RESUMO
OBJECTIVES: The goal of our study was to determine whether hormone therapy alters markers of inflammation in postmenopausal women with chronic stable coronary artery disease (CAD) on appropriate medical management. BACKGROUND: Hormone therapy reduces some markers of inflammation associated with atherosclerosis risk (cell adhesion molecules) but increases levels of another marker of inflammation--C-reactive protein-in healthy postmenopausal women. METHODS: Ten women (average age 66 years; range 59 to 76 years) with CAD on medical management (including aspirin [9], statin lipid-lowering therapy [7], angiotensin-converting enzyme inhibitors [3]) were randomly assigned to conjugated equine estrogens 0.625 mg (combined with medroxyprogesterone acetate 2.5 mg daily in five women with uterus intact) or placebo(s) daily for one month with crossover to the alternate therapy after one month off of hormone treatment in a double-blind study. At the end of each treatment phase, the following markers of inflammation were measured in serum: interleukin-6, C-reactive protein, E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and matrix metalloproteinase-9. RESULTS: Hormone therapy significantly lowered serum levels of cell adhesion molecules E-selectin (46.9+/-18.3 vs. 56.3+/-20.6 ng/mL, p = 0.006), intercellular adhesion molecule-1 (282+/-74 vs. 304+/-78 ng/mL, p = 0.013) and vascular cell adhesion molecule-1 (605+/-218 vs. 657+/-214 ng/mL, p = 0.01) but increased levels of matrix metalloproteinase-9 (648+/-349 vs. 501+/-285 ng/mL, p = 0.02). Interleukin-6 (4.33+/-4.78 vs. 3.04+/-1.47 pg/mL, p = 0.283) and C-reactive protein (0.88+/-1.13 vs. 0.61+/-0.50 mg/dL, p = 0.358) were not significantly elevated on hormone therapy compared with placebo values. CONCLUSIONS: Hormone therapy has divergent effects on serum markers of inflammation in women with CAD. Reduction in levels of cell adhesion molecules may reduce attachment of white blood cells to the vessel wall, but increases in matrix metalloproteinase-9 within the vessel wall could digest and weaken fibrous caps of vulnerable plaques, thus provoking thrombosis.
Assuntos
Proteína C-Reativa/análise , Moléculas de Adesão Celular/sangue , Doença das Coronárias/sangue , Terapia de Reposição de Estrogênios , Interleucina-6/análise , Idoso , Doença das Coronárias/tratamento farmacológico , Estudos Cross-Over , Método Duplo-Cego , Selectina E/sangue , Estrogênios Conjugados (USP)/uso terapêutico , Feminino , Humanos , Inflamação/sangue , Molécula 1 de Adesão Intercelular/sangue , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
Except for a small subset of patients with angina whose survival is improved with coronary artery bypass surgery, chronic stable angina can be appropriately managed with medical therapy in the vast majority of patients. Drug therapy includes aspirin, beta-adrenergic blockers, cholesterol-lowering agents and other anti-ischemic drugs that can ameliorate angina and improve the patient's quality of life. Understanding how and when to use these medicines involves knowledge of the mechanisms of these drugs as well as familiarity with the literature supporting their efficacy in various patient populations.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Angina Pectoris/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Vasodilatadores/uso terapêutico , Angina Pectoris/sangue , Angina Pectoris/complicações , Antioxidantes/uso terapêutico , LDL-Colesterol/sangue , Quimioterapia Combinada , Humanos , Hipercolesterolemia/complicações , Hipolipemiantes/uso terapêutico , Fatores de RiscoRESUMO
Ischemic heart disease is one of the most common disorders managed by family physicians. Stratifying patients according to risk is important early in the course of the disease to identify patients who require invasive (percutaneous or surgical) treatment. Physical examination, clinical history, noninvasive tests and angiography are all helpful in determining who will benefit most from medical therapy, percutaneous revascularization or coronary artery bypass surgery. Surgery improves morbidity and mortality in a well-defined group of patients with left ventricular dysfunction and left main coronary artery disease or triple-vessel disease. Patients with proximal left anterior descending artery disease and moderate or severe ischemia benefit from surgery as well. In all other patients, definitive treatment includes aspirin, beta-adrenergic blockers and lipid-lowering agents. Percutaneous revascularization should be considered primarily a palliative measure, because it has never been shown to improve mortality more than medical therapy.
Assuntos
Angina Pectoris/diagnóstico , Angina Pectoris/terapia , Algoritmos , Angina Pectoris/complicações , Angina Pectoris/fisiopatologia , Doença Crônica , Diagnóstico Diferencial , Ecocardiografia , Teste de Esforço , Humanos , Medição de Risco , Disfunção Ventricular Esquerda/etiologiaAssuntos
Anilidas/farmacologia , Antiarrítmicos/farmacologia , Anilidas/efeitos adversos , Anilidas/farmacocinética , Anilidas/uso terapêutico , Animais , Antiarrítmicos/efeitos adversos , Antiarrítmicos/farmacocinética , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/fisiopatologia , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Encainida , Coração/efeitos dos fármacos , Coração/fisiologia , Hemodinâmica/efeitos dos fármacos , HumanosRESUMO
The influence of methyl beta-D-xylopyranoside on human endothelial cell proteoglycans isolated from the medium and extracellular matrix was investigated. Confluent cultures of human endothelial cells incorporate significant amounts of heparan sulfate (78%), chondroitin sulfate (10%), and dermatan sulfate (12%) into the extracellular matrix. Chondroitin sulfate (35%) and dermatan sulfate (37%) were the major glycosaminoglycans present in the medium. In the presence of methyl beta-D-xylopyranoside, incorporation of labeled proteoglycans into extracellular matrix was diminished by approximately 70%. Heparan sulfate comprised the major proteoglycan present in extracellular matrix (89%) in cells grown in the presence of methyl beta-D-xylopyranoside. In contrast to the incorporation of proteoglycan into extracellular matrix, methyl beta-D-xylopyranoside stimulated the secretion of labeled glycosaminoglycan chains into the medium 2.5-fold. In the presence of methyl beta-D-xylopyranoside, secretion of chondroitin sulfate into the medium was markedly stimulated, with a slight increase in secretion of heparan sulfate. Chondroitin sulfate (62%) and heparan sulfate (34%) were the major labeled glycosaminoglycans present in medium from methyl beta-D-xylopyranoside-treated cultures. The effect of methyl beta-D-xylopyranoside on cell adhesion and detachment was investigated. Cell detachment from extracellular matrix depleted of proteoglycan was significantly faster than detachment from normal matrix. Conversely, human endothelial cells adhered faster to normal matrix than to matrix depleted of proteoglycan.