ABSTRACT
N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels are increased in patients with cancer. In this paper, we test whether NT-proBNP may identify patients who are going to receive a future cancer diagnosis (CD) in the intermediate-term follow-up. We studied 962 patients with stable coronary artery disease and free of cancer and heart failure at baseline. This sample represents a re-analysis of a previous work expanding the sample size and the follow-up. NT-proBNP, galectin-3, monocyte chemoattractant protein-1, high-sensitivity C-reactive protein, high-sensitivity cardiac troponin I (hsTnI), and calcidiol (vitamin D) plasma levels were assessed. The primary outcome was new CD. After 5.40 (2.81-6.94) years of follow-up, 59 patients received a CD. NT-proBNP [HR 1.036 CI (1.015-1.056) per increase in 100 pg/mL; p = 0.001], previous atrial fibrillation (HR 3.140 CI (1.196-8.243); p = 0.020), and absence of previous heart failure (HR 0.067 CI (0.006-0.802); p = 0.033) were independent predictors of receiving a CD in the first three years of follow-up. None of the variables analyzed predicted a CD beyond this time. The number of patients developing heart failure during follow-up was 0 (0.0%) in patients receiving CD in the first three years of follow-up, 2 (6.9%) in those receiving a CD diagnosis beyond this time, and 40 (4.4%) in patients not developing cancer (p = 0.216). These numbers suggest that future heart failure was not a confounding factor. In patients with coronary artery disease, NT-proBNP was an independent predictor of CD in the first three years of follow-up but not later, suggesting that it could be detecting subclinical undiagnosed cancers.
ABSTRACT
Metabolite fingerprinting (metabolomics/metabonomics) is perfectly suited for assessing the biological response following acute coronary syndrome (ACS) as relevant information can be identified in both the change and the absence of change in metabolite concentrations as time progresses post syndrome. During this study the metabolic pattern of plasma from patients at time points 0, four days, two months and six months after the onset of ACS were compared to controls using a non-targeted approach with gas chromatography mass spectrometry (GC-MS). Fatty acid profiles of the sample set were also analysed in a targeted way. The methods were employed with the aim to identify specific biomarkers, which vary with time. Using the non-targeted approach 27 statistically significant metabolites of interest were found: glucose, fructose, myoinositol, pyruvate, lactate, oxalate, citrate, isocitrate, succinate, malate, valine, alanine, serine, glycine, cysteine, threonine, aspartate, tryptophan, tyrosine, 4-hydroxyproline, 2-hydroxybutyrate, 2-aminobutyrate, 2,3,4-trihydroxybutyrate, 3-hydroxybutyrate, creatinine and aminomalonate. In addition, the targeted analysis of 21 fatty acids revealed patients within the group ACS at day 0 had the highest values for all 21. After 4 days, values decreased and were maintained at a lower level during the 6 months. Whereas the overall fatty acid profile did not change, different patterns of concentration trajectories over time were identified, which can reflect the underlying metabolic alterations as a result of the initial ACS, interestingly these levels had not fully reverted six months later.
