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OBJECTIVE: Interleukin-33 (IL-33) has been investigated as a mediator in the pathogenesis of fibrosis in lung, liver, and heart. There is accumulating evidence for the involvement of the IL-33/IL-33 receptor ST2L signalling pathway in systemic sclerosis (SSc). Little is known about the role of serum sST2 in SSc, which is the subject of the present investigation. METHOD: Serum levels of sST2 were measured in 49 patients with SSc, recruited prospectively between November 2017 and March 2019. Patients were divided into those with progressive and those with stable disease. Receiver operating characteristics (ROC) curve analysis was applied to study sST2 as a marker for identifying patients with progressive disease. We used multivariate logistic regression analysis to evaluate the predictive value of sST2 for progressive disease after adjustment for potential confounding factors. RESULTS: Serum sST2 levels in patients with progressive disease were significantly elevated compared with patients with stable disease (mean ± sem: 50.4 ± 4.7 ng/mL vs 29.2 ± 2.97 ng/mL, p < 0.001). ROC curve analysis identified an sST2 cut-off value of 37.8 ng/mL as optimal for discriminating patients with progressive disease from those with stable disease (sensitivity 80.0%, specificity 79.3%, area under the curve 0.80). After controlling for potential confounding factors (age, gender, C-reactive protein, pro-brain natriuretic peptide, and sum of internal medicine comorbidities), sST2 remained predictive of progressive disease (odds ratio 1.070, 95% confidence interval 1.017-1.126, p < 0.009). CONCLUSION: In the present study, sST2 serum levels were predictive of disease progression in patients with SSc.
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Interleucina-33 , Esclerodermia Sistémica , Biomarcadores , Progresión de la Enfermedad , Humanos , Proteína 1 Similar al Receptor de Interleucina-1 , Pronóstico , Curva ROC , Esclerodermia Sistémica/diagnósticoRESUMEN
BACKGROUND AND AIM: It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. METHODS AND RESULTS: We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n=833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n=36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n=21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). CONCLUSIONS: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes.
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Cardiomiopatías Diabéticas/epidemiología , Disfunción Ventricular Izquierda/epidemiología , Remodelación Ventricular , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Estudios Transversales , Cardiomiopatías Diabéticas/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Alemania/epidemiología , Humanos , Incidencia , Modelos Lineales , Masculino , Persona de Mediana Edad , Estado Prediabético , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Ultrasonografía , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
Respiratory acidosis can become a serious problem during protective ventilation of severe lung failure. A pumpless arteriovenous interventional lung assist (iLA) for extracorporeal carbon dioxide removal has been used increasingly to control critical respiratory situations. The present study sought to evaluate the factors determining the efficacy of iLA and calculate its contribution to gas exchange. In a cohort of 96 patients with severe acute respiratory distress syndrome, haemodynamic parameters, oxygen consumption and carbon dioxide production as well as gas transfer through the iLA were analysed. The measurements demonstrated a significant dependency of blood flow via the iLA device on cannula size (mean+/-sd 1.59+/-0.52 L x min(-1) for 15 French (Fr), 1.94+/-0.35 L x min(-1) for 17 Fr, and 2.22 +/-0.45 L x min(-1) for 19 Fr) and on mean arterial pressure. Oxygen transfer capacity averaged 41.7+/-20.8 mL x min(-1), carbon dioxide removal was 148.0+/-63.4 mL x min(-1). Within two hours of iLA treatment, arterial oxygen partial pressure/inspired oxygen fraction ratio increased significantly and a fast improvement in arterial carbon dioxide partial pressure and pH was observed. Interventional lung assist eliminates approximately 50% of calculated total carbon dioxide production with rapid normalisation of respiratory acidosis. Despite limited contribution to oxygen transfer it may allow a more protective ventilation in severe respiratory failure.
