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Background: ATTR-CM is becoming more prevalent, and disease-modifying therapy has been investigated in recent years with promising results. Diflunisal has shown TTR-stabilizing properties assessed by biomarkers and echocardiography, but there are no trials addressing the evolution of morphological changes with CMR. Methods and Results: AMILCA-DIFLU is an exploratory pilot study prospective, single-center, non-randomized, open-label clinical trial. Patients diagnosed with ATTR-CM underwent clinical, functional, biochemical and imaging assessment before and one year after diflunisal therapy initiation. Of the twelve ATTR-CM patients included, only nine patients completed treatment and study protocol in 12 months. To increase the sample size, we included seven real-world patients with one year of diflunisal treatment. Among the group of patients who completed treatment, diflunisal therapy did not show improvement in cardiac disease status as assessed by many cardiac and inflammatory biomarkers, 6MWT and CMR parameters after one year of treatment. However, a non-significant trend towards stabilization of CMR parameters such as LVEF, ECV and T2 at one year was found. When comparing the group of patients who completed diflunisal therapy and those who did not, a significant decrease in the distance performed in the 6MWT was found in the group of patients who completed treatment at one year (−14 ± 81.8 vs. −173 ± 122.2; p = 0.032). Diflunisal was overall well tolerated, showing only a statistically significant worsening in renal function in the group of diflunisal-treatment patients with no clinical relevance or need for treatment discontinuation. Conclusions: In patients with ATTR-CM, treatment with diflunisal was overall well tolerated and tended to stabilize or slow down amyloid cardiac disease progression assessed by CMR parameters, cardiac and inflammatory biomarkers and functional capacity. [ABSTRACT FROM AUTHOR]

Patients with prostate cancer may experience side effects of androgen deprivation therapy (ADT) such as cardiovascular (CV) complications. Oncology team members should actively communicate with patients about these complications. On the other hand, shared decision-making (SDM) has been shown to improve patient-physician communication. We developed brochures focused on CV complications of ADT and SDM. We proceeded to deliver these brochures to participating oncology offices and then carried out a survey of team members in these offices. We obtained responses from 31 oncology team members. Our survey revealed that about half of the participants (48%) rarely applied SDM in their oncology practice, and only about one-third (32%) sometimes applied SDM. After reading our brochures, the majority of respondents could correctly answer questions about SDM and CV complications of ADT. Improvement in scores after reading our materials was significant for both CV complications of ADT and SDM (e.g., CV complications of ADT: z = 6.153, p-value < 0.001, and SDM z = 6.456, p-value < 0.001). Implementation of SDM and an improved awareness of the CV complications of ADT can lead to significant benefits. It is therefore important to take steps to further raise such implementation and awareness among oncology team members in other geographic locations and clinical settings. [ABSTRACT FROM AUTHOR]

Background: Mineral metabolism (MM), mainly fibroblast growth factor-23 (FGF-23) and klotho, has been linked to cardiovascular (CV) diseases. Cardiac rehabilitation (CR) has been demonstrated to reduce CV events, although its potential relationship with changes in MM is unknown. Methods: We performed a prospective, observational, case-control study, with acute coronary syndrome (ACS) patients who underwent CR and control patients (matched by age, gender, left ventricular ejection fraction, diabetes, and coronary artery bypass grafting), who did not. The inclusion dates were from August 2013 to November 2017 in CR group and from July 2006 to June 2014 in control group. Clinical, biochemical, and MM biomarkers were collected at discharge and six months later. Our objective was to evaluate differences in the modification pattern of MM in both groups. Results: We included 58 CR patients and 116 controls. The control group showed a higher prevalence of hypertension (50.9% vs. 34.5%), ST-elevated myocardial infarction (59.5% vs. 29.3%), and treatment with angiotensin-converting enzyme inhibitors (100% vs. 69%). P2Y12 inhibitors and beta-blockers were more frequently prescribed in the CR group (83.6% vs. 96.6% and 82.8% vs. 94.8%, respectively). After six months, klotho levels increased in CR patients whereas they were reduced in controls (+63 vs. −49 pg/mL; p < 0.001). FGF-23 was unchanged in the CR group and reduced in controls (+0.2 vs. −17.3 RU/dL; p < 0.003). After multivariate analysis, only the change in klotho levels was significantly different between groups (+124 pg/mL favoring CR group; IC 95% [+44 to +205]; p = 0.003). Conclusions: In our study, CR after ACS increases plasma klotho levels without significant changes in other components of MM. Further studies are needed to clarify whether this effect has a causal role in the clinical benefit of CR. [ABSTRACT FROM AUTHOR]

