Research with Arctic Peoples: Unique Research Opportunities in Heart, Lung, Blood and Sleep Disorders

Background

Arctic peoples are spread over eight countries and comprise 3.74 million residents of whom 9% are indigenous. Of the eight Arctic countries, Iceland is the only Arctic country entirely within the region traditionally defining Arctic people (the region north of 60 degrees north latitude). Other Arctic countries include Greenland (Denmark), Canada, Norway, Finland, Sweden, Russia, and the United States. Although Arctic peoples are very diverse, there are a variety of environmental and health issues that are unique to the Arctic region and research exploring these issues offers significant opportunities as well as challenges. For the remainder of this document, the terms Eskimo (preferred by Natives in Alaska) and Inuit (preferred by Natives in the remaining Arctic countries) will be used to refer to the same Yupik/Inupiat people.

Working Group Objectives

The day and a half day agenda was divided into three sessions to allow time to address each of the objectives in separate sessions and then to review results as a group to refine recommendations and set priorities. The three Working Group objectives were:

1. Identify and prioritize scientific opportunities for research on heart, lung, blood, and sleep disorders that may be uniquely addressed with Arctic Peoples: Population-based research that might be pursued with Arctic peoples comprises two areas: observational studies and clinical trials/intervention studies. It was useful to identify how these particular designs may be utilized to address research hypotheses that are uniquely addressable in Arctic Peoples. Given the logistical difficulties and high expense, research objectives in the Arctic should be pursued in large part because they can not be done in areas more hospitable to research. Among the research questions that can be addressed most appropriately or uniquely with Arctic peoples, many derive from the unique risk profile of the inhabitants, their geographical isolation, limited dietary choices, high exposure to some contaminants, limited health care delivery (in some areas), and extreme living conditions. To identify research priorities, it was considered essential to obtain a perspective from both the Native Arctic Peoples and the primarily non-Native scientific investigators.
2. Identify obstacles to implementation and methods to address them: Formidable obstacles to health research with Arctic Peoples account, in part, for the dearth of data documenting health problems and offering solutions to those problems. Physical obstacles include harsh weather, the low density of the population, and the lack of options to transport personnel, equipment and samples to and from villages where many Native people reside. Infrastructure problems include lack of trained researchers and research institutions in the regions of opportunity and lack of biomedical research infrastructure including clinic space, imaging equipment, laboratories, freezer space, trained technicians, and housing. Finally, the cultural differences and previous negative experiences of the Eskimo and Inuit people with research offered special challenges to investigators in conducting culturally sensitive and effective research that is scientifically meritorious and of true benefit to the participants and the overall community.
3. Facilitate international comparisons: Since Alaska is the only Arctic state within the United States, U.S. research with Arctic peoples must focus on Alaska. However, the value of international comparisons with the other seven countries with interests in Arctic Research was acknowledged. In fact, this was a major reason for the creation of the International Union for Circumpolar Health (IUCH). Comparisons among the member countries reflected their shared interests and understanding that common research objectives and problems may best be addressed with cooperation, collaboration and standardization. Many members of the IUCH have more extensive experience in biomedical research with Arctic Peoples than has been supported within the United States. Factors that will facilitate international comparisons were addressed to determine how countries can promote a common agenda that will be mutually beneficial.

Working Group Presentations:

Charge to the Working Group: Dr. Barbara Alving, Acting Director, National Heart, Lung, and Blood Institute, provided opening remarks and the charge to the Working Group. She stressed the importance of current efforts between the United States and Canada to build partnerships and collaborations and that the common interest in Natives of the Arctic may offer an additional opportunity. She noted that some of the issues regarding research among Alaska Natives are common to Natives in the lower 48 states as well. She suggested there are multiple opportunities for research and collaboration and that this Working Group would help to prioritize those opportunities. Finally, she thanked the CIHR-Institute for Aboriginal Peoples' Health for co-sponsoring the Working Group and hoped that it would lead to further collaborative efforts with NHLBI.

