The carotid intima-media thickness and arterial stiffness of pediatric mucopolysaccharidosis patients are increased compared to both pediatric and adult controls

Raymond Y. Wang; Kyle D. Rudser; Donald R. Dengel; Elizabeth A. Braunlin; Julia Steinberger; David R. Jacobs; Alan R. Sinaiko; Aaron S. Kelly

doi:10.3390/ijms18030637

The carotid intima-media thickness and arterial stiffness of pediatric mucopolysaccharidosis patients are increased compared to both pediatric and adult controls

Raymond Y. Wang, Kyle D. Rudser, Donald R. Dengel, Elizabeth A. Braunlin, Julia Steinberger, David R. Jacobs, Alan R. Sinaiko, Aaron S. Kelly

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but cardiovascular disease causes mortality in a significant percentage of survivors. Markers must be developed to predict MPS cardiac risk and monitor efficacy of investigational therapies.MPS patients underwent carotid artery ultrasonography from which carotid intima-media thickness (cIMT) and three measures of arterial stiffness were calculated: carotid artery distensibility (cCSD), compliance (cCSC), and incremental elastic modulus (cIEM). MPS carotid measurements were compared to corresponding data from pediatric and adult healthy cohorts. 33 MPS patients (17 MPS I, 9 MPS II, 4 MPS IIIA, and 3 MPS VI; mean age 12.5 ± 4.7 years), 560 pediatric controls (age 13.1 ± 4.0 years), and 554 adult controls (age 39.2 ± 2.2 years) were studied. Age and sex-adjusted aggregate MPS cIMT (0.56 ± 0.05 mm) was significantly greater than both pediatric (+0.12 mm; 95% CI +0.10 to +0.14 mm) and adult (+0.10 mm; 95% CI +0.06 to +0.14 mm) control cohorts; similar findings were observed for all MPS subtypes. Mean MPS cIMT approximated the 80th percentile of the adult cohort cIMT. MPS patients also demonstrated significantly increased adjusted arterial stiffness measurements, evidenced by reduced cCSD, cCSC, and increased cIEM, compared to pediatric and adult control cohorts. Regardless of treatment, MPS patients demonstrate increased cIMT and arterial stiffness compared to healthy pediatric and adult controls. These data suggest that relatively young MPS patients demonstrate a “structural vascular age” of at least 40 years old.

Original language	English (US)
Article number	637
Journal	International journal of molecular sciences
Volume	18
Issue number	3
DOIs	https://doi.org/10.3390/ijms18030637
State	Published - Mar 15 2017

Bibliographical note

Funding Information:
This study was funded by the Lysosomal Disease Network (U54NS065768, RYW, KDR, DRD, EAB, ASK) and the Brian and Caris Chan Family Foundation (RYW). Additional support for this study was provided by R01DK072124-01A3 (JS), R01CA113930-01A1 (JS), UL1RR033183 (the National Center for Research Resources, NCRR to the University of Minnesota), UL1TR000114 (the National Center for Advancing Translational Sciences, NCATS to the University of Minnesota), and UL1TR001414 (NCRR, NCATS to the University of California-Irvine). The Lysosomal Disease Network (U54NS065768) is a part of the NIH Rare Diseases Clinical Research Network (RDCRN), supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at NCATS, the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, National Center for Advancing Translational Sciences, or the National Institutes of Health.

Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Function
Intima
Lysosomal
Media
Mucopolysaccharidosis
Outcome
Stiffness
Structure
Thickness
Treatment
Vascular

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ijms18030637

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372650

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Wang, R. Y., Rudser, K. D., Dengel, D. R., Braunlin, E. A., Steinberger, J., Jacobs, D. R., Sinaiko, A. R., & Kelly, A. S. (2017). The carotid intima-media thickness and arterial stiffness of pediatric mucopolysaccharidosis patients are increased compared to both pediatric and adult controls. International journal of molecular sciences, 18(3), [637]. https://doi.org/10.3390/ijms18030637

The carotid intima-media thickness and arterial stiffness of pediatric mucopolysaccharidosis patients are increased compared to both pediatric and adult controls. / Wang, Raymond Y.; Rudser, Kyle D.; Dengel, Donald R. et al.
In: International journal of molecular sciences, Vol. 18, No. 3, 637, 15.03.2017.

