TY  - JOUR
AB  - Objective While metabolic dysfunction occurs in several pulmonary arterial hypertension (PAH) animal models, its role in the human hypertensive right ventricle (RV) and lung is not well characterised. We investigated whether circulating metabolite concentrations differ across the hypertensive RV and/or the pulmonary circulation, and correlate with invasive haemodynamic/echocardiographic variables in patients with PAH.Methods Prospective EDTA blood collection during cardiac catheterisation from the superior vena cava (SVC), pulmonary artery (PA) and ascending aorta (AAO) in children with PAH (no shunt) and non-PAH controls (Con), followed by unbiased screens of 427 metabolites and 836 lipid species and fatty acids (FAs) in blood plasma (Metabolon and Lipidyzer platforms). Metabolite concentrations were correlated with echocardiographic and invasive haemodynamic variables.Results Metabolomics/lipidomics analysis of differential concentrations (false discovery rate<0.15) revealed several metabolite gradients in the trans-RV (PA vs SVC) setting. Notably, dicarboxylic acids (eg, octadecanedioate: fold change (FC)_Control=0.77, FC_PAH=1.09, p value=0.044) and acylcarnitines (eg, stearoylcarnitine: FC_Control=0.74, FC_PAH=1.21, p value=0.058). Differentially regulated metabolites were also found in the transpulmonary (AAO vs PA) setting and between-group comparisons, that is, in the SVC (PAH-S VC vs Con-S VC), PA and AAO. Importantly, the differential PAH-metabolite concentrations correlated with numerous outcome-relevant variables (e.g., tricuspid annular plane systolic excursion, pulmonary vascular resistance).Conclusions In PAH, trans-RV and transpulmonary metabolite gradients exist and correlate with haemodynamic determinants of clinical outcome. The most pronounced differential trans-R V gradients are known to be involved in lipid metabolism/lipotoxicity, that is, accumulation of long chain FAs. The identified accumulation of dicarboxylic acids and acylcarnitines likely indicates impaired beta-oxidation in the hypertensive RV and represents emerging biomarkers and therapeutic targets in PAH.
AU  - Chouvarine, P.*
AU  - Giera, M.*
AU  - Kastenmüller, G.
AU  - Artati, A.
AU  - Adamski, J.
AU  - Bertram, H.*
AU  - Hansmann, G.*
C1  - 58358
C2  - 48449
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
SP  - 1332-1341
TI  - Trans-right ventricle and transpulmonary metabolite gradients in human pulmonary arterial hypertension.
JO  - Heart
VL  - 106
IS  - 17
PB  - Bmj Publishing Group
PY  - 2020
SN  - 1355-6037
ER  - 

TY  - JOUR
AB  - OBJECTIVE: The comprehensive assaying of low-molecular-weight compounds, for example, metabolomics, provides a unique tool to uncover novel biomarkers and understand pathways underlying myocardial infarction (MI). We used a targeted metabolomics approach to identify biomarkers for MI and evaluate their involvement in the pathogenesis of MI. METHODS AND RESULTS: Using three independent, prospective cohorts (KORA S4, KORA S2 and AGES-REFINE), totalling 2257 participants without a history of MI at baseline, we identified metabolites associated with incident MI (266 cases). We also investigated the association between the metabolites and high-sensitivity C reactive protein (hsCRP) to understand the relation between these metabolites and systemic inflammation. Out of 140 metabolites, 16 were nominally associated (p<0.05) with incident MI in KORA S4. Three metabolites, arginine and two lysophosphatidylcholines (LPC 17:0 and LPC 18:2), were selected as biomarkers via a backward stepwise selection procedure in the KORA S4 and were significant (p<0.0003) in a meta-analysis comprising all three studies including KORA S2 and AGES-REFINE. Furthermore, these three metabolites increased the predictive value of the Framingham risk score, increasing the area under the receiver operating characteristic score in KORA S4 (from 0.70 to 0.78, p=0.001) and AGES-REFINE study (from 0.70 to 0.76, p=0.02), but was not observed in KORA S2. The metabolite biomarkers attenuated the association between hsCRP and MI, indicating a potential link to systemic inflammatory processes. CONCLUSIONS: We identified three metabolite biomarkers, which in combination increase the predictive value of the Framingham risk score. The attenuation of the hsCRP-MI association by these three metabolites indicates a potential link to systemic inflammation.
AU  - Ward-Caviness, C.K.
AU  - Xu, T.
AU  - Aspelund, T.*
AU  - Thorand, B.
AU  - Montrone, C.
AU  - Meisinger, C.
AU  - Dunger-Kaltenbach, I.
AU  - Zierer, A.
AU  - Yu, Z.
AU  - Helgadottir, I.R.*
AU  - Harris, T.B.*
AU  - Launer, L.J.*
AU  - Ganna, A.*
AU  - Lind, L.*
AU  - Eiriksdottir, G.*
AU  - Waldenberger, M.
AU  - Prehn, C.
AU  - Suhre, K.
AU  - Illig, T.*
AU  - Adamski, J.
AU  - Ruepp, A.
AU  - Koenig, W.*
AU  - Gudnason, V.*
AU  - Emilsson, V.*
AU  - Wang-Sattler, R.
AU  - Peters, A.
C1  - 50622
C2  - 42455
CY  - London
SP  - 1278-1285
TI  - Improvement of myocardial infarction risk prediction via inflammation-associated metabolite biomarkers.
JO  - Heart
VL  - 103
IS  - 16
PB  - Bmj Publishing Group
PY  - 2017
SN  - 1355-6037
ER  - 

