RESUMO
Extensive atherosclerotic plaque burden in the lower extremities often leads to symptomatic peripheral artery disease (PAD) including impaired walking performance and claudication. Interleukin-1ß (IL-1ß) may play an important pro-inflammatory role in the pathogenesis of this disease. Interruption of IL-1ß signaling was hypothesized to decrease plaque progression in the leg macrovasculature and improve the mobility of patients with PAD with intermittent claudication. Thirty-eight patients (mean age 65 years; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. The mean vessel wall area (by 3.0 T black-blood magnetic resonance imaging (MRI)) of the superficial femoral artery (SFA) was used to measure plaque volume. Mobility was assessed using the 6-minute walk test. Canakinumab was safe and well tolerated. Markers of systemic inflammation (interleukin-6 and high-sensitivity C-reactive protein) fell as early as 1 month after treatment. MRI (32 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA in either placebo-treated or canakinumab-treated patients. Although an exploratory endpoint, placebo-adjusted maximum and pain-free walking distance (58 m) improved as early as 3 months after treatment with canakinumab when compared with placebo. Although canakinumab did not alter plaque progression in the SFA, there is an early signal that it may improve maximum and pain-free walking distance in patients with symptomatic PAD. Larger studies aimed at this endpoint will be required to definitively demonstrate this. ClinicalTrials.gov Identifier: NCT01731990.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Idoso , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Biomarcadores/sangue , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Alemanha , Humanos , Mediadores da Inflamação/sangue , Claudicação Intermitente/sangue , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/fisiopatologia , Jordânia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Estudo de Prova de Conceito , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
AIM: The current study investigated biochemical and vascular markers of cardiovascular health in adult patients with epilepsy treated with long-term (greater than 1year) ketogenic diet therapy compared with controls. METHOD: Anthropometric measures, serum fasting lipid panel, apolipoproteins A-1 and B, lipoprotein sub-fractions as well as common carotid intima-media thickness (cIMT), and plaque presence were assessed in 20 adult patients with epilepsy on a modified Atkins diet (MAD) for >1year started as an adult compared with 21 adult patients with epilepsy naïve to diet therapy. RESULTS: Patients treated with MAD had significantly lower weight, body mass index, waist and hip circumference, percent body fat, and serum triglyceride levels when compared with control patients. In contrast, they had significantly higher serum levels of small low-density-lipoprotein (LDL) particles and were significantly more likely to have LDL pattern B in which small LDL particles predominate when compared with controls. However, there was no significant difference in cIMT or plaque presence between groups. CONCLUSION: Our results provide clinical evidence demonstrating the cardiovascular safety of a high-fat, low-carbohydrate diet used in adults with epilepsy for at least 12months. It also highlights potential markers of cardiovascular risk - small dense LDL particles - that should be closely monitored in adults treated with diet therapy long-term.
Assuntos
Artérias Carótidas/fisiopatologia , Dieta Rica em Proteínas e Pobre em Carboidratos/métodos , Epilepsia/dietoterapia , Epilepsia/fisiopatologia , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Peso Corporal , Espessura Intima-Media Carotídea , Dieta com Restrição de Carboidratos/métodos , Dieta Rica em Proteínas e Pobre em Carboidratos/efeitos adversos , Epilepsia/sangue , Feminino , Humanos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Peripheral artery disease (PAD) is common and associated with significant morbidity and mortality. Optimal medical management of PAD is required for each patient, irrespective of the decision regarding lower extremity revascularization. The goals include reducing cardiovascular morbidity and mortality and improving quality of life. The approach should consist of aggressive and individualized risk factor modification including smoking cessation, antiplatelet therapy, a statin, and an angiotensin-converting enzyme inhibitor. Exercise is critical for cardiovascular health and highly effective for improving claudication symptoms. Cilostazol may be considered for symptomatic treatment in certain patients.