04 February 2019 by Scott Visovatti

Unique resting and exercise lipidomic profiles of scleroderma-associated pulmonary arterial hypertension

Rationale:

Pulmonary arterial hypertension (PAH) develops in 15% of patients with scleroderma. Screening has improved survival, but current strategies under-diagnose the condition in its earliest, most treatable stage. Given the need for predictive biomarkers, we conducted an untargeted lipidomics study to identify resting and exercise-induced lipid biomarkers of scleroderma-associated PAH.

Methods:

We studied 109 subjects in 3 groups: healthy controls (n=37), scleroderma patients at low risk for PAH using the DETECT algorithm (n=21), and scleroderma patients at high risk for PAH using the DETECT algorithm (n=51). High-risk patients were further sub-divided based upon right heart catheterization hemodynamics: normal pulmonary arterial pressure (mPAP<21 mmHg, n=10), borderline pressure (mPAP>21 mmHg and<25 mmHg, n=21), and PAH (mPAP ≥25 mmHg, n=20). All high-risk patients had normal left-sided filling pressures. Blood was drawn at rest and at peak exercise. Lipids were extracted using a modified Bligh-Dyer method and processed via liquid chromatography mass spectrometry. ANOVA was performed in the setting of rest and exercise. T-tests were performed to evaluate changes associated with exercise within each sub group.

Results:

Subjects in the high-risk scleroderma group had statistically significant elevations in long chain fatty acids (LCFA’s) and very long chain fatty acids (VLCFA’s) at rest, compared to healthy controls and low-risk scleroderma patients (p< 0.00001). Compared to healthy, low-risk scleroderma and high-risk scleroderma with normal mPA pressure groups, statistically significant reductions in LCFA’s were found in the scleroderma-associated PAH and borderline mPAP groups during exercise (p<0.004 and p<0.0008, respectively).

Conclusion:

Resting plasma lipidomic profiles are unique in scleroderma patients at high-risk for the presence of PAH. In addition, altered LCFA metabolism during exercise was found in high-risk scleroderma patients with PAH and borderline mPA pressures. These findings support the further investigation of resting and exercise plasma lipidomic profiles as biomarkers of, or potential contributors to, scleroderma-associated PAH.

 

About the author


profile picture of Scott Visovatti

Scott Visovatti

Assistant Professor

University of Michigan

United States

Key Contributors

Christopher Lewis, MD 1, Charles Burant, MD 2, Vallerie McLaughlin, MD 3, David Pinsky, MD 3, Dinesh Khanna, MD 4, Scott Visovatti, MD 3 : 1.University of Michigan, Department of Internal Medicine; 2.University of Michigan, Department of Internal Medicine, Division of Endocrinology; 3.University of Michigan, Department of Internal Medicine, Division of Cardiovascular Medicine; 4.University of Michigan, Department of Internal Medicine, Division of Rheumatology


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