dyslipidemia diagnosis and management

Management of DyslipidemiaManagement of Dyslipidemia((lecture given to General Practioners in Narshingdhi organized by lecture given to General Practioners in Narshingdhi organized by

local BMA and Beximco )local BMA and Beximco )

Dr. Md.Toufiqur RahmanDr. Md.Toufiqur Rahman MBBS, FCPS, MD, FACC, FESC, FRCP, FSCAI, MBBS, FCPS, MD, FACC, FESC, FRCP, FSCAI,

FAPSC, FAPSIC, FAHAFAPSC, FAPSIC, FAHA

Associate Professor of CardiologyAssociate Professor of Cardiology

National Institute of Cardiovascular DiseasesNational Institute of Cardiovascular Diseases

Sher-e-Bangla Nagar, Dhaka-1207Sher-e-Bangla Nagar, Dhaka-1207

Consultant, Medinova, Malbagh branch.Consultant, Medinova, Malbagh branch.

Honorary Consultant, Apollo Hospitals, Dhaka and Honorary Consultant, Apollo Hospitals, Dhaka and

Life Care Centre, DhanmondiLife Care Centre, Dhanmondi

Categories of Risk FactorsCategories of Risk Factors

Major, independent risk factorsMajor, independent risk factors Life-habit risk factorsLife-habit risk factors Emerging risk factorsEmerging risk factors

Major Risk Factors (Exclusive of LDL Major Risk Factors (Exclusive of LDL Cholesterol) That Modify LDL GoalsCholesterol) That Modify LDL Goals Cigarette smokingCigarette smoking Hypertension (BP Hypertension (BP 140/90 mmHg or on 140/90 mmHg or on

antihypertensive medication)antihypertensive medication) Low HDL cholesterol (<40 mg/dL)Low HDL cholesterol (<40 mg/dL)†† Family history of premature CHDFamily history of premature CHD

– CHD in male first degree relative <55 yearsCHD in male first degree relative <55 years– CHD in female first degree relative <65 CHD in female first degree relative <65

yearsyears Age (men Age (men 45 years; women 45 years; women 55 years)55 years)

† HDL cholesterol 60 mg/dL counts as a “negative” risk factor; its presence removes one risk factor from the total count.

Life-Habit Risk FactorsLife-Habit Risk Factors

Obesity (BMI Obesity (BMI 30) 30) Physical inactivityPhysical inactivity Atherogenic dietAtherogenic diet

Emerging Risk FactorsEmerging Risk Factors

Lipoprotein (a)Lipoprotein (a) HomocysteineHomocysteine Prothrombotic factorsProthrombotic factors Proinflammatory factorsProinflammatory factors Impaired fasting glucose Impaired fasting glucose Subclinical atherosclerosisSubclinical atherosclerosis

DiabetesDiabetes

In ATP III, diabetes is regarded In ATP III, diabetes is regarded as a CHD risk equivalent. as a CHD risk equivalent.

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20% 20% High mortality with established CHDHigh mortality with established CHD

– High mortality with acute MIHigh mortality with acute MI– High mortality post acute MIHigh mortality post acute MI

CHD Risk EquivalentsCHD Risk Equivalents

Other clinical forms of atherosclerotic Other clinical forms of atherosclerotic disease (peripheral arterial disease, disease (peripheral arterial disease, abdominal aortic aneurysm, and abdominal aortic aneurysm, and symptomatic carotid artery disease)symptomatic carotid artery disease)

DiabetesDiabetes Multiple risk factors that confer a 10-Multiple risk factors that confer a 10-

year risk for CHD >20%year risk for CHD >20%

Risk CategoryRisk Category

CHD and CHD riskCHD and CHD riskequivalentsequivalents

Multiple (2+) risk Multiple (2+) risk factorsfactors

Zero to one risk factorZero to one risk factor

LDL Goal LDL Goal (mg/dL)(mg/dL)

