Search

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 results: In 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 m2. 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 85.5 RU/mL) (P, This work was supported by grants from Instituto de Salud Carlos III (ISCIII) and Fondos FEDER (Fondo Europeo de Desarrollo Regional) European Union (PI05/0451, PI14/1567, PI17/01615, and PI17/01495); Spanish Society of Cardiology; Spanish Society of Arteriosclerosis; RECAVA (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares) (RD06/0014/0035); and Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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.

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 at baseline galectin-3, monocyte chemoattractant protein-1 (MCP-1) and N-terminal fragment of brain natriuretic peptide (NT-proBNP) plasma levels. Secondary outcomes were acute ischemia and heart failure or death. Primary outcome was the combination of the secondary outcomes. Results Male patients were 75.0% in T2DM and 76.6% in the non-T2DM subgroup (p=0.609). Age was 61.0 (54–72) and 60.0 (51–71) years, respectively (p=0.092). 232 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. 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 [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 non-diabetic 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 that predicted the development of acute ischemic events and heart failure or death in T2DM patients, while in non-diabetics MCP-1 and NT-proBNP, respectively, predicted these events. Conclusion In CAD patients, cardiovascular events are predicted by galectin-3 plasma levels in patients with T2DM, and by MCP-1 and NT-proBNP in those without T2DM. Effect of Gal-3 on the primary endpoint Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Insituto de Salud Carlos III

Background Disturbances of the components of the mineral metabolism (MM) (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor-23 [FGF23] and klotho) have been linked to cardiovascular disease. However, the available data are controversial, probably because most studies deal with individual rather than with the whole MM components. Purpose To the study the relationship between MM components and cardiovascular events, after controlling for other well-known markers (N-Terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hs-TnI], and high-sensitivity c-reactive protein [hs-CRP]), and relevant clinical variables in stable coronary artery disease (CAD) patients. Methods We analyzed the aforementioned markers in 964 CAD patients and followed them subsequently. The primary outcome (PO) was the composite of ischemic events (acute coronary syndrome, stroke or transient ischemic attack), heart failure and death. Secondary outcomes were any ischemic event and the composite of heart failure and death. Results Median follow-up was 5.39 years (2.81 - 6.92). Age was 60 (52–72) years and 76.2% patients were male. Median glomerular filtration rate was 80.4 (65.3–93.1) ml/min/1.73 m2. 185 patients developed the PO. At the univariate analysis PTH, FGF23, NT-proBNP and hs-TnI were directly associated with the PO, while calcidiol and Klotho were inversely related, and phosphate did not reach statistical significance. However, 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 After dividing patients in two subgroups according to whether they had FGF23 plasma levels above the median (85.5 RU/ml) or not, PTH remained as a predictor of the PO only in the subgroup with FGF23 >85.5 RU/ml (p Conclusion PTH predicts cardiovascular events in CAD patients with elevated FGF23 levels even after taking into account all the other components of MM and controlling for NT-ProBNP, hs-CPR and TnI. There is an interaction between PTH and FGF23 levels, and they should be assessed together when exploring their potential predictive power. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Fondo de Investigaciones Sanitarias

Background and aim Calcidiol (vitamin D metabolite) plasma levels vary with sun exposure (SE). However, it is not known if SE influences its prognostic ability. We have studied the effect of SE on plasma levels of the components of mineral metabolism (calcidiol, fibroblast growth factor-23 [FGF-23], parathormone [PTH], and phosphate [P]) and on their prognostic value in patients with coronary artery disease (CAD). Methods and results We studied prospectively 704 patients with stable CAD. Clinical variables and baseline calcidiol, FGF-23, PTH, and P plasma levels were assessed. We divided the population in two subgroups, according to the period of plasma extraction: High SE (HSE) (April–September) and low SE (LSE) (October–March). The outcome was the development of acute ischemic events (acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Mean follow-up was 2.15 ± 0.99 years. Calcidiol and P levels were higher in HSE group. In the whole population, calcidiol (HR = 0.84 for each 5 ng/ml increase, 95% CI = 0.71–0.99; p = 0.038) and FGF-23 (HR = 1.14 for each 100 RU/ml increase, 95% CI = 1.05–1.23; p = 0.009) were predictors of the outcome, along with age, hypertension, body-mass index, peripheral artery disease, and P levels. In the LSE subgroup, calcidiol (HR = 0.75; 95% CI = 0.57–0.99; p = 0.034) and FGF-23 (HR = 1.34; 95% CI = 1.13–1.58; p = 0.003) remained as predictors of the outcome. In the HSE group calcidiol and FGF-23 had not independent prognostic value. Conclusions In patients with stable CAD, low calcidiol and high FGF-23 plasma levels predict an adverse prognosis only when the sample is obtained during the months with LSE. SE should be taken into account in the clinical practice.

