High Ischemia-Modified Albumin Concentration Reflects Oxidative Stress But Not Myocardial Involvement in Systemic Sclerosis

Abstract

Systemic sclerosis (SSc) is a connective tissue disease characterized by widespread vascular lesions and fibrosis of the skin and internal organs. In SSc, vasospasm causes frequent episodes of reperfusion injury and free-radical-mediated endothelial disruption. Primary myocardial involvement is far more common than initially suspected on clinical grounds (1)(2)(3)(4)(5) and affects survival rates because it is associated with a poor prognosis (6)(7). Myocardial fibrosis is thought to occur secondarily to repeated focal ischemia in the coronary microcirculation as a result of abnormal vasoreactivity, with or without associated structural vascular disease (4)(5). The early and accurate identification of cardiac involvement is therefore of paramount clinical importance. The concentration of ischemia-modified albumin (IMA), as measured by the albumin cobalt binding test (Ischemia Technologies, Inc.), is a new marker to rule out transient myocardial ischemia (8)(9). This test measures the binding of exogenous cobalt to the NH2 terminus of human albumin. In the presence of myocardial ischemia, structural changes occur in the NH2 terminus of albumin, rapidly reducing its capacity to bind transition metal ions after an ischemic event (10). We assessed the accuracy of the albumin cobalt binding test for detecting ischemia in SSc patients and investigated the roles of myocardial ischemia and peripheral oxidative stress in this condition. We also considered carbonyl residues and advanced oxidation protein products (AOPP) as factors indicative of protein oxidation. We included consecutive patients hospitalized for systematic follow-up who fulfilled the American Rheumatism Association preliminary criteria for SSc. The exclusion criteria were pregnancy; symptoms of heart failure, including class III or IV dyspnea (New York Heart Association); venous distension and recent major lower limb edema; pulmonary arterial hypertension (systolic arterial pressure >40 mmHg and/or mean artery pressure >25 mmHg, determined …