Cardiovascular Disease in Obesity: Fact or Fiction?

A high-profile review article by Rema P. Nair, Pharm.D., temporary lecturer in the University of Wyoming College of Health Sciences School of Pharmacy and Jun Ren, M.D., Ph.D., FAHA, associate dean for research in the College of Health Sciences (CHS), which focused on the molecular mechanisms and currently available pharmacotherapeutic interventions in overweight and obesity was recently published in Current Medicinal Chemistry ("Nair RP, Ren J. Pharmacotherapy of obesity - benefit, bias and hyperbole. Curr Med Chem. 2009;16(15):1888-1897").

Their article is one of 33 high impact publications by Dr. Ren's research group during the first five months of 2009. A somewhat related review with an emphasis on the obesity etiology in women by Ren and Robert Kelley, former CHS Dean, entitled "Cardiac Health in Women With Metabolic Syndrome: Clinical Aspects and Pathophysiology" was published recently in Obesity. The group's publications this year have appeared in some of the leading scientific journals including Circulation (selected as one of the 100 most influential journals of the last 100 years in medicine and biology), Journal of American College of Cardiology, Hypertension, Journal of Molecular and Cellular Cardiology, and Journal of Cellular and Molecular Medicine.

Obesity, especially central obesity, is a burning issue for health care world-wide. Dr. Nair's and Dr. Ren's review summarized the current anti-obesity drug therapy aiming at reducing energy/food intake via actions on either gastrointestinal system or the central control of appetite and feeding.

Given the high prevalence of overweight and obesity, Wyoming INBRE, which just received another five years of funding, aims at understanding the pathological causes for obesity and promotes health awareness and medical intervention for body weight control. Both overweight and obesity put these individuals at a high risk for the development of insulin resistance, hypertension, dyslipidemia, type 2 diabetes and coronary heart disease.

A weight loss of between 5% and 10% of the initial body weight has been shown to greatly reduce these health risks associated with overweight and obesity. Typically, the first-line clinical strategy for weight loss is a combination of supervised diet, exercise and behavior modification. Although life style modification can exert beneficial effects in overweight and obese individuals, it is difficult to achieve and maintain weight losses solely by life style change.

Anti-obesity drugs may be used in obese patients (BMI of 30 or greater), or overweight patients with established comorbidities (BMI > 27), where dietary and lifestyle modifications are unsuccessful in achieving a 10% weight reduction following at least three months of the supervised care.

This area of research has drawn some national attention. Dr. Ren's group is the first laboratory to characterize obesity-associated cardiac dysfunction at the single cardiomyocyte levels. Subat Turdi and Nathan Roe, two PhD students working in Dr. Ren's group, are working on projects related to both diet-induced and genetically predisposed obesity. Subat's doctoral dissertation on high fat diet feeding and cellular energy fuel (AMPK) deficiency was chosen by the highly competitive American Heart Association's national meeting presentation in 2008. Four visiting scholars including two physician scientists, will join the Center for Cardiovascular Research and Alternative Medicine (C-CRAM) group this summer to work on obesity in special populations including aging and Alzheimer's disease. In addition, Subat and Ren, in collaboration with Dr. Eric Moorhouse, associate professor with the UW Mathematics Department, are guiding a McNair scholar, Aylin Marquez, to analyze the associated heart defect using computer models (presented at the UW undergraduate research day in May 2009). This group is taking advantage of a wide array of genetic manipulated techniques to study gene overexpression and knockout on obesity and obesity-associated cardiovascular complications.

Facts about obesity (modified from the American Heart Association publications):

Obesity is a major risk factor for coronary heart disease, which can lead to heart attack. Some reasons for this higher risk are known, but others are not. For example, obesity
• raises blood cholesterol and triglyceride levels.
• lowers HDL "good" cholesterol. HDL cholesterol is linked with lower heart disease and stroke risk, so reducing it tends to raise the risk.
• raises blood pressure levels.
• can induce diabetes. In some people, diabetes makes these other risk factors much worse. The danger of heart attack is especially high for these people.

The body mass index formula assesses body weight relative to height. Weight in kilograms is divided by height in meters squared (kg/m2). For adults:
• BMI under 18.5           under weight
• BMI of 18.5-24.9         normal
• BMI of 25-29.9            overweight
• BMI of 30 or greater    obese
• BMI of 40 or greater    extreme obesity

Obesity statistics:
• Among Americans age 20 and older, 142.0 million are overweight or obese (BMI of 25.0 kg/m2 and higher): 73.0 million men; 69.0 million women.
­ Of these, 67.3 million are obese (BMI of 30.0 kg/m2 and higher): 30.7 million men; 36.7 million women.
• Among adults in the US, obesity was associated with nearly 112,000 excess deaths relative to normal weight in 2000.
­ Of these, grade 1 obesity (BMI from 30 to less than 35) was associated with almost 30,000 excess deaths, and grade II-III obesity (BMI 35+) with over 82,000 excess deaths.
• More than 9 million children and adolescents between the ages of 6 and 19 years are considered overweight on the basis of being in the 95th percentile or higher of BMI values in the 2000 CDC growth chart for the United States.
• Overweight adolescents have a 70 percent chance of becoming overweight adults. This increases to 80 percent if one or both parents are overweight or obese.

Posted on Tuesday, May 26, 2009