Atherosclerotic Cardiovascular Disease Risk Assessment

Risk Assessment

Several tools have been developed to determine a patient’s 10-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) guidelines ^,  recommend incorporating the Pooled Cohort Equations  into clinical practice.

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) guidelines  recommend using at least one of the following risk calculators for dyslipidemia screening, all of which include total cholesterol, HDL-C, and systolic blood pressure:

• The Pooled Cohort Equations  calculator is age and sex specific, helps predict 10-year and lifetime risks for ASCVD in patients with or without DM, and incorporates LDL-C measurements. The calculated risk percentage helps determine whether treatment is needed, and if so, what intensity of treatment is needed. The treatment strategy is then focused on reducing the risk rather than on treating cholesterol levels.
• The Framingham Risk Score (Adult Treatment Panel III [ATP-III]) is an algorithm to help predict risk specifically for coronary heart disease (CHD), specifically, in a White population and tends to be more accurate for women. 
• The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of risk factors that predicts progression to clinically overt cardiovascular disease (CVD) or progression of subclinical disease; it is more appropriate for patients 45-85 years old and of select racial/ethnic groups. 
• The Reynolds Risk Score is a risk calculator that includes hsCRP results and family history of premature ASCVD, in addition to other factors. 
• The United Kingdom Prospective Diabetes Study (UKPDS) risk engine calculates ASCVD risk specifically in individuals with type 2 DM. 

Screening

The AACE and ACE have issued the following screening recommendations :

• Individuals with a family history of premature ASCVD or high cholesterol levels should be screened for familial hypercholesterolemia.
• Children at risk for familial hypercholesterolemia should be screened for dyslipidemia at 3 years, between 9 and 11 years, and at 18 years old.
• Adolescents older than 16 years who have ASCVD risk factors, are overweight or obese, or have other symptoms of insulin resistance should be screened for dyslipidemia every 5 years or more frequently.
• Adults with type 1 or type 2 DM should be screened annually for dyslipidemia.
• Men 20-45 years old or women 20-55 years old without ASCVD risk factors should be screened for dyslipidemia every 5 years.
• Men 45-65 years old and women 55-65 years old without ASCVD risk factors should be screened for dyslipidemia at least every 1-2 years. Clinical judgment should be used to modify testing intervals as appropriate.
• Adults older than 65 years with one or no risk factors should be screened for dyslipidemia annually; those with two or more ASCVD risk factors should have a lipid assessment performed.

In 2016, the U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend or discourage screening for dyslipidemia in adults 21-39 years old or in children and adolescents ; however, there is no guidance for patients younger than 40 years in the most recent guideline.  Clinicians should use their judgment.  Nontraditional markers are not recommended for routine screening or risk assessment in asymptomatic adults, and routine testing of children for nontraditional risk factors/biomarkers is also not recommended, due to a lack of convincing data.  Additionally, patients receiving statin therapy should be screened for new-onset DM according to current DM guidelines. 

Laboratory Testing

Traditional Risk Markers

Traditional risk markers are often assessed using a lipid panel. Fasting measurements of total cholesterol, LDL-C, HDL-C, and triglycerides provide the most precise lipid assessment.  Nonfasting measurements can be taken if fasting is impractical. 

Total Cholesterol

A total cholesterol test provides one measurement for the total amount of cholesterol in the blood, including LDL-C, HDL-C, and triglycerides. 

Low-Density Lipoprotein Cholesterol

Although an LDL-C level is usually derived using an equation with other lipid measurements, a direct LDL-C measurement should be ordered in patients with DM, known vascular disease, or a fasting triglyceride level above standard reference limits. 

High-Density Lipoprotein Cholesterol

HDL-C measurements should be part of dyslipidemia screening tests.  Non-HDL-C measurements can be derived by subtracting HDL-C from total cholesterol concentrations. A non-HDL-C level helps determine risk in patients with DM, established ASCVD, or elevated triglycerides; it can also provide information on a patient’s total atherogenic lipoprotein burden. 

Triglycerides

Triglyceride testing can help identify patients with insulin resistance syndrome or those at an increased risk for ASCVD; it should be included in routine screening. 

Nontraditional Risk Markers

High-Sensitivity C-Reactive Protein

An hsCRP measurement can help stratify risk in individuals assessed as having borderline risk or with intermediate or high risk and a normal to low LDL-C measurement. ^,  The USPSTF 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.

Apolipoproteins

In individuals at higher risk of ASCVD, an apolipoprotein B (apoB) evaluation may be helpful to further assess risk and guide decision-making. ApoB measurements are recommended to improve risk prediction  however, the usefulness of apoB in assessing risk for a first ASCVD event is uncertain.  ApoB measurements that reflect LDL particle concentrations and other atherogenic lipoprotein levels may be useful for risk assessment when fasting LDL measurements are impractical,  and measuring apoB may help determine therapy success. 

Lipoprotein(a)

Although there is no recommendation for screening the general population for lipoprotein(a) [Lp(a)] concentrations, Lp(a) testing may be considered in patients with a family history of early ASCVD or to refine the evaluation of patients at moderate risk; high concentrations may support more aggressive control of other lipoprotein factors. 

Lipoprotein Particle Count

Lipoprotein particle number evaluation (eg, with the LipoFit test) may be appropriate for high-risk patients, such as those with type 2 DM, to guide and refine therapy; it is not necessary for routine CVD risk assessment in most individuals.

Lipoprotein-Associated Phospholipase A₂

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is an indicator specifically of vascular inflammation, independent of obesity.  Measurements can provide additional information for risk stratification and can be especially useful in the presence of hsCRP elevations.  Studies have shown that Lp-PLA₂ has greater specificity than hsCRP. Individuals with elevated Lp-PLA₂ and hsCRP concentrations are at substantial risk, even with low or moderately elevated LDL-C levels. 

Genotyping

The apolipoprotein E (APOE) gene is associated with modulation of the plasma lipids profile. APOE genotyping can provide supporting evidence for a diagnosis of premature coronary heart disease; it can also be used to screen individuals with a family history of type III hyperlipoproteinemia. It should be used for CVD risk assessment only and has variable significance in prediction.

Evaluation for variants in the LDLR, APOB, PCSK9, and LDLRAP1 genes may be appropriate in individuals with familial hypercholesterolemia to identify the genetic cause.

Monitoring

Lipid testing is recommended to assess the impact of medication and lifestyle adjustments. A baseline fasting lipid panel should be repeated 1-3 months after statin initiation, after which monitoring with a lipid evaluation should be performed every 3-12 months.  The ACC/AHA guidelines deemphasize fixed goals for LDL and HDL levels and instead support a percentage decrease in LDL-C.  AACE/ACE guidelines recommend treating to achieve lipid targets based on risk category.