NEW LIPID GUIDELINES:WHAT HAS CHANGED?

NEW LIPID GUIDELINES:WHAT NEW LIPID GUIDELINES:WHAT HAS CHANGED?HAS CHANGED?

ASSOC.PROF.DR. OKAN GULELONDOKUZ MAYIS UNIVERSITY

FACULTY OF MEDICINECARDIOLOGY DEPARTMENT

SAMSUN, TURKEY

Novel/Important Aspects-1Novel/Important Aspects-1

Treatment of dyslipidemia should not be considered Treatment of dyslipidemia should not be considered as an isolated process, but rather within the context as an isolated process, but rather within the context of integrated prevention of cardiovascular disease of integrated prevention of cardiovascular disease

in each patient in each patient →the SCORE system→the SCORE system

Anguita M, et al. Rev Esp Cardiol. 2011 Dec;64(12):1090-5.Anguita M, et al. Rev Esp Cardiol. 2011 Dec;64(12):1090-5.

SCORE ScaleSCORE Scale

The preference for the The preference for the SCORE system over other SCORE system over other risk scales is based on the risk scales is based on the fact that it was designed and fact that it was designed and evaluated using evaluated using representative European representative European cohorts.cohorts.

ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2011 Jul;32(14):1769-818.ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2011 Jul;32(14):1769-818.


The SCORE scale allows for The SCORE scale allows for estimating the 10-year risk of estimating the 10-year risk of the first fatal atherosclerotic the first fatal atherosclerotic complication based on the complication based on the following risk factors: following risk factors: AgeAge GenderGender SmokingSmoking Systolic blood pressureSystolic blood pressure Total cholesterolTotal cholesterol



Charts for high and low risk Charts for high and low risk regions in Europe.regions in Europe.

The low risk chartsThe low risk charts→→in in Belgium, Germany, Finland, Belgium, Germany, Finland, France, Greece, Italy, France, Greece, Italy, Spain, Denmark, The Spain, Denmark, The Netherlands, United Netherlands, United Kingdom, Sweden, Norway, Kingdom, Sweden, Norway, Iceland, Ireland, Austria, Iceland, Ireland, Austria, Malta, Portugal, Slovenia, Malta, Portugal, Slovenia, Monaco, San Marino.Monaco, San Marino.



The high risk chartsThe high risk charts→→in in Bulgaria, Macedonia, Russia, Bulgaria, Macedonia, Russia, Moldova, Ukraine, Belarus, Moldova, Ukraine, Belarus, Latvia.Latvia.



SCORE database has shown SCORE database has shown that HDL-C modifies risk at that HDL-C modifies risk at all levels of risk as all levels of risk as estimated from the SCORE estimated from the SCORE cholesterol charts.cholesterol charts.

Risk will be higher than Risk will be higher than indicated in the charts in indicated in the charts in individuals with low HDL-C.individuals with low HDL-C.


Risk will also be higher than indicated in the charts in;Risk will also be higher than indicated in the charts in;

*Socially deprived individuals*Socially deprived individuals*Sedentary subjects and those with central obesity*Sedentary subjects and those with central obesity

*Individuals with diabetes*Individuals with diabetes

*Individuals with low apo A1, increased triglyceride, fibrinogen, *Individuals with low apo A1, increased triglyceride, fibrinogen, homocysteine, apo B, and lipoprotein(a) levels, familial homocysteine, apo B, and lipoprotein(a) levels, familial

hypercholesterolaemia, or increased hs-CRPhypercholesterolaemia, or increased hs-CRP

*Asymptomatic individuals with preclinical evidence of *Asymptomatic individuals with preclinical evidence of atherosclerosisatherosclerosis

*Those with impaired renal function*Those with impaired renal function*Those with a family history of premature CVD*Those with a family history of premature CVD



A particular problem relates A particular problem relates to young people with high to young people with high levels of risk factors.levels of risk factors.

Although the absolute Although the absolute SCORE risk can be low in SCORE risk can be low in young patients, if several young patients, if several risk factors are present, the risk factors are present, the relative risk will be high.relative risk will be high. ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2011 Jul;32(14):1769-818.ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2011 Jul;32(14):1769-818.

