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Background and aimsThis study aimed to assess the role of plasmatic fibroblast growth factor 23 (FGF23) as a prognostic marker after an acute coronary syndrome (ACS).MethodsThis prospective and multicentric study included 1,190 patients with ACS. FGF23 plasma levels and other components of mineral metabolism (calcidiol, parathormone [PTH], klotho, and phosphate), lipids, troponin, high-sensitivity C-reactive protein, N-terminal-pro-brain natriuretic peptide and estimated glomerular filtration rate (eGFR) were measured at discharge. The primary outcome was a combination of acute ischemic events, heart failure (HF) and death. Secondary outcomes were the separate components of the primary outcome.ResultsMedian follow-up was 5.44 (3.03-7.46) years. 294 patients developed the primary outcome. Patients with FGF23 levels below the median were predominantly males, younger, and with lower load of cardiovascular risk factors. Calcidiol and PTH levels were lower among them. Multivariable analysis showed that FGF23 (HR 1.18 [1.08-1.29], p2.ConclusionsFGF23 is a strong, independent predictor of HF and death among patients with ACS. This effect is homogeneous across different subgroups of population and not limited to patients with chronic kidney disease (CKD).

Resumen Antecedentes y objetivos En la enfermedad cardiovascular ateroesclerotica no existe consenso respecto a los instrumentos de estratificacion del riesgo en su prevencion secundaria. Nuestro objetivo consistia en comparar la capacidad discriminativa de las funciones de riesgo de Framingham, REGICOR, SCORE y REACH y las puntuaciones de riesgo Bohula-TIMI y SMART, asi como en evaluar el posible valor anadido de otras variables clinicas en cuanto a la prediccion de recurrencias en pacientes con enfermedad cardiovascular. Metodos Se analizo una cohorte de 269 pacientes con enfermedad cardiovascular establecida (52,8% coronaria, 32% cerebrovascular, 15,2% arteriopatia periferica). Se compararon las funciones de supervivencia de los grupos de riesgo (bajo/intermedio/alto) segun los valores de corte de uso habitual de cada funcion o puntuacion y se calcularon las razones de riesgos instantaneos (RRI) correspondientes a cada una mediante regresion de Cox. Se calculo el Δ C de Harrell, el cat-IRN y el cIRN despues de anadir nuevos factores predictivos a un modelo base que incluia edad, sexo, colesterol total, tabaquismo activo, hipertension arterial y diabetes. Resultados Al cabo de 6 anos de seguimiento (mediana de 4,82 anos) se habian producido 61 eventos (23%). Los grupos de riesgo alto tuvieron un mayor riesgo de recurrencia: SMART (RRI: 3,17 [1,55-6,5]), Framingham (RRI: 3,08 [1,65-5,75]), REGICOR (RRI: 2,71 [1,39-5,27]), SCORE (RRI: 2,14 [1,01-4,5], REACH (RRI: 5,74 [2,83-11,7]) y B-TIMI (RRI: 3,68 [0,88-15,3]). La enfermedad polivascular (3 territorios, RRI: 5,6 [2,2-14,25]), la albuminuria (RRI: 3,55 [2,06-6,11]) y la insuficiencia cardiaca (RRI: 3,11 [1,34-7,25]) tambien incrementaron el riesgo. La capacidad discriminativa (indice C de Harrell) fue baja, pero mejoro tras anadir la albuminuria y la enfermedad polivascular. Ambas variables tambien mejoraron el rendimiento del modelo base (cIRN: 0,326 [0,036; 0,607]). Conclusiones Las funciones de Framingham, REGICOR, SCORE y REACH y las puntuaciones B-TIMI y SMART mostraron un rendimiento bajo, aunque similar, en prevencion secundaria. La albuminuria y la enfermedad polivascular mejoraron el rendimiento predictivo de los principales factores de riesgo cardiovascular clasicos.

Parathormone (PTH) is a component of the Mineral Metabolism (MM) system that has been shown recently to add prognostic value in pts. with stable coronary artery disease (SCAD) and average renal function. However, the influence of renal function on the prognostic role of PTH in pts. with SCAD has not been shown yet.To assess the influence of estimated glomerular filtration rate (eGFR) on the prognostic role of PTH and other MM markers in pts. with SCAD.We analyzed the prognostic value of MM markers (PTH, klotho, phosphate, calcidiol [25-hydroxyvitamin D], and fibroblast growth factor-23 [FGF23]) in 964 pts. with SCAD and eGFR60ml/min/1.73 mAge was 60.0 (52.0-72.0) years, 76.2% of patients were men, and eGFR was 80.4 (65.3-93.1) ml/min/1,73 mIn pts. with SCAD, PTH is an independent predictor of poor outcomes only in those with eGFR60ml/min/1.73 m

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.

The pathophysiological mechanisms underlying Myocardial Infarction with Non-Obstructive Coronary Artery Disease (MINOCA) are still under debate. Lipoprotein (a) [Lp(a)] has proinflammatory and prothrombotic actions and has been involved in the pathogenesis of atherosclerosis. However, no previous studies have linked Lp(a) levels with the probability of developing MINOCA. Moreover, the relationship between MINOCA and the plasma levels of other proatherogenic and proinflammatory molecules such as Interleukin-18 (IL18) and proprotein convertase subtilisin/kexin type 9 (PCSK9) has not been studied. We conducted a prospective, multicenter study involving 1042 patients with acute myocardial infarction (AMI). Seventy-six patients had no significant coronary lesions. All patients underwent plasma analysis on admission. MINOCA patients were younger (57 (47–68) vs. 61 (52–72) years; p = 0.010), more frequently female (44.7% vs. 21.0%; p < 0.001), and had lower rates of diabetes and of Lp(a) > 60 mg/dL (9.2% vs. 19.8%; p = 0.037) than those with coronary lesions; moreover, High Density Lipoprotein cholesterol (HDL-c) levels were higher in MINOCA patients. The absence of Lp(a) > 60 mg/dL and of diabetes were independent predictors of MINOCA, as well as female sex, high HDL-c levels, and younger age. IL-18 and PCSK9 levels were not predictors of MINOCA. During a follow-up of 5.23 (2.89, 7.37) years, the independent predictors of the primary outcome (acute ischemic events or death) in the whole sample were Lp(a) > 60 mg/dL, older age, low estimated Glomerular Filtration rate (eGFR), hypertension, previous heart failure (HF), coronary artery bypass graft, use of insulin, and no therapy with acetylsalicylic acid. In conclusion, in AMI patients, the absence of high Lp(a) levels, as well high HDL-c levels, were independent predictors of the inexistence of coronary artery disease. High Lp (a) levels were also an independent predictor of ischemic events or death.

