65 research outputs found
INSULIN RESISTANCE IS ASSOCIATED WITH METABOLIC SYNDROME BUT NOT WITH ANGIOGRAPHICALLY DETERMINED CORONARY ARTERY DISEASE IN FEMALE PATIENTS
TYPE 2 DIABETES SIGNIFICANTLY MODULATES THE IMPACT OF LOW LEFT VENTRICULAR EJECTION FRACTION ON THE RISK OF CARDIOVASCULAR EVENTS
Reversal strategies for non-vitamin K antagonist oral anticoagulants: a critical appraisal of available evidence and recommendations for clinical managementâa joint position paper of the European Society of CardiologyWorking Group on Cardiovascular Pharmacotherapy and European Society of CardiologyWorking Group on Thrombosis
S-100 B Concentrations Are a Predictor of Decreased Survival in Patients with Major Trauma, Independently of Head Injury.
BACKGROUND
Major trauma remains one of the principle causes of disability and death throughout the world. There is currently no satisfactory risk assessment to predict mortality in patients with major trauma. The aim of our study is to examine whether S-100 B protein concentrations correlate with injury severity and survival in patients with major trauma, with special emphasis on patients without head injury.
METHODS
Our retrospective data analysis comprised adult patients admitted to our emergency department between 1.12. 2008 and 31.12 2010 with a suspected major trauma. S-100 B concentrations were routinely assessed in major trauma patients.
RESULTS
A total of 27.7% (378) of all patients had major trauma. The median ISS was 24.6 (SD 8.4); 16.6% (63/378) of the patients died. S-100 B concentrations correlated overall with the ISS (p<0.0001). Patients who died had significantly higher S-100 B concentrations than survivors (8.2 ÎŒg/l versus 2.2 ÎŒg/l, p<0.0001). Polytraumatised patients with and without head trauma did not differ significantly with respect to S-100 B concentration (3.2 ÎŒg/l (SD 5.3) versus 2.9 ÎŒg/l (SD 3.8), respectively, p = 0.63) or with respect to Injury Severity Score (24.8 (SD 8.6) versus 24.2 (SD 8.1), respectively, p = 0.56). S-100 B concentrations correlated negatively with survival (p<0.0001) in all patients and in both subgroups (p = 0.001 and p = 0.006, respectively).
CONCLUSIONS
S-100 concentrations on admission correlate positively with greater injury severity and decreased survival in major trauma patients, independently of the presence of a head injury. S-100 B protein levels at admission in patients with major trauma may therefore be used to assess outcome in all polytraumatised patients. These measurements should be subject to further evaluation
Genome-Wide Association Analysis for Severity of Coronary Artery Disease Using the Gensini Scoring System
Coronary artery disease (CAD) has a complex etiology involving numerous environmental and genetic factors of disease risk. To date, the genetic 9p21 locus represents the most robust genetic finding for prevalent and incident CAD. However, limited information is available on the genetic background of the severity and distribution of CAD. CAD manifests itself as stable CAD or acute coronary syndrome. The Gensini score quantifies the extent CAD but requires coronary angiography. Here, we aimed to identify novel genetic variants associated with Gensini score severity and distribution of CAD. A two-stage approach including a discovery and a replication stage was used to assess genetic variants. In the discovery phase, a meta-analysis of genome-wide association data of 4,930 CAD-subjects assessed by the Gensini score was performed. Selected single nucleotide polymorphisms (SNPs) were replicated in 2,283 CAD-subjects by de novo genotyping. We identified genetic loci located on chromosome 2 and 9 to be associated with Gensini score severity and distribution of CAD in the discovery stage. Although the loci on chromosome 2 could not be replicated in the second stage, the known CAD-locus on chromosome 9p21, represented by rs133349, was identified and, thus, was confirmed as risk locus for CAD severity
Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study
Background:
Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.
Methods:
We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10â195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106â353 patients with established coronary heart disease and 19â332 deaths in 22 studies or cohorts.
Findings:
The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14â1·83) and the presence of either LPA SNP (1·88, 1·40â2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81â1·11 and either LPA SNP 1·10, 0·92â1·31) or cardiovascular mortality (0·99, 0·81â1·2 and 1·13, 0·90â1·40, respectively) or in the validation studies.
Interpretation:
In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.
Funding:
Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung fĂŒr Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny
Genome-Wide Association Analysis for Severity of Coronary Artery Disease Using the Gensini Scoring System
Coronary artery disease (CAD) has a complex etiology involving numerous environmental and genetic factors of disease risk. To date, the genetic 9p21 locus represents the most robust genetic finding for prevalent and incident CAD. However, limited information is available on the genetic background of the severity and distribution of CAD. CAD manifests itself as stable CAD or acute coronary syndrome. The Gensini score quantifies the extent CAD but requires coronary angiography. Here, we aimed to identify novel genetic variants associated with Gensini score severity and distribution of CAD. A two-stage approach including a discovery and a replication stage was used to assess genetic variants. In the discovery phase, a meta-analysis of genome-wide association data of 4,930 CAD-subjects assessed by the Gensini score was performed. Selected single nucleotide polymorphisms (SNPs) were replicated in 2,283 CAD-subjects by de novo genotyping. We identified genetic loci located on chromosome 2 and 9 to be associated with Gensini score severity and distribution of CAD in the discovery stage. Although the loci on chromosome 2 could not be replicated in the second stage, the known CAD-locus on chromosome 9p21, represented by rs133349, was identified and, thus, was confirmed as risk locus for CAD severity
Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium
BACKGROUND:
The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.
METHODS:
The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.
RESULTS:
Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints.
CONCLUSIONS:
GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
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