Universitätsbibliothek

Estimation of absolute risk of cardiovascular disease (CVD), preferably with population-specific risk charts, has become a cornerstone of CVD primary prevention. Regular recalibration of risk charts may be necessary due to decreasing CVD rates and CVD risk factor levels. The SCORE risk charts for fatal CVD risk assessment were first calibrated for Germany with 1998 risk factor level data and 1999 mortality statistics. We present an update of these risk charts based on the SCORE methodology including estimates of relative risks from SCORE, risk factor levels from the German Health Interview and Examination Survey for Adults 2008–11 (DEGS1) and official mortality statistics from 2012. Competing risks methods were applied and estimates were independently validated. Updated risk charts were calculated based on cholesterol, smoking, systolic blood pressure risk factor levels, sex and 5-year age-groups. The absolute 10-year risk estimates of fatal CVD were lower according to the updated risk charts compared to the first calibration for Germany. In a nationwide sample of 3062 adults aged 40–65 years free of major CVD from DEGS1, the mean 10-year risk of fatal CVD estimated by the updated charts was lower by 29% and the estimated proportion of high risk people (10-year risk > = 5%) by 50% compared to the older risk charts. This recalibration shows a need for regular updates of risk charts according to changes in mortality and risk factor levels in order to sustain the identification of people with a high CVD risk.

Background The impact of risk factors on poor outcome after ischemic stroke is well known, but estimating the amount of poor outcome attributable to single factors is challenging in presence of multimorbidity. We aim to compare population attributable risk estimates obtained from different statistical approaches regarding their consistency. We use a real-life data set from the PROSCIS study to identify predictors for mortality and functional impairment one year after first-ever ischemic stroke and quantify their contribution to poor outcome using population attributable risks. Methods The PROSpective Cohort with Incident Stroke (PROSCIS) is a prospective observational hospital-based cohort study of patients after first-ever stroke conducted independently in Berlin (PROSCIS-B) and Munich (PROSCIS-M). The association of baseline factors with poor outcome one year after stroke in PROSCIS-B was analysed using multiple logistic regression analysis and population attributable risks were calculated, which were estimated using sequential population attributable risk based on a multiple generalized additive regression model, doubly robust estimation, as well as using average sequential population attributable risk. Findings were reproduced in an independent validation sample from PROSCIS-M. Results Out of 507 patients with available outcome information after 12 months in PROSCIS-B, 20.5% suffered from poor outcome. Factors associated with poor outcome were age, pre-stroke physical disability, stroke severity (NIHSS), education, and diabetes mellitus. The order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but population attributable risk estimates varied markedly between the methods. In PROSCIS-M, incidence of poor outcome and distribution of baseline parameters were comparable. The multiple logistic regression model could be reproduced for all predictors, except pre-stroke physical disability. Similar to PROSCIS-B, the order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but magnitudes of population attributable risk differed markedly between the methods. Conclusions Ranking of risk factors by population impact is not affected by the different statistical approaches. Thus, for a rational decision on which risk factor to target in disease interventions, population attributable risk is a supportive tool. However, population attributable risk estimates are difficult to interpret and are not comparable when they origin from studies applying different methodology. The predictors for poor outcome identified in PROSCIS-B have a relevant impact on mortality and functional impairment one year after first-ever ischemic stroke.

Background: The Catechol-O-methyltransferase (COMT) represents the key enzyme in catecholamine degradation. Recent studies suggest that the COMT rs4680 polymorphism is associated with the response to endogenous and exogenous catecholamines. There are, however, conflicting data regarding the COMT Met/Met phenotype being associated with an increased risk of acute kidney injury (AKI) after cardiac surgery. The aim of the current study is to prospectively investigate the impact of the COMT rs4680 polymorphism on the incidence of AKI in patients undergoing cardiac surgery. Methods: In this prospective single center cohort study consecutive patients hospitalized for elective cardiac surgery including cardiopulmonary-bypass (CPB) were screened for participation. Demographic clinical data, blood, urine and tissue samples were collected at predefined time points throughout the clinical stay. AKI was defined according to recent recommendations of the Kidney Disease Improving Global Outcome (KDIGO) group. Genetic analysis was performed after patient enrolment was completed. Results: Between April and December 2014, 150 patients were recruited. The COMT genotypes were distributed as follows: Val/Met 48.7%, Met/Met 29.3%, Val/Val 21.3%. No significant differences were found for demography, comorbidities, or operative strategy according to the underlying COMT genotype. AKI occurred in 35 patients (23.5%) of the total cohort, and no differences were evident between the COMT genotypes (20.5% Met/Met, 24.7% Val/Met, 25.0% Val/Val, p = 0.66). There were also no differences in the post-operative period, including ICU or in-hospital stay. Conclusions: We did not find statistically significant variations in the risk for postoperative AKI, length of ICU or in-hospital stay according to the underlying COMT genotype.

