Showing papers by "Markku S. Nieminen published in 2013"

Large-scale association analysis identifies new risk loci for coronary artery disease

Abstract: Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Abstract: Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Identification of heart rate–associated loci and their effects on cardiac conduction and rhythm disorders

Abstract: Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure.

Abstract: Aims Cinaciguat (BAY 58-2667) is a novel soluble guanylate cyclase activator. This study evaluated the haemodynamic effect and safety of cinaciguat added to standard therapy in patients with acute decompensated heart failure (ADHF). Methods and results In this placebo-controlled, phase IIb study ([NCT00559650][1]), 139 patients admitted with ADHF, pulmonary capillary wedge pressure (PCWP) ≥18 mmHg, left ventricular ejection fraction <40%, and a pre-existing need for invasive haemodynamic monitoring were randomized 2:1 to cinaciguat:placebo (continuous i.v. infusion). The dose was titrated for 8 h and maintained for 16–40 h (starting dose: 100 μg/h). At 8 h, mean PCWP changed from 25.7 ± 5.0 mmHg by −7.7 mmHg with cinaciguat and from 25.0 ± 5.3 mmHg by −3.7 mmHg with placebo ( P < 0.0001). The mean right atrial pressure changed from 12.4 ± 5.3 mmHg by –2.7 mmHg with cinaciguat and from 11.8 ± 4.9 mmHg by –0.6 mmHg with placebo ( P = 0.0019). Cinaciguat also decreased the pulmonary and systemic vascular resistance and the mean arterial pressure, and increased the cardiac index (all P < 0.0001 vs. placebo). Systolic blood pressure changed by –21.6 ± 17.0 mmHg with cinaciguat and –5.0 ± 14.5 mmHg with placebo. Adverse events were experienced by 71 and 45% of patients receiving cinaciguat and placebo, respectively. No adverse effects on the 30-day mortality were seen; however, the trial was stopped prematurely due to an increased occurrence of hypotension at cinaciguat doses ≥200 µg/h. Conclusion Cinaciguat unloaded the heart in patients with ADHF. However, high doses were associated with hypotension. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00559650&atom=%2Fehj%2Fearly%2F2012%2F07%2F09%2Feurheartj.ehs196.atom

Levosimendan: current data, clinical use and future development

Abstract: Levosimendan is an inodilator indicated for the short-term treatment of acutely decompensated severe chronic heart failure, and in situations where conventional therapy is not considered adequate The principal pharmacological effects of levosimendan are (a) increased cardiac contractility by calcium sensitisation of troponin C, (b) vasodilation, and (c) cardioprotection These last two effects are related to the opening of sarcolemmal and mitochondrial potassium-ATP channels, respectively Data from clinical trials indicate that levosimendan improves haemodynamics with no attendant significant increase in cardiac oxygen consumption and relieves symptoms of acute heart failure; these effects are not impaired or attenuated by the concomitant use of beta-blockers Levosimendan also has favourable effects on neurohormone levels in heart failure patients Levosimendan is generally well tolerated in acute heart failure patients: the most common adverse events encountered in this setting are hypotension, headache, atrial fibrillation, hypokalaemia and tachycardia Levosimendan has also been studied in other therapeutic applications, particularly cardiac surgery - in which it has shown a range of beneficial haemodynamic and cardioprotective effects, and a favourable influence on clinical outcomes - and has been evaluated in repetitive dosing protocols in patients with advanced chronic heart failure Levosimendan has shown preliminary positive effects in a range of conditions requiring inotropic support, including right ventricular failure, cardiogenic shock, septic shock, and Takotsubo cardiomyopathy

Cardiac steatosis associates with visceral obesity in nondiabetic obese men.

Abstract: Background: Liver fat and visceral adiposity are involved in the development of the metabolic syndrome (MetS). Ectopic fat accumulation within and around the heart has been related to increased risk of heart disease. The aim of this study was to explore components of cardiac steatosis and their relationship to intra-abdominal ectopic fat deposits and cardiometabolic risk factors in nondiabetic obese men. Methods: Myocardial and hepatic triglyceride (TG) contents were measured with 1.5 T magnetic resonance spectroscopy, and visceral adipose (VAT), abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by magnetic resonance imaging in 37 men with the MetS and in 40 men without the MetS. Results: Myocardial and hepatic TG contents, VAT, SAT, epicardial fat volumes, and pericardial fat volumes were higher in men with the MetS compared with subjects without the MetS (P < .001). All components of cardiac steatosis correlated with SAT, VAT, and hepatic TG content and the correlations seemed to be strongest with VAT. Myocardial TG content, epicardial fat, pericardial fat, VAT, and hepatic TG content correlated with waist circumference, body mass index, high-density lipoprotein cholesterol TGs, very low-density lipoprotein-1 TGs, and the insulin-resistance homeostasis model assessment index. VAT was a predictor of TGs, high-density lipoprotein cholesterol, and measures of glucose metabolism, whereas age and SAT were determinants of blood pressure parameters. Conclusions: We suggest that visceral obesity is the best predictor of epicardial and pericardial fat in abdominally obese subjects. Myocardial TG content may present a separate entity that is influenced by factors beyond visceral adiposity.