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Oxigenación por Membrana Extracorpórea/instrumentación , Pulmón/patología , Respiración Artificial/instrumentación , Síndrome de Dificultad Respiratoria/fisiopatología , Acidosis Respiratoria , Dióxido de Carbono/química , Dióxido de Carbono/metabolismo , Estudios de Cohortes , Oxigenación por Membrana Extracorpórea/métodos , Humanos , Concentración de Iones de Hidrógeno , Oxígeno/química , Consumo de Oxígeno , Presión , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/terapia , Insuficiencia Respiratoria/terapia , RiesgoRESUMEN
PURPOSE: We sought to determine whether noninvasive planimetry by magnetic resonance imaging (MRI) is suitably sensitive and reliable for visualizing the mitral valve area (MVA) and for detecting increases in the MVA after percutaneous balloon mitral valvuloplasty (PBMV). MATERIALS AND METHODS: In 8 patients with mitral valve stenosis, planimetry of the MVA was performed before and after PBMV with a 1.5 T MR scanner using a breath-hold balanced gradient echo sequence (True FISP). The data was compared to the echocardiographically determined MVA (ECHO-MVA) as well as to the invasively calculated MVA by the Gorlin formula at catheterization (CATH-MVA). RESULTS: PBMV was associated with an increase of 0.79 +/- 0.30 cm (2) in the MVA (Delta MRI-MVA). The correlation between Delta MRI-MVA and Delta CATH-MVA was 0.92 (p < 0.03) and that between Delta MRI-MVA and Delta ECHO-MVA was 0.90 (p < 0.04). The overall correlation between MRI-MVA and CATH-MVA was 0.95 (p < 0.0001) and that between MRI-MVA and ECHO-MVA was 0.98 (p < 0.0001). MRI-MVA slightly overestimated CATH-MVA by 8.0 % (1.64 +/- 0.45 vs. 1.51 +/- 0.49 cm (2), p < 0.01) and ECHO-MVA by 1.8 % (1.64 +/- 0.45 vs. 1.61 +/- 0.43 cm (2), n. s.). CONCLUSION: Magnetic resonance planimetry of the mitral valve orifice is a sensitive and reliable method for the noninvasive quantification of mitral stenosis and visualization of small relative changes in the MVA. This new method is therefore capable of diagnosing as well as following the course of mitral stenosis. It must be taken into consideration that planimetry by MRI slightly overestimates the MVA as compared to cardiac catheterization.
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Anatomía Transversal/métodos , Cateterismo/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Estenosis de la Válvula Mitral/diagnóstico , Estenosis de la Válvula Mitral/terapia , Válvula Mitral/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
BACKGROUND: Cardiac growth and function may be modulated in part by trophic effects of neurohormones. Specifically, aldosterone has been shown to stimulate the growth of cardiac myocytes and the accumulation of cardiac extracellular matrix proteins. Moreover, a variant of the aldosterone synthase gene (a cytosine/thymidine exchange at position -344 in the transcriptional regulatory region) has been associated with enlargement and disturbed filling of the left ventricle (LV) in a small sample of young white adults. The aim of the present study was to reinvestigate the implications of aldosterone synthase -344C/T allele status for serum aldosterone levels, blood pressure, and LV structure and function in large population-based samples. METHODS AND RESULTS: Individuals who participated in the echocardiographic substudy of the third MONICA (MONitoring trends and determinants in CArdiovascular disease) survey (n=1445) or in the second follow-up of the first MONICA survey (n=562) were studied by standardized anthropometric, echocardiographic, and biochemical measurements as well as genotyping for aldosterone synthase -344C/T allele status. In both surveys, the distribution of sex, age, arterial blood pressure, and body mass index was homogeneous in the aldosterone synthase genotype groups. Echocardiographic LV wall thicknesses, dimensions, and mass indexes were not significantly associated with a specific aldosterone synthase genotype. Likewise, no association was detectable with echocardiographic measures of LV systolic or diastolic function. Data were consistent in both samples and not materially different in subgroups defined by age, sex, or intake of antihypertensive medication. Finally, no significant association was observed for aldosterone synthase allele status and serum aldosterone levels in the group of 562 individuals. CONCLUSIONS: The data are not in favor of a significant contribution of the C/T exchange at position -344 in the aldosterone synthase transcriptional regulatory region to the variability of serum aldosterone levels, blood pressure, or cardiac size or function as found in 2 white population-based samples.
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Citocromo P-450 CYP11B2/genética , Hipertrofia Ventricular Izquierda/etiología , Polimorfismo Genético , Adulto , Anciano , Aldosterona/sangre , Ecocardiografía , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: The present retrospective analysis of data derived from a population-based study examined the relationship between intake of beta-receptor antagonists and plasma concentrations of the cardiac natriuretic peptides and their second messenger. BACKGROUND: Beta-receptor antagonists are widely used for treatment of cardiovascular disease. In addition to direct effects on heart rate and cardiac contractility, recent evidence suggests that beta-receptor antagonists may also modulate the cross talk between the sympathetic nervous system and the cardiac natriuretic peptide system. METHODS: Plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and their second messenger cyclic guanosine monophosphate (cGMP) were assessed in addition to anthropometric, hemodynamic and echocardiographic parameters in a population-based sample (n = 672), of which 80 subjects used beta-receptor antagonists. RESULTS: Compared to subjects without medication, subjects receiving beta-receptor antagonists were characterized by substantially elevated ANP, BNP and cGMP plasma concentrations (plus 32%, 89% and 18%, respectively, p < 0.01 each). Analysis of subgroups revealed that this effect was highly consistent and present even in the absence of hypertension, left atrial enlargement, left ventricular hypertrophy or left ventricular dysfunction. The most prominent increase was observed in a subgroup with increased left ventricular mass index. By multivariate analysis, a statistically significant and independent association between beta-receptor antagonism and ANP, BNP and cGMP concentrations was confirmed. Such an association could not be demonstrated for other antihypertensive agents such as angiotensin-converting enzyme inhibitors or diuretics. CONCLUSIONS: Beta-receptor antagonists appear to augment plasma ANP, BNP and cGMP concentrations. The current observation suggests an important contribution of the cardiac natriuretic peptide system to the therapeutic mechanism of beta-receptor antagonists.
