Studies of the Heart

The American Heart Association currently invests more than $12 million to supportcardiovascular research in medical institutions throughout Northeast Ohio.

Here's a dose of reality: Heart disease is the No. 1 killer of women in this country. That news came with the disclosure from the American Heart Association that considerable research was being conducted to combat the problem. With three major teaching hospitals in Cleveland, it came as no surprise that some of the studies were being done in our own back yard.

Armed with a $3 million grant, Kimberly Huck, N.D., began investigating nonpharmalogical remedies for minorities (defined as anyone other than Caucasian males) with heart disease.

Working with patients from UHHS, The Cleveland Clinic, MetroHealth Medical Center and hospitals as far west as Sandusky, as far east as Geneva and as far south as Akron, she involved 167 female patients and 100 physicians. Physicians were equipped with booklets outlining current medical guidelines of heart failure and agreed to enroll and educate patients.

Prior to the study it was known that patients initially admitted to the hospital for heart failure often return a second time, and that they opt for a primary care physician instead of a cardiologist.
Half of the patients in the study were provided with a telemonitoring system, reporting daily with information about weight, salt intake and more to a central monitoring system. The other participants communicated solely with their physicians and were manned with healthful guidelines.

Huck stresses "patients have the best outcome if they capture symptoms early and treat them aggressively. Beta blockers and ACE inhibitors are extremely effective, but if we don't find out about the situation until it is in its advanced stages, we won't have the opportunity to do anything."
As for the guidelines she suggests following? "It all comes down to this: adequate exercise, taking in no more than two grams of sodium in your diet, helping to avoid colds and flu by getting a flu vaccine, avoiding alcohol and cigarettes, taking appropriate medications and watching for signs and symptoms."

Irene Katzan, M.D., a vascular neurologist affiliated with MetroHealth Medical Center and The Cleveland Clinic, is investigating differences in the types and management of strokes experienced by African American and white patients.

There are two main types of strokes. The most common, ischemic stroke, occurs in 88 percent of all cases when a blood vessel is blocked, preventing nutrients and oxygen from getting to brain tissue. Clots traveling from the heart and lodging in a blood vessel of the brain cause approximately 20 percent. About 25 percent are the result of hardening of very small blood vessels in the head that are the result of long-standing high blood pressure, diabetes or smoking. Hemorrhagic stroke, the second type, occurs when a blood vessel bursts, resulting in bleeding in the brain.

Katzan is studying 750 African American and white patients hospitalized between 1991 and 1997 in 17 hospitals in Cuyahoga and Geauga counties. She is investigating the difference in the severity of the stroke, its management and the complications arising during the patient's hospital stay (occurrence of pneumonia, blood clots in the veins of the legs as a result of being bedridden and heart attack). She is also determining whether racial factors come into play when determining mortality and disability rates.

"Strokes are the leading cause of disability in this country," she explains. Not only are strokes more prevalent in blacks than whites, but the stroke-related mortality is higher in the African-American population. In fact, mortality rates are expected to double in the next 20 years.

"We know that whites have a higher incidence of carotid artery disease while blacks have a higher rate of narrowing of the intracranial vessels," she says. "What we don't know is whether there is a difference in the overall severity of neurological impairment after stroke. Stroke is the leading cause of morbidity and disability. With the aging of the population, its impact will only get worse."
Preventive measures could be taken. Katzan stresses the need for control of vascular risk factors. "In stroke, blood pressure is more important than it is with heart disease. Nearly fifty percent of all strokes could be eliminated if the person's blood pressure were under control," she explains.

Earlier studies have revealed conflicting results. The largest study thus far involved a Veterans Administration population. Her study takes on a more global perspective, identifying a random sample of all patients, black and white, male and female. The goal is to optimize stroke management and reduce its recurrence. "I'm hoping the study will help chip away at questions of racial disparities," she says.

At the Cleveland Clinic, Dianne Perez, Ph.D., is attempting to find ways to regulate blood pressure and stress. Her neurological research is about adrenergic receptors, the hormones that regulate stress. The receptors are responsible for the surges of adrenaline that are experienced in fight-or-flight responses.

Earlier she had cloned these receptors and activated them to instruct cells to respond to stress.

Today, she is seeking to identify the proteins and genes activated during stress. Should she succeed, she may lead the way to the creation and development of a new class of synthetic drugs capable of blocking the negative effects of stress.

"When we are excited or we exercise, our blood pressure and heart rates go up," she explains. "The adrenergic receptors are the main controlling mechanism for blood pressure and the heart. With heart disease, they increase or decrease in number. Stress makes everything worse."

Her research is being conducted with mice. Taking the cloned gene, she is creating mutations so they constantly experience a heightened stressful state. In humans, this constant release of adrenaline would result in heart failure. In studying the mice, Perez discovered a transition period between the enlargement of the heart and the breaking down of the adrenergic system. She is attempting to find a gene that may be regulated to stop the heart failure that would ensue. "An enlarged heart is always symptomatic of heart failure. It's part of the disease process," she explains. "What we don't understand is why after it enlarges, it fails."

What she has discovered is that in addition to the enlarged heart, the mice experienced a movement disorder similar to Parkinson's Disease, leading her to question whether or not there is a link between the heart and the brain. (She is already aware that many people who suffer from Parkinson's experience heart problems.) The good news for Parkinson's patients is that if Perez's research determines that this is genetic, preventive medications could be created.

To date, she has identified three receptors for the type of adrenergic receptor known as alpha 1. She says she's convinced that if a drug were to be created to regulate one receptor, it could make the necessary corrections so heart failure would not occur. The question becomes what each of the three receptors does, what needs to be corrected and how to avoid side effects. Once she determines the molecular basis for the medications, the pharmaceutical companies can devise a synthetic solution.

"It is my hope that we will come up with a rational drug design. We will understand how the hormones bind with the receptor and design a synthetic drug so that the signal ends up where we want it," she says.
Somehow, hearing Perez speak of her research leads one to believe that day is not far away.

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