Christof Prugger

Complement-binding anti-HLA antibodies and kidney-allograft survival.

BACKGROUNDnAnti-HLA antibodies hamper successful transplantation, and activation of the complement cascade is involved in antibody-mediated rejection. We investigated whether the complement-binding capacity of anti-HLA antibodies plays a role in kidney-allograft failure.nnnMETHODSnWe enrolled patients who received kidney allografts at two transplantation centers in Paris between January 1, 2005, and January 1, 2011, in a population-based study. Patients were screened for the presence of circulating donor-specific anti-HLA antibodies and their complement-binding capacity. Graft injury phenotype and the time to kidney-allograft loss were assessed.nnnRESULTSnThe primary analysis included 1016 patients. Patients with complement-binding donor-specific anti-HLA antibodies after transplantation had the lowest 5-year rate of graft survival (54%), as compared with patients with non-complement-binding donor-specific anti-HLA antibodies (93%) and patients without donor-specific anti-HLA antibodies (94%) (P<0.001 for both comparisons). The presence of complement-binding donor-specific anti-HLA antibodies after transplantation was associated with a risk of graft loss that was more than quadrupled (hazard ratio, 4.78; 95% confidence interval [CI], 2.69 to 8.49) when adjusted for clinical, functional, histologic, and immunologic factors. These antibodies were also associated with an increased rate of antibody-mediated rejection, a more severe graft injury phenotype with more extensive microvascular inflammation, and increased deposition of complement fraction C4d within graft capillaries. Adding complement-binding donor-specific anti-HLA antibodies to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 0.75; 95% CI, 0.54 to 0.97).nnnCONCLUSIONSnAssessment of the complement-binding capacity of donor-specific anti-HLA antibodies appears to be useful in identifying patients at high risk for kidney-allograft loss.

Blood pressure control and knowledge of target blood pressure in coronary patients across Europe: results from the EUROASPIRE III survey.

Background Blood pressure management is a key issue among patients with coronary heart disease (CHD). The present study aimed to identify particular patient groups that may need to be specifically targeted in secondary prevention of CHD. Methods EUROASPIRE III is a cross-sectional study conducted in 2006–2007 among patients up to 80 years of age hospitalized for CHD. Patients from 76 centres in 22 European regions were examined on average 15 months after hospitalization. Logistic regression analysis was applied to investigate factors associated with blood pressure control and knowledge of target blood pressure using the cut-point of less than 140/90u200ammHg. Results Among 7649 patients using antihypertensive medication 50.4% achieved blood pressure control and 49.4% provided accurate knowledge of target blood pressure. Obese patients were less likely to show controlled blood pressure [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.65–0.80] and accurate knowledge of blood pressure target values (OR 0.80, 95% CI 0.72–0.90). Dyslipidaemia was negatively associated with blood pressure control and accurate target knowledge. Patients with diabetes mellitus less frequently achieved blood pressure control (OR 0.89, 95% CI 0.79–0.99). Accurate knowledge of target blood pressure was positively related to blood pressure control (OR 1.12, 95% CI 1.00–1.24). Patients who received advice by a health professional to reduce salt intake, to reduce weight, and to increase physical activity more frequently showed accurate knowledge of blood pressure target values. Conclusion Blood pressure control and knowledge of target blood pressure are inappropriate in the European high-risk population of coronary patients. Particularly CHD patients with obesity, diabetes, and dyslipidaemia need better management and control of elevated blood pressure.

