A Little Belly Fat Can Double the Risk of Death in Coronary Artery Disease Patients

(BUSINESS WIRE)--One of the largest studies of its kind has found that people with coronary artery disease who have even a modest beer belly or muffin top are at higher risk for death than people whose fat collects elsewhere. The effect was observed even in patients with a normal Body Mass Index (BMI). The findings of this Mayo Clinic analysis are published in the May 10 issue of the Journal of the American College of Cardiology.

Researchers analyzed data from 15,923 people with coronary artery disease involved in five studies from around the world. They found that those with coronary artery disease and central obesity, measured by waist circumference and waist-to-hip ratio, have up to twice the risk of dying. That is equivalent to the risk of smoking a pack of cigarettes per day or having very high cholesterol, particularly for men.

The findings refute the obesity paradox, a puzzling finding in many studies that shows that patients with a higher BMI and chronic diseases such as coronary artery disease have better survival odds than normal-weight individuals.

“We suspected that the obesity paradox was happening because BMI is not a good measure of body fatness and gives no insight into the distribution of fat,” says Thais Coutinho, M.D., the study’s lead author and a cardiology fellow at Mayo Clinic. “BMI is just a measure of weight in proportion to height. What seems to be more important is how the fat is distributed on the body,’’ she says.

Francisco Lopez-Jimenez, M.D., the project’s lead investigator and director of the Cardiometabolic Program at Mayo Clinic, explains why this type of fat may be more harmful: “Visceral fat has been found to be more metabolically active. It produces more changes in cholesterol, blood pressure and blood sugar. However, people who have fat mostly in other locations in the body, specifically, the legs and buttocks, don’t show this increased risk.”

The researchers say physicians should counsel coronary artery disease patients who have normal BMIs to lose weight if they have a large waist circumference or a high waist-to-hip ratio. The measure is very easy to use, Dr. Coutinho says: “All it takes is a tape measure and one minute of a physician’s time to measure the perimeter of a patient’s waist and hip.”

The research subjects were diverse, coming from studies in the U.S. (Rochester, Minn. and San Francisco, Calif.), Denmark, France and Korea. The inclusion of different ethnic groups makes the study more applicable to the real world, Dr. Coutinho says.

Other members of the research team are Kashish Goel, M.D.; Daniel Correa de Sa, M.D.; Randal Thomas, M.D.; Veronique Roger, M.D., MPH; and Virend Somers, M.D., Ph.D., of Mayo Clinic; Charlotte Kragelund, M.D., Ph.D.; Lars Kober, M.D., Ph.D.; and Christian Torp-Pedersen, M.D., Ph.D., from Rigshaspitalet, Copenhagen, Denmark; Alka Kanaya, M.D. of the University of California, San Francisco, California; Jong-Seon Park, M.D.; Sang-Hee Lee, M.D.; and Young-Jo Kim, M.D., of Yeungnam University Hospital, Daegu, Korea; and Yves Cottin, M.D., Ph.D.; and Luc Lorgis, M.D., from CHU Bocage, Dijon, France.

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FDA approves Egrifta to treat Lipodystrophy in HIV patients

The U.S. Food and Drug Administration today approved Egrifta (tesamorelin) to treat HIV patients with lipodystrophy, a condition in which excess fat develops in different areas of the body, most notably around the liver, stomach, and other abdominal organs. The condition is associated with many antiretroviral drugs used to treat HIV.

Egrifta, the first FDA-approved treatment for lipodystrophy, is a growth hormone releasing factor (GRF) drug that is administered in a once-daily injection.

"The FDA recognizes the need for therapies to treat patients with HIV-lipodystrophy," said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research. “The presence of excess fat with this condition may contribute to other health problems as well as affect a patient’s quality of life, so treatments that demonstrate they are safe and effective at treating these symptoms are important.”

Whether Egrifta decreases the risk of cardiovascular disease or improves compliance with antiretroviral drugs has not been studied.

Egrifta was evaluated in two clinical trials involving 816 HIV-infected adult men and women with lipodystrophy and excess abdominal fat. Of these, 543 patients received Egrifta during a 26-week, placebo-controlled period. In both studies, patients treated with Egrifta experienced greater reductions in abdominal fat as measured by CT scan, compared with patients receiving another injectable solution (placebo). Some patients reported improvements in their self image.

