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Diabetes is hallmarked by high blood glucose levels, which cause progressive generalised vascular damage, leading to microvascular and macrovascular complications. Diabetes-related complications cause severe and prolonged morbidity and are a major cause of mortality among people with diabetes. Despite increasing attention to risk factors of type 2 diabetes, existing evidence is scarce or inconclusive regarding vascular complications and research investigating both micro- and macrovascular complications is lacking. This thesis aims to contribute to current knowledge by identifying risk factors – mainly related to lifestyle – of vascular complications, addressing methodological limitations of previous literature and providing comparative data between micro- and macrovascular complications.
To address this overall aim, three specific objectives were set. The first was to investigate the effects of diabetes complication burden and lifestyle-related risk factors on the incidence of (further) complications. Studies suggest that diabetes complications are interrelated. However, they have been studied mainly independently of individuals’ complication burden. A five-state time-to-event model was constructed to examine the longitudinal patterns of micro- (kidney disease, neuropathy and retinopathy) and macrovascular complications (myocardial infarction and stroke) and their association with the occurrence of subsequent complications. Applying the same model, the effect of modifiable lifestyle factors, assessed alone and in combination with complication load, on the incidence of diabetes complications was studied. The selected lifestyle factors were body mass index (BMI), waist circumference, smoking status, physical activity, and intake of coffee, red meat, whole grains, and alcohol. Analyses were conducted in a cohort of 1199 participants with incident type 2 diabetes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, who were free of vascular complications at diabetes diagnosis. During a median follow-up time of 11.6 years, 96 cases of macrovascular complications (myocardial infarction and stroke) and 383 microvascular complications (kidney disease, neuropathy and retinopathy) were identified. In multivariable-adjusted models, the occurrence of a microvascular complication was associated with a higher incidence of further micro- (Hazard ratio [HR] 1.90; 95% Confidence interval [CI] 0.90, 3.98) and macrovascular complications (HR 4.72; 95% CI 1.25, 17.68), compared with persons without a complication burden. In addition, participants who developed a macrovascular event had a twofold higher risk of future microvascular complications (HR 2.26; 95% CI 1.05, 4.86). The models were adjusted for age, sex, state duration, education, lifestyle, glucose-lowering medication, and pre-existing conditions of hypertension and dyslipidaemia. Smoking was positively associated with macrovascular disease, while an inverse association was observed with higher coffee intake. Whole grain and alcohol intake were inversely associated with microvascular complications, and a U-shaped association was observed for red meat intake. BMI and waist circumference were positively associated with microvascular events. The associations between lifestyle factors and incidence of complications were not modified by concurrent complication burden, except for red meat intake and smoking status, where the associations were attenuated among individuals with a previous complication.
The second objective was to perform an in-depth investigation of the association between BMI and BMI change and risk of micro- and macrovascular complications. There is an ongoing debate on the association between obesity and risk of macrovascular and microvascular outcomes in type 2 diabetes, with studies suggesting a protective effect among people with overweight or obesity. These findings, however, might be limited due to suboptimal control for smoking, pre-existing chronic disease, or short-follow-up. After additional exclusion of persons with cancer history at diabetes onset, the associations between pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI and incidence of complications were evaluated in multivariable-adjusted Cox models. The analyses were adjusted for age, sex, education, smoking status and duration, physical activity, alcohol consumption, adherence to the Mediterranean diet, and family history of diabetes and cardiovascular disease (CVD). Among 1083 EPIC-Potsdam participants, 85 macrovascular and 347 microvascular complications were identified during a median follow-up period of 10.8 years. Higher pre-diagnosis BMI was associated with an increased risk of total microvascular complications (HR per 5 kg/m2 1.21; 95% CI 1.07, 1.36), kidney disease (HR 1.39; 95% CI 1.21, 1.60) and neuropathy (HR 1.12; 95% CI 0.96, 1.31); but no association was observed for macrovascular complications (HR 1.05; 95% CI 0.81, 1.36). Effect modification was not evident by sex, smoking status, or age groups. In analyses according to BMI change categories, BMI loss of more than 1% indicated a decreased risk of total microvascular complications (HR 0.62; 95% CI 0.47, 0.80), kidney disease (HR 0.57; 95% CI 0.40, 0.81) and neuropathy (HR 0.73; 95% CI 0.52, 1.03), compared with participants with a stable BMI. No clear association was observed for macrovascular complications (HR 1.04; 95% CI 0.62, 1.74). The impact of BMI gain on diabetes-related vascular disease was less evident. Associations were consistent across strata of age, sex, pre-diagnosis BMI, or medication but appeared stronger among never-smokers than current or former smokers.
