Carotid intima-media thickness is increased in patients with treated mucopolysaccharidosis types I and II, and correlates with arterial stiffness

Raymond Y. Wang, Elizabeth A Braunlin, Kyle Rudser, Donald R Dengel, Andrea M. Metzig, Kelly K. Covault, Lynda E. Polgreen, Elsa G Shapiro, Julia Steinberger, Aaron S Kelly

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Abstract

Background: Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but coronary artery disease (CAD) and cardiovascular complications cause mortality in a high percentage of patients. Non-invasive measures of sub-clinical atherosclerosis, such as carotid intima-media thickness (cIMT) and arterial stiffness, may be useful for prediction of CAD outcomes in MPS patients. Objectives: The aim of the study was to determine if cIMT and arterial stiffness are abnormal in MPS I and II patients compared to healthy controls. Methods: MPS patients underwent carotid artery ultrasonography, and electronic wall-tracking software was used to measure cIMT, carotid artery cross-sectional compliance (cCSC), cross-sectional distensibility (cCSD), and incremental elastic modulus (cIEM). Control data from healthy subjects were obtained from a different study that utilized identical testing within the same laboratory. Results: A total of 406 healthy controls and 25 MPS patients (16 MPS I, 9 MPS II) were studied. All MPS patients had or were receiving treatment: 15 patients (6 MPS I, 9 MPS II) were receiving enzyme replacement therapy (ERT), 9 patients (all MPS I) had received hematopoietic stem cell transplant (HSCT), and 1 patient with MPS I had received HSCT and was receiving enzyme replacement therapy (ERT). MPS patients had significantly higher mean (±SD) cIMT (0.56±0.05mm) compared to controls (0.44±0.04mm; adjusted p<0.001). MPS patients also had increased stiffness compared to controls, showing significantly lower cCSC (0.14±0.09mm2/mmHg versus 0.16±0.05mm2/mmHg; adjusted p=0.019), and higher cIEM (1362±877mmHg versus 942±396mmHg; adjusted p<0.001). cCSD in MPS patients was lower than that of controls (29.7±16.4% versus 32.0±8.2%) but was not statistically significant; p=0.12. Among MPS patients, cCSD showed a significant association with cIMT (p=0.047), while the association between cIEM and cIMT approached significance (p=0.077). No significant differences were observed in cIMT, cCSD, cCSC, and cIEM between MPS I and MPS II patients. Conclusions: Despite treatment, MPS patients had higher cIMT compared to healthy controls, indicating this marker of sub-clinical atherosclerosis may be a useful predictor of CAD outcomes. The association of arterial stiffness measures with cIMT suggests that mechanical and structural changes may occur in concert among MPS patients. Although yet to be confirmed, increased cIMT and arterial stiffness in MPS I and II patients may be a consequence of inflammatory signaling pathways triggered by heparan or dermatan sulfate-derived oligosaccharides. Prospective, longitudinal studies will need to be performed in order to evaluate the usefulness of these carotid measurements as predictors of adverse CAD outcomes in MPS patients.

Original languageEnglish (US)
Pages (from-to)128-132
Number of pages5
JournalMolecular Genetics and Metabolism
Volume111
Issue number2
DOIs
StatePublished - Jan 31 2014

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Mucopolysaccharidosis II
Mucopolysaccharidosis I
Carotid Intima-Media Thickness
Vascular Stiffness
Mucopolysaccharidoses
Stiffness
Elastic moduli
Patient treatment
Transplants
Stem cells
Elastic Modulus
Carotid Arteries
Coronary Artery Disease
Ultrasonography
Dermatan Sulfate
Heparitin Sulfate
Compliance
Enzymes
Enzyme Replacement Therapy
Oligosaccharides

Keywords

  • Hunter
  • Hurler
  • Intima-media thickness
  • Marker
  • Mucopolysaccharidosis
  • Vascular disease

