STRONG HEART STUDY I NVESTIGATING C ARDIOVASCULAR D ISEASE IN A MERICAN I NDIANS newsletter strongheart.ouhsc.edu Volume 19, Number 1 June 2007 Working with Scientists Across the Country Helps the Strong Heart Study Benefit our Communities Because the Strong Heart Study (SHS) has been The scientists at CNMC are also working on other ongoing for eighteen years, it has a tremendous projects. One project studies athletes before and collection of data from the blood and urine samples after training and conditioning. They hope to find that were collected, from questionnaires, and from changes in the way certain genes work that might the DNA samples that were stored. As you know, pinpoint what genes control energy use and me- SHS studies are focused on understanding heart tabolism. They are especially interested in a gene disease and its risk factors. There are high rates of called PGC-1 alpha that works with a gene called diabetes and obesity in our communities; therefore, PPAR that has already been studied in SHS. there is a special emphasis on these two risk fac- They also have discovered two genes called TPD tors. The Institutional Review Boards (“IRB’s”, that and BCL-6 that have effects on how cells grow monitor and control research among hu- and multiply (and sometimes cause man participants) and the tribal councils blockages in our arteries). They found review our study plans before each new one change in the TPD gene that exam; and those of you who are partici- makes people more resistant to their pants are given lots of information about own insulin and also develop high what tests we are going to do when you blood fats. The BCL gene seems to sign the consent form. help control energy metabolism in these athletes. The CNMC investiga- Sometimes we have to cooperate with tors will now work with us to test these other well-known, qualified scientists who same genes in the Strong Heart Study are able to do tests that we are not able samples. Trying to find the really im- to do in our own laboratories and clinics. portant ways that our bodies control For example, scientists that we work with metabolism and energy is a slow proc- at Children’s National Medical Center (CNMC) in ess. Sometimes investigators will find a gene or Washington, DC are able to check for very slight marker in one population, but it doesn’t seem to changes in the DNA. The system they developed be important in another population. If investiga- is able to test hundreds of samples in a very short tors can work together to test their findings in dif- period of time and uses only an extremely small ferent populations, it can advance knowledge amount of DNA, so much more research can be faster and further. This will bring us closer to the done on the SHS samples before they are used up. goal of these genetic studies, which is to find ways The plans for the current exams, which were pre- to predict who will become resistant to insulin and sented to the tribes and the IRB’s, included tests develop diabetes, who will have high blood fat lev- for a number of genes such as PPAR, IL-6, throm- els and who is more likely to become overweight; bospondin, lymphotoxin and TLR-4 genes. These or maybe even lead to medicines or other treat- names are complicated but basically they are ments to prevent these problems. By working with genes that make proteins we think are important in other researchers in this way, the SHS makes bet- understanding what causes diabetes and makes ter use of the data and samples to develop better hardening of the arteries happen. prevention and treatment methods sooner. SHS 1 SHS Newsletter June 2007 Second Exam of Family Study in Full Swing The second examination of the family study co- how these data may be used to improve the hort is going strong. As of March 1st all three health of American Indians. Even the central centers were ahead of schedule in recruitment chemistry laboratory at Penn Medical Labora- for the follow-up examination. The Arizona tory in Washington D.C. and the ECG labora- center had examined 315 participants, Okla- tory at Cornell School of Medicine in New York homa had examined 352 participants, and the had to overcome equipment failures. Penn Dakota center had examined 415 participants. Medical Laboratory has struggled with new As with any large project, there are always diffi- equipment for analyzing blood samples that culties as written study protocol, new equip- has not met the high standards required for the ment, new staff, extensive train- Strong Heart Study samples. This ing, and required certification are has delayed the samples for an put to the test. Arizona had to extended period while the manu- overcome a blown gasket on facturer tries to bring the equip- their new van that carries the ul- ment up to acceptable perform- trasound equipment for imaging ance. Samples remain stored and atherosclerosis in the arteries of safe throughout this delay which your neck and legs. The Dako- now appears to be resolved. Re- tas have had to endure the sea- sults from delayed assays are ex- sonal rain that makes many pected in the next few weeks. roads in the reservation difficult, Malfunctioning ECG equipment if not impossible, to use. Okla- caused some of the first exams of homa has struggled to identify the new cycle to be lost because clinic space for the Strong Heart Study exam the storage mechanism was not working prop- facilities. In spite of these challenges, Strong erly. This problem has also been resolved with Heart Study staff have found ways to overcome minimal loss. As these issues are resolved, the all of these issues and have found the study Strong Heart Study staff looks forward to see- participants eager to be part of this multi-center ing the Strong Heart Family Study participants project that is defining the burden of cardiovas- and updating them on their health. Hope to see cular disease in Indian Country and identifying you soon! SHS Impact of Obesity on Cardiac Geometry and Function in a Population of Adolescents: The Strong Heart Study In adults, obesity causes enlargement of the ments of the U.S. population and in most heart and increase weight of the heart muscle countries around the world, we used measures (called hypertrophy) and negatively affects the of the size and function of the heart obtained ability of heart to increase blood supply to the from echocardiograms - - tests performed us- body in response to stresses. In obese adults, ing high-frequency sound aimed at the heart the heart may also be less able to relax after using a probe positioned on the surface of the pumping blood into the arterial tree. Whether or chest. Participants aged 15-20 years in the 4th not these abnormalities also affect the heart of Strong Heart Study examination, the Strong overweight or obese adolescents had not been Heart Family study, had echocardiograms per- well-documented in population-based samples. formed and the findings related to their body weight in relation to their height. Among 460 To address this question, of particular impor- adolescent participants in the 4th Strong Heart tance in view of rising body weight in all seg- (Continued on page 3) 2 SHS Newsletter June 2007 Impact of Obesity on Cardiac Geometry (Continued from page 2) Study examination, 26% had normal body weight was out of proportion with that needed weight by U.S national guidelines, 25% were to pump blood to the body and was also asso- overweight and 49% were obese. Obese, but ciated with clear abnormalities in both the not overweight, adolescent Strong Heart Study pumping function of the heart and its ability to participants were more likely to have in- relax after each heart beat. creased blood glucose, diabetes, abnormal levels of cholesterol and other fats in the blood This study demonstrated that at an early and high blood pressure. When combined, age - - among individuals aged 15 to 20 these abnormalities lead to diagnosis of a re- years - - obesity, and to a lesser extent over- cently-described condition called the weight may negatively influence both aspects “metabolic syndrome” that has been shown to of body metabolism and the size and function predict cardiovascular events in older SHS of the heart. These findings suggest that early participants and in other populations. interventions during childhood and adoles- cence to reduce the prevalence of overweight Among adolescent participants in the Strong and prevent the transition from overweight to Heart Study, both overweight and obese ado- overt obesity may help to reduce the frequency lescents had greater heart weight than the of diabetes and other severe metabolic altera- group with normal body weight. In overweight tions and to avoid unfavorable changes in car- adolescents the increased cardiac weight was diac structure and function, which have in turn adequate to sustain the increased cardiac been demonstrated to be strong predictors of workload associated with high body weight; in cardiovascular events and death. obese adolescents the increased cardiac SHS Control Your Diabetes by Eating Healthy Evidence from previous studies suggests that and vegetables) is associated with good glyce- glycemic control (maintaining normal or near- mic control in diabetic American Indians. normal blood sugar levels) is fundamental to What does this mean for diabetic American In- the management of diabetes and its impor- dians? This study suggests that if you con- tance in reducing or delaying the complica- sume foods that are lower in total fat, satu- tions of diabetes.