Session on Research Priorities

The first speaker, Ms. H. Sally Smith, co-chair of the Working Group and a Yupik Eskimo, is the current Chair of the National Indian Health Board. She provided a broad overview of the health of Alaska Natives and urged the participants to recognize how the interests of NHLBI and CIHR may or may not overlap with those of the Native community. She focused the group's thinking by noting the total population of Alaska is 627,000 people; half live in Anchorage. Natives represent 19% of the state's population and represent a diverse group including Eskimos, Indians and Aleuts. She contrasted the health priorities in 1950 with those of today noting the decrease in infectious diseases, continuing high rates of injuries and accidents, and the increase in chronic diseases including cardiovascular disease. She noted that rates of cardiovascular disease have remained stable in Alaska while declining for two decades in the lower 48 states. Citing results from the Behavioral Risk Factor Survey, she explained that half of all deaths in Alaska Natives can be related to lifestyle choices including high cigarette smoking, rising obesity and diabetes, declining physical activity, and changing diets from subsistence to market foods. In contrast, community concerns focused more on alcohol and substance abuse, declining traditional lifestyle, and the effects of contaminants. She stressed that current needs include a system to monitor the health behaviors of tribes, a surveillance system to monitor chronic disease including disease registries, and intervention studies to prevent and treat diseases with rising incidence.

Barriers to research in Alaska are numerous. Historically, research is seen as not offering much benefit and, perhaps, harming the community. Distrust increased because of investigators taking and never giving back to the community. Often, research results were shared with the scientific community before being shared with the Native community. Other factors creating barriers to research with Arctic Peoples include poor education leading to a lack of understanding of research, limited supply of Native scientists, lack of educational programs to train students interested in biomedical research, and a dearth of mentors to train and inspire students. Potential solutions include creation of mentorships, development of advanced degree programs in Alaska educational institutions, simplification of the grant application and reporting processes, emphasis on community partnerships for research projects, and more rapid response for funding decisions. Distance learning programs may offer a solution to the formidable barrier of geography. Natives have made great progress in managing their health care. Now they want to manage their health research.

Dr. Jeff Reading offered a Native perspective from Canada. As Director of the CIHR - Institute for Aboriginal Peoples' Health (CIHR-IAPH), he presented the conclusions of a report entitled "Dialogue on Northern Research" summarizing a meeting held in early 2004 on priorities for research in Northern Canada. The meeting included Aboriginal representatives, researchers and government agency representatives. He noted that the CIHR-IAPH is very interested in collaborations and partnerships. Several have been developed in the past three years. Requests for applications have been released through the latter for small planning grants as a forerunner to larger grants for actual research. This may offer a model for future collaborations between the United States and Canada. Recommendations from the cited report included increasing capacity within the communities regarding research, giving greater weight to traditional knowledge in reviewing applications, establishing community-based research, and developing an integrated northern policy. Specific needs included better integrated policies, more infrastructure and people for research, more educational alternatives within northern communities, establishing a community relevance review as a necessary step in the research approval process, and consulting with the communities earlier in the process.

Dr. Peter Bjerregaard presented the results of research with the Inuit in Greenland, which represent 90% of the population of Greenland. Unlike the United States, the government of Greenland is run by the Inuit, thus, decisions on research are made by the Greenland government and the researcher. Conditions for research are similar to Northern Alaska and Northern Canada. There are no roads between villages; all transportation is by air or by boat. Health priorities are related to lifestyle: suicides, alcohol, tobacco and the metabolic syndrome. Research priorities include societal development and health, social inequality, child health, interventional research, and human biology and disease. The main obstacle to research with the Inuit in Greenland is a lack of infrastructure. For example, many of the Inuit speak only Greenlandic so interviews must be done in that language. In addition, the low density of the population and high travel costs lead to high costs of research.

Dr. Kue Young presented results from research with the Inuit in Canada. Early data indicated ischemic heart disease of the Inuit was 50% of the rate for whites, cholesterol levels and triglycerides were low, diabetes prevalence was low and dietary intake of polyunsaturated fatty acids was high. Diabetes rates were very low in Canadian Inuit compared to First Nations (Indian Tribes of Canada). Obesity rates were lower for Inuit than those for First Nations but higher than those for Canadian whites. Obesity did not seem to confer the same degree of increase in lipids and blood pressure as for non-Natives. The proportion of the Native population currently smoking cigarettes was very high compared to non-Natives. Genetic risk factors varied but in both directions, e.g., ACE high risk alleles were less frequent, but ApoE high risk alleles were more frequent.