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Antagonistas Adrenérgicos beta/farmacología , Factor Natriurético Atrial/sangre , Corazón/efectos de los fármacos , Péptido Natriurético Encefálico/sangre , Anciano , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos , Sistema Nervioso Simpático/efectos de los fármacosRESUMEN
OBJECTIVES: The study evaluated the contribution of familial predisposition to the risk of left ventricular hypertrophy (LVH). BACKGROUND: Left ventricular hypertrophy is a multifactorial condition that serves as an important predictor of cardiovascular mortality. At present it is unclear whether familial predisposition contributes to the manifestation of LVH. Thus, we determined whether siblings of subjects with LVH are at increased risk to present with an elevation of LV mass or an abnormal LV geometry. METHODS: Echocardiographic and anthropometric measurements were performed in 2,293 individuals who participated in the echocardiographic substudies of population-based MONICA Augsburg surveys. In addition, a total of 319 siblings of survey participants with echocardiographic evidence of LVH were evaluated. The risk of these siblings to present with LVH or abnormal LV geometry was estimated by comparison with 636 subjects matched for gender and age that were selected from the entire echocardiography study base. RESULTS: Blood pressure, body mass index, age, and gender (i.e., known determinants of LV mass) were comparable in LVH-siblings and the matched comparison group. However, septal and posterior wall thicknesses, relative wall thickness as well as LV mass index were significantly elevated in LVH-siblings (p < 0.001, each) whereas LV dimensions did not differ. Likewise, the prevalence of LVH was raised in LVH-siblings, as was the relative risk of LVH after adjustment for confounders (p < 0.05). More specifically, LVH-siblings displayed increased prevalences of concentric remodeling and concentric LVH (p < 0.05) but not of eccentric LVH. CONCLUSIONS: Familial predisposition appears to contribute to increased LV wall thickness, to the development of LV hypertrophy and abnormal LV geometry.
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Predisposición Genética a la Enfermedad/genética , Hipertrofia Ventricular Izquierda/genética , Adulto , Anciano , Índice de Masa Corporal , Volumen Cardíaco/genética , Ecocardiografía , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico , Masculino , Persona de Mediana Edad , Factores de Riesgo , Remodelación Ventricular/genéticaRESUMEN
BNP is a marker of systolic left ventricular dysfunction (LVSD) and heart failure. To assess BNP for the detection of diastolic dysfunction in the general population, we examined 1678 subjects within an age- and sex-stratified survey (MONICA Augsburg). BNP was measured using a commercially available RIA (Shionogi). BNP increased in subjects with diastolic dysfunction (mean 20.3+/-4.7 pg/ml vs. control 9.6+/-0.5 pg/ml, p<0.001), but to a lesser extent than in subjects with LV hypertrophy (LVH, mean 37.3+/-49.1 pg/ml, p<0.001 vs. control) or LVSD (mean 76.2+/-23.2 pg/ml, p<0.001 vs. control). Individuals with sole diastolic abnormality displayed BNP concentrations at the control level (mean 9.7+/-1.7 pg/ml). In univariate analysis, age, BMI, systolic blood pressure, left atrial size, LV mass index, diastolic dysfunction and EF displayed a significant correlation with BNP (p<0.001). However, LV mass index displaced diastolic dysfunction as a significant predictor of BNP in multivariate analysis. Upon ROC analysis, sensitivity and specificity for the detection of diastolic dysfunction by BNP were only 61% and 55%, respectively. Nevertheless, a normal BNP test virtually excluded the presence of diastolic dysfunction and concomitant LVH (NPV 99.9%). Increased BNP concentrations in subjects with diastolic dysfunction are strongly related to LVH. Population-wide screening for diastolic dysfunction with BNP cannot be recommended although a normal BNP test usually excludes diastolic dysfunction and LV hypertrophy.
