Cardiovascular Disease (Traditional Risk Markers) - Risk Markers - CVD (Traditional)

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Adults – obtain baseline lipid testing and repeat testing every 5 years if normal initial baseline testing

Criteria for Diagnosis

  • ACC/AHA calculator (2013) incorporates additional data versus the Framingham ATP III calculator
    • May overestimate risk of atherosclerotic cardiovascular disease (ASCVD) even more excessively than ATP III calculator
    • Four risk groups for statin use
      • Adults with ASCVD – includes stroke, transient ischemic attack, peripheral vascular disease
      • Adults with diabetes, aged 40-75 years with low-density lipoprotein (LDL) levels 70-189 mg/dL
      • Adults with LDL cholesterol levels of ≥190 mg/dL
      • Adults aged 40-75 years who have LDL levels 70-189 mg/dL and ≥7.5% 10-year risk of atherosclerotic cardiovascular disease
  • Framingham ATP III
    • Identify risk factors present for cardiovascular disease (referred to as ASCVD in current ACC/AHA guidelines)
      • Elevated LDL-C – current gold standard diagnostic risk marker
      • Tobacco use
      • Hypertension – blood pressure >140/90 mmHg or on medication for hypertension
      • Low high-density lipoprotein cholesterol (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
  • Initiate lifestyle modifications and/or drug therapy to reduce LDL-C to target concentrations
  • High triglycerides (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 – minimum testing recommendation
    • No consensus guidelines support use of LDL-C subclasses
  • Adults
    • ≤75 years – screen all individuals
    • >75 years – screen individuals who have multiple coronary artery disease risk factors
  • Initial screen – fasting lipid panel with LDL-C, HDL-C, and TG
  • 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
  • ACC/AHA (2013) guideline deemphasizes fixed goals for LDL-C and HDL
    • Lipid measurement – 1-3 months after statin initiation and yearly thereafter

Cardiovascular disease (CVD) (referred to as atherosclerotic cardiovascular disease [ASCVD] in current ACC/AHA guidelines) 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

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 prevalence of hyperlipidemia in children, which mirrors increasing level of obesity
    • ~20% of youth 12-19 years have abnormal cholesterol values

Diagnosis

Indications for Testing

Laboratory Testing

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

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Lipid Panel 0020421
Method: Quantitative Enzymatic

Lipid Panel, Extended 0020468
Method: Quantitative Spectrophotometry/Quantitative Enzymatic

LDL Cholesterol, Direct 0020257
Method: Quantitative Detergent Solubilization/ Enzymatic

Additional Tests Available

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Comments

Standard screen for DM

Triglycerides, Serum or Plasma 0020040
Method: Quantitative Enzymatic

Comments
Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present
 
Negative interference has also been reported with NAPQI (an acetaminophen metabolite), but only when concentrations are at or above those expected during acetaminophen overdose

LDL Subclasses 0050021
Method: Quantitative Electrophoresis

Comments

Not validated to assess CVD risk

HDL Cholesterol 0020053
Method: Detergent Solubilization/Enzymatic

Comments

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite), but only when concentrations are at or above those expected during acetaminophen overdose

Cholesterol, Serum or Plasma 0020031
Method: Quantitative Enzymatic

Comments
Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present
 
Negative interference has also been reported with NAPQI (an acetaminophen metabolite), but only when concentrations are at or above those expected during acetaminophen overdose

Glucose Tolerance Test 0020542
Method: Quantitative Enzymatic

Comments

Diagnose DM and establish criteria for metabolic syndrome

Patient must be fasting

Components include fasting glucose and 2-hr glucose

Apolipoprotein B 0050029
Method: Quantitative Nephelometry

Guidelines

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014; 37 Suppl 1: S81-90. PubMed

ATP III At-A-Glance: Quick Desk Reference. National Heart, Lung, and Blood Institute. Bethesda, MD [Accessed: Jan 2016]

Daniels S, Greer F, Committee on Nutrition. Lipid screening and cardiovascular health in childhood. Pediatrics. 2008; 122(1): 198-208. PubMed

Emerging CV Risk Factors. American Association for Clinical Chemistry. Washington, DC [Accessed: Feb 2015]

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 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): 2486-97. PubMed

