Atherosclerotic Cardiovascular Disease Risk Assessment

Risk Assessment

Several tools have been developed to determine a patient’s 10- and 30-year risk of an ASCVD event. These calculators should be used to establish appropriate treatment.

The American College of Cardiology/American Heart Association (ACC/AHA) joint committee guidelines  recommend incorporating the Predicting Risk of Cardiovascular Disease Events (PREVENT) equations  into clinical practice. The PREVENT-ASCVD equations are applied in adults 30-79 years old without ASCVD who have an LDL-C concentration of 70-189 mg/dL, with categorization as low (<3%), borderline (3% to <5%), intermediate (5% to <10%), or high (≥10%) 10-year risk; consideration of lipid-lowering therapy begins at an estimated risk of 3%. PREVENT-ASCVD estimates are approximately 40% to 50% lower than estimates from the Pooled Cohort Equations for the same risk factor profile. 

The American Association of Clinical Endocrinology (AACE) guideline  recommends assessing patients who have dyslipidemia with a validated risk assessment tool but does not give preference to any particular risk calculator. In addition to the PREVENT equations, the AACE gives the examples of the Pooled Cohort Equations calculator, the Framingham Risk Score, the SCORE2 and SCORE2-OP, the PAHO cardiovascular risk calculator, and the QRISK calculator as tools for ASCVD risk assessment. 

Screening

The ACC/AHA guidelines  recommend all adults be screened with a lipid profile at least every 5 years starting at 19 years of age; more frequent screening is recommended for individuals with additional ASCVD risk factors. Children should be screened for familial hypercholesterolemia or other lipid disorders between 9 and 11 years of age if not previously screened. Screening with a single lipid profile can begin at 2 years of age in individuals with a first- or second-degree relative with familial hypercholesterolemia, severe hypercholesterolemia, or premature ASCVD. 

Laboratory Testing

Traditional Risk Markers

Traditional risk markers are often assessed using a lipid panel. A standard nonfasting or fasting lipid profile is recommended to document baseline lipid levels, and nonfasting samples are acceptable for most individuals. A fasting profile should be obtained in patients with a family history of dyslipidemia or premature ASCVD, a known or suspected disorder of triglyceride metabolism, or an elevated nonfasting triglyceride level. A non-HDL-C level helps determine risk in patients with DM, established ASCVD, or elevated triglycerides, and reporting of non-HDL-C is recommended for all adults and children who undergo a standard lipid profile; it also provides information about a patient’s total atherogenic lipoprotein burden. 

Nontraditional Risk Markers

Lipoprotein(a)

The lipoprotein(a) [Lp(a)] concentration aids in ASCVD risk stratification and should be included in ASCVD risk assessment at least once for all adults.  First-degree relatives of individuals with familial hypercholesterolemia, premature ASCVD, or a high Lp(a) concentration should also be tested for high Lp(a) to identify those with heightened ASCVD risk.  Fasting is not required, and genetic testing for Lp(a) is not advised because the measured concentration is sufficient for risk assessment. For individuals with a borderline 10-year ASCVD risk estimate, Lp(a) may be considered to guide treatment initiation.  Lp(a) measurements may be altered due to inflammation, and Lp(a) may be elevated due to secondary causes such as kidney or liver disease, thyroid disease, pregnancy, menopause, and some medications.  As with apoB, the AACE  found limited utility in incorporating Lp(a) measurement into standard risk assessments. Lp(a) measurement may be considered to guide treatment decisions in patients with intermediate risk. 

Apolipoproteins

Measurement of apoB provides a different risk assessment than LDL-C by directly measuring the number of atherogenic particles, including LDL, very-low-density lipoprotein, and Lp(a). apoB results can be used to improve risk assessment, guide treatment, and assess for inherited lipid disorders in individuals who are not receiving lipid-lowering therapy.  In individuals currently receiving lipid-lowering therapy, apoB can identify residual cardiovascular disease risk and help guide treatment when other traditional risk marker-lowering goals have been reached.  The AACE  found limited utility in incorporating apoB measurement into a risk assessment, but apoB results may be considered to guide treatment in patients with intermediate risk.

High-Sensitivity C-Reactive Protein

Measurement of high-sensitivity C-reactive protein (hsCRP) can help stratify risk in individuals assessed as having a borderline 10-year ASCVD risk.  Elevated hsCRP concentrations on two successive measurements, with no alternative identifiable cause, may prompt initiation of a high-intensity statin to reduce the risk of an ASCVD event in individuals with a borderline 10-year ASCVD risk estimate.  The U.S. Preventive Services Task Force  has determined that there is insufficient evidence to recommend or discourage hsCRP measurement as part of the risk assessment for ASCVD in asymptomatic adults. An hsCRP test should not be performed in patients with current acute illness.

Lipoprotein Particle Evaluation

Lipoprotein particle number evaluation is not routinely recommended as part of estimating ASCVD risk or guiding treatment for individuals with ASCVD. Reported subfraction parameters do not meaningfully reclassify risk beyond a standard lipid profile combined with apoB or Lp(a), and the assays lack standardization across platforms; such testing should be limited to situations in which the result is likely to change management. 

Genotyping

The apolipoprotein E (APOE) gene is associated with modulation of the plasma lipids profile. APOE genotyping can be used to diagnose (or screen individuals with a family history of) type III hyperlipoproteinemia. It is not recommended for routine ASCVD risk prediction, and the 2026 ACC/AHA guidelines do not address APOE genotyping. 

The ACC/AHA  determined it may be appropriate to evaluate individuals with familial hypercholesterolemia for variants in the LDLR, APOB, and PCSK9 genes. The AACE  additionally recommends evaluating for variants in the LDLRAP1, ABCG5/G8, LIPA, and APOE genes.

Monitoring

Lipid testing is recommended to assess the impact of medication and lifestyle adjustments. A baseline lipid panel should be repeated 1-3 months after statin initiation or dose adjustment, after which monitoring with a lipid evaluation should be performed every 6-12 months.  Lipid testing every 12 months is appropriate for patients with no clinical changes and who require no change in therapy.  The ACC/AHA guidelines reinstate absolute LDL-C and non-HDL-C treatment goals stratified by risk category, while retaining percentage reduction in LDL-C as a complementary treatment metric. AACE guidelines  recommend treating to achieve lipid targets based on risk category.