Preventive Medicine
Detecting problems earlier is helping kids stay healthy into adulthood
How do you prevent setting a body up for a heart attack later in life?
Doctors have known for more than 20 years that some babies are genetically predisposed to heart disease. A low birthweight increases the risk of coronary heart disease in adulthood.
The “developmental origins of disease hypothesis” proposes that coronary heart disease and the diseases related to it originate through responses to undernutrition in the womb and in infancy that permanently change the body’s structure, physiology and metabolism. But a sedentary lifestyle and poor eating habits can also put kids on the wrong course toward heart disease. That is where researchers at Cincinnati Children’s are stepping in to come up with strategies to turn things around.
“In our experience, the development of obesity in children and adolescents is a combination of genetic and environmental influences,” says Elaine Urbina, MD, Director of Preventive Cardiology in the Heart Institute at Cincinnati Children’s.
“More often than not, there is a family history of overweight in many family members. This hereditary tendency is compounded by adverse lifestyles shared by the family.”
The ‘v’ in cardiovascular
Today’s generation of children may be the first to have a shorter life expectancy than their parents, and it may be entirely related to the obesity epidemic, Urbina says.
Her job is to research how to keep kids from having a heart attack or stroke when they get older. She is seeing more signs of organ damage in kids as young as 10, who have thick hearts or stiff arteries.
Stiffened arteries make it harder for the heart to relax. In adults, it is called diastolic dysfunction, and it is a precursor of congestive heart failure.
“These changes that we’re seeing in high-risk youth in their adolescence really portend a poor cardiovascular future for them,” Urbina says.
She is fighting back by trying to prevent childhood obesity and using intensive therapies for kids who already have problems like diabetes or multiple cardiovascular risk factors.
Her work starts in the laboratory, where she concentrates on noninvasive vascular imaging techniques to advance what we know about heart disease in kids. That involves using ultrasound to visualize the veins and arteries, measure blood flow to organs and tissues throughout the body and identify blockages to blood flow, such as plaque build-up.
“People forget that cardiovascular disease has a ‘v’ in it,” she says. “There is the vascular part. We’re always focusing on the heart, and there have been noninvasive techniques developed in adults that we’ve now been able to translate down to younger ages.”
Urbina’s interest in preventive cardiology stems from her cardiology fellowship in 1991 at Tulane University in New Orleans, where she joined the world-renowned Bogalusa Heart Study, one of the longest-running epidemiologic studies of cardiovascular risk factors in kids. The study began in 1973 and has tracked the cardiovascular health of the Louisiana town’s residents ever since. It confirms that coronary artery disease begins in childhood and that a healthy diet can make for a good heart.
Expanding vascular imaging for children Cincinnati Children’s recruited Urbina in 2003 to expand our capabilities and our research in pediatric vascular imaging.
Imaging a child’s vessels involves examining the endothelial cells that line the interior surface of the vessels, looking for signs of damage, such as fatty material that could eventually block the arteries if the problem continues into adulthood.
“We’ve examined every type of arterial stiffness in endothelial function testing available and have worked with the manufacturers to adapt tests for pediatric use,” Urbina says. “This really puts us in the forefront of that particular field.”
Detecting problems earlier
Most pediatric heart centers image only hearts, says
Connie McCoy, RVT, a senior research vascular sonographer in our Cardiovascular Imaging Core Research Laboratory. But here,she is responsible for advancing what we know about heart disease by imaging of all the arteries and veins outside of the heart.
McCoy was instrumental in developing our Pediatric Vascular Training Institute, where pediatric researchers come from all over the country to develop expertise in vascular structure and function in kids. She also has performed independent research and presented her most recent findings in March to the American Heart Association epidemiology meeting in Atlanta.
“We certainly see functional and structural changes in kids who have risk factors,” McCoy says. “They might have type 1 or type 2 diabetes. They might have lupus. They might be obese. We know that as these kids age, they can have early events, whether it is heart attack or stroke. We want to know, when does that damage start? And when can we intervene and reverse it?”
She applies imaging techniques to look at kids who are at risk for cardiovascular complications from a variety of diseases in addition to diabetes and obesity, such as hypertension, HIV, chronic kidney disease, obstructive sleep apnea or Turner syndrome.
“Our goal is to develop new strategies, perhaps new protocols in the way that we image, what we look at or what we measure,” she says.
Those strategies likely will involve working with primary care physicians and families earlier, before disease progresses.
“When I first started here, there was an ongoing study about vascular structure of kids with type 2 diabetes,” McCoy says. “We just started seeing them again five years later. They’re heavier and they’re bigger, and their arteries are stiffer and thicker five years later. They’re on the course for early cardiovascular events. The question is, what interventions could have been done in those five years to prevent the progression of their cardiovascular disease?”
Stepping in to help
The vascular imaging McCoy uses to identify risk in diabetes patients can predict cardiovascular problems in patients with Turner syndrome, a chromosomal condition that affects 1 in 2,000 women.