Cite this

@article{938208625a8e440883d9e8bd0e9616be,
title = "Carotid intima-media thickness is increased in patients with treated mucopolysaccharidosis types I and II, and correlates with arterial stiffness",
abstract = "Background: Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but coronary artery disease (CAD) and cardiovascular complications cause mortality in a high percentage of patients. Non-invasive measures of sub-clinical atherosclerosis, such as carotid intima-media thickness (cIMT) and arterial stiffness, may be useful for prediction of CAD outcomes in MPS patients. Objectives: The aim of the study was to determine if cIMT and arterial stiffness are abnormal in MPS I and II patients compared to healthy controls. Methods: MPS patients underwent carotid artery ultrasonography, and electronic wall-tracking software was used to measure cIMT, carotid artery cross-sectional compliance (cCSC), cross-sectional distensibility (cCSD), and incremental elastic modulus (cIEM). Control data from healthy subjects were obtained from a different study that utilized identical testing within the same laboratory. Results: A total of 406 healthy controls and 25 MPS patients (16 MPS I, 9 MPS II) were studied. All MPS patients had or were receiving treatment: 15 patients (6 MPS I, 9 MPS II) were receiving enzyme replacement therapy (ERT), 9 patients (all MPS I) had received hematopoietic stem cell transplant (HSCT), and 1 patient with MPS I had received HSCT and was receiving enzyme replacement therapy (ERT). MPS patients had significantly higher mean (±SD) cIMT (0.56±0.05mm) compared to controls (0.44±0.04mm; adjusted p<0.001). MPS patients also had increased stiffness compared to controls, showing significantly lower cCSC (0.14±0.09mm2/mmHg versus 0.16±0.05mm2/mmHg; adjusted p=0.019), and higher cIEM (1362±877mmHg versus 942±396mmHg; adjusted p<0.001). cCSD in MPS patients was lower than that of controls (29.7±16.4{\%} versus 32.0±8.2{\%}) but was not statistically significant; p=0.12. Among MPS patients, cCSD showed a significant association with cIMT (p=0.047), while the association between cIEM and cIMT approached significance (p=0.077). No significant differences were observed in cIMT, cCSD, cCSC, and cIEM between MPS I and MPS II patients. Conclusions: Despite treatment, MPS patients had higher cIMT compared to healthy controls, indicating this marker of sub-clinical atherosclerosis may be a useful predictor of CAD outcomes. The association of arterial stiffness measures with cIMT suggests that mechanical and structural changes may occur in concert among MPS patients. Although yet to be confirmed, increased cIMT and arterial stiffness in MPS I and II patients may be a consequence of inflammatory signaling pathways triggered by heparan or dermatan sulfate-derived oligosaccharides. Prospective, longitudinal studies will need to be performed in order to evaluate the usefulness of these carotid measurements as predictors of adverse CAD outcomes in MPS patients.",
keywords = "Hunter, Hurler, Intima-media thickness, Marker, Mucopolysaccharidosis, Vascular disease",
author = "Wang, {Raymond Y.} and Braunlin, {Elizabeth A} and Kyle Rudser and Dengel, {Donald R} and Metzig, {Andrea M.} and Covault, {Kelly K.} and Polgreen, {Lynda E.} and Shapiro, {Elsa G} and Julia Steinberger and Kelly, {Aaron S}",
year = "2014",
month = "1",
day = "31",
doi = "10.1016/j.ymgme.2013.11.001",
language = "English (US)",
volume = "111",
pages = "128--132",
journal = "Molecular Genetics and Metabolism",
issn = "1096-7192",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Carotid intima-media thickness is increased in patients with treated mucopolysaccharidosis types I and II, and correlates with arterial stiffness

AU - Wang, Raymond Y.

AU - Braunlin, Elizabeth A

AU - Rudser, Kyle

AU - Dengel, Donald R

AU - Metzig, Andrea M.

AU - Covault, Kelly K.

AU - Polgreen, Lynda E.

