Rapid Communications
Adiponectin in Chronic Thromboembolic Pulmonary Hypertension
2018 Volume 82 Issue 5 Pages 1466-1468
Details
2018 Volume 82 Issue 5 Pages 1466-1468
Background: The correlation between serum adiponectin concentration and hemodynamics or certain metabolic markers in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is unknown.
Methods and Results: We enrolled 30 CTEPH patients who underwent interventional therapy of balloon pulmonary angioplasty or pulmonary endarterectomy. Serum adiponectin concentrations positively correlated with B-type natriuretic peptide (BNP) concentrations, pulmonary vascular resistance, and mean pulmonary arterial pressure. After the therapeutic interventions, serum adiponectin concentrations improved and changes in serum adiponectin concentrations significantly correlated with changes in BNP concentrations.
Conclusions: Adiponectin can be a useful marker for the severity of CTEPH.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a devastating disease characterized by increased pulmonary arterial pressure caused by organic thrombi, which leads to pulmonary artery remodeling and right ventricular failure. An established and standard treatment for CTEPH is pulmonary endarterectomy (PEA),1 but balloon pulmonary angioplasty (BPA) has been shown to be an effective treatment for inoperable CTEPH.2
Insulin resistance (IR) is prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, the clinical outcome for PAH patients with IR is worse than that of patients without IR.3,4 Adiponectin, which is primarily secreted from adipose tissue, contributes to the regulation of energy homeostasis by improving insulin sensitivity.5 Adiponectin has anti-apoptotic, anti-inflammatory, and anti-atherogenic properties.6,7 A recent study demonstrated that plasma adiponectin concentrations are increased in PAH patients compared with controls.8 However, the relationship between serum adiponectin concentration and hemodynamics or IR, as well as changes in adiponectin concentration after therapeutic intervention, have not been examined. In addition, there have been no reports regarding adiponectin concentrations in CTEPH patients. Thus, in the present study we investigated the correlation between serum adiponectin concentration and hemodynamics or certain metabolic markers, and analyzed changes in adiponectin concentration after therapeutic interventions such as PEA or BPA in patients with CTEPH.
We enrolled 30 patients [12 men (40%); mean (±SD) age 63.1±10.5 years] with CTEPH from whom blood had been collected until the final BPA procedure or before PEA at Keio University Hospital between July 2015 and August 2016. As to their baseline medications, 33.3% (n=10) of them were treated with oral phosphodiesterase-5 inhibitors or soluble guanylate cyclase stimulator and 60.0% (n=18) with loop diuretics. Serological parameters [B-type natriuretic peptide (BNP), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C)] were measured in fasting blood samples on the day before catheterization. The following data were obtained on the day of catheterization: fasting serum adiponectin, fasting insulin, and fasting glucose concentrations, hemodynamic data, body weight, medication, and home oxygen therapy. Serum adiponectin concentrations were measured using a latex particle-enhanced turbidimetric immunoassay.9 Serum TG concentrations, the TG to HDL-C ratio, and fasting insulin concentrations are useful markers for identifying patients with IR.10 An IR index was calculated based on homeostasis model assessment of IR (HOMA-R).
Data are presented as the mean±SD or as median values with the interquartile range (IQR), as appropriate. The significance of differences was determined using paired t-tests, the Mann-Whitney U-test, Wilcoxon matched-pairs signed rank test, or Fisher’s exact test, as appropriate. Correlations were assessed by Pearson’s or Spearman’s rank correlation coefficients, as appropriate. Normal distribution in values of changes of both adiponectin and BNP levels was confirmed by Shapiro-Wilk normality test. The performance of the study using patients’ samples and analysis of data were approved by the institutional review boards of Keio University Hospital, and all the patients provided informed consent.
Serum adiponectin concentrations were significantly lower in patients categorized as World Health Organization functional classes (WHO-FC) I and II than in those categorized as WHO-FC III and IV (medium [IQR] 12.7 [8.6–17.1] vs. 21.8 [13.2–34.4] μg/mL, respectively; P=0.022; Figure A). Serum adiponectin concentrations inversely correlated with 6-min walk distance, mixed venous oxygen saturation, body mass index, body weight, insulin levels, TG, TG : HDL-C ratio, HOMA-R, and tricuspid annular plane systolic excursion (Figure B). Furthermore, serum adiponectin concentrations positively correlated with BNP concentrations, pulmonary vascular resistance (PVR), and mean pulmonary arterial pressure (PAP).