Dr. Hakon Hakonarson reported on the efforts of deCode Genetics, to mobilize the resources within Iceland to address genetic causes of disease. The strength for genetic research in Iceland is the phenomenal genealogical database. Records have been linked to genotype and phenotype data including medical records to produce a data base that can quickly and thoroughly explore scientific questions linking many distant relatives. Genotyping included 1200 markers per subject for more than 100,000 subjects. The goal was to identify genes that at least double risk and account for a large percentage of patients. Iceland is an excellent population for this type of research because of its isolation for the past 11 centuries and its elaborate genealogical and medical record systems. However, deCode continues to look for collaborators with extensive genealogical and medical records to facilitate additional research and to replicate findings from the Iceland Study. Since the Iceland population is not Native, there is an opportunity to explore gene-environment interaction by collaborating with studies of the Eskimos/Inuit.

Dr. Larisa Tereshchenko provided results of analyses on the Native population in the Tyumen Region of Siberia, Russia. The indigenous population includes about 38,000 Natives comprising Khants, Selkups, and Yamal Nenets. Diseases with high incidence/prevalence include tuberculosis, rheumatic fever, and congenital heart disease. The prevalence of alcoholism is very high among non-nomadic Yamal Nenets but not among the nomadic Yamal Nenets. The prevalence of hypertension is lower than in the non-Native population. Coronary artery disease incidence is low with few MIs. The prevalence of obesity is low compared to non-Natives. There is an interesting observation of rapidly rising hypertension rates and higher left ventricular hypertrophy for recent non-Native immigrants to the region.

Dr. Barbara Howard presented results from the GOCADAN Study. The study included examinations on 1,214 Eskimo men and women ages 18 and older from the Norton Sound Region of Alaska. Data indicate a high prevalence of atherosclerotic plaques. The prevalence of diabetes, insulin resistance, and the metabolic syndrome are low, particularly compared to American Indians. Hypertension rates were low. Cholesterol levels are about the same as the U.S. population with lower LDL levels and significantly higher HDL levels than the U.S. population. The prevalence of cigarette smoking is very high among Eskimos. Inflammatory markers (high sensitivity C-reactive protein (hsCRP) and fibrinogen) are high and the infectious disease burden is high.

Dr. Elizabeth Nobmann presented data on diet of Alaska Natives, primarily from the GOCADAN study. One major risk factor that differs between traditional Alaska Natives and the U.S. population is diet. Fish consumption among Alaska Natives is six times the consumption of the general U.S. adult population. This difference in fish as well as sea mammal consumption accounts for higher levels among Natives in monounsaturated fatty acid consumption and omega-3 fatty acid consumption, which may be protective. Dietary sources differ by generation with younger generations relying more on market foods. The younger generation has a diet higher in carbohydrates but lower in fat intake, polyunsaturated fatty acids intake, and omega-3 fatty acid intake. Dr. Nobmann indicated that little data are available on the changes in dietary intake by season. She also indicated that there needs to be a commonality of the nutrient data base for foods across countries since items such as fish as well as market foods differ between countries which will make standardization of methods more difficult.

Dr. Laurie Hing Man Chan presented dietary data from the Center for Indigenous Peoples' Nutrition and Environment (CINE) in Canada, with particular emphasis on contaminants. He presented results from three dietary surveys including more than 3,600 Native individuals. Diets are a blend of subsistence or traditional foods and market foods. Analyses show a higher consumption of carbohydrates, sucrose and saturated fat in meals that do not include traditional foods. Traditional foods also contribute to contaminant exposure including mercury, toxaphene and chlordane with higher exposure among the Inuit. However, traditional foods also offer important sociocultural benefits that define Inuit people. Thus, consumption of traditional foods represents a balance of risks and benefits that must be addressed in partnership with the Native communities.

Dr. Peter Bjerregaard presented results from collaborative efforts for studies of the Inuit in Greenland and other countries. He explained that Arctic populations are very diverse. In North America, there are hundreds of recognized tribes, including Inuit, Athabascan Indians, and Cree. In Eurasia, there is even more diversity. However, the Inuit ranging from eastern Siberia, northwest Alaska, Northern Canada and Greenland are more similar and have become the focus of collaborative international efforts. Although simple descriptive statistics were possible, the limited comparability of data circumscribed their application. Data suggest that the pathology of cardiovascular disease is more complex than originally assumed. HDL levels are high across studies. The relation of obesity with lipids varies from the non-Native populations. The metabolic syndrome appears to show gender differences in relation to westernization. The small size of the Inuit populations in any one country, and the homogeneity within country and the heterogeneity among countries in environment, support the need for a circumpolar Inuit study. Obstacles to the existing and future efforts include the lack of synchronization and common protocols among studies across countries, and the need to standardize protocols within country to previous work. International leadership is needed to develop a more coordinated effort.