No clinical risk score is universally accepted for coronary artery disease. In 603 patients (mean age, 61.2 ± 12.3 yr) with stable coronary artery disease, we investigated the predictive power of clinical risk scores derived from the Framingham, the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID), and the Vienna and Ludwigshafen Coronary Artery Disease (VILCAD) studies. Secondary outcomes were the recurrence of an acute thrombotic event (coronary events, strokes, or transient ischemic attacks), or heart failure or death. The primary outcome was the combination of secondary outcomes. During follow-up (duration, 2.08 ± 0.97 yr), 42 patients had an acute thrombotic event; 22, heart failure or death; and 60, the primary outcome. The Framingham score predicted acute thrombotic events: hazard ratio (HR)=1.05; 95% confidence interval (CI), 1.01–1.08; P=0.03; net reclassification index (NRI, calculated to evaluate improvement in prediction gained by adding different risk scores to models constructed with variables excluded from the calculation of that score)=9.7% (95% CI, 9.6–9.8). The LIPID (HR=1.13; 95% CI, 1.04–1.22; P=0.005) and VILCAD scores (HR=1.99; 95% CI, 1.48–2.67; P We conclude that the accuracy of these risk scores varies in accordance with the outcome studied.

BACKGROUND Abnormalities of fibroblast growth factor-23 (FGF-23) plasma levels predict adverse outcomes in patients with coronary artery disease. However, FGF-23 has a different behaviour in the presence of type 2 diabetes mellitus (T2D). We explored whether the presence of T2D affects the predictive power of FGF-23. METHODS In 704 patients with stable coronary artery disease, FGF-23, calcidiol, parathormone (PTH) and phosphate plasma levels were prospectively assessed. The primary outcome was the development of acute ischemic events (acute coronary syndrome, stroke or transient ischemic attack), heart failure or death. RESULTS One hundred seventy-three (24.6%) patients had T2D, without differences in age, sex or estimated glomerular filtration rate as compared with non-diabetic patients. Serum PTH was lower and phosphate higher in T2D than in non-diabetic patients, without differences in FGF-23 or calcidiol levels. During follow-up (2.15 ± 0.99 years), 26 (15.2%) T2D and 51 (9.6%) non-diabetic patients developed the outcome (p = 0.048). T2D patients who developed the outcome had higher FGF-23 [112.0 (59.9, 167.6) vs 68.9 (54.2, 93.0) RU/mL; p = 0.002], PTH [71.3 (47.3, 106.6) vs 51.9 (40.8, 66.2) pg/mL; p = 0.004) and phosphate (3.53 ± 0.71 vs 3.25 ± 0.50 mg/dL; p = 0.017) levels than T2D subjects who remained stable. These differences were not significant in non-diabetic patients. By multivariable Cox proportional hazard model, FGF-23 predicted independently the outcome in T2D patients [hazard ratio = 1.277; 95% CI (1.132, 1.442)] but not in those without T2D. CONCLUSIONS FGF-23 plasma levels predict adverse cardiovascular outcomes in coronary artery disease patients who have T2D but not in those without T2D. This finding should be confirmed in larger studies. Copyright © 2016 John Wiley & Sons, Ltd.

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&ndash, 195) vs. 133 (105&ndash, 173) pg/mL, p = 0.006) and galectin-3 (8.3 (6.5&ndash, 10.5) vs. 7.8 (5.9&ndash, 9.8) ng/mL, p = 0.049) levels as compared to patients without diabetes. Median follow-up was 5.39 years (2.81&ndash, 6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients (Hazard ratio (HR) 1.57 (1.07&ndash, 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&ndash, 1.42), p = 0.017 and HR 1.23 (1.05&ndash, 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.