Greenland P, Alpert J, Beller G, Benjamin E, Budoff M, Fayad Z, Foster E, Hlatky M, Hodgson J, Kushner F, Lauer M, Shaw L, Smith S, Taylor A, Weintraub W, Wenger N, Jacobs A, Smith S, Anderson J, Albert N, Buller C, Creager M, Ettinger S, Guyton R, Halperin J, Hochman J, Kushner F, Nishimura R, Ohman M, Page R, Stevenson W, Tarkington L, Yancy C, American College of Cardiology Foundation, American Heart Association. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2010; 56(25): e50-103. PubMed

Jellinger P, Smith D, Mehta A, Ganda O, Handelsman Y, Rodbard H, Shepherd M, Seibel J, AACE Task Force for Management of Dyslipidemia and Prevention of Atherosclerosis. American Association of Clinical Endocrinologists' Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis. Endocr Pract. 2012; 18 Suppl 1: 1-78. PubMed

Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, Albus C, Benlian P, Boysen G, Cifkova R, Deaton C, Ebrahim S, Fisher M, Germano G, Hobbs R, Hoes A, Karadeniz S, Mezzani A, Prescott E, Ryden L, Scherer M, Syvänne M, Reimer W, Vrints C, Wood D, Zamorano J, Zannad F, European Association for Cardiovascular Prevention & Rehabilitation (EACPR), ESC Committee for Practice Guidelines (CPG). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012; 33(13): 1635-701. PubMed

Stone N, Robinson J, Lichtenstein A, Goff D, Lloyd-Jones D, Smith S, Blum C, Schwartz S, 2013 ACC/AHA Cholesterol Guideline Panel. Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: synopsis of the 2013 American College of Cardiology/American Heart Association cholesterol guideline. Ann Intern Med. 2014; 160(5): 339-43. PubMed

Stone N, Robinson J, Lichtenstein A, Merz N, Blum C, Eckel R, Goldberg A, Gordon D, Levy D, Lloyd-Jones D, McBride P, Schwartz S, Shero S, Smith S, Watson K, Wilson P, American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 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/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 63(25 Pt B): 2889-934. PubMed

U.S. Preventive Services Task Force. Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009; 151(7): 474-82. PubMed

General References

Chopra V, Eagle K. Cardiac biomarkers in the diagnosis, prognosis and management of coronary artery disease: a primer for internists. Indian J Med Sci. 2010; 64(12): 561-73. PubMed

Folsom A. Classical and novel biomarkers for cardiovascular risk prediction in the United States. J Epidemiol. 2013; 23(3): 158-62. PubMed

Gilstrap L, Wang T. Biomarkers and cardiovascular risk assessment for primary prevention: an update. Clin Chem. 2012; 58(1): 72-82. PubMed

Gooding H, de Ferranti S. Cardiovascular risk assessment and cholesterol management in adolescents: getting to the heart of the matter. Curr Opin Pediatr. 2010; 22(4): 398-404. PubMed

LDL cholesterol. New measurements of risk. Mayo Clin Health Lett. 2011; 29(5): 1-3. PubMed

Lepor N, Vogel R, National Cholesterol Education Program Adult Treatment Panel III. Summary of the third report of the National Cholesterol Education Program Adult Treatment Panel III. Rev Cardiovasc Med. 2001; 2(3): 160-5. PubMed

Martin S, Blumenthal R. Concepts and controversies: the 2013 American College of Cardiology/American Heart Association risk assessment and cholesterol treatment guidelines. Ann Intern Med. 2014; 160(5): 356-8. PubMed

Psaty B, Weiss N. 2013 ACC/AHA guideline on the treatment of blood cholesterol: a fresh interpretation of old evidence. JAMA. 2014; 311(5): 461-2. PubMed

Vavuranakis M, Kariori M, Kalogeras K, Vrachatis D, Moldovan C, Tousoulis D, Stefanadis C. Biomarkers as a guide of medical treatment in cardiovascular diseases. Curr Med Chem. 2012; 19(16): 2485-96. PubMed

Viera A, Sheridan S. Global risk of coronary heart disease: assessment and application. Am Fam Physician. 2010; 82(3): 265-74. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology

Jasuja G, Travison T, Davda M, Murabito J, Basaria S, Zhang A, Kushnir M, Rockwood A, Meikle W, Pencina M, Coviello A, Rose A, D'Agostino R, Vasan R, Bhasin S. Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the Framingham Heart Study. J Gerontol A Biol Sci Med Sci. 2013; 68(6): 733-40. PubMed

La'ulu S, Apple F, Murakami M, Ler R, Roberts W, Straseski J. Performance characteristics of the ARCHITECT Galectin-3 assay. Clin Biochem. 2013; 46(1-2): 119-22. PubMed

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

Medical Reviewers

Last Update: January 2016