In discussion, two consistent messages were delivered. First, protocols vary across studies. Second, in spite of differences in methods, distribution of risk factors and disease suggest compelling research opportunities. A carefully focused effort to establish a central database and to synchronize longitudinal surveillance may be the most efficient approach.

Barriers and Solutions to Arctic Research

Dr. Ruth Etzel described the organizations delivering health care to Natives in Alaska. Alaska Natives have made more rapid progress in self determination than many other Native groups in the United States. They have assumed ownership and management of their hospitals and health care centers and are now assuming more responsibility for health research done in their communities. There has been a long history of research with Alaska Natives including the establishment of the Alaska Native serum bank that has been in existence for decades. Another advantage for health research includes the centralized computerized medical record system for all health care for the Alaska Native population initiated many years ago by the Indian Health Service. Dr. Etzel noted the different value systems of traditional Alaska Native communities and non-Native researchers. For example, where Natives lean toward sharing, cooperation and humility, researchers are more inclined to ownership, competitiveness and achievement. As a result, Alaska Natives may view the conduct of research differently from outside researchers. Alaska Natives prefer research that is rooted in the community, not implanted in the community. They seek research that is driven by community needs rather than the researcher's needs.

Dr. Andre Corriveau presented results and perspectives on research from the Northwest Territories (NWT) in Canada. The NWT includes 34 communities and about 41,000 inhabitants; about half are Aboriginal. Eight official languages and another 15 non-Aboriginal languages are spoken there. The government is a consensus-style public government. The population is young but projections over the next two decades indicate those over 45 years old will be the fastest growing component. Thus, chronic diseases are expected to increase. The prevalence of cigarette smoking is much higher in the NWT than all of Canada but declining with time as a result of effective community interventions. Mortality from circulatory diseases is somewhat lower than Canada, cancer mortality is about the same though varying by location and Native status, and mortality rates from injury and respiratory diseases are higher. The incidence of tuberculosis is almost eight times higher in the NWT than all of Canada. Alcohol consumption is higher for all ages for both men and women in the NWT. With regard to health research, the government has moved to issuing research licenses based on ethical and community-support considerations that are required to conduct research or collect specimens within the NWT.

Dr. Sven Ebbesson provided his perspective of barriers and solutions to research with Arctic Peoples based on his work in the Alaska Siberia Project and in the GOCADAN study in Norton Sound Eskimo villages. Barriers to research include the small numbers of researchers in the North, inadequate infrastructure, logistic and climatic difficulties, and unfamiliarity with the needs and customs of the Native population. He stressed the importance of working with and through the village councils for approvals and guidance for research. Most important, he emphasized the need to return meaningful research results to the participants and their community. This will build long term relationships that will lead to better research over time. Dr. Ebbesson stressed the importance of investigators spending adequate time in a given village in order to develop an understanding of the needs, sensitivities and customs of the people. It takes time to understand how villages are organized and to be accepted within the village. He also noted that once the community understands that a primary goal of the research is to reduce health problems, the enthusiastic support follows. The discussions with villagers logically lead to studies to identify risk factors for specific diseases, especially ethnic specific risk factors, to be followed with intervention and prevention studies.

In the extended discussion on barriers and solutions, it was emphasized that training of community members to work on the research project enhances the data collection quality, builds capacity within the community, and enhances communication with participants, and between communities and the researchers. It was pointed out that there is a tension between the Native and the NIH view of research. Researchers base funding decisions on academic credentials and research experience. Natives believe that cultural understanding is at least equally important to the success of research projects within their communities. This needs to be understood by the review committees. Additional efforts need to be made to develop accessible training programs for community people to establish stronger clinical and research credentials for future studies. Grants need to be restructured to begin with planning grants to build collaborations, seek approvals, and plan studies in partnership with Native communities. Time barriers need to be recognized and accommodated.