<100<100

<130<130

<160<160

Three Categories of Risk that Modify Three Categories of Risk that Modify

LDL-Cholesterol GoalsLDL-Cholesterol Goals

ATP III Lipid and ATP III Lipid and

Lipoprotein ClassificationLipoprotein Classification

LDL Cholesterol (mg/dL)LDL Cholesterol (mg/dL)

<100<100 OptimalOptimal

100–129100–129 Near optimal/above Near optimal/above optimaloptimal

130–159130–159 Borderline highBorderline high

160–189160–189 HighHigh

190190 Very highVery high

ATP III Lipid and ATP III Lipid and Lipoprotein Classification Lipoprotein Classification (continued)(continued)

HDL Cholesterol HDL Cholesterol (mg/dL)(mg/dL)

<40<40 Low Low

6060 High High

ATP III Lipid and ATP III Lipid and Lipoprotein Classification Lipoprotein Classification (continued)(continued)

Total Cholesterol (mg/dL)Total Cholesterol (mg/dL)

<200<200 DesirableDesirable

200–239200–239 Borderline highBorderline high

240240 HighHigh

Primary Prevention With Primary Prevention With LDL-Lowering TherapyLDL-Lowering Therapy

Public Health ApproachPublic Health Approach

Reduced intakes of saturated fat and Reduced intakes of saturated fat and cholesterolcholesterol

Increased physical activityIncreased physical activity Weight controlWeight control

Causes of Secondary Causes of Secondary DyslipidemiaDyslipidemia

DiabetesDiabetes HypothyroidismHypothyroidism Obstructive liver diseaseObstructive liver disease Chronic renal failureChronic renal failure Drugs that raise LDL cholesterol and Drugs that raise LDL cholesterol and

lower HDL cholesterol (progestins, lower HDL cholesterol (progestins, anabolic steroids, and corticosteroids)anabolic steroids, and corticosteroids)

Secondary Prevention With Secondary Prevention With LDL-Lowering TherapyLDL-Lowering Therapy

Benefits: reduction in total mortality, Benefits: reduction in total mortality, coronary mortality, major coronary events, coronary mortality, major coronary events, coronary procedures, and strokecoronary procedures, and stroke

LDL cholesterol goal: <100 mg/dLLDL cholesterol goal: <100 mg/dL Includes CHD risk equivalentsIncludes CHD risk equivalents Consider initiation of therapy during Consider initiation of therapy during

hospitalizationhospitalization(if LDL (if LDL 100 mg/dL)100 mg/dL)

LDL Cholesterol Goals and Cutpoints for LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC)Therapeutic Lifestyle Changes (TLC)

and Drug Therapy in Different Risk Categoriesand Drug Therapy in Different Risk Categories

Risk CategoryRisk CategoryLDL GoalLDL Goal(mg/dL)(mg/dL)

LDL Level at Which LDL Level at Which to Initiate to Initiate

Therapeutic Therapeutic Lifestyle Changes Lifestyle Changes

(TLC) (mg/dL)(TLC) (mg/dL)

LDL Level at Which LDL Level at Which to Considerto Consider

Drug Therapy Drug Therapy (mg/dL)(mg/dL)

CHD or CHD Risk CHD or CHD Risk EquivalentsEquivalents

(10-year risk >20%)(10-year risk >20%)<100<100 100100

130 130 (100–129: drug (100–129: drug

optional)optional)

2+ Risk Factors 2+ Risk Factors (10-year risk (10-year risk 20%)20%) <130<130 130130

10-year risk 10–10-year risk 10–20%: 20%: 130130

10-year risk <10%: 10-year risk <10%: 160 160

0–1 Risk Factor0–1 Risk Factor <160<160 160160

190 190 (160–189: LDL-(160–189: LDL-lowering drug lowering drug

optional)optional)

