RESUMO
This study presents the long-term safety data from AFCAPS/TexCAPS, the first primary prevention trial to demonstrate that men and women with average levels of low-density lipoprotein cholesterol (LDL-C) and below average levels of high-density lipoprotein cholesterol (HDL-C) can significantly benefit from long-term treatment to lower LDL-C; lovastatin 20 to 40 mg/day reduced the risk of a first acute major coronary event (fatal or nonfatal myocardial infarction, unstable angina, or sudden death) by 37% (p = 0.00008). This double-blind randomized, placebo-controlled trial, in 6,605 generally healthy middle-aged and older men and women, had prespecified end point and cancer analyses. All analyses were intention-to-treat. Safety monitoring included history, physical examination, and laboratory studies (including hepatic transaminases and creatine phosphokinase [CPK]). All participants, even those who discontinued treatment, were contacted annually for vital status, cardiovascular events, and cancer history. After an average of 5.2 years of follow-up, there were 157 deaths (80 receiving lovastatin and 77 receiving placebo; relative risk [RR] 1.04; 95% confidence interval [CI] 0.76 to 1.42; p = 0.82); of which 115 were noncardiovascular (RR 1.21; CI 0.84 to 1.74; p = 0.31), and of these, 82 were due to cancer (RR 1.41; CI 0.91 to 2.19; p = 0.13). There were no significant differences between treatment groups in overall cancer rates, discontinuations for noncardiovascular adverse experiences, or clinically important elevations of hepatic transaminases or CPK. Among those who used cytochrome P450 isoform (CYP3A4) inhibitors, there were no treatment group differences in the frequency of clinically important muscle-related adverse events. Treatment with lovastatin 20 to 40 mg daily for primary prevention of coronary heart disease was well tolerated and reduced the risk of first acute coronary events without increasing the risk of either noncardiovascular mortality or cancer.
Assuntos
Anticolesterolemiantes/uso terapêutico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença da Artéria Coronariana/prevenção & controle , Lovastatina/uso terapêutico , Idoso , Análise de Variância , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Dieta com Restrição de Gorduras , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Militares , Prevenção Primária , Modelos de Riscos Proporcionais , Fatores de Risco , Texas/epidemiologia , Resultado do TratamentoRESUMO
The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is the first coronary heart disease (CHD) primary prevention trial of the cholesterol-reducing agents called "statins" to include women. For 5608 men and 997 postmenopausal women without clinical evidence of cardiovascular disease (CVD) who had average low-density lipoprotein cholesterol (LDL-C) and below average high-density lipoprotein cholesterol (HDL-C), 20-40 mg/day lovastatin reduced first acute major coronary events (AMCEs) 37% (for those receiving placebo and lovastatin, respectively, 183 and 116 first AMCEs defined as fatal or nonfatal myocardial infarction [MI], unstable angina, or sudden cardiac death; relative risk [RR] 0.63; 95% confidence interval [95% CI] 0.50, 0.79; p < 0.001). Statistically significant reductions in prespecified secondary end points (coronary revascularizations, unstable angina, MI, cardiovascular end point events, and coronary end point events) were also associated with lovastatin treatment in the overall cohort. This paper provides results in women, a prespecified subgroup. Among women, 20-40 mg/day lovastatin reduced LDL-C 25% and increased HDLC 9% (p < 0.001). A prespecified analysis revealed consistency with the overall results regardless of gender (i.e., there were no statistical differences between men and women in risk reduction for first AMCEs with lovastatin). However, the number of women who had an AMCE was small, and there was insufficient power to detect a treatment group difference among women (7 of 499 vs. 13 of 498 first AMCEs in those receiving lovastatin and placebo, respectively; RR 0.54; 95% CI 0.22, 1.35; p = 0.183). Numerical reductions in all prespecified secondary end points were observed for women treated with lovastatin, but again, the numbers of events were small and the differences were not statistically significant. Chronic long-term treatment with lovastatin was well tolerated, with no treatment group differences in the frequency of cancer, muscle symptoms, and clinically important liver enzyme elevations. In AFCAPS/TexCAPS, a consistent pattern of numerical reductions in all prespecified primary and secondary cardiovascular end points was observed in women treated with lovastatin for primary prevention of CHD. However, because of the small number of events, there was insufficient power to detect significant treatment group differences. Lovastatin treatment was associated with statistically significant decreases in LDL-C and increases in HDL-C, and chronic long-term treatment with 20-40 mg/day lovastatin was well tolerated in women.
