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1.
Eur Heart J Acute Cardiovasc Care ; 9(4): 302-312, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32403934

RESUMEN

BACKGROUND: The inflammatory marker long pentraxin 3 (PTX3) has been shown to be a strong predictor of 30-day and one-year mortality after acute myocardial infarction. The aim of this study was to evaluate the kinetic profile of PTX3 and its relationship with interleukin 6 (IL-6), high-sensitive C-reactive protein (hs-CRP) and infarct size. METHODS: PTX3, IL-6 and hs-CRP were measured at predefined time points, at baseline (before percutaneous coronary intervention (PCI)), at 12 and 72 hours after PCI in 161 patients with first-time ST elevation myocardial infarction (STEMI). RESULTS: PTX3 and IL-6 levels increased in the early phase, followed by a gradual decrease between 12 and 72 hours. There were statistically significant correlations between PTX3 and IL-6 in general, for all time points and for changes over time (0-72 hours). In a linear mixed model, PTX3 predicted IL-6 (p < 0.001). PTX3 is also correlated with hs-CRP in general, and at each time point post PCI, except at baseline. PTX3, IL-6 and hs-CRP were all significantly correlated with infarct size in general, and at the peak time point for maximum troponin I. In addition, there was a modest correlation between IL-6 levels at baseline and infarct size at 72 hours after PCI (ρ = 0.23, p = 0.006). CONCLUSIONS: PTX3 had a similar kinetic profile to IL-6, with an early increase and decline, and was statistically significantly correlated with markers of infarct size in STEMI patients post primary PCI. Baseline levels of IL-6 only predicted infarct size at 72 hours post PCI.


Asunto(s)
Proteína C-Reactiva/metabolismo , Interleucina-6/sangre , Miocardio/metabolismo , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/sangre , Componente Amiloide P Sérico/metabolismo , Anciano , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/cirugía , Índice de Severidad de la Enfermedad , Troponina I/sangre , Troponina T/sangre
2.
J Intern Med ; 288(4): 446-456, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32270523

RESUMEN

BACKGROUND: The carnitine precursor trimethyllysine (TML) is associated with progression of atherosclerosis, possibly through a relationship with trimethylamine-N-oxide (TMAO). Riboflavin is a cofactor in TMAO synthesis. We examined prospective relationships of circulating TML and TMAO with acute myocardial infarction (AMI) and potential effect modifications by riboflavin status. METHODS: By Cox modelling, risk associations were examined amongst 4098 patients (71.8% men) with suspected stable angina pectoris. Subgroup analyses were performed according to median plasma riboflavin. RESULTS: During a median follow-up of 4.9 years, 336 (8.2%) patients experienced an AMI. The age- and sex-adjusted hazard ratio (HR) (95% CI) comparing the 4th vs. 1st TML quartile was 2.19 (1.56-3.09). Multivariable adjustment for traditional cardiovascular risk factors and indices of renal function only slightly attenuated the risk estimates [HR (95% CI) 1.79 (1.23-2.59)], which were particularly strong amongst patients with riboflavin levels above the median (Pint  = 0.035). Plasma TML and TMAO were strongly correlated (rs  = 0.41; P < 0.001); however, plasma TMAO was not associated with AMI risk in adjusted analyses [HR (95% CI) 0.81 (0.58-1.14)]. No interaction between TML and TMAO was observed. CONCLUSION: Amongst patients with suspected stable angina pectoris, plasma TML, but not TMAO, independently predicted risk of AMI. Our results motivate further research on metabolic processes determining TML levels and their potential associations with cardiovascular disease. We did not adjust for multiple comparisons, and the subgroup analyses should be interpreted with caution.


Asunto(s)
Enfermedad Coronaria/sangre , Enfermedad Coronaria/complicaciones , Factores de Riesgo de Enfermedad Cardiaca , Lisina/análogos & derivados , Metilaminas/sangre , Infarto del Miocardio/etiología , Anciano , Biomarcadores/sangre , Femenino , Humanos , Lisina/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Riboflavina/sangre
3.
J Intern Med ; 283(6): 578-587, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29573355

