Learn About Your Heart...
Made Simple

By Nicolas Shammas, MD

A new, comprehensive sourcebook for
heart and vascular disease patients

Cardiovascular Health Topics

Statistics about Heart and Blood Vessel Diseases in the United States
Structure and Function of the Heart and Blood Vessels
Diseases of the Blood Vessels of the Heart
Surgical Therapies for the Cardiovascular Patient
Peripheral Vascular Disease
Diseases of the Blood Vessels of the Head and Neck
Strokes: How to Survive Them and How to Prevent Them
Valvular Heart Disease
Heart Rhythms: How to Recognize Them and Treat Them
Congestive Heart Failure
11. Understanding Cardiomyopathy, or Weak Heart Muscle
12. Children and Heart Disease
13. Diseases of the Pericardium
14. Systemic Illnesses, Infections and Drugs that Affect the Heart
15. Erectile Dysfunction: a Vascular Disease
16. Cardiovascular Disease Prevention
17. Heart Healthy Nutritional Tips
18. Cardiac Rehabilitation
19. Medications for Cardiovascular Disorders
20. Heart Tests You Need to Know
21. Learn What to Do in a Medical Emergency
22. How to Choose Your Doctor and Hospital
23. Medical Research and How You Can Get Involved
24. Taking the Next Step — A Few Community Resources to Help You Live More Healthfully
25. How Much Did You Learn from This Book: Take a Simple Test

Drug Compound Restores Youth to Aging Arterial Cells in Elderly Hypertensives

A compound called alagebrium, similar to another used in anti-wrinkle creams, may be useful in reducing the deleterious effects of arterial aging in the majority of elderly Americans with systolic hypertension, a study from researchers at Johns Hopkins shows.

"This is the first demonstration that this class of drugs, known as collagen-crosslink breakers, can turn back the clock and make old arteries behave like young ones," says senior study investigator and geriatric cardiologist Susan Zieman, MD, an assistant professor at The Johns Hopkins University School of Medicine and its Heart Institute.

The Hopkins researchers found that alagebrium, formally known as ALT-711 or 4,5-dimethyl-3-(2-oxo-2-phenylethyl)-thiazolium chloride, reduced stiffening in the vessel wall in the main artery of the neck (carotid artery) by as much as 37 percent. The drug also improved endothelial function, the ability of the vessels' inner lining to relax and dilate in response to increased stress from blood flow, by 102 percent.

Chemically, alagebrium is a so-called crosslink breaker, responsible for destroying the rigid chemical bonds known as advanced glycation endproducts, or AGE for short, that form between body proteins and sugars over time. According to Zieman, both stiffening and reduced capacity of the arteries to expand in response to stress are common effects of aging that occur when the crosslinks form in the body's key structural proteins, such as collagen, or when AGEs interact directly with enzymes that regulate blood flow.

Crosslinking effectively carmelizes the collagen leading to tissue "wrinkles," cataracts, as well as stiffening and increased speed and force of blood flow. These processes are accelerated in diabetics.

The Hopkins findings, presented at the American Heart Association's Scientific Sessions 2005, also suggest that the cellular effects of aging caused by AGE are potent targets for new therapies.

In the Hopkins study, 13 elderly men and women with systolic hypertension took either daily doses of alagebrium (210 milligrams) for eight weeks or a look-alike pill (placebo), containing no active drug. AGE and collagen levels were monitored through blood tests. Stiffness was measured using a small pressure-sensor device called a tonometer.

Ultrasound readings, taken before and after drug therapy, were made as a blood pressure cuff was inflated for five minutes and deflated. This allowed researchers to calculate endothelial function based on how much the blood vessel lining relaxed as a percentage increase of how much the blood vessel could expand.

After treatment with alagebrium, neck arteries became less stiff, as shown by tonometer readings and decreased levels of collagen in the blood as AGE crosslinks were broken down. Analysis of additional pressure-wave readings also showed flatter patterns more closely resembling younger arteries than older, stiffer ones, which have wave patterns with higher peaks.

