RESUMEN
Ambulatory blood pressure monitoring (ABPM) was used to compare the efficacy and tolerability of once-daily telmisartan 40 mg and once-daily losartan 50 mg in Taiwanese patients with mild-to-moderate essential hypertension in a randomised, double-blind, double-dummy, parallel-group study. The initial 2-week placebo run-in phase was followed by randomisation to treatment with telmisartan 40 mg (n = 31) or losartan 50 mg (n = 30) for 6 weeks. The reduction in 18- to 24-h mean (SE) ambulatory diastolic blood pressure (DBP) from baseline was significantly greater with telmisartan 40 mg (-12.1 +/- 1.6 mmHg, p = 0.036) than with losartan 50 mg (-7.0 +/- 1.8 mmHg). The reduction in 18- to 24-h mean (SE) ambulatory systolic blood pressure (SBP) from baseline was also greater with telmisartan 40 mg (-16.0 +/- 2.4 mmHg) than with losartan 50 mg (-11.8 +/- 2.7 mmHg), but did not achieve statistical significance. Telmisartan was well tolerated; no serious adverse events occurred.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Bencimidazoles/administración & dosificación , Benzoatos/administración & dosificación , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Presión Sanguínea/fisiología , Monitoreo Ambulatorio de la Presión Arterial , Método Doble Ciego , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Telmisartán , Resultado del TratamientoRESUMEN
STUDY OBJECTIVES: The differential diagnosis of syndrome X and coronary artery disease (CAD) in patients with evidence of myocardial ischemia may be difficult. The possible difference in coronary calcium detected by electron-beam CT (EBCT) between syndrome X and CAD is rarely evaluated, especially in aged patients with chronic, stable angina. DESIGN AND SETTINGS: Prospective, controlled study at a tertiary referral medical center. PATIENTS AND MEASUREMENTS: Forty patients with syndrome X (85% male) and 53 patients with CAD (89% male) were enrolled. Ten control subjects (90% male) with negative exercise treadmill test results and normal coronary angiographic findings served as control subjects. EBCT determined the coronary calcium scores (CCSs), and standard cardiovascular risk factors of all study subjects were analyzed. RESULTS: The 93 study patients had CCSs that ranged from 0 to 1,857. Coronary calcification was seen in 2 of the 10 control subjects (20%), 21 of the 40 syndrome X patients (52.5%), and 51 of the 53 CAD patients (96.2%) [p < 0.01]. The CCS (median [range]) was significantly lower in syndrome X patients than in CAD patients: 1 (0 to 117) vs 202 (0 to 1,857) [p < 0.001]. Receiver operating characteristic curve analyses also demonstrated that coronary calcification differentiated syndrome X from CAD (area under curve, 0.891; 95% confidence interval, 0.806 to 0.947). Of the CAD patients whose CCSs were < 117 and overlapped with CCSs of syndrome X, multivariate analyses determined CCS > 5 (odds ratio, 13.1; 95% confidence interval, 2.86 to 59.7), hypertension (odds ratio, 6.4; 95% confidence interval, 1.5 to 27.4), and hypercholesterolemia (odds ratio, 6.7; 95% confidence interval, 1.5 to 30.5) to be independent discriminators to differentiate CAD from syndrome X. Patients with CAD had more frequent hypertension than patients with syndrome X. CONCLUSIONS: The coronary calcium detected noninvasively by EBCT was different, though with some overlapping, between patients with syndrome X and CAD. In addition to standard cardiovascular risk factors, CCS determined by EBCT (especially > 117 or = 0) could differentiate between syndrome X and CAD in patients with chronic, stable angina with evidence of myocardial ischemia. Larger trials would be useful to validate CCS on EBCT as a predictor of clinical outcome in these patients.
