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1.
J Crit Care ; 56: 100-105, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31896442

RESUMO

PURPOSE: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly used treatment option for patients in need of mechanical cardiopulmonary support, while available outcome data is limited. The aim of this study was to identify predictors for 30-day in-hospital mortality. MATERIAL AND METHODS: We analyzed baseline characteristics and outcomes of 8351 VA-ECMO procedures performed in Germany from 2007 to 2015. Using a multivariable model, we identified the ten most important variables to allow for prediction of 30-day in-hospital mortality. Based on these variables, we created a mortality prediction score (ECMO-ACCEPTS score) to enhance decision making in patients considered for or treated with VA-ECMO support. RESULTS: Of 8351 patients (71.7% male) 3567 had prior CPR. Mean age was 62 years in the present cohort. The overall 30-day in-hospital mortality was 61%. The ECMO-ACCEPTS score, derived among randomly selected 4175 patients, included ten independent predictors for in-hospital mortality. Internal validation in the remaining 4176 patients confirmed strong differentiation between low and high risk of 30-day in-hospital mortality (r = 0.97 for correlation of predicted with observed mortality, p < .001). CONCLUSIONS: The ECMO-ACCEPTS score might help clinicians to improve risk prediction among VA-ECMO patients for refractory cardiogenic shock.

2.
Lancet ; 394(10215): 2173-2183, 2019 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-31810609

RESUMO

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Medição de Risco/métodos , Adulto , Idoso , Austrália/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia
3.
Eur J Prev Cardiol ; : 2047487319885458, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31707846

RESUMO

BACKGROUND: Modifiable lifestyle risk factors (modRF) of coronary artery disease (CAD) are associated with increased inflammation represented by elevated C-reactive protein (CRP) levels. Lifestyle changes may influence the inflammatory burden in patients with CAD, relevantly modifying the target population for emerging anti-inflammatory compounds. AIMS: The aims of this study were to analyse the association of modRF and CRP levels in CAD patients, and to define a potential target population for anti-inflammatory treatment with and without the optimisation of modRF. METHODS: We included all patients with angiographically documented CAD from the observational cohort study INTERCATH. Patients with recent myocardial infarction, malignancy, infectious disease, and pre-existing immunosuppressive medication including a history of solid organ transplantation were excluded. Overweight (body mass index (BMI) ≥ 25 kg/m2), smoking, lack of physical activity (PA; <1.5 h/week), and poor diet (≤12 points of an established Mediterranean diet score (MDS), range 0-28 points) were considered as modRF. CRP was measured by a high-sensitivity assay (hsCRP) at baseline. We performed multivariable linear regressions with log-transformed hsCRP as the dependent variable. Based on these associations, we calculated potential hsCRP levels for each patient, assuming optimisation of the individual modRF. RESULTS: Of 1014 patients, 737 (73%) were male, the mean age was 69 years, and 483 (48%) had an hsCRP ≥ 2 mg/l. ModRF were significantly overrepresented in patients with hsCRP ≥ 2 mg/l compared to patients with an hsCRP < 2 mg/l (BMI ≥ 25 kg/m2: 76% vs 61%; PA < 1.5 h/week: 69% vs 57%; MDS ≤ 12: 46% vs 37%; smoking: 61% vs 54%; p < 0.05 for all). hsCRP increased with the incremental number of modRF present (median hsCRP values for N = 0, 1, 2, 3, and 4 modRF: 1.1, 1.0, 1.6, 2.4, 2.8 mg/l, p < 0.001). Multivariable linear regression adjusting for age, sex, intake of lipid-lowering medication, and diabetes mellitus revealed independent associations between log-transformed hsCRP and all modRF (BMI ≥ 25 kg/m2: exp(ß) = 1.55, p < 0.001; PA < 1.5 h/week: exp(ß) = 1.33, p < 0.001; MDS ≤ 12: exp(ß) = 1.18, p = 0.018; smoking: exp(ß) = 1.18, p = 0.019). Individual recalculation of hsCRP levels assuming optimisation of modRF identified 183 out of 483 (38%) patients with hsCRP ≥ 2 mg/l who could achieve an hsCRP < 2 mg/l via lifestyle changes. CONCLUSION: modRF are strongly and independently associated with CRP levels in patients with CAD. A relevant portion of CAD patients with high inflammatory burden could achieve an hsCRP < 2 mg/l by lifestyle changes alone. This should be considered both in view of the cost and side-effects of pharmacological anti-inflammatory treatment and for the design of future clinical trials in this field.

