 32 patients with stable CHD and 32 normal control subjects. Levels of circulating oxLDL were measured by a monoclonal antibody 4E6-based competition ELISA. Comparison of oxidative stress marker levels between cases and controls, adjusted for age, revealed significantly higher plasma oxLDL levels (63.32+/-25.49 vs. 37.73+/-20.58 U/l, P=0.001), lower serum levels of autoantibodies against oxLDL (341.53+/-350.46 vs. 796.45+/-1034.2 mU/ml, P=0.021), higher activities of the antioxidant enzymes superoxide dismutase in erythrocytes (951+/-70.2 vs. 771.6+/-191.2 U/g, P=0.032) and glutathione peroxidase in whole blood (GSH-Px: 10714.4+/-3705.4 vs. 5512.2+/-1498.1 U/l, P<0.001). The risk of having CHD was 20.6-fold greater (95% CI, 1.86-228.44, P=0.014) in the highest tertile of the oxLDL distribution than in the lowest, determined by logistic regression analysis on the combined study population after adjustment for age and other potential confounding factors. When the risk associated with GSH-Px levels was calculated, the odds ratio was 305.3 (95% CI, 5.07-18369.95, P=0.006) in the highest tertile compared with the lowest. Our results showed that an oxidative stress occurs in patients with CHD despite being clinically stable and under medical treatment. The combination of oxLDL levels and GSH-Px activity may be useful for the identification of patients with stable CHD.

Anti-inflammatory effect of virgin olive oil in stable coronary disease patients: a randomized, crossover, controlled trial

Objectives:To assess the effect of two similar olive oils, but with differences in their phenolic compounds (powerful antioxidant compounds), on inflammatory markers in stable coronary heart disease patients.Design:Placebo-controlled, crossover, randomized trial.Setting:Cardiology Department of Hospital del Mar and Institut Municipal d’Investigació Mèdica (Barcelona).Subjects:Twenty-eight stable coronary heart disease patients.Interventions:A raw daily dose of 50 ml of virgin and refined olive oil (ROO) was sequentially administered over two periods of 3-weeks, preceded by 2-week washout periods in which ROO was used.Results:Interleukin-6 (P<0.002) and C-reactive protein (P=0.024) decreased after virgin olive oil intervention. No changes were observed in soluble intercellular and vascular adhesion molecules, glucose and lipid profile.Conclusions:Consumption of virgin olive oil, could provide beneficial effects in stable coronary heart disease patients as an additional intervention to the pharmacological treatment.

Nuevos predictores de evolución a bloqueo auriculoventricular en pacientes con bloqueo bifascicular

Introduccion y objetivos Los pacientes con bloqueo bifascicular (BBF) pueden evolucionar a bloqueo auriculoventricular (BAV) avanzado, especialmente en presencia de sincope o intervalo HV prolongado. Otras variables podrian ayudar a definir que pacientes se beneficiaran de un marcapasos (MP) profilactico. Metodos Desde 1998 hasta 2006, hemos estudiado prospectivamente a 263 pacientes consecutivos con BBF en un solo centro. Se analizaron variables clinicas, electrocardiograficas y electrofisiologicas predictoras de evolucion a BAV significativo (segundo y tercer grado). Se implantaron dispositivos de estimulacion siguiendo las guias de la Sociedad Europea de Cardiologia. Los MP fueron programados en modo VVI con frecuencia minima de 40 lat/min. Se definio necesidad de MP la presencia de BAV significativo o de estimulacion ventricular > 10%. Resultados Se incluyo a 249 pacientes (media de edad, 73,4 ± 9,3 anos; 82 mujeres). Tras una mediana de seguimiento de 4,5 (2,16-6,41) anos, se observo necesidad de MP en 102 pacientes, 45 por estimulacion > 10% y 57 por BAV significativo. Las variables que predijeron la necesidad de MP fueron presencia de sincope o presincope (hazard ratio [HR] = 2,06; intervalo de confianza [IC] del 95%, 1,03-4,12), anchura QRS > 140 ms (HR = 2,44; IC del 95%, 1,59-3,76), la insuficiencia renal (HR = 1,86; IC del 95%, 1,22-2,83) y un intervalo HV > 64 ms (HR = 6,6; IC del 95%, 4,04-10,80). La asociacion de los cuatro factores mostro una probabilidad de necesitar el MP del 95% al ano de seguimiento. Conclusiones La clinica sincopal/presincopal, el QRS > 140 ms, la insuficiencia renal y el intervalo HV > 64 ms son predictores independientes de evolucion a BAV en pacientes con BBF.

Novel Predictors of Progression of Atrioventricular Block in Patients With Chronic Bifascicular Block

INTRODUCTION AND OBJECTIVES Patients with chronic bifascicular block (BFB) can progress to advanced atrioventricular block (AVB), especially when syncope or a prolonged HV interval is present. It is possible that other variables could help identify patients who would benefit from prophylactic pacemaker implantation. METHODS The study involved 263 consecutive BFB patients seen at a single center between 1998 and 2006. Clinical, electrocardiographic and electrophysiologic variables were analyzed to identify predictors of progression to significant AVB (i.e. second or third grade). Cardiac pacemakers were implanted in accordance with European Society of Cardiology guidelines. Pacemakers were programmed in the VVI mode with a minimum frequency of 40 beats/min. A pacemaker was required if there was significant AVB or a ventricular pacing percentage >10%. RESULTS In total, the study included 249 patients (mean age, 73.4+/-9.3 years, 82 female). After a median follow-up period of 4.5 years (2.16-6.41 years), a pacemaker was required by 102 patients: 45 had a ventricular pacing percentage >10% and 57 had significant AVB. Factors predictive of the need for a pacemaker were: the presence of syncope or presyncope (hazard ratio [HR]=2.06; 95% confidence interval [CI], 1.03-4.12), QRS width >140 ms (HR=2.44; 95% CI, 1.59-3.76), renal failure (HR=1.86; 95% CI, 1.22-2.83), and an HV interval >64 ms (HR=6.6; 95% CI, 4.04-10.80). The presence of all four risk factors was associated with a 95% probability of needing a pacemaker within 1 year of follow-up. CONCLUSIONS The presence of syncope or presyncope, a QRS width >140 ms, renal failure, and an HV interval >64 ms were independent predictors of progression to AVB in patients with BFB.

