Towards the identification of predictors for pulmonary arterial hypertension (PAH) in sclerodermia (SSC) patients
Cheong, Fei Ying
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Identification of predictors and biomarkers to monitor disease status and progression in patients with Scleroderma or Systemic Sclerosis (SSc) is of great interest due to its elevated morbidity and mortality of the disease. Pulmonary Arterial Hypertension (PAH) is one of the most debilitating and common complications in SSc patients. To date, despite of availability of PAH-specific vasodilators, patients with SSe-associated PAH (SSc-PAH) have a poorer prognosis than patients with idiopathic PAH (IPAH) patients. Therefore, early detection of PAH in SSc patients and prompt initiation of PAH treatment is important to improve clinical outcomes. However, there is currently a lack of reliable and effective biomarkers for screening for SSc-PAH. This pilot cross-sectional retrospective cohort study was designed to identify predictors of development of SSc-PAH. In this study, the primary outcome was a comparison of the change in absolute monocyte count and percent monocytes between patients with SSc without PAH and those with SSc-PAH. The secondary outcome was the change in absolute lymphocyte count and percent lymphocytes in the same patient groups. In addition, we examined several other clinical parameters commonly used to suggest PAH in the SSc population: B-type Natriuretic Peptide (BNP), echocardiography and pulmonary function testing (PFT). We found that patients with limited cutaneous scleroderma and PAH (ISSc-PAH) demonstrated a monocytosis (0.71 K/uL) compared to ISSc subjects (0.56 K/uL, mean difference 0.15 K/uL, p less than 0.03). This difference was no longer apparent if all scleroderma patients were included (SSc= 0.62 K/uL, SSc-PAH = 0.67 K/uL, p less than 0.3). Spearman correlation analysis suggested a weak correlation between absolute monocyte count and mean pulmonary artery pressure (mPAP) (R=0.324, p less than 0.039). Furthermore, we found that SSc and ISSc control groups had higher lymphocyte counts than SSc-PAH patients (mean difference 0.26 K/uL, p less than 0.05) and ISSc-PAH patients (0.35 K/uL, p less than 0.04). When we compared lymphocyte counts of these patients pre-PAH diagnosis, we found SSc-PAH patients had significantly higher lymphocyte counts than SSc patients (mean difference 0.4 K/uL p less than 0.05) and IPAH patients (0.6 K/uL, p less than 0.004) prior to PAH diagnosis. However, there was no significant difference in absolute lymphocyte counts between groups at the diagnosis of PAH. The yearly absolute lymphocyte counts for individual SSc-PAH subjects remained stable prior to the diagnosis of PAH and there was no correlation between absolute lymphocyte counts and mPAP (R=0.117, p = 0.47). In agreement with a previously studies, our SSc-PAH subjects demonstrated elevated levels of BNP compared to SSc patients (268.8 ± 316.8 vs. 47.1 ±44.5, p=0.0007 pg/ ml). We found that BNP levels did not change significantly until approximately one-year prior to the diagnosis of PAH. PFTs demonstrated a gradual increase in the %FVC/ %DLCO ratio as early as four years prior to the diagnosis of PAH. On average, the %FVC/ %DLCO ratio for SSc-PAH patients at the time of PAH diagnosis was 1.8 ± 0.6 compared to 1.5 ± 0.3 four years prior to PAH diagnosis. The mean averages of pulmonary arterial systolic pressure (PASP) estimated by echocardiogram for each subject group was 69.8 ± 4.9 mmHg in the IPAH group 52.9 ± 20.5 mmHg in the SSc-PAH group and 30.9 ± 6.7 mmHg in SSc group; both SSc-PAH and IPAH subjects had severe right ventricular (RV) dilation and hypertrophy. By right heart catheterization (RHC), IPAH patients had greater hemodynamic abnormalities. In this preliminary screening study, we did not find sufficient evidence for the use of monocyte or lymphocyte counts as reliable predictors of the development of PAH in patients with SSc.
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