Assuntos
Anticolesterolemiantes/uso terapêutico , Doença da Artéria Coronariana/prevenção & controle , Lovastatina/uso terapêutico , Idoso , Anticolesterolemiantes/administração & dosagem , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Lovastatina/administração & dosagem , Masculino , Menopausa , Pessoa de Meia-Idade , Militares , Inquéritos Nutricionais , Texas , Resultado do Tratamento , Saúde da MulherRESUMO
AIMS: The Air Force/Texas Coronary Atherosclerosis Prevention Study reported that diet with lovastatin, 20-40 mg daily, reduced the risk for a first coronary event by 37%. Because only 17% of this cohort would have qualified for drug therapy according to current U.S. guidelines, we assessed clinical benefit by risk categories. METHODS AND RESULTS: The main outcome measures were event rates of first acute major coronary events stratified by National Cholesterol Education Program and European criteria and target goal. Both those who would and would not be eligible for drug therapy, according to National Cholesterol Education Program guidelines, benefited from intervention. As expected, drug-eligible participants (event rate: lovastatin 1%/year, placebo 1.87%/year [relative risk 0.53, 95% confidence interval: 0.33, 0.84]) were at greater absolute risk for acute major coronary events than non-eligible participants (lovastatin 0.62%/year, placebo 0.93%/year [relative risk 0.67, 95% confidence interval: 0.51, 0.88]). Similar results were found using European guidelines for coronary risk management. Treatment to a target goal suggested a non-significant trend to greater benefit. CONCLUSIONS: The consistent relative benefit across risk categories suggests that it may be possible to improve identification of at-risk persons who would benefit from primary prevention, and to recommend appropriate goals of such treatment.
Assuntos
Anticolesterolemiantes/uso terapêutico , Doença da Artéria Coronariana/prevenção & controle , Lovastatina/uso terapêutico , Militares , Educação de Pacientes como Assunto , Avaliação de Programas e Projetos de Saúde/métodos , Idoso , LDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Texas/epidemiologiaRESUMO
BACKGROUND: Results of the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) demonstrated that treatment with lovastatin, in addition to modifications of diet and lifestyle, reduced the rate of first acute major coronary events compared with placebo in a cohort that included participants with average to mildly elevated total levels of cholesterol, and below average levels of high-density lipoprotein cholesterol, women, and elderly subjects. OBJECTIVE: To describe the baseline characteristics of the study's cohort. DESIGN: This was a double-blind, placebo-controlled, primary-prevention trial in which Americans with average to mildly elevated total levels of cholesterol [4.65-6.83 mmol/l (180-264 mg/dl)] and no clinical evidence of atherosclerotic cardiovascular disease were randomly allocated either 20-40 mg/day lovastatin or placebo in addition to a low-saturated fat, low-cholesterol diet. Baseline characteristics of the study cohort are described, and the characteristics of a USA reference population based upon NHANES III data are provided for comparison. RESULTS: The study includes 5608 men (85%) and 997 women (15%) with mean total cholesterol level 5.71 +/- 0.54 mmol/l (221 +/- 21 mg/dl), low-density lipoprotein cholesterol level 3.88 +/- 0.44 mmol/l (150 +/- 17 mg/dl), high-density lipoprotein cholesterol 0.96 +/- 0.15 mmol/l (37 +/- 6 mg/dl), and median triglyceride level 1.78 +/- 0.86 mmol/l (158 +/- 76 mg/dl). The mean age is 58 years (ranges 45-73 years for men and 55- 73 years for women). The participants are 89% white, 7% Hispanic, and 3% black. CONCLUSION: Results from AFCAPS/TexCAPS will be applicable to large segments of populations; in the USA alone, eight million share the demographic and baseline-lipid-level characteristics of the study cohort.
