Familial hypercholesterolemia, Frederickson type IIa is an autosomal dominant defect of the LDL receptor that results in increased serum cholesterol levels with normal triglyceride levels. Affecting 1 in 500 individuals, it is a common disorder (Ferri, 2009), but was ruled out due to the patient’s lack of family history and physical indicators. Physical manifestations of familial hypercholesterolemia are tendon xanthomas, arcus corneae and xanthelasmas. The full spectrum of familial-type hyperlipoproteinemias (Frederickson types I, IIa, IIb, III, IV and V) are often manifested by premature CAD and peripheral vascular disease, obesity, abnormal glucose tolerance, arthritic symptoms, gall bladder disease, hepatosplenomegaly, pancreatitis (especially in childhood) and recurrent abdominal pain (Ferri, 2009). The patient did not have any of these clinical findings.
Secondary hyperlipidemia can be caused by diabetes mellitus, hypothyroidism, glucocorticoid use or excess, chronic alcoholism, oral contraceptive use, renal disease or hepatic impairment (Ferri, 2009). All of these causes were ruled out via history (in the case of glucocorticoids, alchohol use and contraceptives) and by the patient’s initial screening lab work (DM, hypothyroid, renal and hepatic disease).
Other and unspecified hyperlipidemia is a diagnosis of exclusion. The patient’s history and exam did not closely fit the profile of the familial hyperlipoproteinemias, and secondary causes were ruled out. It is possible that the patient does have a genetic component to her elevated serum cholesterol levels. However, the treatment (focused on lifestyle and risk modification, lowering non-HDL cholesterol levels, increasing HDL levels, and lowering triglycerides) is the same in any case. Current treatment guidelines for high-, moderate- and low-risk individuals with high cholesterol indicate that therapeutic lifestyle modifications and medications should be chosen for their effects in each of these areas (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [ATP III], 2001, and Grundy, et al., 2004).
Problem list. Medical:
1) Hyperlipidemia (ICD-9 272.4).
2) Therapeutic Regimen Management, Ineffective, related to the patient’s non-adherance to medication therapy and exercise recommendations.
Wellness/strength diagnoses:
3) Health-Seeking Behaviors, related to patient’s continuing to seek care, follow up with labwork and visits, and seeking alternative and complementary treatments.
4) Therapeutic Regimen Management, Readiness for
Enhanced, related to the patient’s stated willingness to see dietician, make dietary modifications, and begin using fish oil supplements.
Plan
CAM Interventions
Per her request, the patient was started on fish oil supplements, 1,200 mg three times daily with meals. In addition to a brief review of low-cholesterol dietary measures in the office, she was referred to a nutritionist for more comprehensive culturally-appropriate dietary counseling in Spanish.
Level of evidence for the CAM interventions. Fish oil (also called omega-3 fatty acids, or alpha-linolenic acid) is recommended by the Natural Standard Research Collaboration (NSRC, 2008 March) to reduce triglyceride levels on a dose-dependent basis. This is a grade [A] recommendation, meaning that there is strong scientific evidence for this use. Fish oil has been shown to increase HDL levels. However, there is evidence to show that fish oil may also increased LDL levels by 5-10%. The American Heart Association recommends that individuals consume fatty fish (anchovies , bluefish, carp, catfish, halibut, herring, lake trout, mackerel, pompano, salmon, striped sea bass, albacore tuna, and whitefish) at least twice a week (NSRC, 2008, March 1). No specific mention is made of supplements or dosing for supplements specifically for hypertriglyceridemia in the information from NSRC. As the patient does not have hyertriglyceridemia, and does have a slightly increased LDL level, it will be important to monitor through follow up.
There is less evidence to support referral to a nutritionist for dietary advice. Thompson, et al. (2003) reviewed the outcomes of 12 studies in which dietary advice for lowering blood cholesterol was given by dieticians, primary care providers, and nurses vs. self help resources. The researchers found that dieticians were better at helping patients lower their blood cholesterol than doctors on a short-term basis, but there was no evidence that dieticians were more effective than self-help measures or nurses. The authors of this study caution that their review was limited by a small group of studies of varying design/strength. A recent review of 38 RCT’s conducted by Brunner, Rees, Ward, Burke, and Thorogood (2007) did find short-term improvement in diet for individuals at cardiovascular risk following dietary advice vs. no advice, so it is prudent to refer this patient, and to continue to emphasize dietary measures at each visit.