Aims: Abnormalities of mineral metabolism (MM) have been related to cardiovascular disorders. There are no reports on the prognostic role of MM after an acute coronary syndrome (ACS). We aim to assess the prognostic role of MM after an ACS. Methods and results: Plasma levels of components of MM [fibroblast growth factor 23 (FGF23), calcidiol, parathormone, klotho, and phosphate], high‐sensitivity C‐reactive protein, and N‐terminal‐pro‐brain natriuretic peptide were measured in 1190 patients at discharge from an ACS. The primary outcome was a combination of acute ischaemic events, heart failure (HF) and death. Secondary outcomes were the separate components of the primary outcome. Age was 61.7 ± 12.2 years, and 77.1% were men. Median follow‐up was 5.44 (3.03–7.46) years. Two hundred and ninety‐four patients developed the primary outcome. At multivariable analysis FGF23 (hazard ratio, HR 1.18 [1.08–1.29], P < 0.001), calcidiol (HR 0.86 [0.74–1.00], P = 0.046), previous coronary or cerebrovascular disease, and hypertension were independent predictors of the primary outcome. The predictive power of FGF23 was homogeneous across different subgroups of population. FGF23 (HR 1.45 [1.28–1.65], P < 0.001) and parathormone (HR 1.06 1.01–1.12]; P = 0.032) resulted as independent predictors of HF. FGF23 (HR 1.21 [1.07–1.37], P = 0.002) and calcidiol (HR 0.72 [0.54–0.97), P = 0.028) were independent predictors of death. No biomarker predicted acute ischaemic events. FGF23 predicted independently the primary outcome in patients with estimated glomerular filtration rate > 60 mL/min/1.73 m2. Conclusions: FGF23 and other components of MM are independent predictors of HF and death after an ACS. This effect is homogeneous across different subgroups of population, and it is not limited to patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]

Aims: Residual congestion at the time of hospital discharge is an important readmission risk factor, and its detection with physical examination and usual diagnostic techniques have strong limitations in overweight and obese patients. New tools like bioelectrical impedance analysis (BIA) could help to determine when euvolaemia is reached. The aim of this study was to investigate the usefulness of BIA in management of heart failure (HF) in overweight and obese patients. Methods and results: Our study is a single‐centre, single‐blind, randomized controlled trial that included 48 overweight and obese patients admitted for acute HF. The study population was randomized into two arms: BIA‐guided group and standard care. Serum electrolytes, kidney function, and natriuretic peptides were followed up during their hospital stay and at 90 days after discharge. The primary endpoint was development of severe acute kidney injury (AKI) defined as an increase in serum creatinine by >0.5 mg/dL during hospitalization, and the main secondary endpoint was the reduction of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels during hospitalization and within 90 days after discharge. The BIA‐guided group showed a remarkable lower incidence of severe AKI, although no significant differences were found (41.4% vs. 16.7%; P = 0.057). The proportion of patients who achieved levels of NT‐proBNP < 1000 pg/mL at 90 days was significantly higher in the BIA‐guided group than in the standard group (58.8% vs. 25%; P = 0.049). No differences were observed in the incidence of adverse outcomes at 90 days. Conclusions: Among overweight and obese patients with HF, BIA reduces NT‐proBNP levels at 90 days compared with standard care. In addition, there is a trend towards lower incidence of AKI in the BIA‐guided group. Although more studies are required, BIA could be a useful tool in decompensated HF management in overweight and obese patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations. Methods and results Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [ n  = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2–12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C -statistics ranged from 0.605 [95% confidence interval (CI) 0.547–0.664] in BACS/BAMI to 0.772 (95% CI 0.659–0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options. Conclusion The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk. [ABSTRACT FROM AUTHOR]