Benefit Beyond LDL Lowering: The Metabolic Benefit Beyond LDL Lowering: The Metabolic Syndrome as a Secondary Target of TherapySyndrome as a Secondary Target of Therapy

General Features of the Metabolic SyndromeGeneral Features of the Metabolic Syndrome

Abdominal obesityAbdominal obesity Atherogenic dyslipidemiaAtherogenic dyslipidemia

– Elevated triglyceridesElevated triglycerides

– Small LDL particlesSmall LDL particles

– Low HDL cholesterolLow HDL cholesterol

Raised blood pressureRaised blood pressure Insulin resistance (Insulin resistance ( glucose intolerance) glucose intolerance) Prothrombotic stateProthrombotic state Proinflammatory stateProinflammatory state

Therapeutic Lifestyle ChangesTherapeutic Lifestyle ChangesNutrient Composition of TLC DietNutrient Composition of TLC Diet

NutrientNutrient Recommended IntakeRecommended Intake Saturated fatSaturated fat Less than 7% of total caloriesLess than 7% of total calories Polyunsaturated fatPolyunsaturated fat Up to 10% of total caloriesUp to 10% of total calories Monounsaturated fat Monounsaturated fat Up to 20% of total caloriesUp to 20% of total calories Total fatTotal fat 25–35% of total calories25–35% of total calories CarbohydrateCarbohydrate 50–60% of total calories50–60% of total calories FiberFiber 20–30 grams per day20–30 grams per day ProteinProtein Approximately 15% of total caloriesApproximately 15% of total calories CholesterolCholesterol Less than 200 mg/dayLess than 200 mg/day Total calories (energy)Total calories (energy) Balance energy intake and expenditure Balance energy intake and expenditure

to maintain desirable body weight/to maintain desirable body weight/prevent weight gainprevent weight gain

• Reinforce reductionin saturated fat andcholesterol

• Consider addingplant stanols/sterols

• Increase fiber intake

• Consider referral toa dietitian

• Initiate Tx forMetabolicSyndrome

• Intensify weightmanagement &physical activity

• Consider referral to a dietitian

6 wks 6 wks Q 4-6 mo

• Emphasize

reduction insaturated fat &cholesterol

• Encouragemoderate physicalactivity

• Consider referral toa dietitian

Visit IBegin LifestyleTherapies

Visit 2Evaluate LDLresponse

If LDL goal notachieved, intensifyLDL-Lowering Tx

Visit 3Evaluate LDLresponse

If LDL goal notachieved, consideradding drug Tx

A Model of Steps in A Model of Steps in Therapeutic Lifestyle Changes (TLC)Therapeutic Lifestyle Changes (TLC)

MonitorAdherenceto TLC

Visit N

Drug TherapyDrug TherapyHMG CoA Reductase Inhibitors HMG CoA Reductase Inhibitors

(Statins)(Statins)

Reduce LDL-C 18–55% & TG 7–30%Reduce LDL-C 18–55% & TG 7–30% Raise HDL-C 5–15%Raise HDL-C 5–15% Major side effectsMajor side effects

– MyopathyMyopathy– Increased liver enzymesIncreased liver enzymes

ContraindicationsContraindications– Absolute: liver diseaseAbsolute: liver disease– Relative: use with certain drugsRelative: use with certain drugs

HMG CoA Reductase HMG CoA Reductase Inhibitors (Statins)Inhibitors (Statins)

StatinStatin Dose RangeDose Range

LovastatinLovastatin 20–80 mg20–80 mgPravastatinPravastatin 20–40 mg20–40 mgSimvastatinSimvastatin 20–80 mg20–80 mgFluvastatinFluvastatin 20–80 mg20–80 mgAtorvastatinAtorvastatin 10–80 mg10–80 mgCerivastatinCerivastatin 0.4–0.8 mg0.4–0.8 mg

HMG CoA Reductase HMG CoA Reductase Inhibitors (Statins) Inhibitors (Statins) (continued)(continued)