4.
Jpn J Radiol ; 37(9): 642-650, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301000

RESUMO

PURPOSE: To investigate the effects of renal denervation (RDN) on left ventricular (LV) mass, myocardial strain and diastolic function in patients with treatment-resistant arterial hypertension by cardiac magnet resonance imaging on a 12-month follow-up. MATERIALS AND METHODS: Sixteen patients (38% female) were examined before and 12 months after RDN. LV morphology and strain were analyzed. Diastolic function was determined by early (EPFR) and atrial peak filling rates (APFR) derived from differential volume-time-curve analysis. Clinical visits included 24-h ambulant blood pressure monitoring (ABPM). RESULTS: Twelve months after RDN LV mass decreased from 80 ± 21 g/m2 to 74 ± 20 g/m2 (P < 0.05). Global radial (35 ± 12% vs. 41 ± 10%, P < 0.05) and longitudinal strain improved (- 15 ± 4% vs. - 17 ± 3%, P < 0.05). Global circumferential strain (- 16 ± 5% vs. - 18 ± 4%, P = 0.12) remained unchanged. The parameter of diastolic LV function PFRR (EPFR/APFR) improved following RDN (0.9 ± 0.4 vs. 1.1 ± 0.5, P < 0.05). Individual changes of LV mass were associated with an increase of EPFR (r = - 0.54, P < 0.05) and a reduction of APFR by trend (r = 0.45, P = 0.08). Systolic ABPM showed a decrease by trend (152 mmHg vs. 148 mmHg, P = 0.08). CONCLUSIONS: After RDN we observed a reduction of LV mass, improvement of global strain and diastolic function.


Assuntos
Coração/fisiopatologia , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/complicações , Rim/cirurgia , Imagem por Ressonância Magnética/métodos , Simpatectomia/métodos , Diástole , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/terapia , Rim/inervação , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Ann Transl Med ; 6(16): 323, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30364059

RESUMO

Patients with established cardiovascular (CV) disease remain at dramatic residual risk for subsequent events, despite growing evidence in secondary prevention and wider dissemination of intensive treatment. This review focuses on new options in secondary risk prevention as presented by these five major randomized controlled trials (RCT): PEGASUS-TIMI 54, COMPASS, FOURIER, ODYSSEY and CANTOS. Three main therapeutic targets are addressed: residual cholesterol, residual inflammatory and residual thrombotic risk. All of the trials reviewed included patients with stable CV disease on optimal medical treatment with a surprising similar mortality. As of now, evolocumab, alirocumab and ticagrelor are on the market, while rivaroxaban and canakinumab are not yet licensed for the treatment of secondary prevention in CV disease. Although life-style modifications and better utilization of established medical treatment options will remain first-line strategy, new medication is just about to enter the market. Secondary prevention in coronary artery disease (CAD) holds a strong potential to reduce subsequent CV events, even CV death. It seems that a combination of an aggressive lipid-lowering treatment in combination with antithrombotic therapy could improve prognosis significantly (at least for distinct subgroups). Against this background, individual efficacy, risk, and costs have to be considered when identifying patients for each new regime.

