Prognostic Significance of Biomarkers in Pulmonary Arterial Hypertension

Abstract

Rationale: Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary vasculature that is characterized by endothelial dysfunction, inflammation, and right ventricular dysfunction.Objectives: The main objective was to determine whether endothelial, inflammatory, and cardiac biomarkers would be associated with the World Health Organization functional assessment and survival in patients with PAH. Methods:We performed a retrospective cohort study of patients with PAH enrolled in the Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension (ASA-STAT). Biomarkers (N-terminal fragment of pro-BNP [NT-pro-BNP], von Willebrand factor [vWF], soluble P selectin, C-reactive protein, total and high-density lipoprotein cholesterol, triglycerides, tumor necrosis factor, IL-6, b-thromboglobulin, and thromboxane B 2 ) were measured at baseline. Patients from the study were followed until lung transplantation, death, or August 1, 2013. Ordinal logistic regression and Cox regression analyses were performed. Measurements and Main Results:Sixty-five patients with PAH were enrolled. The mean age was 51 years, and 86% were women. Higher vWF activity, lower high-density lipoprotein cholesterol, and higher thromboxane B 2 levels were associated with worse World Health Organization functional class after adjustment for age, sex, and etiology of PAH. Higher NT-pro-BNP levels, lower vWF activity, and lower total cholesterol were associated with an increased risk of death or lung transplant after adjustment for age, sex, etiology of PAH, and 6-minute-walk distance. Conclusions:In patients with PAH, lower vWF activity and cholesterol levels and higher NT-pro-BNP levels at baseline were associated with an increased risk of death or transplantation.Clinical trial registered with www.clinicaltrials.gov (NCT00384865).

Serum albumin concentration as an independent prognostic indicator in patients with pulmonary arterial hypertension

“…Serum albumin concentration level was among the strongest predictors of mortality of the studied clinical, hemodynamic, echocardiographic, and laboratory parameters on multivariate analysis. This finding is consistent with studies in other patient populations …”

“…Although pulmonary artery pressures, functional capacity assessments, and patient symptoms are used to guide therapies, prognostication can still be challenging . Studies have identified age, blood pressure, renal function, and biomarker abnormalities as predictors of adverse prognosis, and these clinical variables can be helpful in discussing prognosis with patients and guiding therapy . Although serum albumin concentration has been found to be an important prognostic indicator in numerous other disease processes, limited data are available in the PAH population .…”

“…Studies have identified age, blood pressure, renal function, and biomarker abnormalities as predictors of adverse prognosis, and these clinical variables can be helpful in discussing prognosis with patients and guiding therapy . Although serum albumin concentration has been found to be an important prognostic indicator in numerous other disease processes, limited data are available in the PAH population . In patients with chronic heart failure, lower serum albumin levels have been associated with poor prognosis .…”

NTP42, a novel antagonist of the thromboxane receptor, attenuates experimentally induced pulmonary arterial hypertension

“…Furthermore, in adult PAH patients, 24-h excretion levels of TXB 2 are increased, as compared with normal controls, whereas, in contrast, 24-h excretion of 2,3-dinor-6-keto-prostaglandin F 1α (a stable metabolite of prostacyclin) are significantly decreased [29]. Results from a recent randomised clinical trial of Aspirin and Simvastatin (ASA-STAT) showed that PAH patients with higher levels of TXA 2 were associated with more advanced disease, and with worse clinical outcome/survival [30]. With regards to the TP, employing radioligand binding studies, its expression was shown to be significantly elevated in the right ventricles (RVs) from PAH patients compared to non-diseased controls [31].…”

Update in Pulmonary Vascular Disease 2015

“…Markers of endothelial injury continue to be a focus of research. An initial prospective study of treatment-naive patients found elevated levels of von Willebrand factor (vWF) at baseline to be associated with worse outcome, and a more recent study of patients treated for PAH found low vWF levels to be predictive of worse outcome (14,15). The investigators also observed an inverse association with lung transplant-free survival per 50-mg/dl reduction in total cholesterol, although a mechanism to account for this observation and findings related to vWF in PAH remains unresolved (16,17).…”