2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk☆
Section snippets
Preamble
Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate. (see
Definition and rationale
Cardiovascular disease (CVD), of which ASCVD is the major component, is responsible for >4 million deaths in Europe each year. It kills more women (2.2 million) than men (1.8 million), although CV deaths before the age of 65 years are more common in men (490 000 vs. 193 000) [3]. Prevention is defined as a co-ordinated set of actions, either at the population or individual level, aimed at eradicating and eliminating are synonymous or minimizing the impact of CV diseases and their related
Total cardiovascular risk estimation
CV risk in the context of these Guidelines means the likelihood of a person developing an atherosclerotic CV event over a defined period of time. Total CVD risk expresses the combined effect of a number of risk factors on this risk estimate. In these Guidelines, we address the lipid-related contribution to total CV risk and how to manage it at the clinical level.
Biological role of lipids and lipoproteins
Lipoproteins in plasma transport lipids to tissues for energy utilization, lipid deposition, steroid hormone production, and bile acid formation. Lipoproteins consist of esterified and unesterified cholesterol, TGs, and phospholipids and protein components named apolipoproteins that act as structural components, ligands for cellular receptor binding, and enzyme activators or inhibitors.
There are six major lipoproteins in blood: chylomicrons, very low-density lipoprotein (VLDL),
Treatment targets and goals
In previous EAS/ESC Guidelines for the management of dyslipidaemias [1,113] and other major guidelines on the treatment of blood cholesterol to reduce atherosclerotic CV risk in adults [40,114], the importance of LDL-C lowering to prevent ASCVD is strongly emphasized. The European Task Force felt that limiting the current knowledge on CV prevention only to results from RCTs reduces the exploitation of the potential that is available for the prevention of ASCVD. It is the concordance of the
Lifestyle modifications to improve the plasma lipid profile
The pivotal role of nutrition in the prevention of ASCVD has been extensively reviewed [[125], [126], [127], [128], [129]]. Dietary factors influence the development of CVD either directly or through their action on traditional risk factors, such as plasma lipids, BP, or glucose levels.
Convincing evidence of the causal association between diet and ASCVD risk is, nevertheless, available indirectly from randomized ‘metabolic ward’ studies showing that high saturated fat intake causes increased
Mechanism of action
Statins reduce the synthesis of cholesterol in the liver by competitively inhibiting the enzyme HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis. The reduction in intracellular cholesterol promotes increased LDL receptor (LDLR) expression at the surface of the hepatocytes, which in turn results in increased uptake of LDL from the blood, and decreased plasma concentrations of LDL- and other ApoB-containing lipoproteins, including TG-rich particles.
Low-density lipoprotein cholesterol
The degree of LDL-C
Familial dyslipidaemias
Plasma lipid levels are, to a very large extent, determined by genetic factors. In its more extreme forms this is manifested as familial dyslipidaemias. A number of monogenic lipid disorders have been identified; among these, FH is the most common and is strongly related to CVD (Table 11). In general, in a patient with dyslipidaemia, the pattern of inheritance commonly does not suggest that there is a major single gene (monogenic) disorder causing the abnormality; rather, it stems from the
Inflammation
Recent advances in basic science have established a fundamental role for low-degree chronic inflammation in mediating all stages of atherosclerosis, from initiation through progression and, ultimately, to the rupture of plaque and ensuing thrombotic complications of atherosclerosis. The cellular and molecular interactions involved during atherogenesis are fundamentally not different from those in chronic inflammatory–fibroproliferative diseases, such as rheumatoid arthritis (RA),
Monitoring of lipids and enzymes in patients on lipid-lowering therapy
Evidence concerning which tests should be carried out to monitor lipids in patients on treatment is limited. Similar limited evidence applies to tests of possible toxicity, such as ALT and CK. Recommendations stem from consensus rather than evidence-based medicine.
Response to therapy can be assessed at 6–8 weeks from initiation of therapy, but response to lifestyle may take longer. Standard practice for subsequent follow-up monitoring is 6–12 months, but such monitoring intervals are arbitrary.
Cost-effectiveness of cardiovascular disease prevention by lipid modification
In 2015, there were >85 million people in Europe living with CVD [558]. Aging populations [559], unhealthy diets, smoking, sedentary lifestyles, increasing obesity, and diabetes [[560], [561], [562], [563]] are the main contributors. CVD cost the European Union about €210 billion in 2015, one-half of which was in healthcare costs (∼8% of total healthcare expenditure), and the other half in productivity losses and informal care [558].
In these Guidelines, the Joint Task Force recommends a range
Strategies to encourage adoption of healthy lifestyle changes and adherence to lipid-modifying therapies
Helping patients to change to healthier lifestyle habits is most effectively achieved through formal programmes of preventive care, possibly because of the intensive follow-up and multidisciplinary expertise they provide.608 However, in everyday care, adherence to both healthy lifestyle changes and medication regimens is a challenge to patients and professionals.
A comprehensive patient- and family-centred approach located in one healthcare setting is recommended rather than addressing single
Key messages
- 1.
Cholesterol and risk. Prospective studies, randomized trials, and Mendelian randomization studies have all shown that raised LDL-C is a cause of ASCVD. Throughout the range of LDL-C levels, ‘lower is better’ with no lower threshold, at least down to ∼1 mmoL/L. Lowering LDL-C may yield worthwhile benefits in patients with average or below average LDL-C who are already receiving LDL-C-lowering treatment. The proportional reduction in ASCVD risk achieved by lowering LDL-C (e.g. with a statin,
Gaps in the evidence
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Prospective studies are needed to investigate the incremental value of reclassifying total CV risk and defining eligibility for lipid-lowering therapy based on CAC scores in individuals at moderate or high-risk.
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Outcome-based comparisons of CAC scores vs. assessment of arterial (carotid or femoral) plaque burden by ultrasonography for CV risk reclassification in people at moderate or high-risk are needed.
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Although calibrated country-specific versions of the SCORE system are available for many
‘What to do’ and ‘what not to do’ messages from the guidelines
ESC entities having participated in the development of this document
Associations: Acute Cardiovascular Care Association (ACCA), Association of Cardiovascular Nursing & Allied Professions (ACNAP), European Association of Cardiovascular Imaging (EACVI), European Association of Preventive Cardiology (EAPC), European Association of Percutaneous Cardiovascular Interventions (EAPCI).
Councils: Council for Cardiology Practice, Council on Hypertension, Council on Stroke.
Working Groups: Aorta and Peripheral Vascular Diseases, Atherosclerosis and Vascular Biology,
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The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS).
The disclosure forms of all experts involved in the development of these Guidelines are available on the ESC website www.escardio.org/guidelines.
- 1
Representing the EAS.
- 2
The three chairpersons contributed equally to the document.