Demonstrated Therapeutic BenefitsDemonstrated Therapeutic Benefits

Reduce major coronary eventsReduce major coronary events Reduce CHD mortalityReduce CHD mortality Reduce coronary procedures Reduce coronary procedures

(PTCA/CABG)(PTCA/CABG) Reduce strokeReduce stroke Reduce total mortalityReduce total mortality

Drug TherapyDrug TherapyBile Acid SequestrantsBile Acid Sequestrants

Major actionsMajor actions– Reduce LDL-C 15Reduce LDL-C 15––30%30%– Raise HDL-C 3Raise HDL-C 3––5%5%– May increase TGMay increase TG

Side effectsSide effects– GI distress/constipationGI distress/constipation– Decreased absorption of other drugsDecreased absorption of other drugs

ContraindicationsContraindications– DysbetalipoproteinemiaDysbetalipoproteinemia– Raised Raised TG (especially >400 mg/dL)TG (especially >400 mg/dL)

Bile Acid SequestrantsBile Acid Sequestrants

DrugDrug Dose Dose RangeRange

CholestyramineCholestyramine 4–16 g4–16 g

ColestipolColestipol 5–20 g5–20 g

ColesevelamColesevelam 2.6–3.8 g2.6–3.8 g

Bile Acid Sequestrants Bile Acid Sequestrants (continued)(continued)

Demonstrated Therapeutic Demonstrated Therapeutic BenefitsBenefits

Reduce major coronary eventsReduce major coronary events Reduce CHD mortalityReduce CHD mortality

Drug TherapyDrug TherapyNicotinic AcidNicotinic Acid

Major actionsMajor actions– Lowers LDL-C 5Lowers LDL-C 5––25%25%

– Lowers TG 20Lowers TG 20––50%50%

– Raises HDL-C 15Raises HDL-C 15––35%35%

Side effects: flushing, hyperglycemia, Side effects: flushing, hyperglycemia, hyperuricemia, upper GI distress, hyperuricemia, upper GI distress, hepatotoxicityhepatotoxicity

Contraindications: liver disease, severe gout, Contraindications: liver disease, severe gout, peptic ulcerpeptic ulcer

Nicotinic AcidNicotinic Acid

Drug FormDrug Form Dose Dose RangeRange

Immediate releaseImmediate release 1.5–3 g1.5–3 g(crystalline)(crystalline)

Extended releaseExtended release 1–2 g1–2 g

Sustained releaseSustained release 1–2 g1–2 g

Nicotinic Acid Nicotinic Acid (continued)(continued)


Reduces major coronary eventsReduces major coronary events Possible reduction in total mortalityPossible reduction in total mortality

Drug TherapyDrug Therapy

Fibric AcidsFibric Acids

Major actionsMajor actions– Lower LDL-C 5–20% (with normal TG)Lower LDL-C 5–20% (with normal TG)– May raise LDL-C (with high TG)May raise LDL-C (with high TG)– Lower TG 20–50%Lower TG 20–50%– Raise HDL-C 10–20%Raise HDL-C 10–20%

Side effects: dyspepsia, gallstones, Side effects: dyspepsia, gallstones, myopathymyopathy

Contraindications: Severe renal or hepatic Contraindications: Severe renal or hepatic diseasedisease

Fibric AcidsFibric Acids

DrugDrug DoseDose

GemfibrozilGemfibrozil 600 mg BID600 mg BID FenofibrateFenofibrate 200 mg QD200 mg QD ClofibrateClofibrate 1000 mg 1000 mg

BIDBID

Fibric Acids Fibric Acids (continued)(continued)