Validity and reliability of three commonly used quality of life measures in a large European population of coronary heart disease patients

OBJECTIVEnTo investigate the validity and reliability of the EuroQol-5D (EQ-5D), the 12-item Short-Form Health Survey (SF-12v2), and the Hospital Anxiety and Depression Scale (HADS) in a stable coronary population.nnnSTUDY DESIGNnCross-sectional study EUROASPIRE III.nnnSETTINGnQuality of life data (QoL) were available on 8745 patients hospitalized for coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), acute myocardial infarction (AMI), or myocardial ischemia. They were interviewed and examined at least 6 months after their hospital admission. Reliability and validity of the 3 instruments were tested. Internal consistency, and discriminative, convergent, criterion and construct validity were assessed.nnnRESULTSnCronbachs alpha indicated good internal consistency for all measures (0.73 to 0.87). Discriminative validity analyses confirmed significant QoL differences between known groups: age, gender, educational level. In addition, all hypothesized correlations between QoL constructs (convergent validity) and items (criterion validity) were confirmed with significant correlations. Confirmatory factor analyses indicated good construct validity for HADS and SF-12v2. On country-specific level, results were roughly similar.nnnCONCLUSIONnThe EQ-5D as well as the SF-12v2 and the HADS are reliable and valid instruments for use in a stable coronary population, both on aggregate European level and on country-specific level. However, our results must be generalized with caution, because EUROASPIRE III patients might not be representative for all patients with stable coronary heart disease.

Health related quality of life in coronary patients and its association with their cardiovascular risk profile: Results from the EUROASPIRE III survey

BACKGROUNDnCardiovascular patients are likely to have an impaired health-related quality of life (HRQoL) due to functional and psycho-social limitations. The main objective of this study was to assess the distribution of HRQoL scores in coronary heart disease (CHD) patients across 22 European countries and to identify factors associated with the variation between patients.nnnMETHODSnData from the EUROASPIRE III survey (European Action on Secondary and Primary Prevention by Intervention to Reduce Events), on 8734 patients, were used. Patients with a diagnosis of CHD (coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), acute myocardial infarction (AMI) or myocardial ischemia) were interviewed and examined at least 6 months after their acute coronary event. Quality of life of each patient was measured using 2 standardized questionnaires: the EuroQoL-5D (EQ-5D) and the 12-item short-form health survey (SF-12v2).nnnRESULTSnHRQoL values differed significantly across countries. Lower HRQoL estimates were found in women, older patients, less educated patients, patients with myocardial infarction or ischemia as recruiting diagnosis, patients with a history of stroke and patients who suffered from a recurring CHD event. In addition, HRQoL was significantly associated with current smoking, central obesity, lack of exercise and inappropriate HbA1c control in patients with diabetes. Furthermore the number of risk factors is inversely associated with HRQoL.nnnCONCLUSIONnOverall, a large heterogeneity was observed in HRQoL values between countries and patient groups. There seems to be a significant association between quality of life and patient characteristics with lifestyle risk factors as important determinants of HRQoL.

Treatment potential for dyslipidaemia management in patients with coronary heart disease across Europe: Findings from the EUROASPIRE III survey

OBJECTIVEnDyslipidaemia is among the most important risk factors for coronary heart disease (CHD). The lowering of LDL-cholesterol (LDL-C) yields significant reduction in both morbidity and mortality rates, particularly in patients with established CHD. The aim of this survey was to assess how dyslipidaemia is managed following a coronary event in different places in Europe.nnnMETHODSnCHD patients data from centres in 22 European countries were gathered using standardised methods. In total, 8467 CHD patients with lipid measurements in one central laboratory were included. Trends from 8 countries participating in all three EUROASPIRE surveys (1994-1995, 1999-2000, 2006-2007) were also investigated.nnnRESULTSn51.1% of CHD patients had elevated total cholesterol (≥4.5 mmol/L), 54.5% had raised LDL-C (≥2.5 mmol/L), 36.7% had low HDL-C (<1.0 mmol/L for men and <1.2 mmol/L for women), and 34.7% had increased triglycerides (≥1.7 mmol/L). The use of lipid lowering drugs was 79.8% but it varied considerably, ranging from only 41.6% (Lithuania) to 95.4% (Finland). Over the past decade, in 8 countries the prevalence of hypercholesterolaemia (≥4.5 mmol/L) in CHD patients has decreased from 94.5% in the first to 76.7% in the second and 46.2% in the third survey (p < 0.0001). The use of lipid-lowering drugs increased from 32.3% in the first, to 62.7% in the second and 88.8% in the third survey (p < 0.0001).nnnCONCLUSIONSnAlthough management of dyslipidaemia in CHD patients is improving, a large majority of CHD patients with dyslipidaemia is still inadequately treated and many patients on lipid-lowering therapy are not reaching the treatment goals. Therefore, a considerable potential still exists throughout Europe to reduce CHD mortality and morbidity rates through better treatment of dyslipidaemia.

