2006 AHA Recommends LDL < 70 as reasonable target for secondary

prevention Gender specific HDL targets. Men > 40, Women > 50

JUPITER trial: Benefit for statins in primary prevention, women and patients > 70 years

Metabolic syndrome = HIGH RISK SHARP trial: Statins benefit chronic kidney

disease HPS2 Thrive and AIM HIGH trials

The Critical Questions What evidence supports LDL goals for secondary

prevention? What evidence supports LDL goals for primary

prevention? What is the efficacy and safety of major cholesterol

drugs? Risk assessment tools Alternative treatment targets: APO B, Non-HDL Role of fibrates, niacin, ezetimibe, BAS

What is her risk of future cardiovascular disease? 56 y.o. female Former smoker Sister with ischemic stroke age 54 No family premature coronary artery disease BP138/76 Fasting glucose 109 Total cholesterol 209 HDL 42 Triglycerides 201 BMI 31

Risk Score Estimated Risk Framingham 2% Reynolds 6% Global CVD 10% QRISK 11% Lifetime Risk 39%

Berger. JACC. 2010; 55: 1169-1177.

Access at www.reynoldsriskscore.org

Wickramasinghe, R. Am J Cardio. 2009;103: 1174-1177

Use a coronary calcium score to reclassify patients with intermediate risk. DO reserve CAC testing for patients where results will likely alter management. DO discuss the CAC score in a way that is meaningful for patients DO encourage patients to pursue ideal cardiovascular health even if their score is 0 Do discuss the risk of radiation.

Polonsky,T. Cardiol Clin 30 (2012) 49-55Us

DON’t use to screen patients with symptoms of CAD

DON’T use to follow progression of CAC DON’T use to monitor lipid therapy DON’T use the CAC as an indication for

coronary angiogram

Polonsky,T. Cardiol Clin 30 (2012) 49-55.

Begin with a frank discussion

If BMI >26 recommend weight loss. Low CHO diet best for triglyceride ↓ and

HDL ↑ Lower HDL and triglycerides independent of

weight loss at 6 and 12 months. Atkins 18%↑ HDL, 28% ↓ in triglycerides. Similar to niacin and fibrates.

No change in LDL

Parik,P. JACC 2005 45:9. 1380-2387.

All diets increased HDL and reduced triglycerides

Biggest HDL increase with low carbohydrate diet. 9%

All diets reduced triglycerides 12-17%. How much weight loss? (5-10% of body weight)

Low fat diet reduced LDL 5% High protein lowered insulin levels 12%.

Insulin resistance is a cardiovascular risk factor

Sacks. NEJM 2009;360:859-873

Mediterranean diet reduces heart attack, death and stroke by 28-30% in high risk patients

What did they eat? Fish 3 times/week Beans 3 times/week Olive oil 4 tablespoons/day or 1 ounce walnuts/day 3 fruits a day (minimum) 2 vegetables a day (minimum) No red meat No commercially prepared cakes, cookies or pastries Limit dairy, processed meats 7 glasses of wine per week (if desired)

DOI: 10.1056/NEJMoa1200303 Feb. 23, 2013

AHA Recommends 150 minutes of moderate exercise/week “30 minutes/5 days per week”

Try a Pedometer 3000 steps in 30 minutes is moderate exercise 10,000 steps per day = Weight Loss

3 Grams of soluble fiber lowers LDL 2% 1 TBS = 2 grams soluble fiber 1 c. cooked Steel cut oats = 2 gm soluble fiber 1 apple = 1 gram soluble fiber

1. Recommend as part of the TLC diet 2. 1800 mg plant stanols daily 3. 9.2% LDL lowering 4. 9 % non-HDL lowering 5. No effect on HDL or triglycerides

Benechol Chews Heartwise Rice Milk Benechol Margarine Cholestoff

Maki,K.C. Nutrition 29:1 2013 (96-100)

Martin et al, Am J Cardiol 2012;110:307–313

Lloyd-Jones, D Circulation. 2010;121:586-613

High 10 Year Risk LDL < 7

High Lifetime Risk

LDL < 100

Low Risk LDL <115

O’Keefe. JACC 43:11(2004) 2142-2146

O’Keefe. JACC 43:11(2004) 2142-2146

My LDL GOAL ______ Current LDL ______ CHANGE LDL LOWERING Lose 10 lb. 5-8% Saturated Fat < 7% 8-10% 10 gm. Soluble Fiber/day 3- 5% Plant Stanols 1800 mg/day 5-10%___ TOTAL LDL LOWERING 20-30%

Martin et al. Am J Cardiol 2012;110:307–313.

Prescriber's Letter 2011;18(11):27112

50% still taking statins at 6 months Only 25% at 1 year Explain why you’ve chosen statin therapy Review risk assessment tool results Explain the plan Discuss side effects clearly Question specifically about aches before

starting a statin 8 week, 6 and 12 month followup visits

JUPITER showed ↑ risk of developing new onset diabetes (NOD) if risk factors present

2-4 risk factors for DM→ 14% NOD on atorvastatin 80 mg. FBG > 100 Fasting triglycerides > 150 BMI > 30 Hypertension

Waters, D. JACC 2013 61:2. 148-152.