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.

Background. Mineral metabolism (MM) system and N-terminal pro-brain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in patients with stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in patients with SCAD has not been shown yet. The objective of this study is to assess the influence of NT-ProBNP on the prognostic role of MM markers in patients with SCAD. Methods: We analyzed the prognostic value of MM markers (parathormone (PTH), klotho, phosphate, calcidiol (25-hydroxyvitamin D3), and fibroblast growth factor-23) in 964 patients with SCAD and NT-ProBNP > 125 pg/mL vs. patient with NT-ProBNP ≤ 125 pg/mL included in five hospitals in 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: A total of 622 patients had NT-proBNP > 125 pg/mL and 342 patients had NT-ProBNP ≤ 125 pg/mL. The median follow-up was 5.1 years. In the group of NT-proBNP > 125 pg/mL, the patients were older, and there were more females and smokers than in the group of patients with normal NT-proBNP. Additionally, the proportion of patients with hypertension, atrial fibrillation, ejection fraction < 40%, cerebrovascular attack, or prior coronary artery bypass graft was higher in the high NT-proBNP group. In the high NT-proBNP patients, the predictors of poor prognosis were PTH (HR = 1.06 (1.01−1.10), p < 0.001) and NT-proBNP (HR = 1.02 (1.01−1.03), p = 0.011), along with age (HR = 1.039 (1.02−1.06), p < 0.001), prior coronary artery bypass graft (HR = 1.624 (1.02−2.59), p = 0.041), treatment with statins (HR = 0.32 (0.19−0.53), p < 0.001), insulin (HR = 2.49 (1.59−4.09), p < 0.001), angiotensin receptor blockers (HR = 1.73 (1.16−2.56), p = 0.007), nitrates (HR = 1.65 (1.10−2.45), p = 0.014), and proton pump inhibitors (HR = 2.75 (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 patients with SCAD and NT-ProBNP > 125 pg/mL, PTH and NT-ProBNP, which are markers related to ventricular damage, are predictors of poor outcome. In the subgroup of patients with NT-ProBNP ≤ 125 pgm/L, calcidiol and non-HDL cholesterol, which are more related to vascular damage, are the independent predictors of poor outcome. Then, in patients with SCAD, baseline NT-ProBNP may influence the type of biomarker that is effective in risk prediction. 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, PI17/01495, PI19/00128, PI20/487, and PI20/923); RETOS-Colaboración, Ministry of Science and Innovation (RTC2019-006826-1, DTS 19/00093) 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. Sí

Clinical data indicate that patients with C-reactive protein (CRP) levels higher than 2 mg per liter suffer from persistent inflammation, which is associated with high risk of cardiovascular disease (CVD). We determined whether a panel of biomarkers associated with CVD could predict recurrent events in patients with low or persistent inflammation and coronary artery disease (CAD). We followed 917 patients with CAD (median 4.59 ± 2.39 years), assessing CRP, galectin-3, monocyte chemoattractant protein-1 (MCP-1), N-terminal fragment of brain natriuretic peptide (NT-proBNP) and troponin-I plasma levels. The primary outcome was the combination of cardiovascular events (acute coronary syndrome, stroke or transient ischemic event, heart failure or death). Patients with persistent inflammation (n = 343) showed higher NT-proBNP and MCP-1 plasma levels compared to patients with CRP &lt, 2 mg/L. Neither MCP-1 nor NT-proBNP was associated with primary outcome in patients with CRP &lt, 2 mg/L. However, NT-proBNP and MCP-1 plasma levels were associated with increased risk of the primary outcome in patients with persistent inflammation. When patients were divided by type of event, MCP-1 was associated with an increased risk of acute ischemic events. A significant interaction between MCP-1 and persistent inflammation was found (synergy index: 6.17 (4.39–7.95)). In conclusion, MCP-1 plasma concentration is associated with recurrent cardiovascular events in patients with persistent inflammation.

Background 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 short term. Methods We studied 962 patients with stable coronary artery disease 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 (vitamin D) 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. 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 a receiving a CD in first three years of follow-up. None of the variables analyzed predicted a CD beyond this time. A previous history of heart failure was present in 3.3% of patients receiving a CD in the first three years of follow-up, in 0.0% of those receiving this diagnosis beyond three years, and in 12.3% of patients not developing cancer (p=0.036). Conclusions In patients with coronary artery disease, 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. The existence of previous heart failure does not account for these differences. New studies in large populations are needed to confirm these findings.

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.

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

Patients with coronary artery disease may develop not only ischemic events but also heart failure and death due to previous myocardial damage. The purpose of this study was to test the prognostic value of a panel of plasma biomarkers related to vascular (monocyte chemoattractant protein-1 [MCP-1] and soluble tumor necrosis factor-like weak inducer of apoptosis) and myocardial damage (galectin-3, N-terminal fragment of brain natriuretic peptide [NT-proBNP], and neutrophil gelatinase-associated lipocalin) in 706 patients with chronic coronary artery disease followed for 2.2 ± 0.99 years. Secondary outcomes were the incidence of acute ischemic events (ST elevation myocardial infarction, non-ST elevation acute coronary syndrome, stroke, or transient ischemic attack) and death or heart failure. The primary outcome was the combination of the secondary outcomes. Cox proportional hazards model was used for analysis. Fifty-three patients developed acute ischemic events. Increasing MCP-1 plasma levels (p = 0.002), age, and body mass index predicted this outcome independently. Thirty-three patients developed death and/or heart failure. Galectin-3 (p = 0.007), NT-proBNP plasma levels (p = 0.004), hypertension, glomerular filtration rate, and the use of nitrates and anticoagulants were associated with this outcome independently. The development of the primary outcome was predicted independently by MCP-1 (p