Multiple Biomarkers for the Prediction of Ischemic Stroke The PRIME Study

Objective—To simultaneously evaluate 14 biomarkers from distinct biological pathways for risk prediction of ischemic stroke, including biomarkers of hemostasis, inflammation, and endothelial activation as well as chemokines and adipocytokines. Methods and Results—The Prospective Epidemiological Study on Myocardial Infarction (PRIME) is a cohort of 9771 healthy men 50 to 59 years of age who were followed up over 10 years. In a nested case–control study, 95 ischemic stroke cases were matched with 190 controls. After multivariable adjustment for traditional risk factors, fibrinogen (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03–2.28), E-selectin (OR, 1.76; 95% CI, 1.06–2.93), interferon-&ggr;-inducible-protein-10 (OR, 1.72; 95% CI, 1.06–2.78), resistin (OR, 2.86; 95% CI, 1.30–6.27), and total adiponectin (OR, 1.82; 95% CI, 1.04–3.19) were significantly associated with ischemic stroke. Adding E-selectin and resistin to a traditional risk factor model significantly increased the area under the receiver-operating characteristic curve from 0.679 (95% CI, 0.612–0.745) to 0.785 and 0.788, respectively, and yielded a categorical net reclassification improvement of 29.9% (P=0.001) and 28.4% (P=0.002), respectively. Their simultaneous inclusion in the traditional risk factor model increased the area under the receiver-operating characteristic curve to 0.824 (95% CI, 0.770–0.877) and resulted in an net reclassification improvement of 41.4% (P<0.001). Results were confirmed when using continuous net reclassification improvement. Conclusion—Among multiple biomarkers from distinct biological pathways, E-selectin and resistin provided incremental and additive value to traditional risk factors in predicting ischemic stroke.

Adipocytokines and the risk of ischemic stroke The PRIME Study

Adipocytokines are hormones secreted from adipose tissue that possibly link adiposity and the risk of cardiovascular disease, but limited prospective data exist on plasma adipocytokines and ischemic stroke risk. We investigated associations and predictive properties of 4 plasma adipocytokines, namely resistin, adipsin, leptin, and total adiponectin, with regard to incident ischemic stroke in the PRIME Study.

Major regional disparities in outcomes after sudden cardiac arrest during sports

AIMSnCharacteristics of sudden cardiac arrest (SCA) during sports offers a novel (and unexplored) setting to assess factors associated with disparities in outcomes across regions.nnnMETHODS AND RESULTSnFrom a prospective 5-year community-based French registry concerning SCA during sports in 10-75 year-olds, we evaluated whether outcomes differed significantly between geographic regions. We then determined the extent to which variations in community-related early interventions were associated with regional variations in survival. Among 820 SCA cases studied, overall survival at hospital discharge was 15.7% (95% confidence interval, 13.2-18.2%), with considerable regional disparities (from 3.4 to 42.6%, P < 0.001). Major differences were noted regarding bystander initiation of cardiopulmonary resuscitation (15.3-80.9%, P < 0.001) and presence of initial shockable rhythm (28.6-79.1%, P < 0.001), with higher values of these being associated with better survival rates. The proportion of survivors with favourable neurological outcome at discharge was fairly uniform among survival groups (CPC-1/2, varying from 77.4 to 90.0%, P = 0.83). No difference was observed regarding subjects characteristics and circumstances of SCA occurrence, including delays in resuscitation (collapse-to-call period). With a comparable in-hospital mortality (P = 0.44), survival at hospital discharge was highly correlated with that at hospital admission (regional variations from 7.4 to 75.0%, P < 0.001).nnnCONCLUSIONnMajor regional disparities exist in survival rates (up to 10-fold) after SCA during sports. SCA cases from regions with the highest levels of bystander resuscitation had the best survival rates to hospital admission and discharge.