This is the peer reviewed version of the following article: Clinica e Investigacion en Arterioesclerosis 27.2 (2015) which has been published in final form at http://dx.doi.org/10.1016/j.arteri.2014.06.003

Plasma levels of Proprotein convertase subtilisin/kexin type 9 (PCSK9) and Lipoprotein (a) (Lp(a)) have been associated with poor prognosis in general population. However their clinical value is not clear in stable coronary artery disease (SCAD). We studied 980 patients witn SCAD. At baseline, a

Plasmatic levels of the amino terminal prohormone of brain natriuretic peptide (NT-proBNP) are elevated in patients with a diagnosis of cancer. It is also known that cancer cells produce and secrete it. However, it is not clear if NT-ProBNP would predict the development of tumours in patients with

Introduction:Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI. Methods and analysis:The VITamin D in Acute Myocardial Infarction (VITDAMI) trial is a multicentre, randomised, double-blind, placebo-controlled trial. 144 patients with anterior STEMI will be assigned to receive calcifediol 0.266 mg capsules (Hidroferol SGC)/15 days or placebo on a 2:1 basis during 12 months. Primary objective:to evaluate the effect of calcifediol on LV remodelling defined as an increase in LV end-diastolic volume >= 10\% (MRI). Secondary objectives:change in LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, diastolic function, sphericity index and size of fibrotic area; endothelial function; plasma levels of aminoterminal fragment of B-type natriuretic peptide, galectin-3 and monocyte chemoattractant protein-1; levels of calcidiol (VD metabolite) and other components of mineral metabolism (fibroblast growth factor-23 (FGF-23), the soluble form of its receptor klotho, parathormone and phosphate). Differences in the effect of VD will be investigated according to the plasma levels of FGF-23 and klotho. Treatment safety and tolerability will be assessed. This is the first study to evaluate the effect of VD on cardiac remodelling in patients with STEMI. Ethics and dissemination: This trial has been approved by the corresponding Institutional Review Board (IRB) and National Competent Authority (Agencia Espanola de Medicamentos y Productos Sanitarios (AEMPS)). It will be conducted in accordance with good clinical practice (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use-Good Clinical Practice (ICH-GCP)) requirements, ethical principles of the Declaration of Helsinki and national laws. The results will be submitted to indexed medical journals and national and international meetings. The VITDAMI trial is an investigator initiated study, sponsored by the Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz (IIS-FJD). Funding has been obtained from Fondo de Investigaciones Sanitarias (PI14/01567; http://www.isciii.es/) and Spanish Society of Cardiology (http://secardiologia.es/). In addition, the study medication has been provided freely by the pharmaceutical Company FAES FARMA S.A. (Leioa, Vizcaya, Spain; http://faesfarma.com/). This company was the only funder who collaborated in study design (IG-H). Sí

Abnormalities of mineral metabolism and inflammation may affect the cardiovascular system. We have assessed the relationship of left ventricular hypertrophy (LVH) with inflammation and mineral metabolism. LVH was measured in 146 outpatients with stable coronary artery disease (SCAD) using echocardiography. Calcidiol (a vitamin D metabolite), parathyroid hormone (PTH), fibroblast growth factor-23, high-sensitivity C-reactive protein, MCP-1 (monocyte chemoattractant protein-1), galectin-3, NGAL (neutrophil gelatinase-associated lipocalin), and sTWEAK (soluble TNF-related weak inducer of apoptosis) plasma levels were studied. LVH, defined as septal thickness ≥11 mm, was present in 19.9% of cases. These patients were older [75.0 (61.0-81.0) vs 64.0 (51.0-76.0) years; p=0.002], had higher prevalence of left ventricular ejection fraction (LVEF)>40%, and had higher PTH [84.7 (59.6-104.7) vs 63.2 (49.2-85.2) pg/ml; p=0.007], galectin-3 [9.6 (8.0-11.1) vs 8.3 (6.9-9.9) ng/ml; p=0.037], and NGAL (208.5±87.6 vs 173.9±73.4 ng/ml; p=0.031) plasma levels than those without LVH. Glomerular filtration rate was lower in patients with LVH than in those without it (65.1±20.0 vs 74.7±19.9 mL/min/1.73 m2; p=0.021). There were no significant differences in hypertension (79.3 vs 68.4%; p=0.363) or sex between both groups. Variables showing differences based on univariate analysis and hypertension were entered into a logistic regression analysis. Only age [odds ratio (OR) =1.052 (1.011-1.096); p=0.013], PTH plasma levels [OR=1.017 (1.003-1.031); p=0.021], and LVEF>40% [OR=7.595 (1.463-39.429); p=0.016] were independent predictors of LVH. In patients with SCAD, elevated PTH levels are independently associated with the presence of LVH. Further studies are needed to elucidate the role of PTH in the development of myocardial hypertrophy.

