Estimating net transition probabilities from cross-sectional data with application to risk factors in chronic disease modeling.

A problem occurring in chronic disease modeling is the estimation of transition probabilities of moving from one state of a categorical risk factor to another. Transitions could be obtained from a cohort study, but often such data may not be available. However, under the assumption that transitions remain stable over time, age specific cross-sectional prevalence data could be used instead. Problems that then arise are parameter identifiability and the fact that age dependent cross-sectional data are often noisy or are given in age intervals. In this paper we propose a method to estimate so-called net annual transition probabilities from cross-sectional data, including their uncertainties. Net transitions only describe the net inflow or outflow into a certain risk factor state at a certain age. Our approach consists of two steps: first, smooth the data using multinomial P-splines, second, from these data estimate net transition probabilities. This second step can be formulated as a transportation problem, which is solved using the simplex algorithm from linear programming theory. A sensible specification of the cost matrix is crucial to get meaningful results. Uncertainties are assessed by parametric bootstrapping. We illustrate our method using data on body mass index. We conclude that this method provides a flexible way of estimating net transitions and that the use of net transitions has implications for model dynamics, for example when modeling interventions.

Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry.

BACKGROUND: Pulmonary arterial hypertension (PAH) associated with congenital heart disease is usually the result of a large systemic-to-pulmonary shunt, and often leads to right ventricular failure and early death. The purpose of this study was to determine the prevalence of PAH among adult patients included in a national registry of congenital heart disease and to assess the relation between patient characteristics and PAH. METHODS: Patients with PAH associated with a septal defect were identified from the registry. Gender, age, underlying diagnosis, previous closure, age at repair and NYHA classification were recorded. PAH was defined as a systolic pulmonary arterial pressure (sPAP) greater than 40 mm Hg, estimated by means of echocardiographical evaluation. RESULTS: The prevalence of PAH among all 5970 registered adult patients with congenital heart disease was 4.2%. Of 1824 patients with a septal defect in the registry, 112 patients (6.1%) had PAH. Median age of these patients was 38 years (range 18-81 years) and 40% were male. Of these patients, 58% had the Eisenmenger syndrome. Among the patients with a previously closed septal defect, 30 had PAH (3%). Ventricular septal defect (VSD) was the most frequent underlying defect (42%) among patients with PAH and a septal defect. Female sex (Odds ratio=1.5, p=0.001) and sPAP (Odds ratio=0.04, p<0.001) were independently associated with a decreased functional class. CONCLUSION: PAH is common in adult patients with congenital heart disease. In our registry the prevalence of PAH in septal defects is around 6%. More than half of these patients have the Eisenmenger syndrome, which accounts for 1% of the total population in the CONCOR registry. Whether the prevalence of PAH will decrease in the future as a result of early detection and intervention remains to be awaited.

Beyond the root: dilatation of the distal aorta in Marfan's syndrome.

OBJECTIVE: To investigate dilatory changes of the aorta distal to the root in patients with Marfan's syndrome. METHODS AND RESULTS: Data of 268 patients with Marfan's syndrome who were enrolled in the Euro Heart Survey on adult congenital heart disease were analysed. Data used for this study were baseline characteristics, diameters at four levels of the aorta and events during follow up (dissection, aortic repairs and death). At inclusion, 26 patients had a previous dissection and 53 patients without a previous dissection had undergone elective aortic repair, thus leaving 189 patients without previous dissection or repair. During follow up (median 5.4 years), four patients died. A total of 46 aortic events (dissection or elective surgery) occurred in 45 patients, in the distal aorta in 14 patients (31%). Baseline aortic diameter at the levels distal to the root (arch, descending aorta and abdominal aorta) was greater in patients with than in those without a previous elective aortic root intervention (median 26 mm v 24 mm, p = 0.01; 25 mm v 20 mm, p < 0.01; and 20 mm v 17 mm, p < 0.01, respectively). Multivariate analysis showed that a previous elective aortic intervention was associated with a fourfold increased probability of dilatation of the distal aorta, after adjustment for age and sex (p < 0.01). In patients without a previous intervention, the baseline diameter of the descending aorta was an independent predictor of aortic events (hazard ratio 3.0 per quartile, 95% CI 1.5 to 5.9, p = 0.002). Cause for concern is that complete measurements of the aorta (at least one measurement at each level at baseline or during follow up) were available for only 38% of the patients. CONCLUSIONS: Almost one in every three aortic events occurring during follow up of these patients involved the distal aorta. After elective aortic root replacement, a dilated distal aorta is more common than before. Moreover, an increased diameter of the descending aorta is associated with a higher risk of aortic events in patients without previous dissection or aortic root replacement, independent of the diameter of the aortic root. Careful monitoring of the entire aorta is essential for the optimal management of patients with Marfan's syndrome, especially after elective surgery, but is insufficiently performed in Europe.