RESUMEN
BACKGROUND: Cardiomyopathy is a common side effect of doxorubicin (DOX) chemotherapy. Despite intensive research efforts in the field, there is still no evidence available for routine cardioprotective prophylaxis to prevent cardiotoxicity in the majority of oncological patients at low risk of cardiovascular disease. We have recently demonstrated the advantages of a prophylactic, combined heart failure therapy in an experimental model of DOX-induced cardiomyopathy. In the current work, we focus on individually applied prophylactic medications studied in the same translational environment to clarify their distinct roles in the prevention of DOX cardiotoxicity. METHODS: Twelve-week-old male Wistar rats were divided into 5 subgroups. Prophylactic ß-blocker (BB, bisoprolol), angiotensin-converting enzyme inhibitor (ACEI, perindopril) or aldosterone antagonist (AA, eplerenone) treatments were applied 1 week before DOX administration, then 6 cycles of intravenous DOX chemotherapy were administered. Rats receiving only intravenous DOX or saline served as positive and negative controls. Blood pressure, heart rate, body weight, and echocardiographic parameters were monitored in vivo. Two months after the last DOX administration, the animals were sacrificed, and their heart and serum samples were frozen in liquid nitrogen for histological, mechanical, and biochemical measurements. RESULTS: All prophylactic treatments increased the survival of DOX-receiving animals. The lowest mortality rates were seen in the BB and ACEI groups. The left ventricular ejection fraction was only preserved in the BB group. The DOX-induced increase in the isovolumetric relaxation time could not be prevented by any prophylactic treatment. A decreased number of apoptotic nuclei and a preserved myocardial ultrastructure were found in all groups receiving prophylactic cardioprotection, while the DOX-induced fibrotic remodelling and the increase in caspase-3 levels could only be substantially prevented by the BB and ACEI treatments. CONCLUSION: Primary prophylaxis with cardioprotective agents like BB or ACEI has a key role in the prevention of DOX-induced cardiotoxicity in healthy rats. Future human studies are necessary to implement this finding in the clinical management of oncological patients free of cardiovascular risk factors.
Asunto(s)
Cardiomiopatías , Preparaciones Farmacéuticas , Animales , Doxorrubicina/efectos adversos , Humanos , Masculino , Ratas , Ratas Wistar , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Chemotherapy-induced left ventricular dysfunction represents a major clinical problem, which is often only recognised at an advanced stage, when supportive therapy is ineffective. Although an early heart failure treatment could positively influence the health status and clinical outcome, there is still no evidence of routine prophylactic cardioprotection for the majority of patients without previous cardiovascular history awaiting potentially cardiotoxic chemotherapy. In this study, we set out to investigate whether a prophylactic cardioprotective therapy relative to a conventionally scheduled heart failure treatment is more effective in preventing cardiotoxicity in a rodent model of doxorubicin (DOX)-induced cardiomyopathy. METHODS: Male Wistar rats (n = 7-11 per group) were divided into 4 subgroups, namely negative controls receiving intravenous saline (CON), positive controls receiving intravenous DOX (6 cycles; D-CON), and DOX-treated animals receiving either prophylactic (PRE, started 1 week before DOX) or conventionally applied (POST, started 1 month after DOX) combined heart failure therapy of oral bisoprolol, perindopril and eplerenone. Blood pressure, heart rate, body weight and echocardiographic parameters were monitored in vivo, whereas myocardial fibrosis, capillarisation, ultrastructure, myofilament function, apoptosis, oxidative stress and mitochondrial biogenesis were studied in vitro. RESULTS: The survival rate in the PRE group was significantly improved compared to D-CON (p = 0.0207). DOX increased the heart rate of the animals (p = 0.0193), while the blood pressure (p ≤ 0.0105) and heart rate (p = 0.0029) were significantly reduced in the PRE group compared to D-CON and POST. The ejection fraction remained preserved in the PRE group compared to D-CON or POST (p ≤ 0.0237), while none of the treatments could prevent the DOX-induced increase in the isovolumetric relaxation time. DOX decreased the rate of the actin-myosin cross-bridge cycle, irrespective of any treatment applied (p ≤ 0.0433). The myocardium of the D-CON and POST animals displayed pronounced ultrastructural damage, which was not apparent in the PRE group (p ≤ 0.033). While the DOX-induced apoptotic activity could be reduced in both the PRE and POST groups (p ≤ 0.0433), no treatment was able to prevent fibrotic remodelling or the disturbed mitochondrial biogenesis. CONCLUSION: For attenuating DOX-induced adverse myocardial effects, prophylactic cardioprotection has many advantages compared to a late-applied treatment.
