Making headway in the lab, clinic and community
Many women are still surprised to learn that heart disease, and not cancer, is their number one killer in the United States.
Indeed, more women die from heart disease, stroke and other cardiovascular disorders than from all forms of cancer combined. And women who have a heart attack are more likely to die from one than men.
At UC Davis Health System, researchers and clinicians are engaged in innovative research programs to find solutions to this widespread health threat.
Getting the word out
In addition to investigating vascular biology and conducting translational research in laboratory and clinical settings, cardiologist Amparo Villablanca conducts medical research in the community. Through innovative educational curricula and unique partnerships with national organizations, she is developing and testing models for preventive heart-care delivery and assessing improved outcomes in high-risk women in community settings. Her research in this area is supported by a federal grant and funding from a UC Davis Health System grant.
"While evidence-based medical care in the clinical setting is essential, we also desperately need models of effective interventions in community settings," says Villablanca, professor of cardiovascular medicine, holder of the Frances Lazda Endowed Chair in Women's Cardiovascular Medicine, and founder of the UC Davis Women's Cardiovascular Medicine Program.
"We must help women to better recognize their risks for heart disease and then take steps to reduce those risks before a heart attack or stroke, while we continuously assess new methods that will promote prompt and effective action."
Villablanca is one of four national spokeswomen for the National Institutes of Health's "Heart Truth Campaign," aimed at raising awareness that heart disease is the leading killer of women.
Her community-based research reaches out to high-risk women, particularly those over age 60, in rural areas and in racial and ethnic minority groups who bear disproportionately high heart disease burdens.
Women's forums are held annually in Sacramento. Their lively format – incorporating educational materials, patient testimonials and interactive learning – is setting the standard for public health programs.
Such community education programs have proven successful at building cardiovascular knowledge, increasing awareness in high-risk women and reducing women's clinical risk factors, including abnormal blood pressure and blood glucose and cholesterol levels. The next step, says Villablanca, is to develop strategies to reduce disease inflammatory biomarkers.
"Nearly half a million women die of cardiovascular disease in this country every year," she says.
"Designing scientific approaches that improve, enhance and evaluate outcomes of comprehensive heart care in our model women's heart program and that test the efficacy of preventive interventions in women in community settings is clearly critical."
Homing in on hormones
When endocrinologist Jennifer Lee sees patients who are menopausal, they often ask, "My mother had a heart attack or stroke. What can I do to prevent having one?"
Lee, an assistant professor and epidemiologist in the Department of Internal Medicine's Division of Endocrinology, Clinical Nutrition and Vascular Medicine, can offer prevention advice based on standard risk factors such as body mass index, lipid levels and blood pressure. She knows, however, that improvements in methods for predicting a woman's risk are needed.
"I'd like to provide more useful information," says Lee. "I'd like to better assess my patients' individual risks and offer them the best prevention or treatment strategies."
After menopause, rates of coronary heart disease rise to two to three times higher than those of women of the same age who have not yet gone through menopause. Although replacing hormones seems like a logical solution, results from the Women's Health Initiative on the benefits of hormone replacement therapy were mixed.
"Are the mixed results because not all women are alike?" Lee wonders. "Perhaps a woman's underlying hormone physiology determines what hormonal treatment she might need."
In the laboratory, Lee uses molecular and genetic epidemiological approaches to try to tease out these differences.
In a series of longitudinal population studies and clinical trials, Lee measures blood levels of estrogens and androgens in menopausal women, and tracks their incidence of vascular disease events. Estradiol and testosterone are known to affect inflammation, hemostasis, atherosclerosis and lipid levels, all of which likely contribute to vascular events.
Differences in genes specifying metabolic hormones in women may affect their risk, and identifying these may one day lead to better preventive and therapeutic options.
Lee and UC Davis collaborators also are exploring how hormones that regulate metabolism affect the occurrence and severity of menopausal symptoms. Her presentation of this research received award recognition at the national Society for Epidemiologic Research meeting in June.
"My patients are my inspiration," says Lee. "My goal, as a physician and researcher, is to deliver the best personalized care."
Novel treatment from insect world
Cardiologist and cell biologist Nipavan Chiamvimonvat teamed with a seemingly unlikely collaborator − entomologist Bruce Hammock from the Department of Entomology in the College of Agricultural and Environmental Sciences − to develop a potential new treatment for heart enlargement, one of the most common causes of rhythm disturbances and heart failure in women and men.
Together, they found that an enzyme that plays an important role in how insects develop from larvae into adults is effective in preventing and reducing cardiac cell overgrowth and heart arrhythmias.
High blood pressure and artery disease are, in part, driven by high angiotensin levels, which are associated with increased levels of epoxide hydrolase, an enzyme also found in insects. Epoxide hydrolase is involved in the metabolism of arachidonic acid, a key signaling molecule implicated in diabetes, hypertension and inflammatory disorders. The enzyme degrades anti-inflammatory and anti-hypertensive factors in the heart and blood, according to Chiamvimonvat, leading to pathological changes in the heart and eventual development of heart failure.
Chiamvimonvat, Hammock and other members of their team showed that they could inhibit the enzyme with a new class of drugs − called soluble epoxide hydrolase inhibitors − which also blocked and reversed heart enlargement and heart failure in experimental models. The drug has passed human Phase I clinical trials for safety, and is undergoing Phase II trials to evaluate efficacy in treating diabetes, hypertension and inflammatory diseases. It may one day be found useful for treating a number of major cardiovascular, renal and metabolic disorders.
"UC Davis is a fantastic place for working with talented trainees, meeting visiting scientists and building collaborations," says Chiamvimonvat. "Not only is it conducive to scientific discovery, but to building bridges between basic research and clinical applications. We have high hopes that this discovery will lead to a new avenue of treatment for heart failure − a leading killer that currently has few treatment options."