Lipoprotein particles in patients with pediatric Cushing disease and possible cardiovascular risks

Abstract

Background: Cardiovascular (CV) complications are the most significant cause of mortality in adults with Cushing disease (CD); little is known about CV risk factors in children with CD. Measurement of lipoprotein particles by nuclear magnetic resonance (NMR) spectroscopy is a novel technology to assess CV risk. The objective of the current study is to analyze the NMR lipid profile in pediatric CD patients before and 1 year after remission. Methods: NMR lipid profile was obtained via the Vantera NMR analyzer, using frozen serum samples from 33 CD patients (mean age 13.8 ± 4.0 years) evaluated between 1997 and 2017 at the National Institutes of Health (NIH) Clinical Center (CC). Results: GlycA, triglyceride-rich particles (TRLP medium and very small sizes), LDL particles (LDLP total and large size), HDL particles (HDLP total, medium and small sizes), total cholesterol, LDL cholesterol, HDL cholesterol, GlycA inflammatory biomarker, Apolipoprotein B and Apolipoprotein A1 concentrations showed statistically significant changes after remission of CD (p<0.05). Conclusion: In our study population, most of the lipid variables improved post-CDremission, with the exception of HDL and apoA1, indicating that NMR lipoprotein profile may be a helpful tool in assessing the cardiovascular risk in pediatric patients with CD.

Lipid Abnormalities in Patients With Cushing’s Disease and Its Relationship With Impaired Glucose Metabolism

“…Although most of the lipid parameters changed towards a beneficial cardiovascular direction, the HDL-c level surprisingly showed a decrease after remission of CD. This aberrant change was also observed in a previous study reporting a decrease of HDL particles with a cure of CD ( 21 ). The worsening of the HDL-c level seems to be in accordance with variable alterations of HDL-c level in CS reported in previous studies ( 5 , 23 ).…”

“…Previous data regarding the relationship between lipid profile and the degree of hypercortisolemia is very variable. Higher serum or urine cortisol level has been shown associated with high TG, high LDL-c, and low HDL-c levels ( 6 , 21 , 22 ), while Mancini et al. showed a reverse correlation between TC and LDL-c with morning serum cortisol levels in CS ( 23 ).…”

“…In a longitudinal study, LDL-c levels showed a significant decrease at 1 year following remission of CD, but levels remained higher than healthy controls ( 22 ). In a recent investigation on lipid profile in pediatric CD patients, most of the lipid parameters including TC, LDL-c, HDL-c, and TG-rich particles showed significant improvement at 1-year follow-up after CD is cured, expect for HDL and ApoA1 ( 21 ). In our study, a significant reduction in the incidence of hyperlipidemia and hypercholesterolemia was observed in patients in surgical remission compared to those in non-remission, indicating the effectiveness and necessity of surgical remission in improving lipid metabolism disorders in CD.…”

Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay

“…Based on the lipoprotein analysis, there were no signals present from LDL in this sample. Descriptions and diameter ranges of the normal lipoprotein, lipid, and apolipoprotein parameters reported from the LP4 algorithm have been published [ 5 ].…”

“…Accurate quantitation of lipoprotein classes and subclasses can be accomplished by NMR for three reasons: (1) each class of lipoproteins, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), emits an NMR signal with a unique lineshape enabling their distinction from one another, (2) the amplitudes of these unique NMR signals are directly proportional to the number of particles emitting the signal thereby allowing for accurate quantification, and (3) there is a magnetic property specific to lipoproteins that causes the lipids in larger particles to emit signals that are characteristically different in shape and higher in frequency (chemical shift) from signals emitted by lipids in smaller particles [ 1 , 2 , 3 ]. The mathematical algorithms used to deconvolute the broad methyl signal within the NMR spectrum into the lipoprotein concentrations have improved and are now capable of capturing more lipoprotein subspecies than earlier algorithms [ 1 , 4 , 5 , 6 ].…”