New features in assessment
One of the first innovations of these guidelines is how to assess CV global risk. In fact risk assessment is based on the SCORE (Systemic Coronary Risk Estimation) model, based on European data (2) instead of the previously-used Framingham estimation system.
The SCORE risk uses five variables: age, gender, smoking habit, systolic blood pressure, and total cholesterol. Two charts have been developed: one at low risk for Belgium, France, Greece, Italy, Luxembourg, Spain, Switzerland and Portugal and one for the other European countries. They indicate the absolute risk of having a fatal CV event in 10 years. (3)
The second important new feature is the introduction of HDL-cholesterol charts that modify risk at all levels of risk as estimated from the previous SCORE cholesterol charts. (4)
The final score provides four key areas: very high, high, moderate, and low CV risk, as a basis for treatment decisions. These areas extend the traditional high and low risk groups based on SCORE ≥5% or <5% to a more gradual scale of risk assessment from the dyslipidaemia point of view.
To convert the risk of fatal CVD to risk of total hard CVD multiply by 3 in men and 4 in women, and slightly less in old people.
A relative risk chart is included for younger and middle-aged people that are at low risk.
The risk will be higher than indicated in the charts in:
- Sedentary and obese subjects, especially with central obesity
- Strong family history of premature CV
- Socially deprived individuals
- Low HDL cholesterol or high tryglicerides
- Increased: fibrinogen, homocysteine, apoB, Lp(a), hs-CPR
- Familial hypercolesterolaemia
- Diabetics. Five fold higher in women and three fold higher in men compared to no diabetes
- Chronic kidney disease
The risk will be lower than indicated in the charts in:
- Very high HDL-C levels
- Family history of longevity
The suggested lipidic screening includes: total cholesterol, HDL and LDL cholesterol (use Friedewald formula if tryglicerides < to 400 mg/dl), triglycerides. Lipid profiling is compulsory in: family history of premature CVD, type 2 diabetes, established CVD, smoking, hypertension, BMI ≥30 kg/m2, waist ≥94 cm in men and ≥80 cm in women, chronic inflammatory disease, chronic kidney disease (CKD), The use of ApoB or ApoB/ApoA1 and LPa is suggested only if at high risk and in subjects with a family history of premature CVD. The screening is recommended for men if > 40 years old and > 50 for women. Anticipate if there are other risk factors such as: familial dyslipidaemia, diabetes, hypertension, obesity. It is also pointed out a considerable intra-individual variation in plasma lipids (5-10% for TC, ∞ 20% for TG).
Therapeutic targets
Therapeutic targets are new. Total cholesterol is not a target anymore, in fact it is recommended to be used to estimate total risk (according to the SCORE charts). The new priority in management of hypercholesterolemia is LDL cholesterol (LDL-C).
Treatment targets. The first parameter considered is LDL-C. In Cholesterol Treatment Trialists’ Collaboration 1 mmol reduction of LDL reduced events by 22%. Non-HDL-C (total C – HDL-C) is suggested for further characterization of combined hyperlipidaemia in diabetes, the metabolic syndrome or CKD. Triglycerides add information to CV risk and are indicated for diagnosis and choice of treatment. Preventive actions should be tailored to the patient’s CV risk. Even though lipids are a continuum to make clear clinical goals, some specific targets have been defined according to the SCORE risk categories as in the table below:
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Class of CV risk
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Treatment targets
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Class of recommendation - level of evidence
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Very high risk (established CVD, Type2 diabetes or type 1 diabetes with T.O.D., moderate/severe CKD or a score level ≥ 10%)
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LDL–C < 70 mg/dl (1.8 mmol/L) and/or ≥ 50% reduction when target level cannot be reached
non-HDL-C
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I A
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High risk (markedly elevated single risk factors or a SCORE level ≥ 5 to <10%)
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LDL–C ∞100 mg/dL (<2.5mmol/L)
non-HDL-C <130 mg/dL
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IIa A
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Moderate risk (SCORE level ≥ 1 and 5%)
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LDL-C ∞ 115 mg/dL
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IIa C
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Intervention strategies
Intervention strategies (lifestyle changes/drug intervention) depend on total CV risk measured according to SCORE charts.
