1. Hyperlipidemia: Management of Patients in the Primary Care Setting
Lauren A. Winkler, DNP, RN, FNP-BC

2. Statistics
Dyslipidemia is one of the key risk factors for development of CHD
31.7% of Americans have elevated serum cholesterol levels
1 in 3 Americans have elevated LDL levels
31 million Americans have total cholesterol valuesof 240mg/dl or greater and are considered at high risk of CHD
39.8% of adult Indiana state residents have elevated cholesterol levels

3. Cholesterol Pathophysiology
A type of lipid
Essential components to human cell membranes
Precursor in steroid hormone and bile acid metabolism
Transportation of Cholesterol in the form of lipoproteins
5 Types of Lipoproteins
LDL (Low Density Lipoprotein)
HDL (High Density Lipoprotein)
VLDL (Very-low-density Lipoprotein)
IDL (Intermediate-density Lipoproteins)
Dietary Apolipoproteins

4. Types of Lipoproteins
LDL (Low Density Lipoprotein)- Prominent role in CVD risk!
60-70% of circulating total cholesterol
HDL (High Density Lipoprotein)
20-30% of total cholesterol
VLDL (Very-low-density Lipoprotein)
10-15% of total cholesterol
IDL (Intermediate-density Lipoproteins)
Apolipoproteins
6 major classes
Apo B- increased levels linked to heart disease risk

5. Triglycerides Type of Lipid Store unused calories
Provide energy to body
Circulate body via transportation by lipoproteins
Biomarker for cardiovascular risk

6. Dyslipidemia A result of abnormal lipoprotein metabolism
Elevated cholesterol level increases risk for:
Atherosclerosis
Coronary Heart Disease
Presence of atherosclerosis qualifies as high risk for:
CHD
Symptomatic CAD
PAD
AAA

7. Primary Etiology of dyslipidemia
Genetics
Single gene mutations result in faulty apolipoproteins, receptor, or enzyme resulting in disturbance of production and clearance in LDL, HDL, and triglycerides.
Suspect in patients with premature CHD or with family hx of ASD and total cholesterol >240

8. Familial hypercholesterolemia
Two types:
Heterozygous
Common (1:250)
Homozygous
Rare (1:160, million)
LDL >600
Untreated die in 20’s
Treated, CAD in 30’s

9. SECONDARY Etiology of dyslipidemia
Diet and exercise play a role in the cause and treatment of lipid disorders; Sedentary lifestyle.
Diet: saturated fats and trans-fatty acids, caloric excess, alcohol.
Obesity: associated with elevated triglycerides, physical inactivity with low HDL.
Endocrine disorders
Renal disorders
Hepatic disorders
Immunologic disorders
Medications

10. Drugs associated with dyslipidemia
Diuretics
Beta blockers
Anabolic steroids
Corticosteroids
Estrogens and androgens
Retinoids
Cyclosporine
Protease inhibitors
Atypical antipsychotics

11. Major risk factors for dyslipidemia
Overweight/ Obesity –> most predictive of dyslipidemia
Family hx (parent w/ TC >240)
Family hx of premature CHD
Diabetes Mellitus
Metabolic Syndrome*
Cigarette Smoking
Hypertension
Low HDL (<40)
Age: males > 45, females >= 55

12. Cholesterol Screenings
Pediatrics
Age 2-8yr only if risk factors for premature CVD
Once between age 9- 11yr
Once between age yr
Adults
Every 4-6 years in patients aged without ASCVD
ACC/AHA 2013
Previously- dependent upon age, sex, risk factors

13. ATP III LDL, Total, and HDL Classification
LDL Cholesterol (mg/dl)
< Optimal
Near/Above Optimal
Borderline High
High
> Very High
Total Cholesterol (mg/dl)
< Desirable
200– Borderline high
> High
HDL Cholesterol (mg/dl)
<40 Low
>60 High (good)

14. ATP III LDL, Total, and HDL Classification
LDL Cholesterol (mg/dl)
< Optimal
Near/Above Optimal
Borderline High
High
> Very High
Total Cholesterol (mg/dl)
< Desirable
200– Borderline high
> High
HDL Cholesterol (mg/dl)
<40 Low
>60 High (good)

15. Updated Treatment Guidelines
2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults
Lack of evidence to support treating to LDL-C or non-HDL-c targets
Calculate 10-year ASCVD risk using the Pooled Cohort Equations Cardiovascular Risk Calculator
Focus on ASCVD risk reduction: 4 Statin benefit groups

