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Pediatric heterozygous familial hypercholesterolemia patients have locally increased aortic pulse wave velocity and wall thickness at the aortic root

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Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant disorder that affects 1 in 250 people. Aortic stiffness, measured by pulse wave velocity (PWV), is an independent predictor for cardiovascular events. Young FH patients are a unique group with early vessel wall disease that may serve to elucidate the determinants of aortic stiffness. We hypothesized that young FH patients would have early changes in aortic stiffness compared to healthy, age- and sex-matched reference values. Thirty-three FH patients ( ≥ 7 years age; mean age 14.6 ± 3.3 years; 26/33 on statin therapy) underwent cardiac MRI. PWV was determined using propagation of flow waveform from aortic arch phase contrast images. Distensibility and aortic wall thickness (AWT) were measured at the ascending, proximal descending, and diaphragmatic aorta. Ventricular volumes and left ventricular (LV) myocardial mass were measured from 2D cine images. These parameters were compared to age- and sex-matched reference values. FH patients had significantly higher PWV (4.5 ± 0.8 vs. 3.5 ± 0.3 m/s; p < 0.001), aortic distensibility, and ascending aortic wall thickness (1.37 ± 0.18 vs. 1.30 ± 0.02 mm; p < 0.05) compared to reference. There was no difference in aortic area or descending aortic wall thickness between groups. Young FH patients had aortic changes with increased aortic pulse wave velocity in the setting of increased aortic distensibility, accompanied by increased thickness of the ascending aortic wall. Presence of these early findings in young patients despite the majority being on statin therapy support enhanced screening and aggressive treatment of familial hypercholesterolemia to prevent potential future cardiovascular events.

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Acknowledgements

We thank Dr. Sadia Malik for her research guidance and writing support.

Funding

Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001105 and CTSA NIH Grant UL1-RR024982. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Further support was provided by the Pogue Family Distinguished Chair in Pediatric Cardiology, University of Texas Southwestern Medical Center and the Millennium Science Initiative of the Ministry of Economy, Development, and Tourism of Chile—Nucleus for Cardiovascular Magnetic Resonance grant.

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Tran, A., Burkhardt, B., Tandon, A. et al. Pediatric heterozygous familial hypercholesterolemia patients have locally increased aortic pulse wave velocity and wall thickness at the aortic root. Int J Cardiovasc Imaging 35, 1903–1911 (2019). https://doi.org/10.1007/s10554-019-01626-5

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