Aims: As evidenced by scintigraphy imaging, the prevalence of transthyretin (TTR) cardiac amyloidosis in heart failure patients with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH) ranges between 13% and 19%. The natural evolution of cardiac amyloidosis begins with the deposition of amyloid material in the myocardium, with LVH ensuing at later stages. With current imaging modalities, it is possible to detect TTR cardiac amyloidosis before the hypertrophic stage. The aim of this study was to determine the prevalence of TTR cardiac amyloidosis in HFpEF patients without LVH. Methods and results: The study prospectively enrolled patients admitted for HF with LV ejection fraction (LVEF) ≥ 50% and LV wall thickness <12 mm. TTR cardiac amyloidosis was diagnosed according to accepted criteria, which include positive cardiac 99‐Tc‐DPD scintigraphy in the absence of monoclonal protein expansion in blood. Transthyretin gene sequencing was performed in positive patients. From July 2017 to January 2020, 329 patients with HFpEF and LV thickness <12 mm were identified. After exclusions, 58 patients completed the study with cardiac scintigraphy (79 years, 54% men; median LVEF 60% and LV wall thickness 10.5 mm). Three patients (5.2%) were positive for TTR cardiac amyloidosis; genetic analysis excluded the presence of hereditary TTR amyloidosis. Positive patients baseline characteristics (84 years, 67% men, LVEF 60%, and LV wall thickness 11 mm) were similar to patients without TTR, except for troponin levels (0.05 vs. 0.02 ng/mL, P = 0.03) and glomerular filtration rate (82 vs. 60 mL/min, P = 0.032), which were higher in TTR patients. Conclusions: In a cohort of patients with HFpEF without LVH, the prevalence of TTR cardiac amyloidosis was 5%. Early diagnosis of cardiac involvement in TTR amyloidosis (before manifest LVH) would seem recommendable because newly approved specific treatments can prevent additional deposition of amyloid material. [ABSTRACT FROM AUTHOR]

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 < 0.001) were independent predictors of the primary outcome but also for the secondary outcome of heart failure or death (HR 1.066 [CI 1.016–1.119]; P = 0.009 and HR 1.024 [CI 1.014–1.034]; P < 0.001, respectively). PTH was the only biomarker that predicted ischaemic events (HR 1.052 [1.010–1.096]; P = 0.016). Patients were divided in two subgroups according to FGF23 plasma levels. PTH retained its prognostic value only in patients with FGF23 levels above the median (>85.5 RU/mL) (P < 0.001) but not in patients with low FGF23 levels (P = 0.551). There was a significant interaction between FGF23 and PTH (P = 0.002). However, there was no significant interaction between PTH and both klotho and calcidiol levels. Conclusions: Parathormone is an independent predictor of cardiovascular events in coronary patients, adding complimentary prognostic information to NT‐proBNP plasma levels. This predictive value is restricted to patients with high FGF23 plasma levels. This should be considered in the design of future studies in this field. [ABSTRACT FROM AUTHOR]

It is essential to study the factors associated with the evolution of aortic stenosis progression (ASP) to develop therapies that could reduce it. We studied 283 patients 6 months after acute coronary syndrome (ACS). ASP was defined as an increase in the maximum aortic velocity of at least 0.5 m/s between the echocardiogram performed during ACS hospitalization and the last one recorded in the electronic medical registry. The median follow-up was 72.4 months. Twenty patients (7%) had ASP. A multivariate binary logistic regression analysis was performed showing that PCSK9 plasma levels (OR, 0.668 CI (0.457–0.977); p = 0.038), HS-CRP (OR, 1.034 CI (1.005–1.063); p = 0.022), the presence of dyslipidemia (OR, 4.622 CI (1.285–16.618); p = 0.019), the history of PAD (OR, 9.453 CI (1.703–52.452); p = 0.010), and GFR (OR, 0.962 CI (0.939–0.986); p = 0.002) were independent predicting factors of ASP. In patients with ischemic heart disease, low plasma levels of PCSK9 and elevated levels of HS-CRP are independent predictors of ASP. [ABSTRACT FROM AUTHOR]