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Cardiomiopatías/inducido químicamente , Cardiomiopatías/terapia , Doxorrubicina/efectos adversos , Insuficiencia Cardíaca/terapia , Animales , Apoptosis , Cardiomiopatías/diagnóstico por imagen , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Ecocardiografía , Fibrosis , Insuficiencia Cardíaca/diagnóstico por imagen , Masculino , Miocardio/patología , Miocardio/ultraestructura , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratas Wistar , Análisis de SupervivenciaRESUMEN
Cardiovascular and oncologic diseases are the causes of more than 50 percent of mortality in Europe. In 2015 oncologic and cardiovascular mortality reached 70 percent in Hungary. Patients who receive anticancer therapies are at a 2- to 7-fold greater long-term risk of acute coronary syndrome; also concomittant oncologic diseases further increase the mortality of myocardial infarction. Unfortunately there is not enough data concerning cardiovascular treatment of oncologic patients because they were excluded from most of the studies and registries. Because there is no clear protocol to treat such patients, only small studies and personal experiences could guide our medical therapies. The role of cardio-oncology is even more important, because due to the new treatments the number of tumor survivors rapidly increases. In the US more than 20 millions survivals are expected by 2025 who were treated by any kind of malignant tumors. It is not surprising that in 2014 the American Society of Cardiology declared cardio-oncology as a special and important field in cardiology, and in 2016 European Society of Cardiology released the first cardio-oncologic guideline. In this review we summarize questions and problems concerning the treatment of oncologic patient with ischaemic heart disease based on resent guidelines, published studies and local protocols. Orv Hetil. 2017; 158(43): 1691-1697.
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Cardiología/normas , Enfermedades Cardiovasculares/mortalidad , Oncología Médica/normas , Neoplasias/mortalidad , Femenino , Humanos , Hungría , Masculino , Guías de Práctica Clínica como Asunto , Sistema de Registros , Medición de RiesgoRESUMEN
The aim of the case-control study was to explore the effect of coagulation factor XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery disease, and on FXIII levels. In the study, 687 patients admitted for coronary angiography to investigate suspected coronary artery disease and 994 individuals representing the Hungarian population were enrolled. The patients were classified according to the presence of significant coronary atherosclerosis (CAS) and history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg and for intron K nt29756 C>G polymorphisms; the latter results in the replacement of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele provided significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII levels, and FXIII levels in the lower tertile provided significant protection against MI. It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.
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Enfermedad de la Arteria Coronaria/genética , Factor XIII/genética , Polimorfismo de Nucleótido Simple , Anciano , Alelos , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/patología , Factor XIII/análisis , Factor XIIIa/genética , Femenino , Fibrinógeno/análisis , Genotipo , Heterocigoto , Humanos , Intrones , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Oportunidad Relativa , Factores de RiesgoRESUMEN
We tested the hypothesis that myocardial contractile protein phosphorylation and the Ca(2+) sensitivity of force production are dysregulated in a porcine model of pacing-induced heart failure (HF). The level of protein kinase A (PKA)-dependent cardiac troponin I (TnI) phosphorylation was lower in the myocardium surrounding the pacing electrode (pacing site) of the failing left ventricle (LV) than in the controls. Immunohistochemical assays of the LV pacing site pointed to isolated clusters of cardiomyocytes exhibiting a reduced level of phosphorylated TnI. Flow cytometry on isolated and permeabilized cardiomyocytes revealed a significantly larger cell-to-cell variation in the level of TnI phosphorylation of the LV pacing site than in the opposite region in HF or in either region in the controls: the interquartile range (IQR) on the distribution histogram of relative TnI phosphorylation was wider at the pacing site (IQR = 0.53) than that at the remote site of HF (IQR = 0.42; P = 0.0047) or that of the free wall of the control animals (IQR = 0.36; P = 0.0093). Additionally, the Ca(2+) sensitivities of isometric force production were higher and appeared to be more variable in single permeabilized cardiomyocytes from the HF pacing site than in the healthy myocardium. In conclusion, the level of PKA-dependent TnI phosphorylation and the Ca(2+) sensitivity of force production exhibited a high cell-to-cell variability at the LV pacing site, possibly explaining the abnormalities of the regional myocardial contractile function in a porcine model of pacing-induced HF.