Research output: Contribution to journal › Article › peer-review

Wang, RY, Rudser, KD , Dengel, DR , Braunlin, EA , Steinberger, J , Jacobs, DR, Sinaiko, AR & Kelly, AS 2017, 'The carotid intima-media thickness and arterial stiffness of pediatric mucopolysaccharidosis patients are increased compared to both pediatric and adult controls', International journal of molecular sciences, vol. 18, no. 3, 637. https://doi.org/10.3390/ijms18030637

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title = "The carotid intima-media thickness and arterial stiffness of pediatric mucopolysaccharidosis patients are increased compared to both pediatric and adult controls",

abstract = "Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but cardiovascular disease causes mortality in a significant percentage of survivors. Markers must be developed to predict MPS cardiac risk and monitor efficacy of investigational therapies.MPS patients underwent carotid artery ultrasonography from which carotid intima-media thickness (cIMT) and three measures of arterial stiffness were calculated: carotid artery distensibility (cCSD), compliance (cCSC), and incremental elastic modulus (cIEM). MPS carotid measurements were compared to corresponding data from pediatric and adult healthy cohorts. 33 MPS patients (17 MPS I, 9 MPS II, 4 MPS IIIA, and 3 MPS VI; mean age 12.5 ± 4.7 years), 560 pediatric controls (age 13.1 ± 4.0 years), and 554 adult controls (age 39.2 ± 2.2 years) were studied. Age and sex-adjusted aggregate MPS cIMT (0.56 ± 0.05 mm) was significantly greater than both pediatric (+0.12 mm; 95% CI +0.10 to +0.14 mm) and adult (+0.10 mm; 95% CI +0.06 to +0.14 mm) control cohorts; similar findings were observed for all MPS subtypes. Mean MPS cIMT approximated the 80th percentile of the adult cohort cIMT. MPS patients also demonstrated significantly increased adjusted arterial stiffness measurements, evidenced by reduced cCSD, cCSC, and increased cIEM, compared to pediatric and adult control cohorts. Regardless of treatment, MPS patients demonstrate increased cIMT and arterial stiffness compared to healthy pediatric and adult controls. These data suggest that relatively young MPS patients demonstrate a “structural vascular age” of at least 40 years old.",

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author = "Wang, {Raymond Y.} and Rudser, {Kyle D.} and Dengel, {Donald R.} and Braunlin, {Elizabeth A.} and Julia Steinberger and Jacobs, {David R.} and Sinaiko, {Alan R.} and Kelly, {Aaron S.}",

note = "Funding Information: This study was funded by the Lysosomal Disease Network (U54NS065768, RYW, KDR, DRD, EAB, ASK) and the Brian and Caris Chan Family Foundation (RYW). Additional support for this study was provided by R01DK072124-01A3 (JS), R01CA113930-01A1 (JS), UL1RR033183 (the National Center for Research Resources, NCRR to the University of Minnesota), UL1TR000114 (the National Center for Advancing Translational Sciences, NCATS to the University of Minnesota), and UL1TR001414 (NCRR, NCATS to the University of California-Irvine). The Lysosomal Disease Network (U54NS065768) is a part of the NIH Rare Diseases Clinical Research Network (RDCRN), supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at NCATS, the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, National Center for Advancing Translational Sciences, or the National Institutes of Health. Publisher Copyright: {\textcopyright} 2017 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Wang, Raymond Y.

AU - Rudser, Kyle D.

AU - Dengel, Donald R.

AU - Braunlin, Elizabeth A.

AU - Steinberger, Julia

AU - Jacobs, David R.

AU - Sinaiko, Alan R.

AU - Kelly, Aaron S.