The use of high-sensitive troponin I (hsTnI) in clinical practice is currently limited to the context of the acute coronary syndrome. In stable coronary artery disease (SCAD), its clinical value is not clear. We studied 989 patients with SCAD. At baseline, a complete set of clinical and analytical

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background and Objectives We investigated the relationship of the Syntax Score (SS) and coronary artery calcification (CAC), with plasma levels of biomarkers related to cardiovascular damage and mineral metabolism, as there is sparse information in this field. Methods We studied 270 patients with coronary disease that had an acute coronary syndrome (ACS) six months before. Calcidiol, fibroblast growth factor-23, parathormone, phosphate and monocyte chemoattractant protein-1 [MCP-1], high-sensitivity C-reactive protein, galectin-3, and N-terminal pro-brain natriuretic peptide [NT-proBNP] levels, among other biomarkers, were determined. CAC was assessed by coronary angiogram as low-grade (0-1) and high-grade (2-3) calcification, measured with a semiquantitative scale ranging from 0 (none) to 3 (severe). For the SS study patients were divided in SS, This work was supported by grants from Fondo de Investigaciones Sanitarias [PI14/1567, PI14/00386, PIE13/00051], Spanish Society of Cardiology; Spanish Heart Foundation; Instituto de Salud Carlos III FEDER [FJD biobank grant RD09/0076/00101]; and AbbVie Laboratories

BACKGROUND Patients with coronary heart disease (CHD) without classical cardiovascular risk factors (CRF) are uncommon, and their profile has not been thoroughly studied. In CHD patients, we have assessed the differences in several biomarkers between those with and without CRF. METHODS We studied 704 patients with CHD, analyzing plasma levels of biomarkers related to inflammation, thrombosis, renal damage, and heart failure: hs-CRP (high-sensitivity C-reactive protein), MCP-1 (monocyte chemoattractant protein-1), galectin-3, NT-pro-BNP (N-terminal fragment of brain natriuretic peptide), calcidiol (vitamin D metabolite), fibroblast growth factor-23 (FGF-23), parathormone, and phosphate. RESULTS Twenty patients (2.8%) exhibited no CRFs. Clinical variables were well balanced in both groups, with the logical exceptions of no use of antidiabetic drugs, lower triglyceride and glucose, and higher high-density lipoprotein cholesterol in no-CRF patients. No-CRF patients showed lower hs-CRP (2.574±3.120 vs 4.554±9.786 mg/L; P=0.018), MCP-1 (114.75±36.29 vs 143.56±65.37 pg/ml; P=0.003) and FGF-23 (79.28±40.22 vs 105.17±156.61 RU/ml; P=0.024) and higher calcidiol (23.66±9.12 vs 19.49±8.18 ng/ml; P=0.025) levels. At follow-up, 10.0% vs 11.0% patients experienced acute ischemic event, heart failure, or death in the non-CRF and CRF groups, respectively (P=0.815, log-rank test). The limited number of non-CRF patients may have influenced this finding. A Cox regression analysis in the whole population showed that high calcidiol, and low MCP-1 and FGF-23 plasma levels are associated to a better prognosis. CONCLUSIONS CHD patients without CRFs show a favorable biomarker profile in terms of inflammation and mineral metabolism. Further studies are needed to investigate whether this difference translates into a better prognosis., This work was supported by grants from Fondo de Investigaciones Sanitarias (PI05/0451, PI05/1497, PI05/52475, PI05/1043, PS09/01405, and PI10/00072); Spanish Society of Cardiology; Spanish Heart Foundation; Spanish Society of Arteriosclerosis; RECAVA (RD06/0014/0035); Fundación Lilly; Instituto de Salud Carlos III FEDER (FJD Biobank: RD09/0076/00101); and AbbVie Laboratories

