The presence of abdominal obesity is associated with changes in vascular function independently of other cardiovascular risk factors

https://doi.org/10.1016/j.ijcard.2008.09.005Get rights and content

Abstract

Background

Because of the strong association between abdominal obesity (AO) and other cardiovascular risk factors, it has been difficult to determine which changes in vascular function are directly related to this condition. Our objective was to evaluate the changes in ex-vivo vascular reactivity, circulating levels of adipokines and inflammatory markers associated with the presence of AO in subjects who underwent coronary artery bypass graft (CABG) controlling by the presence of other cardiovascular risk factors.

Methods

Subjects scheduled for a CABG with (n = 17) and without (n = 17) AO (defined as a waist circumference ≥ 90 cm for male or ≥ 80 cm for female) whom were matched by several cardiovascular risk factors, were included in the study. Lipid profile and plasma levels of glucose, insulin, leptin, adiponectin and inflammatory markers were measured. Internal mammary artery segments were used for ex-vivo vascular reactivity experiments and morphometry.

Results

Leptin concentrations were higher and adiponectin concentrations were lower in subjects with AO. No differences were observed in other biochemical or clinical parameters between the groups. No correlation between waist circumference, HOMA index and inflammatory markers were observed. Endothelium-dependent relaxation to acetylcholine was lower, and contractile responses to angiotensin-II were higher in subjects with AO. These changes were not related to differences in vascular morphometry.

Conclusion

In subjects with severe coronary disease, the presence of AO was associated with leptin/adiponectin imbalance, decreased endothelium-dependent relaxation and an enhanced response to angiotensin-II. These changes occurred independently of other cardiovascular risk factors including insulin resistance and levels of inflammatory markers.

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].

References (41)

  • U. Campia et al.

    Role of cyclooxygenase products in the regulation of vascular tone and in the endothelial vasodilator function of normal, hypertensive and hypercholesterolemic humans

    Am J Cardiol

    (2002)
  • A.J. Coats

    Ethical authorship and publishing

    Int J Cardiol

    (2009)
  • M.R. Meyers et al.

    Endothelial dysfunction in obesity: etiological role in atherosclerosis

    Curr Opin Endocrinol Diabetes Obes

    (2007)
  • P. Poirier et al.

    Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss

    Arterioscler Thromb Vasc Biol

    (2006)
  • R. Scaglione et al.

    Obesity and cardiovascular risk: the new public health problem of worldwide proportions

    Expert Rev Cardiovasc Ther

    (2004)
  • International Diabetes Federation

    The IDF consensus worldwide definition of the metabolic syndrome [article online]

    (2005)
  • R. Kahn et al.

    American Diabetes Association; European Association for the Study of Diabetes. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes

    Diabetes Care

    (2005)
  • G.M. Reaven

    The metabolic syndrome: is this diagnosis necessary?

    Am J Clin Nutr

    (2006)
  • J.P. Despres

    Health consequences of visceral obesity

    Ann Med

    (2001)
  • J.P. Despres et al.

    Abdominal obesity and metabolic syndrome

    Nature

    (2006)
  • Cited by (0)

    1

    Current address: 232 HMRC, University of Alberta, Edmonton AB., Canada T6G 2S2.

    View full text