Drug decreases blood vessel stiffness in older people

September 03, 2001

A novel drug that breaks down collagen bonds in the body's blood vessels significantly decreases the stiffness of vessels in older people, according to a study conducted by National Institute on Aging (NIA) scientists and others.* The finding suggests the medication could be a new treatment for high blood pressure, heart failure, and certain complications of diabetes.

ALT-711 (Alteon, Ramsey, New Jersey), a thiazolium-based compound, snips bonds or crosslinks created in the arteries and other tissues when glucose attaches to the protein collagen. Crosslinks are cable-like structures that inhibit the natural flexibility of collagen strands. They tend to proliferate with age. Crosslinks appear to toughen tissues and may contribute to some of the deterioration associated with aging and diabetes, such as elevated systolic blood pressure, stiff arteries, and impaired kidney function.

Independent data from the NIA's Baltimore Longitudinal Study of Aging identifies vascular stiffness as perhaps the most important predictor of mortality from heart disease. The ability to reduce vascular stiffness could have a major influence on reducing deaths from heart disease.

For the study, investigators at nine U.S. clinical centers recruited 93 people over the age of 50 who showed evidence of vascular stiffening, including high systolic blood pressure (greater than 140 mm Hg) and pulse pressure of at least 60 mm Hg.

The participants were randomly divided into two groups--those who received daily doses of ALT-711 and those who were given a placebo daily. After 56 days, arterial pulse pressure--the difference between systolic and diastolic blood pressures--was significantly reduced among those taking the drug compared to the placebo group. In addition, large artery compliance, a measure of artery wall flexibility and blood volume capacity, improved 15 percent in the ALT-711 group compared to no improvement in the placebo group.

No significant drug side effects were noted in the study. Participants in the study who were taking medications to treat high blood pressure were allowed to continue taking these drugs as long as these treatments began at least four weeks before the study commenced and remained unchanged throughout the trial.

The study will appear online Monday at http://circ.ahajournals.org/rapidtrack.shtml as a "Rapid Track" publication of Circulation: Journal of the American Heart Association. The manuscript will be published in the Sept. 25th issue of the journal.

"Arterial stiffening is a major factor in many of the vascular diseases associated with advancing age," said Edward Lakatta, M.D., co-author of the study and chief of the NIA's Laboratory of Cardiovascular Sciences. "The significance of this drug is it alters the properties of the arterial wall and makes it easier for the heart to eject blood into the blood vessels. These results, coupled with prior studies in animals, certainly suggest that ALT-711 may be a safe and efficacious approach to decreasing the impact of arterial stiffness on cardiovascular health."
The research was a joint effort by the NIA, Johns Hopkins University, and Alteon, Inc., as part of the Cooperative Research and Development Act, and was conducted in conjunction with multiple medical institutions.

The National Institute on Aging, one of 25 Institutes that constitute the National Institutes of Health, leads Federal efforts to support and conduct basic, clinical, epidemiological, and social research on aging and the special needs of older people. For more information about the NIA, visit the website at http://www.nih.gov/nia

*D.A. Kass, E.P. Shapiro, M. Kawaguchi, A.R. Capriotti, A. Scuteri, R.C. deGroof, and E.G. Lakatta, "Improved Arterial Compliance by a Novel Advanced Glycation End-Product Crosslink Breaker," Circulation, 2001;104:r8-r14. A. Capriotti and Drs. Kass, Shapiro, and Kawaguchi are affiliated with Johns Hopkins Medical Institutions, Baltimore; Dr. Scuteri and Lakatta are affiliated with the Gerontology Research Center, National Institute on Aging, Baltimore; Dr. deGroof is employed by Alteon, Ramsey, N.J.

NIH/National Institute on Aging

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