Dyslipidemia diagnosis and management

Dyslipidemia, Metabolic Syndrome, Risk factors, Classification, Therapeutic life style changes, Drug treatment, Hypertriglyceridemia,

1. 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

2. 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

3. 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 ³³140/90 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 ³³45 years; women 45 years; women ³³55 years)55 years)
†
HDL cholesterol ³60 mg/dL counts as a “negative” risk
factor; its presence removes one risk factor from the total
count.

4. Life-Habit Risk FactorsLife-Habit Risk Factors
Obesity (BMI Obesity (BMI ³³ 30) 30)
Physical inactivityPhysical inactivity
Atherogenic dietAtherogenic diet

5. 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

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

7. 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

8. 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%

9. Risk CategoryRisk Category
CHD and CHD riskCHD and CHD risk
equivalentsequivalents
Multiple (2+) risk Multiple (2+) risk
factorsfactors
Zero to one risk Zero to one risk
factorfactor
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

10. 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
³³190190 Very highVery high

11. 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
³³6060 High High

12. 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
200–239200–239Borderline highBorderline high
³³240240 HighHigh

13. 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

14. 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)

15. 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 coronary mortality, major coronary
events, coronary procedures, and strokeevents, coronary 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 ³³100 mg/dL)100 mg/dL)

16. 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 Category
LDL 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 ³³100100
³³130 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 ³³130130
10-year risk 10–10-year risk 10–
20%: 20%: ³³130130
10-year risk <10%: 10-year risk <10%:
³³160 160
0–1 Risk Factor0–1 Risk Factor <160<160 ³³160160
³³190 190
(160–189: LDL-(160–189: LDL-
lowering drug lowering drug
optional)optional)

17. 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

18. Therapeutic Lifestyle ChangesTherapeutic Lifestyle Changes
Nutrient 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

19. •Reinforce reduction
in saturated fat and
cholesterol
•Consider adding
plant stanols/sterols
•Increase fiber intake
•Consider referral to
a dietitian
•Initiate Tx for
Metabolic
Syndrome
•Intensify
weight
management
&
physical
activity
•Consider
referral
to a dietitian
6 wks 6 wks Q 4-6 mo

•Emphasize
reduction in
saturated fat &
cholesterol
•Encourage
moderate physical
activity
•Consider referral to
a dietitian
Visit I
Begin Lifestyle
Therapies

Visit 2
Evaluate LDL
response
If LDL goal not
achieved,
intensify
LDL-Lowering Tx
Visit 3
Evaluate LDL
response
If LDL goal not
achieved,
consider
adding drug Tx
A Model of Steps in A Model of Steps in
Therapeutic Lifestyle Changes (TLC)Therapeutic Lifestyle Changes (TLC)
Monitor
Adherence
to TLC
Visit N

20. Drug TherapyDrug Therapy
HMG CoA Reductase Inhibitors HMG CoA Reductase Inhibitors
(Statins)(Statins)
Reduce LDL-C 18–55% & TG Reduce LDL-C 18–55% & TG
7–30%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

21. HMG CoA Reductase HMG CoA Reductase
Inhibitors (Statins)Inhibitors (Statins)
StatinStatin Dose RangeDose Range
LovastatinLovastatin 20–80 mg20–80 mg
PravastatinPravastatin 20–40 mg20–40 mg
SimvastatinSimvastatin 20–80 mg20–80 mg
FluvastatinFluvastatin 20–80 mg20–80 mg
AtorvastatinAtorvastatin 10–80 mg10–80 mg
CerivastatinCerivastatin 0.4–0.8 mg0.4–0.8 mg

22. 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

23. Drug TherapyDrug Therapy
Bile 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)

24. Bile Acid SequestrantsBile Acid Sequestrants
DrugDrug Dose RangeDose Range
CholestyramineCholestyramine 4–16 g4–16 g
ColestipolColestipol 5–20 g5–20 g
ColesevelamColesevelam 2.6–3.8 g2.6–3.8 g

25. 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

26. Drug TherapyDrug Therapy
Nicotinic 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, Contraindications: liver disease,
severe gout, peptic ulcersevere gout, peptic ulcer

27. Nicotinic AcidNicotinic Acid
Drug FormDrug Form Dose Dose
RangeRange
Immediate releaseImmediate release1.5–3 g1.5–3 g
(crystalline)(crystalline)
Extended releaseExtended release1–2 g1–2 g
Sustained releaseSustained release1–2 g1–2 g

28. Nicotinic Acid Nicotinic Acid (continued)(continued)
Demonstrated Therapeutic BenefitsDemonstrated Therapeutic Benefits
Reduces major coronary eventsReduces major coronary events
Possible reduction in total mortalityPossible reduction in total mortality

