Dyslipidemia and Management of Dyslipidemia

Prepared by:

Muhammad Nizam Uddin

CHOLESTEROL A soft waxy substance found among

lipids (fats) in the bloodstream and all cells

Needed for digesting fats, making hormones, building cell walls

Carried in particles called lipoproteins that act as transport vehicles delivering cholesterol to various body tissues to be used, stored or excreted

Excess circulating cholesterol can lead to plaque formation- Atherosclerosis

Structure of Lipoprotein

Metabolism of Plasma Lipid

HMG Co-A reductase is the rate limiting enzyme in the cholesterol synthesis.

Rate Limiting Enzyme

DYSLIPIDEMIA

(A consequence of abnormal lipoprotein metabolism)

Elevated Total Cholesterol (TC) Elevated Low-density lipoproteins (LDL) Elevated triglycerides (TG) Decreased High-density lipoproteins (HDL)

Causes of Dyslipidemia

SINGLE OR MULTIPLE GENE MUTATION –RESULTING IN DISTURBANCE OF LDL, HDL AND TRIGYLCERIDE, PRODUCTION OR CLEARANCE.

Should be suspected in patients with premature heart disease family hx of atherosclerotic dx. Or serum cholesterol level >240mg/dl. Physical signs of hyperlipidemia.

Primary Dyslipidemia

Secondary Dyslipidemia

Sedentary lifestyle Excessive consumption of cholesterol

– saturated fats and trans-fatty acids.

Moderately commonHypothyroidism Pregnancy Cholestatic liver disease Drugs (diuretics, ciclosporin, corticosteroids,

androgens)

Less common Nephrotic syndrome Anorexia nervosa Porphyria Hyperparathyroidism

Secondary Dyslipidemia

Secondary hypertriglyceridaemia

Diabetes mellitus (type 2) Chronic renal disease Abdominal obesity Excess alcohol Hepatocellular disease Drugs (β-blockers, retinoids,

corticosteroids)

Classification of Dyslipidemia and Risk

Clinical manifestation of Dyslipidemia

Different ways of detection of dyslipidemia

During routine health checkup

Clinical manifestation e.g. Xanthelesma

Associated diseases e.g. CHD,DM,HTN

BY DOCTOR BY PATIENT

Lipid measurement

At least 12 hrs fasting

Friedwald formula:LDL-C= TC — HDL-C — ( TG/2.2)

mmol/L

Applicable up to TG: 4mmol/L

Calculation of LDL

TC= HDL + VLDL + LDL

Þ TC = HDL + TG/5 + LDL

Þ LDL= TC — ( HDL + TG/5)

Applicable up to TG: 350 mg/dl

Different Types of Cholesterol

LDL- (“bad” cholesterol) The major cholesterol carrier in the blood. Excess most likely to lead to plaque formation. Goal: LOW

HDL- (“good” cholesterol) Transports cholesterol away from arteries and back to the liver to be eliminated. Removes excess cholesterol from plaques, slowing growth. Goal: HIGH

Normal Level

LDL Cholesterol (mg/dl) HDL Cholesterol (mg/dl)

<100 Optimal < 40 Low100-129 Near/Above Optimal > 60 High (Desirable)130-159 Borderline High160-189 High>190 Very High

Categories of Risk that Modify LDL GoalsCHD and CHD risk equivalents <100Multiple (2+) risk factors <130Zero to one risk factor <160

Major Risk Factors For CHD That Modify LDL Goals

Cigarette smokingHypertension (BP >140/90 or on BP

med)Low HDL cholesterol (<40mg/dl)Family Hx premature CHD- CHD in male 1st degree relative <55 years old- CHD in female 1st degree relative <65 years old

Age (men >45 yrs. women >55 yrs) HDL >60 counts as a “negative” risk factor. It’s presence removes

one risk factor from the total count

Risk Assessment for CHD

DM regarded as a CHD equivalent

For patients with multiple (2+) risk factors

-Perform 10 year risk assessment

For patients with 0-1 risk factor-Most have 10 year risk assessment

<10%; risk assessment scoring unnecessary

Current ATP III Guidelines for Treating LDL Cholesterol

Risk Category

LDL Goal(mg/dl)

LDL level to initiate TLC

LDL level to consider Rx therapy

CHD or Equivalents

<100<70 Ideal

> 100 > 130(100-129 Rx optional)

2+ Risk Factors

<130 > 130 > 130 (10 Year risk 10-20%)> 160 (Risk <10%)

0-1 Risk Factor

<160 > 160 > 190(160-189 Rx optional)

A Model of Steps in Therapeutic Lifestyle Changes (TLC)

Visit 1

Begin TLC

• Emphasize reduction in saturated fat & chol.

