Heading the population-based Dallas Heart Study—an examination of the biological and social foundations of the widening ethnic gap in cardiovascular disease—presents Helen Hobbs with a set of challenges different from those she encounters in her lab work. There are patient-recruitment and privacy issues, specific concerns of the ethnically and economically diverse population, and matters of managing an enormous database. But the payoffs are well worth the effort, says Hobbs. "It's a different kind of science, but it complements the work that I do in the lab very well."

The study, initiated in 1999 with funding from the Donald W. Reynolds Foundation, involves some 3,000 Dallas County residents—half of them African American—who have been extensively interviewed on their medical and family histories; health-care access, practices, and beliefs; environmental exposures; and other details related to socioeconomic status. During home visits, the subjects' blood pressure, heart rate, and weight are recorded, and blood and urine samples are collected for analysis. They also come to the University of Texas Southwestern Medical Center for detailed physiological and imaging studies to assess heart function, body fat distribution, signs of atherosclerosis, and other measures of cardiovascular health. Meanwhile, of course, their DNA sequences are recorded.

"Never has such a large and ethnically diverse population undergone such detailed phenotyping," says Hobbs. "That's what makes the study unique and very valuable in terms of trying to define the genetic underpinnings, along with the nongenetic components, of complex traits." In particular, researchers can begin looking for DNA-sequence variations associated with specific cardiovascular risk factors.

While population-based studies can uncover only the associations between genetic and environmental factors and health—not the underlying mechanisms—they have some advantages over lab-based studies, says Hobbs. For one thing, "they're large and they're random, so they're more representative of the population at large." The ultimate goal—and challenge—is using the information to understand what contributes to premature heart disease and higher cardiovascular death rates among African Americans and to design education, prevention, and treatment strategies to address the problem.

Her focus in the Dallas Heart Study is to probe ethnic differences in lipid and glucose metabolism and discover what these differences mean in terms of heart disease.For example, plasma levels of Lp(a), a lipoprotein known to contribute to the buildup of cholesterol on arterial walls, are 2- to 3-fold higher in African Americans than those in Caucasians and Asians. However, Hobbs has shown in the Dallas Heart Study that high plasma levels of Lp(a) are not associated with increased coronary atherosclerosis in African Americans, for reasons that remain unclear.

In addition, the prevalence of insulin resistance is higher in African Americans than in Caucasians, yet plasma levels of triglycerides—which are usually elevated in people with insulin resistance—are lower in African Americans. The researchers also have uncovered two intriguing differences in lipid metabolism between African American and Caucasian participants, and "we're now trying to identify the genetic basis for these ethnic differences," says Hobbs.

The heart study "is true translational research," Hobbs says. "It's clinical investigation tied to basic science, it brings people from different disciplines together, and it focuses on the community that we care for clinically."

—Nancy Ross-Flanigan

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Reprinted from the HHMI Bulletin,
Spring 2004, pages 18-22.
©2004 Howard Hughes Medical Institute