Treatment Guidelines for Dyslipidemia: Summary of the Expanded Second Version

Jong-Il Son; Sang Ouk Chin; Jeong-Taek Woo

doi:10.12997/jla.2012.1.2.45

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Son, Chin, and Woo: Treatment Guidelines for Dyslipidemia: Summary of the Expanded Second Version

Review

J Lipid Atheroscler 2012;1(2):45-59.

Published online: 31 December 2012

DOI: https://doi.org/10.12997/jla.2012.1.2.45

Treatment Guidelines for Dyslipidemia: Summary of the Expanded Second Version

Jong-Il Son, Sang Ouk Chin, Jeong-Taek Woo

Department of Endocrinology and Metabolism, Kyung Hee University Hospital, Seoul, Korea on behalf of The Committee for Developing Treatment Guidelines for Dyslipidemia, Korean Society of Lipidology and Atherosclerosis (KSLA)

Corresponding Author: Jeong-Taek Woo, Department of Endocrinology and Metabolism, Kyung Hee University Hospital, #1 Hoekidong, Dongdaemoon-gu, Seoul 130-702, Korea Tel: +82-2-958-8128, Fax: +82-2-968-1848, E-mail: jtwoo@khu.ac.kr

Received 22 June 2012 Revised 5 July 2012 Accepted 12 July 2012

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

KSLA published our first version of treatment guidelines for dyslipidemia in 1996, which was based on health examination data gathered by the National Health Insurance Corperation in 1994. A number of academic societies including the Korean Endocrine Society, the Korean Society of Cardiology, the Korean Society for Laboratory Medicine, the Korean Society for Biochemistry and the Korean Nutrition Society participated in the development of this guideline. In 2003, the second version of our guidelines was published based on the Korean National Health and Nutrition Survey (KNHANES) data which was collected in 1998. In 2006, the second version was modified and expanded with using KNHANES data collected in 2005. This article summarizes the recommendations included in the expanded second version of treatment guidelines. The full version of treatment guidelines in Korean is available at the KSLA Homepage (http://www.lipid.or.kr).

Keywords: Dyslipidemia, Treatment, Guideline

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Fig. 1.

Relative risk of ischemic heart disease associated with LDL(A) and HDL(B) cholesterol.

Table 1.

Relative risk of cardiac and cerebrovascular disease associated with various risk factors

Risk factor		IHD	CV	CVD+CV
Smoking	None	1.0	1.0	1.0
	Current	2.1	1.1	1.3
	Ex-smoker	2.2	1.6	1.6
Blood pressure	Normal	1.0	1.0	1.0
	High normal	1.4	1.5	1.5
	Stage 1 hypertension	1.8	2.6	2.6
	Stage 2 hypertension	2.9	4.3	4.3
	Stage 3 hypertension	4.4	9.9	8.8
Total cholesterol	<200 mg/dL	1.0	1.0	1.0
	200-239 mg/dL	1.4	1.0	1.2
	≥240 mg/dL	2.1	1.3	1.6
Fasting blood sugar	<126 mg/dL	1.0	1.0	1.0
Fasting blood sugar	≥126 mg/dL	1.6	1.9	1.8

Abbreviations; IHD: ischemic heart disease, CV: cerebrovascular disease, CVD: cardiovascular disease

Table 2.

ATP III LDL-C goals and cutpoints for TLC and drug therapy in different risk categories and proposed modifications based on recent clinical trial evidence

Risk Category	LDL-C Goal	Initiate TLC	Consider Drug Therapy^**
High risk: CHD^* or CHD risk equivalents^† (10-year risk >20%)	<100 mg/dL (optional goal: <70 mg/dL)^ǁ	≥100 mg/dL^#	≥100 mg/dL^†† (<100 mg/dL: consider drug options)^**
Moderately high risk: 2 risk factors^‡ (10-year risk 10% to 20%)^§§	<130 mg/dL^¶	≥130 mg/dL^#	≥130 mg/dL (100–129 mg/dL: consider drug options)^‡‡
Moderate risk: 2 risk factors^‡ (10-year risk >10%)^§§	<130 mg/dL	≥130 mg/dL	≥160 mg/dL
Lower risk: 0–1 risk factor^§	<160 mg/dL	≥160 mg/dL	≥190 mg/dL (160–189 mg/dL: LDL-lowering drug optional)

^* CHD includes history of myocardial infarction, unstable angina, stable angina, coronary artery procedures (angioplasty or bypass surgery), or evidence of clinically significant myocardial ischemia.