RESUMEN

BACKGROUND: Link between inflammation and atrial fibrillation (AF) has been increasingly recognized. Neopterin, a biomarker of cellular immune activation, may be associated with incident AF. OBJECTIVE: To investigate the association between plasma neopterin levels and risk of an inpatient hospital diagnosis of AF, and to evaluate a joint association of neopterin and a nonspecific inflammatory marker C-reactive protein (CRP) in two prospective cohorts. METHODS: We performed a prospective analysis from a community-based cohort (the Hordaland Health Study (HUSK), n = 6891), and validated the findings in a cohort of patients with suspected stable angina pectoris (the Western Norway Coronary Angiography Cohort (WECAC), n = 2022). RESULTS: In both cohorts, higher plasma levels of neopterin were associated with an increased risk of incident AF after adjustment for age, sex, body mass index, current smoking, diabetes, hypertension and renal function. The multivariable-adjusted hazard ratio (HR) (95% CI) per one SD increment of log-transformed neopterin was 1.20 (1.10-1.32) in HUSK and 1.26 (1.09-1.44) in WECAC. Additional adjustment for CRP did not materially affect the risk association for neopterin. The highest risk of AF was found among individuals with both neopterin and CRP levels above the median (HR: 1.54; 95% CI: 1.16-2.05 in HUSK and HR: 1.67; 95% CI: 1.11-2.52 in WECAC). CONCLUSIONS: Our findings indicate an association of plasma neopterin with risk of an inpatient hospital diagnosis of AF, which remains after adjustment for traditional risk factors as well as for CRP. This study highlights a role of cellular immune activation, in addition to inflammation, in AF pathogenesis.


Asunto(s)
Fibrilación Atrial/diagnóstico , Neopterin/metabolismo , Anciano , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo
4.
Eur J Clin Nutr ; 70(4): 517-22, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26603883

RESUMEN

BACKGROUND/OBJECTIVES: Seasonal variation may reduce the validity of 25-hydroxyvitamin D (25OHD) as a biomarker of vitamin D status. Here we aimed to identify potential determinants of seasonal variation in 25OHD concentrations and to evaluate cosinor modelling as a method to adjust single 25OHD measurements for seasonal variation. SUBJECTS/METHODS: In Caucasian cardiovascular patients (1999-2004), we measured 25OHD by liquid chromatography tandem mass spectrometry in 4116 baseline and 528 follow-up samples. To baseline values, we fitted a cosinor model for monthly concentrations of 25OHD. Using the model, we estimated each patient's adjusted annual 25OHD value. Further, we studied how covariates affected the annual mean 25OHD concentration and seasonal variation of the study cohort. To evaluate the model, we predicted follow-up measurements with and without covariates and compared accuracy with carrying forward baseline values and linear regression adjusting for season, common approaches in research and clinical practice, respectively. RESULTS: The annual mean (59.6 nmol/l) was associated with participants' age, gender, smoking status, body mass, physical activity level, diabetes diagnosis, vitamin D supplement use and study site (adjusted models, P<0.05). Seasonal 25OHD variation was 15.8 nmol/l, and older age (>62 years) was associated with less variation (adjusted model, P=0.025). Prediction of follow-up measurements was more accurate with the cosinor model compared with the other approaches (P<0.05). Adding covariates to cosinor models did not improve prediction (P>0.05). CONCLUSIONS: We find cosinor models suitable and flexible for analysing and adjusting for seasonal variation in 25OHD concentrations, which is influenced by age.


Asunto(s)
Enfermedades Cardiovasculares/sangre , Estaciones del Año , Vitamina D/análogos & derivados , Anciano , Biomarcadores/sangre , Presión Sanguínea , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Estudios de Cohortes , Suplementos Dietéticos , Ejercicio Físico , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Noruega , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitamina D/administración & dosificación , Vitamina D/sangre , Población Blanca
5.
J Intern Med ; 268(4): 367-82, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20698927

RESUMEN

OBJECTIVES: In the Norwegian Vitamin Trial and the Western Norway B Vitamin Intervention Trial, patients were randomly assigned to homocysteine-lowering B-vitamins or no such treatment. We investigated their effects on cardiovascular outcomes in the trial populations combined, during the trials and during an extended follow-up, and performed exploratory analyses to determine the usefulness of homocysteine as a predictor of cardiovascular outcomes. DESIGN: Pooling of data from two randomized controlled trials (1998-2005) with extended post-trial observational follow-up until 1 January 2008. SETTING: Thirty-six hospitals in Norway. SUBJECTS: 6837 patients with ischaemic heart disease. INTERVENTIONS: One capsule per day containing folic acid (0.8 mg) plus vitamin B12 (0.4 mg) and vitamin B6 (40 mg), or folic acid plus vitamin B12, or vitamin B6 alone or placebo. MAIN OUTCOME MEASURES: Major adverse cardiovascular events (MACEs; cardiovascular death, acute myocardial infarction or stroke) during the trials and cardiovascular mortality during the extended follow-up. RESULTS: Folic acid plus vitamin B12 treatment lowered homocysteine levels by 25% but did not influence MACE incidence (hazard ratio, 1.07; 95% CI, 0.95-1.21) during 39 months of follow-up, or cardiovascular mortality (hazard ratio, 1.12; 95% CI, 0.95-1.31) during 78 months of follow-up, when compared to no such treatment. Baseline homocysteine level was not independently associated with study outcomes. However, homocysteine concentration measured after 1-2 months of folic acid plus vitamin B12 treatment was a strong predictor of MACEs. CONCLUSION: We found no short- or long-term benefit of folic acid plus vitamin B12 on cardiovascular outcomes in patients with ischaemic heart disease. Our data suggest that cardiovascular risk prediction by plasma total homocysteine concentration may be confined to the homocysteine fraction that does not respond to B-vitamins.