Asunto(s)
Angina de Pecho/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Angina Microvascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Enfermedad Crónica , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Curva ROCAsunto(s)
Cardiomiopatías/complicaciones , Hemorragia/etiología , Derrame Pericárdico/etiología , Sarcoidosis/complicaciones , Anciano , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/terapia , Hemorragia/diagnóstico por imagen , Hemorragia/terapia , Humanos , Masculino , Derrame Pericárdico/diagnóstico por imagen , Derrame Pericárdico/terapia , Radiografía , Sarcoidosis/diagnóstico por imagen , Sarcoidosis/terapiaRESUMEN
The aim of this study was to evaluate the prevalence of coronary calcification among moderate- to high-risk Chinese patients and to evaluate the ability of the coronary calcium score determined by electron beam computed tomography (EBCT) to predict angiographic coronary artery disease in this population. We enrolled 163 consecutive patients and analyzed their cardiovascular risk factors, coronary calcium scores and coronary angiogram results. One hundred and twenty-five patients (76.7%) had a positive EBCT scan result (coronary calcium score >0). The prevalence of calcification and the calcium scores showed a graded relation to the number of cardiovascular risk factors and age (p < 0.001 for trend). Coronary calcium scores showed statistically significant differences between patients with angiographic evidence of coronary artery disease and patients with normal coronary angiography (p < 0.05), but could not differentiate between patients with significant and insignificant coronary artery disease. Receiver operating characteristic curve analysis showed that a coronary calcium score >5 predicted angiographic coronary artery disease with 93% sensitivity and 86% specificity (area under the curve 0.95 +/- 0.019). Multivariate analysis showed a coronary calcium score >5 to be the strongest independent predictor of angiographic coronary artery disease (odds ratio 120.7, 95% confidence interval 21.7-671.4; p < 0.001). Coronary calcium score determined by EBCT appears to have a similar predictive value in Chinese patients as it does in other ethnic populations that have been reported to date.
Asunto(s)
Calcinosis/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Angiografía Coronaria , Femenino , Humanos , Masculino , Curva ROC , Sensibilidad y Especificidad , Estadística como Asunto , Tomografía Computarizada por Rayos XRESUMEN
Low density lipoprotein (LDL) oxidation and lipid accumulation are thought to enhance the progression of atherosclerosis. Apolipoprotein H (apoH) has been implicated in the development of human atherosclerosis. However, the roles of apoH in the oxidative modification of LDL and cellular accumulation of lipid constituents remained uncharacterized. In this study, the level of plasma apoH was found to be significantly associated with the oxidative susceptibility of LDL in human subjects. Plasma levels of apoH were positively correlated with the lag time but negatively correlated with LDL oxidation rate in conjugated diene formation. By using a J774 A.1 macrophage culture system, we found that apoH could not only inhibit the formation of conjugated diene and thiobarbituric acid-reactive substances, but also reduce the electrophoretic mobility of oxidized LDL. Furthermore, apoH decreased cellular accumulation of cholesterol via a reduction in cholesterol influx and an increase in cholesterol efflux. This is the first demonstration that apoH appears to have "antioxidant"-like effects on LDL oxidation. The results also suggest that apoH can inhibit the translocation of cholesterol from extracellular pools to macrophages, suggesting that apoH may play an important role in the prevention of atherosclerosis.