TY  - JOUR
AB  - Persistent pulmonary hypertension of the newborn (PPHN) is the most common neonatal form and mostly reversible after a few days with improvement of the underlying pulmonary condition. When pulmonary hypertension (PH) persists despite adequate treatment, the severity of parenchymal lung disease should be assessed by chest CT. Pulmonary vein stenosis may need to be ruled out by cardiac catheterisation and lung biopsy, and genetic workup is necessary when alveolar capillary dysplasia is suspected. In PPHN, optimisation of the cardiopulmonary situation including surfactant therapy should aim for preductal SpO2between 91% and 95% and severe cases without post-tricuspid-unrestrictive shunt may receive prostaglandin E1 to maintain ductal patency in right heart failure. Inhaled nitric oxide is indicated in mechanically ventilated infants to reduce the need for extracorporal membrane oxygenation (ECMO), and sildenafil can be considered when this therapy is not available. ECMO may be indicated according to the ELSO guidelines. In older preterm infant, where PH is mainly associated with bronchopulmonary dysplasia (BPD) or in term infants with developmental lung anomalies such as congenital diaphragmatic hernia or cardiac anomalies, left ventricular diastolic dysfunction/left atrial hypertension or pulmonary vein stenosis, can add to the complexity of the disease. Here, oral or intravenous sildenafil should be considered for PH treatment in BPD, the latter for critically ill patients. Furthermore, prostanoids, mineralcorticoid receptor antagonists, and diuretics can be beneficial. Infants with proven or suspected PH should receive close follow-up, including preductal/postductal SpO2measurements, echocardiography and laboratory work-up including NT-proBNP, guided by clinical improvement or lack thereof.
AU  - Hilgendorff, A.
AU  - Apitz, C.*
AU  - Bonnet, D.*
AU  - Hansmann, G.*
C1  - 50143
C2  - 42031
SP  - ii49-ii56
TI  - Pulmonary hypertension associated with acute or chronic lung diseases in the preterm and term neonate and infant. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.
JO  - Heart
VL  - 102
PY  - 2016
SN  - 1355-6037
ER  - 

