Intima-media thickness in severe obesity: links with BMI and metabolic status but not with systemic or adipose tissue inflammation

Abstract

Objective: Obesity is associated with cardiovascular risk and a low-grade inflammatory state in both blood and adipose tissue (AT). Whether inflammation contributes to vascular alteration remains an open question. To test this hypothesis, we measured arterial intima-media thickness (IMT), which reflects subclinical atherosclerosis, in severely obese subjects and explored associations with systemic inflammation and AT inflammation.

Research design and methods: IMT of the carotid artery (C-IMT) and IMT of the femoral artery (F-IMT) were measured in 132 nonobese (control) subjects (BMI 22.3 kg/m2; mean age 44.8 years) and 232 subjects who were severely obese without diabetes (OB/ND; n = 146; BMI 48.3 kg/m2; age 38.2 years) or severely obese with type 2 diabetes (OB/D; n = 86; BMI 47.0; age 49.4 years). In 57 OB/ND subjects, circulating soluble E-selectin, matrix metalloproteinase 9, myeloperoxidase, soluble intracellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, tissue plasminogen activator inhibitor 1, cystatin C, cathepsin S, and soluble CD14 were measured in serum. AT macrophages were quantified by CD68 immunochemistry.

Results: Both C-IMT and F-IMT increased in OB/ND and OB/D patients. In OB/ND patients, age was the sole independent determinant of IMT. No significant association was found with circulating inflammation-related molecules, number of CD68+ cells, or the presence of crown-like structures in visceral or subcutaneous AT of OB/ND patients.

Conclusions: IMT increased with severe obesity but was not influenced by the degree of systemic inflammation or AT macrophage accumulation.

Figure 1

C-IMT (A, C) and F-IMT (B, D) of nonobese (control [C]), OB/ND (OB), and OB/D subjects. A and B: Subjects were classified according to sex, obesity, and diabetes status (striped bars), as indicated. The numbers of subjects in each group are given in Table 1. Comparisons between groups were performed using a Wilcoxon rank-sum test adjusted for age. *P < 0.05 vs. controls of the same sex; &P < 0.05 vs. OB/ND of the same sex. C and D: Nonobese (control) and OB/ND subjects were ranked according to increasing numbers of CV-RFs. OB/D patients were not included in this analysis. The number of subjects is indicated at the bottom of each bar. The mean age and numbers of CV-RFs are shown below the bars. Comparisons between the groups were performed using Tukey test for post hoc comparisons. x-axis dash: no subjects in this category. *P < 0.05 vs. the same sex control and with the same number of CV-RFs. Data are expressed as mean ± SEM. F, female; M, male.

Figure 2

Prevalence of CV-RFs in nonobese (control [C]) and OB/ND (OB) subjects. Data show the percentage of individuals with the indicated risk factors. The number of subjects in each group is given in Table 1. Comparisons between the groups were performed by Fisher exact test. CV-RFs were defined as described in Research Design and Methods. *P < 0.05 vs. controls of the same sex. F, female; FH, family history; HTA, arterial hypertension; M, male.

Figure 3

No relationship between IMT and systemic inflammation or AT inflammation in obese subjects. A: C-IMT (○) and F-IMT (●) values related to systemic inflammation in 57 subjects who were representative of the whole OB/ND group. The index, expressed in arbitrary units (AU), is defined as the geometric mean of circulating concentrations of hsCRP, IL-6, sE-selectin, MMP-9, MPO, sICAM-1, sVCAM-1, tPAI-1, cathepsin S, cystatin C, and sCD14. B: C-IMT and F-IMT values in obese subjects with or without CD68⁺ cells in CLS in visceral and subcutaneous white AT (WAT). CLS⁺ in visceral AT: n = 21; CLS⁺ in subcutaneous AT: n = 43. C and D: C-IMT (○) and F-IMT (●) values related to the amount of CD68⁺ cells in visceral (A) or subcutaneous (B) AT. In A, C, and D, the nonparametric Spearman rank correlation ρ and P values are indicated for an association with C-IMT or F-IMT. Scut, subcutaneous; Vis, visceral.