HYPERLIPIDEMIA Dan O’Connell, MD Montefiore Family Medicine August 2004

METABOLIC SYNDROME Low HDL High Trig Obesity Elevated BP Glucose intolerance

RISKS TO HEALTH Hyperlipidemia Hypertension Diabetes Coronary Artery Disease Congestive Heart Failure

Natural History of Insulin Resistance Age 15 Acanthosis nigrans Age 23 ? PCO –insulin resistance, irreg period, irregular period, hirsutism, obesity Age 25 Dyslipidemia - HDL, Trig Age 30 Gestational DM Age 35 Hyperglycemia Age 40 Diabetes Age 45 Metabolic syn - HTN,DM, dyslipidemia, obesity Age 55 – Acute MI Age 58 Renal insufficiency, renal failure Age 61 vision loss, neuropathy, toe amputation Age 62 – Claudication 2 nd PVD, small CVAs Age 63 - CHF

PRE - JULY RISK>2 risk factors CAD or equiv 3-6 mo diet lifestyle modification Medication >190 GOAL <160 >160 GOAL <130 >130 GOAL <100

AFTER JULY RISK>2 risk factors CAD or equiv 3-6 mo diet lifestyle modification Medication >190 GOAL <160 >160 GOAL <130 >100 GOAL <70

CAD Equivalents AKA atherosclerosis Peripheral Vascular Disease Cerebral Vascular Disease Diabetes (based on 10 yr MI risk equiv of active CAD)

The Nordin Rule? “What do you think is the best goal for LDL?” “It should be less than the HDL.”

STATINS HMG CoA Reductase inhibitors Atorvastatin (lipitor) Simvastatin (zocor) Pravastatin (pravachol) Lovastatin (mevacor) Fluvastatin (lescol) Rosuvastatin (crestor) Risk – elevated LFTs, rhabdo ( CPK)

CASE 1 elevated LDL 42 yo in good health, no tob, no FMH Chol 279 LDL 185 HDL 45 Trig 135

CASE 1 elevated LDL 42 yo – after 2 mo diet, exercise Chol 289 LDL 195 HDL 45 Trig 135

Case 2 - LIPIDS 51 yo HTN, Quit tob last yr p 20 pk-yrs, FMH neg CHOL 260 LDL 155 HDL 35 TRIG 240

NON-HDL CHOLESTEROL Useful when triglycerides very high and LDL cannot be measured Normal triglyceride levels usually contribute 30 points to cholesterol Can calculate “treatable LDL” by: Non-HDL chol = (Total chol) – HDL LDL eq = Non HDL CHOL – 30 OR LDLeq = (CHOL – HDL) - 30

LDL eq CHOL 260 LDL 155 HDL 35 TRIG 240 LDL eq = (260-35) – 30 =195

DYDSLIPIDEMIA Trends in MI – CAD decreasing thru past 50 years, but now DM rapidly increasing 20 th century heart attack – HIGH LDL The beef and+tobacco MI 21 st century MI – LOW HDL, DIABETIC MI The insulin resistant metabolic syndrome MI

NON-HDL CHOLESTEROL CHOL 265 TRIG 400 HDL 35 LDL – unable to calculate LDL eq =?

Low HDL/ high triglycerides Fewer studies on morbidity mortality Statins increase 5-15% Niacin (Niaspan, slo-niacin) increase 10-20%

LIPIDS – case 3 62 yo DM, HTN, on Zocor 40 CHOL 160 LDL 95, HDL 50, trig 100 SGOT/SGPT 110/90 CPK 150

Other lipid meds Fibrates – lower triglycerides Gemfibrazole (lopid) 600 bid Fenfibrate (tricor) – fewer interaction with Statin then gemfibrazole Niacin 250mg – 4000 mg qd – raise HDL Causes flushing min Slo-niacin, niaspan Zetia 10 mg (ezetimibe) – decreased absorbtion Adjunct to statin, or when liver or rhabdo effects 2-5 YEAR RULE!!

Primary prevention vs secondary prevention

Low risk patients Scotland trial, ’96, coronary events measured Measured MI, death, CVA placebo vs statin No treatment 248/3210 =7.7% Treatment (pravastatin 174/3260 = 5.3% RRR? ARR? NNTT?

Low risk patients Scotland trial, ’96, coronary events measured No treatment 248/3210 = 7.7% Treatment (pravastatin) 174/3264 = 5.3% RRR 31% ARR 2.4% NNTT 100/2.4 = 42

Hyperlipidemia – effect of lifestyle change Low sat fat Whole grains, oats, barley (soluble fiber) 10 gm Plant sterols (Benachol margarine) 2gm Almonds 1 oz (30gm) Soy protein 20 gm 30% reduction in LDL (equivalent to statins) JAMA 7/23-30/03

PROVE-IT study Patients admitted for acute coronary syndrome Pravachol 40 (standard) vs Lipitor 80 (intensive) Coronary events (death, MI, CVA) Lipitor 22.4% Pravachol events 26.3%

PROVE-IT Lipitor 22.4% Pravachol 26.3% ?ARR ?RRR ?NNTT

PROVE-IT – COST ANALYSIS Lipitor 22.4% $1400/yr Pravachol 26.3% $900/yr ? Cost per avoided event

NNTT- assuming 30% reduction CAD riskWith RXARRNNTT= 1/ARR 8%5.6%2.4%42 10%7%3%33 15%10.5%4.5%22 20%14%6%17 50%35%15%7

Pediatric hyperlipidemia As per NCEP Diet therapy for LDL > 130 For > age 10, consider medication if >190 after 6 mo diet RX

Statins HMG coA Reductase inhibitors 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors Statins block (inhibit) an enzyme the body needs to produce cholesterol. As a result, LDL cholesterol levels in the blood go down, thereby lowering total blood cholesterol levels. Statins may also affect levels of certain clotting factors in the blood and lower the risk of clot formation. Lowering the risk of clot formation is important because clots can lead to heart attack or stroke. Statins also have anti-inflammatory effects that may help reduce the risk of coronary artery disease (CAD).

Statins Lower LDL 20-60% Elevate HDL 5-15% Studies with Pravastatin, simvastatin, lovastatin show 30-40% decrease in mortality from MI in pts with CAD Lipids return to baseline level 2-3 wks after d/c

Statins Most common side effects :Nausea, diarrhea, constipation, muscle ache, elevated LFTs (1-2%) Fatigue, loss of sense of well being at high doses Increased liver toxicity together with gemfibrazole or niacin Pravastatin not eliminated by P-450, less rhabdomyalysis Cerivastatin (Baycol)withdrawn from market 2001 due to 10x increased incidence of rhabdo, cases of renal failure

Statins Monitor LFTs at 6-12 weeks, then q6-12 mo if normal, or when other new medication added Document if no muscle ache; if + muscle ache, check CPK

Statins - cost DrugDoseCost Atovastatin (Lipitor) 10 mg 80 mg $65 $100 Lovastatin generic (Mevacor) 20 mg 80 mg $50 $180 Pravastatin (Pravachol)40 mg 80 mg $123 $122 Simvastatin (Zocor) 20 mg 80 mg $126 Fluvastatin (Lescol)20 mg 80 mg LA $50 $66 Rosuvastatin (Crestor) 10 mg 40 mg $70 $72