AU - Shapiro, Elsa G

AU - Steinberger, Julia

AU - Kelly, Aaron S

PY - 2014/1/31

Y1 - 2014/1/31

N2 - Background: Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but coronary artery disease (CAD) and cardiovascular complications cause mortality in a high percentage of patients. Non-invasive measures of sub-clinical atherosclerosis, such as carotid intima-media thickness (cIMT) and arterial stiffness, may be useful for prediction of CAD outcomes in MPS patients. Objectives: The aim of the study was to determine if cIMT and arterial stiffness are abnormal in MPS I and II patients compared to healthy controls. Methods: MPS patients underwent carotid artery ultrasonography, and electronic wall-tracking software was used to measure cIMT, carotid artery cross-sectional compliance (cCSC), cross-sectional distensibility (cCSD), and incremental elastic modulus (cIEM). Control data from healthy subjects were obtained from a different study that utilized identical testing within the same laboratory. Results: A total of 406 healthy controls and 25 MPS patients (16 MPS I, 9 MPS II) were studied. All MPS patients had or were receiving treatment: 15 patients (6 MPS I, 9 MPS II) were receiving enzyme replacement therapy (ERT), 9 patients (all MPS I) had received hematopoietic stem cell transplant (HSCT), and 1 patient with MPS I had received HSCT and was receiving enzyme replacement therapy (ERT). MPS patients had significantly higher mean (±SD) cIMT (0.56±0.05mm) compared to controls (0.44±0.04mm; adjusted p<0.001). MPS patients also had increased stiffness compared to controls, showing significantly lower cCSC (0.14±0.09mm2/mmHg versus 0.16±0.05mm2/mmHg; adjusted p=0.019), and higher cIEM (1362±877mmHg versus 942±396mmHg; adjusted p<0.001). cCSD in MPS patients was lower than that of controls (29.7±16.4% versus 32.0±8.2%) but was not statistically significant; p=0.12. Among MPS patients, cCSD showed a significant association with cIMT (p=0.047), while the association between cIEM and cIMT approached significance (p=0.077). No significant differences were observed in cIMT, cCSD, cCSC, and cIEM between MPS I and MPS II patients. Conclusions: Despite treatment, MPS patients had higher cIMT compared to healthy controls, indicating this marker of sub-clinical atherosclerosis may be a useful predictor of CAD outcomes. The association of arterial stiffness measures with cIMT suggests that mechanical and structural changes may occur in concert among MPS patients. Although yet to be confirmed, increased cIMT and arterial stiffness in MPS I and II patients may be a consequence of inflammatory signaling pathways triggered by heparan or dermatan sulfate-derived oligosaccharides. Prospective, longitudinal studies will need to be performed in order to evaluate the usefulness of these carotid measurements as predictors of adverse CAD outcomes in MPS patients.

AB - Background: Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but coronary artery disease (CAD) and cardiovascular complications cause mortality in a high percentage of patients. Non-invasive measures of sub-clinical atherosclerosis, such as carotid intima-media thickness (cIMT) and arterial stiffness, may be useful for prediction of CAD outcomes in MPS patients. Objectives: The aim of the study was to determine if cIMT and arterial stiffness are abnormal in MPS I and II patients compared to healthy controls. Methods: MPS patients underwent carotid artery ultrasonography, and electronic wall-tracking software was used to measure cIMT, carotid artery cross-sectional compliance (cCSC), cross-sectional distensibility (cCSD), and incremental elastic modulus (cIEM). Control data from healthy subjects were obtained from a different study that utilized identical testing within the same laboratory. Results: A total of 406 healthy controls and 25 MPS patients (16 MPS I, 9 MPS II) were studied. All MPS patients had or were receiving treatment: 15 patients (6 MPS I, 9 MPS II) were receiving enzyme replacement therapy (ERT), 9 patients (all MPS I) had received hematopoietic stem cell transplant (HSCT), and 1 patient with MPS I had received HSCT and was receiving enzyme replacement therapy (ERT). MPS patients had significantly higher mean (±SD) cIMT (0.56±0.05mm) compared to controls (0.44±0.04mm; adjusted p<0.001). MPS patients also had increased stiffness compared to controls, showing significantly lower cCSC (0.14±0.09mm2/mmHg versus 0.16±0.05mm2/mmHg; adjusted p=0.019), and higher cIEM (1362±877mmHg versus 942±396mmHg; adjusted p<0.001). cCSD in MPS patients was lower than that of controls (29.7±16.4% versus 32.0±8.2%) but was not statistically significant; p=0.12. Among MPS patients, cCSD showed a significant association with cIMT (p=0.047), while the association between cIEM and cIMT approached significance (p=0.077). No significant differences were observed in cIMT, cCSD, cCSC, and cIEM between MPS I and MPS II patients. Conclusions: Despite treatment, MPS patients had higher cIMT compared to healthy controls, indicating this marker of sub-clinical atherosclerosis may be a useful predictor of CAD outcomes. The association of arterial stiffness measures with cIMT suggests that mechanical and structural changes may occur in concert among MPS patients. Although yet to be confirmed, increased cIMT and arterial stiffness in MPS I and II patients may be a consequence of inflammatory signaling pathways triggered by heparan or dermatan sulfate-derived oligosaccharides. Prospective, longitudinal studies will need to be performed in order to evaluate the usefulness of these carotid measurements as predictors of adverse CAD outcomes in MPS patients.

KW - Hunter

KW - Hurler

KW - Intima-media thickness

KW - Marker

KW - Mucopolysaccharidosis

KW - Vascular disease

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U2 - 10.1016/j.ymgme.2013.11.001

DO - 10.1016/j.ymgme.2013.11.001

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JF - Molecular Genetics and Metabolism

SN - 1096-7192

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