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Hipertrofia Ventricular Izquierda/sangre , Péptido Natriurético Encefálico/sangre , Disfunción Ventricular Izquierda/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Curva ROCRESUMEN
The sympathetic nervous system (SNS) and the cardiac natriuretic peptide system (NPS) are fundamentally important neurohumoral systems for cardiovascular regulation. Their mutual interactions have been subject to numerous experimental and human studies. In the current manuscript, results from in vivo and in vitro studies will be reviewed with a focus on sympathetic outflow on the control of natriuretic peptide release.
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Factor Natriurético Atrial/metabolismo , Cardiomiopatía Dilatada/metabolismo , Miocardio/metabolismo , Sistema Nervioso Simpático/metabolismo , Antagonistas Adrenérgicos beta/uso terapéutico , Animales , Factor Natriurético Atrial/sangre , Factor Natriurético Atrial/uso terapéutico , Barorreflejo/efectos de los fármacos , Cardiomiopatía Dilatada/tratamiento farmacológico , Endotelio Vascular/metabolismo , Humanos , Riñón/metabolismo , Pulmón/metabolismo , Receptores Adrenérgicos/metabolismo , Receptores del Factor Natriurético Atrial/efectos de los fármacos , Receptores del Factor Natriurético Atrial/metabolismo , Sistema Nervioso Simpático/efectos de los fármacosRESUMEN
OBJECTIVE: Activation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) is considered a hallmark of myocardial remodeling. To determine magnitude and relative proportion of activation during the progression to heart failure, we assessed ANP and BNP gene expression in atrial and left ventricular (LV) tissue in a newly developed model of progressive rapid ventricular pacing-induced heart failure in rabbits. METHODS: Six animals underwent progressive pacing with incremental rates (330 beats per min (bpm) to 380 bpm over 30 days), resulting in congestive heart failure (CHF). Five animals underwent pacing at 330 bpm for 10 days only (early LV dysfunction, ELVD) and five additional animals served as control group (CTRL). RESULTS: ELVD was characterized by decreased mean arterial pressure (P=0.05 vs. CTRL) as well as significantly impaired LV function (LV fractional shortening (FS) P<0.01 vs. CTRL) and dilatation (P<0.01 vs. CTRL). CHF was characterized by further decreased mean arterial pressure (P<0.01 vs. ELVD), further impaired LV function (FS P<0.03 vs. ELVD) and dilatation (P<0.01 vs. CTRL). In control animals, significant ANP expression was observed only in atrial tissue (P<0.02 vs. BNP) while BNP expression was ubiquitous but marginal (LV P<0.05 vs. ANP). In ELVD, activation of ANP (atria and LV P<0.05 vs. CTRL) and BNP (atria P<0.05 vs. CTRL, LV n.s.) was observed. In CHF, LV-BNP increased further markedly (P<0.01 vs. CTRL, P<0.05 vs. ELVD) while atrial ANP and BNP expression as well as LV ANP expression remained unchanged (all P=n.s. vs. ELVD). CONCLUSION: The current studies demonstrate differential activation of atrial and LV ANP and BNP under normal conditions and during the progression to heart failure and provide a molecular basis for the superiority of BNP as marker of LV dysfunction and CHF.
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Factor Natriurético Atrial/metabolismo , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Péptido Natriurético Encefálico/metabolismo , Disfunción Ventricular Izquierda/metabolismo , Animales , Factor Natriurético Atrial/genética , Presión Sanguínea/fisiología , Peso Corporal/fisiología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Expresión Génica , Masculino , Miocardio/patología , Péptido Natriurético Encefálico/genética , Tamaño de los Órganos , ARN Mensajero/genética , ConejosRESUMEN
Although angiotensin II (Ang II) has been implicated in the pathophysiology of congestive heart failure, its temporal and regional changes during the development and progression of the disease are poorly defined. Our objective was to assess circulating, renal, cardiac, and vascular Ang II in a canine model of rapid ventricular pacing-induced heart failure that evolves from early left ventricular dysfunction to overt congestive heart failure. Ang II was measured by radioimmunoassay with low cross-reactivity to other angiotensins. Control, early left ventricular dysfunction, and overt congestive heart failure dogs were studied. Early left ventricular dysfunction was characterized by impaired cardiac function, cardiac enlargement, preserved renal perfusion pressure, maintained urinary sodium excretion, and normal plasma renin activity. Overt congestive heart failure was characterized by further impaired cardiac function and cardiac enlargement, reduced renal perfusion pressure, urinary sodium retention, and increased plasma renin activity and plasma Ang II. In early left ventricular dysfunction dogs, renal cortical, renal medullary, ventricular, and aortic Ang II were unchanged, and atrial Ang II was decreased. In overt congestive heart failure dogs, Ang II was increased in the kidney and heart compared with normal dogs and in all tissues compared with early left ventricular dysfunction dogs. The greatest increase in tissue Ang II occurred in the renal medulla. We conclude that early increases in local renal, myocardial, and vascular Ang II do not occur in this model of early left ventricular dysfunction and may even be suppressed. In contrast, increased myocardial and particularly renal Ang II in association with increased circulating Ang II are hallmarks of overt experimental congestive heart failure. These studies provide new insights into the temporal and regional alterations in Ang II during the progression of experimental congestive heart failure.
