SAMFORD UNIVERSITY GLOBAL DRUG INFORMATION SERVICE’S

C L I Ps
CURRENT LITERATURE AND INFORMATION FOR PHARMACISTS
®

http://www.samford.edu/schools/pharmacy/dic
Volume 10 (Issue 31) May 22, 2006

OBESITY AND CARDIOVASCULAR DISEASE

Obesity is a growing epidemic in both adults and children. The incidence of obesity in the United States increased
from 22.9% for the period of 1988-1994 to 30.5% for the period of 1999-2000. Body Mass Index (BMI) is commonly
used to categorize a patient as normal weight, overweight, or obese. Obesity, defined as a BMI of ≥ 30 kg/m
2
, is
associated with numerous co-morbidities including cardiovascular disease, type 2 diabetes, hypertension, certain
cancers, and sleep apnea/sleep-disordered breathing. As a result of the increasing prevalence of obesity, the
American Heart Association (AHA) has evaluated the effects of obesity on heart health. This issue of CLIPs briefly
reviews the updated AHA scientific statement on obesity and heart disease in relation to the effect obesity has on
cardiac structure and function and the cardiovascular benefits of weight loss. If you need further information, please
contact the Samford University Global Drug Information Service at (205) 726-2659.

Poirier P, Giles TD, Bray GA, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and
effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and
Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism.
Circulation. 2006 Feb;113(6):898-918.

Obesity and Cardiovascular Disease
• Obesity is associated with numerous co-morbidities and is as an independent risk factor for cardiovascular
disease (CVD); therefore, obese patients have an increased risk of morbidity and mortality and a reduced life
expectancy.
• An explosive increase in the number of patients with metabolic syndrome (MetS) and obesity has occurred
and an interrelationship between MetS and obesity has been postulated. Data have shown that patients with
MetS have an increased risk of both diabetes and CVD. However, uncertainty has arisen about whether or
not MetS is a syndrome or an independent CVD risk factor.

Cardiovascular Impact of Obesity
• Obesity not only affects the development of heart disease through negatively impacting classic risk factors
such as hypertension, glucose tolerance, and dyslipidemia, but also through a direct effect of increased
adipose tissue on heart structure and function as described below.
• Beyond simply storing fat, adipose tissue also synthesizes and releases peptides that may affect cardiac
functioning. One such peptide, IL-6, controls the synthesis of C-reactive protein, a protein linked to states
of chronic inflammation that may be responsible for precipitating cardiac events.
• Obesity leads to an increase in total blood volume and subsequently increased stroke volume, which over
time may lead to left ventricular hypertrophy or dilated atrial chambers and ultimately diastolic dysfunction.
• Obesity causes an increased amount of fat deposition on the cardiac muscle that induces cellular adaptation
by the heart that may lead to cardiomyopathy.

Disease States Implicated in Obesity
• Obese persons have an increased risk of developing vascular disease, sleep apnea, pulmonary hypertension,
stroke, coronary artery disease, congestive heart failure, arrhythmias, and sudden death.
• Obesity is often associated with venous insufficiency as a result of either diastolic dysfunction or increased
intravascular volume and incompetent venous valves. Resulting venous stasis may predispose obese
patients to ulcers or cellulitis.
• Obese patients in the upper BMI tertile have a 2.42 higher incidence of deep vein thrombosis and pulmonary
embolism than patients in the lowest BMI tertile.
• Obese patients are six times more likely to have hypertension than lean patients. An increase in body weight
of 10 kg is associated with a 3 mm Hg higher systolic and 2.3 mm Hg higher diastolic blood pressure.