Asunto(s)
Colesterol/biosíntesis , Glicoproteínas/farmacología , Lipoproteínas LDL/antagonistas & inhibidores , Macrófagos/efectos de los fármacos , Glicoproteínas de Membrana/farmacología , Arteriosclerosis/sangre , Células Cultivadas , Medios de Cultivo Condicionados/química , Relación Dosis-Respuesta a Droga , Glicoproteínas/sangre , Hospitales de Veteranos , Humanos , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Glicoproteínas de Membrana/sangre , Oxidación-Reducción , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Veteranos , beta 2 Glicoproteína IRESUMEN
BACKGROUND: The detection of coronary artery calcification by electron beam computed tomography (EBCT) has been suggested as an indicator of atherosclerosis and coronary artery disease (CAD). There is no consensus on the correlation between coronary calcification and angiographically significant stenosis on an artery-by-artery basis. OBJECTIVE: To examine the relationship between coronary calcification score (CCS) and the presence of significant CAD on an artery-by-artery basis in patients with stable angina pectoris. METHODS AND RESULTS: EBCT and coronary angiogram (CAG) were evaluated in 71 patients with stable angina and in nine control subjects. The CCSs of each of the four major coronary arteries were highest in patients with significant CAD (n=43), followed by patients with insignificant CAD (n=5), patients with syndrome X (n=23) and control subjects, respectively. Calcification scores of the four major coronary arteries appeared to have different predictive power for significant stenosis on the same vessel. For left main (LM) and left anterior descending (LAD) coronary arteries, CCSs of vessels with significant stenoses were not different from those without significant stenoses (values expressed as medians: LM 0 versus 1; LAD 98.5 versus 70; not significant). Calcification scores of left circumflex (LCX) and right coronary arteries (RCA) were significantly higher in vessels with significant stenosis (LCX 49.5 versus 0; RCA 53 versus 1; P<0.05). CCSs appeared to be moderately useful to predict significant stenoses in these two vessels (areas under receiver operating characteristic curves: LCX 0.68+/-0.08, 95% CI 0.52 to 0.81; RCA 0.71+/-0.08, 95% CI 0.55 to 0.84). CONCLUSIONS: The CCSs of RCA and LCX arteries, but not those of LM and LAD arteries, may predict significant angiographic stenosis on an artery-by-artery basis among patients with stable angina pectoris.
Asunto(s)
Angina de Pecho/complicaciones , Calcinosis/diagnóstico por imagen , Enfermedad Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Análisis de Varianza , Calcinosis/complicaciones , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Angiografía Coronaria , Enfermedad Coronaria/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Factores de Riesgo , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Pulse wave velocity (PWV) is a surrogate marker of arteriosclerosis. It can be measured by recording pressure or flow wave signals at two recording sites of an arterial segment simultaneously or sequentially. However, it is unknown how the values of pulse wave velocity derived from various techniques can be compared. Thus, the aims of the present study were to investigate whether different techniques result in different values of PWV. METHODS: We measured aortic PWV from 101 uremic and non-uremic patients using both applanation tonometry and Doppler velocimetry by sequential method. To evaluate whether there is a difference between the sequentially and simultaneously derived PWV, simultaneous method using 2 tonometer or 2 Doppler probes was also applied in 50 and 23 subjects, respectively. RESULTS: There was no significant difference between PWV derived from sequential and simultaneous tonometry (933+/-310 cm/s and 919+/-301 cm/s,p = 0.09). Likewise, there was no significant difference between PWV derived from sequential and simultaneous velocimetry (778+/-241 cm/s and 761+/-205 cm/s,p = 0.35). However, PWV determined by sequential tonometry was significantly greater than (949+/-315 cm/s and 735+/-208 cm/s, respectively,p < 0.001), yet also significantly correlated with that determined by sequential velocimetry (r = 0.83, p < 0.001). CONCLUSIONS: Sequential applanation tonometry is a practical approach to measure PWV in view of technical convenience and the cost of equipment and manpower. Furthermore, we should be cautious in interpreting PWV derived from different methodologies as greater PWV value might be obtained by applanation tonometry than by Doppler velocimetry.
Asunto(s)
Pulso Arterial , Adulto , Anciano , Femenino , Humanos , Flujometría por Láser-Doppler , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The incidence of syncope increases with age, while aging is also associated with increased arterial wave reflection. HYPOTHESIS: The study was undertaken to determine whether increased arterial wave reflection is a predisposing factor of syncope. METHODS: We recruited 38 patients (28 men and 10 women, mean age 57.2 +/- 20.3 years, range 17-87 years) with a history of syncope within 6 months of entry. The etiology of syncope was documented for each patient by a complete assessment of vasomotor function and cerebral flow. All patients received a comprehensive echocardiographic evaluation of cardiac structure and function. Carotid augmentation index (AI) was estimated noninvasively with the tonometry technique. The results were compared with those from 54 age- and gender-matched controls. RESULTS: The most frequent diagnoses of syncope were postural hypotension (13 patients) and cerebrovascular dysautoregulation (10 patients), and the cause could not be determined in 9 patients. Compared with the control group, the syncope group had a greater AI (20 +/- 21 vs. 10 +/- 15%, p = 0.013). Subgroup analysis of 20 patients aged > 50 years and with the aforementioned diagnoses showed even more striking results: AI, 29 +/- 10 vs. 11 +/- 15%, p < 0.001. The enhanced augmentation in the patients remained when age, systolic blood pressure, height, and heart rate were accounted for. Analysis of the carotid pulse wave suggested that both the timing and intensity of wave reflection were enhanced in patients with a history of syncope compared with controls. CONCLUSIONS: Our results support the hypothesis that enhanced arterial wave reflection is associated with the occurrence of syncope, especially in the elderly.