Serum adiponectin concentrations in patients with chronic thromboembolic pulmonary hypertension (CTEPH). (A) Serum adiponectin concentrations in 17 patients with World Health Organization functional class (WHO-FC) I or II and 13 patients with WHO-FC III or IV. (B) Correlations between log adiponectin concentrations and different clinical parameters (n=30 patients). (C) Changes in serum adiponectin concentrations in 8 patients who underwent an interventional therapy, such as pulmonary endarterectomy or balloon pulmonary angioplasty, from before to 6 months after therapy. The boxes show the interquartile range, with the median value indicated by the horizontal line; whiskers show the range. Symbols indicate individual data points. (D) Correlation between changes (from before to 6 months after therapy) in serum adiponectin and BNP concentrations. 6MWD, 6-min walk distance; BMI, body mass index; BNP, B-type natriuretic peptide; HDL-C, high-density lipoprotein cholesterol; HOMA-R, homeostasis model assessment of insulin resistance; PAP, pulmonary arterial pressure; PVR, pulmonary vascular resistance; SvO2, mixed venous oxygen saturation; TAPSE, tricuspid annular plane systolic excursion in echocardiography; TG, triglycerides.
Data for the 8 patients for whom blood sampling was repeated 6 months after PEA or BPA were also analyzed separately. In addition to significant improvements in hemodynamic parameters from baseline to 6 months after the procedure (PVR from 5.7 [4.8–16.5] to 3.7 [2.6–4.3] Wood units [P=0.016]; mean PAP from 34.5±8.7 to 19.3±4.3 mmHg [P=0.002]), there were significant improvements in serum adiponectin concentrations after the intervention (from 23.1±11.7 to 20.1±9.7μg/mL; P=0.032; Figure C). Furthermore, changes in serum adiponectin concentrations were significantly correlated with changes in BNP (P=0.034; Figure D), but not with changes in metabolic markers such as insulin concentrations (P=0.236), TG (P=0.517), TG : HDL-C ratio (P=0.727), and body weight (P=0.632), hemodynamic markers such as mean PAP (P=0.801), PVR (P=0.701), and cardiac output (P=0.384), and 6-min walk distance (P=0.941).
The present study demonstrated that serum adiponectin concentrations in CTEPH patients before intervention correlated with both markers of IR and hemodynamics, suggesting that adiponectin is a useful marker of both IR and the severity of CTEPH. Serum adiponectin concentrations decreased after PEA or BPA. Changes in adiponectin concentrations correlated with changes in BNP concentrations, despite no correlation with metabolic or hemodynamic markers, suggesting that the decrease in serum adiponectin level after the interventions was mainly affected by the improvement in right heart overload, rather than improvement in the pulmonary circulation. Thus, these findings suggest the importance of measuring serum adiponectin level as a biomarker, rather than the pathophysiology in CTEPH.
Adiponectin is primarily expressed in adipose tissue, but recent studies have reported adiponectin expression in cardiomyocytes.11,12 In patients with chronic heart failure (CHF), increases in BNP are related to the production of adiponectin.13 High adiponectin concentrations have been reported as a predictor of death in patients with CHF.14 These previous findings raise the possibility that, in the case of pulmonary hypertension, pressure- and/or volume-overloaded cardiomyocytes in the right ventricle may produce adiponectin, explaining the relationship between adiponectin and BNP concentrations and raising the possibility of using adiponectin as a biomarker and predictor of death in CTEPH and right heart failure. Furthermore, another study reported that adiponectin has beneficial effects on vascular remodeling in a mouse model of PAH.15 Thus there is a possibility that the increase in adiponectin concentration identified in the present study has a protective effect in CTEPH patients, but further studies are needed to clarify all potential roles of adiponectin in CTEPH.
None.
The authors have no relationships with industry relevant to this study.
