Management of hyperlipedemia

DONE by : Dr. maged al saleh FM R4

SupervisorDr. Alhusen monaur

Consultant FM

السريعة الوجبات حضارةسلوشر / إيريك للمؤلف

الواليات% 70حوالي • في القطعان منفضالت بواسطة بروتينيا تغذى كانت المتحدة

عام حتى .م1997المواشي

• ) أن ) دي اس يو منظمة أجرتها دراسة وجدتكانت% 7,5 المطحون البقر لحم عينات أن

بالسلمونيال .ملوثة

Objectivesi. Understanding the different

modality of management of dyslipidemia.

ii. Screening of patient in family practies.

iii.When to refer your patient.

Prevalence The prevalence of dyslipidemia varies with the

population studied and the definition of dyslipidemia. The incidence is highest in patients with premature

CHD, which is defined as clinically evident disease occurring before 55 years of age in men and before 65 years in women.

In this setting, the prevalence of dyslipidemia is as high as 80 to 88 percent compared to approximately 40 to 48 percent in age-matched controls without coronary disease

In KSA the prevalence of hypercholesterolemia 18-23%.

screening• USPSTF :All men aged 35Y or older and all women aged 45Y or older

should be screened routinely for lipid disorder.Younger adult men aged 20 _ 35 Y and women aged 20 _45

Y should be screened if they have other risk factor for heart diseases.

Clinicians should measure HDL in addition to TC or LDL and found insufficient evidence to recommend for or against measuring TG.

Screen with non fasting sample .All patient should receive periodic counseling regarding Dietary intake and chlesterol .

Normal value of Lipids• LDL

– < 100 →Optimal– 100-129 → Near optimal– 130-159 → Borderline– 160-189→ High– ≥ 190 → Very HighLDL =TC – (TG/5 + HDL).

• Total Cholesterol– < 200 → Desirable– 200-239 → Borderline – ≥240 → High

• HDL– < 40 → Low– ≥ 60 → High

• Serum Triglycerides– < 150 → normal– 150-199 → Borderline– 200-499 → High– ≥ 500 → Very High

oTreatment:

Non pharmacological treatment:1- diatry management:

•

LDL GOAL Initial LDL level MG per dL

patient

Less than 160 More than 160 No CHD but less than 2 rish factors

Less than 130 More than 130 No CHD but = or more than 2 risk factors

Less than 100 More than 100 With CHD

countstep2 step 1

For 6 monthAHA

200mg 300 mg cholesterol

30% of calories

30% of calories

Total fat

7% of calories

10% of calories

Saturated fat

Effect of Lifestyle Modification• Diet

– Decreased saturated fat (decrease LDL)– Replacing saturated and trans unsaturated fats with

unhydrogenated monounsaturated or polyunsaturated fats

– Recommended diet• CHO (whole grains, fruits,veggies) 50-60% total

calories• Dietary fiber 20-30 g/d• Protein 10-25 g/day

– Effect of LDL lowering should be evident in 6-12 months

– Elevated BMI associated with decreased dietary response

– Referral to dietitian helpful

Diet Supplements Fish Oil (source of omega-3 polyunsaturated fatty acids)

• Salmon, flaxseed, canola oil, soybean oil and nuts• At high doses > 6 grams/day reduces TG by inhibition of VLDL-TG

synthesis and apolipoprotein B and increase HDL.• Decrease BP and inhibit platelet aggregation and decrese

viscosity.• Possibly decreases small LDL.• Several studies have shown lower risk of coronary events• Number of undesirable side effects (mainly GI).

Soy • Source of phytoestrogens inhibiting LDL oxidation• 25-50 grams/day reduce LDL by 4-8%• Effectiveness in postmenopausal women is questionable

Garlic• One half to one clove of garlic a day may produce modest 5%

reduction in serum cholesterol

count _Red yeast extraction:• are Contain cholesterol synthesis inhibitors that is a member of statins family

and can lower LDL 10% _15%.

_Antioxidant vitamins (C ,E and beta caroten):• are not cardioprotective and interfere with effects of niacin on HDL-C

Cholesterol-lowering Margarines and fiber preparation :• Benecol and Take Control containing plant sterols and stanols• As py sllium has modest benefit..• Other agents include soluble fiber, nuts (esp. walnuts), green tea• Inhibit cholesterol absorption but also promote hepatic cholesterol

synthesis• 10-20% reduction in LDL and TC however no outcome studies• AHA recommends use only in hypercholesterolemia pts or those with a

cardiac event requiring LDL treatment

count

alcohol : contained in sugar can reduce LDL by 20% _ 30% but data are need on their savity and long term efficacy.

Homocysteine: folic acid, vitamins B6 and B12 not proven to be cardioprotective.

