The presence of abdominal obesity is associated with changes in vascular function independently of other cardiovascular risk factors
Introduction
A growing body of evidence suggests that abdominal obesity (AO) might play a key role in the development of cardiovascular events [1], [2], [3], [4]. The clinical relevance of AO has reached such importance in the evaluation of cardiovascular risk that it has been postulated by the International Diabetes Federation as a primary criterion for the diagnosis of metabolic syndrome [5]. However, the acceptance of this anthropometric parameter as an independent and valuable element for the evaluation of cardiovascular risk is still polemic. Some authors argue that there is no rationale to consider AO a protagonist in the development of the cardiovascular diseases, and that insulin resistance is the key culprit, increasing the risk of developing cardiovascular diseases (CVD) in subjects with this condition in addition to traditional risk factors [6], [7]. On the other hand, there is an extensive body of epidemiological evidence showing that AO is an independent risk factor for the development of CVD [8], [9]. In addition, clinical studies have demonstrated that subjects with increased waist circumference (WC) but without insulin resistance are still at a higher risk of developing cardiovascular events [10], [11], which suggest that there could be other factors, beyond insulin resistance, linking AO and the development of CVD.
Interestingly, and despite this controversy, there are no studies in humans designed to assess the changes in vascular function that are associated with the presence of AO independently of other cardiovascular risk factors. This could be due to the methodological challenges implicit in any study of this condition, in particular, the fact that AO is strongly associated with other cardiovascular risk factors such as hypertension, impaired glucose metabolism and dyslipidemia [12]. Moreover, all these co-morbidities share many common pathophysiological pathways related to the development of endothelial dysfunction and atherosclerosis [3], which confers more complexity to the study of the independent role of each one of these risk factors in the natural history of the CVD.
In order to identify changes in vascular function associated with the presence of AO, the aim of the present study was to evaluate whether the presence of this condition is related to changes in ex-vivo endothelial function and vascular reactivity of internal mammary arteries (IMA) segments, insulin resistance, and plasma levels of adipokines and inflammatory agents in patients who underwent coronary artery bypass graft (CABG). To avoid possible interferences, the results were analyzed by controlling for the presence of other cardiovascular risk factors using a multivariable matching technique.
Section snippets
Methods
Despite being not as specific as other imaging systems for the evaluation of the intra-abdominal adiposity, the measurement of the WC is currently the most widely used parameter to evaluate the presence of AO in a clinical scenario [13]. The presence of AO was defined according to the recommendations of the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute for Latin-American population [5], [14], as the presence of increased waist
Materials
Stock solutions and Krebs were prepared with distilled and deionized water provided by Baxter® laboratory. All products for the Krebs preparation, PE, ACh and Ang II were purchased from SIGMA® Chemicals USA. SNP was provided by ECAR® laboratory.
Clinical and biochemical characteristics
Around 30% of the subjects with severe coronary disease had no history of angina (stable or unstable). In all these patients a coronary angiography was indicated as part of the study of unspecific symptoms such as dyspnoea, acute arrhythmia and syncope. However, the proportion of patients with this condition were comparable between the groups (28% in + AO vs. 34% in − AO, p = 0.41).
As shown in Table 1, there were no significant differences in any of the biochemical or metabolic variables evaluated
Discussion
To our knowledge, this is the first study evaluating, ex-vivo, the changes in the vascular reactivity related to the presence of AO using a human model in which most of the known cardiovascular risk factors were controlled by matching the subjects. The main findings of the present study were that, independently of factors such as age, gender, glucose and insulin plasma levels, HOMA index, lipid profile, tobacco and alcohol consumption, plasma levels of inflammatory markers, physical activity
Funding
This study received funding from Fundación Cardiovascular de Colombia (FCV), Comisión Interministerial de Ciencia y Tecnología de España (SAF2007-61595), Fondo de Investigaciones Sanitarias (FIS PI 060133) and Red Cardiovascular del Fondo de Investigaciones Sanitarias (RD06/0014/0007). C. Rueda-Clausen was supported by a grant from Sociedad Española de Hipertensión - Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA).
Acknowledgments
The authors wish to thank Dr. Jude Morton for style correction and Sandra Ballesteros for her technical support. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [41].
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