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Nontraditional Risk Factors for Cardiovascular Disease Risk Assessment

Guidelines Being Compared:

  1. American College of Cardiology Foundation, American Heart Association (ACCF/AHA). 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 Dec 14;56(25):e50-103. [446 references]
  2. National Academy of Clinical Biochemistry (NACB). Emerging biomarkers for primary prevention of cardiovascular disease and stroke. Washington (DC): National Academy of Clinical Biochemistry; 2009. 70 p. [456 references]
  3. U.S. Preventive Services Task Force (USPSTF). Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009 Oct 6;151(7):474-82. [40 references]

A direct comparison of recommendations for cardiovascular risk assessment in asymptomatic adults using nontraditional risk factors is provided below. The recommendations assume that a global risk assessment incorporating multiple traditional risk factors (e.g., the Framingham Model) has been performed. The USPSTF recommendation specifically applies to those determined to be at intermediate (10%–20%) 10-year risk using traditional factors, and with no history of CHD, diabetes, or any CHD risk equivalent. ACCF/AHA and NACB make selected recommendations for higher risk groups (e.g., those with known diabetes or hypertension); these topics, however, are beyond the scope of this synthesis.

Areas of Agreement

Lipoprotein and Apolipoprotein Assessments

According to ACCF/AHA, measurement of lipid parameters, including lipoproteins, apolipoproteins, particle size, and density, beyond a standard fasting lipid profile is not recommended. NACB similarly found insufficient evidence to recommend routine measurement of lipoprotein subclasses, lipoprotein (a), and apo-B. Situations cited by NACB in which measurement of lipoprotein (a) may be appropriate include if patient is at intermediate risk and uncertainty remains as to the use of preventive therapies, and to identify individuals having a genetic predisposition of CVD if there is a strong family history of premature CVD (identified during global risk assessment). NACB also states that the apo B/apo A-I ratio can be used as an alternative to the usual TC/HDL-C ratio to determine lipoprotein-related risk for CVD. The USPSTF addresses only lipoprotein (a), and makes no recommendation due to insufficient evidence.

C-Reactive Protein (CRP)

All three groups address measurement of CRP for CVD risk assessment in intermediate-risk adults. The USPSTF makes no recommendation due to insufficient evidence. ACCF/AHA states that it may be reasonable in men ≤50 and women ≤60. According to NACB, if global risk is intermediate and uncertainty remains as to the use of preventive therapies, hsCRP measurement might be useful for further stratification into a higher or lower risk category. ACCF/AHA also addresses CRP measurement for the selection of patients for statin therapy, stating it can be useful in men ≥50 years and women ≥60 with LDL-C <130 mg/dL; not on lipid-lowering, hormone replacement, or immunosuppressant therapy; without clinical CHD, diabetes, CKD, severe inflammatory conditions, or contraindications to statins.

ACCF/AHA and NACB address measurement of CRP in patients at other risk stratifications, with ACCF/AHA recommending against measurement in high-risk adults, and in low-risk men <50 years and low-risk women ≤60 years. NACB recommends against measurement in adults with a 10-year predicted risk of <5%.

Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)

ACCF/AHA examined Lp-PLA2 and concluded that it might be reasonable for assessment in intermediate-risk asymptomatic adults. According to NACB, while Lp-PLA2, appears promising, complete evaluation was not possible at the time of guideline publication because of the large amount of pending data.

Fibrinogen and White Blood Cells (WBC)

NACB found that while both fibrinogen and WBC are independent markers of CVD risk, measurement of either is not recommended for this purpose. USPSTF also examined WBC, and makes no recommendation for its measurement due to insufficient evidence.

Homocysteine Level

USPSTF and NACB address homocysteine level screening. USPSTF makes no recommendation because of insufficient evidence; NACB states that screening is not warranted in healthy individuals.

Natriuretic Peptides

Of the two groups to address natriuretic peptides, ACCF/AHA and NACB, neither recommend measurement for CVD risk assessment in asymptomatic adults.

Areas of Difference

Carotid Intima-Media Thickness (IMT), Ankle-Brachial Index (ABI), Calcium Scoring Methods

ACCF/AHA and USPSTF address measurement of carotid IMT, ABI, and CAC for cardiovascular risk assessment in asymptomatic adults at intermediate risk. According to ACCF/AHA, all three are reasonable. The USPSTF, however, makes no recommendation due to insufficient evidence.

Internet citation: National Guideline Clearinghouse (NGC). Guideline synthesis: Nontraditional risk factors for cardiovascular disease risk assessment. In: National Guideline Clearinghouse (NGC) [Web site]. Rockville (MD): Agency for Healthcare Research and Quality (AHRQ); 2012 Feb. [cited YYYY Mon DD]. Available: http://www.guideline.gov.