Adiponectin in Relation to Coronary Plaque Characteristics on Radiofrequency Intravascular Ultrasound and Cardiovascular Outcome / Relação da Adiponectina com as Características da Placa Aterosclerótica ao Ultrassom Intravascular com Radiofrequência e Desfechos Cardiovasculares

Abstract Background: Prospective data on the associations of adiponectin with in-vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking. Objective: To investigate the association of plasma adiponectin with virtual histology intravascular ultrasound (VH-IVUS)-derived measures of atherosclerosis and with major adverse cardiac events (MACE) in patients with established coronary artery disease. Methods: In 2008-2011, VH-IVUS of a non-culprit non-stenotic coronary segment was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS, n = 318) or stable angina pectoris (SAP, n = 263) from the atherosclerosis-intravascular ultrasound (ATHEROREMO-IVUS) study. Blood was sampled prior to coronary angiography. Coronary plaque burden, tissue composition, high-risk lesions, including VH-IVUS-derived thin-cap fibroatheroma (TCFA), were assessed. All-cause mortality, ACS, unplanned coronary revascularization were registered during a 1-year-follow-up. All statistical tests were two-tailed and p-values < 0.05 were considered statistically significant. Results: In the full cohort, adiponectin levels were not associated with plaque burden, nor with the various VH-tissue types. In SAP patients, adiponectin levels (median[IQR]: 2.9(1.9-3.9) µg/mL) were positively associated with VH-IVUS derived TCFA lesions, (OR[95%CI]: 1.78[1.06-3.00], p = 0.030), and inversely associated with lesions with minimal luminal area (MLA) ≤ 4.0 mm2 (OR[95%CI]: 0.55[0.32-0.92], p = 0.025). In ACS patients, adiponectin levels (median[IQR]: 2.9 [1.8-4.1] µg/mL)were not associated with plaque burden, nor with tissue components. Positive association of adiponectin with death was present in the full cohort (HR[95%CI]: 2.52[1.02-6.23], p = 0.045) and (borderline) in SAP patients (HR[95%CI]: 8.48[0.92-78.0], p = 0.058). In ACS patients, this association lost statistical significance after multivariable adjustment (HR[95%CI]: 1.87[0.67-5.19], p = 0.23). Conclusion: In the full cohort, adiponectin levels were associated with death but not with VH-IVUS atherosclerosis measures. In SAP patients, adiponectin levels were associated with VH-IVUS-derived TCFA lesions. Altogether, substantial role for adiponectin in plaque vulnerability remains unconfirmed.

Resumo Fundamento: Faltam dados prospectivos sobre as associações de adiponectina com medidas in-vivo de grau, fenótipo e vulnerabilidade da aterosclerose coronariana. Objetivo: Investigar a associação da adiponectina plasmática com medidas de aterosclerose derivadas de ultrassonografia virtual intravascular (VH-IVUS) e eventos cardíacos adversos importantes (major adverse cardiac events - MACE) em pacientes com doença arterial coronariana estabelecida. Métodos: Em 2008-2011, a VH-IVUS de um segmento coronariano não estenótico não culpado foi realizado em 581 pacientes submetidos à angiografia coronariana para síndrome coronariana aguda (SCA, n = 318) ou angina pectoris estável (APE, n = 263) a partir do estudo de ultrassonografia aterosclerótica-intravascular (ATHEROREMO-IVUS). Sangue foi amostrado antes da angiografia coronária. Foram avaliados a carga de placa coronária, a composição tecidual, as lesões de alto risco, incluindo fibroateroma de capa fina (FCF) derivado de VH-IVUS. Mortalidade por todas as causas, SCA, e revascularização coronária não planejada foram registradas durante um ano de acompanhamento. Todos os testes estatísticos foram bicaudais e os valores de p < 0,05 foram considerados estatisticamente significativos. Resultados: Na coorte completa, os níveis de adiponectina não foram associados à carga de placa, nem a vários tipos de tecido virtual histológico. Entre os pacientes com APE, os níveis de adiponectina (mediana[IIQ]: 2,9(1,9-3,9) µg/mL) foram associados positivamente às lesões FCF derivadas de VH-IVUS, (OR[IC 95%]: 1,78[1,06-3,00], p = 0,030), e inversamente associados a lesões com área luminal mínima (ALM) ≤4,0 mm2 (OR[IC 95%]: 0,55[0,32-0,92], p = 0,025). Em pacientes com SCA, os níveis de adiponectina (mediana[IIQ]: 2,9 [1,8-4,1] µg/mL) não foram associados à carga de placa nem a componentes teciduais. A associação positive de adiponectina ao óbito esteve presente na coorte completa (HR[IC 95%]: 2,52[1,02-6,23], p = 0,045) e (limítrofe) em pacientes com APE (HR[IC 95%]: 8,48[0,92-78,0], p = 0,058). Entre pacientes com SCA, essa associação perdeu significância estatística após ajuste multivariado (HR[IC 95%]: 1,87[0,67-5,19], p = 0,23). Conclusão: Na coorte completa, os níveis de adiponectina foram associados à obito, mas não a medidas de aterosclerose por VH-IVUS. Em pacientes com APE, os níveis de adiponectina foram associados a lesões FCF derivadas de VH-IVUS. Em geral, o papel da adiponectina na vulnerabilidade da placa permanece não confirmado.

Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C-reactive protein do not predict future allograft rejection in heart transplant recipients.

BACKGROUND: Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. METHODS: From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 ± 4 (mean ± standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. RESULTS: The mean age of the patients at HTx was 49 ± 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ∼ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. CONCLUSION: The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.