Asunto(s)
Ácido Fólico/uso terapéutico , Homocisteína/efectos de los fármacos , Isquemia Miocárdica/prevención & control , Vitamina B 12/uso terapéutico , Vitamina B 6/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Cápsulas , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Infarto del Miocardio/etiología , Isquemia Miocárdica/sangre , Isquemia Miocárdica/mortalidad , Cooperación del Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Accidente Cerebrovascular/etiología , Resultado del Tratamiento
6.
Resuscitation ; 81(11): 1566-70, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20638767

RESUMEN

AIMS: A percutaneous left ventricular assist device can maintain blood flow to vital organs during ventricular fibrillation and may improve outcomes in ischaemic cardiac arrest. We compared haemodynamic and clinical effects of a percutaneous left ventricular assist device with a larger device deployed via endovascular prosthesis and with open-chest cardiac massage during ischaemic cardiac arrest. METHODS: Eighteen swine were randomised into three groups. After thoracotomy, coronary ischaemia and ventricular fibrillation was induced. Cardiac output was measured with transit-time flowmetry. Tissue perfusion was measured with microspheres. Defibrillation was performed after 20 min. RESULTS: Cardiac output with cardiac massage was 1129 mL min⁻¹ vs. 1169 mL min⁻¹ with the percutaneous- and 570 mL min⁻¹ with the surgical device (P < 0.05 surgical vs. others). End-tidal CO2 was 3.3 kPa with cardiac massage vs. 3.2 kPa with the percutaneous- and 2.3 kPa with the surgical device (P < 0.05 surgical vs. others). Subepicardial perfusion was 0.33 mL min⁻¹ g⁻¹ with cardiac massage vs. 0.62 mL min⁻¹ g⁻¹ with both devices (P < 0.05 devices vs. massage), cerebral perfusion was comparable between groups (all reported values after 3 min cardiac arrest, all P<0.05 vs. baseline, all P = NS for 3 min vs. 15 min). Return of spontaneous circulation was achieved in 5/6 subjects with cardiac massage vs. 6/6 with the percutaneous- and 4/6 with the surgical device (P = NS). CONCLUSION: The percutaneous device improved myocardial perfusion, maintained cerebral perfusion and systemic circulation with similar rates of successful defibrillation vs. cardiac massage. Increased delivery was not obtained with the surgical device during cardiac arrest.


Asunto(s)
Paro Cardíaco/cirugía , Masaje Cardíaco/métodos , Corazón Auxiliar , Fibrilación Ventricular/cirugía , Animales , Gasto Cardíaco , Distribución de Chi-Cuadrado , Diseño de Equipo , Paro Cardíaco/fisiopatología , Hemodinámica , Análisis de los Mínimos Cuadrados , Microesferas , Distribución Aleatoria , Porcinos , Toracotomía , Resultado del Tratamiento , Fibrilación Ventricular/fisiopatología
7.
Resuscitation ; 80(10): 1197-203, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19631443

RESUMEN

AIMS: A percutaneous left ventricular assist device has been shown to be able to perfuse cardiac and cerebral tissues during cardiac arrest and may be a useful supplement to current methods in resuscitation. We wished to assess device-assisted circulation during cardiac arrest with microspheres injections and continuous end-tidal CO(2) monitoring, and used cerebral microdialysis to detect ischaemia in the brain. METHODS: 12 anaesthetised pigs had microdialysis and pressure catheters implanted via craniotomy. The percutaneous assist device was deployed transfemorally. Ventricular fibrillation was induced by angioplasty-balloon occlusion of the left coronary artery. Cerebral microdialysis samples representing 0-20 and 20-40 min of cardiac arrest with assisted circulation were analysed for markers of cerebral injury (glucose, pyruvate, lactate, and glycerol). RESULTS: Microdialysis showed no ischaemic changes after 20 min of cardiac arrest (P=NS to Baseline for glucose, glycerol, lactate, pyruvate and lactate/pyruvate ratio) in subjects with maintained end-tidal CO(2) values above 1.3 kPa (10 mmHg). After 40 min only lactate showed a significant change compared to Baseline (P<0.05). Microspheres flow to the brain was 57% and myocardial flow was 72% compared to Baseline after 15 min (P<0.05). After 45 min flow declined to 22% and 40% of Baseline, respectively (P=NS vs. 15 min). CONCLUSIONS: A percutaneous left ventricular assist device may prevent ischaemic cerebral injury during cardiac arrest for a limited time. Cerebral injury and tissue perfusion were indicated by end-tidal CO(2).