TY  - JOUR
AB  - OBJECTIVE: To estimate the burden of social inequalities in coronary heart disease (CHD) and to identify their major determinants in 15 European populations. METHODS: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) study comprised 49 cohorts of middle-aged European adults free of CHD (110 928 individuals) recruited mostly in the mid-1980s and 1990s, with comparable assessment of baseline risk and follow-up procedures. We derived three educational classes accounting for birth cohorts and used regression-based inequality measures of absolute differences in CHD rates and HRs (ie, Relative Index of Inequality, RII) for the least versus the most educated individuals. RESULTS: N=6522 first CHD events occurred during a median follow-up of 12 years. Educational class inequalities accounted for 343 and 170 additional CHD events per 100 000 person-years in the least educated men and women compared with the most educated, respectively. These figures corresponded to 48% and 71% of the average event rates in each gender group. Inequalities in CHD mortality were mainly driven by incidence in the Nordic countries, Scotland and Lithuania, and by 28-day case-fatality in the remaining central/South European populations. The pooled RIIs were 1.6 (95% CI 1.4 to 1.8) in men and 2.0 (1.7 to 2.4) in women, consistently across population. Risk factors accounted for a third of inequalities in CHD incidence; smoking was the major mediator in men, and High-Density-Lipoprotein (HDL) cholesterol in women. CONCLUSIONS: Social inequalities in CHD are still widespread in Europe. Since the major determinants of inequalities followed geographical and gender-specific patterns, European-level interventions should be tailored across different European regions.
AU  - Veronesi, G.*
AU  - Ferrario, M.M.*
AU  - Kuulasmaa, K.*
AU  - Bobak, M.*
AU  - Chambless, L.E.*
AU  - Salomaa, V.*
AU  - Söderberg, S.*
AU  - Pajak, A.*
AU  - Jørgensen, T.*
AU  - Amouyel, P.*
AU  - Arveiler, D.*
AU  - Drygas, W.*
AU  - Ferrieres, J.*
AU  - Giampaoli, S.*
AU  - Kee, F.*
AU  - Iacoviello, L.*
AU  - Malyutina, S.A.*
AU  - Peters, A.
AU  - Tamosiunas, A.*
AU  - Tunstall-Pedoe, H.*
AU  - Cesana, G.*
C1  - 47844
C2  - 39509
CY  - London
SP  - 958-965
TI  - Educational class inequalities in the incidence of coronary heart disease in Europe.
JO  - Heart
VL  - 102
IS  - 12
PB  - Bmj Publishing Group
PY  - 2016
SN  - 1355-6037
ER  - 

TY  - JOUR
AB  - OBJECTIVE: Due to the burden of coronary heart disease (CHD), the monitoring of CHD trends is required. This study sought to examine the acute myocardial infarction (AMI) trends in attack and mortality rates, and in 28-day case-fatality, in six European populations during 1985-2010. METHODS: Data consisted of 78 128 AMI events included in eight population-based registries from Finland (several populations), Italy (Brianza and Varese), Germany (Augsburg), France (Haute-Garonne), Spain (Girona) and Estonia (Tallinn). AMI event rates and case-fatality trends were analysed using the annual percentage change (APC) obtained by negative binomial and joinpoint regression. RESULTS: AMI attack and mortality rates decreased in most populations. Finland experienced the steepest decline in attack rates (APC=-4.4% (95% CI -5.1 to -2.9) in men; -4.0% (-5.1 to -2.8), in women). Total-hospital and inhospital case-fatality decreased in all populations except in Tallinn. The steepest decline in total case-fatality occurred in Spain (-3.8% (-5.3 to -2.4) in men; -5.1% (-6.9 to -3.3) in women). Prehospital case-fatality trends differed significantly by population and sex. The trends for all included populations showed a significant decline in AMI event rates and case-fatality, in both sexes and all age groups. However, in women aged 65-74 years, a significant increase in total case-fatality occurred in 2005-2010 (4.7% (0.7 to 8.8)). CONCLUSIONS: AMI event rates and inhospital case-fatality declined in 1985-2010 in almost all populations analysed. Prehospital case-fatality declined only in certain population groups, showing differences by sex. These results highlight the need of specific strategies in AMI prevention for certain groups and populations.
AU  - Dégano, I.R.*
AU  - Salomaa, V.*
AU  - Veronesi, G.*
AU  - Ferrieres, J.*
AU  - Kirchberger, I.
AU  - Laks, T.*
AU  - Havulinna, A.S.*
AU  - Ruidavets, J.B.*
AU  - Ferrario, M.M.*
AU  - Meisinger, C.
AU  - Elosua, R.*
AU  - Marrugat, J.*
AU  - Acute Myocardial Infarction Trends in Europe (AMITIE) Study Investigators (*)
C1  - 44337
C2  - 36829
SP  - 1413-1421
TI  - Twenty-five-year trends in myocardial infarction attack and mortality rates, and case-fatality, in six European populations.
JO  - Heart
VL  - 101
IS  - 17
PY  - 2015
SN  - 1355-6037
ER  - 