Control of main risk factors after ischaemic stroke across Europe: data from the stroke-specific module of the EUROASPIRE III survey

Background Previous cross-sectional surveys in different European countries within the EUROASPIRE programme demonstrated a high prevalence of modifiable risk factors, unhealthy lifestyles and inadequate drug treatment in coronary heart disease patients. Comparable data for ischaemic stroke patients is lacking. Methods A stroke-specific study module was added to the EUROASPIRE III core survey. This cross-sectional multicentre survey included consecutive patients with first-ever ischaemic stroke from four European countries. Data were obtained from medical records, patient interviews and patient examinations within 6–36 months after the stroke event. Control of modifiable risk factors after stroke was evaluated against contemporary European guidelines. Results A total of 881 patients was recruited. Median age was 66 years, 37.5% were female; average time from the stroke event to interview was 550 days. At the time of the interview, 17.6% of stroke patients smoked cigarettes, 35.5% had a body mass index ≥30u2009kg/m2, 62.4% showed elevated blood pressure and 75.7% exhibited elevated LDL cholesterol levels. Antiplatelet drugs or oral anticoagulants were used by 87.2%, antihypertensive medication by 84.4% and statins by 56.8% of stroke patients. Among patients using antihypertensive drugs and lipid-lowering medication at the time of the interview, 34.3% and 34.4%, respectively, achieved target blood pressure and total cholesterol values according to current European guidelines. Conclusion The EUROASPIRE III stroke-specific module shows that secondary prevention and risk factor control in patients after ischaemic stroke need to be improved in four European centres at the time of the study since about half of patients are not achieving risk factor targets defined in European guidelines.

Cardiovascular risk factors and mortality in patients with coronary heart disease.

A priority in preventive cardiology is to reduce the number of recurrent events and to prolong survival in patients with established coronary heart disease (CHD). Aim of the present study was to examine risk factors for long-term mortality in CHD patients who entered routine secondary prevention after a coronary event or intervention. Such patients, from the EUROASPIRE (EUROpean Action on Secondary Prevention through Intervention to Reduce Events) I and II studies in the region of Münster, Germany, were followed over a mean period of 8.0xa0years up to the end of 2005. Patients were up to 70xa0years of age at baseline when they were interviewed and examined using standardised methods. Baseline examination was carried out at least 6xa0months and at a mean of 19.5xa0months after the coronary event or procedure. In 367 patients from EUROASPIRE I and 380 patients from EUROASPIRE II, a total of 125 deaths (16.7%) occurred during follow-up. Multivariate analyses, using Cox proportional hazards models, established diabetes mellitus and smoking as predictors for all-cause mortality with estimated hazard rate ratios (HRRs) of 2.24 (95% confidence interval (CI): 1.43–3.49) and 1.95 (95% CI: 1.23–3.10), respectively. Significant associations were found between diabetes mellitus and cardiovascular (HRR 2.36; 95% CI: 1.31–4.24) as well as CHD mortality (HRR 2.40; 95% CI: 1.25–4.59). Systolic blood pressure was significantly associated with increased cerebrovascular disease mortality (HRR 1.04; 95% CI: 1.01 and 1.08 for 1xa0mmHg increase). In conclusion, long-term mortality in coronary patients from routine secondary prevention is substantial. Diabetes mellitus and smoking represent key issues in patients with established CHD.