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DYSLIPIDEMIA. Denise Reedus , N.P. Piedmont Heart Institute. CHOLESTEROL. A soft waxy substance found among lipids (fats) in the bloodstream and all cells Needed for digesting fats, making hormones, building cell walls

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dyslipidemia

DYSLIPIDEMIA

Denise Reedus, N.P.

Piedmont Heart Institute

cholesterol
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
dyslipidemia a consequence of abnormal lipoprotein metabolism
DYSLIPIDEMIA(A consequence of abnormal lipoprotein metabolism)
  • Elevated Total Cholesterol (TC)
  • Elevated Low-density lipoproteins (LDL)
  • Elevated triglycerides (TG)
  • Decreased High-density lipoproteins (HDL)
primary dyslipidemia etiology
PRIMARY DYSLIPIDEMIA ETIOLOGY
  • 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.
slide6
SECONDARY DYSLIPIDEMIA (Most adult cases of dyslipidemia are secondary in nature in western civilizations)
  • Sedentary lifestyle
  • Excessive consumption of cholesterol – saturated fats and trans-fatty acids.
secondary dyslipidemia medical conditions associated with dyslipidemia
Secondary Dyslipidemia(Medical Conditions Associated with dyslipidemia)
  • Diabetes
  • Hypothyroidism
  • Cholestatic liver disease.
  • Nephrotic syndrome
  • cigarette smoking
secondary dyslipidemia drugs causing mild to moderate degrees of dyslipidemia
SECONDARY DYSLIPIDEMIA (Drugs causing mild to moderate degrees of dyslipidemia)
  • Beta-blockers
  • Thiazide diuretics
  • Antiretroviral drugs
  • Hormonal agents
types of cholesterol
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

Triglycerides- the chemical form in which most fat exists in foods as well as in the body. Present in blood plasma and together with cholesterol, form the plasma lipids. Made in the body from other energy sources like carbohydrates. Calories ingested in a meal and not immediately used by tissues are converted to triglycerides. Hormones regulate the release from fat tissue to meet the body’s needs for energy between meals.

why do we care
Why Do We Care?

According to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Cholesterol in Adults

(NCEP ATP-III):

High LDL levels are a leading cause of coronary heart disease (CHD) and should be the main target of any cholesterol lowering regimen

atp iii lipid and lipoprotein classification
ATP III Lipid and Lipoprotein Classification

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

<100 Optimal < 40 Low in Men

100-129 Near/Above Optimal <50 Low in Women

130-159 Borderline High

160-189 High

>190 Very High

Categories of Risk that Modify LDL Goals

CHD aggressive therapy <70

CHD and CHD risk equivalents <100

Multiple (2+) risk factors <130

Zero to one risk factor <160

major risk factors for chd that modify ldl goals
Major Risk Factors For CHD That Modify LDL Goals

Cigarette smoking

Hypertension (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
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

a model of steps in therapeutic lifestyle changes tlc
A Model of Steps in Therapeutic Lifestyle Changes (TLC)

Visit 1

Begin TLC

Visit 2 (6 wks)

Eval. LDL response

Intensify Tx if not to goal

Visit 3 (6 wks)

Eval LDL response

Consider adding Rx if not to goal

Visit N

Monitor adherence to TLC Q4-6 mos

  • Emphasize reduction in saturated fat & chol.
  • Encourage moderate Physical activity
  • Consider referral to dietician
  • Reinforce dietary recommendations
  • Consider adding plant stanols/sterols
  • Increase fiber intake
  • Consider dietician
  • Evaluate for Metabolic syndrome
  • Intensify wt mgmt & physical activity
  • Consider dietician
nutrient recommendations of tlc diet
Nutrient Recommendations of TLC Diet

NutrientRecommended 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

specific dyslipidemias very high ldl 190mg dl
Specific Dyslipidemias: Very High LDL (> 190mg/dl)

Causes and Diagnosis

  • Genetic disorders

Monogenic familial hypercholesterolemia

Familial defective apolipoprotein B-100 (Apo B)

