Alterations in Biomarkers of Cardiovascular Disease in Active Acromegaly

L. Boero, M. Manavela; L. Gómez Rosso; C. Insua; V. Berardi; M. C. Fornari; F. Brites

Disclosures

Clin Endocrinol. 2009;70(1):88-95. 

In This Article

Abstract and Introduction

Abstract

Objectives: In acromegalic patients, cardiovascular and metabolic comorbidities contribute to enhance mortality. Available data on the lipoprotein profile of these patients are controversial. Our aim was to characterize the lipoprotein profile and emergent biomarkers of cardiovascular disease in active acromegalic patients in comparison with sex- and age-matched healthy controls.
Patients: Eighteen patients with active acromegaly and 18 controls were studied.
Measurements: Glucose levels, hormonal status, lipoprotein profile and C reactive protein (CRP) were evaluated by standardized methods. Cholesteryl ester transfer protein (CETP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured by radiometric techniques, endothelin-1 and vascular cell adhesion molecule (VCAM)-1 by enzyme-linked immunosorbent assay, and leucocytes CD18, CD49d and CD54 by flow cytometry.
Results: After adjusting for body mass index (BMI), acromegalic patients presented a more atherogenic lipoprotein profile, consisting of higher levels of triglycerides and apolipoprotein B and alterations in the ratios which estimate insulin resistance and atherogenic risk. CETP activity was significantly increased in acromegalic patients as compared to controls (168 ± 17 vs. 141 ± 30% per ml h, respectively; P < 0.05). Endothelin-1 levels evidenced an increase in the patients' group (0.9 ± 0.2 vs. 0.7 ± 0.2 ng/l, respectively; P < 0.01) and showed positive and significant correlations with GH, IGF-1 and IGFBP-3 (r = 0.45, 0.42 and 0.44, respectively; P < 0.01 for all of them; with BMI as a fixed variable). Lymphocytes from acromegalic patients showed increased CD49d content (282 ± 59 vs. 246 ± 48 arbitrary units, respectively; P < 0.05).
Conclusions: Taken together, the alterations described seem to contribute to constituting a state of higher propensity for the development of atherosclerotic cardiovascular disease, which adds to the presence of specific cardiomyopathy.

Introduction

In acromegalic patients, cardiovascular, respiratory and metabolic comorbidities contribute to significantly enhance mortality, which doubles the death rates in comparison with healthy population. In fact, average life expectancy in patients with active acromegaly is reduced by approximately 10 years.[1] Accordingly, the integrated evaluation of the atherogenic risk, analysed through the Framingham score, and the coronary artery calcium quantification has shown that 41% of acromegalic patients have an increased risk of coronary atherosclerosis, which is not influenced by the control of acromegaly.[2]

The systemic complications observed in relation to acromegaly seem to be linked to permanently elevated GH and IGF-I levels.[3] The harmful effect of GH and IGF-I excess on cardiac structure and function has been widely demonstrated by in vivo and in vitro studies.[4] Nevertheless, the poor prognosis of acromegalic patients could be not only attributed to the presence of specific cardiomyopathy,[5] but also to atherosclerotic cardiovascular disease. Actually, this high cardiovascular risk could be attributed to the increased incidence of diabetes mellitus, hypertension and lipid disorders in acromegalic patients.

Although several studies agree on reporting the presence of an abnormal lipid and lipoprotein profile in acromegalic patients, controversial data arise when trying to identify the modified specific lipid parameters or when analysing the extent of those alterations. Accordingly, plasma triglyceride and total cholesterol levels have been found to be unchanged[6,7] or increased,[8] and high density lipoprotein-cholesterol (HDL-C) and apolipoprotein (apo) A-I either unchanged[7,9] or low.[10,11]

Regarding emergent biomarkers of cardiovascular disease, most studies have shown elevated lipoprotein (Lp) (a),[9,12] small and dense low density lipoprotein (LDL) particles,[7,11] and fibrinogen[13] in acromegaly. In contrast, Sesmilo et al.[14] showed reduced C reactive protein (CRP) and unchanged homocysteine levels. To our knowledge, no studies have been carried out to evaluate other atherogenic or inflammatory markers such as lipoprotein-associated phospholipase A2 (Lp-PLA2), endothelin-1, and soluble or leucocyte cell adhesion molecules in acromegalic patients in comparison to healthy controls.

The aim of the present study was to further characterize lipid, lipoprotein and apolipoprotein profile, and emergent biomarkers of cardiovascular disease, such as CRP, Lp-PLA2, endothelin-1, vascular cell adhesion molecule-1 (VCAM-1) and leucocyte CD18, CD49d and CD54, in acromegalic patients in comparison with sex- and age-matched healthy controls.

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