• Overall a combination diet with multiple cholesterol-lowering agents causes much more significant LDL reductions .

count2_counsel patient about therapeutic lifestyle changes:

body weight control _regular physical activity_ smoking cessation.

3_Weigt los :can lower fat intake , reduce risk of DM and decrease myocardial work .

4_Exercise:– Moderate intensity exercise (3-4 mi/hr) for 30 minutes on most days of the week.– Early cross-sectional studies comparing middle-aged male runners to

sedentary men suggested a beneficial effect of exercise on lipoproteins] . The runners had significantly lower serum levels of total cholesterol, low density lipoprotein (LDL)-cholesterol, very low density lipoprotein (VLDL)-cholesterol, and triglycerides, and a higher concentration of high density lipoprotein (HDL)-cholesterol.

5_screen for metabolic syndrome:

6_Drugs therapy:

LDL GOALInitial LDL level

MG per dLpatient

Less than 160 More than 190 No CHD but less than 2 riskfactors

Less than 130 more than 160 No CHD but = or more than 2 risk factors

Less than 100 More than 130 With CHD

Treatment Guidelines Always Consider secondary causes of dyslipidemia (DM, hypothyroidism,

obstructive liver disease, CRF or nephrotic syndrome or drugs) All patients with LDL above goal start with adequate trial of lifestyle

modification only but concomitant drug therapy may be appropriate if: LDL >220 or > 190 if >= 2 risk factors Pre-existing CHD or CHD equivalent

If CHD or risk equivalent and? significantly above goal, then start pharmacotherapy (preferably statin) immediately

If CHD or equivalent and LDL goal <100 not achieved on maximal statin (atorvastatin 80 or rosuvastatin 40), then additional agent should be added based on abnormalities in other lipoproteins

In no CHD or CHD equivalent, consider drug therapy with statin if after adequate lifestyle trial: LDL >190 if 0 or 1 risk factor LDL >160 if 2 or more risk factors if 10 yr risk <10%; 130 if risk 10-20%

If persistent elevation in LDL purely, then add bile acid sequestrant or zettia

In patients with ACS, atorvastatin 80 mg/day should be started soon after hospitalization (event reduction and LDL lowering effect) PROVE-IT TIMI 22 Trial, MIRACLE, A to Z trial

Risk Assessment• CHD equivalents:

– Symptomatic carotid artery disease– Peripheral arterial disease– AAA– DM – Multiple risk factors that confer a 10-year risk of CHD > 20%

• Identify major risk factors other than LDL:– Smoking– HTN BP >140/90 or on anti-hypertensive medication– Low HDL <40 mg/dL– Family history premature CHD (CHD in men 1st degree relative <55; women <65 y.o.)– Age (men > or =45; women >or =55)

• Other potential risk factors– Chronic renal insufficiency (Cr > 1.5 mg/dL OR GFR <60 cc/min) per Up-To-Date– Obesity, physical inactivity, impaired fasting glucose, markers for inflammation

• HDL > 60 mg/dL is a negative risk factor• If patient without CHD or equivalent has 2 or more major risk factors, then calculate the

Framingham risk (age,TC,HDL,smoking,SBP)

Validation study found Framingham CHD predictor worked well in white and black population but overestimated risk in Japanese American, Hispanic men and native American women and other studies have shown possible overestimation in European and Asian populations

20

Guidelines for Management of Hypercholesterolemia; The Adult Treatment Panel III (ATPIII)

• Therapeutic lifestyle changes (TLC) and drug therapy for persons in different risk categories

Risk Category LDL-C goal Initiate TLC2 Consider Drug Therapy2

High risk: CHD or CHD equivalents3 (10-year risk4 of CHD >20%)

<100 mg/dL (optional: <70 mg/dL)

≥100 mg/dL ≥100 mg/dL (optional goal: <100 mg/dL)

Moderately high risk: 2+ risk factors5 (10-year risk of CHD 10-20%)

<130 mg/dL (optional: <100 mg/dL)

≥130 mg/dL ≥130 mg/dL (optional: 100-129 mg/dL)

Moderate risk: 2+ risk factors (10-year risk of CHD <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 (optional: 160-190 mg/dL)

Risk factors: cigarette smoking, hypertension, low HDL-C, family history of premature CHD, and age

Treatment guide line

Hypercholosterlemia

hypertriglricde

mia

Elevated LDL• Statins are first choice and selection is based on extent of LDL

reduction, cost and reduction in clinical CHD events as well as presence of renal impairment

• 30-35% decrease in LDL-C with equivalent doses

• Titrate statin dose at 3-4 week intervals

• Doubling statin dose reduced LDL an additional 6%• Consider adding second agent instead of dose increase• Variable drug response depending on endogenous v. exogenous

hypercholesterolemia

• Second agents may include bile acid resins (15%), ezetimibe (20%), or plant stenol/sterol margarine (10%)

• Niacin may be added as a third agent if needed

Treatment of Hyperlipidemia

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.