Girls born with Turner syndrome lack an X chromosome, resulting in short stature or other skeletal anomalies and congenital problems. They are at risk for thyroid disease, high blood pressure and diabetes.
“This condition kills,” says Larry Dolan, MD, Medical Director of the Diabetes Center in the Department of Endocrinology. “But Dr. Philippe Backeljauw and his team are on the road to identifying potentially who is going to be at greater risk. If we have a way to predict who would develop aortic dissection (a tear in the inner wall of the aorta that can be fatal),the question becomes: What’s an effective intervention?”
Philippe Backeljauw, MD, Medical Director of our Turner Syndrome Clinic, is working with Iris Gutmark-Little, MD, and Sarah Lawson, MD, to further the clinical research that might answer this question.
They follow about 170 patients with Turner syndrome, the largest collection of Turner patients in one center in North America. About 75,000 women in the United States have it, Backeljauw says. Some 90 percent have ovarian failure at a young age, and 30 percent have heart disease. Pediatric endocrinologists treat them because they have hormone deficiencies and short stature. Cincinnati
Children’s is the only center in this region that cares for Turner women through adulthood, does large studies and offers a support group.
From a research perspective, Backeljauw’s team is looking at helping young women with Turner syndrome avoid or lessen cardiovascular complications. They are studying the prevalence of hypertension, problems with the pulmonary veins returning blood to the right atrium instead of the left, and in vasculopathy, a disorder of the blood vessels.
This knowledge helps doctors identify the patients at risk for cardiovascular disease and allows them to intervene by working with weight control and anti-hypertension medicines, he says.
His group will continue to study cardiovascular malformations, airway dysfunction and behavioral aspects of patients with Turner syndrome, he says, and they hope to come up with three-dimensional modeling to guide surgeons.
“We are able to provide optimal care for these patients,” he says. “We have the tools and resources to train healthcare professionals and parents in Turner syndrome care. And we have a patient population and manpower to continue to do research studies.”
Understanding Asthma
Everything researchers thought they knew about asthma may just be skin deep.
They are now looking at the skin itself in hopes that it can provide more clues about asthma than the lungs.
“People used to think of asthma as only a lung disease,” says Gurjit “Neeru” Khurana Hershey, MD, PhD, Director of the Division of Asthma Research at Cincinnati Children’s. “And it is, in the sense that it’s your lungs that are affected. But what is it in the lungs that is contributing to the development of asthma?”
She is looking at the role of the epithelial cell in allergic inflammation in asthma. Recent studies have highlighted that the epithelial cell is the most important cell initiating the whole process that leads to asthma, she says.
So whether asthma is triggered by diesel exhaust, air pollution, smoke or mold, that trigger comes in contact with the epithelial cell, and the ensuing inflammation leads to asthma. But no current therapy specifically targets the epithelial cell, so that is the goal.
“One thing we’ve learned is that skin barrier function is an important determinant of asthma,” Khurana Hershey says. “The better your skin works, the less likely you are to get asthma. And if your skin barrier is not good early in life, you’re more likely to have asthma symptoms.”
Researchers have long known eczema is a risk factor for asthma, but they are now learning that some of the genes associated with the development of asthma are actually skin genes.
“It’s not just that the eczema is an allergic disease in the skin that often precedes asthma,” Khurana Hershey says. “There’s something innately wrong with the skin of individuals with eczema. Their skin barrier isn’t normal.”
Researchers can measure skin barrier function in kids as young as 2 to figure out how much water the skin loses and whether the skin barrier works properly.
“It’s not surprising that skin that has eczema on it doesn’t work well,” Khurana Hershey says. “But it is surprising that normal appearing skin of someone with eczema isn’t normal. Even their ‘normal’ skin does not have good barrier function, compared to a person without eczema.”
That, along with genetic studies that indicate that defects in genes important in skin barrier function can promote the development of asthma, tells her that maybe researchers should be thinking about asthma in a different way.
“Maybe the dust and the other things that we’re exposed to, in addition to getting in through the lungs like we thought, are also getting in through the skin and sensitizing us,” she says.
Doing a skin test on a 2-year-old may tell doctors who may be more likely to get asthma. And maybe researchers can figure out how to improve skin barrier early in life as a way to prevent the development of asthma altogether.
“It’s never been tried,” she says. “People have been very focused on other things in the lung. But that’s why our grant is looking at the role of the epithelial cell. We’re not concentrating on epithelial cells in one particular location. We are studying the skin, the gut and the lung.”
The best way to make an impact on a disease like asthma is to study the science behind it to try to identify new targets, Khurana Hershey says. If clinical researchers can compare treatments and decide on the best ones, they can develop guidelines that will help more kids stay healthy as long as possible.
Early intervention, she says, can give kids a better fighting chance.