Assuntos
Anticolesterolemiantes/uso terapêutico , Doença da Artéria Coronariana/prevenção & controle , Dieta com Restrição de Gorduras , Lovastatina/uso terapêutico , Militares , Prevenção Primária/métodos , Idoso , Colesterol/sangue , Estudos de Coortes , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Militares/estatística & dados numéricos , Prevalência , Fatores de Risco , Texas/epidemiologiaRESUMO
BACKGROUND: The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is the first primary-prevention study in a cohort with average total cholesterol (TC) and LDL cholesterol (LDL-C) and below-average HDL cholesterol (HDL-C). Treatment with lovastatin (20 to 40 mg/d) resulted in a 25% reduction in LDL-C and a 6% increase in HDL-C, as well as a 37% reduction in risk for first acute major coronary event (AMCE), defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. This article describes the relation between baseline and on-treatment lipid and apolipoprotein (apo) parameters and subsequent risk for AMCEs. METHODS AND RESULTS: With all available data from the entire 6605-patient cohort, a prespecified Cox backward stepwise regression model identified outcome predictors, and logistic regression models examined the relation between lipid variables and AMCE risk. Baseline LDL-C, HDL-C, and apoB were significant predictors of AMCE; only on-treatment apoB and the ratio of apoB to apoAI were predictive of subsequent risk; on-treatment LDL-C was not. When event rates were examined across tertiles of baseline lipids, a consistent benefit of treatment with lovastatin was observed. CONCLUSIONS: Persons with average TC and LDL-C levels and below-average HDL-C may obtain significant clinical benefit from primary-prevention lipid modification. On-treatment apoB, especially when combined with apoAI to form the apoB/AI ratio, may be a more accurate predictor than LDL-C of risk for first AMCE.
Assuntos
Anticolesterolemiantes/uso terapêutico , Doença da Artéria Coronariana/sangue , Lipídeos/sangue , Lovastatina/uso terapêutico , Doença Aguda , Idoso , Apolipoproteínas/sangue , Estudos de Coortes , Doença da Artéria Coronariana/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Militares , Análise de Regressão , Fatores de Risco , TexasRESUMO
BACKGROUND: The age-related decline in maximal oxygen consumption is attenuated by habitual aerobic exercise. However, the relative effects of training on central and peripheral responses to exercise in older subjects are not known. The present study assessed the contribution of central and peripheral responses to the age-associated decline in peak oxygen consumption and compared the effect of exercise training in healthy older and younger subjects. METHODS AND RESULTS: Ten older and 13 younger men underwent invasive measurement of central and peripheral cardiovascular responses during an upright, staged cycle exercise test before and after a 3-month period of exercise training with cycle ergometry. At baseline, cardiac output and AV oxygen difference during exercise were significantly lower in older subjects. With training, the older and younger groups increased maximal oxygen consumption by 17.8% and 20.2%, respectively. Peak cardiac output was unchanged in both groups. Systemic AV oxygen difference increased 14.4% in the older group and 14.3% in the younger group and accounted for changes in peak oxygen consumption. Peak leg blood flow increased by 50% in older subjects, whereas the younger group showed no significant change. There was no change in peak leg oxygen extraction in the older group, but in the younger group, leg AV oxygen difference increased by 15.4%. CONCLUSIONS: These findings suggest that the age-related decline in maximal oxygen consumption results from a reversible deconditioning effect on the distribution of cardiac output to exercising muscle and an age-related reduction in cardiac output reserve.
