Exploring an Evolution of Understanding: Identification and Management of Familial Hypercholesterolemia
eBrief icon E-Brief, Issue 1:
Therapeutic Lifestyle Modifications for Managing Familial Hypercholesterolemia
James Underberg, MS, MD Faculty Advisor:
Peter P. Toth, MD, PhD

Director of Preventive Cardiology
CGH Medical Center
Sterling, IL
Professor of Clinical Family and Community Medicine
University of Illinois College of Medicine
Peoria, IL
As a follow-up to Med-IQ’s recent CME-certified online publication on familial hypercholesterolemia (FH), this e-brief provides additional information on the recognition and management of cardiovascular risk factors in patients with FH. It focuses on the benefits of lifestyle modifications such as physical exercise, diet, and smoking cessation, as well as management strategies for blood pressure and metabolic syndrome. Clinical studies on lifestyle modifications are also discussed.
Table of Contents
Introduction
Therapeutic Lifestyle Modifications
Management of Other Cardiovascular Risk Factors
Clinical Evaluations of Lifestyle Modifications
Summary
References

Introduction

Familial hypercholesterolemia (FH) is an inherited lipid disorder associated with a high risk of premature coronary heart disease (CHD) and other forms of cardiovascular disease (CVD).1,2 The primary goal of FH treatment is to reduce serum low-density lipoprotein cholesterol (LDL-C) levels by at least 50% to prevent or slow the development of coronary atherosclerosis; nearly all patients will ultimately require lipid-lowering pharmacotherapy to achieve this aggressive target.2 Despite the inevitability of drug therapy, however, therapeutic lifestyle modifications remain of paramount importance to long-term disease management.1 Indeed, the National Lipid Association (NLA) recommends that lifestyle modifications always be instituted in patients with FH.3

Lifestyle modifications can be expected to reduce LDL-C levels by 10% to 16% in patients with FH, which may lower the required dose of lipid-lowering pharmacotherapy.4,5 Moreover, lifestyle changes have beneficial effects on many nonlipid contributors of CVD, which may be especially important in the management of patients with multiple risk factors or established CVD.6 Effective patient counseling on the importance of therapeutic lifestyle modifications (eg, dietary changes, increased physical activity, and smoking cessation) is also a critical cornerstone of FH management.7

Therapeutic Lifestyle Modifications

In 2001, the National Cholesterol Education Program (NCEP) Third Adult Treatment Panel (ATP III) published comprehensive guidelines for cholesterol testing and management, including lifestyle modifications aimed at lowering the risk of CHD in patients with dyslipidemia.6 Ten years later, the 2011 NLA Expert Panel on FH endorsed these recommendations, which remain the gold standard for lifestyle modifications.3,7 The NCEP ATP III guidelines emphasize a multifactorial approach to therapeutic lifestyle modifications that includes dietary changes, increased physical activity, and smoking cessation.6

Dietary Modification
The NCEP ATP III guidelines recommend the Therapeutic Lifestyle Changes (TLC) diet for all patients with lipid abnormalities.6 The TLC diet includes an intake of less than 200 mg of cholesterol per day, as well as a carbohydrate intake level of approximately 50% to 60% of total calories.6 Carbohydrates should be derived predominantly from foods rich in complex carbohydrates including grains (especially whole grains), fruits, and vegetables. The NCEP also advises that the daily energy expenditure should include at least moderate physical activity, burning approximately 200 kcal per day to balance energy intake and expenditure.6 The NLA Expert Panel on FH, echoing these recommendations, emphasized the importance of specific dietary considerations for patients with FH. The NLA encourages clinicians to refer patients with FH to registered dietitians or other qualified nutritionists for guidance on achieving the maximum possible reduction in LDL-C levels through medical nutrition therapy.3