TY  - JOUR
AB  - Objective We aimed to describe current characteristics of patients admitted for acute coronary syndrome (ACS) in Western Europe and to analyse whether international in-hospital mortality variations are explained by differences in patients’ baseline characteristics and in clinical management. Methods We studied a population-based longitudinal cohort conducted in Finland, France, Germany, Greece, Portugal and Spain, and comprising 12 231 consecutive ACS patients admitted in 53 hospitals between 2008 and 2010. Baseline characteristics, clinical management and inhospital outcomes were recorded. Contextual effect of country on death was analysed through multilevel analysis. Results Of all patients included, 8221 (67.2%) had NSTEMI (non-ST-elevation myocardial infarction), and 4010 (32.8%) had STEMI (ST-elevation myocardial infarction). Inhospital mortality ranged from 15.1% to 4.9% for German and Spanish STEMI patients, and from 6.8% to 1.9% for Finnish and French NSTEMI patients (p<0.001 for both). These international variations were explained by differences in patients’ baseline characteristics (older patients more likely to have cardiogenic shock in Germany) and in clinical management, with differences in rates of thrombolysis (less performed in Germany) and primary percutaneous coronary intervention (high in Germany, low in Greece). A remaining contextual effect of country was identified after extensive adjustment. Conclusions Inhospital mortality rates of STEMI and NSTEMI patients were two to three times higher in Finland, Germany and Portugal than in Greece and Spain, with intermediate values for France. Differences in baseline characteristics and clinical management partly explain differences in outcome. Our data also suggest an impact of the healthcare system organisation.  
AU  - André, R.*
AU  - Bongard, V.*
AU  - Elosua, R.*
AU  - Kirchberger, I.
AU  - Farmakis, D.*
AU  - Häkkinen, U.*
AU  - Fusco, D.*
AU  - Torre, M.*
AU  - Garel, P.*
AU  - Araujo, C.*
AU  - Meisinger, C.
AU  - Lekakis, J.*
AU  - Malmivaara, A.*
AU  - Dovali, M.*
AU  - Pereira, M.*
AU  - Marrugat, J.*
AU  - Ferrieres, J.*
C1  - 31237
C2  - 34235
CY  - London
SP  - 1201-1207
TI  - International differences in acute coronary syndrome patients’ baseline characteristics, clinical management and outcomes in Western Europe: The EURHOBOP study.
JO  - Heart
VL  - 100
IS  - 15
PB  - Bmj Publishing Group
PY  - 2014
SN  - 1355-6037
ER  - 

TY  - JOUR
AB  - OBJECTIVE: This time series study aimed to examine the association between daily air temperature and cause-specific cardiovascular mortality in Bavaria, Southern Germany. METHODS: We obtained data from the cities Munich, Nuremberg and Augsburg and two adjacent administrative districts (Augsburg and Aichach-Friedberg), for the period 1990-2006. Data included daily cause-specific cardiovascular death counts, mean daily meteorological variables and air pollution concentrations. In the first stage, data were analysed for Munich, Nuremberg and the Augsburg region separately using Poisson regression models combined with distributed lag non-linear models adjusting for long-term trend, calendar effects and meteorological factors. In a second stage, we combined city-specific exposure-response relationships through a multivariate meta-analysis framework. RESULTS: An increase in the 2-day average temperature from the 90th (20.0°C) to the 99th centiles (24.8°C) resulted in an increase of cardiovascular mortality by 10% (95% CI 5% to 15%) in the pooled analysis, while for a decrease from the 10th (-1.0°C) to the 1st centiles (-7.5°C) in the 15-day average temperature cardiovascular mortality increased by 8% (95% CI 2% to 14%). Strongest consistent risk estimates were seen for high 2-day average temperatures and mortality due to other heart diseases (including arrhythmias and heart failure) and cerebrovascular diseases, especially in the elderly. CONCLUSIONS: Results indicate that, in addition to low temperatures, high temperatures increase cause-specific cardiovascular mortality in temperature climates. These findings may guide planning public health interventions to control and prevent the health effects of exposure to air temperature, especially for individuals at risk for mortality due to heart failure, arrhythmias or cerebrovascular diseases.
AU  - Breitner-Busch, S.
AU  - Wolf, K.
AU  - Peters, A.
AU  - Schneider, A.E.
C1  - 31563
C2  - 34569
CY  - London
SP  - 1272-1280
TI  - Short-term effects of air temperature on cause-specific cardiovascular mortality in Bavaria, Germany.
JO  - Heart
VL  - 100
IS  - 16
PB  - Bmj Publishing Group
PY  - 2014
SN  - 1355-6037
ER  - 