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

Resumen Introduccion y objetivos Determinar el cambio en la mortalidad a corto y medio plazo por infarto agudo de miocardio en Espana y los factores terapeuticos relacionados. Metodos Se identifico y se siguio durante 6 meses a 9.949 pacientes con infarto agudo de miocardio con elevacion del ST ingresados en la unidad coronaria en los registros PRIAMHO I, II y MASCARA realizados en 1995, 2000 y 2005. Resultados En el periodo 1995-2005 aumento (p Conclusiones La mortalidad precoz y a los 6 meses del infarto con elevacion del ST disminuyo en 1995-2005. Los factores terapeuticos relacionados son: incremento de la reperfusion y mayor utilizacion de antitromboticos, bloqueadores beta, inhibidores del sistema renina-angiotensina e hipolipemiantes.

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.

Inflammation plays a pivotal role in the pathophysiology of non-ST elevation acute coronary syndromes (NSTEACS). Intensive statin therapy reduces the recurrence of cardiovascular events after acute coronary syndromes. The aim of this study was to examine nuclear factor-kappa B activity in peripheral blood mononuclear cells, prostaglandin E2 (PGE2) and leukotriene B4 levels, and matrix metalloproteinase-9 (MMP-9) activity in plasma from patients with NSTEACS (at 0 days, 4 days, 2 months, and 6 months), patients with stable coronary artery disease, and healthy controls. On day 4, patients with NSTEACS were randomized to receive atorvastatin 80 mg/day (n = 14) or standard treatment (n = 16) during 2 months to study its effect on these parameters. Nuclear factor-kappa B activity (by electrophoretic mobility shift assay), PGE2 levels (by enzyme-linked immunosorbent assay), and MMP-9 activity (by gelatin zymography) in the plasma of patients with NSTEACS were significantly increased compared with patients with coronary artery disease and healthy controls. At 6 months, MMP-9 activity was normalized, whereas nuclear factor-kappa B activity and PGE2 levels were still increased. Leukotriene B4 plasma levels (by enzyme-linked immunosorbent assay) were similar in patients with NSTEACS and those with coronary artery disease but were significantly higher than those of healthy subjects. There was a significant correlation between plasma PGE2 levels and MMP-9 activity in patients with NSTEACS (r = 0.754, p

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.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.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.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 WileySons, Ltd.

We examined the proteome of circulating monocytes of patients with acute coronary syndrome at different times in comparison to that of patients with stable coronary artery disease. On admission, the expression of 18 spot proteins was altered, 10 of which were totally absent. This pattern changed progressively, and at 6 months, there were no differences with the monocyte proteome of stable patients.

Fundamento y objetivo Aunque la aterosclerosis es una enfermedad generalizada del arbol vascular, existen escasos estudios prospectivos que evaluen transversalmente de modo extenso a pacientes con afectacion clinica de diferentes territorios. Pacientes y metodo Se ha realizado un estudio prospectivo protocolizado de 269 pacientes consecutivos menores de 70 anos atendidos por aterosclerosis sintomatica de cualquier territorio –en un 53% coronario (CI), en un 32% cerebral (VC) y en un 15% periferico (VP)–. Se evaluaron los factores de riesgo y su control, y se realizo un estudio sistematico no invasivo del arbol vascular (ecografia Doppler) con una comparacion entre los grupos segun el territorio indice. Resultados Aunque todos los factores de riesgo estaban representados en los 3 grupos, el sexo masculino, el tabaquismo y la diabetes fueron mas frecuentes en VP y la dislipemia en CI (p Conclusiones El estudio sistematico del arbol vascular detecta lesiones aterosclerosas generalizadas, no sospechadas clinicamente, en algunos casos graves. Son necesarios marcadores que permitan identificar a los pacientes de muy alto riesgo. La enfermedad vascular periferica identifica a un grupo de pacientes de especial riesgo vascular. El grado de control de los factores de riesgo es deficiente, especialmente en VP.

Clinical trials have shown that combining beta-blockers and angiotensin-converting enzyme (ACE) inhibitors has an additive effect in reducing mortality in patients with left ventricular dysfunction following acute myocardial infarction. Whether this additive effect also occurs in unselected post-myocardial infarction patients is unknown.In total, 5397 patients who were discharged from hospital after suffering an acute myocardial infarction were followed for 1 year. The primary endpoint was all-cause mortality. The effects of the medications on 1-year survival were analyzed using a Cox regression model, which included propensity scores for beta-blocker and ACE inhibitor use to take account of any potential imbalance in drug prescription rates.At hospital discharge, 55.9% of patients were receiving beta-blockers and 45.1%, ACE inhibitors. The 1-year mortality rate was 5.5%. Overall, combination of the two medications significantly reduced the 1-year mortality rate (hazard ratio [HR]=0.51; 95% confidence interval [IC], 0.32-0.82); P.005) to a greater extent than ACE inhibitors alone (HR=0.78; 95% CI, 0.54-1.12; P=.2) or beta-blockers alone (HR=0.67; 95% CI, 0.43-1.05; P=.08). The same trend was also observed in low-risk patients without acute heart failure who had an ejection fractionor =40%.In unselected post-myocardial infarction patients, combined prescription of beta-blockers and ACE inhibitors had an additive effect on the 1-year survival rate.