^† CHD risk equivalents include clinical manifestations of noncoronary forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease transient ischemic attacks or stroke of carotid origin or >50% obstruction of a carotid artery), diabetes, and 2+ risk factors with 10-year risk for hard CHD >20%.

^‡ Risk factors include cigarette smoking, hypertension (BP ≥140/90 mm Hg or on antihypertensive medication), low HDL cholesterol (<40 mg/dL), family history of premature CHD (CHD in male first-degree relative <55 years of age; CHD in female first-degree relative <65 years of age), and age (men ≥45 years; women ≥55 years).

^§§ Electronic 10-year risk calculators are available at www.nhlbi.nih.gov/guidelines/cholesterol.

^§ Almost all people with zero or 1 risk factor have a 10-year risk <10%, and 10-year risk assessment in people with zero or 1 risk factor is thus not necessary.

^ǁ Very high risk favors the optional LDL-C goal of <70 mg/dL, and in patients with high triglycerides, non-HDL-C <100 mg/dL.

^¶ Optional LDL-C goal <100 mg/dL.

^# Any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglyceride, low HDL-C, or metabolic syndrome) is a candidate for therapeutic lifestyle changes to modify these risk factors regardless of LDL-C level.

^** When LDL-lowering drug therapy is employed, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels.

^†† If baseline LDL-C is <100 mg/dL, institution of an LDL-lowering drug is a therapeutic option on the basis of available clinical trial results. If a high-risk person has high triglycerides or low HDL-C, combining a fibrate or nicotinic acid with an LDL-lowering drug can be considered.

^‡‡ For moderately high-risk persons, when LDL-C level is 100 to 129 mg/dL, at baseline or on lifestyle therapy, initiation of an LDL-lowering drug to achieve an LDL-C level <100 mg/dL is a therapeutic option on the basis of available clinical trial results.

Table 3.

Targets for dyslipidemia management in Japan Atherosclerotic Society

Principle of therapeutic strategy	Category		Lipid management goals (mg/dL)
Principle of therapeutic strategy		Major risk factors other than LDL-C^*	LDL-C	HDL-C	TG
Primary prevention	I (Low-risk group)	0	<160	≥40	<150
Lifestyle should be changed before	II (Intermediate-risk group)	1-2	<140
Consideration of drug therapy	III (High-risk group)	3 or more	<120
Secondary prevention	History of coronary artery diseases		<100
Both drug therapy and lifestyle modification are considered.	History of coronary artery diseases		<100

Management of serum lipids as well as intervention of other risk factors (smoking, hypertention or diabetes) is necessary.

^* Major risk factors other than LDL-C

Aging (male ≥45 years, female ≥55 years), hypertension, diabetes (including impaired glucose tolerance), smoking, family history of coronary artery disease, low HDL cholesterol (<40 mg/dL)

∙ Category III, if complicated by diabetes mellitus, cerebral infarction or arteriosclerosis obliterans.

Table 4.

Diagnostic criteria of dyslipidemia in Korea

Total cholesterol (mg/dL)
high	≥230
borderline	200-229
normal	<200
LDL cholesterol (mg/dL)
high	≥150
borderline	130-149
normal	100-129
optimal	<100
HDL cholesterol (mg/dL)
low	<40
high	≥60
Triglyceride (mg/dL)
high	≥200
borderline	150-199
normal	<150

Table 5.

Major risk factors of dyslipidemia (except LDL cholesterol)

Smoking
Hypertension
	Systolic blood pressure ≥140 or diastolic ≥90 or using anti-hypertensive drugs
Low HDL cholesterol (<40 mg/dL)
Age
	Men ≥45 years
	Women ≥55 years
Family history of early CHD
	CHD in male first-degree relative <55 years of age; CHD in female first-degree relative <65 years of age

Abbreviations: LDL, low-density lipoprotein: CHD, coronary heart disease

Table 6.

LDL and non-HDL cholesterol goals according to risk category

Risk category	LDL cholesterol goal (mg/dL)	non-HDL cholesterol goal (mg/dL)
High risk group	<100	<130
CHD
Carotid artery disease, peripheral vascular disease, abdominal aortic aneurysm
Diabetes mellitus
10-year CHD risk >20 percent
Moderate risk group	<130	<160
2 or more risk factors (10-year CHD risk ≤20 percent)
Low risk group	<160	<190
0 to 1 risk factor

Table 7.