The most commonly reported side effects in the studies included joint pain (arthralgia), skin redness and rash at the injection site (erythema and pruritis), stomach pain, swelling, and muscle pain (myalgia). Worsening blood sugar control occurred more often in patients treated with Egrifta than with placebo.

Egrifta was developed by Montreal-based Theratechnologies Inc. and marketed in the U.S. by Rockland, Mass.-based EMD Serono.

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Fat Tissue May Be a Source of Valuable Blood Stem Cells, Study Says

/PRNewswire/ -- Bone marrow is a leading source of adult stem cells, which are increasingly used for research and therapeutic interventions, but extracting the cells is an arduous and often painful process. Now, researchers have found evidence that fat tissue, known as adipose tissue, may be a promising new source of valuable and easy-to-obtain regenerative cells called hematopoietic stem and progenitor cells (HSPCs), according to a study prepublished online in Blood, the official journal of the American Society of Hematology.

"It's not outside the realm of possibility that a donor graft of adipose tissue-derived HSPCs might be able to partially replace the need for bone marrow transplantation within 10 years," said lead study author Gou Young Koh, MD, PhD, of the Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST) in Daedeok Science Town, Daejeon, South Korea.

HSPCs are powerful cells that have the ability to regenerate and develop into many different kinds of cells. With advances in technologies and understanding of cell functions, HSPCs are now used to repair damaged tissue and are being studied for their potential to treat a vast array of chronic and degenerative conditions. HSPCs are found in high quantities in the bone marrow, but a certain portion known as extramedullary tissue, found outside of bone marrow, circulate between the marrow and the peripheral blood.

Previous research has found that adipose tissue contains many different types of adult stem cells. In this study, researchers hypothesized that the adipose tissue might be a valuable alternative source of HSPCs as an extramedullary tissue but questioned whether the tissue could provide a sufficient quantity of cells to be used for research and therapeutic purposes.

"We know that adipose tissue and bone marrow tissues share similar properties, so we suspected that valuable stem cells might be found in the adipose regions, offering a unique resource for stem cells that might be easier and less costly to extract," said Dr. Koh.

Within the adipose tissue is a special cell population known as the stromal vascular fraction (SVF), which consists of other undefined stem cells as well as immune, endothelial (blood vessel lining), progenitor (undifferentiated or premature precursor cells), and stromal (connective tissue) cells. Cells in the SVF share similar properties to those in the bone marrow. Both contain a population of cells that have the ability to differentiate into several cell types. In addition, both adipose tissue and bone marrow offer similar environments for optimal stem cell growth and reproduction, including a smaller amount of circulating oxygen and specialized vascular systems as compared with other organs.

The research team characterized the HSPCs in the SVF of mouse adipose tissue with both in vitro and in vivo analyses. They studied the origin of the HSPCs to better predict their behavior and determine whether the quantity of cells could be increased by promoting more frequent HSPC movement between the bone marrow and peripheral blood using granulocyte colony-stimulating factor, or G-CSF, a growth hormone used to encourage development of stem cells. The team found that the more they could mobilize the HSPCs between the bone marrow and the peripheral blood, the more HSPCs they would find in the SVF.

The study results provide compelling evidence that the SVF derived from adipose tissue contains functional HSPCs capable of generating hematopoietic (blood-forming) cells. Importantly, researchers found that the cells were able to differentiate into a variety of hematopoietic cells when tracked for at least 16 weeks post-transplantation, which reflects long-term and permanent reconstitution of donor hematopoietic cells in recipients.

The frequency of HSPCs in the adipose tissue found in the study was significantly less than that found in bone marrow (approximately 0.2 percent of the HSPCs found in total bone marrow). Therefore, researchers wanted to determine whether the SVF might be used practically as an alternative source of HSPCs. Fortunately, according to the researchers, a vast amount of the SVF in adipose tissue can be easily obtained from patients using conventional liposuction and isolation methods that are safe and relatively pain-free.

