Alteração precoce da matriz extracelular e parâmetros diastólicos na síndrome metabólica / Early change of extracellular matrix and diastolic parameters in metabolic syndrome

FUNDAMENTOS: Síndrome Metabólica (SM) está associada com maior risco cardiovascular, porém não está claro se as alterações miocárdicas presentes nessa condição, como a disfunção diastólica, são consequência de mecanismos sistêmicos ou de efeitos diretos no miocárdio. OBJETIVOS: Comparar função diastólica, biomarcadores de atividade da Matriz Extracelular (MEC), inflamação e estresse hemodinâmico, em pacientes com SM e controles saudáveis. MÉTODOS: Pacientes com SM (n = 76) e controles saudáveis (n = 30) foram avaliados clinicamente e submetidos a exame ecocardiográfico e mensuração dos níveis plasmáticos de metaloproteinase-9 (MMP9), inibidor tecidual da metaloproteinase-1 (TIMP1), proteína C reativa ultrassensível (PCR-us), resistência insulínica (HOMA-RI) e NT-proBNP. RESULTADOS: O grupo SM apresentou menor onda E' (10,1 ± 3,0 cm/s vs. 11,9 ± 2,6 cm/s, p = 0,005), maiores valores para onda A (63,4 ± 14,1 vs. 53,1 ± 8,9 cm/s, p < 0,001), razão E/E'(8,0 ± 2,2 vs. 6,3 ± 1,2; p < 0,001), MMP9 (502,9 ± 237,1 vs. 330,4 ± 162,7 ng/mL, p < 0,001), PCR-us (p = 0,001) e HOMA-RI (p < 0,001), sem diferença nos níveis de TIMP1 e NT-proBNP. Na análise multivariada, apenas MMP9 foi independentemente associada a SM. CONCLUSÃO: Pacientes com SM apresentaram diferenças em medidas ecocardiográficas de função diastólica, na atividade da MEC, PCR-us e HOMA-RI em relação aos controles. Porém, somente MMP9 foi independentemente associada com SM. Esses achados sugerem que os efeitos precoces da SM sobre a atividade da MEC podem não ser detectados nas medidas ecocardiográficas de função diastólica usuais.

BACKGROUND: Metabolic syndrome (MS) is associated with increased cardiovascular risk. It is not clear whether myocardial changes showed in this syndrome, such as diastolic dysfunction, are due to the systemic effects of the syndrome, or to specific myocardial effects. OBJECTIVES: Compare diastolic function, biomarkers representing extracellular matrix activity (ECM), inflammation and cardiac hemodynamic stress in patients with the MS and healthy controls. METHODS: MS patients (n=76) and healthy controls (n=30) were submitted to a clinical assessment, echocardiographic study, and measurement of plasma levels of metalloproteinase-9 (MMP9), tissue inhibitor of metalloproteinase-1 (TIMP1), ultrasensitive-reactive-C-Protein (us-CRP), insulin resistance (HOMA-IR) and natriuretic peptide (NT-proBNP). RESULTS: MS group showed lower E' wave (10.1 ± 3.0 cm/s vs 11.9 ± 2.6 cm/s, p = 0.005), increased A wave (63.4 ± 14.1 cm/s vs. 53.1 ± 8.9 cm/s; p < 0.001), E/E' ratio (8.0 ± 2.2 vs. 6.3 ± 1.2; p < 0.001), MMP9 (502.9 ± 237.1 ng/mL vs. 330.4±162.7 ng/mL; p < 0.001), us-CRP (p = 0.001) and HOMA-IR (p < 0.001), but no difference for TIMP1 or NT-proBNP levels. In a multivariable analysis, only MMP9 was independently associated with MS. CONCLUSION: MS patients showed differences for echocardiographic measures of diastolic function, ECM activity, us-CRP and HOMA-IR when compared to controls. However, only MMP9 was independently associated with the MS. These findings suggest that there are early effects on ECM activity, which cannot be tracked by routine echocardiographic measures of diastolic function.

Cost-effectiveness of supervised exercise therapy in heart failure patients.

OBJECTIVE: Exercise therapy in heart failure (HF) patients is considered safe and has demonstrated modest reduction in hospitalization rates and death in recent trials. Previous cost-effectiveness analysis described favorable results considering long-term supervised exercise intervention and significant effectiveness of exercise therapy; however, these evidences are now no longer supported. To evaluate the cost-effectiveness of supervised exercise therapy in HF patients under the perspective of the Brazilian Public Healthcare System. METHODS: We developed a Markov model to evaluate the incremental cost-effectiveness ratio of supervised exercise therapy compared to standard treatment in patients with New York Heart Association HF class II and III. Effectiveness was evaluated in quality-adjusted life years in a 10-year time horizon. We searched PUBMED for published clinical trials to estimate effectiveness, mortality, hospitalization, and utilities data. Treatment costs were obtained from published cohort updated to 2008 values. Exercise therapy intervention costs were obtained from a rehabilitation center. Model robustness was assessed through Monte Carlo simulation and sensitivity analysis. Cost were expressed as international dollars, applying the purchasing-power-parity conversion rate. RESULTS: Exercise therapy showed small reduction in hospitalization and mortality at a low cost, an incremental cost-effectiveness ratio of Int$26,462/quality-adjusted life year. Results were more sensitive to exercise therapy costs, standard treatment total costs, exercise therapy effectiveness, and medications costs. Considering a willingness-to-pay of Int$27,500, 55% of the trials fell below this value in the Monte Carlo simulation. CONCLUSIONS: In a Brazilian scenario, exercise therapy shows reasonable cost-effectiveness ratio, despite current evidence of limited benefit of this intervention.

A prospective, comparative study on the early effects of local and remote radiation therapy on carotid intima-media thickness and vascular cellular adhesion molecule-1 in patients with head and neck and prostate tumors.

BACKGROUND AND PURPOSE: To investigate early vascular changes related to carotid atherosclerotic injury post-radiation therapy (RT), we studied carotid intima-media thickness (IMT) and vascular cellular adhesion molecule (VCAM)-1 at two time-points after RT and compared local and remote irradiation effects in patients with head and neck (HNC) and prostate cancer (PC), respectively. MATERIAL AND METHODS: We prospectively studied patients beginning RT for HNC or PC, performing carotid ultrasound before RT, early after and six months after treatment to measure carotid IMT. Blood samples were simultaneously collected to study VCAM-1 by ELISA. RESULTS: We studied 19 patients with HNC and 24 with PC. Patients with HNC were younger (55 ± 10 years) than PC patients (68 ± 8 years). Early post-RT only HNC patients had an increase in IMT compared to baseline measurements (0.73 ± 0.04 mm vs. 0.80 ± 0.05 mm, p=0.029). On the other hand, VCAM-1 levels decreased in PC patients, remaining unchanged in HNC patients. Late post-RT (six months from previous assessment), neither IMT nor VCAM-1 values changed in both groups. CONCLUSION: Local and remote RT seem to exert differential early effects regarding vascular-related changes: (1) local RT seems to affect vascular structure and increase IMT and (2) RT for PC is associated with reduction in VCAM levels, suggesting systemic modulation of cancer-related factors.