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Insuficiencia Cardíaca/metabolismo , Miofibrillas/metabolismo , Troponina I/metabolismo , Animales , Western Blotting , Estimulación Cardíaca Artificial , Separación Celular , Modelos Animales de Enfermedad , Citometría de Flujo , Inmunohistoquímica , Masculino , Fosforilación , PorcinosRESUMEN
Diastolic heart failure, which is also called as heart failure with preserved ejection fraction, is a clinical syndrome in which patients have signs and symptoms of heart failure, normal or near normal left ventricular ejection fraction (≥ 50%) and evidence of diastolic dysfunction. Recent epidemiological studies have demonstrated that more than half of all heart failure patients have diastolic heart failure. The syndrome is more common in women than in men and the prevalence increases with age. Patients with diastolic heart failure form a fairly heterogeneous group with complex pathophysiologic mechanisms. The disease is often in association with other comorbidities, such as hypertension, diabetes mellitus or obesity. The diagnosis of diastolic heart failure is best achieved by two-dimensional and Doppler echocardiography, which can detect abnormal myocardial relaxation, decreased compliance and increased filling pressure in the setting of normal left ventricular dimensions and preserved ejection fraction. Unlike heart failure with reduced ejection fraction, there is no such an evidence-based treatment for heart failure with preserved ejection fraction, which would improve clinical outcomes. Thus, pharmacological therapy of diastolic heart failure is based mainly on empiric data, and aims to the normalization of blood pressure, reduction of left ventricular dimensions and increased heart rate, maintenance of normal atrial contraction and treatment of symptoms caused by congestion. Beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers may be utilized in patients with diastolic dysfunction, especially in those with hypertension. Beta-blockers appear to be useful in lowering heart rate and thereby prolonging left ventricular diastolic filling time, while diuretic therapy is the mainstay of treatment for preventing pulmonary congestion. Nonetheless, treatment of the underlying disease is also an important therapeutic approach. This review summarizes the state of current knowledge with regard to diastolic heart failure.
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Fármacos Cardiovasculares/uso terapéutico , Insuficiencia Cardíaca Diastólica , Volumen Sistólico , Factores de Edad , Fármacos Cardiovasculares/farmacología , Ensayos Clínicos como Asunto , Diagnóstico Diferencial , Femenino , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/tratamiento farmacológico , Insuficiencia Cardíaca Diastólica/epidemiología , Insuficiencia Cardíaca Diastólica/fisiopatología , Hemodinámica , Humanos , Masculino , Factores SexualesRESUMEN
INTRODUCTION: The effect of factor XIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of coronary artery disease (CAD) has been extensively studied. In this study we investigated how FXIII-A Val34Leu genotypes influence plasma factor XIII levels in patients with coronary sclerosis (CS) and myocardial infarction (MI) and how fibrinogen level modulates this effect. PATIENTS AND METHODS: 955 consecutive patients admitted for coronary angiography were categorized according to the presence or absence of significant CS and the history of MI. The frequency of FXIII-A Val34Leu polymorphism, fibrinogen, FXIII activity and antigen levels were determined. RESULTS AND CONCLUSIONS: CS or MI decreased FXIII levels in patients homozygous for FXIII-A Leu34 allele, but not in heterozygous or wild type patients. In the subgroup of patients with CS, but without the history of MI no significant effect was detected, which suggests that MI has a more prominent role. The specific activity of plasma FXIII was independent of FXIII-A Val34Leu genotype. FXIII and fibrinogen levels significantly correlated in CS+ and MI+ patients. In MI+ patients of Leu/Val or Leu/Leu genotypes and with fibrinogen levels in the lowest quartile, FXIII levels were lower than in the same patient groups, but with higher fibrinogen level. The low-scale continuous activation of blood coagulation in CAD patients could lead to parallel FXIII and fibrinogen consumption. As the same amount of thrombin activates more Leu34 FXIII than Val34 FXIII, increased FXIII consumption might be responsible for the decreased FXIII levels in Leu34 homozygous CAD patients.
Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Factor XIII/análisis , Factor XIII/genética , Vasos Coronarios/patología , Fibrinógeno/análisis , Genotipo , Homocigoto , Humanos , Infarto del Miocardio/sangre , Subunidades de Proteína , EsclerosisRESUMEN
AIM: To examine the effects of sinus rhythm (SR) restoration on N-Terminal pro-BNP (NTP-BNP) in patients with atrial fibrillation (AF). METHODS: Subjects with paroxysmal and persistent AF and absence of organic heart disease were prospectively studied. Chemical or electrical restoration of SR was attempted within 48 hours (n = 37) or >3 weeks (n = 73). Clinical and laboratory (NTP-BNP, 72-hour Holter monitor, and electrocardiogram) assessment were obtained at baseline and at 1, 30, and 180 days after SR restoration. Patients were divided into three predefined "outcome groups": (a) maintenance of SR for 1 month, (b) SR with recurrent paroxysmal AF (PaAF), and (c) early (<30 days) recurrence persistent AF (RAF). RESULTS: Of the 110 patients enrolled, 89 had initial successful SR restoration. Baseline NTP-BNP was 936 pg/mL (interquartile range (IQR) 333-2,026); ratio between baseline and 30-day NTP-BNP was 10.2 (IQR 6.42-22.0) for SR group, 3.3 (IQR 2.45-7.34) for PaAF, and 1.07 (IQR 0.87-1.22) for RAF (P < 0.001). Patients with ratio =3 were more likely to have PaAF (46% vs 3%, OR 30, P < 0.001). CONCLUSION: With SR restoration, NTP-BNP decline is observed up to 1 month. NTP-BNP drop is partially or completely abolished by PaAF and RAF, respectively. NTP-BNP does not predict successful SR restoration.
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Fibrilación Atrial/diagnóstico , Fibrilación Atrial/terapia , Péptido Natriurético Encefálico/sangre , Evaluación de Resultado en la Atención de Salud/métodos , Fragmentos de Péptidos/sangre , Medición de Riesgo/métodos , Anciano , Fibrilación Atrial/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recuperación de la Función , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
INTRODUCTION: This paper assesses the first controlled multicentric investigation of outpatient cardiac rehabilitation in Hungary. Framing and starting of the program was carried out beside the Hungarian experts by the United States Department of Health and Human Services. AIMS: To prove the extreme importance of cardiac rehabilitation, both inpatient and outpatient, after the hospital treatment of cardiac emergencies. METHODS: 531 patients were collected at the beginning of the study from three Hungarian cardiological centers having cardiac surgery and cardiac rehabilitation ward. 167 patients were ranked into the outpatients group (Group A), 311 were rehabilitated in hospital (Group B) and 53 served as control (group C). After physical, ergometric and echocardiographic examinations and psychometric evaluation (Beck and WHOBREF questionnaires) the patients of Group A and B performed a conducted training three times weekly for 3 months. All the patients were examined 3 and 12 months later. RESULTS: Significant improvement of ergometric data was observed in both groups of patients who underwent rehabilitation training, but this was not the case with control patients. This improvement could not be observed after one year. The number of anginal attacks and the need of hospital treatment also showed a significant reduction in Groups A and B. CONCLUSIONS: The data have proved that cardiac rehabilitation has an extremely important role in the stabilisation of heart functions and general health of patients after acute myocardial infarction or heart surgery. It was also proved, that 12-week rehabilitation training is not sufficient to achieve long-term stabilization. Sufficient data have accumulated during the study about the effectiveness and safety of outpatient cardiac rehabilitation as an alternative to inpatient service.