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Angiotensina II/fisiología , Insuficiencia Cardíaca/etiología , Angiotensina II/metabolismo , Animales , Aorta/metabolismo , Perros , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Hormonas/sangre , Riñón/metabolismo , Masculino , Miocardio/metabolismo , Miocardio/patología , Natriuresis , Función Ventricular IzquierdaRESUMEN
Endothelin-1 (ET-1) is a cardiovascular peptide that binds to two distinct receptors, ET(A) and ET(B), resulting in systemic and regional vasoconstriction, alteration in sodium excretion, mitogenesis, and release of other vasoactive peptides such as atrial natriuretic peptide (ANP). A role for ET-1 has been proposed in congestive heart failure (CHF) based on the increase in circulating ET-1 in this cardiovascular disease state. The present study determined the cardiorenal and endocrine responses to chronic selective oral ETA antagonism in experimental CHF. Two groups of conscious dogs underwent 21 days of pacing-induced CHF. These groups included a control untreated group (n = 6) and a group that received an orally active ET(A) receptor antagonist (A-127722, Abbott Pharmaceuticals, 5 mg/kg PO bid, n = 6). Each group was studied at baseline before the onset of CHF and after 14 and 21 days of CHF. Compared with the CHF control group, the ET(A) receptor antagonism group at 14 days of CHF showed lower mean arterial pressure and systemic vascular resistance. Similarly, ET(A) receptor antagonism markedly attenuated the increase in circulating ANP despite similar atrial pressures. At 21 days of CHF, ET(A) receptor antagonism lowered pulmonary artery pressure, pulmonary vascular resistance, and systemic vascular resistance in association with a higher cardiac output. Plasma ANP remained suppressed. Despite the lower mean arterial pressure and circulating ANP in the ET(A) receptor antagonist group, the absolute decrease in sodium excretion from baseline was less compared with the untreated CHF control group. The present investigation supports the conclusion that endogenous ET-1 participates in the systemic and pulmonary vasoconstriction, the elevation of ANP, and the sodium retention that characterize this model of experimental CHF, suggesting a potential therapeutic role for ET(A) receptor antagonism in CHF.
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Antagonistas de los Receptores de Endotelina , Insuficiencia Cardíaca/tratamiento farmacológico , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Pirrolidinas/uso terapéutico , Administración Oral , Animales , Atrasentán , Factor Natriurético Atrial/metabolismo , Perros , Endotelina-1/metabolismo , Insuficiencia Cardíaca/metabolismo , Hemodinámica/efectos de los fármacos , Riñón/metabolismo , Masculino , Receptor de Endotelina A , Sodio/fisiología , Vasoconstricción/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the relationship between circulating angiotensin converting enzyme activity and arterial blood pressure in a population-based sample of 646 middle-aged subjects. RESULTS: After exclusion of subjects taking antihypertensive medication and those with electrocardiographic evidence of myocardial infarction, univariate analyses revealed that systolic blood pressure was significantly correlated with age and with body mass index. Also, angiotensin converting enzyme activity in men (n = 230) was found to be related both to systolic and to diastolic blood pressure. Inclusion of all of the men slightly strengthened the association between angiotensin converting enzyme activity and systolic or diastolic blood pressure. Multilinear regression models that included age, body mass index and antihypertensive therapy as obligatory covariates confirmed an independent correlation between angiotensin converting enzyme activity and systolic or diastolic blood pressure in the men. Furthermore, untreated men from the highest quartile of angiotensin converting enzyme activity displayed significantly higher mean systolic and diastolic blood pressure values than did those from lower quartiles, even after adjustment for covariates. In contrast, untreated women (n = 264) displayed no evidence for such associations between angiotensin converting enzyme activity and blood pressure. CONCLUSION: The data suggest that the variability of serum angiotensin converting enzyme activity occurring in this large population-based sample might be related to the level of arterial blood pressure levels in men.
