February 27, 2007 (Miami) — The concept of the metabolic syndrome has, by now, been widely accepted by many clinicians as a useful and strong indicator of increased risk for diabetes and cardiovascular disease (CVD). However, some clinicians maintain that a diagnosis of metabolic syndrome is unnecessary, because better, more robust predictors of CVD, such as the Framingham Risk Assessment Score, exist, and a diagnosis of metabolic syndrome has no appreciable effect on either prognosis or treatment. This issue was discussed here at the 2007 annual meeting of the American College of Preventive Medicine in a heated debate by 2 prominent representatives of the opposing sides.

First, Gregory Pokrywka, MD, director of the Baltimore Lipid Center in Maryland, outlined his position, according to which metabolic syndrome is a very useful concept, which can be used to predict long-term risk for CVD, particularly in men older than 45 years and — especially — in women older than 55 years.

"Most of the CVD in women in this country comes from women who have the dysmetabolic syndrome," Dr. Pokrywka said. "I believe that's the driving force in CVD in women in this country. Low-density lipoprotein cholesterol (LDL-C) abnormalities are not driving cardiovascular abnormalities; it's triglyceridemia and high-density lipoprotein cholesterol (HDL-C) abnormalities. Multiple studies have suggested that metabolic syndrome may be more predictive of coronary heart disease (CHD) in women than in men."

Metabolic syndrome can also help predict diabetes mellitus, Dr. Pokrywka went on to say. "There is a significant increase in risk if you have 4 of the 5 criteria [that are used to diagnose metabolic syndrome]. You can almost call it a 'super metabolic syndrome,' " he told meeting attendees. "In the West of Scotland study, diabetes went up over 20-fold in patients who had 4 of those 5 criteria.

"We've been taught to look at cholesterol concentrations as a way to predict risk, but cholesterol concentrations are only proxies to what's really going on: lipoprotein abnormalities," Dr. Pokrywka argued. "In our clinic, we use a particle-based approach in the prognosis and diagnosis of our patients with CVD risk [because] the risk is determined by the number of particles, not by the amount of cholesterol."

Triglyceride levels are also very important, according to Dr. Pokrywka. "When I look at a lipid panel of a new patient, the first lipid I always look at is the triglyceride count. We're very focused on LDL-C in this country, and that's part of the reason I think we're only preventing one third of the [cardiac] events in our patients. I look at triglyceride count first because I know as that goes up, the particle count goes up, too."

High triglyceride levels are included in the definition of metabolic syndrome, but not in the Framingham Risk Assessment Score, and that is one of the reasons Dr. Pokrywka thinks metabolic syndrome is a better predictor of CVD. At the end of his talk, he summed up his argument by saying, "The diagnosis of metabolic syndrome serves to identify patients at increased long-term risk for cardiovascular disease, especially older patients, and it can also be used to identify patients at higher risk for diabetes and ischemic stroke."

Representing the opposing view was Mary McGowan, MD, medical director of the Cholesterol Treatment Center at University of Massachusetts Medical Center, who questioned whether making the diagnosis of metabolic syndrome provides a true assessment of risk.

"Are we including the right risk factors in our definition?" she asked. "For one thing, inflammatory markers are not included at all in the definition of metabolic syndrome," she noted. "Maybe if they were, it would be a better definition."

C-reactive protein (CRP) is a highly sensitive marker of inflammation, but it is not included in the definition of metabolic syndrome, Dr. McGowan pointed out. "CRP has been found to be an independent predictor of insulin resistance, and the question is, would the inclusion of CRP in the definition of metabolic syndrome improve the ability to predict risk?" she wondered. "Moreover, several studies have found that CRP is a strong, independent predictor of cardiovascular events, and its predictive value was equal to that of the metabolic syndrome," she said. "So maybe if CRP was included in the definition of metabolic syndrome, maybe we'd have a more robust syndrome," she suggested.

Another potential problem with the metabolic syndrome, according to Dr. McGowan, is that there are many different ways in which it can be defined. "For the World Health Organization (WHO), for example, you have to have diabetes or impaired glucose tolerance to be diagnosed with metabolic syndrome. Their definition also includes high waist-hip ratio, high triglyceride, low HDL, high blood pressure (BP), and microalbuminuria."

On the other hand, the Adult Treatment Panel definition is "very egalitarian," Dr. McGowan contended. "You only have to have 3 of the following 5: elevated fasting blood glucose, large waist circumference, high triglyceride count, low HDL, and high BP.

"So, there are many different ways to diagnose metabolic syndrome," Dr. McGowan said, "and this may result in some patients being falsely reassured, while others may be needlessly or excessively worried."

Finally, Dr. McGowan wondered if the Framingham Risk Assessment Score was a better predictive tool than the diagnosis of metabolic syndrome. She also questioned whether a person diagnosed with metabolic syndrome would be treated differently if the components of metabolic syndrome were diagnosed individually. "Does the treatment of metabolic syndrome differ from the treatment of individual components?" she asked. "If not, then why diagnose metabolic syndrome?"

Regarding the first question, Dr. McGowan cited a number of studies that found no advantage in terms of risk assessment by the unique components of the metabolic syndrome (obesity and high triglyceride levels).

"So, I think we already have a better scoring tool than the metabolic syndrome," she concluded. And regarding the question of whether the treatment of the syndrome would differ from the treatment of the individual symptoms, "I would argue that it wouldn't," she said. "So I would suggest that the clinical emphasis should be on treating effectively the [individual] cardiovascular risk factors that are present."

A show of hands at the end of the session revealed that the audience was equally divided between those who thought that a diagnosis of the metabolic syndrome is helpful and should continue to be used and those who thought that the concept should be abandoned because it has no unique qualities or features with respect to either prognosis or treatment.

ACPM 2007 Annual Meeting: Session 24. Presented February 26, 2007.