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Background: Several clinical studies have evaluated the association between ST2 and outcome in patients with heart failure (HF). However, little is known about the predictive value of frequently measured ST2 levels in patients with acute HF.Objectives: This study sought to describe the prognostic value of baseline and repeated ST2 measurements in patients with acute HF.Methods: In the TRIUMPH (Translational Initiative on Unique and novel strategies for Management of Patients with Heart failure) clinical cohort study, 496 patients with acute HF were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Repeated blood samples (7) were drawn during 1-year follow-up. ST2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured in a central laboratory. The primary endpoint was the composite of all-cause mortality and HF rehospitalization. Associations between repeated biomarker measurements and the primary endpoint were assessed using a joint model.Results: Median age was 74 years, and 37% of patients were women. The primary endpoint was reached in 188 patients (40%) during a median follow-up of 325 days (interquartile range: 85 to 401). The median baseline ST2 level was 71 ng/ml (interquartile range: 46 to 102). After adjustment for clinical factors and NT-proBNP, baseline ST2 was associated with an increased risk of the primary endpoint, and the hazard ratio per 1 SD increase of the baseline ST2 level (on the log2 scale) was 1.30 (95% confidence interval: 1.08 to 1.56; p = 0.005). When repeated measurements were taken into account, the adjusted hazard ratio per 1 SD increase of the ST2 level (on the log2 scale) during follow-up increased to 1.85 (95% confidence interval: 1.02 to 3.33; p = 0.044), adjusted for clinical factors and repeated measurements of NT-proBNP. Furthermore, ST2 levels appeared to elevate several weeks before the time of the primary endpoint.Conclusions: Repeated ST2 measurements appeared to be a strong predictor of outcome in patients with acute HF, independent of repeatedly measured NT-proBNP. Hence ST2 may be helpful in clinical practice for prognostication and treatment monitoring. (TRanslational Initiative on Unique and novel strategies for Management of Patients with Heart failure [TRIUMPH]; NTR1893). [ABSTRACT FROM AUTHOR]

Background Detailed insights in temporal evolution of high-sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post-ACS kinetics of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT), and to determine their intra- and interindividual variation in clinically stable patients. Methods and Results We determined hs-cTnI (Abbott) and hs-cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1-year follow-up. Post-ACS kinetics were studied by linear mixed-effect models. Using the samples collected in the 6- to 12-month post-ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs-cTnI and average hs-cTnT concentration, and the intra- and interindividual variation for both biomarkers. Compared with hs-cTnT, hs-cTnI peaked higher (median 3506 ng/L versus 494 ng/L; P <0.001) and was quicker below the biomarker-specific upper reference limit (16 versus 19 days; P <0.001). In the post-6-month samples, hs-cTnI and hs-cTnT showed modest correlation ( r spearman =0.60), whereas the average hs-cTnT concentration was 5 times more likely to be above the upper reference limit than hs-cTnI. The intraindividual variations of hs-cTnI and hs-cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%. Conclusions Hs-cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post-6-month samples, hs-cTnI and hs-cTnT were clearly not interchangeable, and average hs-cTnT concentrations were much more often above the upper reference limit than hs-cTnI. For both markers, the within-patient variation fell largely below beween-patient variation. Registration URL: https://www.trialregister.nl; unique identifiers: NTR1698 and NTR1106.