Physical Activity
Physical inactivity predisposes patients to the development of multiple cardiometabolic risk factors, including overweight/obesity, atherogenic dyslipidemia, hypertension, and insulin resistance.6 Conversely, physical activity is associated with an improved risk profile, including lower LDL-C and triglyceride levels, increased high-density lipoprotein cholesterol (HDL-C) levels, increased insulin sensitivity, and lower blood pressure. Accordingly, physical inactivity is recognized as a major modifiable risk factor and a direct target for clinical intervention.6 The American Heart Association recommends a weekly goal of at least 150 minutes of moderate exercise or 75 minutes of vigorous exercise (a mix of moderate and vigorous activity).8 Moderate activity should noticeably accelerate the heart rate (eg, a brisk walk), while vigorous activity should cause rapid breathing and a substantial increase in heart rate (eg, jogging).9

Physical activity is also an effective tool for weight maintenance. Patients with FH should be encouraged to maintain a healthy body weight through a combination of physical activity and appropriate caloric intake while following the TLC diet.3 For overweight or obese patients, weight loss is an effective tool for lowering LDL-C levels; each kilogram of weight lost can be expected to reduce LDL-C concentration by approximately 0.8 mg/dL.3,10 Weight loss also results in improved glucose disposal, reductions in triglycerides, and elevations in HDL-C.10,11

Smoking Cessation
Cigarette smoking is a well-known risk factor for CHD and other forms of CVD.6 The NLA recommends smoking cessation to reduce the burden of cardiovascular risk factors and improve the overall lipid profile in patients with FH. Clinicians should screen patients for tobacco use, explain the negative effects of smoking, provide pharmacologic interventions that promote smoking cessation and control withdrawal symptoms, and offer referrals to smoking cessation programs.3

Management of Other Cardiovascular Risk Factors

Although LDL-C reduction is the primary treatment target for most patients with FH, other cardiovascular risk factors can be modified with aggressive lifestyle changes. Specifically, lifestyle modifications are effective first-line approaches to managing overweight/obesity, hypertension, and component features of metabolic syndrome.6

Blood Pressure
According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), treating systolic and diastolic blood pressure to reach targets of less than 140/90 mm Hg decreases the risk of cardiovascular complications.12 Patients with compelling indications, including diabetes mellitus or renal disease, should be treated to a blood pressure goal of 130/80 mm Hg.12 Therapeutic lifestyle changes are recommended for all patients with hypertension (see Table 1). JNC 7 also recommends specific pharmacologic agents, depending on the patient’s comorbid conditions, to achieve blood pressure goals.12

TABLE 1. Therapeutic Lifestyle Modifications for Patients With Hypertension
LIFESTYLE CHANGE EXPECTED SYSTOLIC BP REDUCTION
Body-weight reduction 5-20 mm Hg per 10-kg weight loss
Adoption of the DASH eating plan 8-14 mm Hg
Dietary sodium reduction
(≤ 2.4 g/day)
2-8 mm Hg
Aerobic physical activity
(≥ 30 minutes/day)
4-9 mm Hg
Moderation of alcohol consumption
(≤ 2 drinks/day)
2-4 mm Hg
DASH = Dietary Approaches to Stop Hypertension.
Adapted with permission from Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA. 2003;289:2560-2571.


Metabolic Syndrome
Metabolic syndrome describes the presence of multiple interrelated risk factors that increase the risk of CHD, diabetes, and other chronic diseases.6 The NCEP ATP III defines metabolic syndrome as the presence of three or more of the following factors6:
  • Abdominal obesity (waist circumference > 40 in [102 cm] for men and > 35 in [88 cm] for women)
  • Elevated triglyceride levels (≥ 150 mg/dL)
  • Low HDL-C levels (< 40 mg/dL for men and < 50 mg/dL for women)
  • Elevated blood pressure (≥ 130/85 mm Hg)
  • Elevated fasting glucose (≥ 110 mg/dL)
The primary management strategy for patients with metabolic syndrome is to address its root causes, including overweight/obesity and physical inactivity.6 Patients with metabolic syndrome are candidates for intensified therapeutic lifestyle modifications to reduce the risk of disease progression.6 Lipid and other nonlipid risk factors should also be treated appropriately.