TY  - JOUR
AB  - Objective To assess whether educational class, an index of socioeconomic position, improves the accuracy of the SCORE cardiovascular disease (CVD) risk prediction equation. Methods In a pooled analysis of 68 455 40-64-year-old men and women, free from coronary heart disease at baseline, from 47 prospective population-based cohorts from Nordic countries (Finland, Denmark, Sweden), the UK (Northern Ireland, Scotland), Central Europe (France, Germany, Italy) and Eastern Europe (Lithuania, Poland) and Russia, we assessed improvements in discrimination and in risk classification (net reclassification improvement (NRI)) when education was added to models including the SCORE risk equation. Results The lowest educational class was associated with higher CVD mortality in men (pooled age-adjusted HR=1.64, 95% CI 1.42 to 1.90) and women (HR=1.31, 1.02 to 1.68). In men, the HRs ranged from 1.3 (Central Europe) to 2.1 (Eastern Europe and Russia). After adjustment for the SCORE risk, the association remained statistically significant overall, in the UK and Eastern Europe and Russia. Education significantly improved discrimination in all European regions and classification in Nordic countries (clinical NRI=5.3%) and in Eastern Europe and Russia (NRI=24.7%). In women, after SCORE risk adjustment, the association was not statistically significant, but the reduced number of deaths plays a major role, and the addition of education led to improvements in discrimination and classification in the Nordic countries only. Conclusions We recommend the inclusion of education in SCORE CVD risk equation in men, particularly in Nordic and East European countries, to improve social equity in primary prevention. Weaker evidence for women warrants the need for further investigations.
AU  - Ferrario, M.M.*
AU  - Veronesi, G.*
AU  - Chambless, L.E.*
AU  - Tunstall-Pedoe, H.D.*
AU  - Kuulasmaa, K.A.*
AU  - Salomaa, V.V.*
AU  - Borglykke, A.*
AU  - Hart, N.*
AU  - Söderberg, S.*
AU  - Cesana, G.C.*
AU  - MORGAM Project (Döring, A.
AU  - Wichmann, H.-E.)
C1  - 31241
C2  - 34274
SP  - 1179-1187
TI  - The contribution of educational class in improving accuracy of cardiovascular risk prediction across European regions: The MORGAM Project Cohort Component.
JO  - Heart
VL  - 100
PY  - 2014
SN  - 1355-6037
ER  - 

