Angiopoietin‐like protein 2 and mortality in patients with heart failure—Results from an observational study

BACKGROUND: Heart failure is an advanced form of cardiovascular disease with a high mortality rate. Management of the condition is possible and blood-based biomarkers could help identify the most vulnerable patients. There is mounting evidence of a link between angiopoietin-like protein 2 (ANGPTL2), a secreted glycoprotein involved in inflammation and tissue remodelling, and heart failure. However, no prospective studies have examined whether ANGPTL2 predicts mortality in heart failure, which this study aims to address. METHODS: Mortality was prospectively recorded in a cohort of 303 patients with heart failure over a period of 5 years. Serum ANGPTL2 levels were determined at baseline by means of enzyme-linked immunosorbent assay. RESULTS: At baseline, elevated ANGPTL2 levels were highly significantly associated with increased concentrations of total, LDL- and HDL-cholesterol and with a lower prevalence of male sex, smoking history, cardiovascular disease and statin use. During the five-year follow-up period, 47% of all patients died. When patients were stratified into tertiles based on ANGPTL2 levels, those in the highest tertile exhibited a significantly increased risk of all-cause mortality compared to those in the lowest tertile (hazard ratio = 1.88 [1.23-2.88]; p = .004). After adjustment for potential confounders, including NT-proBNP, the association remained significant, with an adjusted hazard ratio of 1.91 [1.13-3.23]; p = .015. In addition, the inclusion of ANGPTL2 improved the predictive accuracy of a model based on traditional risk factors, as indicated by a significant 24.3% net reclassification improvement. CONCLUSION: Circulating ANGPTL2 is a significant predictor of mortality in patients with heart failure.