While the results did not explain why endothelial function improved, the researchers believe it has to do with the drug's effects on AGE and cell function. Their theory, Zieman says, is that one chemical reaction, the breakdown of AGE crosslinks, both reduces the structural causes of arterial stiffness in the artery wall and alleviates the detrimental effects of AGE on other enzymes or related proteins, possibly nitric oxide and other chemicals causing vessel inflammation.

"These results confirm that this drug does have important effects on the aging process in the arteries, but we still have to prove that there's some benefit to patients in terms of reducing cardiovascular disease," Zieman says. "Our next step will be a study, expected to begin in late 2006, of the drug's potential benefit at preventing or reversing heart failure in the elderly."

Alagebrium has been under investigational study since 1999, originally as a treatment for hypertension. While clinical studies have demonstrated the drug's ability to loosen up stiff arteries, two larger studies in older people with hypertension have not shown significant results in lowering blood pressure.

Emergency bypass surgery on angioplasty patients drops 90%

When life-threatening problems occur during angioplasty procedures, doctors may perform emergency coronary artery bypass graft surgery, but data from the Mayo Clinic indicates that need to send patients to emergency surgery has dropped sharply, according to a study in the Dec. 6, 2005, issue of the Journal of the American College of Cardiology.

"Our review of almost 25 years of data on angioplasty suggests that there has been a dramatic reduction of almost 90 percent in the incidence of coronary artery bypass graft surgery following angioplasty; and this is despite the fact that more recently we are performing angioplasty on very high risk patients," said Mandeep Singh, MD, from the Mayo College of Medicine in Rochester, Minnesota.

The researchers, including lead author Eric H. Yang, MD, reviewed a unique registry of every angioplasty performed at the Mayo Clinic. The registry includes more than 23,000 cases and extends back to the first angioplasty procedure in 1979.

Data from the Mayo registry were divided into three groups: the "pre-stent" era, 1979 to 1994 (8,905 patients); the "initial stent era," 1995 to 1999 (7,605 patients); and the "current stent era," 2000 to 2003 (6,577 patients).

"We knew there had been a reduction, but the magnitude of the reduction was a surprise to us," Dr. Singh said. "The bypass surgery rates, which were close to 3 percent, came down to 0.3 percent in the most recent time period."

Dr. Singh said the fact that angioplasty is being offered to sicker patients now makes the reduction even more remarkable. Patients requiring emergency surgery in the most recent study period had a higher prevalence of high blood pressure and heart failure, and they were more likely to have undergone previous procedures, compared to patients in the earlier study periods.

Dr. Singh said he believes stents may be responsible for much of the reduction in the rate of life-threatening problems during angioplasty procedures. He also pointed to other improvements in drug therapy and device technology that have made angioplasty safer and more successful.

However, among patients who did suffer serious problems during angioplasty and had to be sent into emergency surgery, the researchers did not see an improvement in survival. Death rates were statistically similar in all three study periods, ranging between 10 percent and 14 percent. Dr. Singh pointed out that there were only 41 deaths among patients who underwent emergency bypass surgery, including just two during the 2000 to 2003 study period. He said such small numbers make it difficult to calculate useful statistical comparisons.

The study authors pointed out that this analysis is based on a retrospective review of registry data from the Mayo Clinic only, not a prospective trial at multiple institutions, although Dr. Singh noted that the registry is very large.

In an editorial in the journal, John A. Bittl, MD, from the Ocala Heart Institute, Munroe Regional Medical Center in Ocala, Florida, said that while the sharp decline in emergency bypass surgery on angioplasty patients is welcome news, he is concerned the results may be used by some providers to argue that back-up surgical facilities are no longer needed.

"Almost every hospital wants a share of the lucrative coronary intervention market and every physician hopes that in-laboratory deaths and the need for emergency bypass and will go away completely, but this ideal situation has not been attained," Dr. Bittl said.

"The assessment of elective PCI without on-site bypass surgery underway in some states is a step in the right direction. But, choosing the right metrics is challenging. The only meaningful comparison between hospitals with and without on-site surgery is the rate of death or urgent transfer to another facility within a pre-specified period of time after PCI. One proposal that mixes acute events with late endpoints like repeat revascularizations is manipulative and misleading," he added.

Dr. Bittl wrote that this study has established an important benchmark and should stimulate exploration of ways to improve angioplasty and make it even safer.

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