N1 - Funding Information: This study was funded by the Lysosomal Disease Network (U54NS065768, RYW, KDR, DRD, EAB, ASK) and the Brian and Caris Chan Family Foundation (RYW). Additional support for this study was provided by R01DK072124-01A3 (JS), R01CA113930-01A1 (JS), UL1RR033183 (the National Center for Research Resources, NCRR to the University of Minnesota), UL1TR000114 (the National Center for Advancing Translational Sciences, NCATS to the University of Minnesota), and UL1TR001414 (NCRR, NCATS to the University of California-Irvine). The Lysosomal Disease Network (U54NS065768) is a part of the NIH Rare Diseases Clinical Research Network (RDCRN), supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at NCATS, the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, National Center for Advancing Translational Sciences, or the National Institutes of Health. Publisher Copyright: © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

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N2 - Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but cardiovascular disease causes mortality in a significant percentage of survivors. Markers must be developed to predict MPS cardiac risk and monitor efficacy of investigational therapies.MPS patients underwent carotid artery ultrasonography from which carotid intima-media thickness (cIMT) and three measures of arterial stiffness were calculated: carotid artery distensibility (cCSD), compliance (cCSC), and incremental elastic modulus (cIEM). MPS carotid measurements were compared to corresponding data from pediatric and adult healthy cohorts. 33 MPS patients (17 MPS I, 9 MPS II, 4 MPS IIIA, and 3 MPS VI; mean age 12.5 ± 4.7 years), 560 pediatric controls (age 13.1 ± 4.0 years), and 554 adult controls (age 39.2 ± 2.2 years) were studied. Age and sex-adjusted aggregate MPS cIMT (0.56 ± 0.05 mm) was significantly greater than both pediatric (+0.12 mm; 95% CI +0.10 to +0.14 mm) and adult (+0.10 mm; 95% CI +0.06 to +0.14 mm) control cohorts; similar findings were observed for all MPS subtypes. Mean MPS cIMT approximated the 80th percentile of the adult cohort cIMT. MPS patients also demonstrated significantly increased adjusted arterial stiffness measurements, evidenced by reduced cCSD, cCSC, and increased cIEM, compared to pediatric and adult control cohorts. Regardless of treatment, MPS patients demonstrate increased cIMT and arterial stiffness compared to healthy pediatric and adult controls. These data suggest that relatively young MPS patients demonstrate a “structural vascular age” of at least 40 years old.

AB - Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but cardiovascular disease causes mortality in a significant percentage of survivors. Markers must be developed to predict MPS cardiac risk and monitor efficacy of investigational therapies.MPS patients underwent carotid artery ultrasonography from which carotid intima-media thickness (cIMT) and three measures of arterial stiffness were calculated: carotid artery distensibility (cCSD), compliance (cCSC), and incremental elastic modulus (cIEM). MPS carotid measurements were compared to corresponding data from pediatric and adult healthy cohorts. 33 MPS patients (17 MPS I, 9 MPS II, 4 MPS IIIA, and 3 MPS VI; mean age 12.5 ± 4.7 years), 560 pediatric controls (age 13.1 ± 4.0 years), and 554 adult controls (age 39.2 ± 2.2 years) were studied. Age and sex-adjusted aggregate MPS cIMT (0.56 ± 0.05 mm) was significantly greater than both pediatric (+0.12 mm; 95% CI +0.10 to +0.14 mm) and adult (+0.10 mm; 95% CI +0.06 to +0.14 mm) control cohorts; similar findings were observed for all MPS subtypes. Mean MPS cIMT approximated the 80th percentile of the adult cohort cIMT. MPS patients also demonstrated significantly increased adjusted arterial stiffness measurements, evidenced by reduced cCSD, cCSC, and increased cIEM, compared to pediatric and adult control cohorts. Regardless of treatment, MPS patients demonstrate increased cIMT and arterial stiffness compared to healthy pediatric and adult controls. These data suggest that relatively young MPS patients demonstrate a “structural vascular age” of at least 40 years old.

KW - Function

KW - Intima

KW - Lysosomal

KW - Media

KW - Mucopolysaccharidosis

KW - Outcome

KW - Stiffness

KW - Structure

KW - Thickness

KW - Treatment

KW - Vascular

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The carotid intima-media thickness and arterial stiffness of pediatric mucopolysaccharidosis patients are increased compared to both pediatric and adult controls

Abstract

Bibliographical note

Keywords

UN SDGs

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