Predictive value of electrocardiographic T-wave morphology parameters and T-wave peak to T-wave end interval for sudden cardiac death in the general population.

Abstract: Background— Previous population studies have found an association between electrocardiographic T-wave morphology parameters and cardiovascular mortality, but their relationship to sudden cardiac death (SCD) is not clear. To our knowledge, there are no follow-up studies assessing the association between electrocardiographic T-wave peak to T-wave end interval (TPE) and SCD. We assessed the predictive value of electrocardiographic T-wave morphology parameters and TPE for SCD in an adult general population sample. Methods and Results— A total of 4 T-wave morphology parameters (principal component analysis ratio, T-wave morphology dispersion, total cosine R-to-T, T-wave residuum) as well as TPE were measured from digital standard 12-lead ECGs in 5618 adults (46% men; mean age 50.9±12.5 years) participating in the Finnish population–based Health 2000 Study. After a mean follow-up time of 7.7±1.4 years, 72 SCDs had occurred. In univariable analyses, all T-wave morphology parameters were associated with an increased SCD risk. In multivariable Cox models, T-wave morphology dispersion and total cosine R-to-T remained as predictors of SCD, with T-wave morphology dispersion showing the highest SCD risk (hazard ratio of 1.4 [95% confidence interval 1.1−1.7, P =0.001] per 1 SD increase in the loge T-wave morphology dispersion). In contrast, TPE was not associated with SCD in univariable or multivariable analyses. Conclusions— Electrocardiographic T-wave morphology parameters describing the 3-dimensional shape of the T-wave stratify SCD risk in the general population, but we did not find an association between TPE and SCD.

Cardiac steatosis and left ventricular function in men with metabolic syndrome

Abstract: Background Ectopic accumulation of fat accompanies visceral obesity with detrimental effects. Lipid oversupply to cardiomyocytes leads to cardiac steatosis, and in animal studies lipotoxicity has been associated with impaired left ventricular (LV) function. In humans, studies have yielded inconclusive results. The aim of the study was to evaluate the role of epicardial, pericardial and myocardial fat depots on LV structure and function in male subjects with metabolic syndrome (MetS).

Cardiovascular Events in Patients With Hypertension and Left Ventricular Hypertrophy: A LIFE Study

Abstract: Background: Patients with left ventricular hypertrophy (LVH) have been shown to have increased incidence of sudden cardiac death (SCD). This analysis assessed predictors of SCD in a large cohort of hypertensive patients with ECG LVH. Methods: In the LIFE (n=9,193), a double-blind, randomized, parallel-group trial, 190 patients died suddenly within 24 hours of onset of symptoms during the average 4.8 year follow-up period. Results: Patients with SCD were older, more often male and had higher ECG LVH, albuminuria and more frequent history of atrial fibrillation, diabetes, coronary heart and cerebral vascular disease. SCD was not predicted by systolic or diastolic blood pressure, body mass index, cholesterol, potassium or history of peripheral vascular disease. In multivariate Cox analysis Cornell voltage-duration product predicted SCD (Table) and remained predictive in a subgroup (n=3,617) without history of coronary heart disease or albuminuria. The 1-year Cornell voltage-duration product was more predictive than baseline indicating that regression of LVH is more predictive than baseline LVH. Treatment with losartan compared to atenolol was not associated with a lower SCD rate (HR=0.88 [95% CI: 0.66-1.17], p=0.364). Conclusion: Baseline LVH predicts SCD independent of history of coronary heart disease and other cardiovascular risk factors and remains predictive in the subpopulation without signs of atherosclerosis. Furthermore, losartan vs. atenolol treatment appears to benefit SCD equally.