FDA added Safety Label change Feb 2012 Can occur days to years after starting statins Average time to improvement after

discontinuing statin: 3 weeks Symptoms: Confusion, memory impairment,

amnesia

Bardwaj, S. Clinical Interventions in Aging 2013:8 47–59

Myalgia: Muscle soreness or weakness Myopathy: CK > 10,000 Rhabdomyolosis:

CK > 10,000 Worsening renal function Requiring IV hydration

McKinney, J. Am J Cardiol 2006;97[suppl]:89C–94C

Arca,M. Diab Metab Syndr Obes. 2011:4.155

Female Polypharmacy Vigorous exerciser Age > 80 Low BMI Drug-drug interaction Post major surgery/trauma Comorbidities (Diabetes, hypothyroidism) Genetic predisposition Vitamin D deficiency (<32)

Non-absorbed bile acid sequestrant (BAS) Safe in children > 10 years LDL lowering 18% Add on to statin or use in statin intolerance Contraindicated triglycerides > 500 Hgb A1c lowering of .5% or 14 points fasting

glucose Caution: take phenytoin, glyburide, OCP,

cyclosporine, levothyroxine, warfarin 4 hours prior

Non-HDL, APO B and LDL particle number important in patients with mixed hyperlipidemia, MetS, Type II DM and CKD

High 10 Year Risk Non HDL < 100, Apo B < 80

High Lifetime Risk Non HDL < 130, Apo B < 100

Total cholesterol minus HDL Example: 240 – 40 = 200 Non-HDL Cholesterol

Use when triglycerides are elevated. Advantage: No cost, measure non-fasting Better marker than LDL for atherogenic small

particles Likely to be included in ATP IV

Non HDL goal: LDL + 30

o

Otvos. Am J Cardio 2002; 90:8A. 22-29

Add-on to statins. Beneficial in MetS, DM, BMI > 26 LDL increase if triglycerides above 500 Caution: warfarin interaction with increased INR ↑creatinine occurs with fenofibrate. Lipid effects:

↓ Trig 35-50% ↓ LDL III 27% ↑ HDL 15-25% ↑ HS CRP 15-20%

Reduces triglyceride production New purified pharmaceutical brands (1860

mg EPA) 4 grams = 44 calories Possible prolonged bleeding time Lipid effects:

↓ triglycerides 26-47% ↑ LDL 10-47% ↑ HDL 11-14%

Niacin. Is there outcomes data? AIM-HIGH Heart Protection 2

Adding ER niacin/laropriprant to simvastatin did not significantly reduce risk of MI, CVA or angioplasty in secondary prevention

↓ LDL 10 mg, ↓triglycerides 33 mg, ↑HDL 6 mg Significant adverse effects: diabetic

complication, new onset DM, GI complications and bleeding, pneumonia (30 patients 1000)

Conclusion: “role of ER niacin needs to be reconsidered”

Statins and the Elderly Heart Protection Study: 25% reduction of

stroke, any age PROSPER. 20% reduction death from

CAD/MI. Men and women, average age 75 yrs. Frail elderly more likely to have myopathy

Lipid abnormalities with HIV ↓ LDL, ↓ HDL, ↑ Trig

Lipid effect of Protease inhibitors 28%↑ TC, 96% ↑ Trig

Treat with statins/fibrates/fish oil Statin, antiretroviral interaction Caution ritonavir, azoles, macrolides Use rosuvastatin , pravastatin, fluvastatin Ezetimibe is safe Niacin may worsen insulin resistance

Gutierrez. Arch Int Med. 2012;(172)12:909-919.

TC, LDL and triglycerides increase 20-35% in pregnancy

Colesevelam pregnancy category B, can be taken by nursing mothers

Statins pregnancy category X May inhibit placenta and embryo

growth Ezetimibe pregnancy category C Fenofibrate pregnancy category C

1. NKF: CKD Stages 3-5 is a coronary risk equivalent 2. Lipid abnormalities similar to Metabolic syndrome

1. Low HDL 2. Small, dense LDL 3. Elevated LDL particle number 4. Elevated triglycerides LDL goal 70 Calculate non-HDL C Use statins. They reduce CV events in Stage 3 and 4 CKD Safest statins—atorvastatin, simvastatin, fluvastatin. ↓ dose

risk of myopathy SHARP trial simvastatin and ezetimibe reduced CV events Fenofibrates. Dose reduction 50% if GFR 60-90, 75% if GFR

15-60. Will raise serum creatinine. NKF recommends gemfibrozil

LDL goal 70 Calculate non-HDL C. Goal 100 SHARP trial (simvastatin + ezetimibe) 17%

reduction in CV events Safest statins—atorvastatin, simvastatin,

fluvastatin. ↓ dose risk of myopathy Fenofibrates. Dose reduction 50% if GFR

60-90, 75% if GFR 15-60. Will raise serum creatinine. NKF recommends gemfibrozil

Decrease cholesterol absorption in the intestine and upregulates LDL receptors

Add on to statins or monotherapy LDL↓ 27% added to statin LDL ↓ 18% as monotherapy Lowers Non-HDL and Apo B Outcomes data? Side effect: Diarrhea. Rare myalgia, myopathy

or elevated ALT/AST

FDA no longer recommends routine liver function testing with statins. Baseline liver function testing only.

Repeat lipid panel as early as 6 weeks Appropriate to delay lipid panel for 3 to 4

months if more convenient

1. Assess risk accurately 2. Use a simplified treatment algorithm. 3. Start lifestyle changes at the first visit. 4. Recommend a mediterranean diet 5. Promote ideal cardiovascular health 6. Establish an LDL goal of <70 for high risk 7. Write out a lipid plan. 8. Use statins for high risk 9. Look at targets beyond LDL 10. Follow up at appropriate intervals