Hyperlipidemia Case File
Eugene C. Toy MD, Donald Briscoe, MD, FA AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA AFP, FACG
Case 35
A 56-year-old white man comes in for a routine health maintenance visit. He is new to your practice and has no specific complaints today. He has hypertension for which he takes hydrochlorothiazide. He has no other significant medical history. He does not smoke cigarettes, occasionally drinks alcohol, and does not exercise. His father died of a heart attack at age 60 and his mother died of cancer at age 72. He has two younger sisters who are in good health. On examination, his blood pressure is 130/80 mm Hg and his pulse is 75 beats/min. He is 6-ft tall and weighs 200 lb. His complete physical examination is normal. You order a fasting lipid panel, which subsequently returns with the following results: total cholesterol 242 mg/dl; triglycerides 138 mg/dl; high-density lipoprotein (HDL) cholesterol 48 mg/dl; and low-density lipoprotein (LDL) cholesterol 155 mg/dl.
⯈ What are the indications for statin therapy?
⯈ What other laboratory testing is indicated at this time?
⯈ What is the recommended management at this point?
ANSWER TO CASE 35
Hyperlipidemia
Summary: A 56-year-old white man with well-controlled hypertension is found to have elevated cholesterol on a screening blood test as part of a physical examination. He has no known history of coronary artery disease or of any coronary artery disease risk equivalent.
- Recommendations for statin treatment: American College of Cardiology I American Heart Association (ACC/ AHA) and National Institute for Clinical Evidence (NICE) guidelines recommend treatment with statins based on calculated risk using validated prediction rules.
- Further testing at this time: Blood glucose, creatinine, liver function tests, thyroid-stimulating hormone ( TSH).
- Initial management of his elevated cholesterol: Therapeutic lifestyle changes ( TLCs) with consideration for implementation of statin therapy.
ANALYSIS
Objectives
- Know the risk factors for cardiovascular disease (CVD).
- Know the new ACC/AHA and NICE recommendations for prevention of CVD.
- Know the previous Adult Treatment Panel (ATP) III guidelines for the diagnosis, evaluation, and management of hyperlipidemia.
- Be able to counsel patients on therapeutic lifestyle changes to lower their cholesterol levels.
Considerations
This case illustrates a 56-year-old white man with well-controlled hypertension and total cholesterol 242 mg/dL; triglycerides 138 mg/dL; HDL cholesterol 48 mg/ dL; and LDL cholesterol 155 mg/ dL. Based on the pooled cohort risk equation, his 10-year risk of atherosclerotic cardiovascular disease is 9.3% (based on his age, race, nonsmoking status, controlled hypertension, total cholesterol, and HDL level). Whether medication for cholesterol levels is initiated at this time is based on which of the current recommendations you follow; however, any medication regimen should be accompanied by therapeutic lifestyle changes such as weight loss, exercise, and diet.
Approach To:
High Cholesterol
DEFINITIONS
ACC/ AHA: American College of Cardiology and American Heart Association, which made joint recommendations for cholesterol management based on risk assessment in 2013.
ATP III: The third report of the National Cholesterol Education Program Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, released in 2002.
HDL CHOLESTEROL: High-density lipoprotein cholesterol.
LDL CHOLESTEROL: Low-density lipoprotein cholesterol.
NICE: National Institute for Clinical Excellence based in the United Kingdom, which made recommendations for cholesterol management based on risk assessment.
STATIN: Medication in the β-hydroxy-β-methylglutaryl-coenzyme A (HMGCoA)- reductase inhibitor class. These are the most widely used medications for lowering LDL cholesterol.
CLINICAL APPROACH
Treatment recommendations for high cholesterol are evolving. Previous recommendations were based on the third report of the National Cholesterol Education Program Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, otherwise known as ATP III, released in 2002. New recommendations developed in 2013 by the ACC/ AHA and also recommendations by the NICE developed in the United Kingdom are different from the ATP III and vary in their recommendations from each other. Both new recommendations use risk assessment tools in order to determine if an individual should be treated with a cholesterol medication. The American Academy of Family Physicians (AAFP) later released its qualifications to the new guidelines. Like many changing areas of medicine, the current guidelines for treatment of high cholesterol are actively changing and providers have the opportunity to decide which recommendations to use in collaboration with patients on joint decision making. We will provide the guidelines for comparison and the AAFP qualifications to the new guidelines.
It is important to remember that cholesterol is not a disease. High cholesterol is a risk factor for coronary heart disease (CHD). As such, an individual's cholesterol levels must be interpreted in the context of their overall risks for CHD. The recommended intensity of the statin medication should be proportionate to their risk of CHD: the higher one's risk, the higher the intensity of the statin therapy. It is also important to note that for patients that do not tolerate high-intensity statins, using a lower-intensity statin would still provide some cardiovascular benefit, if the lower-intensity statin can be tolerated.
As mentioned earlier, the ATP III guidelines focused on risk factors to determine treatment and there were set goals for LDL levels to guide treatment. New recommendations no longer recommend treating to a goal LDL and use risk assessment scores in order to determine who should be treated with statin therapy. The classification and management guidelines for ATP III are seen in Table 35-1.
