Atherosclerotic Cardiovascular Disease (ASCVD) Traditional Risk Markers – Cardiovascular Disease Risk Markers (Traditional)

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in the U.S. A traditional lipid panel that includes total cholesterol, LDL, HDL, and triglycerides, is the cornerstone of laboratory testing for cardiovascular disease.

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

Indications for Testing

  • Adult experiencing new atherosclerotic cardiovascular disease (ASCVD) event
  • Adult not currently taking statins, obtain lipid profile (ADA, 2017)
    • At time of diabetes diagnosis
    • At an initial medical evaluation
    • Every 5 years, or more frequently if indicated 

Criteria for Diagnosis

  • ACC/AHA calculator (2013) calculates ASCVD risk based on the Pooled Cohort Equations data
    • May overestimate risk of ASCVD
    • Risk based on age, gender, ethnicity, tobacco use, total cholesterol, HDL, systolic blood pressure, and diabetes status
    • 10 year risk of atherosclerotic event calculated
  • Framingham Risk Score (ATP-III)
    • Identify risk factors present for cardiovascular disease (referred to as ASCVD in current ACC/AHA guidelines)
      • Elevated LDL
      • Tobacco use
      • Hypertension – blood pressure >140/90 mmHg or on medication for hypertension
      • Low HDL – <40 mg/dL
        • HDL ≥60 mg/dL is considered beneficial and removes one risk factor from the total count
      • Family history of early ASCVD – <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 ASCVD risk
      • 20% risk – considered equivalent to 1 ASCVD risk factor
      • Refer to the Framingham criteria-based National Cholesterol Education Program calculator to estimate the patient's 10-year risk of developing ASCVD
      • Other calculators
        • Multi-Ethnic Study of Atherosclerosis (MESA 10-year coronary heart disease risk with coronary artery calcification)
        • Reynolds Risk Score
        • UK Prospective Diabetes Study (UKPDS) 
  • Initiate lifestyle modifications and/or drug therapy to reduce LDL to target concentrations

Laboratory Testing

  • Traditional lipid panel – in adults, obtain baseline and repeat testing every 5 years if normal
    • Panel should include
      • Total cholesterol
      • LDL – calculated
        • If high triglycerides are present, a direct LDL level must be obtained
      • HDL
      • Triglycerides – no consensus guidelines support use of LDL subclasses
    • Fasting tests preferred (especially in individuals with high triglycerides or intermediate risk)
      • Nonfasting tests acceptable if barrier exists to obtaining fasting sample
  • Adult screening recommendations (AACE/ACE 2017)
    • 20-45 years – lipid testing every 5 years
    • 45-65 years – lipid testing every 1-2 years (in the absence of atherosclerotic cardiovascular disease (ASCVD) risk factors)
    • >65 years – screen individuals with ASCVD risk factors
    • Clinical judgment should be used to modify testing intervals as appropriate
  • Do not routinely order expanded lipid panels (particle sizing, nuclear magnetic resonance) as screening tests for cardiovascular disease (Choosing Wisely: Fifteen Things Physicians and Patients Should Question, 2016; American Society for Clinical Pathology)
  • U.S. Preventive Services Task Force (USPSTF, 2016) – insufficient evidence to evaluate the balance of risks versus harms in adults 20-39 years
  • ACC/AHA (2013) guideline de-emphasizes fixed goals for LDL and HDL
    • Target 30% reduction in LDL
    • Lipid measurement – 1-3 months after statin initiation and yearly thereafter
  • AACE (2017) – treat to LDL target based on risk category

Epidemiology

  • Incidence– 750,000 myocardial infarctions annually in U.S. (AACE, 2017)
  • Age – risk increases with age
  • Sex – M>F

Risk Factors for ASCVD

  • Elevated LDL
  • High total cholesterol
  • High non-HDL
  • Tobacco smoking
  • Hypertension – 140/90 mmHg or on medication for hypertension
  • Low levels of HDL – <40 mg/dL
  • Family history of early ASCVD – <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)
  • Chronic kidney disease
  • Physical inactivity

