Circulation. 2001;104:1464-1470
Published online before print September 4, 2001, doi: 10.1161/hc3801.097806
Published online before print September 4, 2001, doi: 10.1161/hc3801.097806
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(Circulation. 2001;104:1464.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Improved Arterial Compliance by a Novel Advanced Glycation End-Product Crosslink Breaker
From the Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, Md (D.A.K., E.P.S., M.K., A.R.C.); the Gerontology Research Center, National Institute on Aging, Baltimore, Md (A.S., E.G.L.); and Alteon Inc, Ramsey, NJ (R.C.D.). A. Scuteri is currently located at the INRCA, Rome, Italy.
This article originally appeared Online on September 4, 2001 (Circulation. 2001;104:r8–r14).Correspondence and reprint requests to David A. Kass, MD, Halsted 500, Johns Hopkins Medical Institutions, 600 N. Wolfe Street, Baltimore, MD 21287. E-mail dkass{at}bme.jhu.edu
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.
Key Words: ALT-711 • arteries • compliance • aging • glycosylation end products, advanced • hypertension
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K. L Moreau, A. J Donato, D. R Seals, C. A DeSouza, and H. Tanaka Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women Cardiovasc Res, March 1, 2003; 57(3): 861 - 868. [Abstract] [Full Text] [PDF]
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M. Kawaguchi, I. Hay, B. Fetics, and D. A. Kass Combined Ventricular Systolic and Arterial Stiffening in Patients With Heart Failure and Preserved Ejection Fraction: Implications for Systolic and Diastolic Reserve Limitations Circulation, February 11, 2003; 107(5): 714 - 720. [Abstract] [Full Text] [PDF]
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E. Kimoto, T. Shoji, K. Shinohara, M. Inaba, Y. Okuno, T. Miki, H. Koyama, M. Emoto, and Y. Nishizawa Preferential Stiffening of Central Over Peripheral Arteries in Type 2 Diabetes Diabetes, February 1, 2003; 52(2): 448 - 452. [Abstract] [Full Text] [PDF]
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E. G. Lakatta and D. Levy Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part I: Aging Arteries: A "Set Up" for Vascular Disease Circulation, January 7, 2003; 107(1): 139 - 146. [Full Text] [PDF]
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S. G. Lage, L. Kopel, C. C. J. Medeiros, R. T. Carvalho, and M. A. Creager Angiotensin II contributes to arterial compliance in congestive heart failure Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1424 - H1429. [Abstract] [Full Text] [PDF]
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A. Cohen-Solal Diastolic heart failure: myth or reality? Eur J Heart Fail, August 1, 2002; 4(4): 395 - 400. [Full Text] [PDF]
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D. Goldsmith, R. MacGinley, A. Smith, and A. Covic How important and how treatable is vascular stiffness as a cardiovascular risk factor in renal failure? Nephrol. Dial. Transplant., June 1, 2002; 17(6): 965 - 969. [Full Text] [PDF]
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