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Presión Sanguínea , Peptidil-Dipeptidasa A/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate brain natriuretic peptide (BNP) as marker of left ventricular (LV) dysfunction and hypertrophy in a population-based sample of 610 middle-aged subjects (50-67 years) who were further characterized with respect to hemodynamic and anthropometric parameters and by echocardiography. RESULTS: Left ventricular (LV) systolic function, LV mass-index, age, gender, heart rate, and medication with beta adrenergic receptor blockers were significant and independently correlated with BNP (multivariate analysis, P < 0.05 each). As compared to subjects with normal LV function and mass-index (control), subjects with LV dysfunction (LV fractional shortening < 28%) or hypertrophy (LV mass-index > 110 g/m2 in women and > 134 g/m2 in men) were characterized by increased BNP. The increase in BNP associated with LV hypertrophy (n = 69, +101% versus control, P < 0.0001) was similar in magnitude to that associated with LV dysfunction (n = 39, +98% versus control, P < 0.03). These increases were markedly exceeded in subjects with severe LV dysfunction (n = 11, LV fractional shortening < 22%, BNP +197% versus control, P < 0.01), particularly in the presence of concomitant hypertrophy (n = 7, +227%, P < 0.01). The predictive values of BNP varied considerably with the degree of LV dysfunction and the presence or absence of concomitant LV hypertrophy. With 0.81, the highest area under the receiver operator characteristic curve was obtained for the detection of severe LV dysfunction and concomitant hypertrophy and sensitivity, specificity, positive and negative predictive value for this condition were 71, 86, 7 and 99.5%, respectively, for a cut-off of 34 pg/ml. CONCLUSIONS: The current study provides new insight into regulation and diagnostic value of BNP in middle-aged subjects and demonstrates important independent effects of LV function and mass upon BNP plasma concentrations. Although measurement of BNP cannot be recommended for the detection of marginally impaired LV function in the population, it may be helpful to suggest or exclude severe LV dysfunction with concomitant hypertrophy.
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Hipertrofia Ventricular Izquierda/metabolismo , Péptido Natriurético Encefálico/metabolismo , Disfunción Ventricular Izquierda/metabolismo , Análisis de Varianza , Factor Natriurético Atrial/metabolismo , Biomarcadores , Ecocardiografía , Femenino , Hemodinámica/fisiología , Humanos , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda/fisiologíaRESUMEN
Many studies have shown that the B-type natriuretic peptides (BNP and NT-proBNP) are proven diagnostic markers for heart failure due to left ventricular systolic dysfunction. The manner in which they are to be used is still being unravelled; most single centre studies have chosen the best concentration of the peptide on ROC analysis as their cut-point resulting in numerous different values for both BNP and NT-proBNP appearing in the literature. We report a different approach of defining an age and sex corrected abnormal concentration for NT-proBNP, derived from normal individuals within a large sample of 3051 subjects pooled from three European epidemiology studies and applying that to the entire population to detect HF and LVD. Three thousand and fifty one subjects were studied. Of these 10% (305) had significant LVD and 3.1% (94) had HF. The median concentrations of NT-proBNP (IQR) in normals, those with LVD and in heart failure subjects were 20 pg/ml (10.30), 117.3 pg/ml (28.145) and 269.6 pg/ml (54.323), P<0.001, respectively. The area under the ROC curve for NT-proBNP for the detection of 'heart failure' was 0.85 and 0.69 for LVD. NT-proBNP was an independent predictor of the presence of HF on multivariate analysis. An abnormal NT-proBNP was defined as being >95th centile for normals, age and sex corrected, and diagnosed HF with a sensitivity of 75% and a negative predictive value of 99%. In an additional analysis in a breathless subgroup of our population, in 30% a raised NT-proBNP concentration could be explained by HF due to LVD, in another 64% the high BNP level was associated with some other structural of functional cardiac abnormality or renal impairment. We were unable to assign a possible cause to the high NT-proBNP values in 5.9% of this breathless subgroup of the population. An abnormal NT-proBNP concentration is an accurate diagnostic test both for the exclusion of HF in the population and in ruling out LVD in breathless subjects. An elevated NT-proBNP merely indicates the presence of 'cardio-renal distress' and should prompt referral for further investigation.