The last objective was to evaluate whether individuals with a high-risk profile for diabetes and cardiovascular disease (CVD) also have a greater risk of complications. Within the EPIC-Potsdam study, two accurate prognostic tools were developed, the German Diabetes Risk Score (GDRS) and the CVD Risk Score (CVDRS), which predict the 5-year type 2 diabetes risk and 10-year CVD risk, respectively. Both scores provide a non-clinical and clinical version. Components of the risk scores include age, sex, waist circumference, prevalence of hypertension, family history of diabetes or CVD, lifestyle factors, and clinical factors (only in clinical versions). The association of the risk scores with diabetes complications and their discriminatory performance for complications were assessed. In crude Cox models, both versions of GDRS and CVDRS were positively associated with macrovascular complications and total microvascular complications, kidney disease and neuropathy. Higher GDRS was also associated with an elevated risk of retinopathy. The discrimination of the scores (clinical and non-clinical) was poor for all complications, with the C-index ranging from 0.58 to 0.66 for macrovascular complications and from 0.60 to 0.62 for microvascular complications.
In conclusion, this work illustrates that the risk of complication development among individuals with type 2 diabetes is related to the existing complication load, and attention should be given to regular monitoring for future complications. It underlines the importance of weight management and adherence to healthy lifestyle behaviours, including high intake of whole grains, moderation in red meat and alcohol consumption and avoidance of smoking to prevent major diabetes-associated complications, regardless of complication burden. Risk scores predictive for type 2 diabetes and CVD were related to elevated risks of complications. By optimising several lifestyle and clinical factors, the risk score can be improved and may assist in lowering complication risk.
Die berufliche Wiedereingliederung von Patienten nach akutem Herzinfarkt stellt sowohl aus gesellschaftlicher wie auch aus individueller Sicht einen entscheidenden Schritt zur vollständigen Rekonvaleszenz dar. Lediglich 10% der Patienten werden durch kardiale Probleme an der Reintegration behindert. Neben medizinischen und berufsbezogenen Faktoren determinieren insbesondere psychosoziale Parameter eine erfolgreiche Wiederaufnahme der Tätigkeit. Verschiedene Programme der Rentenversicherungsträger werden dabei unterstützend angeboten.
Hintergrund In den letzten Jahrzehnten führte die leitliniengerechte Therapie des akuten Myokardinfarktes (MI) zu einer Mortalitätsreduktion in Deutschland, wobei zwischen einzelnen Bundesländern erhebliche Unterschiede beschrieben werden. Ziel war es daher, die aktuelle Versorgungssituation von Patienten mit MI in der Region Nordost-Deutschland (Berlin, Brandenburg [BRB] und Mecklenburg-Vorpommern [MV]) zu untersuchen und Prädiktoren der 1-Jahresmortalität unter Berücksichtigung der regionalen Zuordnung zu identifizieren.
Methode Auf Basis pseudonymisierter Abrechnungsdaten einer gesetzlichen Krankenversicherung wurden für das Jahr 2012 anhand des ICD 10-Codes I21 und I22 von 1 387 084 Versicherten insgesamt 6733 Patienten mit stationärer Aufnahme bei MI gefiltert. Neben der Krankenhaus- und 1-Jahresmortalität wurden potenzielle Prognoseprädiktoren unter Berücksichtigung von Komorbiditäten, periinfarziellen Prozeduren und sekundärpräventiver Pharmakotherapie erfasst und im Ländervergleich analysiert.
