February 25, 2008

A Drop Of Blood To Save Your Heart

Jill Coley  /  Post and Courier

MUSC doctors' heart disease test could help millions

If you have high blood pressure, a doctor might soon be able to prick your finger, squeeze out a few drops of blood and tell you whether you are likely to develop heart disease.

Two Medical University of South Carolina doctors say they are less than five years away from creating a quick, easy test for the more than 72 million Americans who are hypertensive.

Drs. Michael Zile and Frank Spinale want to identify people before they join the 5 million Americans suffering heart failure - an irreparable condition. Research manager Robert Stroud also is credited in the invention.

Once diagnosed with heart failure, 70 percent of people die within five years, Zile said. The vital organ cannot pump blood properly through the body, leading to shortness of breath. Lungs fill with fluid, limbs swell and energy plummets.

While the screening could benefit millions of people, Zile and Spinale are most interested in helping demographics often overlooked in the canon of heart disease – women and minorities.

There is a myth that women are immune to heart disease, Spinale said. In fact, women are twice as likely to die of heart disease than all cancers combined. Further, black women have higher rates of heart disease than their white counterparts. That's why Spinale and Zile's initial trial of 400 people includes 50 percent women and 35 percent blacks.

"Very few forward-looking studies, risk factor studies, have a very high representation of minorities," Spinale said.

Not only do minorities have higher rates of heart disease, blacks suffer greater organ damage and failure. For any given blood pressure, a black person who lives in South Carolina will have twice as high a rate of stroke and twice as high a rate of heart failure as a white person, Zile said.

Deborah Middleton, a 48-year-old administrative assistant, has had high blood pressure since high school. Her mother, who died of heart failure in 2004, was hypertensive and suffered a stroke. Her father, who also had high blood pressure, died in his sleep of a stroke or a heart attack when he was 38.

"If we keep doing what we did in the past, nothing will change," Middleton said.

She manages her blood pressure through medication, diet and exercise. Middleton jumped at the opportunity to participate in the trial. Although she does not know the result of her blood test, she does know that an ultrasound of her heart showed no signs of disease.

Sheila Thompson, a nurse in charge of recruiting for the study, talks to church groups and attends health fairs to get the word out. Thompson, a 45-year-old black woman who is hypertensive, also is participating in the trial.

"We need to know what is the catalyst between hypertension and congestive heart failure," she said. "We know more blacks will be prone to heart failure, but why?"

Theories include education, health care access, genetics and diet, Zile and Spinale said. But until that question is answered, their test can interrupt the progression from hypertension to heart failure by encouraging people to control their high blood pressure.

How the test works

Human blood carries "biomarkers" that signal the presence of disease. One such biomarker is prostate-specific antigen, used to detect prostate cancer. Another is cholesterol, an indicator of vascular disease. Zile and Spinale labored for more than a decade to identify a set of enzymes whose presence in the blood indicates a high probability of heart failure. The doctors and their team examined diseased hearts removed during transplant operations and tested their hypotheses on models.

To explain the heart's structure, Zile compares the organ to bricks and mortar. The bricks are the cardiac muscle cells that contract and relax. The mortar is between the bricks and is made up of proteins called the extracellular matrix. The matrix is a supporting structure for cells. When babies grow in the womb, enzymes tell the matrix how to structure itself and make the heart muscle cells work in a coordinated fashion.

"What happens in that mortar, whether there's more of it or less of it, whether it gets degraded or rebuilt, depends on a set of enzymes," Zile said. After the heart is formed, the enzymes "go to sleep," Spinale said.

But in some people, namely those with high blood pressure or those who have had a heart attack, those enzymes awaken. "It might be the heart is trying to heal itself and reawakens things it knows it needs to shape and fix. But it is a really bad plan," he said.

Too much or too little of the enzymes' influence can affect the heart's performance negatively. By building up the scaffolding or matrix, the heart will become stiff, like blowing up a thick-walled balloon, Zile said. Too little, and the organ weakens.

MUSC investigators have developed a blood test to monitor the level of these enzymes. "Just being able to tell someone they are at greater risk is an enormous benefit to patient care," Zile said. Intervention through management of hypertension is key because by the time the heart remodels in a bad way, it's too late.

"Trying to reverse that process is not very doable," he said.

What's next

The set of enzymes the doctors are testing is patented by MUSC and recently has been licensed to Ortho-Clinical Diagnostics, a subsidiary of Johnson & Johnson, in a $2.1 million agreement. Spinale and Zile also receive funding through the National Heart, Lung and Blood Institute and the Department of Veterans Affairs. The research team is on pace to develop a commercial screening to be used in doctors offices within five years.

Today, the standard of treating hypertension is reducing salt intake and losing weight. In the future, Zile said he hopes to be able to control enzymes through medicine. Spinale and Zile said they feel the dual pressures of money and time to get the test to the public.

"We're running out of money in medical care. We're going to go broke unless we come up with better ways to catch people early in the disease process," Spinale said. "We need to come up with more affordable ways to ration and deliver the care certain patients need and not give it to other patients that don't need it."