New Ways To Think About Old Diseases

By Alice Park

The practice of medicine, doctors are fond of saying, is more art than science. Yet it's the guiding hand of science that directs them to reconsider treatments and make new educated guesses when a patient's symptoms don't go by the book. That's the force that will continue to reshape the way doctors manage heart disease, cancer and obesity in the coming years.

Every year since 1900, with only one exception (1918, when the influenza epidemic claimed more lives), heart disease has had the dubious honor of being the U.S.'s leading killer. Lowering cholesterol levels, specifically the low-density lipoproteins (LDL) that make meats and butter-laden desserts so irresistible to the palate but so hazardous to the heart, was the first step to slowing down the disease. But now physicians are shifting their attention to LDL's do-good partner, high-density lipoprotein (HDL), encouraged by early evidence suggesting it can not only clean out fatty deposits within blood-vessel walls but also cause those plaques to shrink in size. So doctors are asking patients to make simple lifestyle changes, including getting more exercise and eating omega-3 fatty acids, found in certain deepwater fish such as salmon and tuna, because these activities stimulate the liver to churn out more HDL. They also have an added incentive to prescribe the powerful statin drugs that lower LDL because those appear to do double duty, pumping up HDL levels 10% to 15%. And if that isn't enough, they are eyeing the arrival of HDL-boosting pills: Pfizer's torcetrapib is currently in clinical trials in combination with a statin and could be ready for FDA review in a year or two. "It's a look into the future of heart care," says Dr. Roger Blumenthal, director of Johns Hopkins Hospital's preventive cardiology program, of the new focus on HDL.

A similar shift in thinking is occurring among weight-loss researchers. For years, their best measure for how dangerous excess weight could be was body mass index (BMI), a formula that combined height and weight. A high BMI meant that you were carrying too much body mass for your height, putting you at risk of developing diabetes, hypertension, heart disease or stroke. The problem, as physicians quickly found out, was that body mass includes not just excess body fat but muscle as well. So fit people with dense muscle mass would consistently register as overweight and unhealthy. That led Dr. Jean-Pierre Despres, of Laval University in Quebec, to champion another measure for metabolic health: waist circumference. In a series of recent studies, researchers found that a larger waist circumference is a good indicator for metabolic syndrome, a constellation of physiologic changes that can lead to diabetes and heart disease. "I call it a vital sign," Despres says of the simple measure that he believes every doctor should include in every physical exam. "It's as important to know the size of your waistline as it is to know your cholesterol or blood pressure." Such a simple measurement, he says, could serve as a wake-up call for patients; by losing just 2 lbs. to 4 lbs., people with expanded waistlines can dramatically cut their risk of heart disease and hypertension.

It's just that kind of early-warning leverage that cancer doctors are starting to exploit. Their latest strategies take advantage of the fact that some cancers actually show a gender preference. Women who smoke, for example, are three times as likely to develop lung cancer as men who light up, and scientists at Cell Therapeutics found to their surprise that the reason for the difference was estrogen. In the presence of that hormone, which circulates in higher levels in women, lung cells are exposed to more of the carcinogens in cigarette smoke. Harnessing estrogen's ability to speed up some metabolic processes, the scientists piggybacked a potent chemotherapy agent onto a commonly circulating protein, hoping that the presence of estrogen around the lung tumors would also accelerate the cells' ability to open up to the cancer-killing drug. Sure enough, in early studies, women taking the drug who had naturally higher estrogen levels lived longer after their lung-cancer diagnosis than women on the same treatment with lower estrogen levels or men whose disease was diagnosed at the same time. "It's clearly the cutting edge," says Dr. James Bianco, president of Cell Therapeutics. And just the type of thinking that will push medicine to its next frontier.