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Atención Ambulatoria , Procedimientos Quirúrgicos Cardíacos/rehabilitación , Terapia por Ejercicio , Infarto del Miocardio/rehabilitación , Adulto , Anciano , Angina de Pecho/epidemiología , Angina de Pecho/prevención & control , Ecocardiografía , Ergometría , Femenino , Humanos , Hungría/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Pacientes Ambulatorios , Pruebas Psicológicas , Psicometría , Factores de Tiempo , Resultado del TratamientoRESUMEN
Factor XIII (FXIII) activity and antigen levels were determined in 955 patients investigated by coronary angiography. Patients were sub-grouped according to the presence or absence of coronary sclerosis (CS+, CS-) and a positive history of myocardial infarction (MI+, MI-). In females, but not in males, adjusted FXIII activity and antigen levels were significantly elevated in the CS+MI+ group compared to in the CS+MI- group. FXIII levels in the upper tertile were associated with significantly increased risk of MI in females, but not in males.
Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico , Factor XIII/biosíntesis , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Riesgo , Anciano , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores SexualesRESUMEN
INTRODUCTION: The results on the association of factor XIII (FXIII) A subunit (FXIII-A) Val34Leu polymorphism with the risk of myocardial infarction (MI) are rather inconclusive. The original paper and confirmatory reports demonstrated a protective effect of the mutation, but results demonstrating the lack of protection have also been published. Gene-gene and gene-environmental interactions have been proposed to be responsible for the opposing results. As the rate of change in fibrin clot permeability with increasing fibrinogen concentrations decreased stepwise with increasing number of Leu34 alleles it was proposed that the protection by Val34Leu polymorphism become effective only at higher fibrinogen concentrations. However, this hypothesis has not been tested on patients with coronary artery disease. PATIENTS AND METHODS: 955 consecutive patients admitted for coronary angiography were categorized according to the presence or absence of significant coronary sclerosis (CS) and according to positive or negative history of MI. The frequency of FXIII-A Val34Leu polymorphism, and a number of risk factors, including fibrinogen were determined in the patients. FXIII-A Val34Leu polymorphism was also investigated in a population control group of 1146 subjects. RESULTS: The presence of FXIII-A Leu34 allele or homozygous Leu34 genotype did not change the risk of CS or MI in the general Hungarian population. However, when patients with fibrinogen level in the upper quartile were separately investigated, the Leu34 allele provided a statistically significant protection against MI. CONCLUSIONS: Fibrinogen concentration modulates the effect of Leu34 allele on the risk of MI; its protective effect emerges at increasing fibrinogen concentration.