Introduccion y objetivos La combinacion de bloqueadores beta e inhibidores de la enzima de conversion de la angiotensina (IECA) ha demostrado reducir la mortalidad en pacientes con infarto de miocardio y disfuncion sistolica. Sin embargo, no sabemos si esta asociacion presenta efectos aditivos sobre la supervivencia al ano en una poblacion no seleccionada de pacientes con infarto agudo de miocardio con y sin elevacion del segmento ST. Metodos Se realizo un seguimiento durante un ano a 5.397 pacientes dados de alta tras un infarto agudo de miocardio. El criterio de valoracion fue la mortalidad por cualquier causa. Para analizar el efecto de la medicacion se utilizo el modelo de regresion logistica de Cox, en el que se incluyo el propensity score para compensar las posibles desviaciones en la prescripcion de los 2 grupos de farmacos. Resultados En el momento del alta, el 55,9% de los pacientes recibio bloqueadores beta y el 45,1%, IECA. La mortalidad al ano fue del 5,5%. En el grupo total, la combinacion se asocio con una reduccion significativa de la mortalidad (hazard ratio [HR] = 0,51; intervalo de confianza [IC] del 95%, 0,32-0,82); p Conclusiones En una poblacion no seleccionada de pacientes con infarto agudo de miocardio, la prescripcion conjunta de bloquedores beta e IECA en el momento del alta hospitalaria muestra efectos aditivos sobre la supervivencia al ano.

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.

Introduccion y objetivos La enfermedad arterial/vascular periferica frecuentemente se asocia con enfermedad coronaria. El objetivo es evaluar la prevalencia de factores de riesgo cardiovascular tradicionales y emergentes entre pacientes con sindrome coronario agudo (SCA) con o sin enfermedad vascular periferica. Pacientes y metodo Realizamos un estudio prospectivo en 141 pacientes ( Resultados Los pacientes fueron estratificados en 2 grupos de acuerdo con la presencia (n = 37, el 26% del total, grupo SCA-EVP) o ausencia (n = 104, grupo SCA) de enfermedad arterial periferica. Los pacientes del grupo SCA-EVP eran mas viejos y tenian una significativa mayor prevalencia de diabetes e hipertension. Las concentraciones de proteina C reactiva, homocisteina, amiloide A y microalbuminuria fueron significativamente mayores en el grupo SCA-EVP (3,1 frente a 2,18 mg/l [p Conclusiones Varios factores de riesgo cardiovascular tradicionales y emergentes son mas prevalentes en pacientes con SCA y enfermedad arterial periferica, y algunos de ellos son predictores independientes de esta.

Objectives To determine clinical parameters that could predict occult vascular lesions (OVL) in patients with symptomatic atherosclerosis. Patients and methods Prospective evaluation of 269 consecutive patients with symptomatic atherosclerosis (cerebral 32%, peripheral vascular 15%, and coronary 53%): complete laboratory, ultrasound exams (carotids, aorta, heart), ankle-brachial index. OVL were defined as: abdominal aortic aneurysm, carotid artery stenosis >50%, or left ventricular segmental contraction abnormalities when affecting a different vascular bed from the symptomatic. Clinical predictors of OVL were evaluated by logistic regression analysis. Results OVL were found in 35 patients (13%): 12 abdominal aortic aneurysms, 21 carotid artery stenosis and 15 segmental left ventricular contraction abnormalities. OVL were associated with peripheral vascular disease (intermittent claudication or reduced ankle-brachial index), cigarette smoking, increased pulse pressure, microalbuminuria and hyperhomocysteinemia. By multivariate analysis, intermittent claudication (odds ratio 5.8; 95% CI 2.6–12.8) and microalbuminuria (OR 4.2; 95% CI 1.7–10.5) were strong independent predictors of OVL. Similar results were obtained when peripheral vascular disease was defined as reduced ankle-brachial index (OR 5.3; 95% CI 2.4–11.7). Conclusions Clinical and subclinical peripheral vascular disease, as well as microalbuminuria are strong independent predictors of OVL in atherosclerotic patients. A screening study of OVL may be warranted in these patients.

Introduccion y objetivos A pesar de que se conoce el valor pronostico de varios marcadores de inflamacion en el sindrome coronario agudo sin elevacion del segmento ST (SCASEST), aun se ignora que subconjunto de estos proporciona mejor informacion y que grado de asociacion existe entre ellos. El objetivo del estudio SIESTA es establecer el valor pronostico de la proteina C reactiva, fibrinogeno, neopterina, interleucinas 6, 8, 10 y 18, factor de necrosis tumoral, e-selectina, endotelina 1, factor tisular, molecula de adhesion celular vascular-1 (VCAM-1) e intercelular-1 (ICAM-1), proteina plasmatica-A asociada al embarazo (PAPP-A), peptido natriuretico ventricular (tipo B), troponina I o T, leucocitos e isoforma MB de la creatinfosfocinasa (CK-MB), en pacientes con SCASEST. Pacientes y metodo SIESTA es un estudio prospectivo, multicentrico, que incluira a pacientes que hayan presentado dolor toracico sugestivo de sindrome coronario agudo en las ultimas 48 h y alguna de las siguientes condiciones: signos electrocardiograficos de isquemia miocardica, enfermedad vascular documentada o elevacion de la concentracion de troponinas. Se realizara un seguimiento clinico durante un ano, con determinaciones hematologicas y bioquimicas en el momento del ingreso, del alta, y a los 30, 180 y 365 dias. Se validaran las escalas TIMI (Thrombolysis In Myocardial Infarction) y PEPA (Proyecto de Estudio del Pronostico de la Angina). La variable principal estara compuesta de muerte por cualquier causa, muerte de origen cardiaco, infarto de miocardio no letal y angina inestable que requiera hospitalizacion o revascularizacion urgente. La evaluacion individual de cada una de las variables se considerara como objetivo secundario. Este estudio ofrecera valiosa informacion prospectiva acerca del valor pronostico de un importante numero de marcadores inflamatorios en pacientes de origen mediterraneo asistidos en la practica medica habitual.

