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Experimental drug decreases age-related blood vessel stiffening

An experimental drug may reverse stiffening of the cardiovascular system that occurs with aging, according to a national study led by Johns Hopkins physicians.

In a group of older people with vascular stiffening, the drug, ALT-711, significantly reduced arterial pulse pressure, defined as the difference between systolic blood pressure (the upper number) and diastolic blood pressure (the lower number). It also improved the blood vessels' ability to stretch by about 14 percent. Results are to be reported in the Sept. 25 issue of Circulation, an American Heart Association journal, but were posted online Sept. 3. ALT-711 is manufactured by Alteon Inc., Ramsey, N.J.

Vascular stiffening and its related increase in the heart's workload is a "huge epidemiological problem," affecting about half of all individuals over age 60, says David A. Kass, M.D., lead author of the study and professor of medicine and biomedical engineering at Hopkins. "Many recent epidemiological studies have shown that pulse pressure is the leading risk factor for cardiovascular disease in the elderly," he says. Left untreated, the condition can lead to high blood pressure, congestive heart failure, heart attack and other disorders.

ALT-711 works by breaking up chemical links between sugar and proteins called advanced glycosylated (sugar-based) crosslink endproducts, or AGE. In the cardiovascular system, AGE results in a loss of artery elasticity. This leads to an increase in the blood pressure pulse and selective rise in the systolic pressure, putting patients at an increased risk of heart attack, heart failure and coronary artery disease.

The crosslinks form in patients with abnormal sugar control such as diabetics but also with normal aging. They particularly target long-lived proteins, like those that make up the structure of artery walls and are responsible for their ability to stretch. The more crosslinks, the stiffer the related tissues. This affec
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Contact: Karen Blum
kblum@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
5-Sep-2001


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