7.
Biomolecules ; 8(3)2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-30096922

RESUMO

Intrinsic iron release is discussed to have favorable effects in coronary artery disease (CAD). The aim of this study was to evaluate the prognostic relevance of intrinsic iron release in patients with CAD. Intrinsic iron release was based on a definition including hepcidin and soluble transferrin receptor (sTfR). In a cohort of 811 patients with angiographically documented CAD levels of hepcidin and sTfR were measured at baseline. Systemic body iron release was defined as low levels of hepcidin (<24 ng/mL) and high levels of sTfR (≥2 mg/L). A commercially available ELISA (DRG) was used for measurements of serum hepcidin. Serum sTfR was determined by using an automated immunoassay (). Cardiovascular mortality was the main outcome measure. The criteria of intrinsic iron release were fulfilled in 32.6% of all patients. Significantly lower cardiovascular mortality rates were observed in CAD patients with systemic iron release. After adjustment for body mass index, smoking status, hypertension, diabetes, dyslipidemia, sex, and age, the hazard ratio for future cardiovascular death was 0.41. After an additional adjustment for surrogates of the size of myocardial necrosis (troponin I), anemia (hemoglobin), and cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide), this association did not change (Hazard ratio 0.37 (95% confidence interval 0.14⁻0.99), p = 0.047). In conclusion, significantly lower cardiovascular mortality rates were observed in CAD patients with intrinsic iron release shown during follow-up.


Assuntos
Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/mortalidade , Ferro/metabolismo , Idoso , Doença da Artéria Coronariana/diagnóstico , Feminino , Hepcidinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores da Transferrina/química , Receptores da Transferrina/metabolismo , Solubilidade
8.
Atherosclerosis ; 275: 256-261, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29980052

RESUMO

BACKGROUND AND AIMS: Guidelines recommend a healthy diet as a cornerstone of cardiovascular disease (CVD) prevention. Although the Mediterranean diet (MD) is the best studied dietary pattern for CV outcomes, data on association between MD and severity of CAD are limited. Therefore, we analysed dietary data in association with the SYNTAX score in coronary artery disease (CAD) patients from the INTERCATH study. METHODS: The INTERCATH study is an observational study in patients undergoing coronary angiography at the University Heart Center Hamburg. Coronary morphology is assessed by the SYNTAX score. A lifestyle questionnaire collects dietary data with food frequency questions at baseline. Based on seven dietary characteristics, we calculated an established Mediterranean diet score (MDS) with a range of 0-28 points at which 28 points reflect maximal adherence to MD. To investigate the association of MD with severity of CAD, we performed logistic regression analysis after adjustment for confounding factors. RESULTS: Of 1121 patients, 27% were women. The median age was 70.7 years (interquartile range (IQR) 61.1,77.0). CV risk factors were distributed as expected for a CAD cohort (31.3% diabetes, 81.1% arterial hypertension, 34.0% smoking, median BMI 26.6 kg/m2 (IQR 24.1, 30.3), median LDL-C 87 mg/dL (IQR 65.0,116,6). Of all variables included, the strongest correlation with MDS was found for log (hs-CRP) (r = -0.21, p < 0.001). Adherence to MD represented by a higher MDS was significantly associated with a reduced probability for a medium/high risk SYNTAX score of ≥23 with an odds ratio (OR) of 0.923 per point increase of MDS (95% confidence interval 0.869-0.979; p = 0.0079). This association remained significant after adjustment for cardiovascular risk factors (OR 0.934, 95% CI 0.877-0.995, p = 0.035). After further adjustment for log (hs-CRP), the association remained no longer significant (OR 0.955 (0.893-1.022, p = 0.19). CONCLUSIONS: In this contemporary data set, we found an independent association of adherence to MD with a less complex CAD. Hs-CRP correlated significantly with adherence to MD and may be a marker of the vasoprotective effects of MD. These results strengthen the evidence for the protective effect of an MD pattern in CVD prevention.


Assuntos
Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/prevenção & controle , Dieta Mediterrânea , Mediadores da Inflamação/sangue , Comportamento de Redução do Risco , Idoso , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Fatores de Proteção , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
9.
Biomolecules ; 8(3)2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-30037035

