Introduction: Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods: We followed 964 patients with coronary artery disease (CAD), assessing plasma levels of galectin-3, monocyte chemoattractant protein-1 (MCP-1), and N-terminal fragment of brain natriuretic peptide (NT-proBNP) at baseline. The secondary outcomes were acute ischemia and heart failure or death. The primary outcome was the combination of the secondary outcomes. Results. Two hundred thirty-two patients had T2DM. Patients with T2DM showed higher MCP-1 (144 (113–195) vs. 133 (105–173) pg/mL, p = 0.006) and galectin-3 (8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/mL, p = 0.049) levels as compared to patients without diabetes. Median follow-up was 5.39 years (2.81–6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients (Hazard ratio (HR) 1.57 (1.07–2.30); p = 0.022), along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in nondiabetic patients (HR 1.21 (1.04–1.42); p = 0.017 and HR 1.23 (1.05–1.44); p = 0.012, respectively), along with male sex and age. Galectin-3 was also the only biomarker associated with the development of acute ischemic events and heart failure or death in T2DM patients, while, in nondiabetics, MCP-1 and NT-proBNP, respectively, were related to these events. Conclusion: In CAD patients, galectin-3 plasma levels are associated with cardiovascular events in patients with T2DM, and MCP-1 and NT-proBNP in those without T2DM.

Aims There are controversial data on the ability of the components of mineral metabolism (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor-23 [FGF23], and klotho) to predict cardiovascular events. In addition, it is unknown whether they add any prognostic value to other well-known biomarkers. Methods and resultsIn 969 stable coronary patients, we determined plasma levels of all the aforementioned components of mineral metabolism with a complete set of clinical and biochemical variables, including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI), and high-sensitivity C-reactive protein. Secondary outcomes were ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and heart failure or death. The primary outcome was a composite of the secondary outcomes. Median follow-up was 5.39 years. Age was 60 (52-72) years. Median glomerular filtration rate was 80.4 (65.3-93.1) mL/min/1.73 m 2 . One-hundred and eighty-five patients developed the primary outcome. FGF23, PTH, hs-TnI, and NT-proBNP were directly related with the primary outcome on univariate Cox analysis, while Klotho and calcidiol were inversely related. On multivariate analysis, only PTH (HR 1.058 [CI 1.021-1.097]; P = 0.002) and NT-proBNP (HR 1.020 [CI 1.012-1.028]; P < 0.001) were independent predictors of the primary outcome but also for the secondary outcome of heart failure or death (HR 1.066 [CI 1.016-1.119]; P = 0.009 and HR 1.024 [CI 1.014-1.034]; P < 0.001, respectively). PTH was the only biomarker that predicted ischaemic events (HR 1.052 [1.010-1.096]; P = 0.016). Patients were divided in two subgroups according to FGF23 plasma levels. PTH retained its prognostic value only in patients with FGF23 levels above the median (>85.5 RU/mL) (P < 0.001) but not in patients with low FGF23 levels (P = 0.551). There was a significant interaction between FGF23 and PTH (P = 0.002). However, there was no significant interaction between PTH and both klotho and calcidiol levels. Conclusions Parathormone is an independent predictor of cardiovascular events in coronary patients, adding complimentary prognostic information to NT-proBNP plasma levels. This predictive value is restricted to patients with high FGF23 plasma levels. This should be considered in the design of future studies in this field.

