II. Causes: Familial Hypercholesterolemia
-
General Findings
- LDL Cholesterol >190 mg/dl
- Premature, early onset coronary event (age <50 years)
- Coronary events may occur as early as age 17 years in males, and 25 years in females
- Homozygous Familial Hypercholesterolemia
- Corneal arcus senilis
- Xanthomas
- Heterozygous Familial Hypercholesterolemia
- Worldwide Prevalence: 1 in 250 to 350
- Silent severe Hyperlipidemia (LDL Cholesterol >190 mg/dl)
- No physical findings until premature cardiovascular events occur
- References
III. Causes: Other Secondary Causes of Hypercholesterolemia
-
Genetic Cholesterol disorder findings
- See Familial Hypercholesterolemia as above
- LDL Cholesterol >190-200 mg/dl
- Serum Triglycerides > 1000 mg/dl
- HDL Cholesterol < 30 mg/dl
- Hypothyroidism
- Nephrotic Syndrome
- Chronic Liver Disease (Primary Biliary Cirrhosis)
- Dysglobulinemia
- Cushing's Syndrome
- Hyperparathyroidism
- Acute Intermittent Porphyria
- Medications
IV. Screening: Guidelines
-
General counseling for all patients
- Low Fat Diet
- Exercise Program
- Criteria for age to start screening
- NIH as of 2011 recommends screening all ages 9-11 and again at 17-21years
- Treat patients only with significant LDL increase (e.g. >190)
- Goal to identify Familial Hypercholesterolemia
- Age over 20 years (ATP III Guidelines)
- Screen at age 20 and then every 5 years
- Prior guidelines for age to start screening
- Age >34 years in men
- Age >44 years in women
- Ages 2 to 20 years
- Family History of Total Cholesterol >300 mg/dl
- Family History Premature Coronary Artery Disease
- Age under 56 years in men
- Age under 66 years in women
- NIH as of 2011 recommends screening all ages 9-11 and again at 17-21years
- Screening protocol (repeated every 5 years)
- Full Fasting lipid profile preferred (ATP III guide)
- Alternative protocol: Non-Fasting lipid screening
- NCEP reasoning for non-Fasting lipid screening
- Non-Fasting screening improves compliance
- Postprandial Triglyceride rise can be evaluated
- Related to atherosclerosis risk
- Protocol
- Obtain non-Fasting Total Cholesterol with HDL
- Criteria to perform Fasting full lipid panel
- No Cardiac Risk Factors: Cholesterol >240 mg/dl
- Cardiac Risk Factors: Cholesterol >200 mg/dl
- HDL Cholesterol <40 mg/dl
- NCEP reasoning for non-Fasting lipid screening
- Alternative protocol: Non-Fasting Non-HDL Cholesterol
- Non-HDL Cholesterol = VLDL + IDL + LDL
- Correlates very well with outcomes
- Convenient (Patient does not need to fast)
- Goal Non-HDL Cholesterol is 30 higher than LDL goal
V. Evaluation: Framingham Risk Score (FRS)
- http://www.nhlbi.nih.gov/about/framingham/riskabs.htm
- NCEP Framingham Online Calculator
- Results of lowering LDL Cholesterol
- Relative CAD risk reduced 1% per 1% LDL decrease
VI. Management: General
- See Hyperlipidemia Management
-
Coronary Artery Disease Risk Factors
- Positive Risk Factors
- See Cardiac Risk Factors
- Negative Risk Factors (Protective)
- HDL Cholesterol over 60 mg/dl
- Positive Risk Factors
- Available lipid lowering modalities
- Dietary changes
- Low Fat Diet
- Phytosterols (Plant Stanols) lower LDL Cholesterol
- Weight loss for Obesity
- Lowers LDL Cholesterol
- Improves Insulin sensitivity
- Aerobic Exercise
- Raises HDL Cholesterol
- Lowers Triglycerides
- Anti-hyperlipidemic Medications
- Tobacco Cessation (Increases HDL by 30%)
- Dietary changes
VII. Management: Less than two Cardiac Risk Factors
-
Cholesterol Management
- Goal if LDL Cholesterol below 160 mg/dl (ideally <130)
- Low Fat Diet if LDL Cholesterol over 160 mg/dl
- Anti-hyperlipidemic if LDL Cholesterol over 190 mg/dl
- Monitoring
- Desirable lipids: Repeat Lipid panel in 5 years
- Borderline lipids: Repeat lipid panel in 1 year
- Elevated lipids: Repeat lipid panel in 3-6 months
VIII. Management: Two or more Cardiac Risk Factors
-
Cholesterol Management
- Goal LDL Cholesterol below 130 mg/dl
- Low Fat Diet if LDL Cholesterol over 130 mg/dl
- Anti-hyperlipidemic indications
- LDL Cholesterol over 130 (FRS 10 year risk <20%)
- LDL Cholesterol over 160 (FRS 10 year risk <10%)
- Monitoring
- Desirable lipids: Repeat Lipid panel in 1-2 years
- Borderline lipids: Repeat lipid panel in 6 months
- Elevated lipids: Repeat lipid panel in 2-3 months
IX. Management: Coronary Artery Disease or equivalent
-
Coronary Artery Disease equivalents
- Diabetes Mellitus
- Ten year Framingham Risk Score (FRS) 20% or higher
- Abdominal Aortic Aneurysm
- Peripheral Vascular Disease (e.g. Claudication)
- Symptomatic Carotid Artery disease
-
Cholesterol Management
- Goal LDL Cholesterol below 100 (ideally <70 mg/dl)
- Low Fat Diet if LDL Cholesterol above 100 mg/dl
- Anti-hyperlipidemic if LDL Cholesterol over 130 mg/dl
- Monitoring
- Desirable lipids: Repeat Lipid panel in 6-12 months
- Borderline lipids: Repeat lipid panel in 2-3 months
- Elevated lipids: Repeat lipid panel in 6 weeks
X. Management: CAD with multiple uncontrolled risks
- Goal LDL Cholesterol below 70 mg/dl
- Low Fat Diet if LDL Cholesterol above 70 mg/dl
- Anti-hyperlipidemic if LDL Cholesterol over 100 mg/dl
XI. References
- (2001) JAMA 285:2486-97 [PubMed]
- Ahmed (1998) Am Fam Physician 57(9):2192-203 [PubMed]
- Grundy (1997) Circulation 95:2329-31 [PubMed]
- Grundy (1997) Am Fam Physician 55(6): 2250-8 [PubMed]
- Mosca (2002) Am Fam Physician 65(2):217-26 [PubMed]
- Safeer (2002) Am Fam Physician 65(5):871-80 [PubMed]
- Yeshuran (1995) South Med J 88:379-91 [PubMed]