Asunto(s)
Envejecimiento/fisiología , Arterias/fisiopatología , Síncope/fisiopatología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Presión Sanguínea , Arterias Carótidas/fisiopatología , Interpretación Estadística de Datos , Ecocardiografía , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Pulso Arterial , Síncope/etiología , Pruebas de Mesa Inclinada , Ultrasonografía Doppler TranscranealRESUMEN
Coronary artery to left ventricular fistula is an unusual anatomic anomaly consisting of a communication between one of the coronary arteries and the left ventricle. Only sporadic cases have been published in the literature. Diffuse multiple fistulas involving both left and right coronary arteries are even rarer. This report describes a 60-year-old woman with diffuse multiple fistulas communicating between both coronary arteries and the left ventricle. The patient manifested clinically with exertional angina and myocardial ischemia, as evidenced by a positive stress exercise test, which represents the coronary "steal" phenomenon.
Asunto(s)
Anomalías de los Vasos Coronarios/complicaciones , Fístula Vascular/complicaciones , Femenino , Ventrículos Cardíacos , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVE: To investigate the roles of nitric oxide and adenosine triphosphate (ATP)-sensitive potassium channels (KATP) in the shortening of cardiac action potential in endotoxic shock. DESIGN: Prospective animal study with concurrent controls. SETTING: University animal research laboratory. SUBJECTS: Adult Hartley guinea pigs, weighing 300-400 g. INTERVENTIONS: Guinea pigs were anesthetized and mechanically ventilated for 6 hrs. Lipopolysaccharide (LPS) or saline (sham group) were given intravenously. Drug effects were examined at the end of 6 hrs. MEASUREMENTS AND MAIN RESULTS: Plasma nitrate concentration was measured hourly, while guanosine 3',5'-cyclic monophosphate (cGMP) content and action potential duration at 90% of repolarization (APD90) of papillary muscle were examined every 2 hrs in the 6-hr endotoxemia in both the sham and the LPS-treated groups. The basal levels of these three variables showed no difference in the two groups. In the sham group, these variables did not change significantly (n = 14 for plasma nitrate determination; n = 5 for cGMP content measurement; n = 5-14 for APD90 measurement; all p > .05). But in the LPS-treated group, both plasma nitrate concentration and cGMP content of papillary muscle showed time-dependent increases and they were significantly higher than those in the sham group (at the 6th hr, plasma nitrate: 42.6 +/- 7.7 vs. 21.8 +/- 3.1 micromol/L, both n = 14, p < .01; cGMP: 1.52 +/- 0.15 vs. 0.73 +/- 0.08 pmol/mg protein, both n = 5, p < .01). In contrast, APD90 revealed a time-dependent decrease compared with that in the sham group (at the 6th hr, 137.1 +/- 52 vs. 188.2 +/- 4.8 msecs, both n = 14, p < .001). In the following 60-min in vitro recording of action potentials after the end of 6-hr endotoxemia, the shortened APD90 in the LPS-treated group did not recover and remained shorter compared with that in the sham group, in which the APD90 showed no significant changes (at the 60th min, 165.1 +/- 5.7 vs. 200.2 +/- 3.8 msecs, each n = 14, p < .01). However, in the presence of glibenclamide, a specific KATP blocker (100 micromol/L; n = 10), the APD90 could be reversed almost completely to the same value as that in the sham group (n = 14) (196.6 +/- 3.5 vs. 200.2 +/- 3.8 msecs; p > .05), despite glibenclamide having no effect on the APD90 in the sham group. In the LPS-treated group, NG-nitro-L-arginine methyl ester (1 mmol/L; n = 4), methylene blue (10 micromol/L; n = 5), and aminoguanidine (100 micromol/L; n = 4) significantly prolonged the shortened APD90 (192.5 +/- 3.1, 195.0 +/- 3.3, and 176.5 +/- 3.3 msecs, respectively; p < .01, p < .01, and p < .05, respectively, compared with that without these agents, 165.1 +/- 5.7 msecs, n = 14). These agents had negligible effects on the APD90 in the sham group (all p > .05). Furthermore, 8-bromoguanosine-3',5'-cyclic monophosphate (500 micromol/L; n = 5) decreased APD in intact papillary muscle (mean reduction of APD90, 13.5 +/- 3.5%, n = 5; p < .05), an effect abolished by pretreatment with glibenclamide (100 micromol/L; n = 5) that did not have an effect by itself. CONCLUSIONS: In this experimental model, we provide reasonably convincing evidence to suggest that in endotoxic shock, an increase in nitric oxide activity may activate KATP, which plays a major role in the shortening of APD, presumably through a cGMP-dependent pathway.