In this prospective cohort study of 250 stable heart failure patients with trimonthly blood sampling, we investigated associations of 17 repeatedly measured cytokines and cytokine receptors with clinical outcome during a median follow-up of 2.2 (25th-75th percentile, 1.4-2.5) years. Sixty-six patients reached the primary end point (composite of cardiovascular mortality, heart failure hospitalization, heart transplantation, left ventricular assist device implantation). Repeatedly measured levels of 8 biomarkers correlated with clinical outcomes independent of clinical characteristics. Rates of change over time (slopes of biomarker evolutions) remained independently associated with outcome for 15 biomarkers. Thus, temporal patterns of cytokines and cytokine receptors, in particular tumour necrosis factor ligand superfamily member 13B and interleukin-1 receptor type 1, might contribute to personalized risk assessment., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to study temporal changes in metabolite profiles in patients with post-acute coronary syndrome (ACS), in particular prior to the development of recurrent ACS (reACS). Methods: BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective study including patients admitted for ACS, who underwent high-frequency blood sampling during 1-year follow-up. Within BIOMArCS, we performed a nested case-cohort analysis of 158 patients (28 cases of reACS). We determined 151 metabolites by nuclear magnetic resonance in seven (median) blood samples per patient. Temporal evolution of the metabolites and their relation with reACS was assessed by joint modelling. Results are reported as adjusted (for clinical factors) hazard ratios (aHRs). Results: Median age was 64 (25th-75th percentiles; 56-72) years and 78% were men. After multiple testing correction ( p  < 0.001), high concentrations of extremely large very low density lipoprotein (VLDL) particles (aHR 1.60/SD increase; 95%CI 1.25-2.08), very large VLDL particles (aHR 1.60/SD increase; 95%CI 1.25-2.08) and large VLDL particles (aHR 1.56/SD increase; 95%CI 1.22-2.05) were significantly associated with reACS. Moreover, these longitudinal particle concentrations showed a steady increase over time prior to reACS. Among the other metabolites, no significant associations were observed. Conclusion: Post-ACS patients with persistent high concentrations of extremely large, very large and large VLDL particles have increased risk of reACS within 1 year.

Prior studies reported that Myeloperoxidase and Galectin-3, which are biomarkers of coronary plaque vulnerability, are elevated in acute coronary syndrome (ACS) patients. We studied the temporal evolution of these biomarkers early after ACS admission and prior to a recurrent ACS event during 1 year follow-up., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: We aimed to compare the prognostic value of a single "baseline" echocardiogram with repeated echocardiography in stable chronic heart failure (CHF) patients. We hypothesized that repeated echocardiograms would contain incremental prognostic information., Methods: In the prospective Bio-SHiFT study, we performed 332 echocardiograms in 106 patients during a median follow-up of 2.3 years. The endpoint comprised HF hospitalization, left ventricular (LV) assist device implantation, heart transplantation, and cardiovascular death. We compared hazard ratios (HRs; adjusted for N-terminal pro-brain natriuretic peptide) from Cox models for the first available measurement with HRs from joint models, which model individual trajectories based on the repeated measurements and link these to the time-to-event data., Results: The mean age of the patients was 58.1 years; 78.3% were male, 12.6% had New York Heart Association class >II, all had reduced ejection fraction, and the most common HF etiologies were cardiomyopathies (51%) and ischemia (40%). The endpoint occurred in 25 patients. Both the single measurements and the temporal trajectories were significantly associated with the endpoint (adjusted HR Cox model [95% CI] vs adjusted HR joint model [95% CI]): LV ejection fraction, 1.47 (0.93-2.31) vs 1.77 (1.13-2.93); diastolic LV diameter, 1.64 (1.09-2.47) vs 1.68 (1.12-2.57); systolic LV diameter, 1.72 (1.10-2.69) vs 1.68 (1.13-2.63); systolic left atrial diameter, 1.88 (1.18-3.00) vs 2.60 (1.48-4.97); E/A ratio, 2.73 (1.42-5.26) vs 3.87 (1.75-10.13); and E/e' ratio, 2.30 (1.38-3.84) vs 2.99 (1.68-6.19). None of the trajectories from the investigated parameters showed worsening prior to events., Conclusions: Although single baseline or repeatedly measured echocardiographic parameters were associated with the endpoint, all parameters remained on average stable during the 2.3 years of follow-up in this largely minimally symptomatic CHF cohort. Thus, regular echocardiographic monitoring of systolic or diastolic LV function within this time frame does not carry incremental prognostic information over a single