Risk LevelsRisk Levels

Very High Risk:Very High Risk: A calculated SCORE ≥10%A calculated SCORE ≥10% Documented CVD by invasive or non-invasive testingDocumented CVD by invasive or non-invasive testing Type 2 diabetes, type 1 diabetes with target organ Type 2 diabetes, type 1 diabetes with target organ

damagedamage Moderate to severe CKDModerate to severe CKD


Risk LevelsRisk Levels

High Risk:High Risk: A calculated SCORE ≥5 to <10%A calculated SCORE ≥5 to <10% Markedly elevated single risk factorsMarkedly elevated single risk factors

Moderate Risk:Moderate Risk: A calculated SCORE ≥1 to <5%A calculated SCORE ≥1 to <5%

Low Risk:Low Risk: A calculated SCORE <1%A calculated SCORE <1%


Intervention StrategiesIntervention Strategies


Recommendations for lipid analysis as treatment Recommendations for lipid analysis as treatment targets in the prevention of CVD and strengthening targets in the prevention of CVD and strengthening

of strict LDL cholesterol targets for patients with of strict LDL cholesterol targets for patients with very high, high, and intermediate risk levelsvery high, high, and intermediate risk levels



• LDL-CLDL-C→recommended as target for tx →recommended as target for tx (class I A)(class I A)

• TCTC→considered as tx target if other analyses →considered as tx target if other analyses are not available (class IIa A)are not available (class IIa A)

• TG→analysed during the tx of dyslipidaemias TG→analysed during the tx of dyslipidaemias with high TG levels (class IIa B)with high TG levels (class IIa B)


Treatment TargetsTreatment Targets

• Non-HDL-C→considered as a secondary tx Non-HDL-C→considered as a secondary tx target (class IIa B)target (class IIa B)

• Apo B→considered as a secondary tx target Apo B→considered as a secondary tx target (class IIa B)(class IIa B)

• HDL-C or the ratiosHDL-C or the ratios→not recommended as →not recommended as targets for tx (class III C)targets for tx (class III C)


Treatment TargetsTreatment Targets

• In patients at In patients at VERY HIGH CV riskVERY HIGH CV risk→the LDL-C goal is <1.8 →the LDL-C goal is <1.8 mmol/L (<mmol/L (<~~70 mg/dL) and/or ≥50% LDL-C reduction when 70 mg/dL) and/or ≥50% LDL-C reduction when target level can not be reached (class I A)target level can not be reached (class I A)

• In patients at In patients at HIGH CV riskHIGH CV risk→the LDL-C goal <2.5 mmol/L →the LDL-C goal <2.5 mmol/L (<(<~~100 mg/dL) should be considered (class IIa A)100 mg/dL) should be considered (class IIa A)

• In patients at In patients at MODERATE CV riskMODERATE CV risk→the LDL-C goal <3.0 →the LDL-C goal <3.0 mmol/L (<mmol/L (<~~115 mg/dL) should be considered (class IIa C)115 mg/dL) should be considered (class IIa C)


Treatment Targets for LDL-CTreatment Targets for LDL-C

• If non-HDL-C is used, the targets should be;If non-HDL-C is used, the targets should be;<2.6 mmol/L (<<2.6 mmol/L (<~~100 mg/dL) in those at 100 mg/dL) in those at VERY HIGH CV riskVERY HIGH CV risk and and<3.3 mmol/L (<<3.3 mmol/L (<~~130 mg/dL) in those at 130 mg/dL) in those at HIGH CV riskHIGH CV risk (class IIa B)(class IIa B)

• If apo B is available, the targets are;If apo B is available, the targets are;<80 mg/dL in those at <80 mg/dL in those at VERY HIGH CV riskVERY HIGH CV risk and and<100 mg/dL in those at <100 mg/dL in those at HIGH CV riskHIGH CV risk (class IIa B)(class IIa B)


Treatment Targets Other Than LDL-CTreatment Targets Other Than LDL-C

Choice of lipid-lowering drugs in the management of Choice of lipid-lowering drugs in the management of dyslipidaemiasdyslipidaemias



• StatinStatin→prescribe up to the highest recommended dose or →prescribe up to the highest recommended dose or highest tolerable dose to reach the target level (class I A) highest tolerable dose to reach the target level (class I A)

• Statin intolerance→bile acid sequestrants or nicotinic acid Statin intolerance→bile acid sequestrants or nicotinic acid (class IIa B)(class IIa B)


PharmacologicalPharmacologicalTreatment of HypercholesterolaemiaTreatment of Hypercholesterolaemia

• Statin intolerance→a cholesterol absorption inhibitor, alone or Statin intolerance→a cholesterol absorption inhibitor, alone or in combination with bile acid sequestrants or nicotinic acid in combination with bile acid sequestrants or nicotinic acid (class IIb C)(class IIb C)