16. Statin Benefit Groups Patients with clinical ASCVD
Patients with primary elevations of LDL-C >190 mg/dl
Patients with diabetes aged years with LDL-C mg/dl and without clinical ASCVD
Patients without clinical ASCVD or diabetes with LDL-C mg/dl and estimated 10-year ASCVD risk .7.5%

17. (ACC/AHA, 2013)

18. CV Risk Assessment Calculation
ACC/AHA 2013 ASCVD Risk Calculator
(ACC/AHA, 2013)

19. 1. Patients with Clinical ASCVD
Includes:
Acute coronary syndromes
History of MI
Stable or unstable angina
Coronary or other arterial revascularization
Stroke or TIA
Peripheral arterial disease presumed to be of atherosclerotic origin
Age < 75yr and no safety concerns: High-intensity statin
Age >75 yr or safety concerns: Moderate-intensity statin

20. 2. Patients with primary elevations of LDL-C >190 mg/dl
Rule out secondary causes of hyperlipidemia
Age > 21yr: High intensity statin
Goal of 50% reduction in LDL-C
LDL-C lowering non-statin may be considered to further reduce LDL-C

21. 3. Patients aged 40-75 yr with diabetes and LDL-C 70-189mg/dl AND without ASCVD
Moderate intensity statin
Consider high-intensity statin when > 7.5% 10yr ASCVD risk
Adults <40yr or >75 or with LDL<70mg/dl: evaluate risks/benefits/patient preferences when deciding to initiate, continue, or intensify statin therapy

22. 4. Patients without ASCVD or Diabetes with ldl-c mg/dl and estimated 10-year ASCVD risk > 7.5%
Calculate risk assessment every 4-6 years in those not receiving statin therapy
Re-emphasize heart-healthy lifestyle habits and:
Adults 40-75yrs with calculated 10-yr ASCVD risk of >7.5%: Moderate or high-intensity statin
Calculated 10-yr ASCVD risk of 5 - < 7.5%: Consider moderate- intensity statin
Initiation of statin therapy may be considered for adults with LDL-C > 160mg/dl or other evidence of genetic hyperlipidemias, family history of premature ASCVD, hs-CRP> 2.0mg/L, CAC score > 300 Agatston units

23. Low, Moderate, and High Intensity Statins
Low Intensity
Moderate Intensity
High Intensity
Daily dose lowers LDL-C on average by <30%
Daily dose lowers LDL-C on average by approx. 30- <50%
Daily dose lowers LDL-C on average by approx. >50%
Simvastatin 10mg
Pravastatin 10-20mg*
Lovastatin 20mg*
Fluvastatin 20-40mg
Pitavastatin 1mg
Atorvastatin 10*-20mg
Rosuvastatin 5-10*mg
Simvastatin 20-40mg*
Pravastatin 40*-80mg
Lovastatin 40mg*
Fluvastatin XL 80mg
Fluvastatin 40mg BID*
Pitavastatin 2-4mg
Atorvastatin 40-80mg*
Rosuvastatin 20-40mg*
(ACC/AHA, 2013)

24. Statins: LDL Lowering Rates
Lovastatin
Mevacor
20mg=29%
40mg=31%
80mg=48%
Pravastatin
Pravachor
10mg=19%
40mg=34%
Simvastatin
Zocor
10mg=28%
20mg=35%
40mg=40%
Fluvastatin
Lescol
20mg=17%
40mg=23%
80mg=33%
Atorvastatin
Lipitor
10mg=38%
20mg=46%
40mg=51%
80mg=54%
Rosuvastatin
Crestor
5mg=43%
10mg=50%
20mg=53%
40mg=62%
Pitavastatin
Livalo
1mg=30%
2mg=36%
4mg=45%
Contraindications: Active or chronic liver disease, pregnancy (Cat.X), lactation
Use with caution: Age >75yr, concomitant use of cyclosporine, erythromycin, itraconazole, ketoconazole, fibric acid, diltiazem, verapamil, fluoxetine, nefazodone, gemfibrozil, niacin, antifungal agents

25. STATINS Adverse effects
Recheck fasting lipids 4-12 weeks after statin initiation, then every 3-12 months
Doses should be adjusted at 6-week intervals
Baseline LFTs: If normal, no longer need to monitor LFTs on scheduled bases- clinician judgment
Baseline CK measurement may be warranted if increased risk
Advise patient to stop therapy and order creatinin kinase if patient reports muscle discomfort, weakness, or brown urine.
Decrease dose when 2 consecutive values of LDL-C are <40mg/dl
Pravastatin and Rosuvastatin metabolism are least affected by other drugs.
Atorvastatin and Fluvastatin do not requiring renal dosing
Do not take at same time as grapefruit juice
Evening vs. morning dosing?
Adverse effects
Elevated hepatic transaminase
Myopathy
Upper & lower GI complaints
Use with anticoagulant may increase prothrombim time
Older females: new onset diabetes?

