Drug Topics - November 10, 2008 - (Page 44)

Continuing Education COMPLICATIONS OF OBESITY (CVD), osteoarthritis, and gallbladder disease are related to obesity.17 Nearly 325,000 deaths are attributable to obesity indirectly through the incidence and prevalence of hypertension, diabetes, and CVD. 1,2,5,6 The Framingham Offspring study revealed a clear relationship between obesity and CVD, including myocardial infarction.18 Incidence of CVD in men and women followed for 16 years was directly related to the number of heart disease risk factors (diabetes, hypertension, BMI). Small changes in body weight correlated with a change in the coronary heart disease risk. An increase of 2.25 kg or more in 16 years increased the sum of risk factors by 20% in men and 37% in women, while a reduction by 2.25 kg decreased the risk by 48% in men and 40% in women. tes, including insulin, sulfonylureas, and thiazolidinediones (TZD), can contribute to weight gain.3 A 5 to 10% weight loss will have a signiﬁcant impact on clinical markers such as blood glucose, blood pressure, total cholesterol, LDL-cholesterol, and triglycerides. Modest improvements can also be seen in HDL-cholesterol. Studies such as the United Kingdom Prospective Diabetes Study illustrate the impact of dietary modiﬁcation and physical activity on risk reduction in diabetes, blood pressure, and cholesterol.24-25 Agents such as biguanides, TZDs, and incretin mimetics can be used to assist with weight reduction and hyperglycemia.3,24 Hypertension Guidelines from the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure state that the impact of a weight loss of 10 kg on systolic blood pressure (SBP) ranges from 5 to 20 mmHg.19 Weight loss also has an impact on diastolic blood pressure (DBP). Hypertension Prevention Phase II trials evaluated the effect of weight loss on changes in blood pressure. Approximately 1,200 subjects were randomized to usual care or an intervention of diet and physical activity for three years.2021 The results demonstrated a linear relationship between weight loss and blood pressure.20-21 A 5 mmHg reduction in SBP and 7 mmHg in DBP was seen with an 8.8-kg weight loss. These benefits were lost when patients gained the weight back. The Trial of Antihypertensive Interventions and Management reported a weight loss of 5% from baseline. This contributed to reductions in DBP equivalent to a single dose of an antihypertensive medication.12 In many cases hypertension resolves or drastically improves in those who undergo bariatric surgery; however, this change may be temporary as some studies have illustrated a gradual increase in blood pressure 3 to 5 years after surgery, often due to ﬂuctuations in weight status.22 The following mechanisms have been linked with sodium retention and hypertension: sympathetic nervous system activation, renin-angiotensin-aldosterone system activation, and compression of the kidney.19 There are currently no speciﬁc recommendations for the pharmacological treatment of obesity and hypertension. Selection of therapy is often targeted based on the etiology of the disorder. Diabetes Obesity-related diabetes mellitus occurs when excessive storage of triglycerides raises plasma insulin concentrations, eventually leading to insulin resistance. Obesity-related diabetes is familial and modest weight loss improves insulin sensitivity and glycemic control dose dependently.23 Most patients diagnosed with type 2 diabetes are overweight or obese. As discussed, several therapies used to treat diabe- Obstructive sleep apnea Obstructive sleep apnea (OSA) is the intermittent cessation of breathing during sleep due to partial or complete upperairway obstruction, resulting in excessive episodes of apnea and hypopnea. In general, patients with sleep apnea are characterized by a BMI of 30 kg/m2 or greater, abdominal fat distribution, and a large neck girth (>16 inches in women and >17 inches in men).26 The principal effects are diminished residual lung volume and poor pulmonary dynamics caused by increased abdominal pressure on the diaphragm. Evidence suggests that fatty inﬁltration of the accessory muscles of breathing can decrease elasticity of the chest wall. It is evident that fat distribution, independent of total fat, has an inﬂuence on pulmonary function in men. This is hypothesized to be through the effects of visceral fat levels. Approximately 12 to 40% of morbidly obese patients have OSA. Furthermore, sleep apnea is probably underdiagnosed in overweight and obese patients and should be strongly considered in patients with complaints of fatigue, daytime somnolence, snoring, restless sleep, and morning headaches. Gallbladder Disease The risk of gallbladder disease increases in linear relation to BMI.27 This is particularly true in women. The Nurses’ Health Study found that compared to lean women (BMI 30 kg/m2 had a twofold excess risk of experiencing symptomatic gallstones, and women with clinically severe obesity (BMI <45 kg/m2) had a sevenfold excess risk.28 One rationale for the increased risk of gallstones is the high cholesterol turnover related to total body fat. The production of cholesterol is linearly related to body fat in that about 20 mg of additional cholesterol are synthesized for each kilogram of extra body fat.29 Interestingly, the risk of developing gallstones increases during weight loss. This is due to increased bile cholesterol supersaturation, enhanced cholesterol crystal nucleation, and decreased gallbladder contractility. Rapid weight loss is an important predictor of symptomatic gallstones. When the rate of weight loss exceeds 1.5 kg or approximately 1.5% of body weight per week, the risk of gallstone formation increases exponentially.30 W W W.D R U GTO P I C S .C O M 44 DRUG TOPICS N OV. 10, 2008 http://WWW.DRUGTOPICS.COM

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Drug Topics - November 10, 2008 Contents Up Front Up Front in Depth Letters Rx Care Government Community Practice First Responders Clinical Practice Self-Care FDA Safety Page Weighing the Complications of Obesity New Products Viewpoint

Drug Topics - November 10, 2008

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