Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation

Abstract

Soluble urokinase plasminogen activator receptor (suPAR) in plasma is a novel inflammatory marker thought to be released from the cell surface of neutrophils, T cells, and macrophages. Other inflammatory markers, mainly acute phase proteins produced in the liver, have been associated with the incidence of heart failure (HF) and atrial fibrillation (AF). We investigated the association between suPAR and incident HF and AF in a population-based cohort. Soluble urokinase plasminogen activator receptor was measured in 4530 subjects (aged 46–68 years, 61% women), who participated in the Malmö Diet and Cancer study during 1991–1996. Incident cases of HF and AF were identified from the Swedish hospital discharge register during a median follow-up of 16.3 years. During follow-up, 109 subjects (55% men) were diagnosed with new-onset HF and 321 individuals (50% men) with AF. suPAR was significantly associated with increased plasma levels of NT-proBNP (P<0.001). suPAR was significantly associated with incidence of HF [hazard ratio (HR) for the third vs. first tertile 3.33, 95% confidence interval (CI) 1.91–5.81 after adjustment for age and sex; and HR 1.82, 95% CI 1.02–3.27, P for trend 0.018 after adjustment for conventional risk factors and biomarkers]. suPAR was significantly associated with incidence of AF, when adjusted for age and sex (HR 1.40, 95% CI 1.06–1.85). However, this relationship was non-significant after adjustment for conventional risk factors and biomarkers. Soluble urokinase plasminogen activator receptor was associated with increased plasma levels of NT-proBNP and incidence of HF, but not with AF among middle-aged subjects.