Prognostic Utility of Novel Biomarkers of Cardiovascular Stress: The Framingham Heart Study

Study Questions:

What is the added value of new biomarkers including soluble ST2 (sST2), growth differentiation factor-15 (GDF-15), and high-sensitivity troponin I (hs-TnI) for predicting cardiovascular outcomes in a community-based population?


A total of 3,428 individuals (97% of attendees) participating in the sixth examination (1995-1998) of the Framingham Offspring Study had measurement of the three new biomarkers as well as B-type natriuretic peptide and high-sensitivity C-reactive protein. Multivariable-adjusted proportional hazard models were used to assess the individual and combined ability of the biomarkers (combination of five biomarkers classified as multimarkers) to predict adverse outcomes.


Mean age was 59 years and 53% were women. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the three new biomarkers were associated with each endpoint (p < 0.001), except for coronary events. Individuals with multimarker scores in the highest quartile had a threefold risk of death, sixfold risk of heart failure, and twofold risk of cardiovascular events. Addition of the multimarker score to clinical variables led to modest, but highly significant increases in the c-statistic (p = 0.007 or lower) and net reclassification improvement (p = 0.001 or lower).


Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals, and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.


Soluble ST2, GDF-15, and the hs-TnI’s are each expressed or released by cardiovascular tissue in response to mechanical or pathological stress, and are elevated in both heart failure and acute coronary syndromes. The findings support the concept that cardiovascular dysfunction or injury can exist for many years before the onset of overt disease. The cost-effectiveness of using cardiac-derived biomarkers for identifying persons at highest risk for cardiovascular events amid an asymptomatic population will need to be assessed.

Clinical Topics: Acute Coronary Syndromes, ACS and Cardiac Biomarkers

Keywords: Acute Coronary Syndrome, C-Reactive Protein, Biological Markers, Troponin I, Natriuretic Peptide, Brain

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