Jean-Pierre Després, PhD

Disclosures

October 08, 2015

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Size Doesn't Matter, Location Does

My name is Jean-Pierre Després. I am the director of research at the Quebec Heart and Lung Institute in Quebec City, and I am hospital-affiliated with the University of Laval in Quebec, Canada.

Today at the European Society of Cardiology session dealing with the risk of obesity,[1] I would emphasize the notion that such risk is not related to size but rather where the excess fat is located. I'll make the point that, particularly in males, we see an accumulation of fat in the abdominal cavity, a condition that we call visceral obesity, which is a high-risk form of obesity. In women, lower body fat associated with fat accumulation around the thighs and hips is actually protective against cardiovascular complications.

Indeed, more than 25 years ago, we began using CT to scan the abdomen of asymptomatic volunteers.[2] We came to the conclusion, after looking at those abdominal images, that there was a remarkable individual variation in the susceptibility to put on fat in the abdominal cavity around the internal organs, a condition that we have described as visceral fat accumulation. In perfectly matched individuals who had the same weight, same body mass index (BMI), and the same amount of total body fat, we found some individuals who had a lot of intra-abdominal visceral adipose tissue. We documented that those individuals were characterized by what I call a minestrone soup of atherogenic thrombotic inflammatory abnormalities. Some individuals have referred to this condition as insulin resistance syndrome or metabolic syndrome. The atherogenic dyslipidemia, insulin resistance, or inflammatory state that we found to be closely associated with excess visceral fat are clearly metabolic environments that increase the risk of developing type 2 diabetes and cardiovascular disease.

Why Is Abdominal Fat More Dangerous?

Since then, we have been interested in genetic and environmental factors associated with the selective deposition of fat in the abdominal cavity. Now we have a better understanding of why those individuals with excess visceral fat are at an increased risk for cardiovascular outcomes.

It has been suggested that when you have excess intra-abdominal or visceral adipose tissue, it is your subcutaneous fat that is not able to properly expand to a multiplication of subcutaneous fat cells—a process called hyperplasia of subcutaneous adipose tissue. Among individuals who are in a positive energy balance—they eat more than they spend—some get hyperplasia of subcutaneous adipose tissue, and this expanding subcutaneous adipose tissue can act as a protective metabolic sink (protecting the lean organs, the heart, the liver, the kidneys, and the skeletal muscles) against accumulation of dangerous lipids. This is a condition that has been referred to as ectopic fat accumulation or accumulation of fat in lean tissue.

However, if you're among those who cannot expand subcutaneous adipose tissue to hyperplasia, you get a lipid spillover. The excess energy has to be stored somewhere. It is deposited around the heart as epipericardial fat, in the liver and leading to liver steatosis, and infiltrates the skeletal muscles, a little bit like the Kobe steak. Therefore, this leads to substantial deterioration of the risk-factor profile (Figure).

Figure. Adipose tissue hyperplasia vs hypertrophy. Adapted from Després JP. Can J Cardiol. 2012;28:642-652.

Clearly, therefore, what you don't see is the most dangerous form of fat. There is a plethora of imaging studies that have confirmed those early observations. It is clear that when you have too much intra-abdominal visceral adipose tissue, you're more likely to have more fat around the heart, what we call epipericardial fat. You're more likely to have a fatty liver, which will lead to a substantial increase in the risk of developing atherogenic dyslipidemia, type 2 diabetes, and so on. And your fat is infiltrated in your muscles and even in your kidneys, contributing to further exacerbating your risk for hypertension.

So the key take-home message is that there is an enemy within. It's not the fat that you can see subcutaneously that causes major prejudice to cardiovascular health. It is all the fat that is accumulating in the abdominal cavity and in the lean tissue.

How Should We Manage Those Patients?

What are the clinical implications of these notions? Twenty years ago, we suggested that on top of measuring weight, measuring height, and calculating BMI, clinicians should measure waist circumference as a vital sign. Evidence has been shown over the years that, for a given BMI, individuals who have an expanded waistline are more likely to have harmful abdominal visceral fat.[3]

Another key metric that predicts cardiovascular outcomes that we should measure in overweight and obese patients is cardiorespiratory fitness. Many studies have shown that for a given body weight, those who have proper cardiorespiratory fitness are characterized by a major reduction in the risk of developing cardiovascular outcomes.

Therefore, 2 opportunities are missed in clinical practice:

  • Paying attention to detect those who are more likely to have dangerous abdominal fat; and

  • Detecting poorly fit individuals in whom the risk for cardiovascular disease will be markedly increased.

In terms of managing these patients by lifestyle, there is recent evidence from the wonderful PREDIMED study[4] that has shown that just improving nutritional quality by providing olive oil, nuts, and almonds to patients can reduce the risk for cardiovascular disease by 30%. In addition, for a given level of abdominal fat, those who reported being physically active were characterized by a 50% reduction in the risk of developing coronary disease. These prospective data are clearly addressing the whole debate about whether physical activity is useless for weight loss in obese patients. Actually, physical activity is extremely helpful for high-risk obese patients to reduce the risk for coronary heart disease even in the absence of body weight loss.

Therefore, measuring and targeting nutritional quality, measuring and targeting sedentary behaviors, measuring waist circumference, and measuring fitness are wonderful opportunities for clinicians to refine their assessment of the risk for cardiovascular disease and maximize their ability to optimize cardiovascular disease risk reduction in these patients.

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