Experimental drug decreases age-related blood vessel stiffening

Johns Hopkins researchers report from this month's American College of Cardiology meeting

An experimental drug may reverse the stiffening of the cardiovascular system that occurs with aging, according to results of a clinical trial conducted at nine sites throughout the United States and led by Johns Hopkins physicians.

Vascular stiffening and its increase in the pulsing of blood pressure and systolic hypertension is a "huge epidemiological problem," affecting about half of all individuals over the age of 60, says David A. Kass, M.D., professor of medicine and biomedical engineering at Hopkins and principal investigator of the trial.

In a group of older people who had evidence of 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 ability of blood vessels to stretch by up to18 percent. Many recent epidemiological studies have shown that pulse pressure is the leading risk factor for cardiovascular disease in the elderly.

During the trial, researchers studied 93 adults older than age 50 with measurably stiffened blood vessels and a systolic blood pressure of at least 140 mmHg. Patients took a drug tablet or a placebo once a day for eight weeks. Researchers recorded their blood pressure, the flexibility or compliance of their arteries and blood flow through the heart, among other factors.

The medication works by breaking up so-called advanced glycosylated (sugar-based) crosslink endproducts (known as AGE) that form between proteins, and occur with aging and/or the altered body chemistry associated with diabetes. These crosslinks particularly target proteins that are long lived -- such as the structural proteins in the artery wall that are responsible for its ability to stretch. The more crosslinks, the stiffer the related tissues. This affects the cornea, bladder, arteries and possibly the heart. In the cardiovascular system, AGE results in a loss of elasticity. This in turn causes an increase in blood pressure pulsing, a change that is linked to vascular disease and atherosclerosis, and also increases the heart's workload. The latter is linked to an increased risk of heart attack, heart failure and coronary artery disease.

"Prior drugs to treat this common type of blood pressure problem mostly have focused on lowering the mean or average pressure by relaxing the peripheral arteries that regulate resistance," says Kass. "ALT-711 appears to be different. It acts on the larger vessels that regulate stiffness. This may represent a novel therapeutic approach for patients with arterial stiffening associated with aging, diabetes and systolic hypertension."

Related Web sites:
American College of Cardiology 50th Scientific Sessions
http://www.acc.org/2001ann_meeting/home.htm

Information on Heart Disease Treatments at Johns Hopkins
http://www.hopkinsmedicine.org/heartdisease.html