baseline measurement., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background Remodeling biomarkers carry high potential for predicting adverse events in chronic heart failure ( CHF ) patients. However, temporal patterns during the course of CHF , and especially the trajectory before an adverse event, are unknown. We studied the prognostic value of temporal patterns of 14 cardiac remodeling biomarker candidates in stable patients with CHF from the Bio-SHiFT (Serial Biomarker Measurements and New Echocardiographic Techniques in Chronic Heart Failure Patients Result in Tailored Prediction of Prognosis) study. Methods and Results In 263 CHF patients, we performed trimonthly blood sampling during a median follow-up of 2.2 years. For the analysis, we selected all baseline samples, the 2 samples closest to the primary end point ( PE ), or the last sample available for end point-free patients. Thus, in 567 samples, we measured suppression of tumorigenicity-2, galectin-3, galectin-4, growth differentiation factor-15, matrix metalloproteinase-2, 3, and 9, tissue inhibitor metalloproteinase-4, perlecan, aminopeptidase-N, caspase-3, cathepsin-D, cathepsin-Z, and cystatin-B. The PE was a composite of cardiovascular mortality, heart transplantation, left ventricular assist device implantation, and HF hospitalization. Associations between repeatedly measured biomarker candidates and the PE were investigated by joint modeling. Median age was 68 (interquartile range: 59-76) years with 72% men; 70 patients reached the PE . Repeatedly measured suppression of tumorigenicity-2, galectin-3, galectin-4, growth differentiation factor-15, matrix metalloproteinase-2 and 9, tissue inhibitor metalloproteinase-4, perlecan, cathepsin-D, and cystatin-B levels were significantly associated with the PE , and increased as the PE approached. The slopes of biomarker trajectories were also predictors of clinical outcome, independent of their absolute level. Associations persisted after adjustment for clinical characteristics and pharmacological treatment. Suppression of tumorigenicity-2 was the strongest predictor (hazard ratio: 7.55 per SD difference, 95% CI : 5.53-10.30), followed by growth differentiation factor-15 (4.06, 2.98-5.54) and matrix metalloproteinase-2 (3.59, 2.55-5.05). Conclusions Temporal patterns of remodeling biomarker candidates predict adverse clinical outcomes in CHF . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01851538.

Background: It has been shown that intravascular ultrasound (IVUS) and radiofrequency (RF-)IVUS can detect high-risk coronary plaque characteristics., Objectives: The authors studied the long-term prognostic value of (RF-)IVUS-derived plaque characteristics in patients with coronary artery disease (CAD) undergoing coronary angiography., Methods: From 2008 to 2011, (RF-)IVUS was performed in 1 nonstenotic segment of a nonculprit coronary artery in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina. The pre-defined primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause death, nonfatal ACS, or unplanned revascularization. Hazard ratios (HRs) were adjusted for age, sex, and clinical risk factors., Results: During a median follow-up of 4.7 years, 152 patients (26.2%) had MACE. The presence of a lesion with a minimal luminal area ≤4.0 mm 2 was independently associated with MACE (HR: 1.49; 95% CI: 1.07 to 2.08; p = 0.020), whereas the presence of a thin-cap fibroatheroma lesion or a lesion with a plaque burden ≥70% on its own were not. Results were comparable when the composite endpoint included cardiac death instead of all-cause death. The presence of a lesion with a plaque burden of ≥70% was independently associated with the composite endpoint of cardiac death, nonfatal ACS, or unplanned revascularization after exclusion of culprit lesion-related events (HR: 1.66; 95% CI: 1.06 to 2.58; p = 0.026). Likewise, each 10-U increase in segmental plaque burden was independently associated with a 26% increase in risk of this composite endpoint (HR: 1.26 per 10-U increase; 95% CI: 1.03 to 1.52; p = 0.022)., Conclusions: IVUS-derived small luminal area and large plaque burden, and not RF-IVUS-derived compositional plaque features on their own, predict adverse cardiovascular outcome during long-term follow-up in patients with CAD. (The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis-Intravascular Ultrasound Study [AtheroRemoIVUS]; NCT01789411)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We determined the temporal effects of neurohormonal antagonists and loop diuretics on serially assessed (3-monthly) cardiorenal biomarkers, functional status, and clinical outcomes in 250 patients with chronic heart failure (CHF) with reduced ejection fraction. In blood, we measured NT-proBNP, troponin T, C-reactive protein, creatinine, cystatin C; in urine, N-acetyl-beta-d-glucosaminidase and kidney-injury-molecule-1. Angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) were