Clinical Evaluations of Lifestyle Modifications

Several trials have demonstrated the feasibility of implementing therapeutic lifestyle modifications in individuals at high risk of CVD and in those with established disease.13-19 Intensive lifestyle counseling appears to be a key factor for achieving lipid and nonlipid treatment goals, with regular patient/clinician contact improving outcomes for those with multiple cardiovascular risk factors.13

PRO-FIT
The PRO-FIT project is an ongoing, randomized clinical trial designed to evaluate the role of individualized health counseling on CVD risk in patients with FH.14 The personalized intervention includes a combination of tailored Web-based counseling, face-to-face counseling, and telephone booster sessions. Each activity uses motivational interviewing techniques that focus on lifestyle changes concerning diet, physical activity, smoking behavior, and adherence to lipid-lowering therapy.14

This trial launched in 2009 with a target enrollment of 400 individuals with FH. Researchers recruited participants from the national cascade screening program in the Netherlands; all participants had LDL-C levels that were above the 75th percentile based on age and gender.14 In 2012, investigators presented preliminary findings from 181 patients who were randomized to the individualized-counseling group and 159 who were randomized to the usual-care group.15,16 Initial findings suggested a weak, though positive, association between individualized counseling and improvements in lifestyle behaviors and LDL-C levels.15 However, although LDL-C levels decreased in the intervention group, the difference was not statistically significant compared with the usual-care group.15,16 Recruitment to the PRO-FIT trial continues, and additional findings may clarify the potential role of targeted lifestyle interventions in cardiovascular risk factor management in patients with FH.16

Swedish Björknäs Study
A recent Swedish trial showed that intensive lifestyle modifications can be used to reduce cardiovascular risk factors in high-risk primary care patients.17 In the Björknäs study, 151 men and women with established risk factors for CVD—including hypertension, dyslipidemia, diabetes, and/or obesity—were randomly assigned to an intensive lifestyle intervention (n = 75) or standard care (n = 76). The 3-month lifestyle intervention was modeled after the National Institutes of Health’s Diabetes Prevention Program (DPP) and included supervised exercise sessions 3 times per week and 5 dietary counseling sessions followed by regular group meetings for 3 years. Patients in the control group received general advice about diet and exercise in addition to standard medical care. All lifestyle interventions were administered by primary care providers.17

After 36 months, patients in the intensive therapy group reported greater levels of exercise and total physical activity compared with those in the control group (P < 0.001).17 These behaviors correlated with significant improvements in several cardiometabolic risk factors, including17:
  • Reduced waist circumference (–2.2 cm; P = 0.001)
  • Reduced systolic blood pressure (–4.9 mm Hg; P = 0.036)
  • Reduced diastolic blood pressure (–1.6 mm Hg; P = 0.005)
  • Improved aerobic fitness (5%; P = 0.038)
  • Changed smoking status (41% vs. 8% quit, P = 0.04)
STRIP
The Special Turku Risk Intervention Program (STRIP) evaluated the effects of a low-saturated-fat/low-cholesterol diet and repeated dietary counseling in 1,062 children and adolescents, all recruited as infants in well-child clinics.18,19 In the intervention group (n = 540), the diet was introduced to infants at the time of weaning (median age, 7 months) and continued throughout childhood and adolescence. The diet was individualized for each child but, consistent with current recommendations for therapeutic lifestyle targets for cholesterol reduction, the target value for total fat intake was less than 30% of total calories and the target for total cholesterol intake was less than 200 mg/d.18 Counseling in the intervention group included parental dietary education for the first several years and age-appropriate dietary counseling for the child beginning at age 7. Children in the control group (n = 522) received an unrestricted diet and basic health education.18

At age 14, children in the dietary intervention group had significantly lower saturated fat intakes (P < 0.001) and LDL-C levels (P < 0.001) compared with the control group, with no adverse effects on growth or pubertal development.18 A recent follow-up analysis showed that the benefits of repeated dietary counseling persisted into young adulthood.19 Saturated fat intake and LDL-C levels remained significantly lower through age 19 for both sexes in the intervention group, although boys showed an even more favorable lipid profile with additional benefits in very-low-density lipoprotein, intermediate-density lipoprotein, apolipoprotein B, and triglyceride concentrations.19

Summary

Although lipid-lowering drug therapy is an important component of FH management, the critical role of lifestyle interventions in overall risk-factor management should not be overlooked. Multifactorial lifestyle interventions can improve biological risk factors, prevent or delay the onset of CVD and diabetes, and lower the risk of mortality in high-risk patients.20 Furthermore, dietary changes, physical activity, smoking cessation, and other lifestyle interventions improve nonlipid risk factors and may lower required doses of lipid-lowering therapies.6 In light of these clear benefits, therapeutic lifestyle changes should be recommended for all patients with FH, and intensive patient counseling should be provided to maximize patient adherence and therapeutic benefit.