• Target level is not reached→statin combination with a Target level is not reached→statin combination with a cholesterol absorption inhibitor or bile acid sequestrants or cholesterol absorption inhibitor or bile acid sequestrants or nicotinic acid (class IIb C) nicotinic acid (class IIb C)


PharmacologicalPharmacologicalTreatment of HypercholesterolaemiaTreatment of Hypercholesterolaemia

PharmacologicalPharmacologicalTreatment of HypertriglyceridaemiaTreatment of Hypertriglyceridaemia


Drugs Affecting HDL-CDrugs Affecting HDL-C

Nicotinic acidNicotinic acid→the most efficient drug to raise HDL-C and →the most efficient drug to raise HDL-C and should be considered (class IIa A)should be considered (class IIa A)

Statins and fibrates→raise HDL-C with similar magnitude and Statins and fibrates→raise HDL-C with similar magnitude and may be considered (class IIb B)may be considered (class IIb B)


• ↑ ↑ in HDL-C and ↓ in TG on top of ↓ in LDL-C in HDL-C and ↓ in TG on top of ↓ in LDL-C can be achieved by statins.can be achieved by statins.

• StatinStatin++nicotinic acidnicotinic acid→→the adverse effect of the adverse effect of flushing may affect complianceflushing may affect compliance

• StatinStatin++fibratefibrate→→monitor for myopathy; monitor for myopathy; combination with gemfibrozil should be combination with gemfibrozil should be avoidedavoided

• TG are not controlled by statins or TG are not controlled by statins or fibratesfibrates→→n-3 fatty acids to decrease TG n-3 fatty acids to decrease TG furtherfurther


Drug CDrug Combinations for the ombinations for the MManagement anagement of of MMixedixed Dyslipidaemias Dyslipidaemias

Detailed description of treatment targets and Detailed description of treatment targets and prescriptions in special clinical situationsprescriptions in special clinical situations



Management of DyslipidaemiasManagement of Dyslipidaemiasin Different Clinical Settingsin Different Clinical Settings

Familial dyslipidaemiasFamilial dyslipidaemias ChildrenChildren WomenWomen The elderlyThe elderly Metabolic syndrome and diabetes mellitusMetabolic syndrome and diabetes mellitus Patients with acute coronary syndrome and patients undergoing Patients with acute coronary syndrome and patients undergoing

percutaneous coronary interventionpercutaneous coronary intervention Heart failure and valvular diseaseHeart failure and valvular disease Autoimmune diseasesAutoimmune diseases Renal diseaseRenal disease Transplantation patientsTransplantation patients Peripheral arterial diseasePeripheral arterial disease StrokeStroke Human immunodeficiency virus patientsHuman immunodeficiency virus patients


Diabetes MellitusDiabetes Mellitus

Type 1 DM and in the presence of Type 1 DM and in the presence of microalbuminuria and microalbuminuria and renal diseaserenal disease

LDL-C lowering (at least 30%) with statins as the first choice LDL-C lowering (at least 30%) with statins as the first choice (eventually drug combination) irrespective of the basal LDL-(eventually drug combination) irrespective of the basal LDL-

C concentrationC concentration

(class I C)(class I C)



●●Type 2 DMType 2 DM++CVD or CKDCVD or CKD

●●Type 2 DM without CVD+age>40 years+≥1 other CVD risk Type 2 DM without CVD+age>40 years+≥1 other CVD risk factors or markers of target organ damagefactors or markers of target organ damage

●●Primary goal for LDL-C is <1.8 mmol/L (<Primary goal for LDL-C is <1.8 mmol/L (<~~70 mg/dL)70 mg/dL)

●●Secondary goal for non-HDL-C is <2.6 mmol/L (Secondary goal for non-HDL-C is <2.6 mmol/L (~~<100 <100 mg/dL) and for apo B is <80 mg/dLmg/dL) and for apo B is <80 mg/dL

(class I B)(class I B)



Type 2 DMType 2 DM

●●LDL-C <2.5 mmol/L (<LDL-C <2.5 mmol/L (<~~100 mg/dL) is the primary target100 mg/dL) is the primary target

●●Non-HDL-C <3.3 mmol/L (<Non-HDL-C <3.3 mmol/L (<~~130 mg/dL) and apo B <100 130 mg/dL) and apo B <100 mg/dL are the secondary targets mg/dL are the secondary targets

