Elsevier

Atherosclerosis

Volume 290, November 2019, Pages 140-205
Atherosclerosis

2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk

https://doi.org/10.1016/j.atherosclerosis.2019.08.014Get rights and content

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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

  • 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.

  • 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.

  • 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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References (576)

  • R.A. Hegele et al.

    European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management

    Lancet Diabetes Endocrinol

    (2014)
  • E.J. Mills et al.

    Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients

    J. Am. Coll. Cardiol.

    (2008)
  • B.A. Ference et al.

    Impact of lipids on cardiovascular health: JACC health promotion series

    J. Am. Coll. Cardiol.

    (2018)
  • B.A. Ference et al.

    Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis

    J. Am. Coll. Cardiol.

    (2012)
  • B.A. Ference et al.

    Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 x 2 factorial Mendelian randomization study

    J. Am. Coll. Cardiol.

    (2015)
  • A. Varbo et al.

    Remnant cholesterol as a causal risk factor for ischemic heart disease

    J. Am. Coll. Cardiol.

    (2013)
  • B.F. Voight et al.

    Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study

    Lancet

    (2012)
  • B.G. Nordestgaard et al.

    Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology

    J. Lipid Res.

    (2016)
  • S.S. Martin et al.

    Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications

    J. Am. Coll. Cardiol.

    (2013)
  • J.G. Robinson et al.

    Safety of very low low-density lipoprotein cholesterol levels with alirocumab: pooled data from randomized trials

    J. Am. Coll. Cardiol.

    (2017)
  • S.P. Whelton et al.

    Evaluating the atherogenic burden of individuals with a Friedewald-estimated low-density lipoprotein cholesterol <70 mg/dL compared with a novel low-density lipoprotein estimation method

    J Clin Lipidol

    (2017)
  • M.R. Langlois et al.

    Clinical impact of direct HDLc and LDLc method bias in hypertriglyceridemia. A simulation study of the EAS-EFLM Collaborative Project Group

    Atherosclerosis

    (2014)
  • T. Miida et al.

    A multicenter study on the precision and accuracy of homogeneous assays for LDL-cholesterol: comparison with a beta-quantification method using fresh serum obtained from non-diseased and diseased subjects

    Atherosclerosis

    (2012)
  • S.M. Marcovina et al.

    Lipoprotein (a) measurements for clinical application

    J. Lipid Res.

    (2016)
  • S. Tsimikas et al.

    Relationship of lipoprotein(a) molar concentrations and mass according to lipoprotein(a) thresholds and apolipoprotein(a) isoform size

    J Clin Lipidol

    (2018)
  • B.G. Nordestgaard et al.

    Triglycerides and cardiovascular disease

    Lancet

    (2014)
  • L.J. Cartier et al.

    Comparison of fasting and non-fasting lipid profiles in a large cohort of patients presenting at a community hospital

    Clin. Biochem.

    (2018)
  • A.L. Catapano et al.

    ESC/EAS Guidelines for the management of dyslipidaemias

    Eur. Heart J.

    (2016)
  • B.A. Ference et al.

    Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel

    Eur. Heart J.

    (2017)
  • N. Townsend et al.

    Cardiovascular disease in Europe--epidemiological update 2015

    Eur. Heart J.

    (2015)
  • M.T. Cooney et al.

    Re-evaluating the Rose approach: comparative benefits of the population and high-risk preventive strategies

    Eur. J. Cardiovasc. Prev. Rehabil.

    (2009)
  • World Health Organization

    Global status report on noncommunicable diseases 2014

    World Health Organization

    (2014)
  • M.T. Cooney et al.

    Cardiovascular risk-estimation systems in primary prevention: do they differ? Do they make a difference? Can we see the future?

    Circulation

    (2010)
  • J. Perk et al.

    European association for cardiovascular prevention & rehabilitation; ESC Committee for practice guidelines (CPG). European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The fifth Joint task force of the European society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts)

    Eur. Heart J.

    (2012)
  • M.F. Piepoli et al.

    European guidelines on cardiovascular disease prevention in clinical practice: the sixth Joint task force of the European society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European association for cardiovascular prevention & rehabilitation (EACPR)

    Eur. Heart J.

    (2016)
  • M.T. Cooney et al.

    Cardiovascular risk estimation in older persons: SCORE O.P

    Eur J Prev Cardiol

    (2016)
  • J.D. Berry et al.

    Lifetime risks of cardiovascular disease

    N. Engl. J. Med.

    (2012)
  • M. Kavousi et al.

    Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study

    Ann. Intern. Med.

    (2012)
  • J. Yeboah et al.

    Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals

    J. Am. Med. Assoc.

    (2012)
  • C.M. Madsen et al.

    Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies

    Eur. Heart J.

    (2017)
  • J.S. Lin et al.

    Nontraditional risk factors in cardiovascular disease risk assessment: updated evidence report and systematic review for the US Preventive Services Task Force

    J. Am. Med. Assoc.

    (2018)
  • H. Sillesen et al.

    Carotid plaque thickness and carotid plaque burden predict future cardiovascular events in asymptomatic adult Americans

    Eur Heart J Cardiovasc Imaging

    (2018)
  • P. Perrone-Filardi et al.

    Cardiac computed tomography and myocardial perfusion scintigraphy for risk stratification in asymptomatic individuals without known cardiovascular disease: a position statement of the Working Group on Nuclear Cardiology and Cardiac CT of the European Society of Cardiology

    Eur. Heart J.

    (2011)
  • H.M. Den Ruijter et al.

    Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis

    J. Am. Med. Assoc.

    (2012)
  • M.W. Lorenz et al.

    Is carotid intima media thickness useful for individual prediction of cardiovascular risk? Ten-year results from the Carotid Atherosclerosis Progression Study (CAPS)

    Eur. Heart J.

    (2010)
  • I. Cho et al.

    Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study

    Eur. Heart J.

    (2018)
  • M. Kavousi et al.

    Prevalence and prognostic implications of coronary artery calcification in low-risk women: a meta-analysis

    J. Am. Med. Assoc.

    (2016)
  • J.J. Brugts et al.

    The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials

    BMJ

    (2009)
  • C.P. Cannon et al.

    Ezetimibe added to statin therapy after acute coronary syndromes

    N. Engl. J. Med.

    (2015)
  • Cholesterol Treatment Trialists Collaboration et al.

    Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials

    Lancet

    (2010)
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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.

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