inversely associated with cardiac impairment, inflammation, and renal tubular damage, but not with glomerular dysfunction. Diuretics were associated with worse biomarker profiles and with a hazard ratio for adverse clinical outcome of 1.12 (95% confidence interval: 1.03-1.22) per 40 mg higher doses. ACE-inhibitors/ARBs were more frequently downtitrated and diuretics more frequently uptitrated in patients who experienced endpoints than in those who did not. In conclusion, a decrease or withholding of ACE-inhibitors/ARBs solely based on glomerular function is not justified because of the beneficial effects on the heart, inflammation, and renal tubules. Higher and increased diuretic doses mark progression towards endstage CHF., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)

Renal dysfunction is an important component of chronic heart failure (CHF), but its single assessment does not sufficiently reflect clinically silent progression of CHF prior to adverse clinical outcome. Therefore, we aimed to investigate temporal evolutions of glomerular and tubular markers in 263 stable patients with CHF, and to determine if their patient-specific evolutions during this clinically silent period can dynamically predict clinical outcome. We determined the risk of clinical outcome (composite endpoint of Heart Failure hospitalization, cardiac death, Left Ventricular Assist Device placement, and heart transplantation) in relation to marker levels, slopes and areas under their trajectories. In each patient, the trajectories were estimated using repeatedly measured glomerular markers: creatinine/estimated glomerular filtration rate (eGFR), cystatin C (CysC), and tubular markers: urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1, plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL). During 2.2 years of follow-up, we collected on average 8 urine and 9 plasma samples per patient. All glomerular markers predicted the endpoint (univariable hazard ratio [95% confidence interval] per 20% increase: creatinine: 1.18[1.07-1.31], CysC: 2.41[1.81-3.41], and per 20% eGFR decrease: 1.13[1.05-1.23]). Tubular markers, NAG, and KIM-1 also predicted the endpoint (NAG: 1.06[1.01-1.11] and KIM-1: 1.08[1.04-1.11]). Larger slopes were the strongest predictors (creatinine: 1.57[1.39-1.84], CysC: 1.76[1.52-2.09], eGFR: 1.59[1.37-1.90], NAG: 1.26[1.11-1.44], and KIM-1: 1.64[1.38-2.05]). Associations persisted after multivariable adjustment for clinical characteristics. Thus, during clinically silent progression of CHF, glomerular and tubular functions deteriorate, but not simultaneously. Hence, patient-specific evolutions of these renal markers dynamically predict clinical outcome in patients with CHF., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Several clinical studies have evaluated the association between galectin-3 levels and outcome in patients with heart failure (HF). However, little is known about the predictive value of repeated galectin-3 measurements. This study evaluates the prognostic value of repeated time-dependent galectin-3 measurements in acute HF patients., Methods and Results: In the TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients with Heart Failure) clinical cohort study, 496 acute HF patients were enrolled in 14 hospitals in The Netherlands, between 2009 and 2014. Repeated blood samples (7) were drawn during 1-year follow-up. Associations between repeated biomarker measurements and the primary end point were assessed using a joint model. Median age was 74 years and 37% were women. The primary end point, composite of all-cause mortality and HF rehospitalization, was reached in 188 patients (40%), during a median follow-up of 325 days (interquartile range 85-401). The median baseline galectin-3 level was 24 ng/mL (interquartile range 18-34). The mean number of galectin-3 measurements available per patient was 4.3. After adjustment for clinical factors and N-terminal pro-brain natriuretic peptide, there was a weak association between baseline galectin-3 and risk of the primary end point. When repeated measurements were taken into account, the adjusted hazard ratio per 1 SD increase of the galectin-3 level (on the log2 scale) at any time point increased to 1.67 (95% confidence interval, 1.24-2.23, P <0.001). After additional adjustment for repeated N-terminal pro-brain natriuretic peptide measurements, the association remained statistically significant., Conclusions: Repeated galectin-3 measurements appeared to be a strong predictor of outcome in acute HF patients, independent of N-terminal pro-brain natriuretic peptide. Hence, galectin-3 may be helpful in clinical practice for prognostication and treatment monitoring., (© 2017 The Authors and Koninklijke Philips. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Several studies have suggested circulating microRNAs (miRs) are associated with heart failure, but these studies were small, and limited to single miR measurements. We examined 7 miRs which were previously linked to heart failure, and tested whether their temporal expression level predicts prognosis in a prospective cohort of chronic heart failure (CHF) patients., Methods and Results: In 2011-2013, 263 CHF patients were included. At inclusion and subsequently every 3months, we measured 7miRs. The primary endpoint (PE) comprised heart failure hospitalization, cardiovascular mortality, cardiac transplantation and LVAD implantation. Associations between temporal miR patterns and the PE were investigated by joint modelling, which combines mixed models with Cox regression. Mean age was 67±13years, 72% were men and 27% NYHA classes III-IV. We obtained 873 blood samples (median 3 [IQR 2-5] per patient). The PE was reached in 41 patients (16%) during a median follow-up of 0.9 [0.6-1.4] years. The temporal pattern of miR-22-3p was independently associated with the PE (HR [95% CI] per doubling of level: 0.64 [0.47-0.77]). The instantaneous change in level (slope of the temporal miR pattern) of miR-22-3p was also independently associated with the PE (HR [95% CI] per doubling of slope: 0.33 [0.20-0.51]). These associations remained statistically significant after adjustment for temporal patterns of NT-proBNP, Troponin T and CRP., Conclusions: The temporal pattern of circulating miR-22-3p contains important prognostic and independent information in CHF patients. This concept warrants further investigation in larger series with extended follow-up., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Near-infrared spectroscopy (NIRS) is capable of identifying lipid core-containing plaques, which can subsequently be quantified as a lipid core burden index (LCBI). Currently, no data are available on the long-term prognostic value of NIRS in patients with coronary artery disease (CAD)., Objectives: This study sought to determine the long-term prognostic value of intracoronary NIRS as assessed in a nonculprit vessel in patients with CAD., Methods: In this prospective, observational study, NIRS imaging was performed in a nonculprit coronary artery in 203 patients referred for angiography due to stable angina pectoris (SAP) or acute coronary syndrome (ACS). The primary endpoint was the composite of all-cause mortality, nonfatal ACS, stroke, and unplanned coronary revascularization., Results: The 1-year cumulative incidence of the primary endpoint was 10.4%. Cumulative 1-year rates in patients with an LCBI equal to and above the median (43.0) versus those with LCBI values below the median were 16.7% versus 4.0% (adjusted hazard ratio: 4.04; 95% confidence interval: 1.33 to 12.29; p = 0.01). The relation between LCBI and the primary endpoint was similar in SAP and ACS patients (p value for heterogeneity = 0.14). Similar differences between high and low LCBI were observed in pre-specified secondary endpoints., Conclusion: CAD patients with an LCBI equal to or above the median of 43.0, as assessed by NIRS in a nonculprit coronary artery, had a 4-fold risk of adverse cardiovascular events during 1-year follow-up. This observation warrants confirmation by larger studies with extended follow-up. (The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis - Intravascular Ultrasound Study [AtheroRemoIVUS]; NCT01789411)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Several risk factors for coronary heart disease (CHD) have been associated with improved in-hospital survival after myocardial infarction (MI). We aimed to confirm this paradox and assess whether it extends to long-term outcome. In addition, we investigated temporal mortality trends., Methods: We examined the relation between the presence of four modifiable risk factors for CHD (hypertension, dyslipidaemia, diabetes mellitus and smoking) and mortality in 14,434 consecutive patients admitted with MI to a coronary care unit from 1985 to 2008., Results: Two-thirds of MI patients (n = 10,003) had at least one risk factor for CHD on hospital admission. The presence of at least one compared to no CHD risk factors was associated with a favourable 30-day mortality rate (5% vs. 7%, adjusted odds ratio 0.72, 95% confidence interval (CI): 0.62-0.83). There was significant interaction between the presence of CHD risk factors and decade of hospitalization (p = 0.001). The adjusted 10-year mortality hazard ratio (HR) of at least one CHD risk factor compared to none, was 1.2 (95% CI: 1.0--1.4), 0.89 (0.65--1.2) and 0.89 (0.79--0.99) in 1985--1990, 1990--2000 and 2000--2008, respectively. Survival improved over time. Adjusted 10-year mortality fell (adjusted HR [2000--2008 vs. 1985--1990] 0.59 [95% CI: 0.52--0.66] in patients with, and 0.76 [95% CI: 0.65-0.89] in those without CHD risk factors)., Conclusions: The presence of at least one modifiable CHD risk factor was associated with improved outcome after MI. Patients with CHD risk factors benefited from more substantial mortality reductions during the past few decades.