Asunto(s)
Insuficiencia Cardíaca/metabolismo , Péptido Natriurético Encefálico/biosíntesis , Proteínas del Tejido Nervioso/biosíntesis , Fragmentos de Péptidos/biosíntesis , Disfunción Ventricular Izquierda/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Epidemiológicos , Europa (Continente)/epidemiología , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Proteínas del Tejido Nervioso/sangre , Fragmentos de Péptidos/sangre , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/metabolismoRESUMEN
The purpose of the current study was to evaluate myocardial creatinine kinase (CK) and lactate dehydrogenase (LDH) systems in a model of epinephrine-induced cardiomyopathy in rabbits. Eight rabbits received four repetitive epinephrine infusions (300 mg/kg/60 min, i.v.) in 12-day intervals and eight untreated rabbits served as controls (CTRL). Echocardiography demonstrated a significant deterioration of LV function as well as increased LV-diameter and -mass index in catecholamine-induced cardiomyopathy. Histological examination revealed that repetitive catecholamine infusion resulted in LV fibrous areas with collagenous content and an increase in myocyte width (16.9+/-0.8 microm vs. CTRL 12.9+/-0.9; P<0.05). LV dysfunction was associated with a decreased total LV lactate dehydrogenase activity (LDH; 0.43+/-0.03 IU/mg protein vs. CTRL 0.52+/-0.04; P<0.05) whereas total creatinine kinase activity was unchanged (CK; 7.30+/-0.63 IU/mg protein vs. CTRL 9.20+/-0.49, n.s.). Furthermore, myocardial LDH isoenzymes were shifted with a decrease in LDH(1) and an increase in LDH2 and LDH3 (LDH(1): 84.90+/-2.60% vs. CTRL 94.50+/-0.40; LDH2: 7.30+/-1.20% vs. 1.50+/-0.13; LDH3: 5.40+/-0.90% vs. 3.20+/-0.25; all P<0.05). Foetal B-CK isoenzymes were significantly increased (CK-MB 5.30+/-0.66 vs. 2.20+/-0.35%; P<0.05). The current study demonstrates changes in cardiac energy metabolism including an impaired LDH activity with a shift towards anaerobic isoenzymes as well as a more efficient CK system in a model of catecholamine-induced LV dysfunction.
Asunto(s)
Creatina Quinasa/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Disfunción Ventricular Izquierda/enzimología , Animales , Modelos Animales de Enfermedad , Ecocardiografía , Epinefrina , Isoenzimas/metabolismo , Masculino , Miocardio/enzimología , Conejos , Estadísticas no Paramétricas , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/patologíaRESUMEN
We have recently described a modified model of progressive rapid ventricular pacing-induced heart failure which evolves over a period of 38 days. To further characterize left ventricular remodeling during the progression of heart failure, we assessed left ventricular geometry, wall stress, and atrial natriuretic peptide (ANP) gene expression and protein content during control conditions, asymptomatic left ventricular dysfunction, and overt congestive heart failure (CHF). Although asymptomatic left ventricular dysfunction was characterized by a significant increase in systolic and diastolic left ventricular dimension (+30% and +6%, respectively, P<0.05 each) and a marked increase in left ventricular systolic wall stress (+68%, P<0.01), left ventricular ANP gene expression was unchanged as compared to control. In contrast, strong left ventricular ANP gene expression (+449%, P<0.05) was observed during overt CHF in the absence of further significant increases in left ventricular systolic wall stress. The onset of strong left ventricular ANP gene expression was associated with increased ANP content (+88%, P<0.05) and left ventricular mass index (+13%, P<0.05). In contrast, left atrial ANP gene expression and left ventricular diastolic wall stress increased progressively during asymptomatic left ventricular dysfunction (+39%, P=n.s. and +131%, P<0.01) and overt CHF (+76% and +336% vs. control, P<0.01 each). Progressive rapid ventricular pacing is associated with the induction of left ventricular ANP gene expression and protein synthesis exclusively during overt CHF. The current studies provide new insight into the temporal pattern of ANP-activation and the disparity between left ventricular systolic wall stress and ANP-activation in a large animal model of progressive CHF.
Asunto(s)
Factor Natriurético Atrial/genética , Estimulación Cardíaca Artificial , Insuficiencia Cardíaca/etiología , Disfunción Ventricular Izquierda/fisiopatología , Remodelación Ventricular/fisiología , Animales , Factor Natriurético Atrial/metabolismo , Perros , Expresión Génica , Insuficiencia Cardíaca/fisiopatología , Masculino , Factores de TiempoRESUMEN
The current study addresses the functional status and role of the endothelin ET(A) receptor for renal vascular function in rabbits with and without heart failure (epinephrine-induced cardiomyopathy). Under baseline conditions, the ET(A) receptor antagonist BQ-123 did not change basal renal hemodynamics, but completely prevented endothelin-1 (ET-1)-induced renal vasoconstriction. In heart failure, in the presence of elevated plasma ET-1 concentrations (P < .05), renal vasoconstriction in response to exogenous ET-1 was intact. Unlike under baseline conditions, ET(A) receptor antagonism markedly increased renal blood flow (P <.05) and decreased renal vascular resistance (P < .05) in heart failure. The current study provides new insight into the pathophysiology of renal vasoconstriction associated with heart failure and the specific role of the renal ET(A) receptor in this pathophysiologic adaptation.
