Management of Dyslipidemia

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• Management of Dyslipidemia
• (Case Studies)
• Reem Shafeh, MD
• Board Certified Internal Medicine Clinical
  Lipidology. USA
• Consultant of Internal Medicine Clinical
  Lipidology,
• Saints Memorial Medical Center, Massachusetts,
  USA
• Lecturer of Diabetes Metabolism, Alex.
  University

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Drugs Affecting Lipoprotein MetabolismLipid
Lowering Drugs

• Drug Class LDLC HDLC TG
  

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Role of Combination Therapy

• Reasons for use
• To achieve LDL goal when monotherapy is not
  adequate
• To achieve non-HDL goal after LDL goal has been
  achieved (mixed dyslipidemia)
• To reduce TG in severe hypertriglyceridemia (TG gt
  500 mg/dl)

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2007 NLA Safety Task ForceNiacin/Statin
Combination Therapy

• Clinical evidence does not support a general
  myopathic effect of niacin either alone or in
  combination with statins
• No major clinical trial has suggested a potential
  drug interaction between statins and niacin
• Niacin/Statin combination therapy improve all
  atherogenic lipid abnormalities, slows the
  progression and increases the regression of
  coronary atherosclerosis, and reduces residual
  CVD risk

Guyton JR et al. Am J Cardiol 2007 99 22C-31C
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2007 NLA Safety Task ForceFibrate/ Statin
Combination Therapy

• Fibrate statins are associated with increased
  risk for myopathy and rhabdomyolysis
• Fenofibrate has much less potential for
  impairment of statin metabolism, and this
  accounts for the reduced reports of fenofibrate
  statininduced myopathy compared with gemfibrozil
  statin.

Guyton JR et al. Am J Cardiol 2007 99 22C-31C
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• NCEP ATP III Guidelines
• For Management of Dyslipidemia

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NCEP ATP III Guidelines

• For all patients, including patients with high
  TG, or Low HDL), the primary target of therapy is
  LDL-C. Statin is the first line therapy
• Non HDL-C should be a secondary target of therapy
  when TG gt 200 mg/dl. Two approaches- Increase
  the dose of LDL-lowering drug (statin)- Add
  fibrate or nicotinic acid
• If isolated low HDL, TG are lt 200 mg/dl, drugs
  for HDL raising (fibrates or nicotinic acid) can
  be considered in high risk patients. Niacin in
  the first choice
• Third report of NCEP expert panel of detection,
  evaluation and treatment of high
• blood cholesterol in adults (ATP III).
  Circulation 2002 106 3143-421.

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NCEP ATP III Guidelines (Cont.)

• If TG gt500 mg/dl, the initial aim is to prevent
  pancreatitis through TG lowering.
• - Fibrates are the drug class of choice
• - Nicotinic acid or fish oils may be
  considered in case of intolerance or failure of
  fibrates
• - Only after TG lowered to lt 500 mg/dl,
  should attention turn to LDL lowering.
• Third report of NCEP expert panel of detection,
  evaluation and treatment of high
• blood cholesterol in adults (ATP III).
  Circulation 2002 106 3143-421.

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• Clinical Applications

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NCEP ATP III Recommendations for Risk Assessment

• Five major steps.
• - Obtain Fasting Lipid Profile
• - Identify CHD risk equivalents
• - Identify CHD risk factors
• - Calculate 10 year risk of CHD using
  Framingham risk score
• - Determine the risk category and goals of
  therapy

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Step 1

• Obtain a FLP
• 1- Total Cholesterol
• 2- Triglycerides
• 3- LDL-C
• 4- HDL-C

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Step 2

• CHD equivalents factors that place the patient
  at similar risk for CHD as a history of CHD
  itself
• 1- Diabetes Mellitus
• 2- Symptomatic Carotid Artery Disease
• 3- Peripheral Arterial Disease
• 4- Abdominal Aortic Aneurysm
• 5- Multiple Risk factors with a 10 year risk
  of CHD gt 20
• 6- NKF CRF with Cr gt1.5 or GFR lt 60

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Step 3

• Identify major CHD risk factors other than LDL
• 1- Cigarette Smoking
• 2- HTN (BP gt 140/90, or antihypertensive
  medication)
• 3- Low HDL-C (lt40mg/dl)
• 4- Family history of premature CHD (in male
  first degree relatives lt 55 years, in female
  first degree relatives lt 65 years)
• 5- Age (men gt 45 years, women gt55 years)
• HDL-C gt 60 mg/dl counts as a negative risk factor

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Step 4

• Calculate 10 year risk of CHD
• If 2 or more risk factors are present in patients
  without CHD or CHD equivalent calculate the 10
  year risk of CHD using ATP III modification of
  Framingham Risk Tables.
• Risk does not need to be assessed in patients
  without CHD who have 0-1 risk factors
  (individuals in this category usually have 10
  year risk lt 10)