Assuntos
Envelhecimento/fisiologia , Circulação Sanguínea/fisiologia , Exercício Físico/fisiologia , Educação Física e Treinamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Débito Cardíaco/fisiologia , Hemodinâmica/fisiologia , Humanos , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Consumo de Oxigênio/fisiologia , Valores de Referência , Fluxo Sanguíneo Regional/fisiologiaRESUMO
CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas. PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.
Assuntos
Anticolesterolemiantes/uso terapêutico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença das Coronárias/prevenção & controle , Lovastatina/uso terapêutico , Idoso , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Dieta com Restrição de Gorduras , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Valores de Referência , Fatores de Risco , Triglicerídeos/sangueRESUMO
To determine the mechanism responsible for the "placebo effect" seen during serial exercise testing of patients with heart failure, we examined metabolic variables for 81 patients who underwent five baseline exercise tests as part of a multicenter drug trial. The patients were 50 men and 31 women with a mean ejection fraction of 30.1% and a mean age of 69 years. From test 1 to 2, the exercise time increased from 419 +/- 140 to 462 +/- 130 seconds before it reached a plateau over the next three tests. Metabolic measurements at test 1 and test 3 revealed no change in peak oxygen consumption ( 1119 +/- 376 to 1105 +/- 346 ml/min). Maximum heart rate, systolic blood pressure, ventilation, and respiratory exchange ratio also were unchanged. The onset of the anaerobic threshold was delayed from 211 +/- 81 to 238 +/- 93 seconds, but there was no change in oxygen consumption at the anaerobic threshold (810 +/- 222 to 795 +/- 220 ml/min). At a predetermined submaximal level, oxygen consumption, ventilation, and respiratory exchange ratio all decreased to a statistically significant degree. These results indicate that a rapid increase in the mechanical efficiency of walking contributes to the placebo effect among patients with heart failure during serial exercise testing and is independent of changes in conditioning or motivation.
Assuntos
Teste de Esforço , Insuficiência Cardíaca/fisiopatologia , Caminhada/fisiologia , Idoso , Limiar Anaeróbio , Feminino , Hemodinâmica , Humanos , Masculino , Consumo de Oxigênio , Efeito Placebo , Troca Gasosa Pulmonar , Ensaios Clínicos Controlados Aleatórios como Assunto , RespiraçãoRESUMO
The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is a randomized, double-blind, placebo-controlled primary prevention trial. It is designed to test the hypothesis that in addition to a lipid-lowering diet, treatment with lovastatin is more effective than placebo in reducing acute major coronary events (i.e., sudden cardiac death, fatal and nonfatal myocardial infarction, and unstable angina) in a cohort with normal to mildly elevated total (180 to 264 mg/dl) and low-density lipoprotein (LDL) cholesterol (130 to 190 mg/dl) and low high-density lipoprotein (HDL) cholesterol (< or =45 mg/dl for men and < or =47 mg/dl for women). Two sites in Texas, Lackland Air Force Base in San Antonio and the University of North Texas Health Science Center in Fort Worth, will conduct the study. After at least 12 weeks of an American Heart Association Step 1 diet and 2 weeks placebo run-in, 6,605 men and women, ages 45 to 73 and 55 to 73 years, respectively, without clinical evidence of coronary heart disease, are randomized in equal numbers to either lovastatin (20 mg/day) or placebo. Study procedures maintain the blind, allowing titration of lovastatin from 20 to 40 mg/day to achieve an LDL cholesterol goal of < or = 110 mg/dl. All participants are followed until study completion, when 320 participants have had a primary end point or a minimum of 5 years after the last participant is randomized, whichever occurs last. All end points are adjudicated by an independent committee using prespecified criteria. Unique features of this trial are (1) the inclusion of unstable angina in the primary end point to reflect the increasing trend to treat coronary heart disease aggressively before a myocardial infarction has occurred, (2) aggressive pharmacologic intervention, with titration, to attain an LDL cholesterol goal less than the current National Cholesterol Education Panel guidelines for primary prevention, and (3) a cohort that includes women, the elderly, and those with mild to moderate hyperlipidemia and low HDL cholesterol. Compared with earlier studies, results will be applicable to a broader population and may help clarify the role of aggressive LDL cholesterol reduction measures in primary prevention. Treatment of this population is likely to realize the greatest cumulative long-term benefit in the prevention of acute major coronary events.
