position paper: global recommendations for the management ... fileinnovations-2 • assigning...

An International Atherosclerosis Society

Position Paper:

Global Recommendations for the

Management of Dyslipidemia

© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org

Innovations-1

• International position paper based on multiple

lines of evidence

• Identification of non-HDL-cholesterol (non-HDL-C)

as a major form of atherogenic cholesterol

• Definition of atherogenic cholesterol as either

LDL-cholesterol (LDL-C) or non-HDL-C

• Definition of optimal levels of atherogenic

cholesterol (both LDL-C and non-HDL-C) for

primary and secondary prevention


Innovations-2

• Assigning priority to long-term risk categories

over short-term risk

• Adjustment of risk estimation according to

baseline risk of different nations or regions

• Primary emphasis on lifestyle intervention;

secondary emphasis on drug therapy


International Position Paper

• Primary prevention

– Randomized controlled trials

– Epidemiology

– Genetics

– Other lines of evidence

• Secondary prevention

– Mainly randomized controlled trials


Purposes of Position Paper

• To amplify existing national guidelines

• Not to replace national guidelines

• To offer an international frame work for future

guideline development

• To provide a simplified approach to dyslipidemia

management

• To emphasize lifestyle approaches to prevention

of cardiovascular diseases


LDL-C and Non-HDL-C

as Targets of Therapy

• LDL: major atherogenic lipoprotein

• VLDL: additional atherogenic lipoprotein

• Non-HDL: LDL + VLDL

• LDL cholesterol (LDL-C): traditional primary

target for clinical intervention

• Non-HDL cholesterol (Non-HDL-C): appropriate

target for clinical intervention


Advantages of Non-HDL-C as

Target for Clinical Intervention

• Sum of all atherogenic lipoproteins (LDL+ VLDL)

• Does not require fasting for accurate

measurement

• Subsumes most cases of elevated triglycerides

• Growing evidence for greater predictive power

than LDL-C

• Essentially equivalent to apolipoprotein B in

predictive power


Atherogenic Cholesterol

• Either LDL-C or non-HDL-C

• LDL-C is a traditional primary target of

lipid-lowering therapy

– Many national guidelines identify LDL-C as

the target of treatment

• Non-HDL-C is increasingly preferred as

the target of therapy


Optimal Levels of LDL-C and Non-

HDL-C for Primary Prevention

• Optimal levels

– LDL-C < 100 mg/dL (2.6 mmol/L)

– Non-HDL-C < 130 mg/dL (3.4 mmol/L)

• Optimal levels not goals of therapy

• Cholesterol-lowering goals determined by

clinical judgment


Identifying Persons at Long-term

Risk for ASCVD

• Long-term risk takes precedence over

short-term risk for decisions about

dyslipidemia intervention

• Long-term risk = risk to age 80 years


Factors Affecting Long-term Risk

for ASCVD

• Atherogenic lipoproteins (LDL & VLDL) initiate

and promote atherogenesis

– Alone can cause premature ASCVD

• Other risk factors accelerate atherogenesis

– Cigarette smoking

– Hypertension

– Diabetes

– Low HDL

– Genetics (family history)


Levels of Long-term Risk for

ASCVD (up to age 80)