Basis of Risk Assessment

  • Statins shown to reduce LDL concentrations and to reduce cardiovascular mortality in numerous trials
    • Identifying patients who will benefit from drug therapy is important for early prevention and intervention
  • Risk calculators
    • Identify patients at risk for development of ASCVD
    • Provide basis for discussion of lifestyle modification and medication use

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

  • American Academy of Pediatrics (2008) – screen select children and adolescents
    • Family history of dyslipidemia or premature ASCVD
    • Unknown family history
    • ASCVD risk factors
      • Overweight or obese
      • Hypertension
      • Cigarette smoking
      • DM
    • Fasting lipid profile recommended
    • Screen between 2-10 years of age
      • If levels acceptable – repeat every 3-5 years
    • No definitive data exists to show which cholesterol level predicts risk of adult ASCVD
  • AACE/ACE (2017) – screen select children and adolescents
    • Risk for familial hypercholesterolemia (FH)
      • Family history of premature ASCVD or high cholesterol
      • Screen at 3 years of age, 9-11 years of age, and 18 years of age
    • Age ≥16 – screen every 5 years or more frequently if any of the following risk factors present
      • ASCVD risk factors
        • Overweight/obese
        • Insulin resistance syndrome/DM
      • Family history of premature ASCVD
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

Guidelines

ATP III At-A-Glance: Quick Desk Reference. National Heart, Lung, and Blood Institute. Bethesda, MD [Published May 2001; Accessed: Feb 2017]

Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, Witztum JL, American Diabetes Association, American College of Cardiology Foundation. Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care. 2008; 31(4): 811-22. PubMed

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Oct 2017]

Daniels SR, Greer FR, 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: Dec 2016]

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

Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R, Greenland P, Lackland DT, Levy D, O'Donnell CJ, Robinson JG, Schwartz S, Shero ST, Smith SC, Sorlie P, Stone NJ, Wilson PW, Jordan HS, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman M, Pressler SJ, Sellke FW, Shen W, Smith SC, Tomaselli GF, American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129(25 Suppl 2): S49-73. PubMed

Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, Grunberger G, Guerin CK, Bell DS, Mechanick JI, Pessah-Pollack R, Wyne K, Smith D, Brinton EA, Fazio S, Davidson M, Zangeneh F, Bush MA. American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Dyslipidemia and Prevention of Cardiovascular Disease Endocr Pract. 2017; 23(4): 479-497. PubMed

Marathe PH, Gao HX, Close KL. American Diabetes Association Standards of Medical Care in Diabetes 2017. J Diabetes. 2017; 9(4): 320-324. PubMed

Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney M, Corrà U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FD, Løchen M, Löllgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp B, van Dis I, Verschuren WM, Authors/Task Force Members. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice Eur Heart J. 2016; 37(29): 2315-81. PubMed

Stone NJ, Robinson JG, Lichtenstein AH, Goff DC, Lloyd-Jones DM, Smith SC, 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 NJ, Robinson JG, Lichtenstein AH, Merz NB, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz S, Shero ST, Smith SC, Watson K, Wilson PW, 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

US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW, Garcia FA, Gillman MW, Kemper AR, Krist AH, Kurth AE, Landefeld S, LeFevre ML, Mangione CM, Phillips WR, Owens DK, Phipps MG, Pignone MP. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2016; 316(19): 1997-2007. PubMed

General References

Chopra V, Eagle KA. 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 AR. Classical and novel biomarkers for cardiovascular risk prediction in the United States. J Epidemiol. 2013; 23(3): 158-62. PubMed

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

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

Lepor NE, Vogel RE, 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 SS, Blumenthal RS. 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 BM, Weiss NS. 2013 ACC/AHA guideline on the treatment of blood cholesterol: a fresh interpretation of old evidence. JAMA. 2014; 311(5): 461-2. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Jasuja GK, Travison TG, Davda M, Murabito JM, Basaria S, Zhang A, Kushnir MM, Rockwood AL, Meikle W, Pencina MJ, Coviello A, Rose AJ, D'Agostino R, Vasan RS, 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 SL, Apple FS, Murakami MM, Ler R, Roberts WL, Straseski JA. Performance characteristics of the ARCHITECT Galectin-3 assay. Clin Biochem. 2013; 46(1-2): 119-22. PubMed

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

Medical Reviewers

Content Reviewed: 
May 2017

Last Update: October 2017