Facilitating International Comparisons

Dr. Natalie Tomitch, speaking on behalf of the Fogarty International Center (FIC), provided an update on the expanding role of the FIC as the coordinating agency for all Arctic research for the National Institutes of Health. The mission of FIC was to support research and training internationally to reduce disparities in global health. Most support goes to collaborative projects in low and middle income countries. Research grants to other countries to build capacity and establish collaborations are an important component of the FIC mission.

Carl Hild represented the American Society for Circumpolar Health and the International Union for Circumpolar Health (IUCH) for this meeting but noted he had additional perspectives through his affiliations with the Alaska Native Tribal Health Consortium and the University of Alaska Anchorage. He explained that the IUCH, established in 1986, offered an existing organization devoted to collaboration among the eight countries with interest in the Arctic. IUCH also has a journal (International Journal of Circumpolar Health) that is highly relevant to the interests of the Working Group participants. He reviewed the history of international collaborations related to the Arctic and to the development of the IUCH. He suggested there were many other organizations with similar aims related to Arctic research but there was little communication among them and few outcomes as a result of their efforts. He recommended that the Fogarty International Center (FIC), as lead contact for health programs to the Arctic Council, should create an NIH Arctic Research Coordinating Committee to address health disparities and regional capacities and to conduct coordinated circumpolar investigations.

The three person panel to discuss the facilitation of international comparisons included Dr. Bjerregaard, Dr. T. Kue Young, and Dr. Sven Ebbesson. Dr. Bjerregaard reiterated the primary reasons for international collaborations: (1) Inuit/Eskimos are in small numbers scattered through several countries, and (2) collaborations will result in larger numbers and more variation in environmental exposures. The two most important issues for international collaborations are continued exchange of experience and the development of comparable survey instruments for items such as surveillance, diet, physical activity, anthropometry and social network. Dr. Young suggested there was a need for an international network for circumpolar health to promote research, facilitate communication and dissemination, and strengthen health information. He recommended a web site as the best mechanism for communication and data management. He noted it would serve a different purpose from the IUCH because it is focused on the needs of researchers and it would promote collaboration. Dr. Ebbesson urged investigators to get more involved in the community in their efforts to conduct research there. The result is likely to be requests for help with their health problems in the form of intervention and prevention programs, which is the community's main priority. He suggested that there is a need for initial funding for coordination among the interested countries under the sponsorship of a government agency or international organization that wants to assume a leadership role.

The general discussion uncovered the need for seed money and leadership to get international collaborations started, to develop a web site, and to standardize methods. It is clear there are many organizations established but little progress to date as a result. Another idea was to start collaboration by encouraging one country to fund a coordinating center for a specific project and then a principal investigator from each country would seek funding for data collection within his/her country's borders. Immediate opportunities for collaborative efforts may be enhanced by establishing international agreements between health research organizations of relevant countries. An opportunity for such a collaborative agreement may be possible between Canada and the United States. FIC may be able to help facilitate a collaborative agreement although it does not provide funds for such efforts.

The meeting concluded with a list of ten recommendations covering research priorities, barriers and solutions to Arctic Research, and facilitating international comparisons. The recommendations are not presented in priority order.

Recommendations for Research Priorities

1. Primary prevention/intervention studies can be initiated immediately to reduce the incidence of cardiovascular disease (particularly stroke) and respiratory disease (particularly tuberculosis and COPD), and to prevent the development of impending risk factors such as obesity and diabetes.
2. Unique clinical outcomes with unusual prevalence/incidence that may benefit from further epidemiological investigation include high incidence/prevalence of congenital heart disease, rheumatic heart disease, SIDS, RSV, infection and inflammation, anemia and low incidence of deep vein thrombosis (DVT).
3. Risk factors with unusual prevalence that may benefit from further epidemiological investigation include the development of obesity and its relation to CVD risk factor changes, low prevalence of the metabolic syndrome, high levels of HDL, high intake of omega-3 fatty acids, long-term effects of infection/inflammation on atherosclerosis, gender differences in the insulin resistance syndrome in relation to westernization, and the health effects of contaminants and indoor air pollution.
4. Extremes in the physical and social environment offer research opportunities on the effects of contaminants and the effects of season changes including cold, extended light/dark cycles, and dietary patterns on CVD risk factors, on sleep patterns, and on psychological well being. Northern communities also offer some homogenous populations suitable for genetics research and many isolated communities suitable for randomized community-based intervention trials.
5. Methodological research is needed to develop protocols and data collection instruments to standardize surveys of Native populations across countries for recruitment, dietary assessment, definitions of health status, physical activity assessment, socioeconomic status, modernization/westernization, criteria for obesity, and culturally-sensitive interventions.