High LDL-CHigh LDL-C

Therapeutic Lifestyle ChangeTherapeutic Lifestyle Change

Drug TherapyDrug Therapy

Therapy of Choice: StatinTherapy of Choice: Statin

Alternative: Resin or niacin

hypercholesterolemia

Isolated Low HDL• Framingham Heart

Study: MI risk increases by 25% per 5 mg/Dl decrease below mean HDL for men and women

• LIPID and CARE trials: 10 increase in HDL, 29% decrease in event rate in LDL <125 vs 10% decrease in LDL>125

• Evidence in Treatment– VA-HIT trial: strong correlation of

reduction in MI and CHD death with serum HDL achieved with gemfibrozil

• Treatment Indications of Isolated low HDL

– CHD OR CHD equivalent– if first-degree relative early onset

CHD and similar lipid profile• Weight management, exercise, and

smoking cessation• Niacin +/- gemfibrozil• CETP inhibitors (NEW and

investigational)E.g torcetrapib .anacetrapib and

dalcetrapib.

Hypertriglyceridemia• Identify those with hyperchylomicronemia: TG >1000 mg/dL, eruptive xanthomas,

pancreatitis• Familial hypertrig (200-500) or combined hyperlipidemia• Treatment Recommendations:

– After achievement of LDL goal– (150-199): emphasize weight reduction and physical activity– (200-499): non-HDL second target and pharmacologic tx for those with h/o MI or at

high risk– >500: prevention of pancreatitis with non-pharmacologic and pharmacologic therapy– Isolated hypertrig tx indications

• Overt CHD• Strong FH of CHD• Multiple cardiac risk factors

– Statins (atorvastatin or rosuvastatin) if LDL elevated– Fibrates or nicotinic acid– Add fish oil for refractory cases

hypertriglesridemia

References Evidence rating Clinical recommendation

7 .35 B Patients with high serum triglyceride levels should receive counseling about a healthy diet, regular

exercise, and tobacco-use cessation.

7 C After patients with high serum triglyceride levels reach their LDL-C goals, the secondary target

should be reaching non-HDL-C goals (30 mg per dL [0.78 mmol per L] higher than the LDL-C goal).

7 C Fibrates, niacin, or fish oil can be considered to help lower triglyceride and non-HDL-C levels.

7 C Serum triglyceride levels should be lowered in patients with very high triglyceride levels to

prevent acute pancreatitis

Mixed (Combined Hyperlipidemia)

• Elevated LDL and/ or triglycerides

• Objective is to achieve LDL goals

• With very high TG> 400, start with fibrate or niacin

• Then treat LDL with statin

• If LDL-C goal achieved, but TG>200, non-HDL-C should be targeted• Non-HDL goal 30 above LDL goal

• Statin titration dose OR Statin-fibrate OR Statin-Niacin combinations more effective in this type of dyslipidemia but adverse reactions more common with combined treatment so benefit/risk ratio considered

Treatment of Mixed Hyperlipidemia

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.

High LDL-C and TGsHigh LDL-C and TGs

Therapeutic Lifestyle ChangeTherapeutic Lifestyle Change

Drug TherapyDrug Therapy

Achieve the LDL-C goal1STEP

Achieve the non-HDL-C goalIncrease LDL-C lowering or

Add a fibrate, niacin or fish oils2STEP

Overall a combination diet with multiple cholesterol-lowering agents causes much more significant LDL reductions .

Dietary modification complementary by exercise and weight reduction is core of lipid treatment program with pharmacologic therapy reserved for those at higher risk and for persons failing behavioral therapy .

Decease intake cholesterol and saturated fat in controlled setting can reduce TC and LDL by 15% - 30% .

Pharmacological vs combination

Medications for HyperlipidemiaDrug Class Agents Effects (% change) Side Effects

HMG CoA reductase inhibitors LovastatinPravastatin

LDL (18-55), HDL (5-15) Triglycerides (7-30)

Myopathy, increased liver enzymes

Cholesterol absorption inhibitor

Ezetimibe LDL( 14-18), HDL (1-3)Triglyceride (2)

Headache, GI distress

Nicotinic Acid------------------

LDL (15-30), HDL (15-35) Triglyceride (20-50)

Flushing, Hyperglycemia,Hyperuricemia, GI distress, hepatotoxicity

Fibric Acids GemfibrozilFenofibrate

LDL (5-20), HDL (10-20)Triglyceride (20-50)

Dyspepsia, gallstones, myopathy

Bile Acid sequestrants Cholestyramine LDL HDL

No change in triglycerides

GI distress, constipation, decreased absorption of other drugs

When to start statins and when to add?.

