Relation of inflammation to vascular function in patients with coronary heart disease

Abstract

Endothelium plays a pivotal role in the regulation of vascular relaxation. Inflammation may in turn induce endothelial dysfunction and thus increase the risk of atherothrombosis. We investigated 31 men with angiographically verified coronary heart disease, aged 57.7±5.3 years, in regard to endothelium-dependent, acetylcholine-induced, and to endothelium-independent, sodium nitroprusside-induced vasodilatation in the forearm vasculature by strain-gauge plethysmography. Logistic regression analysis served to determine the relation between forearm vascular function and the inflammatory factors measured, concentration of C-reactive protein, subtypes of peripheral blood T-lymphocytes, and other factors potentially affecting endothelial function (lipoprotein and glucose levels). Concentration of C-reactive protein was an independent determinant of endothelium-dependent vascular function (P<0.001 for low dose acetylcholine, P=0.01 for high dose acetylcholine). Other determinants of endothelium-dependent vascular dysfunction were CD8-lymphocytes expressing ICAM-1 (P=0.001), antibodies to oxidized low-density lipoprotein (P<0.001), and body weight (P=0.007). The present data showed an association between inflammatory risk factors linked to atherothrombosis and endothelial dysfunction in coronary heart disease patients. It is possible that endothelial dysfunction in coronary heart disease patients is related to the chronic inflammation or infection coexisting with atherosclerosis.

Introduction

Coronary heart disease (CHD) is considered to be an inflammatory disease [1]. Ongoing inflammation in the vessel wall accelerates progression of atherosclerosis and destabilizes plaques, the rupture of which causes atherothrombosis [2]. As evidence of this, several inflammatory factors have been linked to the progression of CHD [3], [4], [5], [6]. C-reactive protein (CRP) is a marker of systemic inflammation, and its concentration correlates with the presence and severity of coronary artery atherosclerosis and risk for acute cardiovascular events [3], [5], [7]. Circulating activated CD4 and CD8 lymphocytes are suggested to be involved in the inflammatory reaction during episodes of unstable angina [6]. Oxidation of low-density lipoprotein (LDL) occurs in the atherosclerotic plaque and induces generation of antibodies to oxidized LDL. The production of such antibodies may reflect the increased oxidative capacity in the vessel wall due to inflammation [8]. These antibodies have been linked to risk for myocardial infarction [9], [10].

Recently, infection and inflammation have been linked to endothelial dysfunction [11], [12], [13], a systemic manifestation occurring in all stages of atherosclerosis. It is even thought to initiate atherosclerosis [14]. Endothelial dysfunction causes blood-flow deterioration and vessel spasms and impairs thrombosis-resisting mechanisms. Therefore, inflammation in the vessel wall may cause not only plaque rupture, but also endothelial dysfunction, which in turn may exacerbate poor blood flow.

Experimental studies involving inflammation and endothelial function have been published, in our knowledge, only on healthy individuals [13]. In the present study we measured the relation between vascular function and inflammatory factors linked to atherothrombosis in patients with angiographically verified CHD.