Objectives: To study the prognostic value of high-sensitive troponin (hs-cTn) I in stable coronary artery disease. Methods: In total, we studied 705 patients. Secondary outcomes were the incidence of: (1) acute ischemic events and (2) heart failure or death. The primary outcome was the composite of them. Results: Patients with hs-cTnI >0 ng/ml (62.1%) were older, had a lower estimated glomerular filtration rate, more frequent a history of hypertension, atrial fibrillation, ejection fraction 0 was associated with a higher risk of developing the primary outcome [relative risk = 2.360 (1.359-4.099); p = 0.001] and heart failure or death [relative risk = 5.932 (1.806-19.482); p < 0.001], but not with acute ischemic events. Statistical significance was lost after controlling for age. By logistic regression analysis, age [relative risk = 1.026 (1.009-1.044); p = 0.003], ejection fraction 0. Conclusions: In stable coronary disease, hs-cTnI is associated with the incidence of heart failure or death, but this relationship depends on other variables.

Objective Several 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). Methods We 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. Results After 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, This work was supported by grants from Fondo de Investigaciones Sanitarias (PI05/0451, PI05/1497,PI05/2475, PI05/1043, PS09/01405, PI10/ 00072, and PI10/0234, PI14/1567, Programa de Estabilización to LBC); Spanish Society of Cardiology and Spanish Heart Foundation; Spanish Society of Arteriosclerosis; RECAVA (RD06/0014/0035, www. recava.com); Fundación Lilly; and Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101).

Objective: Vitamin D and fibroblast growth factor-23 (FGF-23) are related with cardiovascular disorders. We have investigated the relationship of calcidiol (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse outcomes in patients with coronary artery disease. Methods: Prospective follow-up study of 704 outpatients, attending the departments of Cardiology of four hospitals in Spain, 6-12 months after an acute coronary event. Baseline calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The outcome was the development of acute ischemic events (any acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox regression adjusted for the main confounders was performed. Results: Calcidiol levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23, and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients, respectively. Only 22.4% of patients had glomerular filtration rate< 60 ml/min1.73 m2. After a mean follow-up was 2.15±0.99 years, 77 patients developed the outcome. Calcidiol (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.48-0.94; p = 0.021) and FGF-23 (HR = 1.13; 95% CI = 1.04-1.23; p = 0.005) plasma levels predicted independently the outcome. There was a significant interaction between calcidiol and FGF-23 levels (p = 0.025). When the population was divided according to FGF-23 levels, calcidiol still predicted the outcome independently in patients with FGF-23 levels higher than the median (HR = 0.50; 95% CI = 0.31-0.80; p = 0.003) but not in those with FGF-23 levels below this value (HR = 1.03; 95% CI = 0.62-1.71; p = 0.904). Conclusions: Abnormalities in mineral metabolism are frequent in patients with stable coronary artery disease. In this population, low calcidiol plasma levels predict an adverse prognosis in the presence of high FGF-23 levels, This work was supported by grants from the following: Fondo de Investigaciones Sanitarias (PI05/0451, PI05/1497, PI05/52475, PI05/1043, PS09/01405, and PI10/00072): http://www.isciii.es/ISCIII/es/contenidos/fd-investigacion/fd-financiacion/convocatorias-ayudas-accion-estrategica-salud.shtml; Spanish Society of Cardiology; Spanish Heart Foundation. http://www.secardiologia.es/; Spanish Society of Arteriosclerosis. www.searteriosclerosis.org; RECAVA (RD06/0014/0035); www.recava.com; Fundación Lilly. https://www.lilly.es/nuestra-compania/fundacion-lilly-folder; Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101); http://www.isciii.es/; and AbbVie Laboratories. http://www.abbvie.es/