Objetivo Un porcentaje cercano al 30% de los pacientes con sindrome coronario agudo, elevacion del segmento ST en el electrocardiograma (ECG) y menos de 12 h de evolucion, no recibe tratamiento de reperfusion. En este estudio, se investigan los factores asociados a ese comportamiento y su influencia en la evolucion hasta un ano. Material y metodo El registro PRIAMHO II fue disenado como un estudio de cohorte, con seguimiento a un ano, de pacientes ingresados por infarto agudo de miocardio (IAM) en un periodo de 6 meses, en el ano 2000, en las unidades de cuidados intensivos cardiologicos (UCIC) de 58 hospitales espanoles seleccionados de manera aleatoria. Se analizaron las caracteristicas demograficas y clinicas, la evolucion y la mortalidad, a los 28 dias y al ano, de los pacientes tratados con y sin reperfusion. Resultados Se incluyeron 6.221 pacientes entre el 15 de mayo y el 15 de diciembre de 2000, ingresados en 58 hospitales. De ellos, 3.735 cumplian las indicaciones para reperfusion primaria, pero solo se realizo en 2.675 (71,6%). En el 89,3% de los casos se hizo fibrinolisis y en el resto intervencion percutanea. El analisis univariante mostro que las variables asociadas a no recibir tratamiento de reperfusion son: la edad avanzada, el sexo femenino, los antecedentes de diabetes mellitus, de hipertension arterial o de infarto de miocardio, el retraso en la llegada al hospital, el no poder precisar la localizacion del IAM por el ECG y la clase IV en la clasificacion de Killip. La mortalidad fue superior en los pacientes no reperfundidos, tanto la mortalidad hospitalaria (17,4 frente a 10,3%), como al ano (23,8 frente a 12,9%). En el 1,2% de los pacientes que recibieron fibrinoliticos aparecio un accidente cerebrovascular. Conclusiones Los resultados muestran que solo un 72% de los pacientes con IAM y ST elevado o bloqueo completo de la rama izquierda del haz de His (BCRIHH) que acuden al hospital con menos de 12 h de evolucion, reciben tratamiento de reperfusion. De ellos, un 11% lo reciben mediante intervencionismo percutaneo. Los pacientes que no son tratados con metodos de reperfusion tienen un perfil de riesgo peor, y la mortalidad es superior a corto y, especialmente, a largo plazo.

Introduccion y objetivos Los registros hospitalarios son utiles para conocer el grado de aplicacion de las nuevas evidencias y recomendaciones de las guias de practica clinica. Pacientes y metodo El registro PRIAMHO II es un estudio prospectivo con una seleccion aleatoria de los hospitales espanoles con unidad coronaria y control de calidad externo. Se incluyo a los pacientes con infarto agudo de miocardio ingresados en la unidad coronaria. Se recogieron las caracteristicas clinicas, el tratamiento y la evolucion hospitalaria, asi como la supervivencia a los 28 dias y al ano. Resultados Del 15 de mayo al 15 de diciembre de 2000, 6.221 pacientes fueron registrados en los 58 hospitales que cumplieron los controles de calidad (el 71,6% de los seleccionados). La mortalidad en la unidad coronaria fue del 9,6%, del 11,4% a los 28 dias y del 16,5% al ano. Recibio tratamiento de reperfusion el 71,6% de los pacientes con elevacion del segmento ST y menos de 12 h de evolucion, el 89% con fibrinolisis con un tiempo puerta-aguja de 48 min. La fraccion de eyeccion se midio en el 81% de los pacientes y en el 43% se realizo una prueba de isquemia. Al alta, el 91% recibio al menos un antiagregante; el 56%, bloqueadores beta; el 45%, inhibidores de la enzima de conversion de la angiotensina y el 45%, hipolipemiantes, con un coeficiente de variabilidad superior al 25%, excepto en la aspirina. Conclusiones El porcentaje de pacientes con elevacion del segmento ST que recibio reperfusion puede aumentar, sobre todo a expensas de la angioplastia primaria. Los retrasos son superiores a los recomendados. La estratificacion pronostica subaguda no es sistematica en la funcion ventricular y resulta suboptima en el estudio de isquemia residual. Al alta, la prescripcion de bloqueadores beta, inhibidores de la enzima de conversion de la angiotensina e hipolipemiantes puede aumentar y muestra una importante variabilidad entre los hospitales.

Con la descripcion del genoma humano se ha abierto una nueva manera de estudiar y entender los fenomenos fisiopatologicos. El siglo XX nos permitio conocer multitud de componentes de la celula de modo individual. Sin embargo, el siglo XXI se inicia con un analisis global de los componentes celulares. Gracias al desarrollo de diversas tecnologias, como los chips de ADN, o la electroforesis bidimensional, entre otros, ahora puede estudiarse la expresion de miles de genes, o de las proteinas que codifican, en pocas horas. Ademas, la genomica ha dado paso a la proteomica. La mera enumeracion de los genes no informa de las funciones celulares, pues ninguna celula los expresa todos simultaneamente, sino que, dependiendo del tipo celular y de los estimulos que reciba, expresara una parte variable de su genoma. El resultado sera el proteoma, es decir, un conjunto de proteinas que si son las responsables de las funciones celulares en cada momento, y que es el objeto de estudio de la proteomica. En proteomica cardiovascular ha comenzado a describirse el proteoma de las celulas cardiacas y algunas proteinas nuevas, no identificadas previamente, que estan alteradas en distintas miocardiopatias. Estas proteinas estan implicadas en la produccion de energia, en respuesta al estres, o pertenecen al proteasoma o al citoesqueleto y pueden ser potenciales marcadores de riesgo y constituir nuevas dianas terapeuticas en el futuro. La quimiogenomica aparece como una reciente metodologia que posibilita generar nuevos farmacos a partir de los datos genomicos y proteomicos.

We report the case of a patient followed since childhood for congenital complete atrioventricular block. At 28 years of age, atrioventricular conduction through an accessory pathway with long conduction times was detected. Periods of atrioventricular conduction alternated with periods of atrioventricular block. Sinus tachycardia and 1:1 exclusive conduction through the accessory pathway developed with increased sympathic activity (exercise, isoproterenol infusion). We discuss the special features of this case.

Desde la elaboracion de las Guias de Practica Clinica sobre angina inestable/infarto agudo de miocardio sin onda Q de la SEC en 1999, se han publicado numerosos trabajos cuyas conclusiones hacen recomendable modificar las recomendaciones vigentes hasta la fecha. Los hallazgos mas importantes estan relacionados con el papel emergente de las Unidades de Dolor Toracico en el manejo y la estratificacion inicial de los sindromes coronarios agudos en las unidades de urgencias, los nuevos descubrimientos sobre la eficacia de los inhibidores de la glucoproteina IIb/IIIa, el clopidogrel y las heparinas de bajo peso molecular en el tratamiento farmacologico del sindrome coronario agudo sin elevacion del segmento ST y el papel de la estrategia invasiva precoz para mejorar el pronostico de estos pacientes. En este documento se revisan las evidencias publicadas en estos campos y se actualizan las recomendaciones correspondientes en el manejo de los pacientes con sindrome coronario agudo sin elevacion persistente del segmento ST.

