Joaquín Barba

Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction

To determine the effect of transplantation of undifferentiated and cardiac pre‐differentiated adipose stem cells compared with bone marrow mononuclear cells (BM‐MNC) in a chronic model of myocardial infarction.

Ultrasonic Backscatter and Serum Marker of Cardiac Fibrosis in Hypertensives

Elevations in the serum concentration of the carboxy-terminal propeptide of procollagen type I (PIP) >127 &mgr;g/L have been found to predict severe myocardial fibrosis in hypertensive patients. This study was designed to assess whether ultrasonic reflectivity, evaluated by a real-time integrated backscatter analysis, was related to the severity of myocardial fibrosis as estimated by serum PIP. Thirty-four subjects were included in the study. Serum PIP was measured by specific radio immunoanalysis. Backscatter cyclic variation and maximal intensity were measured in 6 regions throughout the left ventricle. The subjects were divided into 3 groups: 14 normotensives with PIP <127 &mgr;g/L (group 1), 12 hypertensives with PIP <127 &mgr;g/L (group 2), and 8 hypertensives with PIP >127 &mgr;g/L (group 3). The highest cyclic variation was found in group 1 and the lowest in group 3 (5.78±0.25 versus 4.70±0.33 dB, P <0.05), with intermediate values in group 2 (5.10±0.27 dB). No differences in maximal intensity were found among the 3 groups of subjects. Using receiver operating characteristics curves, we observed that a cutoff of 2.90 dB for cyclic variation measured in the apex provided 75% sensitivity and 63% specificity for predicting PIP >127 &mgr;g/L in hypertensives, with a relative risk of 2.50 (95% CI, 0.72 to 34.70). These results show an association between diminished cyclic variation of backscatter and increased serum concentration of PIP in hypertension. Thus, the combination of these 2 parameters may be useful for the diagnosis of severe myocardial fibrosis associated with hypertension.

Is plasma cardiotrophin-1 a marker of hypertensive heart disease?

Objective This study was designed to investigate whether plasma concentration of cardiotrophin-1 (CT-1), a cytokine that induces cardiomyocyte hypertrophy and stimulates cardiac fibroblasts, is related to hypertensive heart disease, as defined by the presence of echocardiographically assessed left ventricular hypertrophy (LVH). Methods The study was performed in 31 normotensive subjects and 111 patients with never-treated essential hypertension (54 without LVH and 57 with LVH). Causes of LVH other than hypertension were excluded after a complete medical workup. A novel enzyme-linked immunosorbent assay was developed to measure plasma CT-1. Results Plasma CT-1 was increased (P < 0.001) in hypertensives compared with normotensives. The value of CT-1 was higher (P < 0.001) in hypertensives with LVH than in hypertensives without LVH. Some 31% of patients without LVH exhibited values of CT-1 above the upper normal limit in normotensives. A direct correlation was found between CT-1 and left ventricular mass index (r = 0.319, P < 0.001) in all subjects. Receiver operating characteristic curves showed that a cutoff of 39 fmol/ml for CT-1 provided 75% specificity and 70% sensitivity for predicting LVH with a relative risk of 6.21 (95% confidence interval, 2.95 to 13.09). Conclusions These results show an association between LVH and the plasma concentration of CT-1 in essential hypertension. Although preliminary, these findings suggest that the determination of CT-1 may be an easy and reliable method for the initial screening and diagnosis of hypertensive heart disease.

Association of plasma acylated ghrelin with blood pressure and left ventricular mass in patients with metabolic syndrome.

Objective The gut-derived hormone, ghrelin, improves cardiac function in healthy individuals and patients with chronic heart failure. The aim of this study was to investigate whether the major isoforms of the hormone, acylated and desacyl ghrelin, are related to inappropriate left ventricular mass in patients with the metabolic syndrome (MetS). Methods and results Plasma concentrations of ghrelin forms were measured in 180 white participants (65 normal weight, 60 obese without MetS and 55 obese with MetS; 56% men). MetS was defined according to Adult Treatment Panel III criteria. The presence of left ventricular hypertrophy (LVH) was diagnosed by sex-specific left ventricular mass/height2.7 cut-off values (>49.2 g/m2.7 for men and >46.7 g/m2.7 for women). Circulating concentrations of acylated ghrelin were increased in obesity and MetS, whereas desacyl ghrelin levels were decreased. Compared with participants in the lowest tertiles, the age-adjusted and sex-adjusted odds of having MetS were lower in the highest category of desacyl ghrelin (odds ratio 0.1, 95% confidence interval 0.1–0.4, P < 0.001). The prevalence of LVH was increased in the highest tertile of acylated ghrelin (odds ratio 3.4, 95% confidence interval 1.7–5.6, P < 0.05). Plasma acylated ghrelin was increased (P < 0.05) in patients with MetS exhibiting LVH compared with those with appropriate left ventricular mass, whereas plasma desacyl ghrelin was not changed (P = 0.490). Conclusion Acylated ghrelin was positively associated with SBP and left ventricular mass indices, even after correction for BMI. These results suggest that the increased acylated ghrelin concentrations may represent a compensatory mechanism to overcome the development of hypertension and LVH in patients with MetS.