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Enfermedad de la Arteria Coronaria/etiología , Factor XIII/genética , Fibrinógeno/análisis , Infarto del Miocardio/etiología , Polimorfismo Genético , Arteriosclerosis , Hungría/epidemiología , Epidemiología Molecular , Mutación Missense , Subunidades de Proteína/genética , RiesgoAsunto(s)
Síndrome Coronario Agudo , Cardiología , Insuficiencia Cardíaca , Isquemia Miocárdica/terapia , Terapia Trombolítica , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/terapia , Cateterismo Cardíaco , Enfermedades Cardiovasculares/epidemiología , Fibrinolíticos/uso terapéutico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/prevención & control , Hormonas/metabolismo , Humanos , Hungría/epidemiología , Mortalidad/tendencias , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Infarto del Miocardio/terapia , Isquemia Miocárdica/complicaciones , Miocardio/metabolismo , Intervención Coronaria Percutánea , Terapia Trombolítica/métodosRESUMEN
Both experimental and human clinical studies executed in the last 5 years suggested that bone marrow derived cells may participate in the healing process after myocardial infarction. A number of small clinical trials indicated mild or moderate beneficial effect of intracoronary administration of bone marrow derived stem cells after myocardial infarction. Most of the studies used mononuclear cell fraction; due to the cellular heterogeneity of this cell population the type of the effective subpopulation was not known. We investigated the safety and functional effects of the autologous bone marrow CD34+ stem cells after intracoronary administration in patients with recent myocardial infarction. 8 patients with impaired left ventricular function were transplanted with CD34+ bone marrow stem cells 12 +/- 1 day after the acute coronary event. 2D-echocardiography, FDG-PET and MIBI-SPECT were performed before transplantation and 6 month later. During the 6-month follow-up the global left ventricular function (basal EF 37.3 +/- 2.9%, after cell therapy 44.8 +/- 4.1%) and regional viability / metabolism increased significantly (17.6 +/- 13.5%). The increase of myocardial perfusion in the infarct region was tendentious but not significant. Our results demonstrate for the first time that the CD34+ subpopulation of bone marrow derived stem cells improves left ventricular function and viability after myocardial infarction.
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Antígenos CD34 , Células de la Médula Ósea , Infarto del Miocardio/complicaciones , Trasplante de Células Madre , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/prevención & control , Función Ventricular Izquierda , Adulto , Ecocardiografía , Femenino , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/fisiopatología , Proyectos Piloto , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Trasplante de Células Madre/efectos adversos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón Único , Resultado del Tratamiento , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/etiología , Remodelación VentricularRESUMEN
The mean cholesterol level of the civilized modern humans is above the one considered "physiological", and a biological gradient exists between serum cholesterol level and cardiovascular events. Clinical studies on cholesterol lowering revealed that cardiovascular risk can be lowered in parallel along this gradient, and the "lower is better" rule appears to be supported by the current evidence. LDL cholesterol level should minimally be reduced on average by 50% to approach the "physiological" cholesterol concentration in order to halt the progression of atherosclerosis. Using the initial doses of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), the first-line lipid lowering drugs, this goal cannot be reached. On the other hand, high doses of statins increase the frequency of adverse events, which should contribute to the common failure of putting patients to their lipid targets in a real-world setting. Consequently, the combination of low dose statins and another cholesterol lowering agent with a mechanism of action different than synthesis inhibition (such as ezetimibe) may be the optimal clinical approach to avoid the dose-dependent adverse events. The ongoing large head-to-head clinical trials will clarify the efficacy and safety of cholesterol lowering combination therapy relative to statins in the reduction of cardiovascular risk.
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Anticolesterolemiantes/uso terapéutico , Enfermedades Cardiovasculares/sangre , Colesterol/sangre , Hipercolesterolemia/tratamiento farmacológico , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/efectos adversos , Azetidinas/uso terapéutico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Ezetimiba , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/complicacionesRESUMEN
UNLABELLED: There are only very few epidemiological data about homocysteine levels in patients suffering from cardiovascular (CV) disease in Hungary, however, homocysteine is a newly recognized, independent risk factor of CV diseases. AIM OF THE STUDY: Therefore, in the present study, data of 1010 East-Hungarian patients with signs of CV disease were analyzed retrospectively for correlation between the level of homocysteine and CV diseases, laboratory parameters, as well as genetic differences. PATIENTS AND METHODS: From the studied patient population a control ("healthy") group has been selected according to the following criteria: lack of previous stroke or stenosis of the carotid arteries or the lower extremities, lack of coronary artery stenosis more than 50%, no previous coronary intervention or an angiography diagnosed progression of the coronary atherosclerosis. RESULTS: The level of homocysteine showed statistically significant negative linear correlation with HDL-cholesterol and the anti-atherogenic ApoAI, and showed a positive correlation with CRP and FXIII activities in the entire patient population. When compared to the control group, homocysteine level was significantly higher in patients with previous stroke or acute myocardial infarction, coronary stenosis, progressive coronary disease, physical inactivity, MTHFR gene polymorphism, low folate or vitamin B12 level in both men and women. In patients with type II diabetes the level of homocysteine was significantly higher only in women. CONCLUSIONS: It can be concluded that the level of homocysteine in patients suffering from various CV diseases is high in Hungary. This may have a prognostic value, and shows that reduction of homocysteine level in these patients may be beneficial.