• Encourage moderate Physical activity

• Consider referral to dietician

Visit 2 (6 wks)

Eval. LDL response

Intensify Tx if not to goal

• Reinforce dietary recommendations

• Consider adding plant stanols/sterols

• Increase fiber intake

• Consider dietician

Visit 3 (6 wks)

Eval LDL response

Consider adding Rx if not to goal

• Evaluate for Metabolic syndrome

• Intensify wt mgmt & physical activity

• Consider dietician

Visit N

Monitor adherence to

TLC Q4-6 mos

Specific Dyslipidemias: Elevated Triglycerides

Classification of Serum Triglycerides

Normal <150 mg/dl Borderline High 150-199 mg/dl High 200-499mg/dl Very High >500 mg/dl

Specific Dyslipidemias: Elevated Triglycerides

Management of Very High Triglycerides (>500 mg/dl)

Goal of therapy: Prevent acute pancreatitis Very low fat diets (< 15% of caloric intake) Triglyceride-lowering drug usually required

(fibrate or nicotinic acid) Reduce triglycerides before lowering LDL

Consequences of dyslipidemia

Atherosclerosis The main Consequence

Acute pancreatitis ( in High TG)

Pathogenesis of Atherosclerosis

Early Atherosclerosis

Early Atherosclerosis

Early Atherosclerosis

Stable Atherosclerotic Plaque

Advanced Atherosclerosis

Unstable Coronary Artery Disease

Management of Dyslipidemia

Risk assessment Treat modifiable risk factors Optimization of lifestyle factors

Non pharmacologic management

Reduce intake of saturated and trans-unsaturated fat to less than 7-10% of total energy

Reduce intake of cholesterol to < 250 mg/day

Replace sources of saturated fat and cholesterol with alternative foods such as lean meat, low-fat dairy products, polyunsaturated spreads and low glycaemic index carbohydrates

Non pharmacologic management

Reduce energy-dense foods such as fats and soft drinks

Increase consumption of cardioprotective and nutrient-dense foods such as vegetables, unrefined carbohydrates, fish, pulses, nuts, legumes, fruit etc.

Adjust alcohol consumption, reducing intake if excessive or if associated with hypertension, hypertriglyceridaemia or central obesity

Non pharmacologic management

Achieve additional benefits with supplementary intake of foods containing lipid-lowering nutrients such as n-3 fatty acids, dietary fibre and plant sterols.

Pharmacologic Management

Nutrient Recommendations of TLC Diet

Nutrient Recommended Intake

Saturated fat < 7% of total calories Polyunsaturated fat Up to 10% of total calories Monounsaturated fat Up to 20% of total calories Total fat 25-30% of total calories Carbohydrates 50-60% of total calories Fiber 20-30 grams/day Protein Approx. 15% of total calories Cholesterol <200 mg/day Total calories Balance energy intake and

expenditure to maintain desirable body

weight/prevent weight gain

Lipid Lowering DrugsHMG-CoA Reductase Inhibitors (Statins)

Partially block an enzyme necessary for formation of cholesterol

Speed removal of LDL from blood 18%-60% reduction in LDL Most effective at lowering LDL; esp. HS dosing Liver enzymes MUST be monitored. Check

baseline, 3mos., then semi-annually (D/C if > 3x normal limits)

Side effects: Myalgias (D/C if total CK >10x normal), rhabdomyolysis

Metabolized by CP450 (watch for drug interactions)

Contraindicated in pregnancy.

Different statins

AtorvastatinSimvastatinRosuvastatinPitavastatinFluvastatin

Pravastatin

Lipid Lowering Drugs

Bile Acid Sequestrants:Cholestyramin , Cholestipol

Convert cholesterol to bile acids Bind bile acids and prevent

reabsorption in the gut May increase triglyceride levels Most common side effects: GI-

constipation Alternative for statins

Lipid Lowering DrugsCholesterol Absorption Inhibitor(Ezetimibea):

Monotherapy or in combination with statin Not recommended with fibrates Reduces LDL number : esp. Lp(a)

hepatic LDL receptor,Inhibit intestinal mucosa transporter NPCILT.

Lipid-Regulating Agent: Omega 3 acid ethyl esters

Omega 3 Fish oil (salmon, herring, mackerel, swordfish, albacore tuna, sardines, lake trout)

Only FDA approved supplement for tx of dyslipidemias

Decreases hepatic production of TG and VLDL Increases LDL size to large buoyant particles

Lipid Lowering DrugsNicotinic Acid/Niacin (B3)

Inhibition of lipolysis

Reduces production and release of LDL Effective in reduction of triglycerides

(<400mg/dl) Increases HDL Very effective in increasing LDL particle

size Monitor liver enzymes and glucose Most common side effect: FLUSHING (take

ASA/ibuprofen 30 min. prior and take with light snack). Decreased with time released formulas

Liver function disterbance Exacerbation of gout and hyperglycemia.

Lipid Lowering Drugs

Fibric Acid Derivatives/Fibrates

M/A: PPAR∞- stimulation metabolism of TG & LDL Very effective in reducing triglycerides

(>400) Increase HDL SIE: Myolgia,Myopathy,Abnormal LFT,Choleclithiasis Containdications: Gallbladder disease,

hepatic disease, renal dysfunction Increase LDL particle size but not

quantity Caution with statins Gemfibrozil, Benza fibrates, feno fibrates.

Monitoring of therapy After 6 weeks ( 12 weeks for fibrates) Parameter:1. Lipid response2. Side effects- CK, LFT3. Others-a) Dietary compliance

b) Exercise c) Cardiovascular signs and

symptomsd) Wt. e) BP

Summary Dyslipidemia(Silent killer)

Artherosclerosis MI,Stroke At least 12 hrs fasting for the

measurement of lipid profile. TLC-very important But usually

ignored Statin-(Commission is better than

omission)widely well tolerated Other risk factors should be

addressed appropriately.

Act Commission is Better than

Omission

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