The ACC and AHA have developed guidelines for selecting patients for statin therapy. Statin therapy is recommended in all patients with known cardiovascular disease or LDL greater than 190 mg/ dL. Statin therapy has been recommended for four additional groups of adults greater than or equal to 21 y ears:
• Patients less than or equal to 75 years with clinical CVD
• Patients with LDL cholesterol greater than or equal to 190 mg/ dL
Data from ATP III report.
• Patients aged 40 to 75 with diabetes and LDL cholesterol greater than or equal to70mg/dL
• Patients aged 40 to 75 with 10-year CVD risk greater than or equal to 7.5% and LDL greater than or equal to 70 mg/ dL
It is reasonable to consider statin therapy after evaluating benefits versus risks in patients with clinical CVD older than 75 years, diabetic patients less than 21 years or greater than 75 years, or with patients whose atherosclerotic CVD (ASCVD) 10-year risk is between 5% and less than 7.5%, and 40 to 75 years with LDL 70 to 189 mg/ dL and without diabetes or clinical CVD. Numerous risk calculators are available online. By determining the individual risk, one can then determine the appropriate management for the patient.
The NICE recommendations for the primary prevention of CVD use the QRISK2 risk assessment tool and begin statin therapy for adults with greater than or equal to 10% 10-year risk. Statin therapy should begin with focus on high intensity and low cost. NICE recommends offering atorvastatin 20 mg for primary prevention if 10-year risk greater than or equal to 10% and to people aged 85 or older. Monitor statin therapy with liver function tests at baseline, at 3 months, and at 12 months. If statin is contraindicated or not tolerated, ezetimibe can be offered. For patients with known CHD, treatment should be started with atorvastatin 80 mg. NICE recommends against use of fibrates, nicotinic acid, anion exchange resins, or omega-3 fatty acids for primary or secondary prevention.
The ACC/AHA and NICE recommendations require risk assessment in order to determine the patient's risk of coronary disease and need for lipid-lowering medication. Several risk assessment tools are available including Framingham risk estimation, QRISK and ASSIGN, pooled cohort equations, and coronary artery calcium scoring. NICE recommends QRISK2 and ACC/ AHA uses pooled cohort equations, which may overestimate risk. Assessment scores can overestimate or underestimate risk in certain groups, so use of the appropriate assessment tool for the patient is important. There is insufficient data to support one assessment tool over another for predicting cardiovascular risk. Comparison of ACC/AHA and NICE guidelines are provided in Table 35-2.
The AAFP released its clinical practice guideline with endorsement of the AHA/ACC recommendations, with qualifications, in June, 2014. The key recommendations are listed in Table 35-3. The qualifications listed by the AAFP were that the CVD risk assessment tool has not been validated and may overestimate risk and a cutoff of 7.5%, rather than 10%, will significantly increase the number of patients on statins. Also, many of the recommendations were based on expert opinion, although some points were evidence based, and 7 out of 15 members of the guideline panel had conflicts of interest.
Evaluation
When high blood cholesterol is identified, an investigation should be performed to evaluate for secondary causes of dyslipidemia. Included among these causes are
Abbreviations: ACCJAHA, American College of Cardiology/American Heart Association; LDL-C, low-density lipoprotein
C; NICE, National Institute for Health and Clinical Excellence.
Data from Dynamed, NICE, and ACCIAHA guidelines.
diabetes, hypothyroidism, obstructive liver disease, and chronic renal failure. Consequently, a reasonable laboratory workup includes fasting blood glucose, TSH, liver enzymes, and a creatinine level. Certain medications, including progestins, anabolic steroids, and corticosteroids, also can result in elevated cholesterol. Consideration should be given to changing or discontinuing these when possible.
Management
TLCs are the cornerstone of all treatments for hyperlipidemia. All patients should be educated on healthier living, including dietary modifications, increased physical activity, and smoking cessation. Weight reduction should be encouraged.
Specific dietary recommendations include limiting trans-fatty acid intake to less than 1 % of total calories, limiting saturated fats to less than 7% of total calories, replacing saturated fats with polyunsaturated fats, and have a total intake of less than 200 mg/ d of cholesterol. Total dietary fat should be kept to no more than
Abbreviations: ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein C.
Data from AAFP Clinical Practice Guideline on Cholesterol.
35% of total calories, with less than 10% polyunsaturated fat. AHA diet and lifestyle modifications include balancing calorie intake and physical activity to achieve or maintain healthy body weight, consuming a diet rich in vegetables and fruits and choose whole-grain, high-fiber foods, consume fish, especially oily fish, at least twice a week, minimize added sugars and sugary beverages, choose low-salt foods, and consume alcohol in moderation. The addition of dietary soluble fiber and plant stanols/sterols can be beneficial as well. Soluble fiber 10 to 25 g and of plant stanols/sterols 2 g can be added to reduce CVD and CHD risk. Referral to a dietician may be helpful as well. When TLC is instituted, regular follow-up must be arranged.
