Lindholm D, et al. - In this secondary analysis of a randomized clinical trial of 6 biomarkers in 17,095 patients with acute coronary syndromes, researchers investigated whether different biomarkers provide prognostic information on cause-specific mortality. They found that baseline levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor-15 (GDF-15) in patients with acute coronary syndrome were related to death due to heart failure as well as due to arrhythmia and sudden cardiac death and therefore, baseline levels of NT-proBNP and GDF-15 were considered as strong markers associated with all-cause death in these subjects. The strongest associations with death due to other vascular or nonvascular causes and possibly with death due to bleeding were shown by GDF-15.

Methods

• This was a secondary analysis biomarker substudy of the Platelet Inhibition and Patient Outcomes (PLATO) trial, wherein, 18,624 patients with acute coronary syndrome were randomized to ticagrelor or clopidogrel from October 2006 through July 2008.
• This substudy included 17,095 patients.
• Researchers assessed death due to myocardial infarction, heart failure, sudden cardiac death/arrhythmia, bleeding, procedures, other vascular causes, and nonvascular causes, as well as all-cause death.
• They also inquired baseline levels of cystatin-C, growth differentiation factor-15 (GDF-15), high-sensitivity C-reactive protein, high-sensitivity troponin I and T, and N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Results

• Participants had median (interquartile range) age 62.0 (54.0-71.0) years, death of 782 (4.6%) of overall 17,095 patients was reported during follow-up.
• Cox models were used and continuous associations between biomarkers and all-cause and cause-specific mortality were modeled, which were then presented as hazard ratio (HR) comparing the upper vs lower quartile.
• The strongest markers for all-cause mortality were NT-proBNP and GDF-15, with adjusted HRs of 2.96 (95% CI, 2.33-3.76) and 2.65 (95% CI, 2.17-3.24), respectively.
• With regard to death attributed to heart failure, NT-proBNP was found to be related to an 8-fold and C-reactive protein, GDF-15, and cystatin-C, to a 3-fold increase in risk.
• Association of NT-proBNP with a 4-fold increased risk and GDF-15 with a doubling in risk, was noted as far as sudden cardiac death/arrhythmia was concerned.
• The strongest associations with other vascular and nonvascular deaths was shown by growth differentiation factor-15, which was also possibly related to death due to major bleeding (HR, 4.91; 95% CI, 1.39-17.43).