Assuntos
Doença da Artéria Coronariana/prevenção & controle , Inibidores Enzimáticos/uso terapêutico , Lovastatina/uso terapêutico , Idoso , LDL-Colesterol/sangue , Doença da Artéria Coronariana/dietoterapia , Dieta com Restrição de Gorduras , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicina Militar , Projetos de Pesquisa , Texas , Resultado do Tratamento , Estados UnidosRESUMO
We have characterized plaque localization, the extent of compensatory artery enlargement, and the effect of heart rate in experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. We altered heart rate by sino-atrial node ablation (SNA) and then fed the animals an atherogenic diet for 6 months. Heart rate was measured at four time points by 24-hour telemetry. Of nine animals with SNA, heart rate was reduced significantly in six (from 148 +/- 11 to 103 +/- 20 beats/min, p < 0.001) and was unchanged in three. Sham-operated monkeys had no significant change in heart rate. On the basis of comparison with the preoperative mean for all 17 animals (136 +/- 22 beats/min), animals were separated into a low-heart-rate (LHR) group (111 +/- 16 beats/min, n = 12) and a high-heart-rate (HHR) group (150 +/- 16 beats/min, n = 5). Blood pressure, serum cholesterol level, and body weight did not differ for the two groups. As in the human, plaques formed predominantly in the proximal portion of the internal carotid artery at the lateral wall opposite the flow divider. Plaque cross-sectional area increased progressively from the relatively uninvolved, adjacent common carotid artery to the mid-sinus region of the internal carotid artery and decreased from the mid-sinus region to the internal carotid artery beyond the sinus. Plaque distribution was the same for the LHR and HHR groups, but lesion area and percent stenosis were greater for the HHR group than for the LHR animals (2.01 +/- 1.19 compared with 0.76 +/- 0.42 mm2 for lesion area [p < 0.02] and 30.7 +/- 4.4% compared with 15.2 +/- 7.3% for stenosis [p < 0.002]).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Arteriosclerose/fisiopatologia , Artérias Carótidas/patologia , Frequência Cardíaca , Animais , Arteriosclerose/patologia , Pressão Sanguínea , Lipídeos/sangue , Macaca fascicularis , MasculinoRESUMO
The purpose of this study was to determine whether age-related alterations in Doppler diastolic filling indexes occur independent of cardiovascular disease and confounding physiologic variables. Ten old (62 to 73 years) and 10 young (21 to 32 years) healthy male volunteers were rigorously screened for cardiovascular disease and underwent comprehensive Doppler echocardiography, radionuclide ventriculography and invasive measurements of right heart and left atrial pressures. There were no differences between the two groups in the physiologic variables of left ventricular mass, volumes, ejection fraction, end-systolic wall stress, left atrial size, heart rate and right atrial, pulmonary artery, pulmonary capillary wedge and systemic arterial pressures. However, there were marked differences in Doppler left ventricular filling indexes. Compared with the young group, the old group had reduced peak early diastolic flow velocity (56 +/- 13 vs. 82 +/- 12 cm/s, p = 0.0002) and increased atrial diastolic flow velocity (59 +/- 14 vs. 43 +/- 10 cm/s, p = 0.009) and had a peak atrial/early flow velocity (A/E) ratio twice that of the young group (1.09 +/- 0.29 vs. 0.54 +/- 0.15, p less than 0.0001). Similar results were obtained for the time-velocity integrals of the peaks. Subjects in the old group also had a markedly reduced peak filling rate (274 +/- 62 vs. 448 +/- 152 ml/s, p = 0.004). In univariate and multivariate regression analyses, peak early and atrial flow velocities were not related to any of the physiologic variables measured once age was accounted for, although peak filling rate, a volumetric measure flow, was related to body surface area as well as age.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Envelhecimento/fisiologia , Ecocardiografia Doppler , Função Ventricular Esquerda/fisiologia , Adulto , Idoso , Diástole/fisiologia , Frequência Cardíaca/fisiologia , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Pressão , Ventriculografia com Radionuclídeos , Valores de Referência , Análise de RegressãoRESUMO
