Novel biomarkers for risk stratification in pulmonary arterial hypertension

Abstract

Risk stratification in pulmonary arterial hypertension (PAH) is paramount to identifying individuals at highest risk of death. So far, there are only limited parameters for prognostication in patients with PAH.95 patients with confirmed PAH were included in the present analysis and followed for a total of 4 years. Blood samples were analysed for serum levels of N-terminal pro-brain natriuretic peptide, highsensitivity troponin T (hsTnT), pro-atrial natriuretic peptide ( proANP), growth differentiation factor 15, soluble fms-like tyrosine kinase 1 and placental growth factor. 27 (28.4%) patients died during a follow-up of 4 years. Levels of all tested biomarkers, except for placental growth factor, were significantly elevated in nonsurvivors compared with survivors. Receiver operating characteristic analyses demonstrated that cardiac biomarkers had the highest power in predicting mortality. In particular, proANP exhibited the highest area under the curve, followed by N-terminal probrain natriuretic peptide and hsTnT. Furthermore, proANP and hsTnT added significant additive prognostic value to the established markers in categorical and continuous net reclassification index. Moreover, after Cox regression, proANP (hazard ratio (HR) 1.91), hsTnT (HR 1.41), echocardiographic right ventricular impairment (HR 1.30) and 6-min walk test (HR 0.97 per 10 m) remained the only significant parameters in prognostication of mortality.Our data suggest benefits of the implementation of proANP and hsTnT as additive biomarkers for risk stratification in patients with PAH. @ERSpublications The cardiac biomarkers proANP and hsTnT may be of use in the assessment of risk stratification in PAH patients http://ow.ly/RJFtn

Growth differentiation factor-15 as candidate predictor for mortality in adults with pulmonary hypertension

“…They found that higher GDF-15 levels were associated with the 4-year mortality risk. However, GDF-15 was not a better prognosticator than NT-proBNP, high-sensitive troponin-T and proatrial natriuretic peptide in their study 22…”

Association of N-Terminal Pro Brain Natriuretic Peptide and Long-Term Outcome in Patients With Pulmonary Arterial Hypertension

“…Four studies in PAH or PAH plus chronic thromboembolic pulmonary hypertension used receiver operating characteristic curve analysis to identify threshold values to predict survival in treatment naïve patients. 9,10,13,14 Cutoff values of 705 ng/L (n=95, Zelniker et al 14 ), 1256 ng/L (n=161, Mauritz et al 13 ), 1400 ng/L (n=55, Fijalkowska et al 9 ), and 1800 ng/L (n=109, Nickel et al 10 ) were identified. Although generally in the range of the high-risk cutoff used in the current guidelines (>1400 ng/L), 5 considerable variability was seen.…”

“…In addition, the lowest-risk tier in the current guidelines, an NT-proBNP level <300 ng/L, 5 was not initially identified in PAH receiver operating characteristic curve analysis (although it is used in excluding acute heart failure in other settings 23 ). Limitations of the current thresholds therefore include the small samples sizes, the lack of separate validation cohorts, the inclusion of only treatment-naïve patients, the variability in the thresholds identified in receiver operating characteristic analyses 9,10,13,14 and the lack of studies specifically designed to identify cutoffs for 3 tiers of risk.…”

The Role of Noninvasive Endpoints in Predicting Long-Term Outcomes in Pulmonary Arterial Hypertension

“…Risk of death at 2 years was increased among patients with higher BNP at baseline [40]. At 4 years, risk of death was increased among patients with NT-proBNP > 704.5 pg/mL at baseline [43]. Increased risk of death at 5 years was associated with baseline levels of BNP > 340 pg/mL [52].…”