Association of Increased Plasma Cardiotrophin-1 With Inappropriate Left Ventricular Mass in Essential Hypertension

Inappropriate left ventricular mass is present when the value of left ventricular mass exceeds individual needs to compensate hemodynamic load imposed by increased blood pressure. The goal of this study was to investigate whether plasma concentration of cardiotrophin-1, a cytokine that induces exaggerated hypertrophy in cardiomyocytes with hypertensive phenotype, is related to inappropriate left ventricular mass in patients with essential hypertension. The study was performed in 118 patients with never-treated hypertension and without prevalent cardiac disease. The left ventricular mass prediction from stroke work (systolic blood pressure×Doppler stroke volume), sex, and height (in meters2.7) was derived. An observed left ventricular mass/predicted left ventricular mass value >128% defined inappropriate left ventricular mass. Plasma cardiotrophin-1 was measured by an enzyme-linked immunosorbent assay. The studies were repeated in a group of 45 patients after 1 year of antihypertensive treatment. At baseline 67 and 51 patients presented with appropriate and inappropriate left ventricular mass, respectively. Plasma cardiotrophin-1 was higher (P<0.001) in patients with inappropriate mass than in patients with appropriate mass and normotensive controls. A direct correlation was found between cardiotrophin-1 and observed left ventricular mass/predicted left ventricular mass ratio (r=0.330, P<0.001) in all hypertensive patients. After treatment, plasma cardiotrophin-1 decreased and increased in patients in which inappropriate left ventricular mass regressed and persisted, respectively, despite a similar reduction of blood pressure in the 2 subgroups of patients. Albeit descriptive in nature, these results suggest the hypothesis that an excess of cardiotrophin-1 may contribute to inappropriate left ventricular growth in hypertensive patients.

Usefulness of plasma cardiotrophin-1 in assessment of left ventricular hypertrophy regression in hypertensive patients.

Objective We investigated whether regression of left ventricular hypertrophy (LVH) in response to antihypertensive treatment is associated with plasma cardiotrophin-1 (CT-1) in hypertensive patients. Methods The study was performed in 47 patients with mild to moderate essential hypertension, and LVH was assessed echocardiographically. The family doctor gave antihypertensive treatment and followed all patients. LVH regression was diagnosed if the baseline left ventricular mass index (LVMI) decreased to normal values after 1 year of treatment. Plasma CT-1 was determined by an enzyme-linked immunosorbent assay. Results The LVMI was normalized in 23 patients (49%) and persisted at an abnormally increased level in 24 patients (51%) after 1 year of treatment, whereas the reduction in clinic and home blood pressure was similar in the two groups: CT-1 decreased (−48%, P < 0.005) and increased (+35%, P < 0.05) in patients in whom LVH regressed and LVH persisted, respectively. Final values of CT-1 were inversely correlated (r = 0.534, P < 0.001) with the decrease in LVMI after treatment in all patients. A significant association (χ2 = 16.87, P < 0.001) was found between normalization of CT-1 and regression of LVH with treatment. A cut-off value of 41 fmol/ml for CT-1 provided a relative risk of 43.13 (95% confidence interval, 4.88–380.48) for detecting LVH regression. Conclusion These results show an association between treatment-induced decrease of plasma CT-1 and LVH regression in essential hypertension. Although preliminary, these findings suggest that the determination of plasma CT-1 may be useful for the follow-up of hypertensive heart disease in routine clinical practice.

Association of plasma cardiotrophin-1 with stage C heart failure in hypertensive patients: Potential diagnostic implications

Cardiotrophin-1 is a cytokine that induces hypertrophy and dysfunction in cardiomyocytes and has been shown to be increased in hypertensive patients. The objective of this study was to evaluate the association of cardiotrophin-1 with heart failure (HF) in hypertensive patients and its usefulness as a biomarker of stage C heart failure. Hypertensive patients without cardiac abnormalities (stage A, n = 64), with left ventricular hypertrophy (LVH) (stage B, n = 58), and with left ventricular hypertrophy and clinical manifestations of chronic heart failure (stage C, n = 39) were studied. Plasma cardiotrophin-1 was measured by an enzyme-linked inmunosorbent assay. Plasma cardiotrophin-1 progressively increased (P < 0.001), along with progression of heart failure stages, in hypertensive patients. Plasma cardiotrophin-1 was directly (r = 0.416, P < 0.001) and inversely (r = 0.263, P < 0.01) correlated with left ventricular (LV) mass index and ejection fraction, respectively, in all hypertensive patients. These associations were independent of a number of potential confounding factors. Receiver operating characteristic curves showed that a cut-off of 48.72 fmol/ml for cardiotrophin-1 provided higher sensitivity for diagnosing stage C heart failure than a cut-off of 375.54 pg/ml for amino-terminal probrain natriuretic peptide (NT-proBNP) (80% vs. 72%). Sixty-four percent of stage C hypertensive patients with NT-proBNP values below 375.54 pg/ml value exhibited cardiotrophin-1 values above 49.16 fmol/ml. These findings indicate that plasma cardiotrophin-1 is associated with progression of heart failure in hypertensive patients. Cardiotrophin-1 measurement may provide additional information to that afforded by NT-proBNP to diagnose stage C heart failure in these patients.

