Risk Assessment and Clinical Management of Children and Adolescents with Heterozygous Familial Hypercholesterolaemia. A Position Paper of the Associations of Preventive Pediatrics of Serbia, Mighty Medic and International Lipid Expert Panel.

Heterozygous familial hypercholesterolaemia (FH) is among the most common genetic metabolic lipid disorders characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth and a significantly higher risk of developing premature atherosclerotic cardiovascular disease. The majority of the current pediatric guidelines for clinical management of children and adolescents with FH does not consider the impact of genetic variations as well as characteristics of vascular phenotype as assessed by recently developed non-invasive imaging techniques. We propose a combined integrated approach of cardiovascular (CV) risk assessment and clinical management of children with FH incorporating current risk assessment profile (LDL-C levels, traditional CV risk factors and familial history) with genetic and non-invasive vascular phenotyping. Based on the existing data on vascular phenotype status, this panel recommends that all children with FH and cIMT ≥0.5 mm should receive lipid lowering therapy irrespective of the presence of CV risk factors, family history and/or LDL-C levels Those children with FH and cIMT ≥0.4 mm should be carefully monitored to initiate lipid lowering management in the most suitable time. Likewise, all genetically confirmed children with FH and LDL-C levels ≥4.1 mmol/L (160 mg/dL), should be treated with lifestyle changes and LLT irrespective of the cIMT, presence of additional RF or family history of CHD.

Cost-effectiveness of optimized adherence to prevention guidelines in European patients with coronary heart disease: Results from the EUROASPIRE IV survey.

BACKGROUND: This study aims to assess the cost-effectiveness of optimized guideline adherence in patients with a history of coronary heart disease. METHODS: An individual-based decision tree model was developed using the SMART risk score tool which estimates the 10-year risk for recurrent vascular events in patients with manifest cardiovascular disease (CVD). Analyses were based on the EUROASPIRE IV survey. Outcomes were expressed as an incremental cost-effectiveness ratio (ICER). RESULTS: Data from 4663 patients from 13 European countries were included in the analyses. The mean estimated 10-year risk for a recurrent vascular event decreased from 20.13% to 18.61% after optimized guideline adherence. Overall, an ICER of 52,968€/QALY was calculated. The ICER lowered to 29,093€/QALY when only considering high-risk patients (≥20%) with decreasing ICERs in higher risk patients. Also, a dose-response relationship was seen with lower ICERs in older patients and in those patients with higher risk reductions. A less stringent LDL target (<2.5 mmol/L vs. <1.8 mmol/L) lowered the ICER to 32,591€/QALY and intensifying cholesterol treatment in high-risk patients (≥20%) instead of high-cholesterol patients lowered the ICER to 28,064€/QALY. An alternative method, applying risk reductions to the CVD events instead of applying risk reductions to the risk factors lowered the ICER to 31,509€/QALY. CONCLUSION: Depending on the method used better or worse ICERs were found. In addition, optimized guidelines adherence is more cost-effective in higher risk patients, in patients with higher risk reductions and when using a less strict LDL-C target. Current analyses advice to maximize guidelines adherence in particular patient subgroups.

Prevalence and management of familial hypercholesterolaemia in coronary patients: An analysis of EUROASPIRE IV, a study of the European Society of Cardiology.

BACKGROUND: Familial hypercholesterolaemia (FH) is a hereditary disorder predisposing to premature coronary heart disease (CHD) and is until now mainly diagnosed clinically on the basis of a classical phenotype. Its prevalence varies and is estimated around 1 in 200-500; in patients with established CHD the prevalence is less well documented. METHODS AND RESULTS: In EUROASPIRE IV data were collected in coronary patients from 24 European countries by means of a standardized interview, bioclinical examination and venous blood sampling. Potential FH was estimated using an adapted version of the Dutch Lipid Clinic Network Criteria. Among the 7044 patients eligible for analysis, the prevalence of potential FH was 8.3%; 7.5% in men and 11.1% in women. The prevalence was inversely related to age with a putative prevalence of 1:5 in those with CHD <50 yrs of age in both sexes. Even among women aged 70 the prevalence was 1:10. Irrespective of age and gender, prevalence differed substantially between European regions; potential FH patients were more likely to smoke, had higher triglycerides levels and their blood pressure was less well controlled. The use of cardioprotective drugs and the prevalences of diabetes, obesity and central obesity were similar. CONCLUSIONS: The prevalence of potential FH in coronary patients is high; the results underscore the need to promote identification of FH in CHD patients and to improve their risk factor profile.