References

  1. Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5:S1-8.
  2. Robinson JG, Goldberg AC. Treatment of adults with familial hypercholesterolemia and evidence for treatment: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5:S18-29.
  3. Ito MK, McGowan MP, Moriarty PM. Management of familial hypercholesterolemias in adult patients: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5:S38-45.
  4. Bruckert E, Rosenbaum D. Lowering LDL-cholesterol through diet: potential role in the statin era. Curr Opin Lipidol. 2011;22:43-48.
  5. Gidding SS, Dennison BA, Birch LL, et al. Dietary recommendations for children and adolescents: a guide for practitioners: consensus statement from the American Heart Association. Circulation. 2005;112:2061-2075.
  6. National Cholesterol Education Program. 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) final report. Circulation. 2002;106:3143-3421.
  7. Daniels SR, Gidding SS, de Ferranti SD. Pediatric aspects of familial hypercholesterolemias: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5:S30-37.
  8. American Heart Association. American Heart Association guidelines for physical activity. Updated November 15, 2012. www.heart.org/HEARTORG/GettingHealthy/PhysicalActivity/StartWalking/American-Heart-Association-Guidelines_UCM_307976_Article.jsp. Accessed December 5, 2012.
  9. Haskell WL, Lee IM, Pate RR, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation. 2007;116:1081-1093.
  10. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56:320-328.
  11. Golay A, Felber JP, Dusmet M, et al. Effect of weight loss on glucose disposal in obese and obese diabetic patients. Int J Obes. 1985;9:181-191.
  12. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA. 2003;289:2560-2571.
  13. Lin JS, O'Connor E, Whitlock EP, et al. Behavioral Counseling to Promote Physical Activity and a Healthful Diet to Prevent Cardiovascular Disease in Adults: Update of the Evidence for the U.S. Preventive Services Task Force. Evidence Synthesis No. 79. AHRQ Publication No. 11-05149-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; December, 2010.
  14. Broekhuizen K, van Poppel MN, Koppes LL, Brug J, van Mechelen W. A tailored lifestyle intervention to reduce the cardiovascular disease risk of individuals with Familial Hypercholesterolemia (FH): design of the PRO-FIT randomised controlled trial. BMC Public Health. 2010;10:69.
  15. Broekhuizen K, Jelsma Gm J, van Poppel Nm M, et al. Is the process of delivery of an individually tailored lifestyle intervention associated with improvements in LDL cholesterol and multiple lifestyle behaviours in people with Familial Hypercholesterolemia? BMC Public Health. 2012a;12:348.
  16. Broekhuizen K, van Poppel MN, Koppes LL, et al. No significant improvement of cardiovascular disease risk indicators by a lifestyle intervention in people with familial hypercholesterolemia compared to usual care: results of a randomised controlled trial. BMC Res Notes. 2012b;5:181.
  17. Eriksson MK, Franks PW, Eliasson M. A 3-year randomized trial of lifestyle intervention for cardiovascular risk reduction in the primary care setting: the Swedish Björknäs Study. PLoS One. 2009;4:e5195.
  18. Niinikoski H, Lagström H, Jokinen E, et al. Impact of repeated dietary counseling between infancy and 14 years of age on dietary intakes and serum lipids and lipoproteins: the STRIP Study. Circulation. 2007;116:1032-1040.
  19. Niinikoski H, Pahkala K, Ala-Korpela M, et al. Effect of repeated dietary counseling on serum lipoproteins from infancy to adulthood. Pediatrics. 2012;129:e704-e713.
  20. Blokstra A, van Dis I, Verschuren WM. Efficacy of multifactorial lifestyle interventions in patients with established cardiovascular diseases and high risk groups. Eur J Cardiovasc Nurs. 2012;11:97-104.
The content of this e-mail is for educational purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient’s medical condition.

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