Scott M. Grundy on Bringing Metabolic Syndrome to Clinical Practice
Special Topic of Metabolic Syndrome Interview, November 2011
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This process
has been slow and it's gone on under the leadership of the NHLBI, which
has been changing. The NHLBI also has a policy of what they call
"evidence review." It has to be an extensive review of all the
literature to create a kind of formula for evidence-based medicine. And
since these are such huge fields, it's very complicated to do those
reviews. By my understanding, that's one factor that slowed down this
whole process of bringing out new guidelines.
As a researcher, what do you consider to be
the most challenging aspect of studying metabolic syndrome?
If you want to get to the basis of the problem, it's a multi-factorial condition. What we've learned about obesity is that it relates to these risk factors through many different pathways and that's of great interest, but it also makes it very complicated to understand, to find out how obesity causes high blood pressure or causes high cholesterol or causes high triglycerides. It's probably several factors for each of those. This is what we study and it's fascinating, but there is just no simple solution to it. That's one challenge.
Another, which I don't know if we'll ever find the solution to, is that after the NCEP ATP-3 guideline came out, drug companies thought they would develop a magic bullet to cure metabolic syndrome. It used to be that you'd treat the cholesterol and the blood pressure, etc. So now we thought that if we can come up with one drug that will cure metabolic syndrome—one pill—that would be fantastic. And it would be, but so far, we haven't been able to find anything that will do it. Maybe the closest thing would be to get a drug against obesity, but that hasn't worked out either.
To treat all risk factors at once is a big challenge. Weight reduction will in fact treat all the relevant risk factors at once. Take away the stimulus for the risk factors, and blood pressure, cholesterol, and triglycerides come down. But it's still a challenge to get the public to change their ways.
What's the most surprising finding that's
come out of metabolic syndrome research in the last decade or
so?
One of the things that surprises everybody and me, too, is how complicated the body fat is. We had no idea that adipose tissue and adipocytes are so metabolically active. They produce a whole set of compounds or products, hormone-like substances, that affect the body's metabolism. That's one big thing. And that's been fascinating, because it's opened up so many other fields of research.
Another surprise, of course, is the statin drugs. Since 1990, we've discovered just how powerful they are for reducing heart attacks. They've emerged as the major drug worldwide. Even in people with metabolic syndrome, they're very effective for preventing heart attacks.
"We had no idea that adipose tissue and adipocytes are so metabolically active."
Why do you think statins work to reduce heart
disease in patients with metabolic syndrome if these patients to not
have high LDL cholesterol?
Well, they prevent atherosclerosis. Here's what I think: LDL cholesterol starts the problem of atherosclerosis and it brings the cholesterol into the artery wall. It's also kind of a toxic protein and by itself it can cause atherosclerosis if cholesterol is high enough. Most people don't have really high cholesterol, so all of us develop atherosclerosis but at a much slower rate when cholesterol is low, than when it's high. If you had really low cholesterol, you probably wouldn't get atherosclerosis at all. But most people in America have LDL cholesterol higher than it should be and that's the driving force.
Now all these other risk factors, like high blood pressure, high triglycerides, diabetes and other factors that go along with metabolic syndrome, they worsen the process because they promote inflammation. Atherosclerosis is an inflammatory process, albeit very low-grade inflammation. That's why I think, as do many others, that these risk factors accelerate atherosclerosis for a given level of cholesterol. The lower the cholesterol, though, the greater the reduction in heart disease.
You described atherosclerosis as an
inflammatory disease. Do you think C-reactive protein should be included
in the diagnosis of metabolic syndrome?
The problem is that it adds another test. People with metabolic syndrome often have some increase in C-reactive protein (CRP), and so it adds information but it also adds another test to routine medical practice. Right now you can make the diagnosis of metabolic syndrome with very simple measures that are routine—measuring cholesterol, triglycerides, glucose, and blood pressure. You don't have to do any special testing. And CRP is a special test, like ApoB as a measure of heart disease risk. That's why we resist including either of those in routine assessment for metabolic syndrome or heart disease risk.
I don't measure CRP routinely because I'm not sure how much more it adds to the routine measurements we're already doing. It does reflect some kind of inflammation process. Although most of the CRP that's increased is actually due to obesity, anyway. Let me explain that real briefly. Adipose tissue makes a cytokine called interleukin-6. This goes to the liver where it stimulates production of CRP. So when you're overweight, you're going to have a high CRP. In that sense, it's just an indication that you have too much fat tissue and we know that already.
If you could boil the last 20 years of
research in this field down to one over-riding message, what would it
be?
I would have two messages. Number one is the importance of lifestyle change. We need to keep on that message. But the other is to have regular medical evaluation of your risk factors. Some of these are silent risk factors and people are unaware of them until they get heart disease. And since this can be prevented, it's a tragedy.
Yet we see it all the time in our patients. They wait too long to pay
attention to their cholesterol and blood pressure, and they often have
atherosclerosis or diabetes by the time they see us. If our patients paid
attention to their risk earlier in life, a lot of disease could be
prevented. Of course, it is up to physicians to test for risk factors for
heart disease and diabetes whenever they evaluate patients. Unfortunately,
this is not always done.
Scott M. Grundy, M.D., Ph.D.
Center for Human Nutrition
University of Texas Southwestern Medical Center at Dallas
Dallas, TX, USA
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SCOTT M. GRUNDY'S MOST CURRENT MOST-CITED PAPER IN ESSENTIAL SCIENCE INDICATORS:
Cleeman JI, et al., "Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)," JAMA-J. Am. Med. Assn. 285(19): 2486-97, 16 May 2001 with 9,066 cites. Source: Essential Science Indicators from Clarivate.
KEYWORDS: METABOLIC SYNDROME, DIABETES, PUBLIC HEALTH, OBESITY EPIDEMIC, RISK FACTORS, INSULIN RESISTANCE, CONSENSUS STATEMENTS, AMERICAN DIABETES ASSOCIATION, NATIONAL CHOLESTEROL EDUCATION PROGRAM, ADULT TREATMENT PANEL, NATIONAL INSTITUTES OF HEALTH, NATIONAL HEART LUNG AND BLOOD INSTITUTE, CHOLESTEROL, TRIGLYCERIDES, BLOOD PRESSURE, ADIPOSE TISSUE, METABOLISM, STATINS, ATHEROSCLEROSIS, LDL, INFLAMMATION, C-REACTIVE PROTEIN, LIFESTYLE CHANGES.
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