Statins in the primary prevention of cardiovascular disease.

Statins are widely used in the evidence-based lowering of cardiovascular disease (CVD) risk. The use of these drugs for secondary prevention of CVD is well founded, but their expanding use in primary prevention--in individuals without documented CVD--has raised some concerns. Firstly, evidence suggests that, in primary prevention, statins substantially decrease CVD morbidity, but only moderately reduce CVD mortality. Secondly, long-term statin use might cause adverse effects, such as incident diabetes mellitus. Thirdly, the cost-effectiveness of such a strategy is unclear, and has to be balanced against the risk of 'overmedicating' the general population. Data clearly support the use of statins for primary prevention in high-risk individuals, in whom the strategy is cost-effective and the benefits exceed the risks. Whether primary prevention is beneficial in individuals at low or moderate risk is not certain. Therefore, the prescription of statins for primary prevention should be individualized on the basis of clinical judgment, particularly for low-risk individuals. In appropriately selected individuals, statins should also be used for primary prevention of ischaemic stroke and transient ischaemic attack.

Population-level changes to promote cardiovascular health.

BACKGROUND: Cardiovascular diseases (CVD) cause 1.8 million premature (<75 years) death annually in Europe. The majority of these deaths are preventable with the most efficient and cost-effective approach being on the population level. The aim of this position paper is to assist authorities in selecting the most adequate management strategies to prevent CVD. DESIGN AND METHODS: Experts reviewed and summarized the published evidence on the major modifiable CVD risk factors: food, physical inactivity, smoking, and alcohol. Population-based preventive strategies focus on fiscal measures (e.g. taxation), national and regional policies (e.g. smoke-free legislation), and environmental changes (e.g. availability of alcohol). RESULTS: Food is a complex area, but several strategies can be effective in increasing fruit and vegetables and lowering intake of salt, saturated fat, trans-fats, and free sugars. Tobacco and alcohol can be regulated mainly by fiscal measures and national policies, but local availability also plays a role. Changes in national policies and the built environment will integrate physical activity into daily life. CONCLUSION: Societal changes and commercial influences have led to the present unhealthy environment, in which default option in life style increases CVD risk. A challenge for both central and local authorities is, therefore, to ensure healthier defaults. This position paper summarizes the evidence and recommends a number of structural strategies at international, national, and regional levels that in combination can substantially reduce CVD.

Cost-effectiveness of optimizing prevention in patients with coronary heart disease: the EUROASPIRE III health economics project.

AIMS: The EUROASPIRE III survey indicated that the guidelines on cardiovascular disease prevention are poorly implemented in patients with established coronary heart disease (CHD). The purpose of this health economic project was to assess the potential clinical effectiveness and cost-effectiveness of optimizing cardiovascular prevention in eight EUROASPIRE III countries (Belgium, Bulgaria, Croatia, Finland, France, Italy, Poland, and the U.K.). METHODS AND RESULTS The individual risk for subsequent cardiovascular events was estimated, based on published Framingham equations. Based on the EUROASPIRE III data, the type of suboptimal prevention, if any, was identified for each individual, and the effects of optimized tailored prevention (smoking cessation, diet and exercise, better management of elevated blood pressure and/or LDL-cholesterol) were estimated. Costs of prevention and savings of avoided events were based on country-specific data. A willingness to pay threshold of €30,000/quality-adjusted life year (QALY) was used. The robustness of the results was validated by sensitivity analyses. Overall, the cost-effectiveness analyses for the eight countries showed mainly favourable results with an average incremental cost-effectiveness ratio (ICER) of €12,484 per QALY. Only in the minority of patients at the lowest risk for recurrent events, intensifying preventive therapy seems not cost-effective. Also, the single impact of intensified cholesterol control seems less cost-effective, possibly because their initial 2-year risk was already fairly low, hence the room for improvement is rather limited. CONCLUSION: These results underscore the societal value of optimizing prevention in most patients with established CHD, but also highlight the need for setting priorities towards patients more at risk and the need for more studies comparing intensified prevention with usual care in these patients.