In patients with coronary heart disease (CHD) the control of the modifiable “traditional” cardiovascular risk factors such as hypertension, dyslipidemia, diabetes, achieving/maintaining normal body weight and smoking cessation is of major importance to improve prognosis. Guideline recommendations for secondary CHD prevention include specific treatment targets for blood pressure, lipid levels, and markers of glucose metabolism for both younger and older patients. Chronic kidney disease (CKD) has been identified as a “non-traditional” risk factor for worse outcome in CHD patients, as it is associated with a markedly increased risk for subsequent CV events and mortality. The specific objectives of the current thesis-project are to investigate (a) the quality of care in a recent sample of German CHD patients and to investigate variation of risk factor control between younger and elder patients (≤70 versus >70 years), (b) to analyze the prevalence of CKD across Europe in stable CHD patients in the outpatient setting and during a hospital stay for CHD, (c) to investigate the level of awareness of CKD in German CHD patients and their treating physicians. Data from the European-wide EUROASPIRE IV study were used that include data on 7998 CHD patients in the ambulatory setting (study visit) and during a hospital stay for CHD (index). The German EUROASPIRE IV study center in Würzburg recruited 536 patients in 2012-2013. Risk factor control was compared against the current recommendations of the European Society of Cardiology. CKD was described by stages of glomerular filtration rate (eGFR) and albuminuria. German patients were asked in an additional kidney specific module whether they have ever been told by a physician about renal impairment. The fact that CKD or acute kidney injury (AKI) was mentioned in prominent parts of the hospital discharge letter as well as correct ICD-coding of CKD or AKI served as a proxy for physician’s awareness of CKD. The majority of German CHD patients was treated with the recommended drug therapies including e.g. β-blockers, anti-platelets and statins. However, treatment targets for blood pressure and LDL-cholesterol levels were not achieved in many patients (45% and 53%, respectively) and glycemic control in diabetic CHD patients with HbA1-levels <7% was insufficient (61%). A minority of patients reported on current smoking (10%), but unhealthy life-styles e.g. overweight/obesity (85%/37%) were frequent. Patterns of care differed between younger and older CHD patients while older patients were less likely to receive the recommended medical CHD-therapy, were more likely to have uncontrolled blood pressure and also to be diabetic. However, a greater proportion of diabetic patients >70 years was achieving the HbA1c target, and less elder patients were current smokers or were obese. About 17% of patients on average had CKD (eGFR< 60 ml/min/1.73m²) in the entire European sample at the study visit, and an additional 10% had albuminuria despite preserved eGFR, with considerable variation among countries. Impaired kidney function was observed in every fifth patient admitted for CHD in the entire European dataset of the EUROASPIRE IV study. Of the German CHD patients with CKD at the study visit, only a third were aware of their renal impairment. A minority of these patients was being seen by nephrologists, however, with a higher likelihood of CKD awareness and specialist care in more advanced stages of CKD. About a third of patients admitted for CHD showed either CKD or AKI during the hospital stay, but the discharge letter mentioned chronic or acute kidney disease only in every fifth of these patients. In contrast, correct ICD coding of CKD or AKI was more complete, but still suboptimal. In summary, quality of secondary prevention in German CHD patients indicates considerably room for improvement, with life-style modifications may become an even greater factor in prevention campaigns than medical treatment into certain target ranges. Preventive therapies should also consider different needs in older individuals acknowledging physical and mental potential, other comorbidities and drug-interactions with co-medication. CKD is common in CHD patients, not only in the elderly. Since CHD and CKD affect each other and impact on worse prognosis of each other, raising the awareness of CKD among patients and physicians and considering CKD in medical therapy may improve prognosis and slow disease progression of CHD as well as CKD.

Background and purpose: Silent atrial fibrillation (AF) and tachycardia (AT) are considered precursors of ischaemic stroke. Therefore, detection of paroxysmal atrial rhythm disorders is highly relevant, but is clinically challenging. We aimed to evaluate the diagnostic value of natriuretic peptide levels in the detection of paroxysmal AT/AF in a pilot study. Methods: Natriuretic peptide levels were analysed in two independent patient cohorts (162 patients with arterial hypertension or other cardiovascular risk factors and 82 patients with retinal vessel disease). N-terminal-pro-brain natriuretic peptide (NT-proBNP) and BNP were measured before the start of a 7-day Holter monitoring period carefully screened for AT/AF. Results: 244 patients were included; 16 had paroxysmal AT/AF. After excluding patients with a history of AT/AF (n=5), 14 patients had newly diagnosed AT/AF (5.8%) NT-proBNP and BNP levels were higher in patients with paroxysmal AT/AF in both cohorts: (1) 154.4 (IQR 41.7; 303.6) versus 52.8 (30.4; 178.0) pg/mL and 70.0 (31.9; 142.4) versus 43.9 (16.3; 95.2) and (2) 216.9 (201.4; 277.1) versus 90.8 (42.3–141.7) and 96.0 (54.7; 108.2) versus 29.1 (12.0; 58.1). For the detection of AT/AF episodes, NT-proBNP and BNP had an area under the curve in receiver operating characteristic analysis of 0.76 (95% CI, 0.64 to 0.88; p=0.002) and 0.75 (0.61 to 0.89; p=0.004), respectively. Conclusions: NT-proBNP and BNP levels are elevated in patients with silent AT/AF as compared with sinus rhythm. Thus, screening for undiagnosed paroxysmal AF using natriuretic peptide level initiated Holter monitoring may be a useful strategy in prevention of stroke or systemic embolism.