The patient was referred for dietary instruction in Spanish by an individual who would be able to take into consideration cultural differences in diet. No studies were found describing culturally-sensitive dietary education for lowering blood cholesterol. However, Hawthorne, Robles, Cannings-John, and Edwards (2008) recently conducted a meta-analysis of 11 studies involving 1,603 members of ethnic minority groups receiving culturally-sensitive education vs. “routine care” for type II diabetes. They found that there was short term improvement in blood sugar control and knowledge, but recommend further studies. The ATP III treatment guidelines from the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) emphasize dietary modification but do not specifically recommend dietician referral. Uphold and Graham (2003) recommend considering referral to a dietician as part of their guidelines for dyslipidemia (Level of evidence: expert consensus [D]).
Other CAM interventions. Although none of the following dietary supplements were mentioned by the patient or recommended to her, red yeast rice (Monascus purpureus), guggulipid (Commiphora mukul), and garlic (Allium sativum L.) have been evaluated for their efficacy in lowering LDL and triglyceride levels, and their effect on HDL levels. Red yeast rice (or Went rice) supplements are created by growing certain strains of yeast on red rice. This supplement has been used in China since approximately 800 A. D. The Natural Standard Research Collaboration (NSRC, 2008 January) lists red yeast rice use as a grade [A] recommendation, meaning there is strong scientific support for its use in lowering LDL and triglyceride levels (see also Heber, Yip, Ashley, Elashoff, Elashoff, & Go, 1999, and Lin, Li, & Lai, 2005). The NSRC emphasizes that conventional pharmacological measures are preferred for lowering cholesterol, due to the lack of regulation and standardization of commercially-available red yeast rice supplements. One strain of yeast in particular, monacolin K, inhibits cholesterol synthesis. It is also known as mevinolin or lovastatin, the active ingredient in Merck’s Mevacor (NSRC, 2008 January). In their review of CAM therapies for hyperlipidemia, Nies, Cymbala, Kasten, Lamprecht, and Olson (2006) caution that due to the monacolin K, patients taking red yeast rice may experience some of the same adverse affects as patients taking conventional statins. Red yeast rice should not be taken in conjunction with statins, or by individuals with hepatic or renal impairment. Caution should be used as red yeast rice supplements may contain varying amounts of the active ingredient.
Guggulipid is an extract from the resin of the mukul myrrh tree (Commiphora mukul) found in India; it is a traditional Ayurvedic treatment. Earlier Indian studies indicated that guggulipid supplements substantially lowered LDL and triglyceride levels and raised HDL levels, but a later RCT of patients eating Western diets did not confirm this, and in fact, showed a slight increase in LDL levels vs. placebo (Szapary, et al., 2003). More recent literature reviews have confirmed this finding (Sahni , Hepfinger, & Sauer, 2005; Nies, et al., 2006).
Garlic use in moderate hypercholesterolemia was recently studied in a randomized, controlled trial (Gardner, et al., 2007). The researchers trialed three different formulations of garlic and placebo found no statistically significant difference in LDL levels for any of the supplements. Nies, et al. (2006) reviewed one meta-analysis, a systematic review and several subsequent studies, and reported that garlic does not significantly affect cholesterol levels. The NSRC lists garlic use for high cholesterol as a grade [B] recommendation, meaning there is good scientific evidence for this use, however, the NLM/NIH MedlinePlus website states: “This remains an area of controversy. Well-designed and longer studies are needed in this area”(NSRC, 2008 February). Based on these studies and reviews, guggulipid supplements and garlic should not be recommended for this patient. Red yeast rice may be used with caution, and only if the patient is not taking Zocor concurrently.
Plan of care and CAM. Because the patient has borderline hyperlipidemia, the fish oil supplement use and the patient’s cholesterol labs will continue to be monitored. A diet low in saturated fats should be followed, as well as a regular exercise plan. These measures are appropriate for borderline hyperlipidemia in a low cardiovascular-risk patient (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [ATP III], 2001). The use of fish oil and culturally-sensitive patient education should be easily integrated into this plan.
Barriers and facilitators to implementation. One barrier to the use of fish oil supplements is the cost. A one-month supply of fish oil capsules at a local drug store costs $5.50, and may be as much as $15-50 at GNC stores. This may be perceived by the patient as expensive, as the Zocor was being provided via samples and the manufacturer’s free prescription drug program. The patient’s willingness to use dietary supplements and resistance to use of Zocor is a facilitator. Also, the supervised exercise regimen sponsored by Bethesda Clinic and local gyms is free of charge (a facilitator), although the limited schedule of the program may be a barrier with the patient’s full-time work schedule.