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).

At present, there is no tool validated by scientific societies for risk stratification of patients with stable coronary artery disease (SCAD). It has been shown that plasma levels of monocyte chemoattractant protein-1 (MCP-1), galectin-3 and pro-B-type natriuretic peptide amino-terminal (NT-proBNP) have prognostic value in this population.To analyze the prognostic value of a clinical risk scale published in Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study and determining its predictive capacity when combined with plasma levels of MCP-1, galectin-3 and NT-proBNP in patients with SCAD.A total of 706 patients with SCAD and a history of acute coronary syndrome (ACS) were analyzed over a follow up period of 2.2 ± 0.99 years. The primary endpoint was the occurrence of an ischemic event (any SCA, stroke or transient ischemic attack), heart failure, or death. A clinical risk scale derived from the LIPID study significantly predicted the development of the primary endpoint, with an area under the ROC curve (Receiver Operating Characteristic) of 0.642 (0.579 to 0.705); P0.001. A composite score was developed by adding the scores of the LIPID and scale decile levels of MCP -1, galectin -3 and NT-proBNP. The predictive value improved with an area under the curve of 0.744 (0.684 to 0.805); P0.001 (P=0.022 for comparison). A score greater than 21.5 had a sensitivity of 74% and a specificity of 61% for the development of the primary endpoint (P0.001, log -rank test).Plasma levels of MCP-1, galectin -3 and NT-proBNP improve the ability of the LIPID clinical scale to predict the prognosis of patients with SCAD.

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/

Introduccion y objetivos Poseemos insuficiente informacion sobre como se trata a los pacientes con infarto agudo de miocardio en Espana. Con el fin de subsanar esta deficiencia, la Seccion de Cardiopatia Isquemica y Unidades Coronarias de la Sociedad Espanola de Cardiologia inicio a finales de 1994 un registro de pacientes con infarto atendidos en las unidades coronarias de los hospitales espanoles, que se mantiene abierto en la actualidad. Metodos El reclutamiento de pacientes se realiza en hospitales con unidad coronaria. Se recogen caracteristicas demograficas, factores de riesgo y antecedentes de enfermedad coronaria asi como complicaciones clinicas y procedimientos diagnosticos y terapeuticos utilizados durante la estancia en la unidad coronaria. Resultados Durante el periodo 1995-1999 se registraron un total de 28.537 pacientes. La edad media aumento ligeramente (de 64,4 ± 12,2 a 65,2 ± 12,7 anos; p Conclusiones En nuestro medio, en el periodo 1995-1999, aumento el porcentaje de pacientes que reciben aspirina, bloqueadores beta e inhibidores de la enzima convertidora de la angiotensina en la fase aguda del infarto. Sin embargo, se estabilizo la utilizacion de tromboliticos y el retraso en su administracion. Disminuyo la estancia media en la unidad coronaria asi como la mortalidad precoz, a pesar de que las caracteristicas clinicas de los pacientes no mejoraron.

Aims To compare the efficacy and tolerability of the antiplatelet agent triflusal with aspirin in the prevention of cardiovascular events following acute myocardial infarction. Methods and results In this double-blind, multicentre, sequential design study, patients were randomized within 24 h of acute myocardial infarction symptom onset to receive triflusal 600 mg or aspirin 300 mg once daily for 35 days. The primary end-point was death, non-fatal myocardial reinfarction or a non-fatal cerebrovascular event. The incidences of these individual outcomes and urgent revascularization were secondary end-points. The null hypothesis of no difference between treatments in the primary combined end-point was accepted with 80% power after recruiting 2124 validated patients (odds ratio (OR) for failure [95% confidence interval (CI)]: 0.882 [0.634-1.227]). Non-fatal cerebrovascular events were significantly less frequent with triflusal (OR [95% CI]: 0.364 [0.146-0.908]; P = 0.030). There was no significant difference between treatments for death (OR [95% CI]: 0.816 [0.564-1.179]; P = 0.278), non-fatal reinfarction (OR [95% CI]: 1.577 [0.873-2.848]; P = 0.131) or revascularization (OR [95% CI]: 0.864 [0.644-1.161]; P = 0.334). Overall, both drugs were well tolerated, although there was a trend towards fewer bleeding episodes with triflusal; significantly fewer central nervous system bleeding episodes were observed in triflusal-treated patients (0.27% vs. 0.97%; P = 0.033). Conclusion Triflusal and aspirin have similar efficacy in preventing further cardiovascular events after acute myocardial infarction, but triflusal showed a more favourable safety profile. Triflusal significantly reduced the incidence of non-fatal cerebrovascular events compared with aspirin.