Ergebnisse Sowohl die Krankenhaus- als auch die 1-Jahresmortalitätsrate der einzelnen Länder (Berlin 13,6 resp. 27,5 %, BRB 13,9 resp. 27,9 %, MV 14,4 resp. 29,0 %) war vergleichbar zur Gesamtrate (13,9 % resp. 28,0 %) und im Ländervergleich weitgehend identisch. Die multiple Analyse der Einflussfaktoren auf die 1-Jahresmortalität identifizierte vor allem die Koronarangiografie (OR 0,42, 95 % KI 0,35 – 0,51, p < 0,001) und die Umsetzung der pharmakologischen Leitlinienempfehlungen (OR 0,14, 95 % KI 0,12 – 0,17, p < 0,001) als wesentliche Maßnahmen zur Risikoreduktion. Bei beiden Einflussfaktoren lagen univariat keine statistischen Unterschiede zwischen den drei Bundesländern vor.
Schlussfolgerung Die vorliegenden Daten lassen auf eine vergleichbare stationäre und poststationäre Versorgung und 1-Jahresprognose von Patienten mit akutem MI in den Bundesländern Berlin, Brandenburg und Mecklenburg-Vorpommern in der untersuchten Population schließen, wobei insbesondere der Durchführung einer Koronarangiografie und der adäquaten Umsetzung einer leitliniengerechten Pharmakotherapie prognostische Bedeutung zukommt.
Background: The Mediterranean Diet (MedDiet) has been acknowledged as a healthy diet. However, its relation with risk of major chronic diseases in non-Mediterranean countries is inconclusive. The Nordic diet is proposed as an alternative across Northern Europe, although its associations with the risk of chronic diseases remain controversial. We aimed to investigate the association between the Nordic diet and the MedDiet with the risk of chronic disease (type 2 diabetes (T2D), myocardial infarction (MI), stroke, and cancer) in the EPIC-Potsdam cohort. Methods: The EPIC-Potsdam cohort recruited 27,548 participants between 1994 and 1998. After exclusion of prevalent cases, we evaluated baseline adherence to a score reflecting the Nordic diet and two MedDiet scores (tMDS, reflecting the traditional MedDiet score, and the MedPyr score, reflecting the MedDiet Pyramid). Cox regression models were applied to examine the association between the diet scores and the incidence of major chronic diseases. Results: During a follow-up of 10.6 years, 1376 cases of T2D, 312 of MI, 321 of stroke, and 1618 of cancer were identified. The Nordic diet showed a statistically non-significant inverse association with incidence of MI in the overall population and of stroke in men. Adherence to the MedDiet was associated with lower incidence of T2D (HR per 1 SD 0.93, 95% CI 0.88-0.98 for the tMDS score and 0.92, 0.87-0.97 for the MedPyr score). In women, the MedPyr score was also inversely associated with MI. No association was observed for any of the scores with cancer. Conclusions: In the EPIC-Potsdam cohort, the Nordic diet showed a possible beneficial effect on MI in the overall population and for stroke in men, while both scores reflecting the MedDiet conferred lower risk of T2D in the overall population and of MI in women.
Objective Depression after stroke and myocardial infarction (MI) is common but often assumed to be undertreated without reliable evidence being available. Thus, we aimed to determine treatment rates and investigate the application of guidelines in these conditions. Methods Databases MEDLINE, EMBASE, PsycInfo, Web of Science, CINAHL, and Scopus were systematically searched without language restriction from inception to June 30, 2017. Prospective observational studies with consecutive recruitment reporting any antidepressant treatment in adults with depression after stroke or MI were included. Random-effects models were used to calculate pooled estimates of treatment rates. Results Fifty-five studies reported 32 stroke cohorts (n = 8938; pooled frequency of depression = 34%, 95% confidence interval [CI] = 29%-38%) and 17 MI cohorts (n = 10,767; pooled frequency of depression = 24%, 95% CI = 20%-28%). In 29 stroke cohorts, 24% (95% CI = 20%-27%) of 2280 depressed people used antidepressant medication. In 15 MI cohorts, 14% (95% CI = 8%-19%) of 2381 depressed people used antidepressant medication indicating a lower treatment rate than in stroke. Two studies reported use of psychosocial interventions, indicating that less than 10% of participants were treated. Conclusions Despite the high frequency of depression after stroke and MI and the existence of efficacious treatment strategies, people often remain untreated. Innovative strategies are needed to increase the use of effective antidepressive interventions in patients with cardiovascular disease.