Independent Association of Fibrinogen with Carotid Intima-Media Thickness in Asymptomatic Subjects

Background: Fibrinogen has been found to be an independent risk factor for cardiovascular disease. Both genetic and environmental factors contribute to its variability in plasma. However, whether the relation between fibrinogen and carotid intima-media thickness (IMT) is independent of those factors has not been established. Therefore, the aim of this study was to investigate the relations of plasma fibrinogens and the –455 G/A Bβ-fibrinogen polymorphism with the carotid IMT in a series of asymptomatic subjects. Methods: Markers of inflammation, C-reactive protein (CRP) and leukocytes, and endothelial perturbation (von Willebrand factor, vWF) were measured in 135 subjects. All individuals underwent a complete clinical examination and lipid measurements (cholesterol and its fractions HDL and LDL and triglycerides). The carotid IMT was measured by B-mode ultrasound in the common carotid artery. Results: Patients in the highest fibrinogen tertile had a significantly higher BMI (p < 0.01), LDL-cholesterol (p < 0.01), leukocyte count, CRP and vWF (p < 0.001). In the univariate model a strong positive relationship was found between plasma fibrinogen and carotid IMT (p < 0.01). Fibrinogen also correlated positively with age, BMI, arterial systolic pressure, cholesterol, cholesterol-LDL, smoking, CRP and vWF (p < 0.01). In the multivariate analysis, the association of fibrinogen with carotid IMT remained significant (p < 0.01) after adjustment for all the parameters analyzed. Conclusion: In a population sample of adults without clinically overt atherosclerotic disease, elevated fibrinogen was related to carotid IMT independent of a wide range of important confounding variables.

Ultrasonic backscatter and diastolic function in hypertensive patients.

This study was designed to assess whether ultrasonic reflectivity, evaluated by a real-time integrated backscatter analysis, was related to the severity of diastolic dysfunction, as studied by Doppler echocardiography in patients with essential hypertension. One hundred nine subjects were included in the study. Diastolic function was assessed by mitral-inflow Doppler ultrasound recordings. Backscatter cyclic variation and maximal intensity were measured in 6 regions throughout the left ventricle. The subjects were classified in 5 groups according to blood pressure and diastolic function: 29 normotensives with normal diastolic function (group 1), 18 hypertensives with normal diastolic function (group 2), 47 hypertensives with a delayed relaxation pattern (group 3), 11 hypertensives with a pseudonormal filling pattern (group 4), and 4 hypertensives with a restrictive filling pattern (group 5). The highest cyclic variation was found in groups 1 and 2, the lowest in groups 4 and 5 (5.7±0.2 dB in group 1 and 5.7±0.2 dB in group 2 versus 2.9±0.3 dB in group 4 and 2.1±0.4 dB in group 5;P <0.001), with intermediate values in group 3 (5.2±0.2 dB). Cyclic variation was inversely correlated with left ventricular chamber stiffness (P <0.05) and directly correlated with midwall fractional shortening (P <0.02) in all hypertensives. No differences in maximal intensity were found among the 5 groups of subjects. These results show an association between diminished cyclic variation of backscatter and deterioration of diastolic function in hypertensive patients. Thus, alterations in this parameter may be useful for the assessment of diastolic dysfunction in hypertension.

Estudio de riesgo vascular en Navarra: objetivos y diseño. Prevalencia del síndrome metabólico y de los factores mayores de riesgo vascular

Background. To determine in a representative sample of the population the prevalence of risk factors and metabolic syndrome; their association with sub-clinical atherosclerotic lesions and their impact on cardiocerebrovascular disease 10 years after. Material and Methods. (Phase 1) Cross sectional survey of a random sample stratified by age and sex of the population of Navarre aged between 35 and 84. Antecedents, risk factors, physical and analytical exploration. (Phase II) Ten year follow-up cohort study, in 500 exposed to MS and 500 not exposed persons, aged between 45 and 74 years; with an 82.25% power to detect a risk ratio of 2; with analytical and image markers of sub-clinical atherosclerosis. (Phase III) Follow up of vascular events at ten years. Results. The subjects recruited were 6,553; excluded or not found 871; the final sample was 5,682 (2,644 men and 3,038 women); 4,168 (73,4%) took part in the study. The prevalence of MS was 22.1% (95%CI 20.5 - 23.7) for men and 17,2% (95%CI 15.8 - 18.5) for women. The main cardiovascular RF were high compared to other geographical areas except for HDL cholesterol. The rate was 8.5% (95%CI 7.4 - 9.6) for men and 1.7% (95%CI 1.3 - 2.2) Conclusions. There are important differences in risk between sex, being worst for men. The high figures for HDL cholesterol and the low prevalence of MS might mean a lower risk of vascular events in Navarra.