Two founder mutations in the alpha-tropomyosin and the cardiac myosin-binding protein C genes are common causes of hypertrophic cardiomyopathy in the Finnish population

Abstract: Background. Hypertrophic cardiomyopathy (HCM) is predominantly caused by a large number of various mutations in the genes encoding sarcomeric proteins. However, two prevalent founder mutations for HCM in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes have previously been identified in eastern Finland. Objective. To assess the prevalence of these founder mutations in a large population of patients with HCM from all over Finland. Patients and methods. We screened for two founder mutations (TPM1-D175N and MYBPC3-Q1061X) in 306 unrelated Finnish patients with HCM from the regions covering a population of ∼4,000,000. Results. The TPM1-D175N mutation was found in 20 patients (6.5%) and the MYBPC3-Q1061X in 35 patients (11.4%). Altogether, the two mutations accounted for 17.9% of the HCM cases. In addition, 61 and 59 relatives of the probands were found to be carriers of TPM1-D175N and MYBPC3-Q1061X, respectively. The mutations showed regional clustering. TPM1-D175N was pre...

Plasma IgA antibody levels to malondialdehyde acetaldehyde-adducts are associated with inflammatory mediators, obesity and type 2 diabetes

Abstract: Aim. Obesity and type 2 diabetes (T2D) associate with increased oxidative stress. Malondialdehyde acetaldehyde (MAA) adducts have been suggested to be one of the antigenic epitopes in MDA-LDL responsible for the antibody recognition. Our aim was to investigate the associations between plasma IgA antibodies to MAA-LDL, inflammatory markers, adipokines, obesity, and T2D.Methods. IgA to MAA-LDL were measured in a subsample (n = 1507) of the Finnish Health 2000 survey. The associations between antibody levels, obesity, TNF-α, IL-6, high-sensitivity (hs) CRP, resistin, adiponectin, fasting plasma (fp) glucose, fp-insulin, glycosylated hemoglobin (Hb-A1C), and T2D were investigated.Results. IgA to MAA-LDL associated positively with fasting plasma insulin. IgA to MAA-LDL were higher among subjects with T2D (P < 0.001) compared to subjects with normal glucose metabolism. IgA to MAA-LDL associated with obesity, but was not independently (P = 0.002, not significant after correction for multiple tests) assoc...

Impact of overweight and obesity on cardiac benefit of antihypertensive treatment

Abstract: Background and aims Increased body mass index (BMI) has been associated with increased cardiovascular morbidity and mortality in hypertension. Less is known about the impact of BMI on improvement in left ventricular (LV) structure and function during antihypertensive treatment. Methods and results Annual BMI, echocardiograms and cardiovascular events were recorded in 875 hypertensive patients with LV hypertrophy during 4.8 years randomized treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy. Patients were grouped by baseline BMI into normal ( n = 282), overweight ( n = 405), obese ( n = 150) and severely obese groups ( n = 38) (BMI ≤24.9, 25.0–29.9, 30.0–34.9, and ≥35.0 kg/m 2 , respectively). At study end, residual LV hypertrophy was present in 54% of obese and 79% of severely obese patients compared to 31% of normal weight patients (both p 2.7 , higher BMI predicted less LV hypertrophy reduction and more reduction in LV ejection fraction (both p 2 higher baseline BMI predicted a 5% higher rate of cardiovascular events and 10% higher cardiovascular mortality over 4.8 years (both p Conclusions In hypertensive patients in the LIFE study, increased BMI was associated with less reduction of LV hypertrophy and less improvement in LV systolic function which may contribute to the observed higher cardiovascular event rate of treated hypertensive patients.

Subgingival Bacterial Burden in Relation to Clinical and Radiographic Periodontal Parameters

Abstract: Background: This cross-sectional study characterizes the association between subgingival bacterial profile and periodontal parameters in patients assigned to coronary angiography because of cardiologic problems, which may affect the oral microbiota.Methods: Pooled subgingival bacterial samples were collected from 477 dentate individuals during the oral examinations, along with periodontal probing depth (PD) and assessments of bleeding on probing (BOP) and radiographic alveolar bone loss (ABL). The checkerboard DNA–DNA hybridization assay was used to determine the levels of 29 oral bacteria, which were divided into three bacterial complexes.Results: All bacterial combinations from the etiologic bacterial group and each species from the red complex were significantly associated (P <0.001) with grade of ABL. The prevalence of the etiologic bacterial group and the level of each species were also associated strongly with the proportion of sites with PD 4 to 5 mm and ≥6 mm, BOP, and ABL, except Aggregatibacter ...

Subgingival Aggregatibacter actinomycetemcomitans associates with the risk of coronary artery disease

Abstract: Aim We investigated the association between angiographically verified coronary artery disease (CAD) and subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsy ...