RESUMO

Acute myocardial infarction remains a leading cause of morbidity and mortality. While iron deficient heart failure patients are at increased risk of future cardiovascular events and see improvement with intravenous supplementation, the clinical relevance of iron deficiency in acute coronary syndrome remains unclear. We aimed to evaluate the prognostic value of iron deficiency in the acute coronary syndrome (ACS). Levels of ferritin, iron, and transferrin were measured at baseline in 836 patients with ACS. A total of 29.1% was categorized as iron deficient. The prevalence of iron deficiency was clearly higher in women (42.8%), and in patients with anemia (42.5%). During a median follow-up of 4.0 years, 111 subjects (13.3%) experienced non-fatal myocardial infarction (MI) and cardiovascular mortality as combined endpoint. Iron deficiency strongly predicted non-fatal MI and cardiovascular mortality with a hazard ratio (HR) of 1.52 (95% confidence interval (CI) 1.03-2.26; p = 0.037) adjusted for age, sex, hypertension, smoking status, diabetes, hyperlipidemia, body-mass-index (BMI) This association remained significant (HR 1.73 (95% CI 1.07⁻2.81; p = 0.026)) after an additional adjustment for surrogates of cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide, NT-proBNP), for the size of myocardial necrosis (troponin), and for anemia (hemoglobin). Survival analyses for cardiovascular mortality and MI provided further evidence for the prognostic relevance of iron deficiency (HR 1.50 (95% CI 1.02⁻2.20)). Our data showed that iron deficiency is strongly associated with adverse outcome in acute coronary syndrome.


Assuntos
Síndrome Coronariana Aguda/complicações , Anemia Ferropriva/epidemiologia , Infarto do Miocárdio/epidemiologia , Síndrome Coronariana Aguda/metabolismo , Idoso , Anemia Ferropriva/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Prevalência , Prognóstico , Troponina/metabolismo
10.
Biomolecules ; 8(3)2018 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-29958400

RESUMO

Iron is essential in terms of oxygen utilization and mitochondrial function. The liver-derived peptide hepcidin has been recognized as a key regulator of iron homeostasis. Since iron metabolism is crucially linked to cardiovascular health, and low hepcidin was proposed as potential new marker of iron metabolism, we aimed to evaluate the prognostic value of hepcidin in a large cohort of patients with coronary heart disease (CHD). Serum levels of hepcidin were determined at baseline in patients with angiographically documented CHD. The main outcome measure was non-fatal myocardial infarction (MI) or cardiovascular death. During a median follow-up of 4.1 years, 10.3% experienced an endpoint. In Cox regression analyses for hepcidin the hazard ratio for future cardiovascular death or MI was 1.03 (95% confidence interval (CI) 0.91⁻1.18, p = 0.63) after adjustment for sex and age. This association virtually did not change after additional adjustment for body mass index (BMI), smoking status, hypertension, diabetes, dyslipidemia, and surrogates of cardiac function (NT-proBNP), size of myocardial necrosis (troponin I), and anemia (hemoglobin). In this study, by far the largest evaluating the predictive value of hepcidin, hepcidin levels were not associated with future MI or cardiovascular death. This implicates a limited, if any, role for hepcidin in secondary cardiovascular risk prediction.


Assuntos
Doença das Coronárias/metabolismo , Hepcidinas/sangue , Ferro/metabolismo , Infarto do Miocárdio/epidemiologia , Idoso , Estudos de Coortes , Doença das Coronárias/sangue , Doença das Coronárias/complicações , Doença das Coronárias/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Prognóstico , Análise de Regressão
11.
J Am Heart Assoc ; 7(6)2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29545259

