The ‘precursor’ syndrome

Catch a problem early and you prevent serious illness and suffering. But are we creating a bonanza for the pharmaceutical industry in the process?

Up until 2003, if your systolic blood pressure was 120 to 129 and your diastolic pressure was 80 to 84, you could have been pretty happy about those numbers. Your doctor would have told you that your blood pressure was normal and to keep up the good work.

But then updated blood pressure guidelines came out and, sorry, bad news: with those same readings, you’d now be considered prehypertensive. You wouldn’t be prescribed any medication unless you had some other health problem like heart failure or diabetes. But you’d be warned about the perils of high blood pressure and coached to lose a few pounds and exercise.

Diagnosis is traveling ‘upstream’
Prehypertension is an example of a growing tendency to identify conditions and create new diagnoses before full-fledged illness sets in. Before osteoporosis, there’s a moderate bone-loss condition called osteopenia. Mild cognitive impairment is a designation for the memory problem that precedes Alzheimer’s disease. With diabetes and heart disease it’s complicated, but many researchers believe that they share a “precondition.” It goes by several names: metabolic syndrome, insulin resistance syndrome, syndrome X. The condition isn’t defined by a single lab test, but by whether you have three of the following: abdominal obesity, high levels of triglycerides, a low level of “good” HDL cholesterol, high blood pressure, and high blood sugar (see box).

Metabolic syndrome checklist You have metabolic syndrome if you have three of the following:   A waist greater than 40 inches for men, 35 inches for women   A triglyceride (blood fat) level of 150 mg/dL or higher   A “good” HDL cholesterol level of less than 40 mg/dL for men, less than 50 mg/dL for women   Systolic (the top number) blood pressure of 130 mm Hg or higher and diastolic (the bottom number) of 85 mm Hg or higher   A fasting glucose level of 110 mg/dL or higher Source: National cholesterol Education Program, ATP III Guidelines

Measure it and the diagnoses will come
The precondition condition is partly a creature of science’s genius for peering into our bodies and its seemingly limitless capacity for measurement. There also have been a cadre of clever people who figured out how to do these things on a mass scale at a reasonable cost. Osteopenia, for example, wouldn’t be diagnosed nearly as often if it weren’t for dual-energy x-ray absorptiometry (DXA) — and, increasingly, ultrasound machines — that make noninvasive, painless measurement of bone density possible. It’s not a coincidence that the metabolic syndrome diagnosis came into being after it became easy to do a full “lipid profile” that includes LDL cholesterol, HDL cholesterol, and triglycerides. Even without high-tech measurements, epidemiologic research sometimes sets in motion a similar dynamic. Epidemiologists comb through mounds of data to find risk factors for certain diseases. If they find them, those risk factors aren’t the disease, so a new label is used — a precondition of some kind. (Naturally, not everyone with the risk factors gets the disease.) Screening programs for early stages of a disease (often cancer) stir up similar issues.

In the name of prevention
But the stated intention behind these diagnostic categories is disease prevention. The logic is familiar enough: Catch something early, and you can prevent its most serious consequences. But that thinking only works if (a) you know that the condition tends to progress to the full-blown disease, and (b) you can do something to stop — or at least slow down — that progression.

Metabolic syndrome seems to fit that bill nicely. Research has shown that a large percentage of people with the syndrome go on to develop diabetes, have a heart attack, or both. And losing weight and getting exercise have been shown to reduce the chances of either problem happening.

The prehypertension category was created for a slightly different reason. The experts who drew up the updated guidelines used data showing that cardiovascular risk (for heart attack and stroke) from increasing blood pressure begins at readings as low as 115 systolic, 75 diastolic. So prehypertension isn’t so much predictive (although it may be) as the starting line for elevated risk. For that reason, it’s likely (although skeptics say it is unproved) that recognizing and “treating” (remember, no pills, just diet and exercise) prehypertension could save you from a stroke or heart attack.

Mild cognitive impairment, however, is problematic. People who meet the diagnosis develop Alzheimer’s disease at a rate of about 15% per year, so it does predict an illness. But at this point there’s no proven way to keep Alzheimer’s disease from developing. That may change. Researchers may find drugs or other means for slowing the progression. Some individuals and families find the diagnosis helpful because it gives them a chance to prepare for Alzheimer’s.

The drawbacks
Diagnosis sometimes has bad psychological effects. Before the label you have the confident outlook of a healthy person. Afterward, you think of yourself as diseased or destined for illness. Will having preconditions make the large ranks of the worried well get even larger?

Another major concern is that pharmaceutical companies will rush in to exploit these diagnoses. Critics of the industry accuse it of rampant “condition branding” — creating or heightening awareness of conditions simply to create or widen the market for a drug. The drug companies respond that they’re coming up with medications for undertreated diseases.

Research is hinting that statins (Lipitor, Zocor, other brands) and some of the diabetes drugs (metformin and the thiazolidinediones like Avandia) may keep people with metabolic syndrome from getting heart disease or diabetes. In isolation, that’s good news. Fewer people will get sick. But will nondrug approaches like weight loss through diet and exercise stand a chance once the pharmaceutical marketing machine kicks into gear?

The advantages
Heart attack, stroke, Alzheimer’s disease, diabetes — they rob millions of their health and steal years of life away. They also cost a lot in medical bills. By identifying the precursors to these conditions and working with their patients to hold them in check, doctors could prevent untold suffering.

And the consequence needn’t be more pills than we’re already taking. For osteopenia, the best medicine isn’t alendronate (Fosamax), but exercise that involves bearing some weight, because it strengthens your bones. If and when the metabolic syndrome diagnosis really catches on, we shouldn’t jump to statin prescriptions as a treatment, but first make a concerted effort to shed weight, eat better, and get more exercise.