26. Management of Hyperlipidemia
Heart Healthy Lifestyle Habits
Emphasize reduction in saturated fat & cholesterol
Encourage moderate physical activity
Consider referral to a dietitian
Healthy food changes
Weight reduction
Physical activity
Smoking cessation
Limit alcohol

27. Ezetimibe (zetia) First-line non-statin medication therapy to consider
Zetia: 10 mg once daily
Effects: 18% LDL decrease % HDL increase
8% TG decrease
(25% LDL decrease when added to statin)
Contraindication: Hepatic insufficiency
Pregnancy category C
Adverse effects: Upper & lower GI complaints, myopathy, fatigue
Ezetimibe + simvastatin = Vytorin
Ezetimibe + atorvastatin =Liptruzet
**No indication of improved outcomes with ezetimibe

28. Bile Acid Sequestrants
Cholestyramine (Questran Light): One 5-g packet or scoop 1-2 times/day (max 4-6 packs or scoops/day in 2-3 divided dose)
Colestipol (Colestid): 5-g packet or scoop 1-6 pkts/scoops per day in divided doses or
Tablets: 2-g 1-2 times/day and increasing by 2-g 1-2 times/day at 1-2 month intervals (max 16-g/day)
Colesevelam HCL (Welchol): 3 tabs BID (4-6 tabs daily if addition to statin)
Lipid effect LDL decrease 15-30%
HDL increase 3-5%
TG no change or increase
Contraindications: Familial dysbetalipoproteinemia
Caution: Triglycerides>300
Pregnancy Category C
Side Effects: Constipation, flatulence, nausea, decreased vitamin/medication absorption, elderly=risk of fecal impaction

29. Nicotinic acid Effect: Niaspan Labs – LFT, BG, & uric acid
Lowers total cholesterol and triglycerides
Increases HDL (22-26%)
Niaspan
>16 years; 500 mg HS for 4 weeks, then
1 g daily for weeks 5-8, then titrate to patient response & tolerance; do not increase by more than 500mg in a 4 week period; max 2g/day
Labs – LFT, BG, & uric acid
Caution - Gout, DM, hyperuricemia, pregnancy category C
Side Effects-Flushing, hypotension, nausea, gout, elevated blood sugar levels, hepatotoxicity

30. Fibric Acid Derivatives or fibrates
To lower serum triglycerides
Lipid effects LDL decrease 5-20%
HDL increase 10-20%
TG decrease %
Gemfibrozil: 600mg BID 30 mins before AM & PM meals
Fenofibrate (Tricor, Lipofen, Lofibra): mg daily; 6-8 wk intervals (max 160mg/day)
Fenofibric acid (Fibricor, Trilipix): mg PO daily; adjust dose q4-8 weeks
Labs- Liver function tests
Contraindications- Severe renal or hepatic disease
Caution-Hx gallstones; increased risk of rhabdomyolysis with statins; potentiates effects of anticoagulants
Side Effects-Dizziness, dyspepsia, diarrhea, blurred vision

31. Omega-3 Fatty Acids (Lovaza, Vascepa)
Combination of EPA and DHA omega-3 fatty acids, 1 gram capsules
Adjunct to diet
Only for severe hypertriglyceridemia (>500mg/dl)
Reduces triglycerides 45%
Raises HDL 9.1%
Raisess LDL 44.5%
Dosage: 4gm/day
Caution: fish and shellfish allergies, may increase bleeding times
Side effects: Belching, “fishy” taste in mouth

32. PCSK9 Inhibitors Praluent (alirocumab) Repatha (evolocumab)
Mechanism of action: PCSK9-specific antibodies block degradation of LDL receptors in the liver, causing the liver to clear plasma levels of LDL-C
Indications:
Goals not achieved on maximally tolerated statin and ezetimibe for secondary prevention or familial hypercholesterolemia
Not recommended for use in primary prevention patients in the absence of familial hypercholesterolemia*
Dosing:
Repatha (evolocumab): 140mg SC q2wk / 420mg SC qmonth [~$14,100/year]
Praluent (alirocumab): 75mg SC q2wk [~$14,600/year]