Background: The presence of pathologic Q waves on admission electrocardiogram (ECG) in patients with anterior ST‐elevated myocardial infarction (STEMI) has been related to adverse cardiac outcomes. Our study evaluates the prognostic value of QRS complex and Q waves in patients with STEMI undergoing percutaneous coronary intervention. Methods: We prospectively analyzed the specific characteristics of QRS complex and pathologic Q waves on admission and on discharge ECG in 144 patients hospitalized for anterior STEMI. We correlated these findings with the development of left ventricular systolic dysfunction (LVSD), appearance of heart failure (HF) or death during follow‐up, and levels of several biomarkers obtained 6 months after the index event. Results: Multivariate logistic regression analysis showed that QRS width (odds ratios [OR] 1.05, p =.001) on admission ECG and the sum of Q‐wave depth (OR 1.06, p =.002) on discharge ECG were independent predictors of LVSD development. Moreover, QRS width on admission ECG was related to an increased risk of HF or death (OR 1.03, p =.026). Regarding biomarkers, QRS width on admission ECG revealed a statistically significant relationship with the levels of NT‐pro‐BNP at 6 months (0.29, p =.004); the sum of Q‐wave depth (0.27, p =.012) and width (0.25, p =.021) on admission ECG was related to the higher levels of hs‐cTnI; the sum of the voltages in precordial leads both on admission ECG (−0.26, p =.011) and discharge ECG (0.24, p =.046) was related to the lower levels of parathormone. Conclusions: Assessment of QRS complex width and pathologic Q waves on admission and discharge ECGs aids in predicting long‐term prognosis in patients with STEMI. [ABSTRACT FROM AUTHOR]

Background Takotsubo syndrome is a frequent entity; however, it has never been described after a mitral valve surgery. Case summary  We present the case of a 79-year-old woman, with background of atrial fibrillation and a left atrial appendage closure device, who was admitted for elective mitral valve replacement, because of asymptomatic severe primary mitral regurgitation. Biologic mitral valve was implanted without incidences, but in the postoperative, she developed cardiogenic shock. Electrocardiogram (ECG) showed inverted T waves in precordial leads and an echocardiography showed severe left ventricular (LV) dysfunction with mid to distal diffuse hypokinesis, and better contractility in basal segments. Troponin levels were mildly elevated. With the suspicion of a postoperative acute coronary syndrome, a coronary angiography was performed and showed no significant coronary lesions. The haemodynamic situation was compromised for the next 48 h, in which vasoactive support and intra-aortic balloon counterpulsation were implemented. After 48 h, the haemodynamic situation suddenly improved. The ECG was normalized, and a control echocardiogram showed partial recovery of the LV function with resolution of regional wall motion abnormalities. The patient could be discharged at 1 week. The clinical picture was interpreted as a stress cardiomyopathy after mitral valve surgery. Discussion  Takotsubo syndrome is a threatening condition; complications in acute phase could lead to a fatal outcome. Mitral valve surgery has to be considered as a trigger for this entity, after excluding coronary involvement, specially of left circumflex artery. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is characterized by increased circulating levels of parathormone (PTH) and fibroblast growth factor 23 (FGF23), bone disease, and vascular calcification, and is associated with adverse outcomes. We studied the prevalence of mineral metabolism disorders, and the potential relationship between decreased estimated glomerular filtration rate (eGFR) and CKD-MBD in coronary artery disease patients in a cross-sectional study of 704 outpatients 7.5 ± 3.0 months after an acute coronary syndrome. The mean eGFR (CKD Epidemiology Collaboration formula) was 75.8 ± 19.1 ml/min/1.73 m(2). Our patients showed lower calcidiol plasma levels than a healthy cohort from the same geographical area. In the case of men, this finding was present despite similar creatinine levels in both groups and older age of the healthy subjects. Most patients (75.6 %) had an eGFR below 90 ml/min/1.73 m(2) (eGFR categories G2-G5), with 55.3 % of patients exhibiting values of 60-89 ml/min/1.73 m(2) (G2). PTH (r = -0.3329, p < 0.0001) and FGF23 (r = -0.3641, p < 0.0001) levels inversely correlated with eGFR, whereas calcidiol levels and serum phosphate levels did not. Overall, PTH levels were above normal in 34.9 % of patients. This proportion increased from 19.4 % in G1 category patients, to 33.7 % in G2 category patients and 56.6 % in G3-G5 category patients (p < 0.001). In multivariate analysis, eGFR and calcidiol levels were the main independent determinants of serum PTH. The mean FGF23 levels were 69.9 (54.6-96.2) relative units (RU)/ml, and 33.2 % of patients had FGF23 levels above 85.5 RU/ml (18.4 % in G1 category patients, 30.0 % in G2 category patients, and 59.2 % in G3-G5 category patients; p < 0.001). In multivariate analysis, eGFR was the main predictor of FGF23 levels. Increased phosphate levels were present in 0.7 % of the whole sample: 0 % in G1 category patients, 0.3 % in G2 category patients, and 2.8 % in G3-G5 category patients (p = 0.011). Almost 90 % of patients had calcidiol insufficiency without significant differences among the different degrees of eGFR. In conclusion, in patients with coronary artery disease there is a large prevalence of increased FGF23 and PTH levels. These findings have an independent relationship with decreased eGFR, and are evident at an eGFR of 60-89 ml/min/1.73 m(2). Then, mild decreases in eGFR must be taken in consideration by the clinician because they are associated with progressive abnormalities of mineral metabolism. [ABSTRACT FROM AUTHOR]

