Improved arterial compliance by a novel advanced glycation end-product crosslink breaker

D. A. Kass, E. P. Shapiro, M. Kawaguchi, A. R. Capriotti, A. Scuteri, R. C. DeGroof, E. G. Lakatta

Research output: Contribution to journalArticlepeer-review

Abstract

Background - Arterial stiffening with increased pulse pressure is a leading risk factor for cardiovascular disease in the elderly. We tested whether ALT-711, a novel nonenzymatic breaker of advanced glycation end-product crosslinks, selectively improves arterial compliance and lowers pulse pressure in older individuals with vascular stiffening. Methods and Results - Nine US centers recruited and randomly assigned subjects with resting arterial pulse pressures >60 mm Hg and systolic pressures >140 mm Hg to once-daily ALT-711 (210 mg; n=62) or placebo (n=31) for 56 days. Preexisting antihypertensive treatment (90% of subjects) was continued during the study. Morning upright blood pressure, stroke volume, cardiac output, systemic vascular resistance, total arterial compliance, carotid-femoral pulse wave velocity, and drug tolerability were assessed. ALT-711 netted a greater decline in pulse pressures than placebo (-5.3 versus -0.6 mm Hg at day 56; P=0.034 for treatment effect by repeated-measures ANOVA). Systolic pressure declined in both groups, but diastolic pressure fell less with ALT-711 (P=0.056). Mean pressure declined similarly in both groups (-4 mm Hg; P<0.01 for each group, P=0.34 for treatment effect). Total arterial compliance rose 15% in ALT-711-treated subjects versus no change with placebo (P=0.015 versus ALT-711), an effect that did not depend on reduced mean pressure. Pulse wave velocity declined 8% with ALT-711 (P<0.05 at day 56, P=0.08 for treatment effect). Systemic arterial resistance, cardiac output, and heart rate did not significantly change in either group. Conclusions - ALT-711 improves total arterial compliance in aged humans with vascular stiffening, and it may provide a novel therapeutic approach for this abnormality, which occurs with aging, diabetes, and isolated systolic hypertension.

Original languageEnglish (US)
Pages (from-to)1464-1470
Number of pages7
JournalCirculation
Volume104
Issue number13
DOIs
StatePublished - Sep 25 2001

Keywords

  • ALT-711
  • Aging
  • Arteries
  • Compliance
  • Glycosylation end products, advanced
  • Hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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