Subgingival Bacterial Burden in Relation to Clinical and Radiographic Periodontal

Abstract: Background: This cross-sectional study characterizes the association between subgingival bacterial profile and periodontal parameters in patients assigned to coronary angiography because of cardiologic problems, which may affect the oral microbiota. Methods: Pooled subgingival bacterial samples were collected from 477 dentate individuals during the oral examinations, along with periodontal probing depth (PD) and assessments of bleeding on probing (BOP) and radiographic alveolar bone loss (ABL). The checkerboard DNA–DNA hybridization assay was used to determine the levels of 29 oral bacteria, which were divided into three bacterial complexes. Results: All bacterial combinations from the etiologic bacterial group and each species from the red complex were significantly associated (P <0.001) with grade of ABL. The prevalence of the etiologic bacterial group and the level of each species were also associated strongly with the proportion of sites with PD 4 to 5 mm and ‡6 mm, BOP, and ABL, except Aggregatibacter actinomycetemcomitans. Levels of Gram-negative oral bacteria correlated significantly with those of Gram-positive species (r = 0.840, P <0.001). In multiple logistic regression analysis, the prevalence of the etiologic bacterial group, levels of Gram-negative bacteria and Treponema denticola, and the prevalence of Porphyromonas gingivalis and T. denticola associated significantly with ABL, whereas other bacterial complexes and levels of Grampositive species did not. Conclusions: Although levels of Gram-negative and -positive species paralleled periodontal parameters, only the species considered etiologic were associated with ABL. J Periodontol 2013;84:1809-1817.

Management of acute heart failure and the effect of systolic blood pressure on the use of intravenous therapies.

Abstract: Aims:To examine the use of the treatments for acute heart failure (AHF) recommended by ESC guidelines in different clinical presentations and blood pressure groups.Methods:The use of intravenous diuretics, nitrates, opioids, inotropes, and vasopressors as well as non-invasive ventilation (NIV) was analysed in 620 patients hospitalized due to AHF. The relation between AHF therapies and clinical presentation, especially systolic blood pressure (SBP) on admission, was also assessed.Results:Overall, 76% of patients received i.v. furosemide, 42% nitrates, 29% opioids, 5% inotropes and 7% vasopressors, and 24% of patients were treated with NIV. Furosemide was the most common treatment in all clinical classes and irrespective of SBP on admission. Nitrates were given most often in pulmonary oedema and hypertensive AHF. Overall, only SBP differed significantly between patients with and without the studied treatments. SBP was higher in patients treated with nitrates than in those who were not (156 vs. 141 mmHg, p<0...

Diagnostic efficacy of myeloperoxidase to identify acute coronary syndrome in subjects with chest pain

Abstract: Background. Early diagnosis of acute coronary syndrome (ACS) is frequently a challenging task.Aims. To assess the role of novel biomarkers to identify ACS.Methods. Concentrations of lipids, lipoproteins, oxidized LDL (oxLDL), high-sensitivity C-reactive protein (hsCRP), paraoxonase-1 (PON1), secretory phospholipase A2 (sPLA2), and myeloperoxidase (MPO) were measured in 703 patients (mean age 65.5 ± 11.2 years; 422 men, 281 women) without diabetes mellitus assigned to coronary angiogram. The subjects were divided into three groups: ACS (n = 242), stable angina pectoris (SAP) (n = 242), and normal coronary artery (NCA) (n = 219).Results. HDL-cholesterol (HDL-C) (P < 0.001) and apolipoproteinA-I concentrations (P < 0.0001) were lowest in subjects with ACS. LDL-C (P = 0.008) and non-HDL (P < 0.0001) were higher in the ACS group than in the SAP group. Leukocyte count (P < 0.0001), oxLDL (P < 0.05), hsCRP (P < 0.001), sPLA2 (P < 0.05), and MPO (P < 0.0001) were highest in the ACS group. In multivariate ...

Outcome up to one year following different reperfusion strategies in acute ST-segment elevation myocardial infarction: The Helsinki-Uusimaa Hospital District registry of ST-Elevation Acute Myocardial Infarction (HUS-STEMI)

Abstract: Aims:Current guidelines prefer primary percutaneous coronary intervention (pPCI) over fibrinolysis in the treatment of acute ST-elevation myocardial infarction (STEMI). Pre-hospital fibrinolysis followed by early invasive evaluation is an alternative that we have used in patients presenting within three hours of symptom onset. We made a survey of patients suffering an acute STEMI over one year to assess mortality and adverse events following either pPCI or fibrinolysis.Methods and results:Of the 448 consecutive STEMI patients, 194 were treated with pPCI and 176 underwent fibrinolysis; 78 patients received no reperfusion treatment within 12 hours (NRT group). The median TIMI risk scores were 4.0, 3.0 and 4.0 in the pPCI, fibrinolysis and NRT groups, respectively (p<0.001). Mortality at one year was 14.4% following pPCI, 5.1% following fibrinolysis and 12.8% in the NRT group (p=0.011 across all groups and p=0.003 between pPCI and fibrinolysis, adjusted for differences in risk factors). The one-year composit...

