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

Background High 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). Objectives We 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. Methods We 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. Results HDL-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. Conclusions HDL-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.