Treatment of Hyperlipidemia

Case 1. A patient with CAD and a severe LDL elevation.

A 54 y.o. woman who is s/p stent placement 4 years ago returns for yearly evaluation. Is clinically stable. Lipid profile documents Total Chol of 220, HDL is 35, Triglycerides are 225, LDL is calculated as 140. Current medications include simvastatin 80mg/day, aspirin 325 mg/day, Atenolol 50 mg/day. Other risk factors include hypertension, ex-smoker, mild obesity.

High Risk Patients: The National Cholesterol Adult Treatment Panel III defines high-risk patients as those with CHD or risk equivalent ( Type II diabetes, Peripheral Vascular Disease or Framingham 10 Year risk of > 20%).

Primary goal is LDL < 100mg/dL. but a goal of < 70mg/dL is suggested for high risk CAD patients such as those with diabetes or multiple risk factors. Secondary goals include Triglycerides < 200 mg/dL and HDL > 40, the higher the better. Control of other risk factors is also indicated.

Case Discussion: In this patient, the simvastatin, even at 80 mg per day, is not sufficient to meet the LDL goal of < 70 mg/dL. An initial intervention would be to switch to a more potent statin, either atorvastatin 80 mg/day or rosuvastatin at 40 mg/day. If the LDL goal at 1 month follow is not reached, consider combination therapy by adding either ezetamibe 10 mg/day which will lower LDL an additional 10-20% or niacin (or Niaspan) which at an eventual starting dose of 1500 mg/day will lower LDL roughly 8-10% but also increase HDL by 20% and lower triglycerides. Treatment of his obesity with a calorie-restricted diet and a walking program will also help in the long term but will not have substantial LDL effects in the short-term.

Case 2. Middle-aged male with Metabolic Syndrome.

A 54 y.o. man is seen by his Internist for general preventive care. Cardiac risk factors include a positive FH (for premature CAD and Type II diabetes) along with borderline hypertension, and mild obesity (Ht 5’8", Wt 178 lbs, BMI 27.4,Waist 40"). Lipid profile includes Tot Chol of 190, HDL 28, Triglycerides 210, LDL calculates at 120. BP is 138/88, fasting glucose is 111.

Discussion of case: This patient does not qualify as a "high-risk" patient by NCEP Guidelines because there is no known vascular disease or diabetes, yet, in my opinion, he constitutes a preventive emergency. Technically, he qualifies as being at moderate risk, and has "Metabolic Syndrome" by having 5/5 characeristics of the 3/5 required to diagnose this syndrome (Waist> 40",HDL < 40, Triglycerides >150, BP >130/85, gluc > 110). Using the Framingham risk calculator his 10 year risk of death/MI calculates at 10% but the Framingham score does not incorporate his family history of premature CAD, his borderline glucose level, nor his obesity. Thus, his risk is probably higher than 10%. The NCEP Guidelines would suggest that his LDL of < 130 is adequate but many experts would further qualify his level of risk by considering a high-sensitivity C Reactive Protein (hsCRP), an electron beam calcium score, a carotid ultrasound looking for intimal thickening, or a simple exercise stress test. A positive measure on any of these should lower the threshold for statin use.

The NCEP recommends that prior to medication use, "TLC" (therapeutic lifestyle changes) should be instituted for metabolic syndrome. These include a diet that is low in saturated fat and cholesterol, and a diet that is hypocaloric to help induce weight loss. An increase in physical activity is also recommended, generally in the form of a walking program. If the patient is good with numbers and can keep dietary records you can make a calorie recommendation. Daily maintenance calories can be estimated by multiplying body weight in pounds by 12. Thus, to maintain weight, a 200 lb individual takes in 2400 cal/day. A pound of fat = 3600 calories, so if you can decrease daily calorie intake by 500 cal/day, one will lose 1 lb per week (7 x 500=3500 cal). Also note that walking a mile roughly = 100 cal. Pocket sized calorie counting handbooks are available at bookstores.

After TLC’s are instituted, and the patient is re-evaluated, physician should have a low threshold for pharmacologic treatment of all risk factors and aspirin therapy should be instituted.

Combination Lipid Lowering Therapy: Patients with severe LDL elevations, patients with mixed hyperlipidemia, and patients with severe triglyceride elevations often require combination lipid lowering therapy. For severe LDL elevations, the combination of statins, ezetimibe, and resins is often considered and niacin can be added as well. For mixed hyperlipidemias, statins may be combined with fibrates or niacin but these combinations should be carefully monitored for muscle symptoms and myositis, with measurement of CK enzymes. For severe hypertriglyceridemia, fibrates may be combined with niacin and/or fish oil. For complex cases, referral to our lipid clinic should be considered.

Reference:

Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 285(19):2486-97

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ. J Am Coll Cardiol. 2004 Aug 4;44(3):720-32.

COST EFFECTIVENESS OF LDL-CHOLESTEROL LOWERING DRUGS

Comments and Disclaimer: These estimates compiled by P.Ades MD in 2003-04 using the Costco Website for retail medication prices and medical literature estimates of LDL-Lowering effects. There was no industry support for this analysis.