The Clinical Significance of HbA1c in Operable Chronic Thromboembolic Pulmonary Hypertension

Richter, Manuel J.; Milger, Katrin; Haase, Sarah; Sommer, Natascha; Tello, Khodr; Seeger, Werner; Mayer, Eckhard; Wiedenroth, Christoph B.; Grimminger, Friedrich; George, Wolfgang; Ghofrani, Hossein Ardeschir; Guth, Stefan; Gall, Henning

doi:10.1371/journal.pone.0152580

Cited by 7 publications

(10 citation statements)

References 45 publications

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“…Recent research by our group and others demonstrates dysregulated glucose and insulin metabolism in IPAH 6,7,25,26 and CTEPH. 11,12 The metabolomic data generated in this report corroborate these findings, evidencing both elevated lipids (a well-known contributor to peripheral insulin resistance) and elevated dicarboxyl fatty acids. Dicarboxyl fatty acids can be generated by a secondary mechanism (ω-oxidation, suggesting lipid availability beyond the rate of tissue-level beta-oxidation) or through lipid peroxidation.…”

Section: Discussionsupporting

confidence: 80%

Plasma metabolomic profile in chronic thromboembolic pulmonary hypertension

Heresi¹,

Mey

Bartholomew³

et al. 2020

Pulm. circ.

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We aimed to characterize the plasma metabolome of chronic thromboembolic pulmonary hypertension patients using a high-throughput unbiased omics approach. We collected fasting plasma from a peripheral vein in 33 operable chronic thromboembolic pulmonary hypertension patients, 31 healthy controls, and 21 idiopathic pulmonary arterial hypertension patients matched for age, gender, and body mass index. Metabolomic analysis was performed using an untargeted approach (Metabolon Inc. Durham, NC). Of the total of 862 metabolites identified, 362 were different in chronic thromboembolic pulmonary hypertension compared to controls: 178 were higher and 184 were lower. Compared to idiopathic pulmonary arterial hypertension, 147 metabolites were different in chronic thromboembolic pulmonary hypertension: 45 were higher and 102 were lower. The plasma metabolome allowed us to distinguish subjects with chronic thromboembolic pulmonary hypertension and healthy controls with a predictive accuracy of 89%, and chronic thromboembolic pulmonary hypertension versus idiopathic pulmonary arterial hypertension with 80% accuracy. Compared to idiopathic pulmonary arterial hypertension and healthy controls, chronic thromboembolic pulmonary hypertension patients had higher fatty acids and glycerol; while acyl cholines and lysophospholipids were lower. Compared to healthy controls, both idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients had increased acyl carnitines, beta-hydroxybutyrate, amino sugars and modified amino acids and nucleosides. The plasma global metabolomic profile of chronic thromboembolic pulmonary hypertension suggests aberrant lipid metabolism characterized by increased lipolysis, fatty acid oxidation, and ketogenesis, concomitant with reduced acyl choline and phospholipid moieties. Future research should investigate the pathogenetic and therapeutic potential of modulating lipid metabolism in chronic thromboembolic pulmonary hypertension.

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Section: Discussionsupporting

confidence: 80%

Plasma metabolomic profile in chronic thromboembolic pulmonary hypertension

Heresi¹,

Mey

Bartholomew³

et al. 2020

Pulm. circ.

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“…Simple pre-operative non-invasive biomarkers of small vessel vasculopathy in CTEPH, such as plasma HDL-C, offer an opportunity in improve patient selection. Metabolic dysregulation in CTEPH has been previously suggested by Richter et al [ 37 ]. These investigators studied the utility of glycosylated hemoglobin A1C (HbA1C) in operable CTEPH patients, baseline HbA1C levels were associated with baseline cardiac index, right atrial pressure, peak oxygen uptake and change in total distance walked during 6MWT post PTE [ 37 ].…”

Section: Discussionmentioning

confidence: 93%

“…Metabolic dysregulation in CTEPH has been previously suggested by Richter et al [ 37 ]. These investigators studied the utility of glycosylated hemoglobin A1C (HbA1C) in operable CTEPH patients, baseline HbA1C levels were associated with baseline cardiac index, right atrial pressure, peak oxygen uptake and change in total distance walked during 6MWT post PTE [ 37 ]. Elevated HbA1c suggests the presence of insulin resistance and the metabolic syndrome, conditions where low HDL-C is a prominent feature.…”