Objectives: Proton-pump inhibitors (PPIs) seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD), mainly in those using clopidogrel. We analysed the impact of PPIs on the prognosis of patients with stable CAD. Methods: We followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1) acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and 2) heart failure (HF) or death. Results: Patients on PPIs were older [62.0 (53.0–73.0) vs. 58.0 (50.0–70.0) years; p = 0.003] and had a more frequent history of stroke (4.9% vs. 1.1%; p = 0.004) than those from the non-PPI group, and presented no differences in any other clinical variable, including cardiovascular risk factors, ejection fraction, and therapy with aspirin and clopidogrel. Follow-up was 2.2±0.99 years. Seventy-eight patients met the primary outcome, 53 developed acute ischaemic events, and 33 HF or death. PPI use was an independent predictor of the primary outcome [hazard ratio (HR) = 2.281 (1.244–4.183); p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use. PPI use was also an independent predictor of HF/death [HR = 5.713 (1.628–20.043); p = 0.007], but not of acute ischaemic events. A propensity score showed similar results. Conclusions: In patients with CAD, PPI use is independently associated with an increased incidence of HF and death but not with a high rate of acute ischaemic events. Further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-ofconcept 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 Española 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. [ABSTRACT FROM AUTHOR]

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<14 and SS≥14. Multivariate linear and logistic regression analyses were performed. Results: MCP-1 predicted independently the SS (RC = 1.73 [95%CI = 0.08–3.39]; p = 0.040), along with NT-proBNP (RC = 0.17 [95%CI = 0.05–0.28]; p = 0.004), male sex (RC = 4.15 [95%CI = 1.47–6.83]; p = 0.003), age (RC = 0.13 [95%CI = 0.02–0.24]; p = 0.020), hypertension (RC = 3.64, [95%CI = 0.77–6.50]; p = 0.013), hyperlipidemia (RC = 2.78, [95%CI = 0.28–5.29]; p = 0.030), and statins (RC = 6.12 [95%CI = 1.28–10.96]; p = 0.013). Low calcidiol predicted high-grade calcification independently (OR = 0.57 [95% CI = 0.36–0.90]; p = 0.013) along with ST-elevation myocardial infarction (OR = 0.38 [95%CI = 0.19–0.78]; p = 0.006), diabetes (OR = 2.35 [95%CI = 1.11–4.98]; p = 0.028) and age (OR = 1.37 [95%CI = 1.18–1.59]; p<0.001). During follow-up (1.79 [0.94–2.86] years), 27 patients developed ACS, stroke, or transient ischemic attack. A combined score using SS and CAC predicted independently the development of the outcome. Conclusions: MCP-1 and NT-proBNP are independent predictors of SS, while low calcidiol plasma levels are associated with CAC. More studies are needed to confirm these data. [ABSTRACT FROM AUTHOR]