Indications to statins :I. If LDL more than 130 mg per dl .II. In very high risk persons establish CVD +:• ACS• Multiple major risk factors e.g. DM.• Sever and poorly controlled risk factors e.g

smoking . • Metabolic syndrome even if LDL less than 100

mg per dl but more than 70 mg per dl .

Comparable Efficacy of Statins

Special considerations:No renal dosing: Atorvastatin and Fluvastatin

Use in chronic liver disease: pravastatin or rosuvastatin

Less drug interactions: pravastatin, fluvastatin, rosuvastatin (not metabolized via CYP3A4)

Less muscle toxicity: Pravastatin and Fluvastatin

Cost-effectiveness: Rosuvastatin, atorvastatin, fluvastatin

What are the options when statin therapy does not get the LDL-C to goal?

• Treatment intensity related to risk• Increase dose, if therapeutic range permits• Add Zetia or “resin”• Add plant stanol/sterol products• If other lipid abnormalities present add:

• Fibrates or niacin

©2005 .American College of Physicians. All Rights Reserved.

Estrogenso It lead to decrease LDL and increase HDL

cholesterol.o HRT failed to produce improve Cardiovascular

outcome.o No longer recommended for prevention of CHD.o Estrogen + progestin failed to in reducing

cardiovascular morbidity and mortality.

Monitoring: it performed by measurement of LDL

beginning 6-8 weeks after initiation of therapy and then every 3-4 month until control established.

Frequent monitoring for development of abnormality in serum chemistries e.g liver enzymes with use certain drugs .

آداب نبوية للطعام الطعام .• على الصحية الجلسة

اإلتكاء . • عدمالطعام . • قبل التسميةباليمين . • األكلاإلنسان . • يلي مما األكلنشبع ) ( . • ال أكلنا وإذا نجوع حتى نأكل ال قوم نحنلقيمات • آدم ابن حسب ، بالثلث Tدائما عليكأنفاس . • بثالثة الشربالشراب .• في النفخ عدموغيرها .• القربة فم من الشرب عدماأليمن .• الجانب على النوم

كتاب الطب النبوي البن القيم الجوزية

Special considerations Elderly

DM

Metabolic syndrome

Nephrotic syndrome

CRF

Elderly• Should be individualized based on chronologic and physiologic age• Cardiovascular Health Study showed benefit in primary prevention in

>65 y.o.• All major statin trials and VA-HIT trial have shown reduction of

atherothrombotic stroke with lipid-lowering• ATP III recommends diet as first line of primary intervention but drugs

can be considered if multiple risk factors possibly with LDL >160• Underutilization of lipid-lowering drugs in elderly due to

– Concern for safety (hapatic/renal impairment)– Time course to benefit

Adults With DM• Both primary and secondary intervention trials

have shown benefit and reduction of CVD in diabetic subgroups treated with lipid-lowering agents (HPS and CARE trial showed significant outcome improvement with statins even at LDL <116).

• Despite their often elevated TG and low HDL due to insulin resistance, etc. LDL should be primary goal.

• Niacin-Statin combination can be particularly effective.

• LDL goal <100 and threshold for drug tx is 130 and optional 100-129 if diet effective.

Metabolic Syndrome• Treatment Recommendations:

–Weight reduction and exercise–LDL goal is same as in patient w/o MS–If LDL goal reached, then focus on TG if

>200?–Fibrates and nicotinic acid are good choices

for elevated TG

Hyperlipidemia in Nephrotic Syndrome• Treatment rationale

–Tx of underlying disease (i.e. steroids in minimal change disease)

–Little benefit in diet therapy.–Best drug tx is statins–ACE-Inhibitor or ARB by decreasing protein

excretion cause 10-20% reduction in TC and LDL

CRF and Dialysis• Hypertriglyceridemia

– Diminished clearance due to apo C-III and reduction in lipoprotein lipase and hepatic triglyceride lipase

– Usually not enough elevation to increase coronary risk– Diet modification preferable over drug therapy because

of risk of rhabdomyolysis• Statins should be used to lower LDL <100 or better yet <80

as CKD considered CHD risk equivalent. • Atorvastatin and fluvastatin better choices. Hydrophilic

statins safer and dose adjustment needed with CrCl <30.

REFERAL

dieticianLipid

specialist

Referances الجوزية القيم البن النبوي الطب سلوشر اليريك السريعة الوجبات حضارة Family medicine a practical approach . Primary care medicine for gorll 5th edition. Up-to-date 2009 . Family medicine swansns 6th edition. Aafp January 2002 and may 2007 . Approach to dyslipimia –maryam zamanian . Hyperliedrmia – michele ritter. Management hyperlipedemia – dr. james chan. Optimal management of dyslipi demia 2008 –joel niznick. Hyperlipedemia dr . Istvan nagy. Update in lipid management 2005 – robert A kneisberg.

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