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.
Bibliographical noteFunding 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.
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