Before starting treatment it is suggested to evaluate possible secondary causes both in hypercholesterolaemia and hypertriglyceridaemia (HTG).
Non pharmacologic therapy on LDL: modest effect of physical activity and loss of weight on LDL cholesterol. More efficient on HDL, triglycerides, and insulin sensibility.
Dietary factors
Dietary factors may influence atherogenesis both directly and through effects on lipid and glucose levels, and blood pressure. The most important dietary recommendations to reduce TC and LDL-C include
the preferred intake of cereals (whole grains), vegetables, legumes, fruits, lean meat and fish, skimmed milk, egg white, fat-free dressing, nuts, seeds.
The suggested cooking procedures are: grilling, boiling and steaming.
For the first time nutraceuticals are taken into consideration. Soy protein, dietary fibre, n-3 unsaturated fatty acids, policosanol and yeast rice can be used either as alternatives or in addition to lipid-lowering drugs. Two grams of phytosterols (sistosterol, campesterol or stigmasterol) can lower LDL cholesterol of about 7-10%. Monacolins, present for instance in red rice, lower TC and LDL-C. Vegetable fibres (5-15 g/day) lower LDL-C. Although diet has an important influence on dyslipidaemias and clinical outcomes, these supplementation products still need to be properly evaluated in clinical trials. Some RCTs are necessary to allow their extensive use in clinical practice.
Pharmacological therapy
The fundamental role of statins in hypercholesterolaemia is highlighted and an algorithm is provided for their best use (5). Practical recommendations on the type and dose of statins are given to reach the targeted LDL-cholesterol.
The benefits of LDL cholesterol reduction are independent from the type of statin. Stains should be titrated at the highest tolerated dose to reach the target. Other effective drugs are: fibrates, nicotinic acid, bile acid sequestrants and ezetimibe. They should be used in case of statin intolerance or added if targets are not reached.
Hypertriglyceridaemia (HTG) (TG > 200 mg/dL) must be treated with lifestyle measures and, in subjects at high total CV risk, with fibrates and niacin (first choice), niacin + laropiprant, n-3 fatty acids, statin + nicotinic acid, statin + fibrate.
A low HDL-C may be treated by niacin, statins and fibrates (may be attenuated in people with type 2 diabetes), and cholesterol ester transfer protein (CETP) direct inhibition such as torcetrapib, dalcetrapib, and anacetrapib.
Clear recommendations are given for monitoring lipids and drug adverse events.
Special populations are considered in these guidelines
First of all young and old people.
Children (it is suggested to start pharmacologic therapy in over 18 year olds). Focus should be diet and treatment of underlying metabolic disorders. Elderly: a high risk group who could benefit from lipid-lowering therapy. It is recommended to start lipid-lowering drugs at a low dose and titrate with caution. Women have a lower CV risk than men. 50 year old women have the same risk as 40 year old men. The impact of lipid lowering is similar in both sexes. Lipid lowering drugs should not be given when pregnancy is planned, during pregnancy, and during the breast feeding period. In acute coronary syndrome (ACS) high doses are recommended from the first to the fourth day of the beginning of ACS. In these patients it is recommended to recheck LDL after 4-6 weeks and to regulate doses on LDL target.
Subjects with metabolic syndrome are at high risk of CVD. In fact their lipid pattern generates atherogenic dyslipidaemia that is one of the major risk factors for CVD in people with type 2 diabetes
Another important group are the familial forms (only hypercholesterolemia and familial combined) that occur in 1.5% to 2% of the population).
Heart failure (HF) and valvular disease do not require statins. N-3 PUFAs may be indicated in HF.
Autoimmune and renal disease, transplant patients, peripheral arterial disease, stroke, and HIV patients are also treated and require special attention from a dyslipidaemic point of view. These patients are at high CV risk and can develop a secondary dyslipidaemia.
Finally, as with any chronic disease, it is useful to develop a strategy to increase adherence to lifestyle changes and drug therapies. Implementation of the guidelines is crucial to their success at national level. The Guidelines suggest an interdisciplinary approach and the involvement of National Societies of Cardiology.
The full text of the ESC/EAS Guidelines for the Management of Dylipidaemias can be found here.