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Background NT-proBNP plasma levels may predict a future cancer diagnosis(CD)in patients with coronary artery disease(CAD).In this paper we test whether this could merely represent the detection of increased NT-proBNP levels in subclinical tumors. Methods We studied 962 patients with stable CAD and free of cancer and heart failure at baseline. NT-proBNP, galectin-3, monocyte chemoattractant protein-1,high-sensitivity C-reactive protein, high-sensitivity cardiac troponin I(hsTnI),and calcidiol plasma levels were assessed.The primary outcome was new CD. Results After 5.40(2.81-6.94)years of follow-up,59 patients received a CD.We divided the population in three subgroups: those not developing cancer during follow-up (group A;N=903),and those receiving a CD in the first 3 years of follow up(group B; N=30),or later (group C;N=29).At baseline, 3.3% of patients of group B,0.0% in groups C and 12.3% in group A(p=0.036) presented a previous history of heart failure.In group B,NT-proBNP[HR1.036 CI(1.015-1.056)per increase in 100 pg/ml;p=0.001],previous atrial fibrillation[HR3.140 CI(1.196-8.243);p=0.020],and previous heart failure[HR0.067 CI(0.006-0.802);p=0.033]were independent predictors of CD at multivariate analysis.In group C there were not significant predictors of CD. Conclusions In patients with CAD,NT-proBNP is 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.New studies in large populations are needed to confirm these findings. What is already known about this topic? It has been linked in previous studies that NT-Pro-BNP elevation could be related to future diagnosis of some cancers especially renal tumors. It has also seen that NT-ProBNP is related to mortality in cancer patients.Finally, our group has previously seen that NT-Pro-BNP predicts cancer diagnosis in patients with myocardial infarction. What does this article add? According to our previous investigations this study support the idea that NT-Pro-BNP is a good marker for further cancer diagnosis not only in patients with myocardial infarction but across the spectrum of the whole CAD

Background: Mineral Metabolism (MM) system and N-terminal probrain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in SCAD has not been shown yet Methods: We analyzed the prognostic value of MM markers (parathormone [PTH], klotho, phosphate, calcidiol [25-hydroxyvitamin D3], and fibroblast growth factor-23) in 964 pts. with SCAD and NT-ProBNP>125 pg/ml vs pts. with NT-ProBNP≤125 pg/ml included in five hospitals of Spain. The main outcome was the combination of death, heart failure, and ischemic events (any acute coronary syndrome, ischemic stroke, or transient ischemic attack). Results: 622 pts. had NT-proBNP>125 pg/ml and 342 pts. had NT-ProBNP≤125 pg/ml. Median follow-up was 5.1 years. In the group of NT-proBNP>125 pg/ml patients were older, and there were more females and smokers than in pts. with normal NT-proBNP.In high NT-proBNP pts., the predictors of poor prognosis were PTH [HR=1.00 (1.00-1.00) p<0.001] and NT-proBNP [HR=1.006 (1.00-1.01) p=0.011], along with age [HR=1.039 (1.02-1.06) p<0.001], prior coronary artery by-pass graft [HR=1.624 (1.02-2.59) p=0.041], treatment with statins [HR= 0.315 (0.19-0.53) p<0.001], insulin [HR=2.490 (1.59-4.09) p<0.001], angiotensin receptor blockers [HR= 1.726 (1.16-2.56) p=0.007], nitrates [HR= 1.645 (1.10-2.45) p=0.014], and proton pump inhbitors [HR= 2.754 (1.74-4.36) p<0.001]. In the NT-proBNP≤125 pg/ml subgroup, poor prognosis predictors were plasma levels of non-high-density lipoprotein (non-HDL) cholesterol [HR=1.01 (1.00-1.02) p=0.014] and calcidiol [HR= 0.96 (0.92-0.99) p=0.045], as well as treatment with verapamil [HR=11.28 (2.54-50.00) p=0.001], and dihydropyridines [HR= 3.16 (1.63-6.13) p=0.001], Conclusion: In pts. with SCAD and NT-ProBNP>125 pg/ml, PTH and NT-ProBNP, that are markers related with ventricular damage, are predictors of poor outcome. In the subgroup of pts. with NT-ProBNP≤125 pgm/l, calcidiol and non-HDL cholesterol, more related to vascular damage, are the independent predictors of poor outcome. Then, in pts. with SCAD, baseline NT-ProBNP may influence the type of biomarker that should be used for risk prediction.