Asunto(s)
Isquemia Encefálica/prevención & control , Circulación Cerebrovascular , Paro Cardíaco/complicaciones , Corazón Auxiliar , Fibrilación Ventricular/fisiopatología , Enfermedad Aguda , Animales , Velocidad del Flujo Sanguíneo , Isquemia Encefálica/etiología , Isquemia Encefálica/fisiopatología , Cateterismo Cardíaco , Paro Cardíaco/fisiopatología , Hemodinámica , Hemoglobinas/análisis , Ácido Láctico/sangre , Microdiálisis , Microesferas , Porcinos , Resistencia Vascular , Fibrilación Ventricular/complicaciones , Fibrilación Ventricular/terapia
8.
Heart ; 95(15): 1245-9, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19406735

RESUMEN

OBJECTIVE: To explore doctor-patient interactions and decision-making processes before high-risk cardiac surgery or intervention with special attention to existential challenges. DESIGN, SETTING AND PARTICIPANTS: We conducted a qualitative study with data drawn from doctor-patient dialogues preceding high-risk procedures. The study setting was the cardiac department of a university hospital with 24-hour emergency service. We recruited a purposive sample of 10 patients and eight doctors. The patients were categorised as high-risk patients in accordance with EuroSCORE and established angiographic procedural high-risk criteria. Transcripts from the dialogues were analysed with systematic text condensation, inspired by discourse analysis. MAIN OUTCOME MEASURE: Accounts of doctor-patient interaction reflecting existential aspects of the decision-making process. RESULTS: The main existential concerns identified in the doctor-patient interactions were surviving uncertainty, negotiating responsibility and trusting the doctor's proficiency. When handling uncertainty, doctors imparted complex information about risk, warnings and recommendations, while patients sought and trusted the doctors' advice. Though the decisions were made in asymmetrical power relations, they were based on a shared responsibility discussed and defined throughout the dialogues. The patients expressed a profound confidence in the doctor's ability to get them through the high-risk treatment and give the best help possible. CONCLUSIONS: Uncertainty, mortality, responsibility and trust are fundamental existential issues concerning both patients and doctors before high-risk procedures, with an impact on decision-making processes. Increasing focus on underlying existential conditions, ethical reasoning and power relations in medical education may improve the quality of shared decision-making and informed consent related to high-risk treatment.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/psicología , Toma de Decisiones , Relaciones Médico-Paciente , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Satisfacción del Paciente , Investigación Cualitativa , Medición de Riesgo , Factores de Riesgo , Responsabilidad Social , Confianza
9.
J Med Ethics ; 34(11): 767-71, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18974406

RESUMEN

BACKGROUND AND OBJECTIVES: Physicians are exposed to matters of existential character at work, but little is known about the personal impact of such issues. METHODS: To explore how physicians experience and cope with existential aspects of their clinical work and how such experiences affect their professional identities, a qualitative study using individual semistructured interviews has analysed accounts of their experiences related to coping with such challenges. Analysis was by systematic text condensation. The purposeful sample comprised 10 physicians (including three women), aged 33-66 years, residents or specialists in cardiology or cardiothoracic surgery, working in a university hospital with 24-hour emergency service and one general practitioner. RESULTS: Participants described a process by which they were able to develop a capacity for coping with the existential challenges at work. After episodes perceived as shocking or horrible earlier in their career, they at present said that they could deal with death and mostly keep it at a distance. Vulnerability was closely linked to professional responsibility and identity, perceived as a burden to be handled. These demands were balanced by an experience of meaning related to their job, connected to making a difference in their patients' lives. Belonging to a community of their fellows was a presupposition for coping with the loneliness and powerlessness related to their vulnerable professional position. CONCLUSIONS: Physicians' vulnerability facing life and death has been underestimated. Belonging to caring communities may assist growth and coping on exposure to existential aspects of clinical work and developing a professional identity.