Introduccion y objetivos A pesar de que la trombolisis se ha incorporado a las guias de practica clinica sobre el tratamiento del infarto agudo de miocardio, existe escasa informacion sobre su utilizacion en la practica clinica en Espana. Metodos Estudio de cohorte con seguimiento a 1 ano de pacientes ingresados por infarto agudo de miocardio en 1995 en 24 hospitales espanoles. Se analizaron las diferencias clinicas y el pronostico de los pacientes tratados con o sin trombolisis. Resultados De los 5.242 pacientes con infarto agudo de miocardio ingresados, 2.191 (42%) fueron tratados con fibrinoliticos (intervalo, 23-63%). El resto no recibio tratamiento por no tener elevacion del segmento ST (35%), presentar alguna contraindicacion (16%), retraso prehospitalario > 12 h (35%) u otras causas (15%). Los pacientes tratados eran, en general, de menor riesgo por tener menores retrasos prehospitalarios, ser mas jovenes, con menor porcentaje de mujeres y diabeticos, y menos antecedentes de angina o infarto. El retraso medio en administrar el tratamiento fue de 3 h, mientras que el retraso intrahospitalario medio fue de 50 min dependiendo unicamente del hospital de ingreso, siendo menor en los hospitales pequenos. Un 49% de los pacientes recibio t-PA, un 46% estreptocinasa y un 5% otros farmacos. Aunque se administro mas t-PA en pacientes jovenes, fumadores, con infartos anteriores, onda Q y con demoras prehospitalarias cortas, el determinante principal fue el hospital de ingreso (intervalo de administracion: 9-96%). Los pacientes no tratados con fibrinoliticos presentaron mas complicaciones durante la fase aguda, requirieron mas procedimientos y tratamientos invasivos y tuvieron mayor mortalidad a 28 dias (el 17 frente al 10%; p Conclusiones En Espana no se siguen suficientemente las guias de practica clinica sobre tratamiento trombolitico por estar infrautilizado, especialmente en los pacientes de mayor riesgo, existir importantes demoras prehospitalarias e intrahospitalarias, y una enorme variabilidad entre los hospitales en su grado de utilizacion, tiempos de administracion y eleccion del farmaco, que no se explican por las caracteristicas de los pacientes. A pesar de ello, la mortalidad de los pacientes que recibieron trombolisis fue un 20% inferior a la de los no tratados, tras corregir por los demas factores con valor pronostico.

Este trabajo representa la actualizacion, por parte de la Seccion de Cardiopatia Isquemica y Unidades Coronarias de la Sociedad Espanola de Cardiologia, de las Guias de Actuacion Clinica para el manejo de la Angina Inestable y del Infarto sin elevacion del segmento ST. Ademas de las normas habituales referidas al manejo del enfermo ingresado, se ha considerado necesario ampliar estas recomendaciones al manejo extrahospitalario y en el area de urgencias, tanto porque es la fase de maxima mortalidad, como por la efectividad que un manejo adecuado tiene precisamente en esa fase inicial. La conducta en el area extrahospitalaria ante un enfermo con dolor toracico sospechoso de isquemia miocardica debe centrarse en el traslado rapido al centro hospitalario, realizacion de ECG, y la administracion de nitroglicerina sublingual y aspirina. El manejo en el area de urgencias se basa en la atencion clinica inmediata y monitorizacion, asi como acceso al desfibrilador. El trazado ECG determina, habitualmente en este entorno, la aplicacion de un protocolo determinado de tratamiento. Si existe elevacion del segmento ST debe organizarse el tratamiento de reperfusion en el menor tiempo posible (veanse Guias de infarto agudo de mioacrdio). Si no existe elevacion del ST, debe valorarse primero la probabilidad de isquemia coronaria y seguidamente la estratificacion de riesgo, que son esenciales para un adecuado manejo. En estas guias se propone una nueva estratificacion de riesgo simplificada, que entre otras cosas determina el lugar adecuado de ingreso: ingreso en unidad coronaria, si existen factores de riesgo elevado o modificadores de riesgo; por el contrario, si existe estabilidad clinica y factores pronosticos de riesgo intermedio, ingreso en el area de hospitalizacion. En los casos de riesgo ligero se recomienda el tratamiento ambulatorio Manejo en la unidad coronaria. Se describen las medidas generales (monitorizacion, analgesia). En el tratamiento antitrombotico se anade a la antiagregacion con acido acetilsalicilico, las indicaciones de los nuevos antiplaquetarios y a la administracion de heparina i.v., las heparinas de bajo peso molecular y los inhibidores directos de la trombina. El tratamiento antiisquemico se basa en: nitroglicerina i.v., betabloqueantes y antagonistas del calcio. Actualmente, el manejo de las complicaciones (angina refractaria, disfuncion del ventriculo izquierdo, insuficiencia mitral, progresion a infarto agudo de miocardio, etc.) implica la indicacion de coronariografia. Cuando el sustrato anatomico lo permite, la revascularizacion en la angina inestable, debe contemplar la intervencion percutanea sobre la arteria responsable como primera opcion. La utilizacion de stents y anti IIb-IIIa han mejorado el resultado de esta intervencion. Manejo en la planta de hospitalizacion. En esta fase debe realizarse la instauracion de tratamiento medico de mantenimiento y la estratificacion de riesgo con pruebas funcionales, que pueden indicar la necesidad de coronariografia antes del alta para valorar la revascularizacion. El diseno de la estrategia en prevencion secundaria debe realizarse en colaboracion con asistencia primaria.

Introduccion y objetivos Existe escasa informacion sobre el manejo del infarto agudo de miocardio y los resultados del mismo en Espana. El estudio PRIAMHO (Proyecto de Registro de Infarto Agudo de Miocardio HOspitalario) ha desarrollado una metodologia estandarizada para registrar informacion sobre el manejo de los pacientes con esta patologia y sus caracteristicas. Se presentan los resultados sobre la variabilidad entre hospitales en el manejo y mortalidad a un ano del infarto de miocardio. Metodos Se trata de un estudio de cohorte con seguimiento a 1 ano. Se registraron todos los pacientes dados de alta durante un ano con diagnostico de infarto agudo de miocardio en 24 hospitales espanoles que cumplieron los requisitos para participar, asi como sus caracteristicas demograficas, clinicas y evolutivas y los detalles de su manejo cuando ingresaron en las unidades de cuidados intensivos coronarios. Se utilizaron definiciones estandarizadas tanto en el diagnostico como en las variables medidas. Se garantizaron la confidencialidad de la identidad de los pacientes y el anonimato de los centros participantes. Resultados Las 24 unidades de cuidados coronarios registraron 5.242 (77,6%) de los 6.756 pacientes con infarto agudo de miocardio de sus hospitales. En 12 centros existia un laboratorio de hemodinamica y en 7 cirugia coronaria. El tiempo entre el inicio de los sintomas y la primera monitorizacion fue de aproximadamente 2 h. Un 16,6% desarrollo edema agudo de pulmon o shock cardiogenico, y el 41,8% recibio trombolisis. La mediana del tiempo sintomas-trombolisis fue de 3 h. Se observo una elevada variabilidad en el uso de los betabloqueantes, la trombolisis, la ecocardiografia, la coronariografia y la revascularizacion entre los hospitales. La mortalidad en la unidad de cuidados intensivos coronarios fue del 10,9% y paso al 14,0% a los 28 dias y al 18,5% al ano, con una notable variabilidad entre centros. Cuatro presentaron mayor mortalidad entre sus pacientes independientemente de la proporcion de hipertension, de diabetes, de mujeres, de infarto anterior, de infarto sin onda Q, de la edad y de la gravedad de los mismos. Conclusiones Los resultados de este estudio ponen de manifiesto que la mortalidad precoz y tardia por infarto agudo de miocardio continua siendo elevada en nuestro medio en la era de la reperfusion y que existe una importante variabilidad en el manejo y evolucion de estos pacientes que no se explica por las diferencias en el tipo de enfermos entre centros.

