RESUMEN
BACKGROUND: Kidney failure (stage 5 chronic kidney disease [CKD]) is an independent risk factor for stent thrombosis (ST). Moderate (stage 3-4) CKD and proteinuria are both associated with adverse cardiovascular events, including worse outcomes after myocardial infarction (MI). Whether moderate CKD and proteinuria increase the risk of ST after MI is not known. This study evaluated the risk of ST associated with moderate CKD and dipstick proteinuria. METHODS: We retrospectively analyzed clinical and laboratory data from 956 non-stage 5 CKD patients who were admitted with MI and received intracoronary stenting. Clinical follow-up was collected at 1 year for definite or probable ST, as well as for all-cause mortality, nonfatal MI or death, and target vessel revascularization or coronary artery bypass graft surgery. RESULTS: After adjustment for multiple clinical and biochemical covariates, patients with both estimated glomerular filtration rate (GFR) of 15 to 59 mL min(-1) 1.73 m(-2) and > or =30 mg/dL dipstick proteinuria had increased cumulative incidence of ST (hazard rate [HR] 3.69, 95% CI 1.54-8.89), all-cause mortality (HR 2.68, 95% CI 1.34-5.37), and nonfatal MI or death (HR 3.20, 95% CI 1.77-5.81) at 1 year. In addition, estimated GFR of 15 to 59 mL min(-1) 1.73 m(-2) was a significant independent predictor of ST (HR 2.61, 95% CI 1.33-5.10). Dipstick proteinuria > or =30 mg/dL was associated with a trend toward increased risk for all outcomes. CONCLUSIONS: In an acute MI population, moderate CKD was identified as a novel prognostic marker for ST. In addition, patients with both decreased GFR and proteinuria had higher incidences of all-cause mortality and nonfatal MI or death than patients with either condition alone.
Asunto(s)
Reestenosis Coronaria/complicaciones , Fallo Renal Crónico/etiología , Infarto del Miocardio/complicaciones , Revascularización Miocárdica/instrumentación , Proteinuria/etiología , Stents , Urinálisis/métodos , Anciano , Causas de Muerte , Reestenosis Coronaria/epidemiología , Reestenosis Coronaria/orina , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/orina , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/cirugía , North Carolina/epidemiología , Pronóstico , Proteinuria/epidemiología , Proteinuria/orina , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: After myocardial infarction (MI), biomarkers can be helpful to identify patients who might benefit from more intensive therapies. The prothrombin time-derived fibrinogen (PTDF) assay is widely available and relatively inexpensive. We determined whether PTDF predicts events in patients with MI and compared this assay with brain natriuretic peptide (BNP) and C-reactive protein (CRP). METHODS: We retrospectively analyzed data from 915 patients admitted with MI. Follow-up was collected at 1 year for major adverse cardiac events (MACE) defined as death from any cause, nonfatal MI or death, target vessel revascularization, or coronary artery bypass grafting. RESULTS: Patients in the fourth quartile of PTDF were older and had more risk factors but fewer ST-elevation MI and lower peak troponin values. The fourth quartiles of PTDF, CRP, and BNP were associated with increased MACE compared with the first quartiles with hazard ratios of 2.08 (1.30-3.33), 1.94 (1.22-3.07), and 2.56 (1.57-4.18), respectively, findings that remained significant after adjustment. When outcomes by strata of PTDF were examined, CRP failed to add additional prognostic value. Higher BNP levels predicted MACE in the upper but not lower stratum of PTDF. CONCLUSION: In patients with MI, PTDF is a predictor of MACE at 1 year, with equivalent value compared to BNP and CRP. With low PTDF levels, neither BNP nor CRP adds prognostic value. At elevated PTDF values, higher BNP, but not CRP, identifies a higher-risk population. Therefore, PTDF can be substituted for CRP, with BNP being useful in the presence of elevated PTDF.