Asunto(s)
Adaptación Psicológica , Actitud Frente a la Muerte , Cuerpo Médico de Hospitales/psicología , Médicos/psicología , Cuidado Terminal/psicología , Adulto , Anciano , Empatía , Existencialismo/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Relaciones Médico-Paciente , Médicos de Familia/psicología , Investigación Cualitativa , Estrés Psicológico
10.
J Intern Med ; 262(2): 244-53, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17645592

RESUMEN

OBJECTIVES: A high level of total homocysteine (tHcy) is a risk marker for cardiovascular disease (CVD), and is related to inflammation. We wanted to test the effect of homocysteine-lowering B-vitamin therapy, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on inflammatory markers associated with atherosclerosis. DESIGN: Single centre, prospective double-blind clinical interventional study, randomised in a 2 x 2 factorial design. SUBJECTS AND METHODS: Ninety patients (21 female) with suspected coronary artery disease (CAD), aged 38-80 years, were blindly randomised into one of four groups of daily oral treatment with (A) folic acid (0.8 mg)/vitamin B12 (0.4 mg)/vitamin B6 (40 mg), (B) folic acid/vitamin B12, (C) vitamin B6 alone or (D) placebo. Blood samples were collected before and after 6 months of treatment. RESULTS: Before intervention, median levels of the analytes were: tHcy 11.0 micromol L(-1), neopterin 8.1 nmol L(-1), soluble CD40 ligand (sCD40L) 3.9 ng mL(-1), interleukin (IL)-6 1.9 pg mL(-1), C-reactive protein (CRP) 1.9 mg L(-1) and low-density lipoprotein (LDL) cholesterol 3.3 mmol L(-1). tHcy was significantly associated with neopterin (r = 0.49, P < 0.001) and with IL-6 (r = 0.29, P = 0.01), but not with CRP or sCD40L. Neither treatment with folic acid/B12 nor with B6 induced significant changes in any of these inflammatory biomarkers (P >or= 0.14). In patients receiving folic acid/B12 (groups A and B), tHcy was reduced with 33% (P < 0.001). CONCLUSIONS: In patients with stable CAD, homocysteine-lowering therapy with B-vitamins does not affect levels of inflammatory markers associated with atherogenesis. Failure to reverse inflammatory processes, may partly explain the negative results in clinical secondary B-vitamin intervention trials.


Asunto(s)
Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Homocisteína/sangre , Complejo Vitamínico B/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Ligando de CD40/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Método Doble Ciego , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/sangre , Tasa de Filtración Glomerular , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Neopterin/sangre , Estudios Prospectivos , Resultado del Tratamiento , Vitamina B 12/administración & dosificación , Vitamina B 12/sangre , Vitamina B 6/administración & dosificación , Vitamina B 6/sangre , Complejo Vitamínico B/sangre
11.
Cardiovasc Res ; 52(2): 306-13, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11684079

RESUMEN

OBJECTIVE: The sulfur containing tetradecylthioacetic acid (TTA) has a profound effect on lipid metabolism and may also exert antioxidant and anti-inflammatory actions and thereby counteract coronary stenosis after angioplasty balloon injury. This study examined the possible modulatory effects of TTA, delivered locally, on coronary stenosis in minipigs and the underlying mechanisms of action. METHODS: Coronary balloon angioplasty injury using an oversized balloon was performed to 40 coronary arteries (20 minipigs, Sus Scrofa, Gammelsroed) followed by delivery of placebo or TTA via a local drug delivery balloon catheter. TTA was radiolabelled in four pigs. Quantitative coronary angiography and intracoronary ultrasound (ICUS) were performed before and after injury, and after 4 weeks of follow-up. The arteries were examined with histomorphometry. The antioxidant and anti-inflammatory effects of TTA were examined on LDL oxidation and stimulated release of interleukin (IL)-2 and IL-10 in human peripheral blood mononuclear cells (PBMC), respectively. RESULTS: Radioactive TTA was present in the coronary wall after 4 weeks. Angiographic minimal luminal diameter (mean+/-S.E.M.) in the placebo and TTA group was 1.3+/-0.1 vs. 2.2+/-0.2 mm (P<0.01) at follow-up, stenosis rate was 55 and 20% (P<0.01). Remodeling was -0.56+/-0.12 in the TTA group and -1.28+/-0.09 in the placebo group (P<0.01). TTA significantly prolonged the lag time of LDL oxidation. In phytohemagglutinin stimulated PBMC, TTA significantly decreased IL-2 levels and increased IL-10 levels suggesting a marked anti-inflammatory net effect. CONCLUSIONS: Local delivery of TTA reduces coronary artery stenosis after PTCA as assessed by both angiographic, histomorphometric and ICUS examinations by influencing vessel remodeling rather than intimal hyperplasia. The underlying mechanism(s) seem to involve antioxidant and anti-inflammatory effects of this fatty acid analogue.


Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Antiinflamatorios/administración & dosificación , Antioxidantes/administración & dosificación , Estenosis Coronaria/prevención & control , Vasos Coronarios/lesiones , Sulfuros/administración & dosificación , Administración Tópica , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Células Cultivadas , Cobre , Angiografía Coronaria , Estenosis Coronaria/etiología , Estenosis Coronaria/metabolismo , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/metabolismo , Femenino , Humanos , Interleucina-10/análisis , Interleucina-2/análisis , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Lipoproteínas LDL/metabolismo , Masculino , Modelos Animales , Oxidación-Reducción , Sulfuros/metabolismo , Sulfuros/farmacología , Porcinos Enanos , Ultrasonografía Intervencional
12.
Atherosclerosis ; 158(2): 269-75, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11583704

RESUMEN

BACKGROUND: tetradecylthioacetic acid (TTA) is a synthetic long-chain fatty acid analogue that inhibits the oxidative modification of low-density lipoprotein particles in vitro. We examined the influence of TTA on the arterial wall response after balloon angioplasty injury in a rabbit iliac model. METHODS AND RESULTS: 14 rabbits were randomized to receiving either TTA fatty acids 800 mg daily perorally (weight 3.6+/-0.1 kg) or to normal diet (weight 3.5+/-0.5 kg, P=NS). Angioplasty was performed via right carotidotomy on both iliac arteries using an oversized balloon catheter, the TTA group being pretreated for 3 weeks. After angioplasty, the lumen diameter was 2.37+/-0.18 versus 2.36+/-0.13 mm for the TTA and control groups, respectively (P=NS). At 10 weeks follow-up angiography, minimal luminal diameter was 1.64+/-0.27 versus 1.13+/-0.52 mm for the TTA and control groups respectively (P<0.05). Histomorphometry did not show significant differences in intimal hyperplasia between the two groups (maximal intimal thickness 0.22+/-0.04 versus 0.19+/-0.10 mm, P=NS and intimal area 0.32+/-0.12 versus 0.36+/-0.23 mm(2), P=NS for the TTA and the control groups, respectively). In the heart, the sum of the n-3 fatty acids was 8.9+/-2.7 in the TTA group versus 4.3+/-0.2 mol% in the control group (P<0.05). The anti-inflammatory fatty acid index, calculated as (22:5 n-3+22:6 n-3+20:3 n-6)/20:4 n-6, was 0.76+/-0.10 vs. 0.25+/-0.03 for the TTA and control groups, respectively (P<0.05). In vitro TTA (100 microM) reduced the proliferation of human smooth muscle cell by more than 50%. CONCLUSION: treatment with TTA is associated with positive arterial remodeling after angioplasty injury. The significance of the in vitro inhibition of human smooth muscle cell proliferation needs to be further elucidated.


Asunto(s)
Angioplastia de Balón/efectos adversos , Antioxidantes/farmacología , Arteria Ilíaca/patología , Sulfuros/farmacología , Animales , Cateterismo , División Celular , Células Cultivadas , Constricción Patológica/prevención & control , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-6 , Ácidos Grasos Insaturados/análisis , Arteria Ilíaca/diagnóstico por imagen , Arteria Ilíaca/efectos de los fármacos , Arteria Ilíaca/lesiones , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Miocardio/química , Conejos , Radiografía , Túnica Íntima/diagnóstico por imagen , Túnica Íntima/patología , Túnica Media/diagnóstico por imagen , Túnica Media/patología
13.
Am J Clin Nutr ; 74(1): 130-6, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11451728

RESUMEN

BACKGROUND: Few population-based studies have assessed relations between plasma or serum total homocysteine (tHcy) and all-cause mortality. OBJECTIVE: Our goal was to study associations between plasma tHcy and all-cause, cardiovascular, and noncardiovascular mortality. DESIGN: This was a prospective cohort study of 2127 men and 2639 women aged 65-67 y in 1992-1993 when they were recruited as part of a population-based national cardiovascular screening program carried out in Hordaland County, Norway. RESULTS: During a median of 4.1 y of follow-up, 162 men and 97 women died. A strong relation was found between plasma tHcy and all-cause mortality. The association was highly significant for noncardiovascular and for cardiovascular causes of death. In a comparison of individuals having tHcy concentrations of 9.0-11.9, 12.0-14.9, 15.0-19.9, or > or = 20 micromol/L with individuals having a tHcy concentration < 9 micromol/L, adjusted mortality ratios were 1.4, 1.9, 2.3, and 3.6 (P for trend = 0.0002) for noncardiovascular and 1.3, 2.1, 2.6, and 3.5 (P for trend = 0.0002) for cardiovascular causes of death. A tHcy increment of 5 micromol/L was associated with a 49% (95% CI: 28%, 72%) increase in all-cause mortality, a 50% (95% CI: 21%, 85%) increase in cardiovascular mortality (121 deaths), a 26% (95% CI: -2%, 63%) increase in cancer mortality (103 deaths), and a 104% (95% CI: 44%, 289%) increase in noncancer, noncardiovascular mortality (33 deaths). CONCLUSION: Plasma tHcy is a strong predictor of both cardiovascular and noncardiovascular mortality in a general population of 65-72-y-olds. These results should encourage studies of tHcy in a wider perspective than one confined to cardiovascular disease.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Homocisteína/sangre , Neoplasias/mortalidad , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Estudios Prospectivos , Factores de Riesgo
14.
Scand Cardiovasc J ; 35(2): 101-6, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11405484