Reduce progression of coronary Reduce progression of coronary lesionslesions

Reduce major coronary eventsReduce major coronary events

LDL-cholesterol goal: <100 mg/dLLDL-cholesterol goal: <100 mg/dL Most patients require drug therapyMost patients require drug therapy First, achieve LDL-cholesterol goalFirst, achieve LDL-cholesterol goal Second, modify other lipid and non-Second, modify other lipid and non-

lipid risk factorslipid risk factors

Secondary Prevention: Drug TherapySecondary Prevention: Drug Therapyfor CHD and CHD Risk Equivalentsfor CHD and CHD Risk Equivalents

Progression of Drug Therapy in Primary Prevention

If LDL goal not achieved, intensifyLDL-lowering therapy

If LDL goal not achieved, intensify drug therapy or refer to a lipid specialist

Monitor response and adherence to therapy

• Start statin or bile acid sequestrant or nicotinic acid

• Consider higher dose of statin or add a bile acid sequestrant or nicotinic acid

6 wks 6 wks Q 4-6 mo

• If LDL goal achieved, treat other lipid risk factors

Initiate LDL-lowering drug therapy

Metabolic SyndromeMetabolic Syndrome

SynonymsSynonyms

Insulin resistance syndromeInsulin resistance syndrome (Metabolic) Syndrome X(Metabolic) Syndrome X Dysmetabolic syndromeDysmetabolic syndrome Multiple metabolic syndromeMultiple metabolic syndrome

Metabolic Syndrome Metabolic Syndrome (continued)(continued)

CausesCauses

Acquired causesAcquired causes– Overweight and obesityOverweight and obesity– Physical inactivityPhysical inactivity– High carbohydrate diets (>60% of energy High carbohydrate diets (>60% of energy

intake) in some personsintake) in some persons

Genetic causesGenetic causes


Therapeutic ObjectivesTherapeutic Objectives

To reduce underlying causesTo reduce underlying causes– Overweight and obesityOverweight and obesity– Physical inactivityPhysical inactivity

To treat associated lipid and non-lipid risk factorsTo treat associated lipid and non-lipid risk factors– HypertensionHypertension– Prothrombotic stateProthrombotic state– Atherogenic dyslipidemia (lipid triad)Atherogenic dyslipidemia (lipid triad)


Management of Overweight and ObesityManagement of Overweight and Obesity

Overweight and obesity: lifestyle risk factorsOverweight and obesity: lifestyle risk factors Direct targets of interventionDirect targets of intervention Weight reductionWeight reduction

– Enhances LDL loweringEnhances LDL lowering– Reduces metabolic syndrome risk factorsReduces metabolic syndrome risk factors

Clinical guidelines: Obesity Education InitiativeClinical guidelines: Obesity Education Initiative– Techniques of weight reductionTechniques of weight reduction


Management of Physical InactivityManagement of Physical Inactivity

Physical inactivity: lifestyle risk factorPhysical inactivity: lifestyle risk factor Direct target of interventionDirect target of intervention Increased physical activityIncreased physical activity

– Reduces metabolic syndrome risk factorsReduces metabolic syndrome risk factors– Improves cardiovascular functionImproves cardiovascular function

Clinical guidelines: U.S. Surgeon General’s Clinical guidelines: U.S. Surgeon General’s Report on Physical ActivityReport on Physical Activity

ATP III GuidelinesATP III Guidelines

Specific DyslipidemiasSpecific Dyslipidemias

Specific Dyslipidemias: Specific Dyslipidemias: Very High LDL Cholesterol (Very High LDL Cholesterol (190 190

mg/dL)mg/dL)Causes and DiagnosisCauses and Diagnosis

Genetic disordersGenetic disorders– Monogenic familial hypercholesterolemiaMonogenic familial hypercholesterolemia

– Familial defective apolipoprotein B-100Familial defective apolipoprotein B-100

– Polygenic hypercholesterolemiaPolygenic hypercholesterolemia

Family testing to detect affected Family testing to detect affected relativesrelatives

Specific Dyslipidemias:Specific Dyslipidemias:Very High LDL Cholesterol (Very High LDL Cholesterol (190 mg/dL) 190 mg/dL)