Asunto(s)
Potenciales de Acción/fisiología , Adenosina Trifosfato/fisiología , Óxido Nítrico/fisiología , Canales de Potasio/fisiología , Choque Séptico/fisiopatología , Potenciales de Acción/efectos de los fármacos , Adenosina Trifosfato/antagonistas & inhibidores , Animales , GMP Cíclico/análisis , Inhibidores Enzimáticos/farmacología , Gliburida/farmacología , Guanidinas/farmacología , Cobayas , Lipopolisacáridos , Azul de Metileno/farmacología , NG-Nitroarginina Metil Éster/farmacología , Músculos Papilares/química , Factores de TiempoRESUMEN
BACKGROUND: Irbesartan is a newly developed angiotensin II receptor antagonist. Its antihypertensive efficacy and safety in Taiwanese patients with mild to moderate hypertension remains to be determined. METHODS: This was a multicenter, double-blind, randomized, parallel group study. One hundred and sixteen patients from three centers were enrolled. After a placebo lead-in period of 14 days, 55 patients (24-75 years-of-age) who had a mean seated diastolic blood pressure of 95 to 110 mmHg were randomized to once-daily treatment with irbesartan 150 mg or enalapril 10 mg. Doses were doubled at week 4 if trough seated diastolic blood pressure was 90 mmHg or more. Trough blood pressure was measured at zero, two, four and eight weeks of treatment. RESULTS: Both treatments lowered blood pressure with no significant difference in efficacy between treatment groups. Irbesartan 150 mg to 300 mg provided reductions in trough seated systolic and diastolic blood pressures at week 8 of -16.5 mmHg and -7.2 mmHg, respectively, with 36% of patients having a favorable response. Similarly, enalapril 10 mg to 20 mg reduced systolic and diastolic blood pressure by -10.6 mmHg and -5.0 mmHg, respectively, with a response rate of 43%. Headache, malaise and dizziness were the major adverse reactions observed in both groups. The incidence of drug-related cough was significantly higher with enalapril (18%) than with irbesartan (0%). CONCLUSIONS: Irbesartan 150 mg to 300 mg once daily was as effective in lowering blood pressure as enalapril 10 mg to 20 mg once daily. Both irbesartan and enalapril were well tolerated, while there was a significantly lower incidence of cough with irbesartan compared with enalapril.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Enalapril/uso terapéutico , Hipertensión/tratamiento farmacológico , Tetrazoles/uso terapéutico , Adulto , Anciano , Compuestos de Bifenilo/efectos adversos , Método Doble Ciego , Enalapril/efectos adversos , Femenino , Humanos , Irbesartán , Masculino , Persona de Mediana Edad , Tetrazoles/efectos adversosRESUMEN
BACKGROUND: The incidence of postinfarct cardiac events can be reduced through secondary prevention by lipid regulation. The relationship between early-detected lipids and prognosis was investigated prospectively in 97 non-diabetic patients with acute myocardial infarction (AMI). METHODS: Blood samples were analyzed in five evolving stages of AMI: 1) immediately after admission (< 24 hours after the onset of symptoms); 2) on the second day after admission (< 48 hours after the onset of symptoms); 3) on the seventh day after admission; 4) two weeks after the AMI; and 5) three months after the AMI. Cardiac events, including congestive heart failure, reinfarction, unstable angina, ventricular tachyarrhythmia and sudden cardiac death were evaluated at a mean follow-up of 26 months. RESULTS: Serial measurements in 75 cases with complete follow-up showed that all lipids except lipoprotein(a) had a decline in plasma level after patients were admitted to hospital. The concentrations of lipids three months postinfarct approached the admission values. Age, body mass index, vessel number, severity of vessel disease and the initial values of lipids on admission had no influence on postinfarct cardiac events in these patients. CONCLUSIONS: The results indicate that the plasma levels of lipids detected within 24 hours after AMI can be used as the baseline lipid levels. Nevertheless, the impact of these lipids on the adverse outcomes in non-diabetic AMI patients should be further studied in a large-scale study.