Section: Discussionmentioning

confidence: 93%

Plasma levels of high density lipoprotein cholesterol and outcomes in chronic thromboembolic pulmonary hypertension

Khirfan

Tejwani

et al. 2018

PLoS ONE

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BackgroundHigh Density Lipoprotein Cholesterol (HDL-C) has various anti-inflammatory, anti-atherogenic, anti-oxidant and anti-coagulant properties that improve vascular function. The utility of HDL-C as a biomarker of severity and predictor of survival was described in patients with pulmonary arterial hypertension (PAH). No prior study has assessed the utility of HDL-C in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH).ObjectivesWe aim to measure HDL-C levels in CTEPH patients and compare it to those in PAH patients and controls and determine HDL-C associations with markers of disease severity, hemodynamics and mortality in CTEPH.MethodsWe retrospectively included patients with CTEPH, identified from the Cleveland Clinic Pulmonary Hypertension Registry. All patients had right heart catheterization (RHC) and imaging studies consistent with CTEPH. We collected demographics, co-morbidities, baseline laboratory data including plasma HDL-C, six-minute walk test (6MWT), echocardiography and RHC. HDL-C levels were compared to a cohort of patients with cardiovascular risk factors and a previously published PAH cohort.ResultsHDL-C levels were available for 90 patients with CTEPH (age: 57.4±13.9 years; female 40%), 69 patients with PAH (age: 46.7±12.8 years; female 90%) and 254 control subjects (age: 56.7±13 years; female 48%). HDL-C levels in CTEPH patients were lower compared to controls and higher compared to PAH patients (median, IQR: CTEPH: 44, 34–57 mg/dl; PAH: 35.3, 29–39 mg/dl; Control: 49, 40–60 mg/dl; p < 0.01 for both pairwise comparisons). In CTEPH, higher HDL-C was associated with decreased prevalence of right ventricular dilation on echocardiography (p = 0.02). 57 patients with CTEPH underwent pulmonary thromboendarterectomy, higher HDL-C was associated with a larger decrement in postoperative pulmonary vascular resistance (PVR) (r = 0.37, p = 0.049). HDL-C was not associated with mortality or other markers of disease severity.ConclusionsHDL-C levels in CTEPH patients were lower compared to control subjects, but higher compared to PAH patients. Higher HDL-C in CTEPH was associated with less right ventricular dilation and greater decrement in postoperative PVR. These data suggest that HDL-C may be a useful marker of small vessel disease in CTEPH.

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“…Richter et al . () also presented a positive correlation between HbA1c concentration and mPAP and a negative correlation between HbA1c levels and 6 min walk distance and cardiac index in chronic thromboembolic pulmonary hypertension (CTEPH) patients. The survival rate in PH patients with DM was worse than in PH patients without DM (Belly et al .…”

Section: Vascular Function In Hyperglycaemiamentioning

confidence: 92%

Pulmonary vascular dysfunction in metabolic syndrome

Willson

Watanabe

Tsuji‐Hosokawa

2018

The Journal of Physiology

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Metabolic syndrome is a critically important precursor to the onset of many diseases, such as cardiovascular disease, and cardiovascular disease is the leading cause of death worldwide. The primary risk factors of metabolic syndrome include hyperglycaemia, abdominal obesity, dyslipidaemia, and high blood pressure. It has been well documented that metabolic syndrome alters vascular endothelial and smooth muscle cell functions in the heart, brain, kidney and peripheral vessels. However, there is less information available regarding how metabolic syndrome can affect pulmonary vascular function and ultimately increase an individual's risk of developing various pulmonary vascular diseases, such as pulmonary hypertension. Here, we review in detail how metabolic syndrome affects pulmonary vascular function.

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The Clinical Significance of HbA1c in Operable Chronic Thromboembolic Pulmonary Hypertension

Cited by 7 publications

References 45 publications

Plasma metabolomic profile in chronic thromboembolic pulmonary hypertension

Plasma metabolomic profile in chronic thromboembolic pulmonary hypertension

Plasma levels of high density lipoprotein cholesterol and outcomes in chronic thromboembolic pulmonary hypertension

Pulmonary vascular dysfunction in metabolic syndrome

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