Indications for Testing

• ATP III guidelines
  • Adults >20 years – obtain baseline lipid testing and repeat testing every 5 years

Criteria for Diagnosis

• Identify risk factors present for CVD 
  • Elevated LDL-C – current gold standard diagnostic risk marker
  • Tobacco use
  • Hypertension – blood pressure >140/90 mmHg or on medication for hypertension
  • Low HDL-C – <40 mg/dL
    • HDL-C ≥60 mg/dL is considered beneficial and removes one risk factor from the total count
  • Family history of early CVD – <55 years in first-degree male relative or <65 years in first-degree female relative
  • Increased age – men ≥45 years; women ≥55 years
• If >2 risk factors are present, assess Framingham criteria projections for 10-year CVD risk
  • A 20% risk is considered equivalent to one CVD risk factor
  • Refer to the Framingham criteria-based National Cholesterol Education Program calculator to estimate the patient's 10-year risk of developing CVD 
    • This simplified calculator provides quick assessment and may overestimate CVD risk 
    • See the NIH-NACEP ATP III Guidelines At-A-Glance Quick Desk Reference for further guideline information
• Treatment goals are determined by final risk category

  Source	Risk	Target LDL-C
  American Diabetes Association (ADA)/ American College of Cardiology (ACC) Consensus (2008)	Highest Known CVD DM plus ≥1 risk factor(s) for CVD	<70 mg/dL
  	High ≥2 risk factors for CVD DM (no other CVD risk factors)	<100 mg/dL
  ADA Practice  Guidelines (2010)	DM	<100 mg/dL
  	Known CVD plus DM	<70 mg/dL
  ATP III  Guidelines (2004)	Very high Known CVD plus DM or metabolic syndrome	<70 mg/dL
  	High Known CVD DM CVD risk factor	<100 mg/dL
  	Intermediate	<130 mg/dL
  	Low	<160 mg/dL

  • Initiate lifestyle modifications and/or drug therapy to reduce LDL-C to target concentrations
  • High TG (>150 mg/dL)
    • Lifestyle modifications
    • If TG ≥200 mg/dL, non-HDL-C target is set 30 mg/dL higher than LDL-C target

Laboratory Testing 

• Determine lipoprotein concentrations using fasting lipid testing 
  • LDL-C, HDL-C and TG are the minimum recommendation
  • No consensus guidelines support use of LDL-C subclasses

• Initial screen – fasting lipid panel with LDL-C, HDL-C and TG

• If LDL-C remains elevated after 3 months of therapy or recommended diet and exercise modifications, assess for presence of metabolic syndrome (ATP III guidelines)
  • Criteria for metabolic syndrome 
    • Waist circumference >40 inches (male), >35 inches (female) 
    • TG ≥150 mg/dL
    • HDL-C <40 mg/dL (male), <50 mg/dL (female)
    • Fasting glucose ≥100 mg/dL
  • If patient meets criteria for metabolic syndrome, consider LDL-C target concentration of <70 mg/dL
• ADA/ACC consensus – consider Apo B monitoring in patients with LDL-C <130 mg/dL with a goal of 80 mg/dL in highest-risk patients

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in the U.S.

Epidemiology

• Prevalence – 1.2 million myocardial infarctions annually in U.S.
• Age – risk increases with age
• Sex – M>F

Risk Factors for CVD

• Elevated low-density lipoprotein cholesterol (LDL-C) – ≥130 mg/dL
  • For detection, evaluation and treatment of high blood cholesterol in adults, refer to National Heart, Lung and Blood Institute Guidelines
• Tobacco smoking
• Hypertension – 140/90 mmHg or on medication for hypertension
• Low levels of high-density lipoprotein cholesterol (HDL-C) – <40 mg/dL
• Family history of early CVD – <55 years in first-degree male relative or <65 years in first-degree female relative
• Increasing age – men ≥45 years; women ≥55 years
• Diabetes mellitus (DM)

Basis of Risk Assessment

• Statins shown to reduce LDL-C concentrations and to reduce cardiovascular mortality in numerous trials
  • Identifying patients who will benefit from drug therapy is important for early prevention and intervention
• Adult Treatment Panel (ATP) III guidelines (Framingham Heart Study)
  • Identify patients at risk for development of CVD
  • Develop plan of action for at-risk patients, including target goals for LDL-C and triglycerides (TG)

Clinical Background

Epidemiology

• Prevalence – in last 10 years, increasing evidence of hyperlipidemia in children, which mirrors increasing level of obesity
  • ~20% of youth 12-19 years have abnormal cholesterol values