Prevention of cardiovascular disease guided by total risk estimations--challenges and opportunities for practical implementation: highlights of a CardioVascular Clinical Trialists (CVCT) Workshop of the ESC Working Group on CardioVascular Pharmacology and Drug Therapy.

This paper presents a summary of the potential practical and economic barriers to implementation of primary prevention of cardiovascular disease guided by total cardiovascular risk estimations in the general population. It also reviews various possible solutions to overcome these barriers. The report is based on discussion among experts in the area at a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy that took place in September 2009. It includes a review of the evidence in favour of the "treat-to-target" paradigm, as well as potential difficulties with this approach, including the multiple pathological processes present in high-risk patients that may not be adequately addressed by this strategy. The risk-guided therapy approach requires careful definitions of cardiovascular risk and consideration of clinical endpoints as well as the differences between trial and "real-world" populations. Cost-effectiveness presents another issue in scenarios of finite healthcare resources, as does the difficulty of documenting guideline uptake and effectiveness in the primary care setting, where early modification of risk factors may be more beneficial than later attempts to manage established disease. The key to guideline implementation is to improve the quality of risk assessment and demonstrate the association between risk factors, intervention, and reduced event rates. In the future, this may be made possible by means of automated data entry and various other measures. In conclusion, opportunities exist to increase guideline implementation in the primary care setting, with potential benefits for both the general population and healthcare resources.

A view at the future--a dynamical, protocol-based and computationally intensive approach in cardiovascular risk assessment.

Knowledge of cardiovascular risk factors is increasing. At the same time, risk estimation becomes more and more difficult. The need for a more comprehensive, but more individually based approach is evident. To achieve this aim, we propose a systems biology approach in cardiovascular risk assessment. This means that a large amount of health data, describing many aspects of the health-status of patients, is collected and computed and the results are compared with existing knowledge. Finally, a clinical model is created, which can be the first step in ongoing research protocol, aimed at assessing cardiovascular risk. By using this approach, all potentially relevant risk factors can be identified on a small sample. Moreover, risk groups can be more specifically defined, based on the "natural" clustering of data, according to their predictive load. We tested this possibility on an example of hyperhomocysteinemia which is a well-known complex cardiovascular risk factor.

Drug therapy of cardiovascular risk factors: guidelines versus reality in primary health care service.

AIM: To determine the monthly costs of prescription drugs for the treatment of hypertension, hypercholesterolemia, and diabetes mellitus and their share in the total prescription drugs expenditures allowed by the Croatian Institute for Health Insurance. METHODOLOGY: Hypertension, hypercholesterolemia, and diabetes mellitus were diagnosed in 4,916 patients in three general practitioner (GP) offices in the Zagreb area in January 2005. The monthly cost of medications prescribed by the GPs for the treatment of these three diseases was obtained by summarizing the prices of all antihypertensive, lipid-lowering, and antidiabetic drugs prescribed in one month. The monthly medication costs for each disease separately and all three diseases together were compared with the total prescription drug expenditures approved by the Croatian Institute for Health Insurance. RESULTS: Hypertension was diagnosed in 1,112 (22.6%), hypercholesterolemia in 324 (6.5%), and diabetes mellitus in 359 (7.3%) patients. Monthly cost of all medications prescribed for these three diseases accounted for 81.2% of the total amount approved for medications by the Croatian Institute for Health Insurance. Antihypertensive drugs accounted for 51.1%, antidiabetic drugs for 11.7% for, and lipid-lowering treatment for 18.4%. The medications were prescribed most often to patients older than 65 years (93.6%). CONCLUSION: GPs are strongly obligated by the annual contract with the Croatian Institute for Health Insurance to keep the medication expenses within the approved amount. However, the approved amount is spent mostly on the drug treatment of hypertension, hypercholesterolemia, and diabetes mellitus as the main cardiovascular risk factors.