pulmonary artery vasoreactivity in patients with idiopathic pulmonary arterial hypertension

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1 Supplementary material Jonas K, Magoń W, Waligóra M, et al. High density lipoprotein cholesterol levels and pulmonary artery vasoreactivity in patients with idiopathic pulmonary arterial hypertension Pol Arch Intern Med doi: /pamw.4306 Please note that the journal is not responsible for the scientific accuracy or functionality of any supplementary material submitted by the authors. Any queries (except missing content) should be directed to the corresponding author of the article. Supplementary Methods Hypertension was diagnosed in patients with elevated systolic or diastolic blood pressure (BP) 140 or 90 mmhg, respectively or patients having been prescribed a BP-lowering drugs for high BP[1, 2]. Diabetes was diagnosed based on the plasma glucose criteria of the American Diabetes Association[3, 4], either the fasting plasma glucose or the 2-h plasma glucose value after a 75-g oral glucose tolerance test. Obesity was defined as BMI 30 kg/m2, and overweight as BMI 25 kg/m2 and < 30 kg/m2[5], [6], [7].

2 Supplementary Figure S1 Comparison of: 6MWD, HDL-C, hscrp and creatinine levels between long-term responders and female non-responders. Dots represent values of the parameters in long-term responders (vertical axis) and corresponding values in female non-responders (horizontal axis). The line represents hypothetical distribution of the parameters if no differences between subgroups are present. Abbreviations: 6MWD, six minute walk distance, m; HDL-C, high-density lipoprotein cholesterol, mg/dl; hscrp, high-sensitivity C-reactive protein, mg/l;

3 creatinine, μmol/l Supplementary Table S1 The area under curve (AUC) based variable importance scores based on the Conditional Random Forest approach. Mean 2.50% 97.50% Creatinine CI RA pressure HDL-C NT-proBNP The mean and quantiles are based on 500 repetitions of the algorithm[8] The positive values indicate that the feature carries significant information about the predictor (as the AUC drops after removing this feature), whereas the negative values indicate the feature carries no more predictive power than an independent variable. Abbreviations: CI, cardiac index; HDL-C, high-density lipoprotein cholesterol; NT-proBNP, N-terminal pro-brain natriuretic peptide; RA, right atrium

4 Supplementary Table S2 The strength of association between the ΔmPAP and its most informative predictors as shown in the Lasso and Random Forest model. Coefficient Estimate P-value HDL-C Creatinine RA pressure CI Abbreviations: CI, cardiac index; HDL-C, high-density lipoprotein cholesterol; RA, right atrium Supplementary Table S3 Results (non-zero coefficients) of the LASSO-based variable selection for the binomial model with indicator of the event 'long-term response' as the dependent variable. Results are based on 8-fold cross-validation. Variable Coefficient 6-MWD HDL-C Hs-CRP Creatinine

5 Abbreviations: 6-MWD, six minute walk distance; hscrp, high-sensitivity C-reactive protein; Il-1β, interleukin 1β; Il-6, interleukin 6; NT-proBNP, N-terminal pro-brain natriuretic peptide; PA, pulmonary artery; PVR, pulmonary vascular resistance; RA, right atrium; WHO-FC, WHO Functional Class Supplementary References 1. Kopec G, Podolec P, Podolec J, et al. Atherosclerosis progression affects the relationship between endothelial function and aortic stiffness. Atherosclerosis. 2009; 204: Czarnecka D, Jankowski P, Kopec G, et al. Polish Forum for Prevention Guidelines on Hypertension: update Kardiol Pol. 2017; 75: American Diabetes A. 2. Classification and Diagnosis of Diabetes. Diabetes Care. 2016; 39 Suppl 1: S Malecki M, Kozek E, Zozulinska-Ziolkiewicz D, et al. Polish Forum for Prevention Guidelines on Diabetes: update Kardiol Pol. 2017; 75: Zahorska-Markiewicz B, Podolec P, Kopec G, et al. Polish Forum for Prevention Guidelines on overweight and obesity. Kardiol Pol. 2008; 66: Kopeć G, Moertl D, Jankowski P, et al. Pulmonary artery pulse wave velocity in idiopathic pulmonary arterial hypertension. Can J Cardiol. 2013; 29: Perk J, De Backer G, Gohlke H, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012; 33: Janitza S, Strobl C, Boulesteix AL. An AUC-based permutation variable importance measure for random forests. BMC Bioinformatics. 2013; 14: 119.

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