Elsevier

Atherosclerosis

Volume 188, Issue 1, September 2006, Pages 142-149
Atherosclerosis

Inverse correlation between coronary blood flow velocity and sICAM-1 level observed in ischemic heart disease patients

https://doi.org/10.1016/j.atherosclerosis.2005.10.011Get rights and content

Abstract

Systemic factors and blood flow velocity related to atherosclerosis have been examined mainly separately or by in vitro studies. The aim of our study was to investigate the association between local coronary blood flow (corrected TIMI frame count, CTFC) and systemic atherosclerosis-related inflammatory parameters such as soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (Il-6), high sensitivity C-reactive protein (hsCRP) and von Willebrand factor (vWF) in humans. We enrolled the following groups of ischemic heart disease (IHD) patients: patients with coronary stenosis and stable (CAD, n = 96) or unstable angina (ACS, n = 27), patients with documented myocardial ischemia and normal coronary angiogram (NEG, n = 68). Patient groups showed only marginal differences in CTFC or sICAM-1 levels. In contrast, when IHD patients were studied individually, general positive correlation was found between CTFC and sICAM-1 level (r = 0.33; in NEG r = 0.25; in CAD r = 0.37; in ACS r = 0.61), being the strongest in ACS. The relation was independent from age, gender, BMI, smoking, hypertension, diabetes, previous myocardial infarction, family history of IHD, medication, hsCRP, IL-6 and vWF levels. (odds ratio, OR = 6.4; CI 95%: 2.43–16.84; p < 0.05). Nevertheless, correlation between CTFC and IL-6, hsCRP, vWF levels was not found.

These results indicate inverse correlation between coronary blood flow and adhesion molecule production independently from conventional cardiovascular risk factors and inflammatory markers.

Introduction

Atherosclerosis is a chronic inflammatory process, in which several acute phase reactants, cytokines and cellular adhesion molecules are implicated [1], [2]. In addition to these systemic factors, local mechanical forces (blood flow, shear stress) may also play important role in determining the rate of atherosclerosis progression [3]. In human coronary arteries, atherosclerotic plaques are found where the local flow is disturbed. Continuous relation between low shear stress and increased rate of luminal narrowing was observed [3], [4]. The possible link between local hemodynamic changes and systemic inflammatory processes is proven by in vitro studies. Recently, mechanical forces have been identified as regulators of gene expression in endothelial cells; sustained shear stress downregulates atherogenic and upregulates growth-arrest genes [1], [5], [6]. Despite intensive studies about possible impact of coronary flow and systemic factors on atherosclerosis in vitro and in animal models, the interaction between coronary blood flow and serum marker production in humans has been rarely described [5], [7], [8].

We examined whether there was a correlation between coronary blood flow as a local mechanical factor and inflammatory serum markers as indicators of systemic atherosclerotic process in patients with different forms of ischemic heart disease (IHD).

Global corrected TIMI frame count (CTFC) defined as a mean CTFC of three main coronaries was used to describe global coronary blood flow [9]. Among measured inflammatory markers, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and von Willebrand factor (vWF) are indicated as independent risk factors in a variety of IHD, especially in unstable coronary syndrome [10], [11]. Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein expressed by mainly endothelial cells and leukocytes; plasma concentration of its soluble form was found to be associated with subsequent incidence of chronic ischemic heart disease [12], [13], [14], [15]. Moreover, blood flow can be a potential determinant of the plasma concentration of soluble intercellular adhesion molecule-1 [16]. Accumulating evidence suggests that all of the above mentioned proteins are not simply markers, but also contribute directly to the inflammatory process [1], [8], [17], [18]. We hypothesized that possible correlation between blood flow and inflammatory molecule production might suggest a relationship with pathophysiological importance.

Based on analysis of the above mentioned parameters in different ischemic heart disease patient groups, significant positive correlation was found between CTFC and sICAM-1 levels. Our finding emphasizes a general relationship between local coronary blood flow and systemic sICAM-1 production independently from such factors as gender, age, BMI, hypertension, diabetes mellitus, smoking, previous myocardial infarction, family history of IHD, medication, hsCRP, IL-6 and vWF levels.

Section snippets

Patients and study groups

We recruited 191 cardiovascular patients with angina pectoris undergoing coronary angiography at our institution consecutively. All of them had typical chest pain and 93% had evidence of resting or provoked myocardial ischemia (Table 1). Patients with coexisting diseases, such as malignancies, autoimmune diseases or current infections, were excluded. Three patient subgroups were formed: (i) patients with documented myocardial ischemia and no detectable coronary stenosis with normal coronary

Baseline characteristics

Baseline clinical and biological profiles of the subjects, medication on admission and the results of non-invasive ischemia provocation tests in the study population are shown in Table 1.

There were no significant differences among the three groups in their baseline values in terms of BMI, lipid parameters (serum cholesterol, HDL, LDL, triglycerides), ejection fraction measured by echocardiography and family history of cardiovascular disease. The incidence of conventional risk factors such as

Discussion

Regarding the pathomechanism of IHD, previous studies have largely focused on the association between atherosclerosis and inflammation or atherosclerosis and local blood flow separately. The relationship between systemic (inflammatory) factors and local blood flow in humans has been rarely investigated. In our study, correlation was found between CTFC and sICAM-1 plasma level in IHD patient population, and the relation is independent from age, gender, BMI, smoking, hypertension, diabetes,

Acknowledgements

The study was supported by research grants from the Hungarian Science Foundation (OTKA T042605 and KO-2709/2003), from the Hungarian Ministry of Health (ETT 086/2003, ETT 583/2003) and from the Hungarian Ministry of Education (NKFP 1/044/2001). ETZ is a recepient of the “Bolyai” Scholarship Grant of the Hungarian Academy of Sciences. We are indebted to E. Csoti and E. Fischer for the expert technical assistance. We thank M. Pribliczky MD for her contribution in the enrollment of healthy blood

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    The first two authors contributed equally to this work.

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