N-Terminal Pro-Brain Natriuretic Peptide Is Associated with a Future Diagnosis of Cancer in Patients with Coronary Artery Disease

Abstract

ObjectiveSeveral papers have reported elevated plasma levels of natriuretic peptides in patients with a previous diagnosis of cancer. We have explored whether N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels predict a future diagnosis of cancer in patients with coronary artery disease (CAD).MethodsWe studied 699 patients with CAD free of cancer. At baseline, NT-proBNP, galectin-3, monocyte chemoattractant protein-1, soluble tumor necrosis factor-like weak inducer of apoptosis, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin I plasma levels were assessed. The primary outcome was new cancer diagnosis. The secondary outcome was cancer diagnosis, heart failure requiring hospitalization, or death.ResultsAfter 2.15±0.98 years of follow-up, 24 patients developed cancer. They were older (68.5 [61.5, 75.8] vs 60.0 [52.0, 72.0] years; p=0.011), had higher NT-proBNP (302.0 [134.8, 919.8] vs 165.5 [87.4, 407.5] pg/ml; p=0.040) and high-sensitivity C-reactive protein (3.27 [1.33, 5.94] vs 1.92 [0.83, 4.00] mg/L; p=0.030), and lower triglyceride (92.5 [70.5, 132.8] vs 112.0 [82.0, 157.0] mg/dl; p=0.044) plasma levels than those without cancer. NT-proBNP (Hazard Ratio [HR]=1.030; 95% Confidence Interval [CI]=1.008-1.053; p=0.007) and triglyceride levels (HR=0.987; 95%CI=0.975-0.998; p=0.024) were independent predictors of a new cancer diagnosis (multivariate Cox regression analysis). When patients in whom the suspicion of cancer appeared in the first one-hundred days after blood extraction were excluded, NT-proBNP was the only predictor of cancer (HR=1.061; 95%CI=1.034-1.088; p<0.001). NT-proBNP was an independent predictor of cancer, heart failure, or death (HR=1.038; 95%CI=1.023-1.052; p<0.001) along with age, and use of insulin and acenocumarol.ConclusionsNT-proBNP is an independent predictor of malignancies in patients with CAD. New studies in large populations are needed to confirm these findings.

Plasma Levels of Monocyte Chemoattractant Protein-1, n-Terminal Fragment of Brain Natriuretic Peptide and Calcidiol Are Independently Associated with the Complexity of Coronary Artery Disease

“…In this regard, although initially described in the brain, it is now known to be secreted by the ventricular myocardium [ 5 ], and it is being used for the diagnosis of heart failure [ 4 , 5 ], having also prognostic value in patients with cardiovascular disease [ 2 ]. More recently, NT-proBNP levels have been shown to increase in patients with cancer [ 34 – 37 ]. Given that natriuretic peptides have been shown to have antiproliferative effects [ 38 – 40 ] it has been hypothesized that NT-proBNP plasma levels could increase in response to the excessive cell proliferation present in cancer [ 37 ].…”

“…More recently, NT-proBNP levels have been shown to increase in patients with cancer [ 34 – 37 ]. Given that natriuretic peptides have been shown to have antiproliferative effects [ 38 – 40 ] it has been hypothesized that NT-proBNP plasma levels could increase in response to the excessive cell proliferation present in cancer [ 37 ]. Then, the possibility exists that NT-proBNP plasma levels could also increase in response to the cell proliferation present in atherosclerosis, and that theoretically should be especially important in cases of extensive and severe CAD.…”

Levels of NT-proBNP and troponin T in cancer patients - mini-review

“…However, NT-pro BNP could have predictive power beyond cardiovascular risk [5]. In fact, this biomarker is associated with a higher risk of death in patients with cardiovascular diseases and in elderly subjects [7]. It is very helpful in the differential dia gnosis of dyspnoea.…”

Natriuretic Peptides: The Case of Prostate Cancer

“…ANP inhibits the amiloride-sensitive Na + /H + exchanger isoform 1, thus disrupting cancer cell pH homeostasis and reducing cell survival [ 49 , 50 , 51 ]. However, some groups [ 38 , 52 , 53 , 54 ] reported that plasma BNP levels are elevated in patients with cancer and suggested that these increases are due to the cardiac response to cancer-related inflammation. Indeed, BNP is upregulated at the transcriptional and translational levels by pro-inflammatory cytokines in myocardiocytes [ 55 ] and patients with hematologic malignancies have elevated levels of N-terminal –proBNP, related to a possible myocardium response to the setting of the cancer [ 56 , 57 ].…”

“…All the physiological effects of natriuretic peptide hormones are mediated by the interaction with the cell surface natriuretic peptide receptor A (NPRA; high affinity) and natriuretic peptide receptor C (NPRC; low affinity) [ 54 ]. ANP overexpression decreases NPRA levels in cells by a feedback inhibition.…”