29. 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 Contraindications: Severe renal or
hepatic diseasehepatic disease

30. Fibric AcidsFibric Acids
DrugDrug DoseDose
GemfibrozilGemfibrozil 600 mg BID600 mg BID
FenofibrateFenofibrate 200 mg QD200 mg QD
ClofibrateClofibrate 1000 mg BID1000 mg BID

31. Fibric Acids Fibric Acids (continued)(continued)
Demonstrated Therapeutic BenefitsDemonstrated Therapeutic Benefits
Reduce progression of coronary Reduce progression of coronary
lesionslesions
Reduce major coronary eventsReduce major coronary events

32. 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 Therapy
for CHD and CHD Risk Equivalentsfor CHD and CHD Risk Equivalents

33. Progression of Drug Therapy
in Primary Prevention
If LDL goal
not achieved,
intensify
LDL-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
sequestran
t 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

34. Metabolic SyndromeMetabolic Syndrome
SynonymsSynonyms
Insulin resistance syndromeInsulin resistance syndrome
(Metabolic) Syndrome X(Metabolic) Syndrome X
Dysmetabolic syndromeDysmetabolic syndrome
Multiple metabolic syndromeMultiple metabolic syndrome

35. 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

36. Metabolic Syndrome Metabolic Syndrome (continued)(continued)
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 To treat associated lipid and non-lipid
risk factorsrisk factors
–HypertensionHypertension
–Prothrombotic stateProthrombotic state
–Atherogenic dyslipidemia (lipid triad)Atherogenic dyslipidemia (lipid triad)

37. Metabolic Syndrome Metabolic Syndrome (continued)(continued)
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 Clinical guidelines: Obesity Education
InitiativeInitiative
–Techniques of weight reductionTechniques of weight reduction

38. Metabolic Syndrome Metabolic Syndrome (continued)(continued)
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 Clinical guidelines: U.S. Surgeon
General’s Report on Physical ActivityGeneral’s Report on Physical Activity

39. ATP III GuidelinesATP III Guidelines
Specific DyslipidemiasSpecific Dyslipidemias

40. Specific Dyslipidemias: Specific Dyslipidemias:
Very High LDL Cholesterol (Very High LDL Cholesterol (³³190 mg/dL)190 mg/dL)
Causes and DiagnosisCauses and Diagnosis
Genetic disordersGenetic disorders
–Monogenic familial Monogenic familial
hypercholesterolemiahypercholesterolemia
–Familial defective apolipoprotein B-100Familial defective apolipoprotein B-100
–Polygenic hypercholesterolemiaPolygenic hypercholesterolemia
Family testing to detect affected Family testing to detect affected
relativesrelatives

41. Specific Dyslipidemias:Specific Dyslipidemias:
Very High LDL Cholesterol (Very High LDL Cholesterol (³³190 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

42. Specific Dyslipidemias: Specific Dyslipidemias:
Elevated TriglyceridesElevated Triglycerides
Classification of Serum TriglyceridesClassification of Serum Triglycerides
Normal Normal <150 mg/dL<150 mg/dL
Borderline highBorderline high150–199 mg/dL150–199 mg/dL
HighHigh 200–499 mg/dL200–499 mg/dL
Very highVery high ³³500 mg/dL500 mg/dL

43. Specific Dyslipidemias: Specific Dyslipidemias:
Elevated Triglycerides (Elevated Triglycerides (³³150 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

44. Specific Dyslipidemias: Specific Dyslipidemias:
Elevated TriglyceridesElevated Triglycerides
Causes of Elevated TriglyceridesCauses of Elevated Triglycerides (continued)(continued)
High carbohydrate diets (>60% of energy High carbohydrate diets (>60% of energy
intake)intake)
Several diseases (type 2 diabetes, chronic Several diseases (type 2 diabetes, chronic
renal failure, nephrotic syndrome)renal 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

45. 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 VLDL cholesterol: denotes atherogenic remnant
lipoproteinslipoproteins
Non-HDL cholesterol: secondary target of therapy Non-HDL cholesterol: secondary target of therapy
when serum triglycerides are when serum triglycerides are ³³200 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

46. Specific Dyslipidemias: Specific Dyslipidemias:
Elevated TriglyceridesElevated Triglycerides
Management of Very High TriglyceridesManagement of Very High Triglycerides
((³³500 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

47. 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, Certain drugs (beta-blockers, anabolic steroids,
progestational agents)progestational agents)

48. Thank Thank
you allyou all