Asunto(s)
Endotelina-1/fisiología , Circulación Renal/fisiología , Disfunción Ventricular Izquierda/fisiopatología , Agonistas Adrenérgicos , Animales , Gasto Cardíaco Bajo/inducido químicamente , Gasto Cardíaco Bajo/fisiopatología , Chinchilla , Antagonistas de los Receptores de Endotelina , Epinefrina , Hemodinámica/fisiología , Masculino , Neurotransmisores/sangre , Péptidos Cíclicos/farmacología , Conejos , Receptor de Endotelina A , Receptores de Endotelina/fisiología , Circulación Renal/efectos de los fármacos , Vasoconstricción/efectos de los fármacosRESUMEN
OBJECTIVE: Cardiac growth may be modulated in part by the trophic effects of neurohormones. The aim of the present study was to investigate the relation between the basal activity of the renin-angiotensin-aldosterone system and left ventricular mass. DESIGN: A population based sample of 615 middle-age subjects was studied by standardised echocardiography; anthropometric measurements; and biochemical quantification of renin, pro-renin, angiotensinogen, angiotensin converting enzyme (ACE), and aldosterone. RESULTS: Echocardiographic left ventricular mass index correlated significantly with arterial blood pressure, age, and body mass index. In addition, in men ACE activity was significantly related to left ventricular mass index in univariate (P = 0.0007) and multivariate analyses (P = 0.008). Men with left ventricular hypertrophy presented with significantly higher serum ACE concentrations than those with normal left ventricular mass index (P = 0.002). In both men and women serum aldosterone was strongly related to septal and posterior wall thickness. Furthermore, in women serum aldosterone was positively and independently associated with left ventricular mass index (P = 0.0001). This effect was most prominent in hypertensive women. Finally, women with left ventricular hypertrophy presented with significantly higher serum aldosterone (P = 0.01). No significant associations with left ventricular mass index were observed for angiotensinogen, renin, or pro-renin. CONCLUSIONS: The data suggest that the variability of serum ACE or aldosterone, as occurred in this large population based sample, may contribute to the modulation of left ventricular mass.
Asunto(s)
Aldosterona/sangre , Hipertrofia Ventricular Izquierda/sangre , Peptidil-Dipeptidasa A/metabolismo , Sistema Renina-Angiotensina/fisiología , Factores de Edad , Anciano , Presión Sanguínea , Índice de Masa Corporal , Ecocardiografía , Femenino , Humanos , Hipertensión/sangre , Hipertensión/diagnóstico por imagen , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
Recent reports indicate that the prognostic implications of left ventricular hypertrophy (LVH) are more profound in women than in men. The prognosis of LVH is also related to the underlying geometric pattern. We therefore assessed the relation of separate and concurrent influences of obesity and hypertension on gender-specific patterns of LV adaptation. Five hundred and twenty participants of a community-based study (aged 52 to 67 years) were examined by M-mode echocardiography. Study subjects were divided into four groups: normals, obese, hypertensives, and subjects presenting with both obesity and hypertension. The groups were compared for various measures of left ventricular mass (LVM) and geometry. Relative to normal subjects, the increments in wall thickness, ventricle diameters, and LVM were all significant and of similar magnitude for obese men and women. Likewise, hypertensive men and women showed similar relative increments of LVM and wall thickness but no changes in end-diastolic internal diameters. Accordingly, obesity was predominantly associated with eccentric hypertrophy (men +/- 14%, women +17%, P<0.05 vs normals) and hypertension with concentric hypertrophy (men +16%, women +30%, P<0.01 vs normals). Women with concurrent obesity and hypertension presented with a further increase of LVM and wall thickness above values in the merely obese or hypertensive (P<0.001) and they displayed LVH more frequently than only obese or hypertensive women (P<0.05). We conclude that the hearts of postmenopausal women respond more susceptibly to the concurrence of hypertension and obesity. In particular the prognostically less favourable concentric LVH is a common finding. Our study may help to explain the higher risk associated with LVH in women.