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111 | 2012
Annuaire du Collège de France 2010-2011
Résumé des cours et travaux 111e année
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Metabolic Syndrome as a Powerfulcardiovascular Risk Factor | Non-Invasive Imaging of Atherosclerosis

Lars Lind
p. 890-892

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Metabolic Syndrome as a Powerfulcardiovascular Risk Factor

1As far as we know, the Metabolic syndrome (MetS ) was first described in German in the 1920-ties. It was later redescribed by two groups in 1988. In 1998, the first uniform definition of the syndrome was given by WHO, but three years later the NECP/ATP III- committee suggested the definition that has been most commonly used in epidemiological research. By this definition, a subject with the MetS should show at least 3 out of maximal 5 disturbances in major cardiovascular risk factors, namely high blood pressure, diabetes/impaired glucose tolerance, hypertriglyceridemia, low HDL levels and abdominal obesity measured by waist circumference. According the NCEP criteria, 17% of middle-aged males in Sweden (the ULSAM study) showed the MetS in the early 70-ties. 20 years later, the prevalence of the MetS have rise to 22%. In another Swedish cohort, PIVUS, the prevalence at age 70 was 23%, a prevalence being higher in women then in men.

2When incidence of cardiovascular (CV) mortality was followed for 28 years in the ULSAM cohort, the NCEP definition of the MetS was more powerful as a risk factor that the WHO definition. When later the incidence of the most common CV disorders myocardial infarction, stroke and heart failure were followed for 33 years, the MetS at age 50 was associated with a two-fold increased risk of myocardial infarction and heart failure, but a significant increased risk of stroke.

3By MRI, abdominal obesity could the quantified subcutaneous and visceral fat mass.

4Both the amount of subcutaneous and visceral fat were related to the MetS, but while visceral fat mainly was related to glucose and triglycerides, the subcutaneous fat was mainly related to HDL and blood pressure. Also insulin resistance was closely related to the MetS, both when evaluated by the HOMA insulin resistance index, a marker of hepatic insulin resistance in the fasting state, or by the gold standard euglycemic hyperinsulinemic clamp technique. Insulin resistance was, like the MetS, found to be a major risk factor for future myocardial infarction and heart failure, but less so for stroke.

5An analysis of a number of environmental pollutants in the PIVUS study showed that many of those pollutants were increased in subjects with the MetS and in those who developed diabetes and abdominal obesity over the coming 5 years. Future animal studies are needed to confirm if environmental pollutants are drivers of the MetS.

Non-Invasive Imaging of Atherosclerosis

6In the past, luminography of a desired arterial segment had been the method of choice to evaluate atherosclerosis. This still commonly used in the setting of coronary angiography by which atherosclerosis is graded by the percent stenosis of the vessel.

7However, it has become more and more apparent that most atherosclerotic plaques by outward remodelling of the vessel wall grow without occluding the lumen and the fact that the plaques most prone to rupture and to form thrombosis, and thereby inducing myocardial infarction and stroke, are only causing a stenosis of some 30-50%. Furthermore, it has been shown that most of those “vulnerable” plaques contain a large lipid-rich necrotic core, a thin fibrous cap and a high degree of inflammation caused by infiltration of macrophages and other immuno-competent cells. Thus, imaging in the future has not only have to show the part of the plaque that is not occluding the artery and thereby not visible at luminography, but also have to be able to image the composition of the plaques, including the degree of inflammation.

8In the PIVUS study including 1016 subjects aged 70 from the general population of Uppsala, atherosclerotic plaques were found in one of the carotid arteries by ultrasound in about one-third of the population, while bilateral plaques were found in another third of the population. These plaques were generally quite small and only some 2-3% showed plaques being significantly blood flow limiting. The majority of these plaques were rather echolucent at visual inspection. When applying a digitalized technique to quantify the echogenecity in the plaques, the echogenecity was related to BMI, HDL, a marker of lipid oxidation and glutathion, a marker of ROS generation. When the echogenecity was measured also in the “normal” carotid artery wall, the intima-media complex, the echogenecity at this location was related to the same set of risk factors and was also related to the echogenecity in the overt plaques. Furthermore, when evaluated in another cohort, the ULSAM study of males aged 75 years, those with an echolucent intima-media complex showed an increased risk of CV death over 5 years follow-up compared to those belonging to the middle-tertile of echogenecity values.

9Coronary arteries could be evaluated non-invasively by CT angiography with contrast given intra-venously. This technique has a very high sensitivity to detect plaques compared to traditional angiography, but the specificity is somewhat lower due to the problems to assess the vessel being highly calcified. The amount of coronary calcium is predictive for future CV events and a high degree of correlation has been found between the radiographic intensity of the plaques and the echogenecity measured by ultrasound, suggesting that plaque characterization could be performed also by CT coronary angiography.

10MRI coronary angiography is not feasible to perform on arteries that move, like the coronary arteries, but could well be applied to the carotid arteries. By using several image sequences the content in the plaques could be quantified and the amount of lipids, haemorrhage and calcium in the plaques could be quantified. Furthermore, by analysing the uptake of Gd-contrast in the plaques a marker of inflammation has been described.

11Also positron emission tomography (PET) could but injection with labelled glucose quantified inflammation in plaques, and we are currently using a combination of MRI, PET and CT scanning in order to perform a comprehensive evaluation of carotid artery atherosclerotic plaques.

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Cours et travaux du Collège de France. Annuaire 111e année, Collège de France, Paris, avril 2012, p. 890-892. ISBN 978-2-7226-0156-7

Référence électronique

Lars Lind, « Metabolic Syndrome as a Powerfulcardiovascular Risk Factor | Non-Invasive Imaging of Atherosclerosis », L’annuaire du Collège de France [En ligne], 111 | 2012, mis en ligne le 22 novembre 2013, consulté le 24 avril 2018. URL :

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Lars Lind

Professeur à l’Université d’Uppsala (Suède)

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Droits d’auteur

Collège de France

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