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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.
Highlights
The mucopolysaccharidoses (MPSs) are a group of inborn errors of metabolism linked by a deficiency in one of eleven lysosomal hydrolases that degrade glycosaminoglycans (GAGs), modified glycan components such as heparan, keratan, dermatan, and chondroitin sulfate found in cells and extracellular matrix throughout the body
MPS patients frequently die of cardiovascular disease, which often worsens despite development of treatments such as hematopoietic stem cell transplantation (HSCT) and intravenous enzyme replacement therapy (ERT) [2,3,4,5,6,7,8]
We corroborated this finding in a larger, dual-center assessment of 25 MPS Type I and II patients and discovered that our predominantly pediatric cohort of MPS patients demonstrated increased carotid artery stiffness compared to a healthy pediatric control cohort [12]
Summary
The mucopolysaccharidoses (MPSs) are a group of inborn errors of metabolism linked by a deficiency in one of eleven lysosomal hydrolases that degrade glycosaminoglycans (GAGs), modified glycan components such as heparan, keratan, dermatan, and chondroitin sulfate found in cells and extracellular matrix throughout the body. We previously utilized non-invasive carotid artery ultrasonography to demonstrate that carotid intima-media thickness (cIMT) [10], an in vivo marker of intimal medial proliferation, in patients with MPSs was significantly thicker than matched controls [11]. We corroborated this finding in a larger, dual-center assessment of 25 MPS Type I and II patients and discovered that our predominantly pediatric cohort of MPS patients demonstrated increased carotid artery stiffness compared to a healthy pediatric control cohort [12]
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