RESUMO

BACKGROUND: Percutaneous mitral valve edge-to-edge repair (pMVR) with a MitraClip is beneficial for the clinical symptoms of patients irrespective of the ejection fraction (EF). Nevertheless, the consequences on hemodynamics are poorly understood. Therefore, we used data from noninvasive pressure-volume loops to investigate the left ventricular (LV) remodeling of patients after pMVR dependent on their baseline EF. METHODS AND RESULTS: In 130 patients with successful pMVR, the end-diastolic pressure-volume relationship (EDPVR) and end-systolic pressure-volume relationship were estimated noninvasively from echocardiographic data. We compared EDPVR and end-systolic pressure-volume relationship at discharge and follow-up between patients with a reduced EF (<40%) and patients with a mid-ranged or preserved EF (≥40%). Reduced EF was present in 71 patients (54%). Mean follow-up duration was 277±117 days. We observed a significant reduction in degree of mitral regurgitation and an improvement in functional status at follow-up irrespective of baseline EF. In patients with a mid-ranged or preserved EF, the EDPVR and end-systolic pressure-volume relationship were shifted leftwards, suggesting an improvement in LV function. In contrast, in patients with a reduced EF, EDPVR and end-systolic pressure-volume relationship remained stable, although comparison with the baseline data indicates a rightward shift of the EDPVR. This indicates that there is no improvement in LV function after pMVR in patients with reduced EF. CONCLUSIONS: The pMVR is associated with improved clinical symptoms in all patient subgroups. However, it leads to different hemodynamic responses. In patients with mid-ranged or preserved EF, we found reverse remodeling with reduced LV dilatation and increased contractility. In contrast, in patients with reduced EF, we observed no reverse remodeling and no improvement in LV function.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia Doppler de Pulso , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Contração Miocárdica , Fenótipo , Recuperação de Função Fisiológica , Sistema de Registros , Estudos Retrospectivos , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Pressão Ventricular
12.
Clin Ther ; 39(11): 2311-2320.e2, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29103665

RESUMO

PURPOSE: Although the efficacy of lipid-lowering medication (LLM) in patients with coronary artery disease (CAD) is well established, the majority of patients fail to achieve their LDL-C goals. The evidence for measurement of LDL-C to achieve these goals is limited. The goal of the present study, therefore, was to analyze ambulatory LLM management in relation to performance of LDL-C measurements and achieved LDL-C levels after the initial diagnosis of CAD. METHODS: The study followed up a subcohort of 200 patients with newly diagnosed CAD of the INTERCATH trial, an observational study including patients undergoing coronary angiography. In addition to baseline information, data were collected on LLM, performance of lipid measurements, and laboratory results at a minimum of 6 months' postdischarge. FINDINGS: The mean age of the sample was 67.9 years, and 36.0% were women. In 34.5% of all patients, no measurement of LDL-C levels was performed during follow-up. We found no differences in baseline characteristics between patients with and without LDL-C measurements during follow-up. In patients with measurement of LDL-C levels, the frequency of intensification of statin medication according to LDL-C reduction was higher compared with those patients without LDL-C measurement (23.6% vs 4.3%; P < 0.001); all other categories of intensity adjustment were comparable. In patients with 3 LDL-C measurements, achieved LDL-C levels were significantly lower (mean, 81 mg/dL), and a higher proportion reached an LDL-C level <70 mg/dL (44.7%) compared with patients with 1 (95 mg/dL [P = 0.013]; 21.8%) or 2 (91 mg/dL [P = 0.037]; 28.9%) LDL-C measurements despite comparable LDL-C levels at baseline. Ezetimibe was used in 3.5% of the entire study cohort. IMPLICATIONS: We found no differences in patient characteristics between patients with and without LDL-C measurements after being newly diagnosed with CAD. Performance and frequency of LDL-C measurements were clearly associated with better, higher frequency of intensification of statin medication, lower achieved LDL-C levels, and a higher proportion of patients achieving the LDL-C goal of <70 mg/dL. These results suggest an important role of LDL-C measurements for secondary prevention after the initial diagnosis of CAD.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Idoso , LDL-Colesterol/sangue , Estudos de Coortes , Ezetimiba/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Secundária/métodos
13.
Front Cardiovasc Med ; 4: 57, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28979897

RESUMO

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.

14.
Lancet Diabetes Endocrinol ; 5(7): 534-543, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28566218

RESUMO

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 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 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 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, 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 für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.