(class I B)(class I B)


Moderate to Severe Chronic Kidney Moderate to Severe Chronic Kidney DiseaseDisease

Primary target of therapy→Primary target of therapy→LDL-C LDL-C reductionreduction

LDL-C loweringLDL-C lowering ↓ CVD risk in CKD ↓ CVD risk in CKD patientspatients

Statins→slow the rate of kidney fx Statins→slow the rate of kidney fx loss modestly and thus protect loss modestly and thus protect against the development of ESRD against the development of ESRD requiring dialysis (class IIa C)requiring dialysis (class IIa C)


Moderate to Severe Chronic Kidney Moderate to Severe Chronic Kidney DiseaseDisease

Statins→beneficial effect on Statins→beneficial effect on pathological proteinuria (>300 pathological proteinuria (>300 mg/day); considered in stage 2-4 mg/day); considered in stage 2-4 CKD patients (class IIa B)CKD patients (class IIa B)

Statins (as monotherapy or in Statins (as monotherapy or in combination with other combination with other drugs)→considered to achieve LDL-C drugs)→considered to achieve LDL-C <1.8 mmol/L (<<1.8 mmol/L (<~~70 mg/dL)(class IIa 70 mg/dL)(class IIa C)C)


Familial HypercholesterolaemiaFamilial Hypercholesterolaemia

FHFH is suspected in subjects with is suspected in subjects with CVD aged <50 years (♂) or <60 years (♀), CVD aged <50 years (♂) or <60 years (♀), relatives with premature CVD,relatives with premature CVD, known FH in the family.known FH in the family.

Confirm the diagnosis with clinical criteria or with DNA Confirm the diagnosis with clinical criteria or with DNA analysis. analysis.

Family screening is indicated when a patient with HeFH is Family screening is indicated when a patient with HeFH is diagnosed.diagnosed.


Familial HypercholesterolaemiaFamilial Hypercholesterolaemia

HeFHHeFH→high dose statin (whenever needed in combination with→high dose statin (whenever needed in combination withcholesterol absorption inhibitors and/or a bile acidcholesterol absorption inhibitors and/or a bile acidsequestrant)(class I C)sequestrant)(class I C)

Treatment targets;Treatment targets; For high risk subjects→LDL-C<2.5 mmol/L (<For high risk subjects→LDL-C<2.5 mmol/L (<~~100 mg/dL)100 mg/dL) For very high risk subjects→LDL-C<1.8 mmol/L (<For very high risk subjects→LDL-C<1.8 mmol/L (<~~70 mg/dL)70 mg/dL) If targets can not be reached, max reduction of LDL-C by drug If targets can not be reached, max reduction of LDL-C by drug

combinations in tolerated dosescombinations in tolerated doses(class IIa C)(class IIa C)


Heart Failure and Valvular DiseasesHeart Failure and Valvular Diseases

n-3 PUFAs (1 g/day)n-3 PUFAs (1 g/day)→to be added to →to be added to optimal tx in patients with HF (class optimal tx in patients with HF (class IIb B)IIb B)

Cholesterol-lowering therapy by Cholesterol-lowering therapy by statins→not indicated in patients with statins→not indicated in patients with moderate to severe HF (NYHA III-IV)moderate to severe HF (NYHA III-IV)(class III A)(class III A)

Lipid-lowering tx→not indicated in Lipid-lowering tx→not indicated in patients with valvular disease without patients with valvular disease without CAD (class III B)CAD (class III B)


Peripheral Arterial DiseasePeripheral Arterial Disease

PADPAD is a high risk condition and lipid- is a high risk condition and lipid-lowering therapy (mostly statins) is lowering therapy (mostly statins) is recommended (class I A)recommended (class I A)

Statins→recommended to reduce the Statins→recommended to reduce the progression of carotid atherosclerosis progression of carotid atherosclerosis (class I A) (class I A)

Statins→recommended to prevent the Statins→recommended to prevent the progression of aortic aneurysm (class I progression of aortic aneurysm (class I C)C)


The ElderlyThe Elderly

Tx with statins→recommended for elderly Tx with statins→recommended for elderly patients with established CVD in the same patients with established CVD in the same way as for younger patients (class I B)way as for younger patients (class I B)

Elderly people often have comorbidities and Elderly people often have comorbidities and have altered pharmacokineticshave altered pharmacokinetics