Asunto(s)
Lípidos/sangre , Infarto del Miocardio/sangre , Anciano , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Humanos , Persona de Mediana EdadRESUMEN
To investigate whether systemic endothelial function on forearm resistance vessels is related to angiographic restenosis after coronary stenting, 47 men who underwent elective coronary stenting were divided into 2 groups according to the presence (n = 20) or absence (n = 27) of in-stent restenosis 6 months after the procedure. Another 19 risk factor-matched men with normal coronary angiograms served as the control group. Forearm blood flow was assessed by venous occlusive plethysmography. Basal forearm blood flow was similar between restenosis, nonrestenosis, and control groups (2.63 +/- 0.19, 2.58 +/- 0.14, and 3.23 +/- 0.13 ml/100 ml forearm tissue per minute, respectively). In all 3 groups, forearm blood flow increased significantly during reactive hyperemia (5.75 +/- 0.7, 11. 32 +/- 1.23, and 14.52 +/- 1.36 ml/100 ml forearm tissue per minute, p <0.05, respectively) and remained unchanged after sublingual administration of nitroglycerin. The percentage change of forearm blood flow during reactive hyperemia was significantly lower in the restenosis group (117.3 +/- 18.3%) than in the nonrestenosis group (354.2 +/- 46.5%, p <0.01). This difference was still present after sublingual nitroglycerin (37.6 +/- 21.2% vs 226.4 +/- 40.5%, p <0. 01). In contrast, percentage change of hyperemic forearm blood flow was significantly lower in patients with angina (117.5 +/- 49.5%) than in those without angina (290.1 +/- 37.4%, p <0.05) at follow-up. In all patients, the angiographic loss index was correlated negatively to the percentage change of hyperemic forearm blood flow (r = -0.33, p <0.01) and positively to the percentage change of forearm vascular resistance during reactive hyperemia (r = 0.33, p <0.01). In patients with angiographic restenosis after coronary stenting, forearm reactive hyperemia was more impaired compared with those without angiographic restenosis. Systemic endothelial dysfunction might be either a marker or one of the confounding factors in the development of late restenosis after coronary stenting.
