Abstract
ObjectivesWe hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1), a stable endothelin-1 precursor fragment, is of prognostic value in patients with chronic heart failure (CHF), beyond other prognosticators, including N-terminal pro-B-type natriuretic peptide (NT-proBNP).MethodsWe examined 491 patients with systolic CHF (age: 63±11 years, 91% men, New York Heart Association [NYHA] class [I/II/III/IV]: 9%/45%/38%/8%, 69% ischemic etiology). Plasma CT-proET-1 was detected using a chemiluminescence immunoassay.ResultsIncreasing CT-proET-1 was a predictor of increased cardiovascular mortality at 12-months of follow-up (standardized hazard ratio 1.42, 95% confidence interval [CI] 1.04–1.95, p = 0.03) after adjusting for NT-proBNP, left ventricular ejection fraction (LVEF), age, creatinine, NYHA class. In receiver operating characteristic curve analysis, areas under curve for 12-month follow-up were similar for CT-proET-1 and NT-proBNP (p = 0.40). Both NT-proBNP and CT-proET-1 added prognostic value to a base model that included LVEF, age, creatinine, and NYHA class. Adding CT-proET-1 to the base model had stronger prognostic power (p<0.01) than adding NT-proBNP (p<0.01). Adding CT-proET-1 to NT-proBNP in this model yielded further prognostic information (p = 0.02).ConclusionsPlasma CT-proET-1 constitutes a novel predictor of increased 12-month cardiovascular mortality in patients with CHF. High CT-proET-1 together with high NT-proBNP enable to identify patients with CHF and particularly unfavourable outcomes.
Highlights
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide secreted mainly by endothelial cells [1,2]
Over the last several years, circulating natriuretic peptides have become widely accepted as diagnostic and prognostic measures in all stages of chronic heart failure (CHF) [5,6], and other complementary neurohumoral markers are intensively studied in this field [7,8]
Median levels of plasma CT-proET-1 increased with increasing New York Heart Association (NYHA) class (Figure 1)
Summary
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide secreted mainly by endothelial cells [1,2] It is produced by other cells associated with cardiovascular homeostasis such as smooth muscle cells, cardiomyocytes, and macrophages [1,2]. It is presumed that the assessment of circulating ET-1 might represent a marker of disease progression and prognosis in patients with CHF [3,4]. This issue is of a particular clinical importance, as the prognostic evaluation in this group of patients still remains a challenge. Over the last several years, circulating natriuretic peptides have become widely accepted as diagnostic and prognostic measures in all stages of CHF [5,6], and other complementary neurohumoral markers are intensively studied in this field [7,8]
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