Risk Level Total Risk

High > 45%

Moderately high 30-44%

Moderate 15-29%

Low < 15%

Lloyd-Jones/Framingham Risk

Algorithm

Cholesterol (mg/dL) 180-199 200-239 > 240

Systolic BP (mmHg) 120-139 140-159 > 160

Cigarette smoking 0 0 +++

Diabetes 0 0 +++


Risk for CVD Morbidity by Age 80*

Risk Factor Men Women

None 5% 8%

> 1 minor 25% 10%

> 1 moderate 38% 22%

1 major 45% 25%

> 2 major 60% 45%

* For United States


Framingham Heart Study

Recalibration Coefficients for CHD


Cohort Combined M & F Cohort Male Female

Australia 0.90 Britain 0.57

France 0.41 Switzerland 0.48 0.44

Germany 0.43

Ireland 0.76

Italy 0.37

NE Spain 0.37

New Zealand 1.15

Scotland 0.91

UK 0.76


Cohort Male Female

China 0.36

Japanese American 0.50

Korean 1.02 0.96

Native American 0.80 0.70

Rural India 1.0 0.8

Urban India 1.81 1.54

Framingham Heart Study

Recalibration Coefficients for CHD

Qualitative High-Risk Conditions

• Familial hypercholesterolemia

• Diabetes + other risk factors

• Chronic kidney disease


Long-term Risk Algorithms

• Lloyd-Jones/Framingham

– Adjustments for specific countries

• QRISK

– Developed for UK

• Adjustments for ethnicity

– May apply to Western Europe


IAS Recommendations for Cholesterol-Lowering Therapy at Different Risk Levels

Risk Level

to Age 80s

Low

(< 15%)

Moderate

(15-24%)

Moderately

High

(25-40%)

High

(> 40%)

Therapeutic

Intensity

Moderate Moderately

High

High

Specific

Therapy

Public

health

guidelines

MLT

+CLD

optional

MLT

+CLD

consideration

MLT

+CLD

Indicated

MLT = Maximal lifestyle therapy CLD = Cholesterol-lowering drug


Optimal Levels of Atherogenic

Cholesterol vs. Goals of Therapy

• Optimal levels represent those that produce a

maximal risk reduction through reasonably

available therapies

• Goals of therapy depend on clinical judgment

and are based on projected efficacy, cost-

effectiveness, and safety of available therapies

• When drug therapies are employed, optimal

levels usually represent a reasonable goal of

therapy


Lifestyle Therapies:

LDL-Raising Lipids

• Reduce intake of saturated fatty acids to <

7% of total calories, and at least to < 10%

• Lower intake of trans fatty acids to < 1% of

total calories

• Reduce dietary cholesterol to < 200 mg/day



Total Fat • The IAS recommends flexibility in the intake of total fat

depending on cultural preferences, such as:

– Lower fat intakes of 20-25% of calories or even lower

(as is typical in Pacific Rim countries)

– Or higher fat intakes of 30-35% of calories or even

higher (as is typical in Mediterranean countries)

• Any fat intake above the recommended for saturated and

trans fatty acids should be in the form of unsaturated

fatty acids

• Irrespective of the total fat content of the diet, nutrient

needs must be met and energy intake should be

appropriate for maintenance of a healthy body weight



Total Calories

• Body mass index (BMI) should be

measured in all patients

• Control intake of total calories to achieve

and maintain a desirable weight

• If desirable weight is defined by BMI,

employ national standards for BMI



Other Dietary Factors • Maintain relatively high intakes of fruits, vegetables, and

fiber

• Replace excess saturated fatty acids with either complex,

fiber-rich carbohydrates (with emphasis on whole grains)

or monounsaturated/polyunsaturated fatty acids

• Consume some fish rich in n-3 fatty acids

• Other cardioprotective foods include nuts, seeds, and

vegetable oils

• Consider using plant sterols/stanols (2 g/day) and

soluble/viscous fiber (10 to 25 g/day) as a dietary adjunct

to further lower LDL-C levels



Other Dietary Factors

• Eat foods low in sodium and high in potassium

• Dietary sodium should be less than 2 g per day

and < 1500 mg for individuals at risk

• For individuals who choose to consume alcohol,

not more than 2 servings daily for men and 1

serving daily for women is advised



Physical Activity

• Engage in approximately 30 minutes of

moderate intensity physical activity daily

• The activity should be aerobic, 40-75% of

aerobic capacity, for 5-7 days a week, for 30-60

minutes per day

• For individuals trying to lose weight it is

recommended that these individuals eventually

progress to higher amounts of exercise (e.g.

250-300 min/week or > 2000 kcal/week of

leisure-time physical activity)


Metabolic syndrome

• The metabolic syndrome is a multiplex risk factor

for ASCVD

• Obesity and physical inactivity contribute

importantly to development of the metabolic

syndrome

• For patients with this syndrome, weight

reduction and increased physical activity can

reduce metabolic risk factors


© 2013 International Atherosclerosis Society. All rights reserved.