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Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Homocisteína/sangre , Hiperhomocisteinemia/complicaciones , Hiperhomocisteinemia/epidemiología , Adulto , Anciano , Proteína C-Reactiva/metabolismo , Factor de Transcripción COUP II/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/genética , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Factor XIII/metabolismo , Femenino , Ácido Fólico/análogos & derivados , Ácido Fólico/sangre , Ácido Fólico/genética , Humanos , Hungría/epidemiología , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/genética , Modelos Lineales , Masculino , Persona de Mediana Edad , Selección de Paciente , Polimorfismo Genético , Estudios Retrospectivos , Factores de Riesgo , Vitamina B 12/sangreRESUMEN
OBJECTIVE: Saphenous venous grafts (SVGs) are established choices for coronary artery bypass grafting (CABG); however, their lumen patency is limited. Our goal was to investigate the risk factors of SVG degeneration. METHODS: Seventy-five patients (mean age, 57.5±10.4 years) with 133 SVG conduits who had cardiac catheterization ≥1 year after CABG were selected; follow-up period was 67.6±36.8 months. Patients were divided into 3 groups according to angiographic status at follow up [intact: <20% (n=23); narrowed: 20-99% (n=24); and occluded (n=28)]. Baseline clinical conditions were evaluated in relation to follow-up angiography. As onset date of chronic total occlusions is usually uncertain, they arise typically from thrombotic lesions; thus, their value in evaluation is limited. RESULTS: There were no significant differences between the 3 groups in clinical parameters. Linear correlation analysis found significant (p<0.01) positive connection of SVG disease (luminal diameter reduction 20-99%) with C-reactive protein (CRP) and homocysteine (Hcy), as well as between CRP and Hcy. Multiple regression analysis showed plasma Hcy level to be significantly related to graft diameter reduction normalized to time elapsed until angiography in narrowed grafts: 1 µmol/L increase of Hcy was associated with 0.053%/month decrease in lumen diameter (p<0.01; R2=0.428); extrapolating: +10 µmol/L higher Hcy level during 5 years is associated with 32.1% lumen reduction. CONCLUSION: Medium- to long-term SVG degeneration is related to elevated plasma total Hcy in patients with sub-occlusive graft stenosis, while in cases with intact SVGs, the beneficial local flow conditions may protect the grafts from degeneration.
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Puente de Arteria Coronaria , Oclusión de Injerto Vascular , Homocisteína/sangre , Anciano , Angiografía Coronaria , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Factores de Riesgo , Vena Safena , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
BACKGROUND AND PURPOSE: Previously, 30 untreated hypertensive patients were investigated by transcranial Doppler (TCD) monitoring during physical exercise, and changes of hemodynamic parameters were compared with those of age matched healthy subjects. After 3-year antihypertensive (AHT) treatment, these hypertensives were investigated again. The aim of this study was to compare the cerebral hemodynamic changes in the regularly treated and noncompliant (untreated) hypertensives during ergometer cycling. METHODS: Nineteen of 30 previously untreated hypertensive patients could be investigated again using the same method as before. Eleven were regularly treated (treated hypertensive [T-HT] group), and 8 did not take their AHT medications due to lack of compliance (noncompliant hypertensive [NC-HT] group). Blood pressure, heart rate, end-tidal CO2 (etCO2; Capnogard capnograph), and bilateral middle cerebral artery mean blood flow velocity (MV) were continuously monitored during ergometer cycling according to the World Health Organization protocol. Values of 2-minute loading were analyzed. RESULTS: Median loading time did not differ significantly between the T-HT and NC-HT groups. After 2 minutes of cycling in treated patients, the ratio of MV and etCO changes (DeltaMV/DeltaetCO2) showed similar values as before therapy (P = .38), whereas in noncompliant patients, a further worsening of the ratio of DeltaMV/DeltaetCO2 could be observed (P = .04). CONCLUSION: The decrease of arteriolar vasodilation (ie, the ratio of DeltaMV/DeltaetCO2) could be demonstrated in the NC-HT group after 3 years. TCD combined with ergometer cycling is a useful method for evaluation of cerebral hemodynamic changes after AHT therapy.