The role of heart rate in the development of coronary atherosclerosis was assessed in adult male cynomolgus monkeys (Macaca fascicularis). Heart rate was lowered in six animals by surgical ablation of the sinoatrial node. A sham procedure, which included all of the surgical steps except for sinoatrial node ablation, was carried out in eight animals. All of the monkeys were fed an atherogenic high cholesterol diet for 6 months, and heart rates were monitored repeatedly by telemetry during 24-hour test periods. Coronary atherosclerosis in animals with postoperative heart rates less than the preoperative mean for all of the animals that underwent surgery was less than half that of animals with heart rates above the mean or of diet-fed control animals not subjected to surgery. Groups did not differ in blood pressure, serum lipids, or body weight. These results suggest that heart rate in itself may contribute to the mechanisms by which behavioral patterns and physical training influence coronary artery disease.
Assuntos
Arteriosclerose/etiologia , Vasos Coronários , Frequência Cardíaca , Animais , Pressão Sanguínea , Peso Corporal , Colesterol/sangue , Dieta Aterogênica , Macaca fascicularis , Masculino , Contração Miocárdica , Triglicerídeos/sangueRESUMO
Evidence of a clotted false lumen in patients with acute aortic dissection has been considered to be a primary indication for medical rather than surgical therapy. A review of recent publications shows that 14 of 15 such patients survived with medical management. We present three patients who had radiographic, surgical, or necropsy evidence of acute aortic dissection with a clotted false lumen, who suffered further dissection in spite of adequate medical therapy. Our experience indicates that this condition is not as stable as it has been considered in the past. Consequently, we believe that great caution should be exercised in the application of medical therapy and in the follow-up of patients who demonstrate evidence of a clotted false lumen in an acute aortic dissection. Surgical treatment is indicated at the earliest sign of clinical or radiographic deterioration during medical therapy.
Assuntos
Aneurisma Aórtico/diagnóstico por imagem , Dissecção Aórtica/diagnóstico por imagem , Doença Aguda , Idoso , Dissecção Aórtica/terapia , Aorta Torácica , Aneurisma Aórtico/terapia , Aortografia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Experiments were designed to test autologous rectus sheath as a replacement for the thoracic aorta in the growing dog. Adequacy of graft function was determined by angiography at 4 month intervals; stress-strain measurements and microscopic examination were made at the time of autopsy. A 3 cm tubular graft of rectus sheath tissue was employed as an aortic graft in 13 mongrel puppies. Nine puppies (70%) were long-term survivors and were put to death between 6 and 22 months postoperatively. No deaths were due to graft failure. Angiographic studies demonstrated patency of the graft without development of pressure gradients. An increase in diameter of the aorta (21.25%) and the rectus sheath graft %22.87%) were demonstrated in all cases. During the time of observation, the compliance of the growing aorta (93,120 dynes/cm2) decreased to one fourth that of the control aortic tissue (24,800 dynes/cm2), whereas the compliance of the rectus sheath graft (547,1000 dynes/cm2) decreased to only one eighth that of the control rectus sheath (47,400 dynes/cm2). Tensile strength is maintained in both the growing aorta (4.5 x 10(7) dynes/cm2) and the rectus sheath graft (4.7 x 10(7) dynes/cm2; p less than 0.05). Microscopic examination showed no calcification, thinning, or weakness. Vascularization of the graft had occurred, with cellular proliferation and development of more than 30 lamellar-like units in the media and an adventitia-like surface.