Criteria for Clinical Diagnosis

of the Metabolic Syndrome Measures Categorical Cut Points

Elevated Waist Circumference Population- and country-specific

definitions

Elevated triglycerides > 150 mg/dL (1.7 mmol/L)

Reduced HDL-C < 40 mg/dL (1.0 mmol/L) in males

< 50 mg/dL (1.3 mmol/L) in females

Elevated blood pressure Systolic > 130 and/or diastolic > 85

mm Hg

Elevated fasting glucose > 100 mg/dL

www.athero.org

Population Male

(cm)

Female

(cm)

Population Male

(cm)

Female

(cm)

Asian ≥ 90 ≥ 80 Canadian ≥ 102 ≥ 88

Chinese ≥ 85 ≥ 80 Ethnic Central

and So. American

≥ 94 ≥ 80

European ≥ 94 or

≥ 102

≥ 80 or

≥ 88

Middle Eastern,

Mediterranean

≥ 94 ≥ 80

Japanese ≥ 85 ≥ 90 Sub-Saharan

African

≥ 94 ≥ 80

USA ≥ 102 ≥ 88 © 2013 International Atherosclerosis Society. All rights reserved.

Current Recommended Waist Circumference

Thresholds for Abdominal Obesity

Drug Therapy for Primary

Prevention • Statins are first line therapy for achieving the optimal

levels of atherogenic cholesterol in higher risk persons

• In those who are statin intolerant, several options are

available: switching statins, reducing statin dose, every

other day statins, use of alternate drugs (ezetimibe, bile

acid resins, niacin) alone or in combination, and

maximizing lifestyle intervention

• When drugs are used for primary prevention, intensity of

therapy should be sufficient to achieve optimal levels of

atherogenic cholesterol


Secondary Prevention: Achieving an

Optimal Atherogenic Cholesterol Level

• The optimal LDL-C in patients with established

ASCVD is < 70 mg/dL (1.8 mmol/L) (or non-

HDL-C of < 100 mg/dL [2.6 mmol/L])

• Most patients with ASCVD deserve maximal

statin therapy when it is tolerated

• To achieve an LDL-C < 70 mg/dL (1.8 mmol/L)

some patients will require add-on drugs to

statins (i.e. ezetimibe and/or bile acid resins)


Secondary Prevention:

Intolerance to High-Dose Statins

• In patients who cannot tolerate high-dose

statins, an alternative is to combine a

moderate dose of statin with either

ezetimibe or bile acid-binding resin


Secondary Prevention: Patients

with Hypertriglyceridemia

• For those with high triglycerides, nicotinic acid or

a fibrate are alternative add-on drugs

• However, risk reduction with combined drug

therapy comparable to that with high-dose

statins has not been documented in RCTs

• Subgroup analysis of RCTs and atherosclerosis

imaging provides some evidence of benefit of

combined drug therapy


Secondary Prevention: Importance

of Maximal Lifestyle Therapy

• Even in patients who are treated with

maximal cholesterol-lowering drugs,

lifestyle therapies should be continued and

emphasized

• Maximal lifestyle therapies have the

potential to give additional risk reduction

beyond drug therapy


Secondary Prevention: Full

Attention to Non-Lipid Risk Factors

• Cigarette smoking

• Hypertension

• Diabetes mellitus

• Obesity

• Physical inactivity

• Prothrombotic state


IAS Panel Members

• Scott M. Grundy (Chair)

• Hidenori Arai

• Philip Barter

• Thomas P. Bersot

• D. John Betteridge

• Rafael Carmena

• Ada Cuevas

• Michael H. Davidson

• Jacques Genest

• Y. Antero Kesäniemi

• Shaukat Sadikot

• Raul D. Santos

• Andrey Susekov

• Rody Sy

• Lale Tokgozoglu

• Gerald F. Watts

• Dong Zhao


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