Asunto(s)
Circulación Cerebrovascular/fisiología , Ejercicio Físico/fisiología , Hipertensión/fisiopatología , Adulto , Antihipertensivos/uso terapéutico , Estudios de Casos y Controles , Prueba de Esfuerzo , Femenino , Estudios de Seguimiento , Hemodinámica/fisiología , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Factores de Tiempo , Ultrasonografía Doppler TranscranealRESUMEN
Heart failure represents a major public health problem in the industrialized countries and despite of optimal medical treatment its mortality remains high. The history of its management reflects growth and changes in our understanding of its pathophysiology. In the past, pharmacological treatment of heart failure was aimed only at relieving edema and improving hemodynamics. Today, however, a major aim of treatment is to antagonize the sympathetic nervous system and renin-angiotensin-aldosterone system, to avert harmful effects of neurohormonal activation on the myocardium and peripheral vessels. Currently, the major pharmacological treatments for heart failure are diuretics, ACE inhibitors, beta-blockers and (in NYHA classes III-IV) aldosterone antagonists. Some patients may also require specific treatment with additional drugs (e.g. anti-arrhythmia agents, anticoagulants, or vasodilators) or procedures such as coronary revascularization, or implantable devices such as pacemakers and implantable cardioverter defibrillators, or resynchronization devices. Patients with end-stage heart failure may require cardiac transplantation or ventricular assist devices. This review is summarized the recent practical drug therapy of heart failure and the results of the newer clinical trial.
Asunto(s)
Insuficiencia Cardíaca , Antagonistas Adrenérgicos beta/uso terapéutico , Angiotensina II/antagonistas & inhibidores , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedad Crónica , Desfibriladores Implantables , Glicósidos Digitálicos/uso terapéutico , Diuréticos/uso terapéutico , Antagonistas de los Receptores de Endotelina , Eritropoyetina/uso terapéutico , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/prevención & control , Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Humanos , Hungría/epidemiología , Factores Inmunológicos/uso terapéutico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Marcapaso Artificial , Péptido Hidrolasas/efectos de los fármacos , Prevención Primaria/métodos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Vasopresinas/antagonistas & inhibidoresRESUMEN
Myocardial infarction became more frequent mainly in the developed countries in the past decades. Beside the pharmacological (thrombolysis, beta-blockers, ACE-inhibitors, antiplatelet- and lipid-lowering drugs, etc.) and interventional (percutaneous coronary intervention, intraaortic balloon pump, resynchronization therapy, left ventricular assist devices etc.) procedures the quality of life of patients and the morbidity and mortality data were improved. However we experience development of heart failure following myocardial infarction because of significant cell loss and left ventricular remodeling. Until now there was not any therapeutic procedure affecting via cardiomyocyte renewal, but in the last 5 years the myocardial stem cell therapy was introduced to human clinical phase. In this review the authors summarized the general features of stem cells, why these cells are in the focus of the interest and their preclinical and clinical applications in myocardial infarction. Promising issues suggests, that intramyocardial implantation of autologous bone marrow derived stem cells become a new therapeutic modality in treatment of myocardial infarction. The stem cell therapy and regenerative medicine would open new perspectives in cardiology. However it is very important to remark, that this, as every medical procedure can be dangerous and can cause side effects. A lot of molecular and cellular mechanism of cell therapy is not clear at present, that's why we should be careful with this opportunity holding in our hands. We have to plan multicenter clinical trials to evaluate the long term safety and efficacy of the procedure.