Ab1172 Neutrophil-to-Lymphocyte Rate as a Screening Test for Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is one of the main causes of mortality in patients with systemic sclerosis (SSc). Its prevalence ranges between 13 and 35% with echocardiography and between 8 and 12% with right heart catheterization (RHC), which is the gold standard for its diagnosis. Currently, SSc-PAH screening is based on consensus recommendations from European Society of Cardiology/European Respiratory Society (ESC/ERS), Australian Scleroderma Interest Group (ASIG), and DETECT algorithms. These screening approaches have been shown to have very high sensitivity and negative predictive value (NPV). Unfortunately, they have poor positive predictive value (PPV), which increases the rate of false positives and these strategies may not be affordable in developing countries. Low-cost tests for early detection of SSc-PAH are an unmet need. Neutrophil/lymphocyte ratio (NLR) has emerged as potential biomarkers of systemic inflammation in rheumatic diseases. Lately, some studies in South Korea and Turkey have shown a correlation of NLR with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity, modified Rodnan skin score (mRSS), PAH and interstitial lung disease (ILD) [1]. However, the manifestations of SSc present variability in different populations. Could NLR be used as a low-cost screening test for SSc-PAH in the Mexican-Mestizo population. Objectives: To investigate the usefulness of NLR as a screening test for SSc-HAP. Methods: A cross-sectional study, which included patients > 18 years of age with a diagnosis of SSc according to EULAR/ACR 2013 criteria and diagnosis of PAH based on the presence in the echocardiogram of tricuspid regurgitant jet velocity of > 3 meters/second. Patients with corticosteroid use, malignancy, iron deficiency anemia and active infections were excluded. European Scleroderma Trials and Research Group (EUSTAR) disease activity index was used to determine activity. NLR, ESR, CRP, EUSTAR disease activity score, mRSS, nailfold videocapillaroscopy (NVC) pattern and ILD were compared between patients with and without SSc-PAH using U Mann-Whitney and chi-squared test. Spearman´s correlations between NLR and EUSTAR activity index, mRSS, NVC pattern, ILD, ESR and CRP were analyzed. Receiver operating characteristic analysis was performed to assess the best cutoff value for detecting SSc-PAH. Test characteristics, including sensitivity, specificity, PPV, NPV and diagnostic accuracy (DA) were calculated. Multivariate logistic regression analysis (MLRA) for SSc-PAH with their odds ratio (OR) and 95% confidence intervals (95% CI) was conducted establishing NLR as predicting factor adjusted by age, duration and activity of SSc. Results: Of 87 patients with SSc, 95.4% were women. The mean age [standard deviation (SD)] was 49.11 (14.3) years. The median of disease duration [interquartile range 25-75 (IQR)] was 7 (4-12) years and subtype of limited cutaneous SSc was presented in 87.4% of patients. A total of 33 (37.9%) patients had SSc-PAH. Medians of NLR, ESR and EUSTAR activity index were higher in SSc-PAH patients (p < 0.01). ILD and active NVC pattern were more frequent in the group with SSc-PAH (p = 0.003). For NLR, the cut-off value was 2.79 and the area under the curve (AUC) was 0.737 (95% CI 0.623-0.852; p < 0.001), with sensitivity, specificity, PPV, NPV and DA of 66.7%, 74.1%, 61.0%, 78.4% and 71.3% respectively (Figure 1). NLR had a strong correlation with ILD (r = 0.661), a moderate correlation with EUSTAR activity index (r = 0.526) and with CRP (r = 0.426) (p < 0.001). MLRA showed that NLR > 2.79 (OR 4.38, 95% CI 1.34-14.28; p = 0.014) remained associated with a higher risk of SSc-PAH. Conclusion: Although NLR shows lower sensitivity and NPV than DETECT, ASIG and ESC/ERS screening strategies, it has better specificity and PPV than them. NLR may be a regular screening test and a low-cost biomarker to complement the detection of SSc-HAP in Mexican-Mestizo patients. Also, NLR is associated with an increased risk of SSc-HAP. However, these observations need to be confirmed in larger prospective studies. REFERENCES: [1] Tezcan D et al. Acta Dermatovenerol Alp Pannonica Adriat. 2020;29(3):101-107. Acknowledgements: Rheumatology department, UMAE-HE CMNO, IMSS, Guadalajara, Jalisco, México. Disclosure of Interests: None declared.