Other Interventions
How conventional interventions fit into the patient’s plan. When treating high cholesterol conventionally, patients are divided into high-, moderate- and low-risk groups based on Framingham cardiovascular risk factors and comorbidity (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [ATP III], 2001). For low-risk individuals like this patient, therapeutic lifestyle modification is a first-line treatment. Therapeutic lifestyle modification includes dietary measures such as limiting total fat intake to 30% or less of calories, polyunsaturated up to 10% of total calories, monounsaturated fat up to 20% of total calories, and saturated fats <7% of total calories, no more than 200 mg of cholesterol, and increasing fiber intake to 20 to 30 gm/day (Ferri, 2009). Regular exercise programs are also recommended (ATP III). Pharmacological measures include HMG-CoA reductase inhibitors (statins), bile acid sequestrants, nicotinic acid, fibric acids and cholesterol absorption inhibitors, depending on the lipid profile. All of these measures are evidence-based (using clinical trials, prospective epidemiological studies and meta-analyses), but the ATP III does not use a scale to specifically grade the individual recommendations. Rakel (2007) lists statins as level of evidence [A] for their ability to significantly reduce MI, stroke, coronary mortality and general mortality in both the primary care setting and hospitalized patients.
Nonpharmacological measures include the lifestyle modifications discussed above and a nutritionist consult (see CAM interventions). Specific dietary measures to improve her cholesterol profile may be considered: Increasing use of oat cereal and decreasing use of butter. Oat cereal vs. wheat cereal has been studied in overweight men; the oat cereal was found to decrease LDL levels without decreasing HDL levels or increasing triglycerides (Davy, et al., 2002). Specially-formulated margarine vs. butter (as spreads and in baked goods) was studied in families in the Dallas-Fort Worth area. Families who used the margarine spread had a statistically significant decrease in LDL levels (Denke, Adams-Huet, & Nguyen, 2000). Neither of these trials were placebo-controlled or blinded, although subjects were randomly assigned to treatment groups. The level of evidence for recommendations based on these studies is not strong [B-C], but the patient would probably benefit from using high-fiber oat cereals and low-fat margarine spreads.
Implications of conventional interventions for the prescribed CAM. It appears that for this patient, conventional interventions via therapeutic lifestyle modifications (diet and exercise) will be adequate. It is possible that the patient was resistant to using Zocor because it was prescribed before she had a chance to attempt lifestyle modification to lower her borderline high cholesterol. CAM treatment (in the form of fish oil supplements and culturally-sensitive dietary advice) will be monitored via follow up and lab work. The patient will be encouraged to begin/continue an exercise regimen and dietary changes. She is scheduled for follow up (with lipids and CMP) in 6 months, and it is hoped that she will have good results from these measures.
References
Brunner, E. J., Rees, K., Ward, K., Burke, M., Thorogood, M. (2007). Dietary advice for reducing cardiovascular risk. Cochrane Database of Systematic Reviews 2007, Issue 4. Retrieved November 16, 2008 from http://www.mrw.interscience.wiley.com.ezproxy.ttuhsc.edu/
cochrane/clsysrev/articles/CD002128/frame.html
Davy, B. M., Davy, K. P., Ho, R. C., Beske, S. D., Davrath, L. R. & Melby, C. L. (2002). High-fiber oat cereal compared with wheat cereal consumption favorably alters LDL-cholesterol subclass and particle numbers in middle-aged and older men. The American Journal of Clinical Nutrition, 76(2), 351-358. Retrieved November 13, 2008 from http://ejournals.ebsco.com/direct.asp
?ArticleID=425EB4E9E9B6705CE507
Denke, M. A., Adams-Huet, B. & Nguyen, A. T. (2000). Individual cholesterol variation in response to a margarine- or butter-based diet: A study in families. JAMA, 284(21), 2740-2747.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. (2001). 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. 285(19), 2486-2497.
Ferri, F. F. (2009). Ferri’s clinical advisor: Instant diagnosis and treatment. Philadelphia: Mosby.
Gardner, C. D., Dawson, L. D., Block, E., Chatterjee, L. M., Kiazand, A., Balise, R. R., et al. (2007). Effect of raw garlic vs. commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia: A randomized clinical trial. Archives of Internal Medicine, 167(4):346-53.
Grundy, S. M., Cleeman ,J. I., Bairey Merz, C. N., Brewer, H. B., Clark, L. T., Hunninghake, D. B. et al. (2004). Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation, 110(2), 227-239.
Hawthorne, K., Robles, Y., Cannings-John, R., Edwards, A. G. K. (2008). Culturally appropriate health education for type 2 diabetes mellitus in ethnic minority groups. Cochrane Database of Systematic Reviews 2008, Issue 3. Retrieved November 17, 2008 from http://www.mrw.
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Rakel, R. E. (2007). Textbook of family medicine (7th ed.). Philadelphia: Saunders.
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Tags: Cholesterol, hyperlipidemia, LDL
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