Metabo — Is a small waistline a measure of health?

What’s in a name? It’s called “metabo” in Japan and “metabolic syndrome” here, but is it a real medical syndrome? Does having it mean you’re more likely to have a heart attack or die prematurely?

While having a trim waistline to avoid the dreaded metabo and reduce medical costs has become a popular health mandate, is it evidence-based?

Metabolic syndrome is a relatively new term, but it may be surprising to learn that there is no consensus among medical professionals of what it is, what causes it, what it means, or even how to define it. Or, even if it’s real at all. Metabolic syndrome, also called insulin resistance syndrome or Metabolic Syndrome X, is a highly controversial label. But the general public is rarely let in on the debate.

Riddle of risk factors

Metabolic syndrome is a compilation of risk factors — waist circumference, blood pressure, blood sugar, and triglyceride and blood lipids (cholesterol). Some say that the more of these indices that are “high,” the greater the risk for heart disease.

But can grouping risk factors together make a stronger risk factor, or even make a new disease? And does treating risk factors — treating correlations as causations — make the underlying disease process go away and help us live longer? Or, is a smaller belt size to prevent heart disease like going braless to reduce risks for breast cancer?

To date, traditional cardiac risk factor scores have proven poor predictors of who will get heart disease or die prematurely. This new syndrome is used to support the importance of treating each of its risk factors and getting those numbers in line with certain thresholds (cut-offs that differ depending on who has written the clinical guideline). Getting good numbers accounts for the most-prescribed pharmaceuticals, used chronically by adults. Under this new syndrome, waist circumference has also become the new BMI, to compel people to lose weight and adopt healthy diets and lifestyles.

But if metabolic syndrome is a real disease phenomenon, no one has yet figured out the underlying disease process or cause. Theories abound to explain it, however, all based on other correlations — such as low dietary magnesium or dairy products, small birthweight, endocrine abnormalities, smoking, sleep deprivation, stress and the release of adrenalin, yo-yo dieting, anger, sedentary lifestyles, depression and heredity, with the genes and mutations linked to it identified. The fact that each of the indices being used to define it also rise naturally as most people age, is widely ignored.

Studies by multiple scientists have abundantly shown, however, that the syndrome itself has nothing to do with obesity, fat mass, percentage body fat or BMI, and it has been identified in people of all sizes. Yet, being fat continues to be popularly blamed for metabo and the term has even come to connotate obesity.

But in light of the growing body of evidence for the "obesity paradox," attention has recently turned from BMI to waist circumference as the visible sign of this syndrome and of people at risk of heart disease and premature death. Some studies have reported higher risks associated with greater waist-to-hip ratios (sometimes called pot belly, beer belly, apple shape, and middle-aged spread). These observational correlations have typically suffered from weak, untenable associations; failure to account for confounding factors (such as age, dieting, stress, genetics or fitness); reverse causations that can skew interpretations; and use of surrogate endpoints, rather than solid clinical endpoints such as all-cause mortality.

But one of the longest, largest studies in the world examining long-term cardiovascular health and actual mortality had specifically looked at high BMI and waist circumference and found no correlations. The Aerobics Center Longitudinal Study (ACLS), led by researchers at the Cooper Clinic in Dallas, followed 21,925 men (ages 30-83) from 1971 and 1989. The men had received extensive medical evaluations, including body composition, labwork, cardiac work-ups and fitness measured using maximal treadmill tests, and were then followed for 8 years. Three out of five obese men proved to be cardiovascularly fit. The results were published in the March, 1999 issue of the American Journal of Clinical Nutrition.

Looking at BMI itself, the researchers found no relationship to cardiovascular disease deaths or all-cause mortality. Splitting hairs, the relative risks (adjusted for age, smoking, alcohol, and family history) among fit obese men were slightly lower than lean men who were fit (RR=0.92 and 1.00, respectively). Waist circumference showed nearly identical risks among the fit men.

But among the unfit men, the small-waisted men (<87cm) had double the risks for cardiovascular disease deaths and all-cause mortality than the large-waisted men (≥99cm) (RR=4.88 versus 2.40). Adjusting for smoking, high blood pressure and cholesterol didn’t change the results. As the authors concluded, “the health benefits of leanness are limited to fit men.” It’s the thinner men for whom we should be especially promoting increased physical activity. “Fit men in the highest quartile of waist girth had no elevated risk of all-cause mortality and had much lower mortality risk than unfit men in the lowest quartile of waist girth.”

In other words, having a small waist was not a measure of lower risks and having a larger waist size was not a measure of higher risks. Exactly the opposite of what is popularly believed.

Since metabo and waist circumferences continue to be promoted in popular press and by public health officials as signs of impending heart disease and premature death, have they been supported as measures of health risks in more recent studies? Two recently published studies examined metabolic syndrome to determine if it’s a valid clinical label. They looked for any relationships between metabolic syndrome and heart disease or premature death. Their findings received little notice, but since your job and insurance may depend on this evidence, you deserve to hear what they found and the other side of the issue.

Nail in the Coffin

Last week, the analysis of two large prospective clinical trials was published in Lancet, examining the associations between metabolic syndrome and risks for cardiovascular disease and diabetes among seniors, those most at risk of dying. As the authors explained, the evidence to date has found only modest associations between the metabolic syndrome and risks for vascular events among middle-aged people — but those associations are so insignificant that the metabolic syndrome does not enhance risk predictions among this age group. This has led a number of medical professionals to question the value of the metabolic syndrome at all. So, for this study, they looked at its potential value among elderly.