Assuntos
Biomarcadores/sangue , Doença das Coronárias/mortalidade , Estudos de Associação Genética , Lipoproteína(a)/sangue , Lipoproteína(a)/genética , Polimorfismo de Nucleotídeo Único , Estudos de Coortes , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Doença das Coronárias/genética , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida
15.
Eur Heart J ; 38(32): 2490-2498, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-28449027

RESUMO

Aims: As promising compounds to lower Lipoprotein(a) (Lp(a)) are emerging, the need for a precise characterization and comparability of the Lp(a)-associated cardiovascular risk is increasing. Therefore, we aimed to evaluate the distribution of Lp(a) concentrations across the European population, to characterize the association with cardiovascular outcomes and to provide high comparability of the Lp(a)-associated cardiovascular risk by use of centrally determined Lp(a) concentrations. Methods and results: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 56 804 participants from 7 prospective population-based cohorts across Europe with a maximum follow-up of 24 years. All Lp(a) measurements were performed in the central BiomarCaRE laboratory (Biokit Quantia Lp(a)-Test; Abbott Diagnostics). The three endpoints considered were incident major coronary events (MCE), incident cardiovascular disease (CVD) events, and total mortality. We found lower Lp(a) levels in Northern European cohorts (median 4.9 mg/dL) compared to central (median 7.9 mg/dL) and Southern European cohorts (10.9 mg/dL) (Jonckheere-Terpstra test P < 0.001). Kaplan-Meier curves showed the highest event rate of MCE and CVD events for Lp(a) levels ≥90th percentile (log-rank test: P < 0.001 for MCE and CVD). Cox regression models adjusted for age, sex, and cardiovascular risk factors revealed a significant association of Lp(a) levels with MCE and CVD with a hazard ratio (HR) of 1.30 for MCE [95% confidence interval (CI) 1.15‒1.46] and of 1.25 for CVD (95% CI 1.12‒1.39) for Lp(a) levels in the 67‒89th percentile and a HR of 1.49 for MCE (95% CI 1.29‒1.73) and of 1.44 for CVD (95% CI 1.25‒1.65) for Lp(a) levels ≥ 90th percentile vs. Lp(a) levels in the lowest third (P < 0.001 for all). There was no significant association between Lp(a) levels and total mortality. Subgroup analysis for a continuous version of cube root transformed Lp(a) identified the highest Lp(a)-associated risk in individuals with diabetes [HR for MCE 1.31 (95% CI 1.15‒1.50)] and for CVD 1.22 (95% CI 1.08‒1.38) compared to those without diabetes [HR for MCE 1.15 (95% CI 1.08‒1.21; HR for CVD 1.13 (1.07-1.19)] while no difference of the Lp(a)- associated risk were seen for other cardiovascular high risk states. The addition of Lp(a) levels to a prognostic model for MCE and CVD revealed only a marginal but significant C-index discrimination measure increase (0.001 for MCE and CVD; P < 0.05) and net reclassification improvement (0.010 for MCE and 0.011 for CVD). Conclusion: In this large dataset on harmonized Lp(a) determination, we observed regional differences within the European population. Elevated Lp(a) was robustly associated with an increased risk for MCE and CVD in particular among individuals with diabetes. These results may lead to better identification of target populations who might benefit from future Lp(a)-lowering therapies.


Assuntos
Doenças Cardiovasculares/etiologia , Lipoproteína(a)/fisiologia , Adulto , Biomarcadores/metabolismo , Doenças Cardiovasculares/mortalidade , Europa (Continente)/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Lipoproteína(a)/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Características de Residência/estatística & dados numéricos , Medição de Risco
16.
Minerva Cardioangiol ; 65(4): 331-335, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28146144

RESUMO

BACKGROUND: Aorto-ostial lesions as well as bifurcation lesions still provide challenges in percutaneous coronary intervention (PCI), as meticulous stent placement is needed. The Szabo-technique, which uses a second wire to anchor the stent at the ostium, may be helpful here. In this article, we will provide detailed information on the technique including video material as well as procedural and long-term follow-up data of a cohort of patients treated with this technique. METHODS: A retrospective single-centre study was performed in patients undergoing Szabo-PCI from 2014 to 2016 (N.=28). RESULTS: Indications for PCI were elective in 53% and urgent/emergent in 47%. Target vessel was the ostial right coronary artery in 43%, the ostial left main artery in 7%, the proximal left anterior descending artery in 29% and the proximal circumflex artery in 21% of the cases. Primary success rate was 86%. In the other 14%, delivery of the stent failed due to a high-grade calcification. There were no periprocedural complications. During the follow-up time (mean 308 days) there was one case of cardiovascular and one case of non-cardiovascular death without any stroke events. In one case target lesions revascularisation was necessary. CONCLUSIONS: The Szabo-technique offers a feasible and safe approach for PCI of ostial and bifurcation lesions. Calcified lesions seem to be a challenging aspect.