RESUMEN

OBJECTIVE: Antioxidants have been suggested to reduce restenosis after balloon angioplasty. A novel sulphur-containing fatty acid, tetradecylthioacetic acid (TTA), with antioxidant properties, is efficiently incorporated into cellular phospholipids. We have determined the uptake and retention of TTA after local coronary artery delivery in 20 pigs. DESIGN: Radiolabelled TTA was delivered to 40 main coronary arteries via a multiporous coronary angioplasty balloon catheter inflated before, after, or without overstretch vessel injury. The animals were killed at intervals of up to 6 weeks post-procedure. The radioactivity of the tissue sections was determined as nmol TTA/g tissue. RESULTS: Concentrations of TTA in the coronary arteries were 1.84 +/- 0.45 nmol/g up to 24 h, 1.50 +/- 0.96 nmol/g at 2 weeks, 0.22 +/- 0.11 nmol/g at 4 weeks and a trace was present at 6 weeks (p-value for trend <0.01). The arterial wall uptake at the delivery site was higher than distal to delivery (1.84 +/- 0.37 vs 0.55 +/- 0.13 nmol/g, p = 0.006) and perivascular fat (p < 0.01) but not higher than in the myocardium. Infusion before, after or without vessel injury was not important for tissue concentration. CONCLUSIONS: After local coronary artery delivery, the antioxidant TTA is taken up by the arterial wall in which it is retained for at least 4 weeks.


Asunto(s)
Angioplastia Coronaria con Balón/métodos , Antioxidantes/farmacología , Enfermedad Coronaria/prevención & control , Sulfuros/farmacología , Animales , Antioxidantes/uso terapéutico , Angiografía Coronaria , Enfermedad Coronaria/metabolismo , Enfermedad Coronaria/terapia , Bombas de Infusión Implantables , Metabolismo de los Lípidos , Recurrencia , Sulfuros/uso terapéutico , Porcinos
15.
Scand Cardiovasc J ; 35(1): 14-8, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11354565

RESUMEN

OBJECTIVE: In Norway "Transmyocardial laser revascularization" as a routine method was prohibited by the Ministry of Health in 1995 due to lacking evidence of treatment effect and concerns about procedural morbidity and mortality. In 1999 Norwegian health authorities asked for a re-evaluation of the method based on a systematic review of literature. METHODS: Medline and Embase were searched and a total of 267 articles were identified. Publications were classified by an expert panel according to type of study and importance for the project. RESULTS: Based on the literature review the panel concluded that heart laser treatment does not have a life-saving effect, nor does it improve myocardial function. However, the method has a considerable short-term symptomatic effect, the mechanism of which is not understood. Neoangiogenesis, denervation and placebo may play a role. Based on the report the Norwegian health authorities recommended use of this method be restricted to scientific trials only. CONCLUSIONS: Based on a systematic literature review it was concluded that the only documented effect of heart laser treatment is symptom relief, the mechanism for which is unclear. It could partly or totally be a placebo effect. A conflict of interest may arise when new technologies are to be implemented in health care. The communication between professionals evaluating scientific results and decision makers is challenging. Quality assurance of this process may be obtained by use of expert panels working under the auspices of an official institution.


Asunto(s)
Cardiopatías/mortalidad , Cardiopatías/cirugía , Terapia por Láser/mortalidad , Terapia por Láser/tendencias , Revascularización Miocárdica/mortalidad , Revascularización Miocárdica/tendencias , Humanos , Terapia por Láser/efectos adversos , Revascularización Miocárdica/efectos adversos , Noruega , Tasa de Supervivencia
17.
Am Heart J ; 140(4): 690-6, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11011347

RESUMEN

BACKGROUND: Cardioversion or defibrillation of cardiac arrhythmias is often necessary in acutely ill cardiac patients. The electrical current may cause elevation of biochemical markers used to diagnose acute myocardial infarction. Therefore it is important to find cardiac markers with high specificity for myocardial necrosis. The purpose of this study was to assess the effects of elective cardioversion of atrial fibrillation or flutter on troponin T and I among conventional markers in patients with no evidence of acute ischemia. METHODS AND RESULTS: Fifty-seven consecutive patients underwent 1 to 4 direct current shocks (mean cumulative energy 407 J, range 100 to 920 J) under general anesthesia. At baseline, all had normal troponin levels; 50 patients (mean age 68 years, range 33 to 84 years) had normal cardiac enzymes and were included in the final analysis. Blood samples were drawn at baseline, and 1 to 2, 6 to 8, and 20 to 24 hours after cardioversion. The troponin levels were unaffected by cardioversion in all patients, whereas creatine kinase and myoglobin increased more than 10-fold. Creatine kinase MB mass and aspartate aminotransferase were above reference limits in 18% and 24% of patients, respectively, 20 to 24 hours after cardioversion. There was a significant association between elevated creatine kinase, myoglobin, and creatine kinase MB levels with cumulated energy delivered as well as when possible confounders such as age and sex were adjusted for. High international normalized ratio with warfarin use was associated with increased levels of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and myoglobin. CONCLUSIONS: The increase of conventional biochemical markers after direct current cardioversion is positively associated with cumulative energy delivered and international normalized ratio (INR) values; neither influences levels of the cardiac troponins.