Pharmacotherapy may be considered in patients with ASCVD risk greater than 7.5% for ACC/AHA and 10% for NICE. TLC should continue to be reinforced and encouraged even when starting medications. In someone with known CHD, statin therapy is recommended in all guidelines. The first-line pharmacotherapy for LDL cholesterol reduction is a statin. Statins not only reduce LDL cholesterol but also reduce the rates of coronary events, strokes, cardiac death, and all-cause mortality. Ezetimibe is recommended as the second therapy for patient who cannot tolerate any level of statin or have contraindications. A list of medications available for treatment of hyperlipidemia is included on Table 35-4.
Cholesterol treatment is an example where new recommendations can create controversy in the management of chronic disease. The recommendations for evaluation, treatment, and ongoing management of high cholesterol have changed significantly over recent years with a focus on risk assessment. New development of treatments will also lend to ongoing changes in the new future.
Data from ATP Ill report, ezetimibe product information, and Sullivan, Olsson AG, Scott R, et al.
CASE CORRELATION
- See Cases 20 (Chest Pain) and 30 (Hypertension).
COMPREHENSION QUESTIONS
35.1 A 62-year-old smoker with a known history of CHD presents for establishment of care. He has normal blood pressure. His LDL cholesterol is 105 mg/ dL, HDL cholesterol is 28 mg/ dL, and total cholesterol is 170 mg/dL. According to the NICE guidelines, what medication therapy should be initiated at this time?
A. Ezetimibe
B. Atorvastatin
C. Niacin
D. Gemfibrozil
35.2 A 55-year-old woman presents to your office for follow-up. She was discharged from the hospital 1 week ago following a heart attack. She has quit smoking since then and vows to stay off cigarettes forever. Her lipid levels are total cholesterol 240 mg/dL, HDL 50 mg/dL, LDL 150 mg/dL, and triglycerides 150 mg/ dL. Which of the following is the most appropriate management at this time?
A. Institute therapeutic lifestyle changes alone.
B. Institute therapeutic lifestyle changes and start on a statin.
C. Start on a statin.
D. Institute therapeutic lifestyle changes and start on a statin and nicotinic acid.
35.3 A 48-year-old man with no significant medical history and no symptoms is found to have elevated cholesterol at a health screening. Which of the following tests is part of the routine evaluation of this problem?
A. ECG
B. Stress test
C. Complete blood count (CBC)
D. Thyroid-stimulating hormone
ANSWERS
35.1 B. This patient has known CHD and should be started on statin therapy.
35.2 B. This patient has known CHD, documented by her recent myocardial infarction. All guidelines recommend therapeutic lifestyle changes as an integral part of care. With known CHD, statin therapy is also indicated. ACC/AHA guidelines would recommend high-intensity statin therapy.
35.3 D. Hypothyroidism is a potential cause of secondary dyslipidemia. A TSH is a reasonable test to perform in this setting. There is no indication to screen for CHD with an ECG or stress test in this asymptomatic person. Other tests to perform could include fasting blood glucose, liver enzymes, and a measurement of renal function.
CLINICAL PEARLS
⯈ Lipid levels must always be interpreted in the context of the individual's overall risk factors for CHD.
⯈ Statins have the best data to support improvement in outcomes that are clinically significant, such as heart attacks, strokes, and death. Unless there is a contraindication, a statin should be the first medication used for cholesterol reduction.
⯈ Remind patients who are taking lipid-lowering medications that lifestyle modifications are still necessary. Medications are not a substitute for a healthy lifestyle.
REFERENCES
American Academy of Family Physicians Clinical Practice Guideline: Cholesterol. Available at: http:// www.aafp.org/patient-care/ clinical-recommendations/all/ cholesterol.html. Accessed May 12, 2015.
Grundy SM, Cleeman JI, Merz CN, et al. NCEP report: implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227-239.
Hypercholesterolemia (2015, April 27). In DynaMed Plus [database online]. EBSCO Information Services. Available at: http://dynamed.com/. Accessed May 12, 2015.
National Cholesterol Education Program. The third report of the NCEP Expert Panel on the detection, evaluation and treatment of high blood cholesterol in adults. Item no: 02-5215; 2002.
National Institute for Health and Care Excellence (NICE). Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. BM]. 2014 Jul 17;349:g4356.
Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/ AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology I American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 suppl 2):Sl-S45.
Rader DJ, Hobbs HH. Disorders oflipoprotein metabolism. In: Kasper D, Fauci A, Hauser S, et al., eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY : McGraw-Hill Education; 2015. Available at: http://accessmedicine.mhmedical.com. Accessed May 25, 2015.
Sullivan D, Olsson AG, Scott R, et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA. 2012;308(23 ):2497-2506.
Van Horn L, McCain M, Kris-Etherton PM, et al. The evidence for dietary prevention and treatment of cardiovascular disease.] AM Diet Assoc. 2008 Feb;108(2):228-331.
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