Vulnerable plaques

Hidden Time Bombs: Methodist Researchers Work to Diffuse Vulnerable Plaques

BY ERIN FAIRCHILD

Death is often the first sign of heart disease. Seemingly out of the blue, a friend or loved one will have a massive, deadly heart attack. Without symptoms such as chest pain or fatigue — common telltale signs of an impending heart attack — many patients are unable to foresee the tragedy.

Researchers at the Methodist DeBakey Heart Center and The Methodist Hospital Research Institute (TMHRI) are working to understand how this phenomenon occurs. Interventional cardiologists Dr. Juan Granada and Dr. Albert Raizner are conducting research to uncover why atherosclerotic plaques, which build up inside the arteries, can cause anything from small heart attacks to massive heart attacks and sudden death.

“Many people have blockages in their arteries due to the buildup of plaques,” Granada said. “Some of those plaques are benign, but some may become very dangerous. The challenge is to determine which ones are vulnerable to rupture and cause deadly events.”

Plaque development is a natural, though not necessarily healthy, process that begins in early childhood and progresses as we age. When it forms along the inside lining of an artery and ruptures, it produces a clot that blocks blood flow to the heart and deprives it of much-needed oxygen. Granada, Raizner and their research teams are looking at ways to determine, through the validation of several imaging techniques, which plaques are dangerous and susceptible to rupture and which are stable and therefore less likely to cause damage.

Methodist has one of the top research facilities in the country for studying vulnerable plaques — those plaques that may not obstruct blood flow or cause symptoms such as chest pain, but suddenly become very unstable, break off and result in deadly clots. A normal stress test may not pick up a vulnerable plaque because these tests look for obstructions and by nature, these lesions may be non-obstructive.

The teams’ research has begun to provide a better understanding of what makes plaque vulnerable. Thus far, they have learned that inflammation of the artery at the site of the plaque debilitates the region and makes the plaque very soft, compared to stable plaques, which are hard. Also, plaques with high concentrations of cholesterol and debris, and those with a thin lining of scar tissue are more likely to rupture and cause damage.

Through grants from TMHRI, Weill Medical College of Cornell University and the Houston Texans professional football team, and gifts from the community, the interdisciplinary research team from Methodist, Weill Cornell and the University of Houston have many studies under way. Current investigations include cellular and molecular research, imaging and diagnostics and therapeutic studies. (See sidebar.)

“The accurate detection of dangerous plaques in asymptomatic people could have a tremendous impact in public health and economics by preventing many deaths, suffering and disabilities,” Granada said. “As research and technology advance, we’ll be able to use imaging to screen people for these lesions. In the future, as technological advances allow it, this type of screening may become as common as getting a mammogram or a colonoscopy.”

Granada, Raizner and cardiologist Dr. Greg Kaluza received a grant from the Houston Texans to develop an animal model that emulates human plaque formation so that they can better understand the process by which dangerous plaques evolve. Their study is aimed at speeding the development of new ways to prevent, stabilize and treat them.

Raizner said that while great strides have been made in the past 20 years in the treatment of heart attacks, the events leading up to them are poorly understood and frustratingly unpredictable. “Vulnerable plaques are hidden time bombs. This is a pattern we hope to stop,” he said.

A promising new treatment for vulnerable plaques also is being studied at Methodist. Kaluza is working on the development of a stent made of material that is absorbed

ADDITIONAL MEMBERS OF THE VULNERABLE PLAQUE RESEARCH GROUP

PLAQUE Eli Lev,MD, researcher and cardiologist with the Methodist DeBakey Heart ARTERY WALL Center (MDHC), is studying the relationship between platelets and stem cells for strategies to help prevent or heal life-threatening ruptures. David Wallace-Bradley,a University of Houston research associate on the team, is using catheter-based intravascular ultrasound imaging technology to see inside plaques and identify their cholesterol and inflammatory makeup, to better help determine which plaques are dangerous and in need of treatment. Ioannis Kakadiaris, PhD, professor at the University of Houston, is developing a method to detect the newly formed vessels around the plaque using intravascular ultrasound. John Mahmarian, MD,nuclear cardiologist at MDHC, uses noninvasive computer tomography angiography to see the structure of a patient’s plaque. Shankar Vallabhajosula, PhD, researcher at Weill Medical College of Cornell University, uses positron emission topography and nuclear tracers to detect regions with a high degree of inflammation.

Dr. Albert Raizner

into the artery over time. If an area in a patient’s artery has been identified as being at risk, this type of stent may stabilize the region, making it less likely to break off and clot.

Methodist also has the only angiographic suite in the Texas Medical Center that is designed for experimental endovascular imaging and tissue characterization for animal research. The suite has experimental cardiac catheterization capabilities at a quality that is robust enough for humans but sized for animals.

This laboratory is one of two labs in the nation with dedicated intravascular ultrasound software that gives researchers the ability to see inside arteries and determine whether the plaque has characteristics that show it is at risk.

“We’ve assembled an interdisciplinary team of outstanding researchers, in collaboration with Weill Cornell and University of Houston, who have expertise in cardiology, molecular imaging and diagnostic imaging, to conduct some of the most advanced basic, translational and clinical research on vulnerable plaques,” Granada said. “We’re exploring new territory, and we hope to stop this disease in its tracks.”

New Theories, But the Advice Remains the Same

Until recently, it was widely believed that most heart attacks were caused by the gradual build up of plaque in the arteries, which restricted blood and oxygen flow to the heart. Now it is believed that most heart attacks may be caused by hidden vulnerable plaque that suddenly ruptures causing clots and blockages. This may explain why some apparently healthy people suffer from heart attacks and strokes. Once researchers develop a better understanding of vulnerable plaque, new treatments and detection methods may follow. In the meantime, what can you do to keep your cardiovascular system healthy? Heed your physician’s advice: Continue to get regular checkups Maintain a healthy weight Eat a heart-healthy diet Quit smoking Control your diabetes, blood pressure and cholesterol Get some exercise

Did you know?

A 12- to 13-point reduction in blood pressure can reduce heart attacks by 21 percent, strokes by 37 percent, and all deaths from cardiovascular disease by 25 percent. During 1999-2002, nearly 25 percent of U.S. adults had high cholesterol levels or were being treated with medication. Only 63 percent of those with high levels were aware of it. A 10 percent decrease in total blood cholesterol levels may reduce the incidence of coronary heart disease by as much as 30 percent. For more heart-healthy tips, visit methodisthealth.com