(continued)(continued)

ManagementManagement

LDL-lowering drugsLDL-lowering drugs– Statins (higher doses)Statins (higher doses)– Statins + bile acid sequestrantsStatins + bile acid sequestrants– Statins + bile acid sequestrants + nicotinic Statins + bile acid sequestrants + nicotinic

acidacid

Specific Dyslipidemias: Specific Dyslipidemias: Elevated TriglyceridesElevated Triglycerides

Classification of Serum TriglyceridesClassification of Serum Triglycerides

Normal Normal <150 mg/dL<150 mg/dL Borderline highBorderline high 150–199 150–199

mg/dLmg/dL HighHigh 200–499 200–499

mg/dLmg/dL Very highVery high 500 mg/dL500 mg/dL

Specific Dyslipidemias: Specific Dyslipidemias:

Elevated Triglycerides (Elevated Triglycerides (150 mg/dL)150 mg/dL)

Causes of Elevated TriglyceridesCauses of Elevated Triglycerides

Obesity and overweightObesity and overweight Physical inactivityPhysical inactivity Cigarette smokingCigarette smoking Excess alcohol intakeExcess alcohol intake


Causes of Elevated TriglyceridesCauses of Elevated Triglycerides (continued)(continued)

High carbohydrate diets (>60% of energy intake)High carbohydrate diets (>60% of energy intake) Several diseases (type 2 diabetes, chronic renal Several diseases (type 2 diabetes, chronic renal

failure, nephrotic syndrome)failure, nephrotic syndrome) Certain drugs (corticosteroids, estrogens, Certain drugs (corticosteroids, estrogens,

retinoids, higher doses of beta-blockers)retinoids, higher doses of beta-blockers) Various genetic dyslipidemiasVarious genetic dyslipidemias

Specific Dyslipidemias: Specific Dyslipidemias: Elevated Triglycerides Elevated Triglycerides (continued)(continued)

Non-HDL Cholesterol: Secondary TargetNon-HDL Cholesterol: Secondary Target

Non-HDL cholesterol = VLDL + LDL cholesterolNon-HDL cholesterol = VLDL + LDL cholesterol= (Total Cholesterol – HDL cholesterol)= (Total Cholesterol – HDL cholesterol)

VLDL cholesterol: denotes atherogenic remnant lipoproteinsVLDL cholesterol: denotes atherogenic remnant lipoproteins Non-HDL cholesterol: secondary target of therapy when Non-HDL cholesterol: secondary target of therapy when

serum triglycerides are serum triglycerides are 200 mg/dL 200 mg/dL (esp. 200–499 mg/dL)(esp. 200–499 mg/dL)

Non-HDL cholesterol goal: Non-HDL cholesterol goal: LDL-cholesterol goal + 30 mg/dLLDL-cholesterol goal + 30 mg/dL


Management of Very High TriglyceridesManagement of Very High Triglycerides ((500 mg/dL)500 mg/dL)

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

(fibrate or nicotinic acid)(fibrate or nicotinic acid) Reduce triglycerides Reduce triglycerides before before LDL lowering LDL lowering

Specific Dyslipidemias: Specific Dyslipidemias: Low HDL CholesterolLow HDL Cholesterol

Causes of Low HDL Cholesterol (<40 mg/dL)Causes of Low HDL Cholesterol (<40 mg/dL)

Elevated triglyceridesElevated triglycerides Overweight and obesityOverweight and obesity Physical inactivityPhysical inactivity Type 2 diabetesType 2 diabetes Cigarette smokingCigarette smoking Very high carbohydrate intakes (>60% energy)Very high carbohydrate intakes (>60% energy) Certain drugs (beta-blockers, anabolic steroids, progestational Certain drugs (beta-blockers, anabolic steroids, progestational

agents)agents)

Thank Thank you allyou all

dyslipidemia diagnosis and management

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