Exercise guideline for improving dyslipidemia

Exercise pattern	Frequency	Intensity	Duration
Aerobic exercise	3-5 days/week	HRR or VO₂R (40%/50-70%)	40-60 minute	Active exercise of major muscle group
		HRmax (55%/65-90%)		2000 kcal/week
		Perceived exertion (12-16)		200-300 minute/week
Strength training	2-3 days/week	Stop 2-3 times before maximum number of times can be lifted	3-20 times per set	Exercise should involve all major muscle groups
Stretching	2-3 days/week (minimum)	Should pain-free when maximal stretching	15-30 seconds
	5-7 days/week (optimal)		2-4 times

Abbreviations; HRR: heart rate reserve, VO₂R: oxygen consumption reserve, HRmax: maximal heart rate

Table 8.

Summary of the major drugs used for treatment of dyslipidemia

Drug Class	Agents and Daily Doses	Lipid/Lipoprotein effects	Side effects	Contraindications
HMG CoA reductase inhibitors (statins)	Lovastatin (20-80 mg)	LDL ↓ 8-55%	Myopathy	Absolute :
	Pravastatin (20-40 mg)	HDL ↑ 5-15%	Increased liver enzymes	Active or chronic liver disease
	Simvastatin (20-80 mg)	TG ↓ 7-30%		Relative :
	Fluvastatin (20-80 mg)			Concomitant use of certain drugs
	Atorvastatin (10-80 mg)
	Rosuvastatin (5-80 mg)
	Pitavastatin (1-4 mg)
Bile acid sequestrants	Cholestyramine (4-16 g)	LDL ↓ 5-30%	Gastrointestinal distress	Absolute : dysbetalipoproteinemia TG >400 mg/dL
	Colestipol (5-20 g)	HDL ↑ 3-5%	Constipation	Absolute : dysbetalipoproteinemia TG >400 mg/dL
	Colesevelam (2.6-3.8 g)	TG No change or increase	Decreased absorption of other drugsㅤ	Relative : TG >200 mg/dL
Nicotinic acid	Immediate release (crystalline) nicotinic acid (1.5-3 g)	LDL ↓ 5-25%	Flushing	Absolute :
	Immediate release (crystalline) nicotinic acid (1.5-3 g)	HDL ↑ 0-20%	Hyperglycemia	Chronic liver disease Severe gout
	Extended release nicotinic acid (1-2g)	TG ↓ 20-50%	Hyperuricemia	Relative :
	Extended release nicotinic acid (1-2g)		Upeer GI distress	Diabetes Hyperuricemia Peptic ulcer disease
	Sustained release nicotinic acid (1-2 g)		Hepatotoxicity	Diabetes Hyperuricemia Peptic ulcer disease
Fibric acids	Gemfibrozil 600 mg bid	LDL ↓ 5-20%	Dyspepsia	Absolute :
	Fenofibrate 200 mg	HDL ↑ 0-20%	Gallstones	Severe renal disease
	Clofibrate 1000 mg bid	TG ↓ 0-50%	Myopathy	Severe hepatic disease
	Bezafivrate 400-600 mg/day	TG ↓ 0-50%	Myopathy	Severe hepatic disease
Cholesterol absorption inhibitor	Ezetimibe 10 mg	LDL ↓ 20%		Absolute :
	Vytorin (Ezetimibe + Simvastatin)	HDL ↑ 1-2%		Severe hepatic disease
	Vytorin (Ezetimibe + Simvastatin)	TG ↓ 10%		Severe hepatic disease
Omega-3 fatty acids	Omega-3 fatty acids 1-4 g	TG ↓ 8-30%	fishy smell
Omega-3 fatty acids	Omega-3 fatty acids 1-4 g	TG ↓ 8-30%	skin eruption

Table 9.

Secondary causes of increasing LDL cholesterol level

Diabetes mellitus

Hypothyroidism

Obstructive lung disease

Chronic kidney disease

Nephrotic syndrome

Drugs - corticosteroid, anabolic steroid, progesterone

Table 10.

Secondary causes of hypertriglyceridemia and low HDL cholesterol

Hypertriglyceridemia
	Obesity
	Physical inactivity
	Smoking
	High carbohydrate diet
	Alcohol
	Diseases-diabetes, chronic kidney disease, nephrotic syndrome
	Drugs - corticosteroid, β-blocker, estrogen, retinoids
Low HDL cholesterol
	Obesity
	Physical inactivity
	Smoking
	High carbohydrate diet
	Hypertriglyceridemia
	Disease - diabetes
	Drugs - corticosteroid, β-blocker, progesterone

Table 11.