Prognostic Value of NT-proBNP and an Adapted Monin Score in Patients With Asymptomatic Aortic Stenosis

INTRODUCTION AND OBJECTIVES Our objective was to assess the prognostic value of NT-proBNP in patients with asymptomatic moderate/severe aortic stenosis and to validate an adapted Monin score using natriuretic peptide levels in our setting. METHODS Prospective study of 237 patients with degenerative asymptomatic moderate/severe aortic stenosis. NT-proBNP was determined in all patients, who were then followed up clinically. The adapted Monin score was defined as follows: (peak velocity [m/s]×2)+(logn NT-proBNP×1.5)(+1.5 if woman). A clinical event was defined as surgery, hospital admission due to angina, heart failure or syncope, or death. RESULTS A total of 51% were women, and the mean age was 74 years. Mean (SD) echocardiographic values were as follows: peak velocity 4.14 (0.87) m/s; mean gradient, 43.2 (16.0) mmHg; aortic valve area, 0.87 (0.72) cm(2), and aortic valve area index, 0.49 (0.14) cm(2)/m(2). The median NT-pro-BNP value was 490.0 [198.0-1312.0] pg/mL. There were 153 events during follow-up (median 18 months). The optimum NT-proBNP cut-point was 515 pg/mL, giving event-free survival rates at 1 and 2 years of 93% and 57%, respectively, in patients with NT-proBNP <515 pg/mL compared with 50% and 31% in those with NT-proBNP >515 pg/mL. Patients were divided into quartiles based on the Monin score. Event-free survival at 1 and 2 years was 87% and 79% in the first quartile, compared with 45% and 28% in the fourth quartile, respectively. CONCLUSIONS NT-proBNP determination provides prognostic information in patients with asymptomatic moderate/severe aortic stenosis. The adapted Monin score is useful in our setting and allows a more precise prognosis than does the use of NT-proBNP alone.

Effect of correction of anemia on echocardiographic and clinical parameters in patients with aortic stenosis involving a three-cuspid aortic valve and normal left ventricular ejection fraction.

The objective of the study is to investigate the impact of anemia (defined as hemoglobin concentration of <12 g/dl in women and 13 g/dl in men) on prognosis and to study the effect of recovery from anemia on echocardiographic and clinical parameters in patients with aortic stenosis (AS). This was a prospective study in 315 patients with moderate or severe AS. Patients with anemia received oral iron (ferrous sulfate with mucoproteose, 160 mg iron/day) and erythropoietin, if needed, or intravenous iron, if necessary. The following tests were performed before and after normalization of hemoglobin values: echocardiogram, 6-minute walk test, N-terminal B-type natriuretic peptide, and measures of depression, cognitive impairment, and dependence. Patient mean age was 74 years (SD 9). Mean follow-up was 25 months (SD 8). Anemia prevalence in the overall group was 22% (n = 70). Patients who are anemic had a higher rate of complications at follow-up (mortality, hospital admission, or need for valve procedure; 80% vs 62%, p = 0.009). In total, 89% of patients recovered from anemia, with a mean time to recovery of 4.6 weeks (SD 1.4). Improvements were observed on echocardiographic parameters of peak velocity (4.1 to 3.7 m/s, p = 0.02) and mean gradient (44 to 35 mm Hg, p = 0.02). Performance on the 6-minute walk test improved from 235 to 303 m (p <0.001). Median N-terminal B-type natriuretic peptide value decreased from 612 to 189 pg/dl (p <0.001). In conclusion, patients with AS and anemia have a worse prognosis than those without anemia. Resolution of anemia is associated with improvements in echocardiographic parameters and functional status, suggesting that treatment of iron deficiency is a relevant option in the management of patients with AS, particularly in nonoperable cases.

Phenotype and genotype characterization and twin association in patients with Anderson-Fabry cardiomyopathy.

Anderson-Fabry disease (FD), an X-linked recessive lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-Gal A) activity, is associated with cardiac manifestations including arrhythmias, valvular abnormalities, and cardiomyopathy. Early initiation of enzyme replacement therapy (ERT) may have the potential to delay the underlying clinical outcomes in patients with FD. Clinical electrocardiogram (ECG) and echocardiography were used to characterize the cardiomyopathy. Diagnosis of FD was performed by measuring the α-Gal A activity in plasma and mutation analysis by direct sequencing using capillary electrophoresis. We identified four adult hemizygous male patients with cardiomyopathy and other symptoms related to FD; two of them were monozygotic twins. In all cases, ECG and echocardiography showed severe left ventricular (LV) hypertrophy. Some years later, all patients showed typical symptoms of FD, including angiokeratomas and neurological, renal, gastrointestinal, and ocular involvement. A deficiency of α-Gal A activity and point mutations in exon 5 of the GLA gene were detected in all patients. ERT (agalsidase-alfa) was administered every other week as a 0.2 mg/kg intravenous infusion over 40 min. In conclusion, these findings highlight the importance of screening middle-aged patients with LV hypertrophy for the early detection of FD, particularly in direct-line relatives such as twins.