Possible mechanism linking sFRP3 release during LV wall stress and non-linear association with survival.

<p>Increased wall stress [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133970#pone.0133970.ref001" target="_blank">1</a>] may induce the release of sFRP3 from fibroblasts [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133970#pone.0133970.ref002" target="_blank">2</a>]. Depending on concentration of sFRP3 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133970#pone.0133970.ref003" target="_blank">3</a>], this may lead to insufficient, balanced or excess inhibition of the Wnt [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133970#pone.0133970.ref004" target="_blank">4</a>] in the presence of inflammation and lead to a non-linear association with survival [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133970#pone.0133970.ref005" target="_blank">5</a>].</p

Effect of sFRP3 on the association between other predictors and outcome.

<p>BMI, body mass index; NYHA, New York Heart Association; eGFR, estimated glomerular filtration rate; ApoB, apolipoprotein B; ApoA-1, apolipoprotein A-1; NT-proBNP, amino-terminal pro-brain natriuretic peptide; CRP, C-reactive protein; T2 sFRP3, middle tertile secreted frizzled related protein 3.</p><p>Effect of sFRP3 on the association between other predictors and outcome.</p

Discriminatory properties of sFRP3.

<p>Area under curve (AUC) and 95% Confidence interval (CI) of sFRP3 as a categorical (1. and 3. tertile <i>vs</i>. 2. tertile) variable, corresponding <i>p</i>-value.</p

Kaplan-Meier curves for the primary end point (panel A), as well as for all-cause (B) and CV (C) mortality according to tertile sFRP3 concentration.

<p>T1, lowest tertile serum sFRP3; T3, highest tertile serum sFRP3. Patients with T2 sFRP3 showed a markedly better outcome than patients in T1 and T2; <i>p</i><0.001 for the primary end point and all-cause mortality, <i>p</i><0.002 for CV mortality.</p

Kaplan Meier plots showing the association between tertiles of sFRP3 and all-cause mortality in the GISSI-HF-HF trial stratified according to age and presence of ischemic heart disease.

<p><b>A.</b> ischemic HF <70 years of age <b>B.</b> ischemic HF >70 years of age <b>C.</b> non-ischemic HF > 70 years <b>D.</b> all-cause mortality in CORONA using cut-off derived from the GISSI-HF-HF trial.</p

Clinical and biochemical baseline characteristics stratified by tertile values of sFRP3.

<p>NT-proBNP and CRP are displayed as median value (interquartile range). Other variables are shown as number (percentage of total) or as mean (standard deviation) where appropriate. <i>P</i>-value Trend, <i>p</i>-value for trend across all tertiles; <i>P</i>-value 2^nd, <i>p</i>-value for 2^nd tertile compared to 1^st and 3^rd tertile combined.NYHA, New York Heart Association; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; LDL, low-density lipoprotein; HDL, high-density lipoprotein; ApoB, apolipoprotein B; ApoA-1, apolipoprotein A-1; eGFR, estimated glomerular filtration rate; MDRD, modification of diet in renal disease; CRP, C-reactive protein; NT-proBNP, amino-terminal pro-brain natriuretic peptide; sFRP3, secreted frizzled related protein 3; ACE, angiotensin converting enzyme; ARB, angiotensin II receptor blocker.</p><p>Clinical and biochemical baseline characteristics stratified by tertile values of sFRP3.</p

Multivariable analysis of intermediate levels of sFRP3 as a predictor of outcome.

<p>sFRP3, 2^nd tertile <i>vs</i>. 1^st and 3^rd tertile, as predictor of outcome. All Hazard Ratios (HR) are given as HR (95% confidence interval). C index, Δ; difference in C index between fully adjusted model with and without inclusion of sFRP3, corresponding (<i>p</i>-value). Net Reclassification Improvement (NRI); calculated from C-indexes for fully adjusted models with and without inclusion of sFRP3, corresponding (<i>p</i>-value). Unadjusted (n = 1444). The models are adjusted as follows: Step 1 (n = 1441): Ejection fraction, New York Heart Association functional class, age, body mass index, diabetes mellitus, sex, intermittent claudication and heart rate. Step 2 (n = 1428): All variables from Step 1 as well as ApoB/Apo A-1 ratio and estimated glomerular filtration rate. Step 3 (1194): all variables from Step 2 as well as C-reactive protein and amino-terminal pro B-type natriuretic peptide. CV, cardiovascular; WHF, worsening heart failure.</p><p>Multivariable analysis of intermediate levels of sFRP3 as a predictor of outcome.</p

Additional file 1: of Elevated plasma heparin-binding protein is associated with early death after resuscitation from cardiac arrest

Baseline characteristics and clinical factors in all FINNRESUSCI patients and in patients with blood samples. Description of data: a table reporting the main clinical characteristics of the patients included in the overall FINNRESUSCI trial and the patients included in the present biomarker substudy. (DOCX 14 kb

Data_Sheet_1_Patient-reported outcome measures in patients with familial cerebral cavernous malformations: results from the Treat_CCM trial.PDF

BackgroundThe Phase 1/2 Treat_CCM randomized controlled trial for people with familial cerebral cavernous malformations (FCCMs) confirmed the safety of propranolol and suggested beneficial effects on intracerebral hemorrhage or new focal neurological deficits, but the effects on patient-reported outcome measures have not been reported.MethodsParticipants completed self-reported questionnaires at baseline, 1 and 2 years. Depression was assessed with the Beck Depression Inventory-II (BDI-2); Anxiety with the State–Trait Anxiety Inventory X1 and X2 (STAI X-1 and STAI X-2); and Quality of Life with the Short Form 36 (SF-36), split into the physical and mental component scales (PCS and MCS). Differences between treatment groups and the general population were assessed. Change over time by treatment was assessed by means of mixed models.ResultsIn total, 71 participants (48 propranolol and 23 standard care) were enrolled, of whom 61 (73%) completed questionnaires at baseline and 2-year FU. At baseline, no differences between treatment groups for any of the questionnaires were present. Twenty (31.7%) patients were considered depressed at baseline, while this proportion was lower in the propranolol group after 2 years (28.6% vs. 55.5%, p = 0.047). The STAI X-1 and X-2 scores were stable over time. PCS was lower in FCCM patients as compared with the general Italian population, while the MCS was similar to the general population. No effect of propranolol was found for both PCS and MCS.ConclusionDepression is common among patients with FCCM. Patients randomized to propranolol had a lower proportion of participants with depression after 2 years.Clinical trial registration: https://clinicaltrials.gov/, identifier (NCT03589014).</p

Additional file 1: of Renal function estimation and Cockcroft–Gault formulas for predicting cardiovascular mortality in population-based, cardiovascular risk, heart failure and post-myocardial infarction cohorts: The Heart ‘OMics’ in AGEing (HOMAGE) and the high-risk myocardial infarction database initiatives

Supplemental Material. Table S1. Linearity tests for each formula using restricted cubic splines with 3 knots. Table S2. Cox-regression models according to the different formulas (categorized for “renal function” stages) and age subgroups. Table S3. Improvement indices for glomerular filtration rate estimation formulas in comparison to body surface area. Figure S1. Association between “renal function” formulas and cardiovascular mortality in each population setting using restricted cubic splines with y-axis in log scale. Figure S2. Calibration assessment for “renal function” formulas within each population. (DOCX 883 kb