Metabolic Disorders

Update on Fen-Phen and Heart-Valve Problems

Published: October, 2000

Two recent studies are adding to the data concerning fen-phen and heart-valve problems. These studies should offer some reassurance to patients who took this combination of weight-loss drugs.

Researchers from Harvard Medical School evaluated echocardiograms performed on 226 people who took fen-phen as part of a long-term study from September 1994 to September 1997. Shortly after the manufacturer’s voluntary withdrawal of fen-phen, the medications were stopped and the patients underwent testing to determine if any heart-valve problems had developed. The echocardiograms showed that not one patient had severe valvular disease. Mild leaking of the aortic valve was detected in 12 patients, and three patients exhibited moderate aortic-valve leaking — a total of 15 (6.6%) patients. Three subjects (1.3%) had moderate leaking of the mitral valve. To compare the rate of heart-valve problems in these patients to the rate one might expect to see in the general population, investigators turned to data collected as part of the Framingham Heart Study (the long-term epidemiological study being conducted in a Boston suburb). They found nearly the same rates of aortic- and mitral-valve leaking in the Framingham volunteers as in the diet-drug study participants.

A second study published in the November 23, 1999, issue of the American Heart Association journal, Circulation, suggests that heart-valve abnormalities in individuals who took dexfenfluramine (Redux) may dissipate. Although study findings did link the drug to mild aortic-valve disease and moderate mitral-valve problems, it also noted that valve problems might eventually go away after drug use is stopped.

Using echocardiograms to spot heart-valve abnormalities, investigators evaluated 223 patients who had taken dexfenfluramine for an average of seven months. The tests were performed an average of 8.5 months after the participants stopped taking the drug. None of the former dexfenfluramine users was found to have severe mitral valve disease or moderate (or worse) aortic-valve disease, but 7.6% had either mild aortic-valve disease or moderate mitral-valve problems. People who had stopped treatment less than eight months before the echocardiogram were twice as likely to have valve problems than those who had been off dexfenfluramine for longer, suggesting the problem regresses.

Could it be that these diet pills are safe after all? An editorial in the Journal of the American College of Cardiology accompanied publication of the Harvard study and asked whether there was adequate proof of any increase in risk from fen-phen. No one is ready to go so far as to suggest that these drugs should return to the market, but a reasonable conclusion at this point is that there is an increased risk of heart-valve problems, though the risk is probably quite small.

Regardless of the relative risks and merits of fen-phen — and of diet drugs in general — weight loss remains a problem that cannot be solved by any "magic bullet." Medications may help a little in some patients, and surgical solutions might be considered for severely overweight individuals. However, for most of us, regular exercise and careful attention to how many calories we eat remain the best strategies for successful and lasting weight loss.

Journal of the American College of Cardiology, Vol. 34, No. 4, pp. 1153–58.
Circulation, Vol. 100, No. 21, pp. 2161–67.

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The Health Burden of a Few Extra Pounds

According to an extensive study conducted by the American Cancer Society, even being moderately overweight adds a significant burden to your health. This research looked at the relationship between body-mass index and the risk of death. It also examined the influence of smoking, disease, race, and age on the weight-related risk.
Body-mass index (BMI) combines height and weight measures to gauge body mass. It is calculated by dividing your weight in kilograms by the square of your height in meters. The simplest way to calculate your BMI is to use a table that lists the BMI for various weights and heights. (Check your BMI.)

The study investigators followed more than one million adults between 1982 and 1996 and found that being moderately to severely overweight greatly increases a person’s chance of early death from cancer, cardiovascular disease, and other illnesses. Smoking and the presence of disease exacerbated this risk.

The lowest risk of death was associated with BMIs of 23.5 to 24.9 in men and 22.0 to 23.4 in women. Death rates then increased as BMI increased. Even exceeding the upper end of the ideal range by just a point or two appeared hazardous. The risk of death from cardiovascular disease increased significantly in men after a BMI of 26.5 and in women after 25.0 in men. And the most obese white men and women (35+ BMI) were at least twice as likely to die than their healthy cohorts. For instance, a 5 ft. 9 in. male weighing 150 pounds has a BMI of 22. Add just 30 lbs. to this person, and the BMI increases to 27, already raising his health risks. At a 35 BMI, our 5 ft. 9 in. male would weigh 240 pounds, and have increased his risk of dying from cancer by 40% and cardiovascular disease by almost 100%. Smoking and the presence of disease decreased the chance of survival regardless of the subject’s BMI.