BACKGROUND: Reduced left ventricular ejection fraction (LVEF) ≤30% is the most powerful prognostic indicator for sudden cardiac death (SCD) in patients after myocardial infarction (MI), but there are little data about long-term changes of LVEF after revascularization and the following implantation of a cardioverter defibrillator (ICD).
METHODS: We performed a retrospective analysis of 277 patients with reduced LVEF at least 1month after MI and complete revascularization. Patients (median time post-MI 23.4months; 74.3% after PCI, 25.7% after CABG were assigned either to group 1 (LVEF<30%) or group 2 (LVEF 30-40%). Biplane echocardiography was redone after a mean follow-up of 441±220days.
RESULTS: LVEF increased significantly in both two groups (group 1: 26.2±4.8% to 32.4±8.5%; p<0.001; group 2: 38.2±2.5% to 44.4±9.6%; p<0.001). However, statistical analysis of first and second LVEF measurement by means of a LOWESS regression and with an appropriate correction of the regression towards the mean effect revealed only a moderate increase of the mean LVEF from 35 to 37% (p<0.001) with a large interindividual variation.
CONCLUSIONS: The impact of early revascularization on LVEF appears to be low in the majority of post-MI heart failure patients. Owing to the high variability, a single measurement may not be reliable enough to justify a decision on ICD indication.
Hintergrund: In Deutschland stellt der akute Myokardinfarkt (MI) eine der häufigsten Todesursachen dar. Als Ursache für regionale Unterschiede bei den Mortalitätsraten werden divergente Versorgungsstrukturen vermutet. Ziel der Untersuchung war, diese Fragestellung anhand anonymisierter krankenkassenbasierter Abrechnungsdaten zu evaluieren.
Methodik: Standardisierte Hospitalisierungs- sowie Krankenhaus- und Ein-Jahres-Mortalitätsraten nach MI wurden anhand anonymisierter Versichertendaten einer gesetzlichen Krankenkasse für das Jahr 2012 und die Bundesländer Berlin, Brandenburg und Mecklenburg-Vorpommern ermittelt (n=1.387.084, 46.3% male, 60.9 ± 18,2 years). Weiterhin wurden prädiktive Einflussfaktoren auf die Ein-Jahres-Mortalität, auf die Durchführung invasiver Prozeduren und auf eine leitliniengerechte pharmakotherapeutische Sekundärprävention analysiert.
Ergebnisse: 6.733 Patienten (73,7 ±13,0 Jahre, 56,7% männlich) wurden identifiziert. Obwohl für das Bundesland Berlin eine höhere Hospitalisierungsrate als in Mecklenburg-Vorpommern ermittelt werden konnte, ließen sich bei der Krankenhaus- und 1-Jahres-Mortalität keine signifikant abweichenden Raten zwischen den Bundesländern beobachten. Die Durchführung einer Koronarangiographie (OR: 0,42 [0,35-0,51]) und eine leitliniengerechte Pharmakotherapie (OR: 0,14 [0,12-0,17] waren mit einer geringeren 1-Jahres-Mortalität assoziiert. Die Durchführung einer Koronarangiographie und eine leitliniengerechte Pharmakotherapie von Patienten nach Myokardinfarkt wurde hingegen primär durch Alter und Geschlecht, nicht aber durch das Bundesland determiniert.
Folgerung: Eine regional divergierende stationäre und postinfarzielle Versorgung auf Bundesland-Ebene kann anhand der vorliegenden Daten nicht nachgewiesen werden.