Scholze et al. BMC Public Health 2010, 10:529 http://www.biomedcentral.com/1471-2458/10/529 angiotensin II receptor blockers (ARBs), angiotensin converting enzyme (ACE) inhibitors, calcium channel blockers, diuretics and beta-blockers) were derived from an analysis of IMS Health pharmaceutical national sales data for all main antihypertensive drug classes pre- scribed in 2007 to patients with an ICD-10 code for hypertension. Treated patients were also assumed to have associated costs for primary care visits to the clinic for check-ups, tests and assessment of hypertensive medication which were derived from country specific publications [35-37]. For the treated group the model took into account the differential adherence rate [38] and relative risk of treatment-related new onset diabetes between the drug classes [39]. For both treated and untreated patients the incidence of cardiovascular events and prevalence of type 2 dia- betes and their associated costs were estimated. Cardio- vascular events included acute myocardial infarction, congestive heart failure, unstable angina, stroke and death. Incidence and costs of events were derived from the literature [11,13,40-45]. The prevalence of type 2 diabetes in the hypertensive population was derived from a European national survey [31] and costs derived from published country-specific data [46]. The cost data in the model takes the viewpoint of the health service and includes hypertension drug costs, management of hypertension in primary care and costs associated with the treatment and management of cardi- ovascular events and type 2 diabetes. The cost of each of these elements was calculated by multiplying the quantity of the resource used or the number of events with the unit price. All costs were inflated to 2008 prices and presented in Euros. Analyses The burden of illness model was created in Access. The Access model generated epidemiological numbers and costs which were then exported to excel for analysis. The model was quality controlled by cross-checking epi- demiological and cost data with other published reports. To address uncertainty around the mean in the overall cost of illness estimate, we conducted a univariate sensi- tivity analysis, where one factor at a time was varied while keeping all other factors constant at their base-case value. We assessed the impact on cost-of-illness of; only including incident rather than prevalent type 2 diabetes, varying the continuation rate, drug cost, cardiovascular cost and type 2 diabetes cost by plus and minus 20%; and applying a discount rate of 3% to future costs. Results Prevalence and risk groups The prevalence of hypertension with MetS in the gen- eral population of Germany, Spain and Italy was 36%, Page 4 of 12 11% and 10% respectively in 2008. In Germany of all subjects with hypertension over half (61%) complied with the ATP III criteria for MetS. In Spain and Italy this proportion was much lower with 22% and 21% respectively. By 2020 the proportion of the hypertensive population with MetS was forecast to increase to 78%, 45% and 43% in Germany, Spain and Italy respectively giving a prevalence in the general population of hyper- tension with MetS of 48% in Germany and 22% in Spain and Italy. Germany had a higher proportion of hyper- tensive subjects with three or four other components of MetS (36%) compared to Spain (8%) and Italy (7%) (fig- ure 2). Figure 3 outlines the prevalence of each individual MetS component in patients with hypertension in 2008 and 2020. The most prevalent component was abdom- inal obesity which reached a prevalence of 62%, 40% and 44% in hypertensive patients in Germany, Spain and Italy respectively in 2008. This was followed by high tryiglycerides, and then impaired fasting glucose. All MetS components were forecast to rise with the preva- lence of abdominal obesity and impaired fasting glucose increasing the most. Consequences of disease The incidence of cardiovascular disease and mortality was around two-fold higher in hypertensive subjects with MetS compared to those without in all three coun- tries. The prevalence of type 2 diabetes was around six fold higher in subjects with MetS (table 1). The inci- dence of cardiovascular disease and mortality and the prevalence of type 2 diabetes increased incrementally with each additional component of MetS. The total number of cardiovascular events, deaths and cases of type 2 diabetes are forecast to rise over 100% in Spain and Italy respectively between 2008 and 2020 and by around 50% in Germany (table 1). Costs Table 2 details the total annual cost-of-illness of hyper- tension with and without MetS in 2008 and 2020 in Germany, Spain and Italy. Total annual costs of hyper- tension with MetS amounted to €24,427, €1,909 and €4,877 million respectively in Germany, Spain and Italy in 2008. These costs represented 82%, 42% and 45% of the total annual costs of hypertension. By 2020, keeping costs set at 2008 prices, these annual costs of hyperten- sion with MetS were forecast to rise by 59%, 179%, 157% in Germany, Spain and Italy respectively (table 2). The largest component of the total annual cost of hypertensive patients with MetS was the treatment and management of the consequence of disease rather than the management of hypertension itself including physi- cian and drug costs. Prevalent type 2 diabetes and