Background: We aimed to study sex-related differences in temporal trends in short- and long-term mortality from 1985 to 2008 in patients hospitalized for acute myocardial infarction., Methods and Results: We included a total of 14 434 consecutive patients admitted to our intensive coronary care unit between 1985 and 2008 for myocardial infarction. A total of 4028 patients (28%) were women. Women were more likely to present with a higher risk profile and were equally likely to receive pharmacological and invasive reperfusion therapy compared with men. Women had a higher unadjusted mortality rate at 30 days (odds ratio, 1.3; 95% confidence interval, 1.1-1.5) and during 20 years (hazard ratio, 1.1; 95% confidence interval, 1.0-1.2) of follow-up. After adjustment for baseline characteristics, 30-day mortality was equal (adjusted odds ratio, 1.0; 95% confidence interval, 0.85-1.2) but the hazard for 20-year mortality was lower (adjusted hazard ratio, 0.77; 95% confidence interval, 0.66-0.90) in women compared to men. For 30-day mortality, there was no significant interaction between sex and age, diagnosis, or diabetes mellitus. Survival improved between 1985 and 2008. Temporal mortality reductions between 1985 and 2008 were at least as high in women as in men with myocardial infarction for both 30-day mortality and long-term mortality hazard., Conclusions: The fact that adjusted mortality rates for men and women treated for myocardial infarction in an intensive coronary care unit were similar and declined markedly over a 24-year period suggests that both sexes benefit from the evidence-based therapies that have been developed and implemented during this time period.

Objective: To study temporal trends in short- and long-term outcome after myocardial infarction (MI) according to diabetes status., Research Design and Methods: We included all 14,434 consecutive patients admitted for ST-segment elevation MI or non-ST-segment elevation MI at our center between 1985 and 2008. The study patients were compared according to prevalent diabetes. Temporal trend analyses were performed by comparing decades of admission (1985-1989 vs. 1990-1999 vs. 2000-2008)., Results: A total of 2,015 (14%) of the patients had prevalent diabetes. The risk of presenting with diabetes increased from 8 to 17% from 1985 to 2008. Diabetic patients presented with a higher prevalence of cardiovascular risk factors. With time, the use of evidence-based therapies increased in both patients with and without diabetes. Diabetes is associated with a 1.5-fold increased risk of mortality at the 20-year follow-up. Ten-year mortality decreased over time in patients with diabetes, from 53% in 1985-1989 to 39% in 2000-2008 (adjusted hazard ratio 0.56 [95% CI 0.43-0.73]), and in those without diabetes, from 38% in 1985-1989 to 29% in 2000-2008 (0.66 [0.60-0.73]; P interaction = 0.83). Patients with diabetes benefitted from a higher 30-day and 10-year absolute survival increase., Conclusions: Temporal mortality reductions after MI between 1985 and 2008 were at least as high in patients with diabetes compared with those without diabetes. However, long-term mortality remained higher in diabetic patients. Awareness of the high-risk profile of diabetic patients is warranted and might stimulate optimal medical care and outcome.

Anemia is common in hospitalized cardiac patients and is associated with adverse outcomes. The aim of this study was to identify the association of anemia with early and long-term outcomes in patients with acute coronary syndromes (ACSs). Included were 5,304 consecutive patients (73% men, 61 ± 12 years of age) admitted to a coronary care unit from 1985 through 2008 for ACS. According to the World Health Organization, anemia was defined as serum hemoglobin levels <13 g/dl for men and <12 g/dl for women. Anemia was divided into tertiles to compare mild, moderate, and severe anemia to nonanemia. For trend analyses the study population was categorized in 3 groups: 1985 to 1990, 1991 to 2000, and 2001 to 2008. Outcome measurements were all-cause mortality at 30-days and 20 years. Anemia was present in 2,016 patients (38%), of whom 655 had mild anemia, 717 moderate anemia, and 646 severe anemia. Median follow-up duration was 10 years (range 2 to 25). Compared to nonanemia, adjusted hazard ratios (HRs) for mortality at 30 days were 1.40 for moderate anemia (95% confidence interval [CI] 1.04 to 1.87) and 1.67 for severe anemia (95% CI 1.25 to 2.24). At 20 years HRs were 1.13 for moderate anemia (95% CI 1.01 to 1.27) and 1.39 for severe anemia (95% CI 1.23 to 1.56). In addition, survival during hospitalization improved over time. Compared to 1985 to 1990 adjusted HRs were 0.52 for 1991 to 2000 (95% CI 0.41 to 0.66) and 0.36 for 2001 to 2008 (95% CI 0.25 to 0.51). In conclusion, presence and severity of anemia is an important predictor of higher in-hospital and long-term mortality after ACS. In addition, since the 1980s in-hospital outcome of patients with ACS and anemia has improved., (Copyright © 2012 Elsevier Inc. All rights reserved.)