ST2 may not be a useful predictor for incident cardiovascular events, heart failure and mortality

OBJECTIVES: We hypothesised that soluble ST2 (sST2) levels can identify people with elevated risk of subsequent cardiovascular disease (CVD) and add to existing risk prediction algorithms.

BACKGROUND: ST2 is a receptor for the inflammatory cytokine IL33. Increased sST2 levels have been associated with heart failure and death in acute myocardial infarction patients and in the general population.

METHODS: We measured high-sensitivity sST2 in 8444 men and women (25-74 years) from the FINRISK97 prospective population cohort. Cox proportional hazards modelling evaluated the ability of sST2 to predict fatal and non-fatal heart failure, CVD (coronary heart disease, stroke), diabetes, and death over 15 years follow-up. Discrimination and reclassification statistics for 10-year absolute risks compared the ability of sST2 to improve upon Framingham risk factors (FRF), N-terminal pro-brain natriuretic peptide (NT-proBNP), renal function (eGFR) and prevalent valvular heart disease (VHD).

RESULTS: sST2 showed suggestive but non-significant associations with heart failure {(HR per 1 SD of log sST2 1.06; 95% CI 0.96 to 1.17 (562 events))}, and with CVD (1.01 95% CI 0.94 to 1.08) (914 events) after adjustment for FRF, NT-proBNP, eGFR and VHD. sST2 significantly predicted death from all causes following similar adjustment ({HR 1.09 (95% CI 1.01 to 1.19) (974 events))}. No improvement in the c-index was observed for models adding sST2 to the risk factors.

CONCLUSIONS: In a healthy general population from Finland, sST2 did not improve long-term prediction of cardiovascular events including heart failure or all-cause mortality.