Polygenic hypercholesterolemia

  • Family testing to detect affected relatives
specific dyslipidemias low hdl
Specific Dyslipidemias: Low HDL

Causes of Low HDL (<40 mg/dl)

  • Elevated triglycerides
  • Overweight and obesity
  • Physical Inactivity
  • Type 2 diabetes
  • Cigarette smoking
  • Very high carb. intakes (>60% energy)
  • Medications (some beta blockers, anabolic steroids, progestational agents)
specific dyslipidemias elevated triglycerides
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 triglycerides23
Specific Dyslipidemias: Elevated Triglycerides

Causes of Elevated Triglycerides

  • Obesity and overweight
  • Physical Inactivity
  • Cigarette smoking
  • Excess alcohol intake
  • High carb. diets
  • Several diseases (Type 2 DM, chronic renal failure, nephrotic syndrome
  • Medications (corticosteroids, estrogens, retinoids, higher doses of beta blockers
specific dyslipidemias elevated triglycerides24
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
advanced lipid analysis
Advanced Lipid Analysis
  • LDL type “floats” around in the blood
  • Most LDL around 260 Angstroms
  • 5% smaller diameter LDL particle leads to a 50% increase in rate of uptake by the arterial wall
  • LDL particle <258 Angstroms more atherogenic
  • Large LDL: Pattern A
  • Small LDL: Pattern B (bad)
  • Not measured in traditional lipid profiles
advanced lipid analysis lp a
Advanced Lipid Analysis: Lp(a)
  • Fairly large molecule but easily oxidized (more toxic)
  • Protein “tail” can stimulate blood clotting
  • Not affected by foods; appears to be genetic
  • Not affected much by “statins” or fibrates
  • Niacin, vitamin E combat tendency to be oxidized
  • Lowering LDL to <80-100 also minimizes toxicity
advanced lipid analysis berkeley heart labs vap nmr lipoprofile
Advanced Lipid Analysis(Berkeley Heart Labs/ VAP/ NMR LipoProfile)
  • Who Needs Advanced lipid analysis?
  • CHD, DM, or CHD equivalent
  • Metabolic Syndrome
  • Multiple Risk Factors
  • Family Hx premature CHD
  • Isolated low HDL cholesterol
lipid lowering drugs
Lipid Lowering Drugs

HMG-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)
lipid lowering drugs30
Lipid Lowering Drugs

Bile Acid Sequestrants

  • 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 drugs31
Lipid Lowering Drugs

Cholesterol Absorption Inhibitor: Zetia

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

Lipid-Regulating Agent: Omega 3 acid ethyl esters (Lovaza)

  • 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 drugs32
Lipid Lowering Drugs

Nicotinic Acid/Niacin

  • 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 (Niaspan)
lipid lowering drugs33
Lipid Lowering Drugs

Fibric Acid Derivatives/Fibrates

  • Very effective in reducing triglycerides (>400)
  • Increase HDL
  • Containdications: Gallbladder disease, hepatic disease, renal dysfunction
  • Increase LDL particle size but not quantity
  • Caution with statins
cholesterol control with foods and herbs
Cholesterol Control With Foods and Herbs
  • Fiber: Decreases LDL; increases HDL
  • Carrots/Grapefruit: Fiber and pectin (whole fruits most beneficial)
  • Avocado: monounsaturated fat
  • Beans: High in fiber, low fat; contain lecithin
  • Phytosterols: sesame, safflower, spinach, okra, strawberries, squash, tomatoes, celery, ginger.
  • Shiitake mushrooms: contain lentinan (25% reduction in animal studies)
  • Garlic, onion oil: lowers chol. 10-33%
  • Omega 3 fish oils
  • Red Yeast Rice: a natural substance that inhibits HMG-CoA reductase. Same ingredient in Lovastatin.
what is on the horizon
What Is On the Horizon?
  • Glabridin(licorice root/anise plants): Inhibits oxidation of LDL
  • Study of genetic alterations: cholesterol medications tailored to specific genetic profiles
  • Microsomal triglyceride transfer protein (MTP): the gene for MTP provides blueprint for production of the protein that helps assemble LDL. Those who carry 2 copies of a variant form of the gene had LDL levels 22% lower than those who had one or no copy of the variant. Some drug companies have already begun looking at MTP inhibitors to help lower LDL
  • Lecithin-cholesterol acetyltransferase (LCAT): an enzyme bound to HDL acts as a powerful antioxidant (reduce oxidation of chol.)
  • Thyroid hormones: Molecules similar to thyroid hormones could assist with weight loss and cholesterol reduction. 2 kinds of receptors that receive the hormone and pass its signal to the body.
cholesterol meds in the news
Cholesterol Meds in the News