Drug selection according to type of dyslipidemia

Only LDL elevation
	statin, ezetimibe, nicotinic acid, resin, mono- or combination therapy
LDL + TG(<500 mg/dL) elevation
	primary- statin, nicotinic acid secondary - primary drug + fibrate or nicotinic acid or omega-3 fatty acid
Cholesterol + TG(>500 mg/dL) elevation
	primary - fibrate, nicotinic acid secondary - primary drug + fibrate or nicotinic acid or omega-3 fatty acid
Only TG elevation
	statin, fibrate, nicotinic acid, omega-3 fatty acid

Table 12.

Drug information about statins

Drug : Lovastatin, Pravastatin, Simvastatin, Fluvastatin, Atorvastatin, Rosuvastatin, Pitavastatin
Lipid profile : LDL ↓18-55%, HDL ↑5-15%, TG ↓7-30%
Effects : Decrease mortality of CHD, stroke, CVD
Contraindication
	Absolute : active liver disease, pregnancy, lactation
	Relative : other drugs (cyclosporin, macrolide, antifungal, cytochrome P-450 inhibitors)
Side effects : hepatotoxicity, myopathy
Dosing :
	Lovastatin : 20-80 mg/day with evening meal
	Pravastatin : 5-40 mg/day before sleeping
	Simvastatin : 20-80 mg/day before sleeping
	Fluvastatin : 20-80 mg/day before sleeping
	Atorvastatin : 10-80 mg/day
	Rosuvastatin : 5-40 mg/day
	Pitavastatin : 1-4 mg/day

Table 13.

Drug information about fibrates

Drug : Bezafibrate, ciprofibrate, gemfibrozil, fenofibrate
Lipid profile : LDL ↓5-20%, HDL ↑10-15%, TG ↓25-50%
Effects : Decrease incidence of CHD
Contraindication
	Absolute : severe liver disease, gallstone
	Should be cautious when used with statin
Side effects : hepatotoxicity, myopathy
Dosing :
	Benzafibrate : 400-600 mg/day, 1-3 times per day
	Fenofibrate : 160-200 mg/day, just after meal
	Gemfibrozil : 600-1200 mg/day, 2 times per day, 30 minutes before meal

Table 14.

Drug information about nicotinic acids

Drug : Nicotinic acid, Acipimox
Lipid profile : LDL ↓5-25%, HDL ↑15-35%, TG ↓20-50%
Effects : Decrease incidence of CHD
Contraindication
	Absolute : severe liver disease, severe gout
	Relative : diabetes, hyperuricemia, peptic ulcer disease
Side effects : flushing, dyspepsia, hepatotoxicity (especially sustained released form), gout, hyperglycemia
Dosing :
	Immediate release (crystalline) nicotinic acid 1.5-3 g/day
	Extended release nicotinic acid 1-2 g/day
	Sustained release nicotinic acid : 1-2 g/day

Table 15.

Drug information about omega 3 fatty acids

Drug : omega-3 fatty acid

Lipid profile : TG ↓8-30%

Effects : Decrease incidence of CHD

Contraindication : none

Side effects : fishy smell, skin eruption

Dosing : omega-3 fatty acids 1-4 g/day

Table 16.

Drug information about bile acid sequestrants

Drug : cholestyramine, colestipol
Lipid profile : LDL ↓15-30%, HDL ↑3-5%, TG mildly increase
Effects : Decrease incidence of CHD
Contraindication : TG >400 mg/dl
Side effects : constipation, dyspepsia, gallstone, inhibition of other drug absorption
Dosing :
	Cholestyramine : 8-24 g/day, 2 times per day, with mea
	Cholestipol : 10-30 g/day, 2 times per day, with meal

Table 17.

Treatment of dyslipidemia for primary prevention of CVDs in elderly

	Targeted Patients	Treatment Goal
NCEP	1. Absence of general weakness : LDL >190 mg/dL
NCEP	2. 2 or more CVD risk factors : LDL >160 mg/dL
Society of Geriatric Cardiology	1. No history of CVD who aged 65-80 years : Total cholesterol >240 mg/DL	1. Total cholesterol <200 mg/dL
	2. one or more risk factor of CVD : LDL >160 mg/dL	2. LDL <130 mg/dL
	3. No history of CVD who aged more than 80 years + who have hyperlipidemia : consider dietary change or pharmacotherapy	2. LDL <130 mg/dL

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