Diagnosis

Indications for Testing

• Obesity
• Family history of early hyperlipidemia
• Diabetes mellitus

Laboratory Testing

• Lipid profile

  	Cholesterol	LDL
  Acceptable	<170 mg/dL	<110 mg/dL
  Borderline	170-199 mg/dL	110-129 mg/dL
  Elevated	≥200 mg/dL	≥130 mg/dL

Screening

• U.S. Preventive Services Task Force (USPSTF, 2007) – insufficient evidence to recommend screening
• American Academy of Pediatrics (2008) – screen children and adults (fasting lipid profile)
  • Recommended if family history of CVD or other CVD risk factors 
  • No definitive data exists to show which cholesterol level predicts risk of adult CVD
  • If levels acceptable, repeat every 3-5 years

Tests generally appear in the order most useful for common clinical situations

Guidelines

• Daniels SR, Greer FR. Lipid Screening and Cardiovascular Health in Childhood. Pediatrics. Version Vol. 122 No. 1 July 2008, pp. 198-208, [] 
• Emerging CV Risk Factors. American Association for Clinical Chemistry. Washington, DC [Accessed: 23 Oct 2009] 
• Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement. United States Preventive Services Task Force - Independent Expert Panel. 2009 November 24. NGC:007462

General

• Acharjee S, Qin J, Murphy SA, McCabe C, Cannon CP. Distribution of traditional and novel risk factors and their relation to subsequent cardiovascular events in patients with acute coronary syndromes (from the PROVE IT-TIMI 22 trial). Am J Cardiol. 2010; 105 (5) :619-623.PubMed
• Assmann G, Guerra R, Fox G, Cullen P, Schulte H, Willett D, Grundy SM. Harmonizing the definition of the metabolic syndrome: comparison of the criteria of the Adult Treatment Panel III and the International Diabetes Federation in United States American and European populations. Am J Cardiol. 2007; 99 (4) :541-548.PubMed
• Benjamin EJ, Dupuis J, Larson MG, Lunetta KL, Booth SL, Govindaraju DR, Kathiresan S, Keaney JF Jr, Keyes MJ, Lin JP, Meigs JB, Robins SJ, Rong J, Schnabel R, Vita JA, Wang TJ, Wilson PW, Wolf PA, Vasan RS. Genome-wide association with select biomarker traits in the Framingham Heart Study. BMC Med Genet. 2007; 8 Suppl 1 :S11-.PubMed
• 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) :2486-2497.PubMed
• Gaze DC. The role of existing and novel cardiac biomarkers for cardioprotection. Curr Opin Investig Drugs. 2007; 8 (9) :711-717.PubMed
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• Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110 (2) :227-239.PubMed
• Hausenloy DJ, Yellon DM. Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels. Postgrad Med J. 2008; 84 (997) :590-598.PubMed
• Lau JF, Smith DA. Advanced lipoprotein testing: recommendations based on current evidence. Endocrinol Metab Clin North Am. 2009; 38 (1) :1-31.PubMed
• Lepor NE, Vogel RE. Summary of the third report of the National Cholesterol Education Program Adult Treatment Panel III. Rev Cardiovasc Med. 2001; 2 (3) :160-165.PubMed
• Shlipak MG, Ix JH, Bibbins-Domingo K, Lin F, Whooley MA. Biomarkers to predict recurrent cardiovascular disease: the Heart and Soul Study. Am J Med. 2008; 121 (1) :50-57.PubMed
• Tognarini DP, Sullivan DR, Thomas DW, Sikaris K. Reducing CVD risk - integration of clinical and laboratory criteria. Aust Fam Physician. 2008; 37 (6) :422-427.PubMed
• Vasudevan MM, Ballantyne CM. Advances in lipid testing and management in patients with diabetes mellitus. Endocr Pract. 2009; 15 (6) :641-652.PubMed
• Wood FO, de Lemos JA. Sorting through new biomarkers. Curr Cardiol Rep. 2008; 10 (4) :319-326.PubMed

ARUP Institute for Clinical and Experimental Pathology®

• Rawlins ML, La'ulu SL, Moon N, Roberts WL. Performance characteristics of an immunoturbidimetric assay for lipoprotein-associated phospholipase A2. Clin Chim Acta. 2009; 406 (1-2) :66-70.PubMed

Acromegaly
Cardiovascular Disease (Non-traditional Risk Markers)
Heart Failure
Ischemic Heart Disease
Metabolic Syndrome
Nicotine & Metabolites
Polycystic Ovarian Syndrome
Renal Function Markers