Vascular endothelial growth factor and soluble P-selectin in acute and chronic congestive heart failure

Abstract

Because congestive heart failure (CHF) is characterized clinically by tissue hypoxia, we hypothesized that there would be evidence of neovascularization, possibly resulting from this process. To test this, we measured levels of vascular endothelial growth factor (VEGF), associated with angiogenesis, in the plasma of patients with varying degrees of CHF (presenting acutely and in the chronic phase) and compared levels with those in healthy controls. To test the hypothesis of a link between VEGF and platelet activation and a tendency to hypercoagulability in CHF, 1,2 we also measured plasma levels of fibrinogen and soluble P-selectin, because these markers of coagulation and platelet activation have previously been shown to increase in patients with chronic CHF. 2 Our methods to testing these hypotheses were cross sectional (comparing patients with acute and chronic CHF with healthy controls), interventional (examining markers before and after successful treatment of acute CHF), and using a follow-up approach (at which time we questioned whether or not plasma markers could predict those at risk of mortality). ••• We recruited consecutive patients admitted with acute CHF secondary to impaired left ventricular systolic function, which was documented as an ejection fraction 40%, either by echocardiography, radionuclide imaging, or left ventriculography on admission, or within the previous 6 months. Patients were excluded from the study for the following criteria: concomitant acute coronary syndromes; infection or pyrexial illness; recent (3 months) myocardial infarction or stroke; unstable angina or ventricular arrhythmias; chronic and systemic illnesses including renal failure, hepatic impairment, cancer, and inflammatory connective tissue disease; and use of oral steroids or hormone replacement therapy. Baseline results from patients with acute CHF (i.e., subjects presenting acutely with severe symptomatic disease) were compared with 2 age- and gender-matched control groups; these were outpatients with chronic stable CHF in sinus rhythm (chronic CHF) and healthy control subjects recruited from among healthy hospital staff and from subjects attending the hospital for hernia repairs, varicose vein procedures, or other relatively minor operations. Subjects with CHF were classified according to the New York Heart Association (NYHA) criteria, with class I to II being no or mild symptoms and class III to IV being moderate to severe symptoms. Left ventricular ejection fraction was estimated using transthoracic M-mode echocardiography. All healthy controls had no clinical evidence of vascular, metabolic, neoplastic, diabetic, or in flammatory disease on careful history, examination, and routine laboratory tests. Blood tests were performed in patients with acute decompensated CHF between days 1 and 7 after hospital admission, and again at 3 months after standard treatment for heart failure according to local guidelines. 3 Patients were followed up for clinical end points that consisted of all-cause mortality and hospitalizations for stroke, myocardial infarction, thromboembolism, unstable angina, and revascularization for up to 6 months. Citrated plasma and serum were obtained from