Recommended to start lipid-lowering Recommended to start lipid-lowering medication at a low dose and then titrate medication at a low dose and then titrate with caution to achieve target lipid levels with caution to achieve target lipid levels which are the same as in the younger which are the same as in the younger subjects (class I C)subjects (class I C)


WomenWomen

Statin txStatin tx→recommended →recommended for primary for primary prevention of CAD in high risk womenprevention of CAD in high risk women

StatinsStatins→recommended→recommended for secondary for secondary prevention in women with the same prevention in women with the same indications and targets as in menindications and targets as in men

Lipid-lowering drugs should not be given Lipid-lowering drugs should not be given when pregnancy is planned, during when pregnancy is planned, during pregnancy or during the breast-feeding pregnancy or during the breast-feeding periodperiod


Relevance of lifestyle changes not just in the Relevance of lifestyle changes not just in the reduction of total risk, but also in the specific reduction of total risk, but also in the specific

treatment of dyslipidemias.treatment of dyslipidemias.



Lifestyle ChangesLifestyle Changes

The guidelines place a great The guidelines place a great amount of emphasis on the amount of emphasis on the effects of lifestyle changes on effects of lifestyle changes on the different plasma lipids the different plasma lipids associated with the associated with the atherosclerotic process.atherosclerotic process.

The recommendations related The recommendations related to lifestyle changes are to lifestyle changes are presented in detail, including presented in detail, including which foods are more or less which foods are more or less advisable, physical activity, advisable, physical activity, and smoking cessation.and smoking cessation.



Consumption of fruits, Consumption of fruits, vegetables, legumes, nuts, vegetables, legumes, nuts, wholegrain cereals and wholegrain cereals and bread, fish (especially oily). bread, fish (especially oily).

Saturated fat should be Saturated fat should be replaced with those foods replaced with those foods and with monounsaturated and with monounsaturated and polyunsaturated fats and polyunsaturated fats from vegetable sources.from vegetable sources.



Energy intake should be adjusted to Energy intake should be adjusted to prevent overweight and obesity. prevent overweight and obesity.

Reduce energy intake from:Reduce energy intake from: total fat to <35%total fat to <35% saturated fat to <7%saturated fat to <7% trans fats to <1%trans fats to <1% dietary cholesterol to <300 mg/day dietary cholesterol to <300 mg/day

The intake of beverages and foods with The intake of beverages and foods with added sugars, particularly soft drinks, added sugars, particularly soft drinks, should be limited.should be limited.



Dietary supplements and functional foods:Dietary supplements and functional foods:

2 g/day of phytosterols2 g/day of phytosterols→→lower TC and LDL-C by 7–10% lower TC and LDL-C by 7–10% when consumed with the main meal.when consumed with the main meal.

Foods enriched with water-soluble fibresFoods enriched with water-soluble fibres→→recommended for recommended for LDL-C lowering (5–15 g/day).LDL-C lowering (5–15 g/day).

2–3 g/day of fish oil (rich in long chain n-3 fatty 2–3 g/day of fish oil (rich in long chain n-3 fatty acids)acids)→→reduce TG levels by 25–30%.reduce TG levels by 25–30%.



Salt intake <5 g/daySalt intake <5 g/day

Alcohol consumption:Alcohol consumption: <10-20 g/day for women<10-20 g/day for women <20-30 g/day for men<20-30 g/day for men

Regular physical exercise for at least Regular physical exercise for at least 30 minutes/day every day30 minutes/day every day

Use and exposure to tobacco Use and exposure to tobacco products should be avoidedproducts should be avoided


We should We should develop implementation strategies bearing always indevelop implementation strategies bearing always in mind that the aim of the guidelines is to assist themind that the aim of the guidelines is to assist the physicians in physicians in

selecting the best management strategiesselecting the best management strategies for treating for treating dyslipidaemia in an individual patient anddyslipidaemia in an individual patient and having a reliable having a reliable

guidance in this is definitely betterguidance in this is definitely better than having none. than having none.

Reiner Z. Eur J Cardiovasc Prev Rehabil. 2011; 18(5): 724-7.Reiner Z. Eur J Cardiovasc Prev Rehabil. 2011; 18(5): 724-7.

Guidelines are Nothing without Guidelines are Nothing without ImplementationImplementation

THANK YOUTHANK YOU

ONDOKUZ MAYIS UNIVERSITY, SAMSUN, TURKEYONDOKUZ MAYIS UNIVERSITY, SAMSUN, TURKEY

NEW LIPID GUIDELINES:WHAT HAS CHANGED?

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