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NCEP ATP III guidelines for estimate of 10-year
risk for CHD in men and women
MEN
WOMEN

• Age Points
• 20-34 -9
• 35-39 -4
• 40-44 0
• 45-49 3
• 50-54 6
• 55-59 8
• 60-64 10
• 65-69 11
• 70-74 12
• 75-79 13

• Age Points
• 20-34 -7
• 35-39 -3
• 40-44 0
• 45-49 3
• 50-54 6
• 55-59 8
• 60-64 10
• 65-69 12
• 70-74 14
• 75-79 16

Total Cholesterol Points
Age 20-39 40-49 50-59 60-69
70-79 lt 160 0 0
0 0 0 160-199
4 3 2
1 0 200-239 7
5 3 1
0 240-279 9 6
4 2 1 gt 280
11 8 5
3 1
Total Cholesterol Points
Age 20-39 40-49 50-59 60-69
70-79 lt 160 0 0
0 0 0 160-199
4 3 2
1 1 200-239 8
6 4 2
1 240-279 11 8
5 3 2 gt 280
13 10 7
4 2
Points
Age 20-39 40-49 50-59
60-69 70-79 Non-smoker 0
0 0 0
1 Smoker 8 5
3 1 1
Points
Age 20-39 40-49 50-59
60-69 70-79 Non-smoker 0
0 0 0
1 Smoker 9 7
4 2 1
HDL Points gt 60 -1 50-59
0 40-49 1 lt 40 2
HDL Points gt 60 -1 50-59
0 40-49 1 lt 40 2
Systolic BP Untreated Treated lt
120 0
0 120-129 0
1 130-139 1
2 140-159 1
2 gt 160 2
3
Systolic BP Untreated Treated lt
120 0
0 120-129 1
3 130-139 2
4 140-159 3
5 gt 160 4
6
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NCEP ATP III guidelines for estimate of 10-year
risk for CHD in men and women
WOMEN
MEN

• Total Points 10-Year Risk
• lt0 lt 1
• 0 1
• 1 1
• 2 1
• 3 1
• 4 1
• 5 2
• 6 2
• 7 3
• 8 4
• 9 5
• 10 6
• 11 8
• 12 10
• 13 12
• 14 16
• 15 20
• 16 25

Total Points 10-Year Risk lt9
lt 1 9
1 10
1 11
1 12
1 13 2
14 2 15
3 16
4 17
5 18
6 19 8
20 11
21 14 22
17 23
22 24
27 gt25
gt30
10-Year Risk
10-Year Risk
www.mobilelipidclinic.com, www.nih.gov/ncep
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Step 5

• Determine the risk category that establish the
  LDL goal (or Non- HDL goal if TG gt 200 mg/dl) ,
  when to initiate lifestyle changes, and when to
  consider drug therapy.

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Revised ATP III Guidelines

• If TG gt 200 mg/dl, Non HDL goal is 30 mg/dl
  higher than LDL goal
• If TG very high (gt500 mg/dl), the initial aim is
  to prevent pancreatitis through TG lowering.
• After reaching LDL and non HDL goals, If isolated
  low HDL, consider treatment for high risk
  patients

ATP III optional goal High risk by NKF
guidelines High risk by AHA/CDC guideline
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Case 1

• 65-year-old woman with history of hypertension
  and pre-diabetes. No history of smoking. Family
  history significant for diabetes.
• BMI 30 Kg/m2
• Waist circumference 95 Cm
• BP 160/100
• BUN, Cr Normal
• EKG Normal
• Fasting glucose 120
• LFTs Normal
• TC 300 mg/dl
• TG 387 mg/dl
• HDL 49 mg/dl
• LDL 174 mg/dl
• Non-HDL 251

Q1 Does this patient need treatment?
How? Q2What are his goals of therapy?
Step 1 FLP Step 2 Is his risk equivalent to
CAD? Step 3 How many risk factors he has? Step
4 What is his Framingham risk score? Step 5
what are his goals?
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Case 1

• 2 risk factors (age HTN)
• Risk Score 14 (Age 65y 12 TC 300 4
  smoking 0 SBP 160 4 HDL 49 1 ) 21
  points 14 10-year risk
• Not CAD risk equivalent
• ATP III risk stratification Moderate High Risk
• LDL goal lt 130 ( lt 100 optional)
• Non-HDL goal lt 160 (lt 130 optional)

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Case 1
TC 300 mg/dl TG 387 mg/dl HDL 49 mg/dl LDL
174 mg/dll