Asunto(s)
Enfermedad Coronaria/fisiopatología , Enfermedad Coronaria/terapia , Antebrazo/irrigación sanguínea , Hiperemia/etiología , Stents , Anciano , Angiografía Coronaria , Endotelio Vascular/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pletismografía , RecurrenciaRESUMEN
Information from clinical and pharmacokinetic studies of angiotensin-converting enzyme inhibitors (ACEIs) has come from subjects who are mostly male and Caucasian, but the use of ACEIs extends to populations worldwide. Significant differences between Chinese in general and male Caucasians have been demonstrated in the pharmacokinetics/dynamics of other drug classes that could have implications for the use of ACEIs in the Chinese population. These include: significant Chinese/Caucasian genetic variation in the renin-angiotensin system based on an insertion/deletion (O/D) polymorphism of the ACE gene; the genetic determination of plasma ACE activity in the Chinese population; and genetic factors involving the disease substrate which may also influence the response to treatment. Oral and IV pharmacokinetic data from various studies of Chinese and Caucasian subjects are available for cilazapril, fosinopril, and perindopril, and pharmacodynamic data are available for eight different ACEIs. Based on these data, there are few differences among the pharmacokinetics of ACEIs between Chinese and Caucasians. Most ACEIs showed good blood pressure lowering efficacy in Chinese (benazepril, enalapril, fosinopril and spirapril), with perhaps less blood pressure lowering with cilazapril or a relatively shorter-term effect with cilazapril or perindopril compared to Caucasions. Chinese experience more cough from ACEIs (captopril and enalapril) than Caucasians. Data suggest that fosinopril may not induce cough in as many subjects as other ACEIs, and this seems to be true of Chinese as well. The mechanism, currently unknown, could involve fosinopril's dual elimination pathway (hepatic and renal). Pharmacokinetic data also support the use of fosinopril in congestive heart failure where elimination pathways may be impaired. In conclusion, ethnic differences between Chinese and Caucasians with respect to ACE and AGT gene polymorphism, which might be expected to differentially affect the action of ACEIs in these two ethnic groups, do not, in fact, have such an effect. Rather, differences among the ACEIs appear to be more important. Journal of Human Hypertension (2000) 14, 163-170.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Pueblo Asiatico , Pueblo Asiatico/genética , China/etnología , Humanos , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/genética , Población BlancaRESUMEN
BACKGROUND: Platelets are believed to play a role in the ischemic complications of coronary angioplasty, such as abrupt closure of coronary vessels during or soon after the procedure. Accordingly, we evaluated the effect of a chimeric monoclonal antibody abciximab, directed against the platelet glycoprotein IIb/IIIa receptor, in patients undergoing angioplasty who were at high risk for ischemic complications. This receptor is the final common pathway for platelet aggregation. METHODS: In a prospective, double-blind trial, we randomly assigned 42 patients to receive a bolus and an infusion of placebo or a bolus and an infusion of abciximab. Low-dose, weight-adjusted heparin (initial dose of 70 U/kg of body weight) was used in both groups. Patients underwent coronary angioplasty for high-risk clinical situations involving unstable angina or high-risk coronary morphologic characteristics. The primary study end-point consisted of any of the following: death, nonfatal myocardial infarction, unplanned surgical revascularization, unplanned repeat percutaneous procedure, unplanned implantation of a coronary stent, or insertion of an intra-aortic balloon pump for refractory ischemia within 30 days of randomization. RESULTS: Compared with placebo, the abciximab resulted in a trend toward reduction in periprocedural myocardial infarction from 15% to 0%, although the differences were not statistically significant (p = 0.099). There were no significant differences between the two groups in the risk of major and minor bleeding and the need for blood transfusion. CONCLUSIONS: Inhibition of platelet glycoprotein IIb/IIIa receptor with abciximab, together with low-dose, weight-adjusted heparin, had a favorable trend toward the reduction of periprocedural myocardial infarction in patients undergoing high-risk angioplasty, without increasing the risk of hemorrhage.
Asunto(s)
Angioplastia Coronaria con Balón , Anticuerpos Monoclonales/uso terapéutico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Abciximab , Adulto , Anciano , Coagulación Sanguínea , Enfermedad Coronaria/sangre , Enfermedad Coronaria/terapia , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Little information is available concerning the effect of late coronary stenting in patients with recent myocardial infarction, especially long-term results. We retrospectively reviewed our results of 57 stent placements in 52 consecutive patients who received stents at an infarct-related lesion 24 hr to 30 days after an acute myocardial infarctions (median, 14 days). The average age was 67 years; 90% were male. Two patients who suffered from acute stent thrombosis received revascularization again and two early deaths were due to refractory cardiogenic shock before discharge. Mean patient clinical follow-up was 18.3 +/- 6.5 months. There were 1 subacute stent thrombosis, 1 cardiogenic death, and 10 patients (20.8%) in total suffering from angina class II to IV. Angiographic follow-up was performed in 36 patients (80%) at a mean of 7.5 +/- 3.1 months. Of these 36 patients, only 1 (3% of the total population undergoing follow-up angiography) had reocclusion at follow-up, but restenosis existed in 18 patients (50%). We conclude that there is still relatively high incidence of angiographic recurrence that is often silent in long-term follow-up, though the long-term result of late stenting in recent MI is low incidence of reocclusion.
