Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome

Hypertension. 2012 Jan;59(1):92-7. doi: 10.1161/HYPERTENSIONAHA.111.180919. Epub 2011 Nov 14.


Hutchinson-Gilford progeria syndrome is a rare, segmental premature aging syndrome of accelerated atherosclerosis and early death from myocardial infarction or stroke. This study sought to establish comprehensive characterization of the fatal vasculopathy in Hutchinson-Gilford progeria syndrome and its relevance to normal aging. We performed cardiovascular assessments at a single clinical site on the largest prospectively studied cohort to date. Carotid-femoral pulse wave velocity was dramatically elevated (mean: 13.00±3.83 m/s). Carotid duplex ultrasound echobrightness, assessed in predefined tissue sites as a measure of arterial wall density, was significantly greater than age- and sex-matched controls in the intima-media (P<0.02), near adventitia (P<0.003), and deep adventitia (P<0.01), as was internal carotid artery mean flow velocity (P<0.0001). Ankle-brachial indices were abnormal in 78% of patients. Effective disease treatments may be heralded by normalizing trends of these noninvasive cardiovascular measures. The data demonstrate that, along with peripheral vascular occlusive disease, accelerated vascular stiffening is an early and pervasive mechanism of vascular disease in Hutchinson-Gilford progeria syndrome. There is considerable overlap with cardiovascular changes of normal aging, which reinforces the view that defining mechanisms of cardiovascular disease in Hutchinson-Gilford progeria syndrome provides a unique opportunity to isolate a subset of factors influencing cardiovascular disease in the general aging population.

Trial registration: NCT00425607.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aging / physiology*
  • Ankle Brachial Index
  • Blood Flow Velocity / physiology
  • Blood Pressure / physiology
  • Carotid Arteries / physiology
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / epidemiology*
  • Carotid Artery Diseases / physiopathology*
  • Carotid Intima-Media Thickness
  • Child
  • Child, Preschool
  • Female
  • Femoral Artery / physiology
  • Humans
  • Male
  • Progeria / epidemiology*
  • Progeria / physiopathology*
  • Progeria / therapy
  • Prospective Studies
  • Pulsatile Flow / physiology
  • Vascular Stiffness / physiology

Associated data