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1.
Circ Cardiovasc Genet ; 7(1): 80-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24399159

RESUMO

BACKGROUND: Vascular Ehlers-Danlos syndrome (VEDS) causes reduced life expectancy because of arterial dissections/rupture and hollow organ rupture. Although the causative gene, COL3A1, was identified >20 years ago, there has been limited progress in understanding the disease mechanisms or identifying treatments. METHODS AND RESULTS: We studied inflammatory and transforming growth factor-ß (TGF-ß) signaling biomarkers in plasma and from dermal fibroblasts from patients with VEDS. Analyses were done in terms of clinical disease severity, genotype-phenotype correlations, and body composition and fat deposition alterations. VEDS subjects had increased circulating TGF-ß1, TGF-ß2, monocyte chemotactic protein-1, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and leptin and decreased interleukin-8 versus controls. VEDS dermal fibroblasts secreted more TGF-ß2, whereas downstream canonical/noncanonical TGF-ß signaling was not different. Patients with COL3A1 exon skipping mutations had higher plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and VEDS probands had abnormally high plasma C-reactive protein versus affected patients identified through family members before any disease manifestations. Patients with VEDS had higher mean platelet volumes, suggesting increased platelet turnover because of ongoing vascular damage, as well as increased regional truncal adiposity. CONCLUSIONS: These findings suggest that VEDS is a systemic disease with a major inflammatory component. C-reactive protein is linked to disease state and may be a disease activity marker. No changes in downstream TGF-ß signaling and increased platelet turnover suggest that chronic vascular damage may partially explain increased plasma TGF-ß1. Finally, we found a novel role for dysregulated TGF-ß2, as well as adipocyte dysfunction, as demonstrated through reduced interleukin-8 and elevated leptin in VEDS.


Assuntos
Síndrome de Ehlers-Danlos/sangue , Inflamação/sangue , Fator de Crescimento Transformador beta/sangue , Adipocinas/sangue , Adolescente , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Composição Corporal , Proteína C-Reativa/análise , Criança , Colágeno Tipo III/antagonistas & inibidores , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Síndrome de Ehlers-Danlos/etiologia , Síndrome de Ehlers-Danlos/genética , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Estudos de Associação Genética , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta1/análise , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta2/análise , Fator de Crescimento Transformador beta2/sangue , Adulto Jovem
2.
J Am Coll Cardiol ; 63(1): 33-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24080110

RESUMO

OBJECTIVES: The aim of this study was to assess the pattern of the adoption of internal mammary artery (IMA) grafting in the United States, test its association with clinical outcomes, and assess whether its effectiveness differs in key clinical subgroups. BACKGROUND: The effect of IMA grafting on major clinical outcomes has never been tested in a large randomized trial, yet it is now a quality standard for coronary artery bypass graft (CABG) surgery. METHODS: We identified Medicare beneficiaries ≥66 years of age who underwent isolated multivessel CABG between 1988 and 2008, and we documented patterns of IMA use over time. We used a multivariable propensity score to match patients with and without an IMA and compared rates of death, myocardial infarction (MI), and repeat revascularization. We tested for variations in IMA effectiveness with treatment × covariate interaction tests. RESULTS: The IMA use in CABG rose slowly from 31% in 1988 to 91% in 2008, with persistent wide geographic variations. Among 60,896 propensity score-matched patients over a median 6.8-year follow-up, IMA use was associated with lower all-cause mortality (adjusted hazard ratio: 0.77, p < 0.001), lower death or MI (adjusted hazard ratio: 0.77, p < 0.001), and fewer repeat revascularizations over 5 years (8% vs. 9%, p < 0.001). The association between IMA use and lower mortality was significantly weaker (p ≤ 0.008) for older patients, women, and patients with diabetes or peripheral arterial disease. CONCLUSIONS: Internal mammary artery grafting was adopted slowly and still shows substantial geographic variation. IMA use is associated with lower rates of death, MI, and repeat coronary revascularization.


Assuntos
Ponte de Artéria Coronária/economia , Ponte de Artéria Coronária/métodos , Artéria Torácica Interna/transplante , Medicare/economia , Infarto do Miocárdio/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Infarto do Miocárdio/economia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Estados Unidos/epidemiologia
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