Although there have been many important gains in the treatment of cardiovascular disease, it remains the leading killer of men more than 45 and women more that 65 years old. Much of the improvements in cardiovascular disease in the last two decades are related to improved surgical procedures and/or the chronic use of expensive medications. There is a clear need to identify "medically valuable" foods, learn how these foods work and define how to use them most effectively to prevent disease. For many years, historical and epidemiological evidence has suggested benefits of grape products with respect to cardiovascular disease. Chronic and moderate consumption of grape products, primarily in the form of wine, has been associated with decreased risk of myocardial infarction, stroke and reduction in blood cholesterol. However, the data currently available is limited to grape products in the presence of alcohol, and the mechanisms of cardioprotection have not been addressed. Researchers at Columbus Children's Research Institute (CCRI) on the campus of Columbus Children's Hospital conducted a study examining the effect of non-alcoholic grape product in vascular endothelial (a layer of flat cells that line blood and lymphatic vessels) dysfunction--an initiating event in coronary artery disease. The findings were presented May 5 at the 2003 Pediatric Academic Societies' (PAS) annual meeting.

"We were quite surprised by the favorable effects we were able to detect in this relatively small number of normal healthy adults," said John Anthony Bauer, Ph.D., investigator in the Center for Developmental Pharmacology and Toxicology at CCRI. "These results are important because the grape product not only significantly increased overall blood vessel performance, but it also completely prevented endothelial dysfunction after the subjects consumed a high-fat meal. This suggests that, similar to wine, grapes without alcohol do contain the necessary nutrients to improve the health of blood vessels, and that consuming favorable foodstuffs can influence the effects of unfavorable ones."

The researchers tested the hypothesis that a standardized product from fresh grapes improves endothelial performance in normal subjects, alone or in combination with a standardized high-fat meal. Participants received a reconstituted grape product as 36g/100ml (bid 21d) or a controlled solution with identical sugar content. Endothelial function was assessed through brachial artery flow response (ultrasound) at -30, +45, +90 and +180 minutes after the first and 41st doses. The participants also received a high-fat meal with or without grape product at the 42nd dose. A single dose of grape product had an effect on endothelium-dependent response relative to a sugar control solution, which did not cause any significant alteration in endothelial function. Furthermore, multiple dosing and a chronic consumption of grape product for 21 days caused significant improvement in baseline endothelial performance on day 22. The improved endothelial response was also associated with an increased antioxidant capacity in plasma. Intake of a single high-fat meal was associated with a significant reduction in endothelial function. The grape product nullified this effect, but the protective grape effect was not associated with a reduction of high-fat induced hypertriglycerides.

"One of the objectives of our study was to identify if non-alcoholic grape product would have the same benefits as wine," said Dr. Bauer. "It is well known that alterations in the performance of endothelial cells happen very early in cardiovascular disease and consuming grapes in wine has shown to improve the cell's performance. Therefore, an important part of our study was to determine if favorable effects could be seen in normal, healthy adults, rather than patients with a pre-existing cardiovascular condition. We wanted to determine if the simple consumption of grapes could have a favorable effect on blood vessel performance and perhaps prevent the initial development of cardiovascular disease."

Dr. Bauer plans to conduct a larger-scale study to learn more about the findings and to determine what are the key ingredients responsible for the effects. "Most of the research on coronary artery disease and the effects of grapes and wine studied patients who either already have the disease, but our research focused on normal, healthy people under the age of 40," said Dr. Bauer. "We feel it is important to conduct further research to understand how grapes and other foods can continue to benefit cardiovascular health. We are also trying to learn more about how genetics play a role in the potential value of such foods. For example, some people may gain more from certain foods than others, and some children with suspected risk factors may gain the most in staving off premature vascular diseases."

Columbus Children's Hospital ranks among the top 10 in National Institutes of Health research awards and grants to freestanding children's hospitals in the country. With nearly 500,000 patient visits each year, Children's Hospital is a 111-year-old pediatric healthcare network treating newborns through age 21. In 2002, the Children's Research Institute conducted more than 250 research projects and is the home of the Center for Injury Research and Policy along with other Centers of Emphasis encompassing gene therapy; molecular and human genetics; vaccines and immunity; childhood cancer; cell and vascular biology; developmental pharmacology and toxicology; and biopathology. Pediatric Clinical Trials International (PCTI), a site management organization affiliated with the hospital, also coordinated more than 50 clinical trials. In addition to having one of the largest ambulatory programs in the country, Children's offers specialty programs and services. Each year, more than 75,000 consumers receive health and wellness education, and 2,000 students from 93 institutions and 500 residents receive training at Children's. More information on Children's Hospital of Columbus is available by calling (614) 722-KIDS (5437) or through the hospital's Web site at http://www.columbuschildrens.com.

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Meeting: Pediatric Academic Societies