Asunto(s)
Angioplastia Coronaria con Balón , Infarto del Miocardio/terapia , Stents , Anciano , Angiografía Coronaria , Femenino , Estudios de Seguimiento , Humanos , Masculino , Infarto del Miocardio/diagnóstico por imagen , Recurrencia , Estudios Retrospectivos , Stents/efectos adversos , Trombosis/etiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Coronary artery stents have been used widely to prevent acute closure as a bailout procedure, or to decrease restenosis after balloon angioplasty. Stent use has increased substantially in recent years due to the ease and simplicity with which stents provide a predictable angiographic result. However, few data exist on the long-term safety of stents. This case report describes a 63-year-old male patient who developed intimal dissection after balloon angioplasty and who underwent coronary stent placement of a sheathed stent (half Palmaz-Schatz stent, 3.5 mm in diameter and 7 mm in length) as a bailout procedure. Postdilatation with a 3.5-mm balloon was performed at the maximum pressure of 14 atmospheres with a satisfactory angiographic result. However, an aneurysmal dilatation at the stent site was noted three months later. High-pressure stent use without immediately visible vascular dissection by angiography may not be effective for prevention of coronary aneurysm development in a case such as this. Aneurysmal dilatation may be a late complication in cases of coronary artery stent placement.
Asunto(s)
Angioplastia/efectos adversos , Aneurisma Coronario/etiología , Stents/efectos adversos , Angioplastia Coronaria con Balón , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This study examined thepharmacokinetics and pharmacodynamics of fosinopril (IVand oral) in Chinese subjects to determine whether they were different from a group of somewhat heavier and older Western control subjects previously published using the same methods. It was an open-label, randomized, balanced, two-way crossover study comparing oral and IV pharmacokinetics in 12 healthy Chinese subjects in a clinic in Taiwan. Each subject received 10 mg of oral fosinopril or 7.5 mg of IV fosinoprilatin a randomized sequence with sampling for fosinoprilat concentrations over 48 hours. Standard pharmacokinetics, including AUC, Cmax Tmax, T 1/2, Vss, bioavailability, total clearance, and renal and nonrenal clearance, were determined as well as pharmacodynamic effects on angiotensin-converting enzyme (ACE) activity. Following oral administration of 10 mg fosinopril, AUC0-T and AUCinf were 1,556 +/- 586 ng x hr/mL and 1,636 +/- 620 ng x hr/mL, respectively; T 1/2 was 17.4 +/- 11.4 hr; Cmax was 183.4 +/- 59.4 ng/mL; and median Tmax was 4.0 hr, with > 99% protein binding. Following IV administration of 7.5 mg fosinoprilat, AUC0-T and AUCinf were 7,727 +/- 2,638 ng x hr/mL and 7,816 +/- 2,693 ng x hr/mL, respectively; T 1/2 was 13.0 +/- 5.2 hr; and median Tmax was 4.0 hr, with 99.5% +/- 0.22% protein binding and a Vss of 5,850 +/- 2,780 mL. Bioavailability was 22.3% +/- 7.9%. Percent urinary excretion was 7.6% +/- 2.6% after oral dosing and 42.6% +/- 6.1% after IV dosing. After IV, dosing total clearance was 1,088 +/- 439 mL/hr, renal clearance was 472 +/- 213 mL/hr, and nonrenal clearance was 617 +/- 246 mL/hr. ACE inhibition was essentially complete through 12 hours and markedly reduced through 24 hours. Compared to a somewhat heavier and older previously reported control group, pharmacokinetic values were similar except for a slightly lower AUC and total clearance in Chinese and a statistically significantly lower nonrenal clearance. Pharmacodynamic effects on ACE activity were essentially identical. There is no reason to expect significant differences in fosinopril dosing or effect in a Chinese population compared to a Western population.