TY  - JOUR
AB  - OBJECTIVE: The implantable cardioverter defibrillator (ICD) is the gold standard therapy to prevent life-threatening arrhythmias. Phobic anxiety predicts ventricular arrhythmia in coronary heart disease patients, but little is known about phobic anxiety in ICD patients. This study aimed to identify determinants and the course of phobic anxiety in ICD patients. PATIENTS: 140 outpatients living with an ICD (mean age 56±14 years, 66% men). MAIN OUTCOME MEASURES: Phobic anxiety was assessed with the Symptom Checklist-90 Revised at a mean of 27±21 months (range 3-109) post-ICD placement (baseline) and after an average follow-up of 41±18 months (range 10-82). Multivariate linear regression models considered sociodemographic factors, clinical variables and psychological scales as potential determinants of phobic anxiety scores. RESULTS: ICD patients reported more than 10-fold higher levels of phobic anxiety than a previous representative population survey (2.6±3.4 vs 0.2±0.4). Greater age (p=0.003), previous shock experience (p=0.007), depressed mood (p<0.001) and hypochondriasis (p=0.005) were associated with higher phobic anxiety scores at baseline. Multimorbidity (p=0.030) and higher baseline phobic anxiety (p<0.001) determined greater phobic anxiety at follow-up. Younger age (p=0.029) and an elevated number of non-cardiac diseases (p=0.019) were both associated with an increase in phobic anxiety scores from baseline to follow-up. More patients had high phobic anxiety levels (score >4) at follow-up compared with baseline (31% vs 24%; p=0.048). CONCLUSIONS: Phobic anxiety was comparably high and persisted over time in ICD patients. Modifiable determinants of phobic anxiety were identified, which may inform tailored interventions to improve ICD patients' distress and perhaps also prognosis.
AU  - Cho, E.Y.*
AU  - von Känel, R.*
AU  - Marten-Mittag, B.*
AU  - Ronel, J.*
AU  - Kolb, C.*
AU  - Baumert, J.J.
AU  - Ladwig, K.-H.
C1  - 7469
C2  - 29729
SP  - 806-812
TI  - Determinants and trajectory of phobic anxiety in patients living with an implantable cardioverter defibrillator.
JO  - Heart
VL  - 98
IS  - 10
PB  - BMJ Publishing Group
PY  - 2012
SN  - 1355-6037
ER  - 

TY  - JOUR
AB  - BACKGROUND: It has been suggested that a higher calcium intake might favourably modify cardiovascular risk factors. However, findings of an ultimately decreased risk of cardiovascular disease (CVD) are limited. Instead, recent evidence warns that taking calcium supplements might increase myocardial infarction (MI) risk. OBJECTIVE: To prospectively evaluate the associations of dietary calcium intake and calcium supplementation with MI and stroke risk and overall CVD mortality. METHODS: Data from 23 980 Heidelberg cohort participants of the European Prospective Investigation into Cancer and Nutrition study, aged 35-64 years and free of major CVD events at recruitment, were analysed. Multivariate Cox regression models were used to estimate HRs and 95% CIs. RESULTS: After an average follow-up time of 11 years, 354 MI and 260 stroke cases and 267 CVD deaths were documented. Compared with the lowest quartile, the third quartile of total dietary and dairy calcium intake had a significantly reduced MI risk, with a HR of 0.69 (95% CI 0.50 to 0.94) and 0.68 (95% CI 0.50 to 0.93), respectively. Associations for stroke risk and CVD mortality were overall null. In comparison with non-users of any supplements, users of calcium supplements had a statistically significantly increased MI risk (HR=1.86; 95% CI 1.17 to 2.96), which was more pronounced for calcium supplement only users (HR=2.39; 95% CI 1.12 to 5.12). CONCLUSIONS: Increasing calcium intake from diet might not confer significant cardiovascular benefits, while calcium supplements, which might raise MI risk, should be taken with caution.
AU  - Li, K.R.*
AU  - Kaaks, R.*
AU  - Linseisen, J.
AU  - Rohrmann, S.*
C1  - 7526
C2  - 30142
SP  - 920-925
TI  - Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg).
JO  - Heart
VL  - 98
IS  - 12
PB  - BMJ Publishing Group
PY  - 2012
SN  - 1355-6037
ER  - 

TY  - JOUR
AU  - Rohrmann, S.*
AU  - Linseisen, J.
AU  - Kaaks, R.*
AU  - Li, K.*
C1  - 11381
C2  - 30641
SP  - 1751-1752
TI  - Problems with epidemiological approach and conclusions - the response.
JO  - Heart
VL  - 98
IS  - 23
PB  - BMJ Publishing Group
PY  - 2012
SN  - 1355-6037
ER  - 

TY  - JOUR
AU  - Schweikert, B.
AU  - Hahmann, H.*
AU  - Leidl, R.
C1  - 5692
C2  - 23829
SP  - 62-67
TI  - Validation of the EuroQol questionnaire in cardiac rehabilitation.
JO  - Heart
VL  - 92
PY  - 2006
SN  - 1355-6037
ER  -