Drug
decreases blood vessel
stiffness in older people
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.