Asunto(s)
Fibrilación Atrial/sangre , Aleteo Atrial/sangre , Creatina Quinasa/sangre , Cardioversión Eléctrica , Miocardio/metabolismo , Mioglobina/sangre , Troponina/sangre , Adulto , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Aleteo Atrial/fisiopatología , Aleteo Atrial/terapia , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos
18.
Undersea Hyperb Med ; 27(3): 131-5, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11191158

RESUMEN

To determine if professional diving leads to morphologic and/or functional cardiologic changes, Doppler-echocardiography was performed in 20 professional saturation divers (average 15 yr diving experience) and compared to 20 control persons (policemen) who were matched for age (35-45 yr) and number and duration of training sessions. The policemen were taller than the divers, therefore the echocardiographic dimensions but not the functional variables were normalized for body surface area. The groups were comparable for resting and maximal treadmill exercise heart rate, blood pressure, oxygen uptake, and respiratory exchange ratio. Thickness of left ventricular (LV) anterior and posterior wall in end diastole and end systole, and left ventricular mass were similar in the two groups. The systolic functional parameters, LV ejection fraction, and fractional shortening were on average normal in both groups, although one of the divers had low values. Their LV chamber dimensions, wall thickness, diastolic parameters, and exercise capability were normal. The diastolic functional parameters were equal in the two groups. These results suggest that professional divers have normal size and mass of the heart, no diastolic functional changes, and a normal average systolic function.


Asunto(s)
Buceo/fisiología , Ecocardiografía Doppler , Adulto , Presión Sanguínea , Superficie Corporal , Estudios de Casos y Controles , Estudios Transversales , Prueba de Esfuerzo , Corazón/anatomía & histología , Frecuencia Cardíaca , Humanos , Contracción Miocárdica , Consumo de Oxígeno , Respiración
19.
Am J Cardiol ; 85(6): 698-702, 2000 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-12000042

RESUMEN

Immediate removal of the femoral artery sheath after coronary angioplasty may allow rapid mobilization and reduces the number of in-hospital days. We studied the early and 1-month clinical and angiographic follow-up of patients having heparin reversed with protamine after implantation of phosphorylcholine-coated metal (Divysio) stents, followed by removal of the femoral artery sheath. Fifty patients (37 men, mean age 59 +/- 10 years) with stable angina pectoris and a single totally occluded artery (1 unprotected left main stem, 15 left anterior descending, 11 left circumflex, 23 right) underwent coronary angioplasty. Antithrombotic medication was salicylic acid 75 to 160 mg before, heparin bolus 7,500 IU during, and protamine sulfate 25 mg and oral ticlopidine 250 mg after the procedure. Angiography was performed after 30 minutes and at 1 month. The mean number of stents was 1.4 +/- 0.6/lesion, with a mean final diameter of 2.69 +/- 0.40 mm. One stent thrombus was detected after 30 minutes and was treated with balloon dilatation. One patient underwent emergency bypass surgery for non-stent-related problems. Forty-six patients were mobile after 5 hours, and 2 after >5 hours. At 1 month there had been no major coronary end points, rehospitalizations, groin bleeding, or more thrombi. One episode of transient pulmonary edema occurred after protamine injection. Thirty-eight patients (79%) had no angina at 1 month, maximal bicycle exercise capacity increased from 128 +/- 42 to 160 +/- 45 W (p <0.05), and left ventricular ejection fraction increased from 63% to 68% (p <0.05). Thus, reversal of heparin with protamine sulfate after implantation of a phosphorylcholine-coated stent enables early mobilization. This approach seems safe in patients with 1 -vessel total occlusions and angioplasty could be performed as an outpatient procedure.


Asunto(s)
Enfermedad Coronaria/terapia , Ambulación Precoz , Antagonistas de Heparina/uso terapéutico , Protaminas/uso terapéutico , Stents , Angioplastia Coronaria con Balón , Materiales Biocompatibles Revestidos , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Heparina , Humanos , Masculino , Persona de Mediana Edad , Fosforilcolina/administración & dosificación , Factores de Tiempo
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