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 <40%, and therapy with angiotensin-converting enzyme inhibitors, diuretics and acenocumarol. The follow-up period was 2.2 ± 0.99 years. Fifty-three patients suffered an acute ischemic event, 33 died or suffered heart failure and 78 developed the primary outcome. By univariate Cox's regression analysis, hs-cTnI >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 <40% [relative risk = 4.099 (2.043-8.224); p < 0.001], use of anticoagulants [relative risk = 2.785 (1.049-7.395); p = 0.040] and therapy with angiotensin-converting enzyme inhibitors [relative risk = 1.471 (1.064-2.034); p = 0.020], and estimated glomerular filtration rate [relative risk = 0.988 (0.977-0.999); p = 0.027] were associated with hs-cTnI >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. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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<0.001). NT-proBNP was an independent predictor of cancer, heart failure, or death (HR=1.038; 95%CI=1.023-1.052; p<0.001) along with age, and use of insulin and acenocumarol. Conclusions: NT-proBNP is an independent predictor of malignancies in patients with CAD. New studies in large populations are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels are increased in patients with cancer. In this paper, we test whether NT-proBNP may identify patients who are going to receive a future cancer diagnosis (CD) in the intermediate-term follow-up. We studied 962 patients with stable coronary artery disease and free of cancer and heart failure at baseline. This sample represents a re-analysis of a previous work expanding the sample size and the follow-up. NT-proBNP, galectin-3, monocyte chemoattractant protein-1, high-sensitivity C-reactive protein, high-sensitivity cardiac troponin I (hsTnI), and calcidiol (vitamin D) plasma levels were assessed. The primary outcome was new CD. After 5.40 (2.81–6.94) years of follow-up, 59 patients received a CD. NT-proBNP [HR 1.036 CI (1.015–1.056) per increase in 100 pg/mL; p = 0.001], previous atrial fibrillation (HR 3.140 CI (1.196–8.243); p = 0.020), and absence of previous heart failure (HR 0.067 CI (0.006–0.802); p = 0.033) were independent predictors of receiving a CD in the first three years of follow-up. None of the variables analyzed predicted a CD beyond this time. The number of patients developing heart failure during follow-up was 0 (0.0%) in patients receiving CD in the first three years of follow-up, 2 (6.9%) in those receiving a CD diagnosis beyond this time, and 40 (4.4%) in patients not developing cancer (p = 0.216). These numbers suggest that future heart failure was not a confounding factor. In patients with coronary artery disease, NT-proBNP was an independent predictor of CD in the first three years of follow-up but not later, suggesting that it could be detecting subclinical undiagnosed cancers. [ABSTRACT FROM AUTHOR]

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 < 2 mg/L. Neither MCP-1 nor NT-proBNP was associated with primary outcome in patients with CRP < 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. [ABSTRACT FROM AUTHOR]

Our purpose was to assess a possible association of inflammatory, lipid and mineral metabolism biomarkers with coronary artery ectasia (CAE) and to determine a possible association of this with acute atherotrombotic events (AAT). We studied 270 patients who underwent coronary angiography during an acute coronary syndrome 6 months before. Plasma levels of several biomarkers were assessed, and patients were followed during a median of 5.35 (3.88–6.65) years. Two interventional cardiologists reviewed the coronary angiograms, diagnosing CAE according to previously published criteria in 23 patients (8.5%). Multivariate binary logistic regression analysis was used to search for independent predictors of CAE. Multivariate analysis revealed that, aside from gender and a diagnosis of dyslipidemia, only monocyte chemoattractant protein-1 (MCP-1) (OR = 2.25, 95%CI = (1.35–3.76) for each increase of 100 pg/mL, p = 0.001) was independent predictor of CAE, whereas mineral metabolism markers or proprotein convertase subtilisin/kexin type 9 were not. Moreover, CAE was a strong predictor of AAT during follow-up after adjustment for other clinically relevant variables (HR = 2.67, 95%CI = (1.22–5.82), p = 0.013). This is the first report showing that MCP-1 is an independent predictor of CAE, suggesting that CAE and coronary artery disease may share pathogenic mechanisms. Furthermore, CAE was associated with an increased incidence of AAT. [ABSTRACT FROM AUTHOR]

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