• First target is LDL reduction (STATIN)
• Patient was started on Rosuvastatin 10 mg/day
• 12 weeks later TC 225, LDL 105, HDL 52, TG 340,
  Non-HDL 173
• Second target is Non-HDL-C (Fibrate/Niacin)
• Fenofibrate started at 160 mg/d
• 12 weeks later TC 198, LDL 101, HDL 54, TG 215,
  Non-HDL 144
• Optional Add Niacin, or Increase dose of statin

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Case 2

• 53 year old male cigarette smoker who is on no
  medications has the following physical and
  laboratory findings
• Height 170 cm
• Weight 90 Kg
• Waist circumference 99 cm
• BP 132/88
• Eyes Bilateral corneal arcus
• Skin no tendon xanthoma
• TC 240 mg/dl
• TG 190 mg/dl
• HDL 32 mg/dl
• LDL 170 mg/dl
• Lp (a) 25 mg/dl
• Fasting glucose 108 mg/dl

Q1 Does he need treatment? Q2What are his goals
of therapy?
Step 1 FLP Step 2 Is his risk equivalent to
CAD? Step 3 How many risk factors he has? Step
4 What is his Framingham risk score? Step 5
what are his goals?
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Case 2

• 3 risk factors (age smoking low HDL)
• Risk Score 25 (Age 53y 6 TC 240 4
  smoking 3 SBP 132 1 HDL 32 2 ) 16
  points 25 10-year risk
• CAD risk equivalent
• LDL goal lt 100
• Non-HDL goal lt 130
• HDL goal gt 40

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Case 2
TC 240 mg/dl TG 190 mg/dl HDL 32 mg/dl LDL
170 mg/dll Fasting glucose 108 mg/dl

• Patient was placed on Atorvastatin 10 mg and
  follow up lipid profile was as follows
• TC 172 mg/dl
• TG 165 mg/dl
• HDL 33 mg/dl
• LDL 106 mg/dl
• Glucose 107 mg/dl

Q1 What is next? A- Add extended release Niacin
1g/d? B- Add Welchol 3750 mg/d? C- Add
Fenofibrate 160 mg/d? D- Change Atorvastatin 10
mg to Rusovastatin 10 mg/d? E- Titrate
Atorvastatin to 20 mg/d?
TC 155 mg/dl TG 170 mg/dl HDL 34 mg/dl LDL 87
mg/dl Glu 107 mg/dl
TC 160 mg/dl TG 160 mg/dl HDL 33 mg/dl LDL 99
mg/dl Glu 107 mg/dl
TC 162 mg/dl TG 160 mg/dl HDL 35 mg/dl LDL 95
mg/dl Glu 107 mg/dl
TC 167 mg/dl TG 120 mg/dl HDL 35 mg/dl LDL
106 mg/dl Glu 107 mg/dl
TC 161 mg/dl TG 128 mg/dl HDL 38 mg/dl LDL 97
mg/dl Glu 115 mg/dl
E
D
C
A
B
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Case 3

• 54 year old female presents for ? Initiation of
  lipid lowering therapy.
• Height 160 cm
• Wt 68 Kg
• Waist Circumference 92 cm
• BP 136/88 mmHg
• Father died at age 56 of MI, mother died at age
  70 of diabetes complications, her siblings, age
  52, 50, and 78 are alive and well.
• She is sedentary
• TC 210 mg/dl
• TG 180 mg/dl
• HDL 45 mg/dl
• LDL 129 mg/dl
• Fasting glucose 111 mg/dl
• Lp (a) 60 mg/dl (Nlt 30)
• Hs-CRP 2.0 mg/dl
• Homocysteine 14 mcmol/l (N lt 10)

Q1 Does she need treatment? Q2 What are her ATP
III goals?
Step 1 FLP Step 2 Is her risk equivalent to
CAD? Step 3 How many risk factors she has? Step
4 What is her Framingham risk score? Step 5
what are her goals?
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Case 3

• NO single risk factor
• Not CAD risk equivalent
• Risk score 2 (Age 54y 6 TC 210 4 no
  smoking 0 SBP 136 2 HDL 45 1 ) 13
  points 2 10-year risk
• ATP III LDL goal lt 160
• Non-HDL goal lt 190
• NCEP ATP III strongly encourage PHYSICIAN
  JUDGMENT in patient like this, with multiple
  borderline risk factors and evidence of
  preclinical disease

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Message to Take Home

• Statin therapy is the initial therapy for
  dyslipidemia except in those with severe
  hypertriglyceridemia )TG gt 500 mg/dl)
• Add a second or third agent when LDL or non HDL
  goal is not achieved
• For those patients with high TG or low HDL-C,
  addition of a fibrate or nicotinic acid to
  LDL-lowering therapy should be considered to
  achieve non-HDL goals
• Combination therapy holds great promise for
  optimizing all lipid subfractions and reducing
  residual CVD risk

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• THANK YOU