Johns Hopkins Medical InstitutionsOffice of Communications and Public Affairs
March 2001
JOHNS HOPKINS RESEARCHERS REPORT FROM THIS MONTH'S AMERICAN COLLEGE OF CARDIOLOGY MEETING
The following news tips are based on abstracts or posters to be presented at the American College of Cardiology's 50th Scientific Sessions, held March 18-21 in Orlando, Fla.
To pursue either of these stories, please contact Karen Blum at 410-955-1534 or [email protected]. Please observe the embargoes.
EXPERIMENTAL DRUG DECREASES AGE-RELATED BLOOD VESSEL STIFFENING (*Late-breaking Clinical Trial*: Embargoed for Monday, March 19, at 10 a.m. EST)
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."
ARM BLOOD FLOW COULD PREDICT HEART ATTACK RISK (Embargoed for Sunday, March 18, at 3 p.m. EST)
A lowered ability of blood vessels in the arm to respond to stress is associated with increased heart size -- an important risk factor for heart disease, according to a Johns Hopkins study.
In the work, on 35 people ages 55 to 75 with mild hypertension, the researchers used magnetic resonance imaging (MRI) to measure the size of the heart's left ventricle, its main pumping chamber. Next, they temporarily put a tight cuff on the patients' left arms to stop blood flow, then used ultrasound to measure the amount of blood flow once the cuff was loosened. This test was a measure of the ability of endothelial cells lining the blood vessels to expand or contract in response to stress and other physiological demands such as exercise.
The results? The amount of blood flow through blood vessels in the arm after the cuff was released was tied directly to the heart size. The better the ability of the vessels to respond to the stress of increased blood flow when the cuff was released, the more normal the heart size, and vice versa. An enlarged heart is dangerous and contributes to a person's risk of heart attack, stroke or heart failure.
"The reduced ability to respond to increased blood flow in these peripheral blood vessels may be an early marker for cardiac problems," says Kerry J. Stewart, Ed.D., senior author of the study and director of cardiac rehabilitation and clinical exercise physiology at Hopkins. "This dysfunction causes resistance to blood flow. As a result, the heart works harder and becomes enlarged. These findings suggest that it may be important to diagnose and treat problems in the peripheral blood vessels as a way of preventing or reducing the health consequences of an enlarged heart."
Stewart and his team are studying whether regular exercise can improve the responses of peripheral blood vessels to stress.
--JHMI--
Related Web sites:
American College of Cardiology 50th Scientific Sessionshttp://www.acc.org/2001ann_meeting/home.htm
Information on Heart Disease Treatments at Johns Hopkinshttp://www.hopkinsmedicine.org/heartdisease.html
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