Assuntos
Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea/métodos , Stents , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
17.
Clin Res Cardiol ; 105(11): 901-911, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27364941

RESUMO

BACKGROUND: The complexity of coronary artery disease (CAD) is a predictor of cardiovascular events in patients with >50 % diameter stenosis as determined by SYNTAX score. Here, we compare the Gensini score to SYNTAX in patients with CAD as well as apply the Gensini score in patients with nonobstructive CAD (NOB-CAD), defined by ≤50 % diameter stenosis, were the SYNTAX score cannot be utilized to define future risk. METHODS: The AtheroGene study enrolled 2316 patients [861/37.2 % with acute cardiovascular syndrome (ACS) and 1500/62.8 % with stable CAD (SCAD)]. Of these, 1966 had obstructive CAD (OB-CAD) with SYNTAX and Gensini scores available and 291 events with either cardiovascular mortality or non-fatal myocardial infarction were recorded. Furthermore, 350 patients had NOB-CAD with only Gensini score and 36 events. Median follow-up time was 4.9 years. RESULTS: In the OB-CAD cohort the SYNTAX and the Gensini score predicted outcome. Kaplan-Meier curve analysis with the dichotomized Gensini score showed a significant result (p = 0.04) in the NOB-CAD cohort. Cox Regression analysis after adjustment showed a hazard ratio (HR) of 1.33 and p = 0.04 for the Gensini score in the NOB-CAD cohort. Receiver operating characteristic curve (ROC) analysis provided the highest area under the curve (AUC) regarding the outcome for the Gensini score with 0.65 (p = 0.004). Comparing the SYNTAX and Gensini score in this cohort showed improved discrimination of patients with events by the Gensini score (p = 0.02). CONCLUSION: The Gensini score predicted events in patients with ≤50 % diameter lesions. Utilization of this score is useful to define risk in NOB-CAD patients.


Assuntos
Síndrome Coronariana Aguda/diagnóstico por imagem , Angiografia Coronária , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/mortalidade , Idoso , Área Sob a Curva , Estenose Coronária/complicações , Estenose Coronária/mortalidade , Feminino , Alemanha , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
18.
JAMA Cardiol ; 1(4): 397-404, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27438315

RESUMO

IMPORTANCE: Rapid and accurate diagnosis of acute myocardial infarction (AMI) currently constitutes an unmet need. OBJECTIVE: To test a 1-hour diagnostic algorithm to diagnose AMI using a high-sensitivity troponin I assay with a new cutoff level of 6 ng/L. DESIGN, SETTING, AND PARTICIPANTS: The Biomarkers in Acute Cardiac Care study is a prospective study that investigated the application of the troponin I assay for the diagnosis of AMI in 1040 patients presenting to the emergency department with acute chest pain from July 19, 2013, to December 31, 2014. Results were validated in 2 independent cohorts of 4009 patients. Final follow-up was completed on July 1, 2015, and data were assessed from July 2 to December 15, 2015. EXPOSURE: Acute chest pain suggestive of AMI. MAIN OUTCOMES AND MEASURES: Accurate diagnosis or exclusion of AMI and 12-month mortality in patients with acute chest pain. RESULTS: Of the 1040 patients included from the study cohort, 673 (64.7%) were male and had a median age of 65 (interquartile range, 52-75) years. With application of a low troponin I cutoff value of 6 ng/L, the rule-out algorithm showed a high negative predictive value of 99.8% (95% CI, 98.6%-100.0%) after 1 hour for non-ST-segment elevation MI type 1. The 1-hour approach was comparable to a 3-hour approach. Similarly, a rule-in algorithm based on troponin I levels provided a high positive predictive value with 82.8% (95% CI, 73.2%-90.0%). Moreover, application of the cutoff of 6 ng/L resulted in lower follow-up mortality (1.0%) compared with the routinely used 99th percentile (3.7%) for this assay. Two independent cohorts further validated the performance of this algorithm with high negative and positive predictive values. CONCLUSIONS AND RELEVANCE: Patients with possible AMI can be triaged within 1 hour after admission with no loss of safety compared with a 3-hour approach, when a low and sensitive cutoff is applied. This concept enables safe discharge or rapid treatment initiation after 1 hour.