Asunto(s)
Proteína C-Reactiva/análisis , Fibrinógeno/análisis , Infarto del Miocardio/sangre , Péptido Natriurético Encefálico/sangre , Stents , Anciano , Angioplastia Coronaria con Balón , Puente de Arteria Coronaria/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Infarto del Miocardio/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Tiempo de Protrombina , Recurrencia , Estudios Retrospectivos , Medición de Riesgo/métodosRESUMEN
INTRODUCTION: Patients with non-O blood groups have higher plasma von Willebrand factor (vWF) levels than those with type O. vWF mediates platelet adhesion, aggregation and thrombosis. These considerations likely explain the prior observations that non-O patients have higher rates of arterial and venous thromboembolic events. However, the effect of blood group status on size of MI, procedural findings and outcomes after PCI for MI have not been reported. METHODS: We analyzed 1198 patients who underwent percutaneous coronary intervention for acute myocardial infarction between 10/03 and 8/06, and who had ABO blood group status and clinical follow-up. RESULTS AND CONCLUSIONS: Patients with O blood type were slightly older (62 +/- 13 vs. 60 +/- 13 years; p = 0.017) had a higher prevalence of hypercholesterolemia (67% vs. 58%; p = 0.002), and had a higher burden of atherosclerosis with more vascular disease (17% vs. 13%; p = 0.017) and higher prevalence of previous PCI (22% vs. 17%; p = 0.025). Non-O blood group patients had larger infarcts as measured by median peak troponin (33 vs. 24; p = 0.037), total CK (721 vs. 532; p = 0.012) and CK-MB (101 vs. 68; p = 0.010). At PCI, non-O patients had increased visible thrombus and reduced TIMI flow pre-procedure. However, there were no differences in procedural success, in-hospital blood transfusion or occurrence of MACE at 1 year follow-up. Our data demonstrate that non-O compared to O blood groups patients have higher thrombus burden despite less extensive atherosclerosis. Nevertheless, outcomes at 1 year were similar.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Angioplastia Coronaria con Balón , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Anciano , Aterosclerosis/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hipercolesterolemia/epidemiología , Masculino , Persona de Mediana Edad , Miocardio/patología , Necrosis/patología , Prevalencia , Pronóstico , Análisis de Supervivencia , Terapia Trombolítica , Factores de Tiempo , Resultado del Tratamiento , Factor de von Willebrand/metabolismoRESUMEN
Prognostic markers are needed to identify patients with acute coronary syndrome (ACS) who are at high risk for adverse events. Although the search for new biomarkers is quite active, prognostic information is available from routine hematologic tests, such as the complete blood count. For example, elevated white blood cell counts during ACS are associated with increased risk of mortality, heart failure, shock, and left ventricular dysfunction. Anemia is associated with increased risk of mortality, whereas elevated platelet counts predict poorer clinical and angiographic outcomes. In this review, we summarize the literature regarding the use of clinical hematology tests including white blood cell count, hemoglobin and hematocrit values, and platelet count as prognostic markers in patients with ACS, and we describe potential mechanisms to explain these associations.
Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/sangre , Biomarcadores/sangre , Hematócrito , Hemoglobinas , Humanos , Leucocitos , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Pronóstico , Factores de RiesgoRESUMEN
OBJECTIVE: To determine the magnitude of posture-related changes in blood components. SUBJECTS AND METHODS: Twenty-eight healthy subjects were studied between 1995 and 2004 at the Vanderbilt Autonomic Dysfunction Center, Nashville, Tenn. Lying and standing plasma volume (PV) and hematocrit (Hct) values were determined for each subject. RESULTS: Individual PV decreases on standing ranged from 6% to 25%. The absolute mean +/- SD PV shift was 417+/-137 mL (range, 149-717 mL). The mean +/- SD change in Hct was from 37.7%+/-2.8% while supine to 41.8%+/-3.2% within 30 minutes of standing. This absolute increase in Hct of 4.1%+/-1.3% represents a relative increase of 11.0%+/-3.6% from lying to standing. CONCLUSIONS: Changes in posture can lead to substantial changes in Hct, which may be attributed mistakenly to blood loss or acute anemia and result in a cascade of unnecessary diagnostic costs. In reality, these changes represent postural pseudoanemia, a normal physiological response to a change in position from standing to lying (and vice versa).
Asunto(s)
Anemia/fisiopatología , Hematócrito , Postura/fisiología , Adulto , Anemia/sangre , Colorantes/administración & dosificación , Azul de Evans/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravenosas , Masculino , Volumen Plasmático/fisiología , Radiofármacos/administración & dosificación , Valores de Referencia , Estudios Retrospectivos , Albúmina Sérica Radioyodada/administración & dosificaciónRESUMEN
The term 'metanephrines' is used to indicate the two catechol 3-O-methylated metabolites of epinephrine (E) and norepinephrine (NE): metanephrine and normetanephrine (NMN). The corresponding 3-O-methylated metabolite of dopamine is usually referred to as 3-methoxytyramine rather than 3-methoxydopamine and is not generally considered a "metanephrine". O-Methylation occurs outside the sympathetic neuron and neuroeffector junction. Metanephrines are products of the enzyme catechol-O-methyltransferase (COMT). Subsequent conjugation with sulfate or deamination by monoamine oxidase (MAO) followed by reduction to vanilmandelic acid (VMA) facilitates urinary excretion. For the clinician, measurement of normetanephrine provides an index of norepinephrine released during sympathetic nervous system activity, whereas metanephrine concentration provides an indication of adrenal medullary metabolism of epinephrine prior to its discharge into the circulation. Plasma epinephrine concentration is the preferable index of adrenal medullary epinephrine discharge. Pheochromocytomas, with their protean clinical manifestations, may be diagnostic challenges, but assay of metanephrines, especially plasma metanephrine, can be particularly helpful in diagnosis. These COMT metabolites may also help in elucidation of still undiscovered genetic and acquired disorders of catecholamine metabolism.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , Catecolaminas/metabolismo , Metanefrina/sangre , Metanefrina/orina , Animales , Enfermedades del Sistema Nervioso Autónomo/sangre , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/orina , Biomarcadores/sangre , Biomarcadores/orina , Catecol O-Metiltransferasa/fisiología , Humanos , Modelos Químicos , Modelos NeurológicosRESUMEN
