Hypercholesterolemia is a major risk factor for cardiovascular diseases, which are the leading cause of death worldwide . In patients with hypercholesterolemia, current guidelines recommend lifestyle interventions and, if necessary, medication to reduce high plasma cholesterol [2,3]. Medication such as statins is both effective in the prevention of cardiovascular events as well as cost-effective in patients with known or at high risk of developing cardiovascular disease [4,5].
However, little is known about the cost-of-illness associated with hypercholesterolemia in the routine care setting. Most studies assessing costs in patients with hypercholesterolemia have been economic evaluations of clinical trials. Costs arising in the usual care setting may be different from costs arising in the setting of a clinical trial with visits and tests scheduled as well as therapies. In routine care, there are a variety of factors influencing costs such as adherence of patients with their medication and/or lifestyle measures , the prevalence of concomitant diseases, or medication costs which may differ in the two settings. For health policy making and resource allocation, costs arising in the usual care setting are more relevant than costs arising in clinical trials.
As part of the ORBITAL - Open Label Primary Care Study: Rosuvastatin Based Compliance Initiatives To Achievements of LDL Goals - study, we retrospectively assessed both direct costs by medical resource use and disease-related productivity loss due to days off-work and early retirement in the six months preceding study enrolment. The ORBITAL Study which has been described in detail elsewhere  is a randomised controlled trial evaluating the effectiveness of an adherence-enhancing program in patients with statin therapy. In the present analysis, we combine individual patient data from the ORBITAL study with the prevalence of treated hypercholesterolemia in Germany and demographic changes up to year 2050 in order to project future costs arising for this disease.
2) Cost-of-illness associated with hypercholesterolemia in the ORBITAL Study
A total of 7640 patients with an indication for treatment of hypercholesterolemia according the European Guidelines on cardiovascular disease prevention in clinical practice were included in the ORBITAL study . In these patients, disease-related costs amounted to a mean of 2498 ± 4898 Euros per patient over six months. Direct costs comprised 44% and indirect costs 56% of total costs. To assess 12-month costs, we redoubled the 6-month direct costs. With regard to indirect costs, we redoubled days off-work. For costs of early retirement, we assumed the same rate during the first six months as observed in the six months of our original study but added the costs of another six months to derive 12-month costs. Costs over 12 months thus amounted to a mean of 4947 Euros with a standard deviation of 9700.
Costs over 12 months were approximately 5000 Euros per patient.
Mean costs per patient arising over 12 months in the ORBITAL study per age group are shown in Table 1. For the age group 80+ we assumed similar costs as for the age group 70-79.
Table 1: Mean costs per patient in each age group during 12 months in the ORBITAL study
|Age (years)||Mean costs in Euro ± SD||Mean costs in Euro ± SD|
|Men||Total costs||Direct costs|
|20-29||1686 ± 1669||888 ± 1106|
|30-39||4756 ± 9159||2732 ± 5708|
|40-49||5208 ± 9444||1972 ± 3846|
|50-59||7363 ± 11645||2416 ± 4564|
|60-69||6354 ± 11064||2057 ± 4051|
|70-79||2302 ± 4288||2302 ± 4288|
|20-29||850 ± 665||793 ± 671|
|30-39||2116 ± 4601||1711 ± 4450|
|40-49||4750 ± 10105||2273 ± 6824|
|50-59||5921 ± 10526||2211 ± 4676|
|60-69||3847 ± 8973||2005 ± 5345|
|70-79||2443 ± 6028||2441 ± 6028|
Abbreviation: SD = standard deviation
Abbreviation: SD = standard deviation
The ORBITAL study included patients between November 2002 and February 2004, with the majority of costs in the retrospective analyses arising in the year 2002. As the year 2007 was the first year of our current cost projection, we adjusted the baseline ORBITAL costs assuming an annual inflation-rate of 1.5% during the last 5 years. The choice of this rate was supported by data of the Federal Health Monitoring .
3) Demographic projection
For the analyses of future cost trends, we used demographic population projections up to the year 2050, assuming a birth rate of 1.4 per year, a net-migration rate of 200,000 per annum in Germany, and an increasing life expectancy up to 81 years in men and 87 years in women, respectively . We calculated population trends for each year from 2007 to 2050. Between 2007 and 2050, there will be a considerable age shift with an increasing proportion of older age groups. However, the total population size is going to decrease until 2050.
4) Prevalence of hypercholesterolemia
For the prevalence of treated hypercholesterolemia in Germany, we referred to the results of the German National Health Survey . We multiplied the prevalence of treated persons with hypercholesterolemia in each age group (Table 1) with the projected number of persons in the respective age group. We assumed the prevalence to remain constant during the projected time period. As there was no data available for the age group 80+ years, we used the same prevalence as for the age group 70-79 years.
Table 2: Prevalence of hypercholesterolemia in the German population aged 18-79 years 
|Age (years)||Mean Prevalence %||Mean Prevalence % treated|
Figure 1 shows the estimated number of treated patients during the projected time period.
Figure 1: Projected number of treated patients with hypercholesterolemia from 2007 to 2050
5) Cost projection of hypercholesterolemia in Germany
The estimated number of treated persons in Germany was multiplied with mean 12-month costs as derived from the ORBITAL study for each age group. As indirect costs are less robust with their calculation depending on a number of uncertain factors such as methods used (human capital vs. friction method approach) or job market situation, we focused on direct costs in the estimation of projected costs.
Figure 2 shows the projected costs of hypercholesterolemia taking into account demographic changes from 2007 to 2050. For the presentation of yearly costs, we did not discount as discounting would lead to the false impression of decreasing costs. Total annual costs increase by approximately 15% up to the year 2027, reaching a maximum of 15.5 billion Euros. After 2027, costs start to decrease reaching an estimated 12.7 billion in the year 2050 (direct costs: 6.9 billion in the year 2007, 8.1 billion Euros in 2030, and 7.3 billion Euros in 2050).
For the calculation of cumulative costs, on the other hand, we discounted at an annual rate of 5% . Total costs (discounted) until 2050 amounted to 266.4 billion Euros, total direct costs (discounted) to 141.3 billion Euros, respectively.
Figure 2: Projected costs of hypercholesterolemia in Germany from 2007 to 2050 (not discounted)
The present cost-of-illness analysis shows that costs associated with hypercholesterolemia and its cardiovascular complications are considerable. As projected for future decades, costs will continue to increase until they reach a peak in the year 2027. Due to a net decrease in population size until 2050, costs will then gradually level off.
There are some limitations in our estimation of costs. As we used cost data from patients with hypercholesterolemia of the ORBITAL-study, our results are only generalisable to patients with lipid-lowering therapy. The real burden of hypercholesterolemia is likely to be considerably higher than in our analyses. As shown by the National Health Survey, only a relatively small percentage of patients with hypercholesterolemia actually receive treatment. Therefore, our calculation should be seen as a conservative approach. Furthermore, it should be kept in mind that this calculation extends the study data far beyond the observation period. No observational data were available for the lifetime extrapolation of costs in patients with hypercholesterolemia. Additionally, the present study tries to predict future developments by extrapolation of current observations. Therefore, we were not able to take into account possible future changes such as new therapeutic or diagnostic options.
To conclude, the considerable economic burden associated with hypercholesterolemia indicates the need to assess long-term cost-effectiveness of health care programs in patients with this disorder.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.