Additional file 1: Table S1. of Exploratory analysis of the neutrophil to lymphocyte ratio in patients with pulmonary arterial hypertension

Correlation of differential blood count parameters with functional and hemodynamic parameters of patients with PAH. (DOCX 13 kb

Additional file 4: Table S3. of Exploratory analysis of the neutrophil to lymphocyte ratio in patients with pulmonary arterial hypertension

Association of the neutrophil/lymphocyte ratio with demographic, functional and hemodynamic parameters, as well as co-morbidities. (DOCX 16 kb

Additional file 3: Figure S1. of Exploratory analysis of the neutrophil to lymphocyte ratio in patients with pulmonary arterial hypertension

Receiver operating characteristics (ROC) across transplantation-free survival: ROC analyses across the range of relative numbers of neutrophils and the neutrophil/lymphocyte ratio in all patients with PAH, in patients with incident PAH and in patients with PAH without cardiovascular risk factors. (PDF 285 kb

Kaplan-Meier Curves According to Troponin Categories as Measured by Contemporary-Sensitivity, High-Sensitivity and Super-Sensitivity Assays for MACE and HF after Adjustment for Age and Gender.

<p>Dotted lines indicate the 95% confidence intervals. MACE = major adverse cardiac events, cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = highly sensitive troponin I measured by high-sensitivity assay, ss-cTnI = troponin I measured by super-sensitivity assay. Please see the footnote to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090063#pone-0090063-t002" target="_blank">Table 2</a> for the cut points of the troponin categories.</p

Hazard Ratios from Cox Regression Models for Baseline Troponin Assessed by Contemporary-Sensitivity, High-Sensitivity and Super-Sensitivity Assays for Various Endpoints after Adjustment for the Framingham Risk Score.

<p>Shown are the hazard ratios for continuous troponin concentration per 1-SD increment and for categorical troponin concentration, comparing the highest with the lowest defined category. Please see the footnote to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090063#pone-0090063-t002" target="_blank">Table 2</a> for cut points of the categories.</p><p>Abbreviations: MACE = major adverse cardiac events, CVD = cardiovascular disease, MI = myocardial infarction, HF = heart failure, HR = hazard ratio, CI = confidence interval, cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = highly sensitive troponin, ss-cTnI = supersensitive troponin, ns = not significant.</p

Baseline Characteristics of the Study Population by Gender.

<p>Persons with prevalent MACE and pregnant women have been excluded. Binary variables are shown in absolute counts and percentages. For continuous variables the median and the IQR are shown.</p><p>MI = Myocardial infarction, MACE = major adverse cardiac events, BP = blood pressure, HDL = high-density-lipoprotein, CRP = c-reactive protein, NT-proBNP = N-terminal pro-brain natriuretic peptide, IQR = interquartile range, CVD = cardiovascular disease, cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = troponin I measured by high-sensitivity assay, ss-cTnI = troponin measured by super-sensitivity assay</p

Net Reclassification Improvement (NRI) and Clinical NRI for Various Endpoints for Baseline Troponin Assessed by Contemporary-Sensitivity, High-Sensitivity and Super-Sensitivity Assays in Addition to the Standard Framingham Risk Score.

<p>NRI = net reclassification improvement, clinical NRI = NRI for individuals with an intermediate 10-year risk (5–20%) according to the Framingham Risk Score, MACE = major adverse cardiac events, CVD = cardiovascular disease, MI = myocardial infarction, HF = heart failure, cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = troponin I measured by high-sensitivity assay, ss-cTnI = troponin I measured by super-sensitivity assay, ns = not significant.</p

Absolute and Relative Distributions of Troponin I Concentrations in the Study Population.

<p>The categories were defined as follows. For the contemporary-sensitivity assay, troponin category 1 is 0–1 pg/mL (lowest observed non-zero value), category 2 is 1–10 pg/mL (LOD), and category 3 is >10 pg/mL. For the high-sensitivity assay, troponin category 1 is 0–1.9 pg/mL (LOD), category 2 1.9–5.1 pg/mL (same percentile as 10 pg/mL for contemporary troponin), and category 3 is >5.1 pg/mL. For the super-sensitivity assay, troponin category 1 is 0–1.0 pg/mL (median limit of detection), category 2 1.0–5.1 pg/mL (according to the percentiles of contemporary troponin), and category 3 is >5.1 mg/mL.</p><p>cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = troponin I measured by high-sensitivity assay, ss-cTnI = troponin I measured by super-sensitivity assay, LOD = limit of detection.</p

Figure 1

<p>A Cerebral vascular anatomy is not influenced by genotype. Representative cerebral vasculature india ink staining in WT and TG mice. * Branching of internal carotid artery, white dash: partially hidden location of anastomosis of internal carotid and basilar territories. Less intense staining of vessels in the depicted WT animal is due to small differences in india ink perfusion pressure. No systematic difference in vascular architecture was observed (WT n = 4, TG n = 4). B Transtemporal laser doppler analysis of relative cortical blood flow dynamics after insertion of filament shows no difference between WT and TG mice. Baseline was defined as pre-ischemia cerebral blood flow and defined as 100%. WT n = 3, TG n = 3.</p

Cerebral DDAH activity is not increased in hDDAH-1 transgenic mice despite a significant difference in hDDAH-1 expression and translation.

<p>Muscular DDAH activity is increased but generally lower than cerebral DDAH activity. A Quantitative PCR. Relative expression in TG vs. WT mice. (n = 7–8) B Western blot, brain homogenate. Beta-tubulin and DDAH-1 antibodies (n = 3) C Cerebral and muscular DDAH activity. Brain and muscle homogenate (n = 6–8) D ADMA concentration. Brain homogenate (n = 6–8). Error bars represent standard deviation. WT wildtype; TG hDDAH-1 transgenic animals, n.s. not significant, ** p<0.01.</p