Soluble ST2 Is Associated with All-Cause and Cardiovascular Mortality in a Population-Based Cohort: The Dallas Heart Study

BACKGROUND: ST2, part of the interleukin-1 receptor family, is released from cardiac myocytes under mechanical strain. Soluble ST2 (sST2) concentrations are associated with adverse cardiac events in high-risk cohorts. We evaluated the association of sST2 with all-cause and cardiovascular mortality in a large, low-risk population-based cohort. METHODS: Plasma sST2 was measured in 3294 subjects from the Dallas Heart Study, a probability-based population cohort. We categorized participants into undetectable (reference group) or quartiles of detectable sST2 concentrations. Associations with all-cause and cardiovascular mortality were assessed over a median 8.3 years of follow-up. RESULTS: sST2 concentrations were not significantly associated with most traditional risk factors, prevalent subclinical cardiovascular disease, or nonfatal cardiac events. However, a higher proportion of African Americans had detectable concentrations of sST2 than non-African Americans (44% vs 21%, respectively, P < 0.0001). In addition, sST2 concentrations were significantly associated with markers of inflammation. Increased sST2 was associated with increased all-cause mortality (P-trend <= 0.0001) and cardiovascular mortality (P-trend = 0.0004). In fully adjusted models, those in the highest quartile of detectable sST2 were at increased risk for all-cause death compared to those with undetectable sST2 concentrations (adjusted hazard ratio 2.1, 95% CI 1.4-3.2, P = 0.0009). CONCLUSIONS: In a low-risk population, sST2 does not associate with traditional cardiovascular risk factors or nonfatal cardiovascular events but is higher in African Americans and is associated with increased all-cause and cardiovascular mortality. Further investigation is needed regarding the role of sST2 in risk prediction, particularly among African Americans. (C) 2012 American Association for Clinical Chemistry