Predicting recovery of myocardial function by electrocardiography after acute infarction.

Abstract: Background In acute ischemic left ventricular (LV) dysfunction, distinguishing viable myocardium is clinically important. Methods Body surface potential mapping (Electrocardiography [ECG] with 123 leads), was recorded in 62 patients with acute coronary syndrome (ACS). ECG variables were computed from de- and repolarization phases. LV segmental wall motion was assessed by echocardiography acutely and after 1 year. Results The number of dysfunctional segments (DFS) diminished during follow-up in 37 patients (recovery group) and remained the same or increased in 25 patients (nonrecovery group). Acutely, DFS was 5.7 ± 2.1 versus 4.4 ± 2.4 (P = 0.02), and peak CK-MBm 141 ± 157 versus 156 ± 167 μg/L (P = 0.78) in the recovery versus nonrecovery group. At follow-up, DFS was 1.9 ± 1.7 versus 6.5 ± 2.6 (P < 0.001). The best ECG variable to predict decrease in DFS depended on the region of acute LV dysfunction: The best variable in the left anterior descending region was the integral of the first QRS integral (area under the curve [AUC] 0.82, P = 0.002); in the right coronary artery region, this was the integral of the ST segment (AUC 0.98, P = 0.003); and in the left circumflex region, the area including the ST segment and the T wave (AUC 0.97, P = 0.006). Conclusions In ACS patients, computed ECG variables predict recovery of LV function from ischemic myocardial injury, even in the presence of comparable CK-MBm release and LV dysfunction.

Acute heart failure precipitated by acute coronary syndrome - patient characteristics, management and survival

Abstract: Purpose: Acute coronary syndrome (ACS) may precipitate up to one third of acute heart failure (AHF) cases. As scientific data is scarce, we assessed characteristics, management and survival of patients with ACS as a precipitating factor of AHF (AHF-ACS). Methods: Data of 620 patients hospitalized due to AHF were prospectively collected in a multicenter study. All-cause mortality was assessed during 12 months follow-up. The data were compared between patients with and without ACS. Comparisons between groups were performed by χ2 test, t-test or Mann-Whitney U as appropriate. Survival analyses were performed using Kaplan-Meier method and multivariable logistic regression. Results: AHF-ACS patients (32%) had significantly more often coronary artery disease, diabetes and hypercholesterolemia as underlying diseases. Most of the AHF-ACS patients presented with de novo AHF (61% vs 43% in non-ACS, p<0.001). There were no significant differences between the two groups in blood pressure, heart rate or biochemistry (eGFR, sodium, hemoglobin, CRP) on admission. Intravenous nitrates, furosemide, opioids, inotropes and vasopressors as well as non-invasive ventilation and invasive coronary procedures (angiography, PCI, CABG) were used significantly more often in AHF-ACS patients (p<0.001 for all). Although survival at 12 months was similar in the two groups, early mortality was significantly higher in patients with AHF-ACS (Figure). In fact, ACS was a significant predictor of 30-day prognosis in multivariable analysis (adjusted OR 1.9, 95% CI 1.06-3.52, p=0.033). ![Figure][1] Figure 1 Conclusion: AHF-ACS patients differ from those without ACS in terms of underlying diseases and treatment, but not in clinical parameters measured on admission. ACS in AHF was independently related to increased short-term mortality. [1]: pending:yes

The role of cardiorenal biomarkers for risk stratification in the early follow-up after hospitalisation for acute heart failure.

Abstract: Context: Cardiorenal biomarkers (CBs) predict outcome in acute heart failure (AHF).Objective: To evaluate CBs in early follow-up prognostication.Methods: In 124 AHF patients, levels of CystatinC, NT-proBNP and TroponinI measured five weeks from admission (W5) and relative change from day 2 (D2) were assessed for 6-month prognosis (mortality/HF hospitalization).Results: The combined end-point occurred in 33 patients (27%). D2-, W5-cystatin≥ median, and lack of ≥30%decrease in NT-proBNP were independent predictors of outcome. Additionally, a risk score established from W5 CBs identified patients with very high event rate.Conclusions: CBs at early follow-up of AHF may guide risk stratification.