ST2 may not be a useful predictor for incident cardiovascular events, heart failure and mortality
Maria F Hughes1, Sebastian Appelbaum2, Aki S Havulinna3
1Department of General and Interventional Cardiology, Hamburg University Heart Center, Hamburg, Germany German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Lübeck/Kiel, Germany Centre of Excellence for Public Health Northern Ireland, Queens University Belfast, Belfast, UK MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Insights
Soluble ST2 (sST2) did not improve cardiovascular disease risk prediction in a general Finnish population. While sST2 levels were not associated with heart failure or death, they did predict all-cause mortality.
Area of Science:
- Cardiovascular Medicine
- Biomarkers
- Epidemiology
Background:
- ST2 is a receptor for the inflammatory cytokine IL33.
- Elevated soluble ST2 (sST2) levels are linked to heart failure and mortality.
- The role of sST2 in predicting cardiovascular events in the general population requires further investigation.
Purpose of the Study:
- To investigate if soluble ST2 (sST2) levels can identify individuals at elevated risk of subsequent cardiovascular disease (CVD).
- To determine if sST2 adds to existing risk prediction algorithms for CVD events.
- To evaluate sST2's predictive ability for heart failure, CVD, diabetes, and death over 15 years.
Main Methods:
- High-sensitivity sST2 was measured in 8444 individuals (25-74 years) from the FINRISK97 cohort.
- Cox proportional hazards modeling assessed sST2's predictive capacity for various health outcomes.
- Model performance was compared using discrimination and reclassification statistics against established risk factors.
Main Results:
- sST2 showed non-significant associations with heart failure and CVD after adjusting for traditional risk factors.
- sST2 significantly predicted all-cause mortality (HR 1.09; 95% CI 1.01 to 1.19).
- Adding sST2 to risk models did not improve the c-index for predicting cardiovascular events.
Conclusions:
- In a healthy Finnish general population, sST2 did not enhance long-term prediction of cardiovascular events, including heart failure.
- sST2 did not improve the prediction of all-cause mortality when added to established risk factors.
- The study suggests sST2 may not be a valuable standalone biomarker for cardiovascular risk stratification in this population.
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.
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