Black Women proved the exception. Even the heaviest black women saw only a 20–30% increase in their risk of death — opposed to the nearly 100% increase in risk for similarly overweight white women. This confirms the findings of previous studies, and could be related to how differences in how the two groups of women store and process fat.

The study’s conclusion regarding the health effects of extreme leanness is more controversial. While subjects with BMIs under 18.0 experienced a moderately higher risk of death, researchers believe this was more likely a function of an unrecognized disease that resulted in lower body weight, rather that being underweight itself.

Debating the consequences of extreme leanness is academic. Only 7.7% of the US population have BMIs lower than 20. Obesity, however, is a public health threat. Nearly one- third of Americans are moderately overweight (25.0 to 29.9 BMI) and almost one- quarter are significantly overweight (30+ BMI). For more information on obesity and approaches to weight loss, see page 853 of the Family Health Guide.

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Surgery for Severe Obesity

Two recent studies offer some hope for people who suffer from "clinically severe obesity" (generally, a body mass index greater than 40). For these people, whose weight poses serious health risks, conventional diet and drug interventions are usually unsuccessful. A last resort has been surgery to limit the number of calories the body absorbs. But there have always been concerns about the benefits versus the risks of surgery. Two procedures, the Roux-en-Y gastric bypass and adjustable laparoscopic gastric banding, each appear highly effective at promoting weight loss in obese individuals.

In the Roux-en-Y gastric bypass procedure, surgeons divide the patient’s stomach in two and create a small pouch from the upper stomach. They then connect the small intestine directly to this pouch, bypassing the rest of the stomach. When the patient eats or drinks, the food passes from the esophagus into the small pouch, which can hold only two to three ounces. Because the pouch is so limited, the person feels full and satisfied after eating only a small amount of food.

In a study conducted through the Mayo Clinic, surgeons performed the gastric bypass procedure on obese patients and found that after one year, the patients followed up had lost 68% of their excess body weight. This weight loss remained fairly consistent over four years. Many patients also reported that their appetites had decreased. As an added benefit, a number of individuals were able to reduce their high blood pressure, diabetes, and anti-inflammatory medications. Yet some patients in the study suffered complications from the surgery, such as wound infection, hernias, and bowel obstruction. Despite this, the procedure proved to be successful overall. After three years, 93% of the patients contacted were satisfied with the results.

Traditionally, gastric bypass is performed through a long incision in the patient’s abdomen. Doctors at the Lahey Clinic have eliminated the need for the long incision through the use of laparoscopic techniques during surgery. The surgeons make six half-inch-long incisions in the abdomen through which they can use surgical instruments and a laparoscope to view the abdominal cavity. The Lahey Clinic reports that this technique results in weight loss similar to the traditional surgical technique, yet is safer and less invasive — patients recover more quickly and do not have the risk of complications associated with a long incision.

The other procedure for obesity that boasts good results is adjustable laparoscopic gastric banding. With this technique, surgeons use a laparoscope to place an adjustable silicone band around the stomach, forming two pouches. As with the bypass technique, patients with the band feel full after eating a small amount of food because the first pouch of the stomach is small. In addition, the narrow passageway between the two pouches slows down the transfer of food. Doctors can use radiography to view the condition of the band and, if needed, can adjust the size of the passageway between the two pouches by injecting or aspirating a saline solution into a tube connected to the band.

In a Swiss study, patients who underwent the banding procedure lost an average of 14% of their total weight six months after the procedure and 18% after twelve months. These results sound great, but complications, such as problems with the band, were frequent, occurring in 34 out of 98 patients. Despite that, the study claims that complications led to unsatisfactory weight loss in only one of the patients. Nineteen other patients did not lose significant amounts of weight as a result of poor compliance.

As with any weight loss treatment, both gastric bypass and banding surgery require that the patient adopt new eating habits. Physicians must also monitor these patients to make sure that they do not develop vitamin and mineral deficiencies. But given the apparent success of each technique, surgery for clinically severe obesity may be an attractive alternative to diet and drug intervention, despite the risks involved.
October 2000 Update

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