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

Abstract

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.

Plasma metabolomic profile in chronic thromboembolic pulmonary hypertension

“…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 (o-oxidation, suggesting lipid availability beyond the rate of tissue-level beta-oxidation) or through lipid peroxidation.…”

“…11 Our group recently reported decreased high-density lipoprotein cholesterol levels in CTEPH patients, which correlated with higher postoperative pulmonary vascular resistance. 12…”

“…11 Our group recently reported decreased high-density lipoprotein cholesterol levels in CTEPH patients, which correlated with higher postoperative pulmonary vascular resistance. 12 With the advent of new metabolomic platforms, we now have the ability to measure small molecules in biologic samples using a high-throughput unbiased approach. Metabolomics provides a snapshot of the physiological state of a tissue/organ or the whole body, and can uncover the relative activity in different metabolic pathways.…”

High-Fat Diet Attenuates the Improvement of Hypoxia-induced Pulmonary Artery Hypertension in Mice During Reoxygenation.

“…It has been reported by Khirfan et al that plasma levels of HDL-C in PAH patients were lower than those in controls, and that low HDL-C was associated with PAH patient mortality [21]. In current study, mice fed with HFD exhibited higher HDL-C and RVSP.…”

HDL Cholesterol as a Marker of Disease Severity and Prognosis in Patients with Pulmonary Arterial Hypertension

“…When compared to controls, CTEPH patients were characterized by lower HDL cholesterol levels but higher when compared to the PAH population. In this group higher HDL was associated with less prominent right ventricular dilation and a more favorable effect of pulmonary thromboendarterectomy [86]. This suggests that HDL cholesterol may be a useful marker in pulmonary vascular diseases of different origin.…”