The authors used the most accepted definition of metabolic syndrome from the Third Report of the National Cholesterol Education Program, as well as each of its five individual health indices used in the definition. They identified metabolic syndrome, as measured using actual clinical exams and laboratory tests, among 4,812 adults (age 70-82) in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) and looked for associations with the development of cardiovascular disease and diabetes during 3.2 years of follow-up. They also corroborated their findings examining a second prospective study, the British Regional Heart Study, of 2,737 nondiabetic men (age 60–79) followed for an additional 7 years.

To cut to the chase, in both studies there was no difference in BMIs or waist circumferences or fasting blood sugars or triglyceride levels between the adults who did and didn’t develop heart disease. There was no association between metabolic syndrome, as well as each of its individual criteria, and heart disease. Odds ratios (adjusted for age, etc.) were all untenable and hugged null, with high blood sugars and obesity associated with slightly lower risks. Waist circumference, which had been measured in the British study, was also unrelated to cardiovascular events.

“We recorded no evidence that people with or without existing vascular disease at baseline differed with respect to the prevalence of metabolic syndrome,” said the authors.

Looking at metabolic syndrome in relationship to risks for diabetes, they reported that a high fasting glucose, alone, was associated with a higher risk for having a diagnosis of diabetes later confirmed among these elderly seniors, more so than any of the metabolic syndrome measures individually or together. In fact, the authors concluded, most studies show that sugar on its own, along with questions about family history, etc. are just as good to screen for the need for more tests to identify diabetes, “so why do you need these [metabolic syndrome] criteria?” As lead author, professor Naveed Sattar with the University of Glasgow, Scotland, told Heartwire on May 22^nd: “It's not rocket science.”

The authors concluded that metabolic syndrome “has no benefit in risk stratification for cardiovascular disease in elderly people. This finding is clinically relevant since most vascular events occur in individuals older than 60 years.” While this analysis was on elderly, the authors said, “our findings concur with data in middle-aged populations for whom criteria for metabolic syndrome are inferior to, and do not enhance conventional methods for, risk prediction of coronary heart disease.”

Professor Sattar said to Heartwire: “It's clear to me that the criteria for metabolic syndrome have no role in clinical medicine; categorically none.”

An accompanying editorial in that same issue of Lancet by professor Richard Kahn, Ph.D., Chief Scientific and Medical Officer of the American Diabetes Association, said, this analysis “put yet another nail in the coffin of the metabolic syndrome.”

Cardiovascular Health Study

The results of the Cardiovascular Health Study were published in the May issue of the Archives of Internal Medicine. The authors had examined the relationship between the metabolic syndrome and death among 4,258 adults (age 65+) in the United States between 1989 and 2004.

Was there even a relationship? And can metabolic syndrome be used to help predict who might be at higher risk of dying?

Since there are multiple different definitions for metabolic syndrome, each using slightly different cut-offs and health risk factors, these authors evaluated the risks associated with metabolic syndrome using all of the different official definitions: the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII); the International Diabetes Foundation; and the World Health Organization.

Each study participant had had their metabolic syndrome components clinically assessed by medical professionals, including body measurements (weight, height, waist and hip circumference), and other clinical examinations (blood pressure; fasting blood lipids, glucose and insulin; and glucose tolerance tests. The adults in this study were free of prediagnosed cardiovascular disease. Participants received annual physical examinations and interim 6-month telephone contacts through 1999 and 6-month telephone contacts thereafter. Deaths were confirmed by a mortality review committee using information from hospital records, death certificates, autopsy and coroner reports, insurance records, obituaries and interviews with physicians or next of kin.

After 15 years of follow-up, 2,116 deaths had occurred. Among the nondiabetics: 4.12% of those without metabolic syndrome had died compared to 4.44% of those with metabolic syndrome, as defined by ATPIII. After factoring for age, smoking, gender, race, physical activity, education level and alcohol use, there was no tenable relative risks associated with metabolic syndrome (adjusted RR=1.16). Using the IDF definition for metabolic syndrome, 4.18% compared to 4.32% had died, and the authors were again unable to find an association with metabolic syndrome (adjusted RR=1.11). The relative risks associated with metabolic syndrome using the WHO definition were similarly null and not above random chance (adjusted RR=1.18). In other words, metabolic syndrome, regardless of how it is defined, cannot credibly be used to predict who is at higher risk of dying prematurely.

The authors then examined the risks of mortality associated with each of the specific health risk factors used in the definitions of metabolic syndrome. There was no tenable association between mortality and any of the health risk factors taken individually, even when adjusting for confounding factors, as above. The relative risks all hugged null (RR=1.0). Blood lipids (HDL-cholesterol, triglycerides, etc.) and obesity were unrelated to mortality. Splitting hairs, high triglyceride levels among women, were even associated with a 21% lower risk of mortality.*

What about waist measurements? Among men and women, large waist circumferences — for men ≥102cm (≥40.16 inches) and for women ≥88cm (≥34.7 inches) — were associated with slightly lower risks, 4% and 5%, respectively.

So, even among Americans with waist circumferences much larger than the Japanese regulations (35.5 inches and 33.5 inches for men and women, respectively), there was no association with higher risks. With no association at all, there’s no possible source for causation and certainly no support for mandating treatment or interventions. The evidence continues to point out to us that this isn’t about health.

© 2008 Sandy Szwarc

*The researchers found only diabetes (fasting glucose >113 mg/dL on meds) and high blood pressures (>149mmHg systolic on medications) were associated with higher risks, but even those were modest (RR= 1.39 and 1.32, respectively).