Significance of serum uric acid in pulmonary hypertension due to systemic sclerosis: a pilot study.

Systemic sclerosis is a connective tissue disease, which may lead to elevated pulmonary arterial pressure due to pulmonary arterial hypertension and/or left ventricular diastolic dysfunction. Uric acid (UA) has been shown to be elevated in patients with pulmonary hypertension (PH) and heart failure. We aimed to investigate the potent relationship between serum UA and pulmonary pressure as well as functional capacity in patients with SSc. We studied 66 patients (mean age 57.7±12.1years, 63 women), presenting with SSc. Systolic pulmonary artery pressure assessed by echocardiography, lung function tests, six-minute walk test (6MWT) and serum UA levels were recorded in all patients. In 24 (36%) patients, the diagnosis of PH was established by echocardiography (systolic pulmonary artery pressure ≥40 mmHg). Patients with PH had higher UA serum levels compared to patients without PH (5.1±2.1 mg/dl vs. 4.2±0.9 mg/dl, p=0.04). Among patients with PH, UA values were inversely correlated with the SMWT distance (r=-0.51, p=0.01). Serum UA values increased in proportion to the functional capacity in PH patients with scleroderma. Further investigations in prospective studies will unfold in detail the pathophysiological significance of UA in SSc patients with PH and determine its role as a prognostic marker in the assessment and monitoring of the disease.

N-terminal probrain natriuretic peptide as a biochemical marker in the evaluation of bosentan treatment in systemic-sclerosis-related pulmonary arterial hypertension.

The purpose of our study was to investigate the effect of bosentan treatment on surrogate markers in patients with systemic-sclerosis-related pulmonary arterial hypertension (SScPAH). We studied ten SScPAH patients (nine female, median age 58 years, median duration of disease 9 years). Six-minute walk test (SMWT) and plasma N-terminal probrain natriuretic peptide (NT-proBNP) levels were recorded from patients at baseline and after 20 weeks under bosentan treatment. Wilcoxon paired signed rank test was applied in order to compare NT-proBNP levels and SMWT at baseline and week 20. At week 20, NT-proBNP levels were decreased from a median of 474 fmol/ml (range, 212-1407 fmol/ml) at baseline to 238 fmol/ml (range, 198-335 fmol/ml; p=0.002). Mean SMWT distance increased from a baseline median value of 323 m (range, 224-368 m) to 372 m (range, 232-530 m), representing a nonsignificant increase. Our results suggest that NT-proBNP is a biochemical surrogate marker, which could be used to evaluate the effects of bosentan or other vasodilation therapy in SScPAH.

Left atrial volume and N-terminal pro-B type natriuretic peptide are associated with elevated pulmonary artery pressure in patients with systemic sclerosis.

Early detection of pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) is essential as it leads to substantial morbidity and mortality irrespective of its etiology. The aim of our study was to determine whether noninvasive biochemical and/or echocardiographic indices can predict the presence of PH in these patients. We prospectively studied 66 patients (mean age of 57.7 +/- 12.1 years, 63 women) with SSc without clinical manifestations of heart failure. All patients underwent standard and tissue Doppler echocardiography. Plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) levels were also measured. In 24 (36%) patients, the diagnosis of PH was established by echocardiography (systolic pulmonary artery pressure value > or =40 mmHg). Left atrial (LA) volume, NT-proBNP, ADMA, ratio of early transmitral filling velocity to early diastolic velocity of the mitral annulus (mitral E/E (m)), and right ventricular myocardial performance index (MPI) were univariate predictors of PH. In multivariate analysis, NT-proBNP, LA volume, and right ventricular MPI were independent predictors of PH in SSc patients. LA volume and NT-proBNP may be useful noninvasive markers for the prediction of elevated pulmonary artery pressure in patients with SSc. These parameters should be considered when assessing this population for risk stratification and for identification of patients demanding further investigation and institution of specific therapy for the disease at the time when it is most likely to be effective.

Neurohormonal activation in patients with systemic sclerosis-related pulmonary arterial hypertension.

Systemic sclerosis (SSc) is a connective tissue disease, which may lead to pulmonary artery hypertension (PAH). N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biologic marker for the diagnosis and treatment of congestive heart failure. The aim of our study was to investigate the potential role of the plasma NT-proBNP assay in the assessment of functional status and right heart performance in systemic sclerosis-related pulmonary hypertension (SScPAH). Systolic pulmonary artery pressure (sPAP) assessed by echocardiography, six-minute walk test (SMWT) and plasma NT-proBNP levels were recorded from 45 SSc patients. Mean value of NT-proBNP for SSc patients with PAH (n=14) was 691.7+/-325.7 fmol/L compared to 417.4+/-167.1 fmol/L for patients without PAH (n=31) (p=0.0007). In SSc patients we found a statistically significant correlation between NT-proBNP values and sPAP (r=0.32, p=0.03). Amongst SScPAH patients, NT-proBNP values were significantly correlated with sPAP (r=0.73, p=0.003) and inversely correlated with the SMWT (r=-0.60, p=0.02). These results suggest NT-proBNP as a useful additional biological tool in the evaluation and management of SScPAH patients.