Vytorin (Zocor + Zetia)

  • ENHANCE trial
  • New England Journal of Medicine
  • 720 FH patients over one year
  • Endpoint: Carotid artery intima-media thickness (CIMT) per ultrasound
  • Findings: Vytorin did not reduce CIMT compared to Zocor alone
  • TAKE HOME: It’s NOT just about the numbers
cholesterol meds in the news39
Cholesterol Meds in the News

Crestor

  • JUPITER trial
  • Does Crestor reduce major CV events in pts with no existing symptoms, low-normal LDL but higher CRP (c-reactive protein: marker of inflammation)?
  • Study D/C’d: early findings confirm reduced deaths and CV risks
  • The ONLYstatin shown to reduce Atherosclerotic plaque
other interesting studies
Other Interesting Studies

Atherosclerosis: Maternal smoking disturbs lipid profiles in adult offspring

  • Children ages 5-19 years (N=350)
  • Total chol. in children whose mothers smoked increased by 4.6mg/dl more each decade than total chol. levels in other children.
  • Could lead to an increase of 10mg over a 30 year period
other interesting studies41
Other Interesting Studies

The American Journal of Human Genetics :

Researchers have identified a novel genetic determinant of dyslipidemia and possibly CVD

  • Genotyping of 1955 volunteers with HTN
  • 25 serum and urine biochemical tests
  • Compared with genome-wide data from 2 other studies of individuals with DM
  • Found 2 proteins that were associated with a 6% increase in non-fasting serum levels of LDL chol.
other interesting studies42
Other Interesting Studies

American Journal of Medicine: Framingham Offspring Study suggests that at least HALF of U.S. citizens will develop dyslipidemia at some point in their lives

  • 4701 participants who were ages 30-54 yrs in 1971
  • During the following 30 years, 6 in 10 developed borderline-high (> 130) LDL and 4 in 10 developed high (>160) LDL
  • Study possible suggests that over 70% of Americans may be eligible for statin treatment at some stage of their lives
other studies the good news
Other Studies: The GOOD News

Nutrition,Metabolism and Cardiovascular Diseases:Drinking moderate amounts of beer appears to improve the lipid profile of healthy adults (esp. women)

  • 57 healthy Spanish volunteers (29 women)
  • Abstain for 30 day wash out period, then drink moderate (330ml for women, 660ml for men) amounts of beer for 30 days
  • HDL increased from 60.7-66.8 mg/dl in women and from 44.2-46.5 mg/dl in men
  • HDL decreased during the 30 day wash out period
other studies the good news44
Other Studies: The GOOD News

Journal of Nutrition: People with dyslipidemia can improve their lipid profiles by drinking cocoa

  • 160 volunteers drank 10.0, 19.5 or 26 g/day of cocoa or placebo
  • After 4 weeks, all groups but placebo had lower LDL levels
  • Most significant reductions in those with baseline LDL > 125
  • LDL decreased from 160 to 152
  • HDL increased from 57 to 62
  • Decrease in (apo) B and oxidized LDL cholesterol
  • Polyphenols in cocoa, tea, wine, fruit and vegetables may lead to decrease in atherosclerotic disease
case study 1
Case Study 1

35 YO male, a police officer. 5’11’’, weight=258 (BMI=35, obese)

Hx: hypertension, anxiety. Has taken testosterone supplements in past, now uses “body building” shakes.