The frequency of coronary heart disease in a community is usually measured by myocardial infarction incidence and mortality rates. The measurement of the prevalence of angina pectoris may, however, become a convenient way of assessing coronary heart disease morbidity in the future. The aim of this study was to determine the prevalence of angina and validity of the Rose questionnaire in the Spanish population aged from 45 to 74 years. A cross-sectional study was conducted in 10,248 subjects (45-74 years), representative of the Spanish population. The WHO Rose questionnaire was used and a construct validation against regional mortality rates and cardiovascular risk factor prevalence was devised. The overall angina prevalence increased with age both in men and women, but was higher in the latter (7.3% and 7.7%, respectively). Angina prevalence also increased with the number of cardiovascular risk factors present and correlated with regional CHD mortality rates (r = 0.66). Sensitivity and specificity results of the Rose questionnaire were low when tested against exercise test (52.9% and 52.1%, respectively). As conclusions, Rose questionnaire is a reliable tool for assessing angina prevalence in the Spanish population which is similar to that of other industrialized countries with higher myocardial infarction morbidity and mortality.

En los primeros anos de intervencionismo coronario la alerta quirurgica inmediata en el propio centro fue absolutamente necesaria. El incremento en el numero de procedimientos, el aumento de la experiencia de los cardiologos y el perfeccionamiento de los materiales empleados, especialmente la aparicion de los stents intracoronarios, ha ido introduciendo los conceptos de «proximo quirofano disponible» y de intervencionismo en centros sin cirugia cardiaca. Para definir unas normas para la realizacion de angioplastias coronarias en centros sin cirugia cardiaca se revisan las complicaciones en las que es necesaria la cirugia en el marco de una angioplastia y la situacion de la angioplastia sin cirugia en distintos paises. Este conjunto de datos permiten elaborar unas recomendaciones sobre la realizacion de angioplastias coronarias en centros sin cirugia cardiaca, en las que se tienen en cuenta las caracteristicas del centro, del cardiologo intervencionista, del laboratorio de hemodinamica, de las lesiones y del consentimiento informado.

Introduccion La estimulacion auricular (AAI) es el modo de estimulacion recomendado como el mas adecuado en pacientes con enfermedad del nodo sinusal, a pesar de lo cual es el menos empleado en nuestro medio. La posible progresion a bloqueo auriculoventricular es la razon para implantar sistemas VVI o DDD. Hemos empleado marcapasos AAI en pacientes con enfermedad del nodo sinusal, que ademas presentaran un punto de Wenckebach igual o superior a 120 antes de la implantacion. Pacientes y metodos Cuarenta y cinco pacientes diagnosticados de enfermedad del nodo sinusal (ENS) que recibieron marcapasos auriculares (AAI) fueron seguidos de forma prospectiva y analizados de forma retrospectiva. Se valoro la aparicion de trastornos de la conduccion auriculoventricular y de taquiarritmias auriculares. Todos ellos presentaban un punto de Wenckebach igual o superior a 120 y no tenian evidencia de trastornos de conduccion intraventricular, antes de la implantacion. Cuatro pacientes dejaron de acudir a las revisiones y no fue posible completar su seguimiento. En los restantes 41 pacientes, 21 varones, de edad media ± DE 68 ± 12, el seguimiento medio fue de 56 meses (10-110). No hubo desplazamiento de ningun electrodo pero se produjo una rotura tardia de electrodo. No se produjeron agotamientos de bateria. Resultados Veintiocho de los 41 pacientes permanecen en modo de estimulacion AAI tras un seguimiento medio de 68,5 meses (44-110). Cinco presentaron fibrilacion auricular cronica a una media de 23 meses (10-39) despues de la implantacion. De ellos, 4 presentaban episodios de fibrilacion auricular paroxistica antes de la implantacion del generador. Ocho fallecieron (edad media 84 anos) durante el seguimiento (10-79 meses tras la implantacion). Las causas de la muerte fueron no cardiovasculares en 5 y por accidente cerebrovascular agudo en 3. No hubo complicaciones tromboembolicas perifericas. Ningun paciente presento progresion a bloqueo auriculoventricular sintomatico. Un paciente desarrollo un punto de Wenckebach asintomatico durante el sueno mientras recibia digital y amiodarona, desapareciendo el bloqueo al suspender la medicacion. Conclusion La estimulacion auricular aislada, AAI, es un modo seguro y estable de estimulacion definitiva para pacientes con enfermedad del nodo sinusal. Si se realiza una seleccion correcta, la progresion a bloqueo auriculoventricular es improbable.

En los ultimos anos se ha producido un desarrolloespectacular de las exploraciones no invasivasen el campo de la cardiologia clinica. De hecho,existen excelentes publicaciones monograficas sobrecada una de las tecnicas no invasivas mas habitualesen cardiologia, y sin embargo resulta pocofrecuente encontrar articulos que traten el temade una manera integrada, partiendo de las situacionesclinicas mas habituales. En este articulo revisaremos la pauta a seguir enlos pacientes que presentan dolor toracico, anginade pecho estable e inestable, sin olvidar a los pacientesque acaban de padecer un infarto agudo demiocardio. Ademas trataremos con profundidad elpapel de las tecnicas no invasivas en el diagnosticode la cardiopatia isquemica en las mujeres y en lospacientes con trastornos de la conduccion intraventricular,asi como su utilidad en los pacientesrevascularizados y en los que padecen enfermedadvascular periferica.