Assuntos
Algoritmos , Biomarcadores/sangue , Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Sensibilidade e Especificidade
19.
Clin Res Cardiol ; 104(6): 500-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25608615

RESUMO

BACKGROUND: With an increasing number of complex and repeated percutaneous coronary interventions (PCI), radiation-induced hazards for patients and operators remain an important issue in fluoroscopy-guided procedures. Our objective was to evaluate radiation exposure during coronary angiographic procedures and assess the efficacy of a four-step program to reduce radiation exposure during coronary angiography (CAG) and PCI. METHODS AND RESULTS: A retrospective single-center analysis was performed in patients undergoing CAG or PCI in the first 6 months of 2012 vs. the first 6 months of 2014 (n = 3,107 procedures). During 2013, a four-step protocol was established in our hospital. It contained measures to reduce radiation exposure, including a frame rate reduction from 15 to 7.5 frames per second, the use of fluoroscopy storage, strict use of beam collimation, and repeat training on radiation safety. After adjustment for confounding variables, a dose-area product (DAP) reduction of 54.2% was observed subsequent to implementation of the four-step protocol. Independent predictors of DAP were age [odds ratio (OR) 1.01], body surface area (OR 5.47), prior coronary artery bypass grafting (OR 1.44), radial access (OR 1.16), PCI (OR 2.36), female gender (OR 0.91), and the implementation of the four-step program (OR 0.46). CONCLUSION: A simple four-step protocol led to a significant reduction in radiation exposure in diagnostic and interventional coronary procedures without significant drawbacks in image quality. Hence, radiation safety programs are of paramount importance and should be established to improve patient and operator safety with regard to radiation-induced hazards.


Assuntos
Angiografia Coronária/métodos , Fluoroscopia/métodos , Intervenção Coronária Percutânea/métodos , Exposição à Radiação/prevenção & controle , Fatores Etários , Idoso , Angiografia Coronária/efeitos adversos , Feminino , Fluoroscopia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Doses de Radiação , Exposição à Radiação/análise , Lesões por Radiação/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
20.
J Clin Invest ; 122(3): 1119-30, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22354168

RESUMO

Cardiac pacemaker cells create rhythmic pulses that control heart rate; pacemaker dysfunction is a prevalent disorder in the elderly, but little is known about the underlying molecular causes. Popeye domain containing (Popdc) genes encode membrane proteins with high expression levels in cardiac myocytes and specifically in the cardiac pacemaking and conduction system. Here, we report the phenotypic analysis of mice deficient in Popdc1 or Popdc2. ECG analysis revealed severe sinus node dysfunction when freely roaming mutant animals were subjected to physical or mental stress. In both mutants, bradyarrhythmia developed in an age-dependent manner. Furthermore, we found that the conserved Popeye domain functioned as a high-affinity cAMP-binding site. Popdc proteins interacted with the potassium channel TREK-1, which led to increased cell surface expression and enhanced current density, both of which were negatively modulated by cAMP. These data indicate that Popdc proteins have an important regulatory function in heart rate dynamics that is mediated, at least in part, through cAMP binding. Mice with mutant Popdc1 and Popdc2 alleles are therefore useful models for the dissection of the mechanisms causing pacemaker dysfunction and could aid in the development of strategies for therapeutic intervention.


Assuntos
Moléculas de Adesão Celular/metabolismo , Proteínas Musculares/metabolismo , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Animais , Relógios Biológicos , Bradicardia/genética , Eletrocardiografia/métodos , Eletrofisiologia/métodos , Frequência Cardíaca , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Fenótipo , Estrutura Terciária de Proteína , Telemetria/métodos , Fatores de Tempo
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