Family Hx: Father, paternal grandfather-DM

Labs: FBS=79, TSH normal

case study 146
Case Study 1

Visit 1 Visit 2 Visit 3

TC= 167 164 158

TG=539 288 260

HDL= 18 24 28

LDL= ? 95 88

Tricor started Niaspan Levaza

(intolerant)

case study 2
Case Study 2

39 YO male (hasn’t been in for 2 years) c/o frequent urination, excessive thirst, blurred vision.

Hx: Mod. Obesity, BMI= 33

Family Hx: Mother DM

Meds: None

Non-fasting Accucheck= 297 (3 hrs PP)

case study 3
Case Study 3

62 YO Female with CHD s/p CABG wanted me to manage lipids. Also has Hypertension.

Meds: Plavix, Atenolol, lisinopril, Atorvastatin (stopped by pt.-myalgias)

Current labs:

TC= 248

Trig= 144

HDL= 41

LDL= 156

case study 350
Case Study 3
  • Changed atenolol to Coreg
  • Started Pravachol 20mg
  • Disease management/diet counseling
  • Resume walking 3-4 days/week
  • Repeat labs:

TC=190 Increase Pravachol …178

Trig= 130 to 40mg …128

HDL= 39 …41

LDL= 112 …98

framingham risk prediction score
Framingham Risk Prediction Score
  • 47 YO Female
  • Labs: TC= 178 Trig= 133 LDL= 110 HDL= 35
  • BP: 162/98
  • Hx: Smoker, non-diabetic

What is 10 Year CHD Risk?

framingham risk prediction score52
Framingham Risk Prediction Score
  • 47 YO Female
  • Labs: TC= 178 Trig= 133 LDL= 110 HDL= 35
  • BP: 162/98
  • Hx: Smoker, non-diabetic

What is 10 Year CHD Risk?

10% Compared to average of 5% for her age group

treatment of dyslipidemias medication comparison chart
Treatment of Dyslipidemias(Medication Comparison Chart)

Which Medication(s) slows coronary athersclerosis, lowers LDL, increases HDL but has no effect on triglycerides?

treatment of dyslipidemias medication comparison chart54
Treatment of Dyslipidemias(Medication Comparison Chart)

Which Medication(s) slows coronary athersclerosis, lowers LDL, increases HDL but has no effect on triglycerides?

Mevacor

ncep atp iii lipid goals
NCEP ATP III Lipid Goals

What is the recommended LDL goal for a healthy normo-tensive, non-smoking 46 year old male whose father died of a massive MI at the age of 52?

ncep atp iii lipid goals56
NCEP ATP III Lipid Goals

What is the recommended LDL goal for a healthy normo-tensive, non-smoking 46 year old male whose father died of a massive MI at the age of 52?

<130 for 2 risk factors

(age >45 and father with premature CAD)

final question
Final Question!!!!!

58 Year old Male (smoker)

Fam. Hx: Mother with NIDDM, sister died age 70 from MI

BP= 156/86 Pulse 78

Labs: TC= 310, TG= 250, HDL=29, LDL=156, FBS=88

  • What is Framingham 10 year Risk score?
  • Based on score, what is LDL goal?
  • Name 2 cholesterol medications (Brand) that would be most appropriate for his treatment.
final question58
Final Question!!!!!

58 Year old Male (smoker)

Fam. Hx: Mother with NIDDM, sister died age 70 from MI

BP= 156/86 Pulse 78

Labs: TC= 310, TG= 250, HDL=29, LDL=156, FBS=88

  • What is Framingham 10 year Risk score? 27%
  • Based on score, what is LDL goal? <100
  • Name 2 cholesterol medications (Brand) that would be most appropriate for his treatment. Niaspan, any “statin” except Mevacor, any of the combination meds
thank you
Thank You
  • Questions?
  • Glenda Summerville