ABSTRACT
Activity of rheumatoid arthritis (RA) has been evaluated by various biomarkers including matrix metalloproteinase (MMP)-3, but the relationship between the levels of biomarkers and elevation of pulmonary artery systolic pressure (PAs) has not been evaluated in detail. We sought to determine the utility of MMP-3 with other biomarkers for the prediction of PAs in patients with RA. Blood samples for biomarkers and echocardiography were obtained in 100 consecutive patients with RA. PAs was measured by continuous-wave Doppler echocardiography and was correlated with laboratory findings. PAs had a fair correlation with MMP-3 (r = 0.53, p < 0.001) and a weak correlation with KL (Krebs von den Lungen)-6 (r = 0.36, p < 0.001) and rheumatoid factor (r = 0.25, p = 0.011). MMP-3 had a fair correlation with pulmonary vascular resistance (r = 0.42, p < 0.001), but MMP-3 was not related to cardiac output (r = 0.09, p = 0.352). Thirty-nine patients had impaired left ventricular diastolic function. There was no significant differences in PAs and pulmonary vascular resistance (PVR) between the patients with and without impaired left ventricular diastolic function. When 5 variables (age, MMP-3, C-reactive protein, KL-6, and rheumatoid factor) were used in the multivariate analysis, MMP-3 (partial regression coefficient = 0.553, p < 0.001) emerged as the most important variable related to the elevation of PAs. Nine patients (9%) were diagnosed to have pulmonary hypertension by echocardiography. MMP-3 value of 245 ng/ml was the optimal cut-off value for the prediction of pulmonary hypertension (sensitivity: 100%, specificity: 67%, area under the curve 0.89). Thus, a close relation of MMP-3 with PAs and PVR indicate that rise in PAs in patients with RA was ascribed to increase in PVR due to underlying systemic inflammation-mediated pulmonary vascular remodeling.
Subject(s)
Arthritis, Rheumatoid/enzymology , Blood Pressure/physiology , Hypertension, Pulmonary/enzymology , Matrix Metalloproteinase 3/blood , Pulmonary Artery/physiopathology , Vascular Resistance/physiology , Aged , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/physiopathology , Biomarkers/blood , Echocardiography, Doppler , Female , Humans , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Pulmonary Artery/diagnostic imagingABSTRACT
BACKGROUND: Intravascular hemolysis has been reported in patients with cardiac valve prostheses, but intravascular hemolysis in patients with mitral regurgitation with native valve has not been evaluated in detail. We designed a study to elucidate the impact of regurgitation flow on intravascular hemolysis in patients with primary mitral regurgitation by measuring erythrocyte creatine. METHODS: Erythrocyte creatine was enzymatically assayed in 29 patients with moderate to severe primary mitral regurgitation and 12 age-matched healthy volunteers. The size and characteristics of mitral regurgitation were determined by color Doppler echocardiography. RESULTS: Erythrocyte creatine was significantly higher in patients with eccentric jet (n=17, 2.64±0.77µmol/g Hb) than that of central jet (n=12, 1.68±0.13µmol/g Hb) and control subjects (1.39±0.25µmol/g Hb). Patients with eccentric jet had a significantly lower erythrocyte count and hemoglobin (385±58 x104/µL and 116±19g/l) compared to those with central jet (450±47×104/µL and 137±14g/l) and control subjects (433±31×104/µL and 134±19g/l). There were no significant differences in age, estimated glomerular filtration rate, pulmonary artery systolic pressure, left atrial size and left ventricular end-diastolic dimension between patients with eccentric jet and central jet. CONCLUSIONS: Intravascular hemolysis associated with subclincal anemia in patients with eccentric jet was due to the destruction of erythrocyte by collision of the eccentric jet to the atrial wall.