Norepinephrine and epinephrine are critical determinants of minute-to-minute regulation of blood pressure. Here we review the characterization of two syndromes associated with a genetic abnormality in the noradrenergic pathway. In 1986, we reported a congenital syndrome of undetectable tissue and circulating levels of norepinephrine and epinephrine, elevated levels of dopamine, and absence of dopamine-beta-hydroxylase (DBH). These patients appeared with ptosis and severe orthostatic hypotension and lacked sympathetic noradrenergic function. In two persons with DBH deficiency, we identified seven novel polymorphisms. Both patients are compound heterozygotes for a variant that affects expression of DBH protein via impairment of splicing. Patient 1 also has a missense mutation in DBH exon 2, and patient 2 carries missense mutations in exons 1 and 6. Orthostatic intolerance is a common syndrome affecting young women, presenting with orthostatic tachycardia and symptoms of cerebral hypoperfusion on standing. We tested the hypothesis that abnormal norepinephrine transporter (NET) function might contribute to its etiology. In our proband, we found an elevated plasma norepinephrine with standing that was disproportionate to the increase in levels of dihydroxphenylglycol, as well as impaired norepinephrine clearance and tyramine resistance. Studies of NET gene structure revealed a coding mutation converting a conserved alanine residue in transmembrane domain 9 to proline. Analysis of the protein produced by the mutant cDNA demonstrated greater than 98% reduction in activity relative to normal. The finding of genetic mutations responsible for DBH deficiency and orthostatic intolerance leads us to believe that genetic causes of other autonomic disorders will be found, enabling us to design more effective therapeutic interventions.
Asunto(s)
Catecolaminas/genética , Catecolaminas/fisiología , Dopamina beta-Hidroxilasa/deficiencia , Dopamina beta-Hidroxilasa/genética , ADN Complementario/metabolismo , Dopamina/biosíntesis , Exones , Heterocigoto , Humanos , Modelos Biológicos , Modelos Químicos , Mutación , Mutación Missense , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática , Simportadores/metabolismo , SíndromeRESUMEN
BACKGROUND: The baroreflex normally serves to buffer blood pressure against excessive rise or fall. Baroreflex failure occurs when afferent baroreceptive nerves or their central connections become impaired. In baroreflex failure, there is loss of buffering ability, and wide excursions of pressure and heart rate occur. Such excursions may derive from endogenous factors such as stress or drowsiness, which result in quite high and quite low pressures, respectively. They may also derive from exogenous factors such as drugs or environmental influences. METHODS AND RESULTS: Impairment of the baroreflex may produce an unusually broad spectrum of clinical presentations; with acute baroreflex failure, a hypertensive crisis is the most common presentation. Over succeeding days to weeks, or in the absence of an acute event, volatile hypertension with periods of hypotension occurs and may continue for many years, usually with some attenuation of pressor surges and greater prominence of depressor valleys during long-term follow-up. With incomplete loss of baroreflex afferents, a mild syndrome of orthostatic tachycardia or orthostatic intolerance may appear. Finally, if the baroreflex failure occurs without concomitant destruction of the parasympathetic efferent vagal fibers, a resting state may lead to malignant vagotonia with severe bradycardia and hypotension and episodes of sinus arrest. CONCLUSIONS: Although baroreflex failure is not the most common cause of the above conditions, correct differentiation from other cardiovascular disorders is important, because therapy of baroreflex failure requires specific strategies, which may lead to successful control.
Asunto(s)
Barorreflejo , Hipertensión/etiología , Postura , Taquicardia/etiología , Enfermedades del Nervio Vago/etiología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Barorreflejo/fisiología , Presión Sanguínea , Diagnóstico Diferencial , Frecuencia Cardíaca , Humanos , Hipertensión/diagnóstico , Hipertensión/terapia , Taquicardia/diagnóstico , Taquicardia/terapia , Enfermedades del Nervio Vago/diagnóstico , Enfermedades del Nervio Vago/terapiaRESUMEN
This review outlines current knowledge concerning fluid intake and volume homeostasis in ageing. The physiology of vasopressin is summarized. Studies have been carried out to determine orthostatic changes in plasma volume and to assess the effect of water ingestion in normal subjects, elderly subjects, and patients with dysautonomias. About 14% of plasma volume shifts out of the vasculature within 30 minutes of upright posture. Oral ingestion of water raises blood pressure in individuals with impaired autonomic reflexes and is an important source of noise in blood pressure trials in the elderly. On the average, oral ingestion of 16 ounces (473ml) of water raises blood pressure 11 mmHg in elderly normal subjects. In patients with autonomic impairment, such as multiple system atrophy, strikingly exaggerated pressor effects of water have been seen with blood pressure elevations greater than 75 mmHg not at all uncommon. Ingestion of water is a major determinant of blood pressure in the elderly population. Volume homeostasis is importantly affected by posture and large changes in plasma volume may occur within 30 minutes when upright posture is assumed.