CONTINUED NEXT PAGE
Disease States Implicated in Obesity (continued)
• Sleep apnea or sleep disordered breathing prevalence rises dramatically in obese patients because of their
increased demand for ventilation and breathing workload, respiratory muscle inefficiency, decreased
functional reserve capacity and expiratory reserve volume, and closure of peripheral lung units.
• The consequences of sleep apnea include an increase risk of diurnal hypertension, nocturnal dysrhythmias,
pulmonary hypertension, right and left ventricular failure, myocardial infarction, and stroke along with an
increased mortality rate.
• The prevalence of pulmonary hypertension in combination with obstructive sleep apnea is approximately
15% to 20% and is associated with morbid obesity particularly during exercise.
• According to results from the Physicians’ Health Survey, the risk of ischemic or hemorrhage stroke in males
increases by 4% and 6%, respectively, with each 1-unit increase in BMI.
• Obesity is associated with advanced atherosclerosis in adults and convincing evidence is available that
obesity early in life accelerates the progression of atherosclerosis decades before the appearance of clinical
manifestations.
• People who are obese are predisposed to CHF because obesity promotes hypertension, diabetes, and CHD.
The risk of CHF is increased by 5% in men and 7% in women for each 1-unit increase in BMI.
• Obesity increases the risk of arrhythmias and sudden death even in the absence of cardiac dysfunction due to
increased heart rate and abnormal OT
c
interval.
Effects of Weight Loss on Obesity and Cardiovascular Disease
• Weight loss strategies are employed to prevent or improve CHD risk factors in obese patients.
• Therapies that can promote weight loss through a negative energy balance include dietary intervention,
physical activity, pharmacotherapy and surgery. Behavioral modification in combination with weight loss
therapies is also necessary to enhance and maintain weight loss.
• Cardiovascular benefits of weight loss include the following: decreased stroke volume, decreased cardiac
output, decreased pulmonary capillary wedge pressure, decreased left ventricular mass, improvement in left
ventricular diastolic and systolic dysfunction, decreased resting oxygen consumption, decreased systemic
arterial pressure, decreased filling pressures of the right and the left side of the heart, decreased resting heart
rate, decreased QT
c
interval, and an increased HRV. Most importantly, weight reduction causes a decrease in
blood pressure and its associated neurohormones.
• The method of weight loss is usually inconsequential; however, some benefits of weight loss are not obtained
surgically. Weight loss by surgical means causes little change in systemic arterial resistance or a decrease in
pulmonary capillary wedge pressure.
Risks of Weight on Obesity and Cardiovascular Disease
• Weight loss through starvation, liquid protein diets, very-low-calorie diets, and surgery can potentially prolong
the QT
c
interval and induce life-threatening arrhythmias.
• Sibutramine hydrochloride (Meridia

) and orlistat (Xenical

) are efficacious in treating obesity and associated
co-morbidities.
• Sibutramine hydrochloride, a centrally acting drug approved for long-term use, has not been reported to
induce valvular abnormalities; however, this agent does increase blood pressure and heart rate.
Sibutramine should not be used in patients with untreated hypertension, CHD, CHF, arrhythmias, or stroke.
• While both fenfluramine (Pondimin
®
) and dexfenfluramine (Redux
®
) were removed from the market in the
1990’s, phentermine (e.g., Fastin
®
, Ionamin
®
, Adipex-P
®
) has not been associated with valvular dysfunction.
Obesity and the Future of Healthcare Services
• Abdominal obesity and total healthcare expenditures have been demonstrated to be positively correlated in
institutional settings.
• Increased physical activity early in life may become the most cost-effective non-pharmacological therapy to
decrease obesity.
• Patients should be informed about expected weight loss results to avoid unrealistic expectations. The primary
target should not be body weight normalization, but weight loss to improve cardiovascular risk factors.
Conclusion
• Obesity is a chronic metabolic disorder associated with CVD and increased morbidity and mortality rates.
• Evidence has shown that weight loss in obese patients reduces risk factors for CVD and diabetes.

Prepared by: Ashley Saunders, Pharm.D. Candidate Reviewed by: Stacy Lauderdale, Pharm.D., BCPS

2

Obesity and cardiovascular disease. CLIPs – Current Literature and Information for Pharmacists. May 22, 2006;10(31):1-2.