Recommendations for Barriers and Solutions

1. To assure that future research efforts are conducted in a culturally-sensitive and respectful way, follow guidelines already established by Indigenous Peoples such as the WHO-CINE guidelines (http://www.cine.mcgill.ca/IA.htm#indigenous) or the Alaska Federation of Natives Guidelines (http://www.ankn.uaf.edu/afnguide.html) or the NSF guidelines (http://www.arcus.org/guidelines/pdf.html).
2. Develop training programs that are easily accessible to Natives seeking to broaden their career goals to become clinicians and research investigators.
3. Promote hiring and training of Native staff as a component of all research funded with Native populations as a way of building capacity within research populations and improving the conduct and quality of research studies.

Recommendations for Facilitating International Comparisons

1. Encourage the Fogarty International Center to lead an effort in organizing an international consultation for the purpose of establishing a collaborative study of Arctic Peoples.
2. Establish international agreements of cooperation to initiate a circumpolar Inuit Study to overcome the high costs of research and the small samples within any one country, and to incorporate the diversity of environment among Inuit communities that exists across circumpolar countries.

Summary

By design, this Working Group focused primarily on heart, lung, blood and sleep disorders because of the mission of the sponsoring agencies. Larger, more coordinated, efforts that expand the scope of investigation to other chronic diseases may be much more efficient given the high cost and formidable barriers to research within and among countries with interest in Arctic Research. The Working Group participants would welcome such an omnibus research effort. However, in the absence of such an effort, the Working Group acknowledged that the interest and leadership provided by the current Working Group participants represented the most promising opportunity to address research with Arctic People. It is hoped that these recommendations will be explored by health agencies, both individually and collaboratively, within and among Arctic countries in the coming year to enhance the research agenda with Arctic Peoples.

Members

Working Group:

Co-chairs:

Barbara Howard, Ph.D., MedStar Research Institute, Washington D.C., USA 
H. Sally Smith, Chair, National Indian Health Board, Dillingham, Alaska, USA

Members:

Peter Bjerregaard, M.D., National Institute of Public Health, Copenhagen, Denmark 
Hing Man Chan, Ph.D., Center for Indigenous People's Nutrition and Environment, McGill University, Canada 
Andre' Corriveau, M.D., Department of Health and Social Services, Yellowknife Northwest Territories , Canada 
Sven O.E. Ebbesson, Ph.D., University of Virginia, Charlottesville, VA, USA 
Ruth Etzel, M.D., Ph.D., Anchorage Native Primary Care Center, Anchorage, AK, USA 
Hakon Hakonarson, M.D., deCODE Genetics, Reykjavik, Iceland 
Carl Hild, Institute for Circumpolar Health Studies, University of Alaska Anchorage, Anchorage, AK, USA 
Elizabeth Nobmann, Ph.D., IDM Consulting, Anchorage, Alaska, USA 
J Redding, M.D., Canadian Institutes of Health Research - Institute of Aboriginal People's Health, Victoria, BC, Canada 
L Tereshchenko, M.D., Washington University, St. Louis, MO, USA 
Natalie Tomitch, Ph.D., Fogarty International Center, National Institutes of Health, Washington D.C., USA 
T. Kue Young, M.D., Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada

NHLBI Staff:

B Alving, E. Bookman, J De Jesus, RR Fabsitz, C Jaquish, D Lathrop, T Manolio, J Olson, PJ Savage, P Sholinsky, P Sorlie, R Tracy

Observers:

P Chen, L Commanda, A Gordon, P Pehrsson, CR Perry, JT Petherick, C Ryan

NHLBI Planning Group

Richard R. Fabsitz, Ph.D., Division of Epidemiology and Clinical Applications 
Carl Hunt, Ph.D., National Center for Sleep Disorder Research 
Jared Jobe, Ph.D., Division of Epidemiology and Clinical Applications 
David Lathrop, Ph.D., Division of Heart and Vascular Diseases