"These study results suggest that more HSPCs might be obtained from the stromal vascular fraction through increased mobilization of these cells from the bone marrow using G-CSF," said Dr. Koh. "So once a technology can be defined to purify HSPCs from the stromal vascular fraction, we believe adipose tissue may be a good alternative and novel resource for obtaining functional and transplantable HSPCs."

The research team is actively extending their research in this area, including plans for a human clinical study. They also emphasize the need for a clinically safer and more efficient method for isolating the HSPCs from the adipose tissue.

The American Society of Hematology (www.hematology.org) is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology. ASH provides Blood: The Vital Connection (www.bloodthevitalconnection.org), a credible online resource addressing bleeding and clotting disorders, anemia, and cancer. The official journal of ASH is Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, which is available weekly in print and online.

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Not enough vitamin D in the diet could mean too much fat on adolescents

Too little vitamin D could be bad for more than your bones; it may also lead to fatter adolescents, researchers say.

A Medical College of Georgia study of more than 650 teens age 14-19 has found that those who reported higher vitamin D intakes had lower overall body fat and lower amounts of the fat in the abdomen, a type of fat known as visceral fat, which has been associated with health risks such as heart disease, stroke, diabetes and hypertension.

The group with the lowest vitamin D intake, black females, had higher percentages of both body fat and visceral fat, while black males had the lowest percentages of body and visceral fat, even though their vitamin D intake was below the recommended levels. Only one group – white males – was getting the recommended minimum intake of vitamin D.

“This study was a cross-section so, while it cannot prove that higher intake of vitamin D caused the lower body fat, we know there is a relationship that needs to be explored further," says Dr. Yanbin Dong, a molecular geneticist and cardiologist at the MCG Gerogia Prevention Institute.

Dr. Dong, who also co-directs the MCG Diabetes & Obesity Discovery Institute, and Inger Stallman-Jorgensen, a research dietician at the GPI, present their findings this week at the American Heart Association’s Joint 49th Conference on Cardiovascular Disease Epidemiology and Prevention and Nutrition, Physical Activity and Metabolism in Palm Harbor, Fla.

The pair will next study whether it is feasible for teens to take a daily vitamin D supplement in pill form. Those results will help them design a larger study to explore the relationship between vitamin D intake and body fat levels in teens.

“We already know that encouraging teens to get an adequate amount of vitamin D in their diets will help promote a healthy body as they grow and develop,” Ms. Stallman-Jorgensen says. “Now we need to do intervention studies where we give teens vitamin D supplements to determine if there is a cause and effect relationship between vitamin D intake and fat.”

The American Academy of Pediatrics recommends adolescents get at least 400 units of vitamin D per day – either from milk or sun exposure. There are typically 100 units in one 8-ounce glass of whole milk. The recommended daily dose from the sun would require at least 30 minutes of adequate exposure to direct sunlight two or three times a week at peak hours, between noon and 3 p.m.

Ms. Stallman-Jorgensen said there are many reasons teens don't get enough vitamin D, which has been linked to the prevention of diabetes, cancer and cardiovascular disease.

“As humans, our largest source of vitamin D should be the sun. But we don’t spend enough time outdoors to get enough sun exposure and when we do, we’re often covered up and wearing sunscreen," she said. "We can get vitamin D from certain foods, like fatty fish and liver, but it’s not in a lot of foods that we commonly consume. In this country, our milk is fortified with vitamin D. Unfortunately, teens just don’t drink enough milk to get their daily requirements.”

She points out that low sunlight during the winter months reduces the amount of vitamin D the skin produces, and that darker-skinned people obtain less vitamin D from the sun because the extra melanin in their skin filters out more sunlight.

Some people can't tolerate milk because they lack the enzyme that processes lactose, the natural sugar in milk, though "most people can handle it in small amounts,” Ms. Stallman says.

Cultural issues may also be at play, Ms. Stallman-Jorgensen says.

“Most teens want to drink sodas and sugary drinks. It’s not cool to drink milk – they think of it as more of a food for babies,” she said.

Potential study participants had their weekday and weekend diets tracked by researchers seven times during a three-month period. Those who provided at least four diet reports were included in the final group of 659.

Body fat percentages were measured by dual energy X-ray absorptiometry scans, which can measure total body composition. Visceral fat was measured in a subset of 432 teens.

Jennifer Hilliard
Medical College of Georgia

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