Description

Cardiovascular risk assessment comprises the means and processes to predict the probability of developing a cardiovascular disease. These are a group of tests and health factors that have been proven to indicate a person's chance of having a cardiovascular event such as a heart attack or stroke. This policy addresses genetic markers that are associated with cardiovascular disease risk. Terms such as male and female are used when necessary to refer to sex assigned at birth.

Policy 
Application of coverage criteria is dependent upon an individual’s benefit coverage at the time of the request.

1. For individuals 18 years of age or older, lipid panel testing (see Note 1) is considered MEDICALLY NECESSARY under any of the following conditions:
   1. To screen for cardiovascular disease (CVD) risk:
      1. Every 4 years for individuals ages 18 to 79 years.
      2. Annually for individuals at increased risk for cardiovascular disease (as defined by 2013 ACC/AHA Pooled Cohort Equations (PCEs) to calculate 10-year risk of CVD events [see Note 2]).
   2. Annually for individuals at an increased risk of dyslipidemia due to any of the following conditions:
      1. Obesity or metabolic syndrome
      2. Nephrotic syndrome
      3. Hypothyroidism
      4. Hyperthyroidism
      5. Pancreatitis
      6. Diabetes
      7. Chronic kidney disease
      8. Cushing syndrome
      9. Pregnancy
      10. Cholestatic liver disease
      11. Lipid metabolism disorders, such as Gaucher disease in adults
   3. For individuals who are about to begin or who are currently receiving statin therapy, at the following intervals:
      1. To establish baseline levels before initiating statin therapy.
      2. Every four to twelve weeks after initiation or change of therapy.
      3. Annually when no medication changes have occurred.
   4. Annually for individuals on a long-term drug therapy that requires lipid monitoring (e.g., Accutane, anti-psychotics).
   5. For HIV positive individuals who are about to begin or who are currently receiving antiretroviral therapy (ART), at the following intervals:
      1. To establish baseline levels before initiating ART.
      2. Every one to three months after initiation or change of therapy.
      3. Every six to twelve months when no medication changes have occurred.
2. Measurement of apolipoprotein B (apoB) is considered MEDICALLY NECESSARY for any of the following situations:
   1. For individuals with hypertriglyceridemia.
   2. For individuals with diabetes mellitus.
   3. For individuals with obesity or metabolic syndrome.
   4. For individuals with other dyslipidemias (such as very low LDL-C).
   5. For individuals who are on lipid therapy.
   6. For individuals who are suspected to have familial dysbetalipoproteinemia or familial combined hyperlipidemia.
3. For individuals 18 years of age or older, measurement of lipoprotein a (Lp[a]) once per lifetime is considered MEDICALLY NECESSARY.
4. For individuals for whom a risk-based treatment decision is uncertain (after quantitative risk assessment using ACC/AHA PCEs to calculate 10-year risk of CVD events [see Note 2]), testing for C-reactive protein with the high-sensitivity method (hs-CRP) is considered MEDICALLY NECESSARY at the following frequency:
   1. For initial screening, two measurements at least two weeks apart.
   2. If the initial screen was abnormal, follow-up screening is allowed up to once per year.

The following does not meet coverage criteria due to a lack of available published scientific literature confirming that the test(s) is/are required and beneficial for the diagnosis and treatment of an individual’s illness.

5. For all other cardiovascular disease risk assessments not described above, testing for CRP is considered NOT MEDICALLY NECESSARY.
6. For CVD risk assessment and stratification in the outpatient setting, measurement of high-sensitivity cardiac troponin T (hs-cTnT) is considered NOT MEDICALLY NECESSARY.
7. For CVD risk assessment screening, evaluation, and management, homocysteine testing is considered NOT MEDICALLY NECESSARY.
8. For CVD risk assessment, measurement of novel lipid and non‒lipid biomarkers (e.g., apolipoprotein AI, apolipoprotein E, B-type natriuretic peptide, cystatin C, fibrinogen, leptin, LDL subclass, HDL subclass) is considered NOT MEDICALLY NECESSARY.
9. Other than simple lipid panels (see Note 1), CVD risk panels consisting of multiple individual biomarkers intended to assess CVD is considered NOT MEDICALLY NECESSARY.
10. For CVD risk assessment, measurement of serum intermediate density lipoproteins is considered NOT MEDICALLY NECESSARY.
11. For CVD risk assessment, measurement of lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered NOT MEDICALLY NECESSARY.
12. For all situations, measurement of long-chain omega-3 fatty acids in red blood cell membranes, is considered NOT MEDICALLY NECESSARY.
13. All other tests for assessing CVD risk is considered NOT MEDICALLY NECESSARY. 

NOTES:

Note 1: A simple lipid panel is generally composed of the following lipid markers:

• Total cholesterol
• HDL cholesterol
• LDL cholesterol
• Triglycerides

Certain calculated ratios, such as the total/HDL cholesterol may also be reported as part of a simple lipid panel.

Other types of lipid testing (i.e., apolipoproteins, lipid particle number or particle size, lipoprotein [a]) are not considered to be components of a simple lipid profile.

Note 2: 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk (Goff et al., 2014): Risk factors include gender, age, race, smoking, hypertension, diabetes, total cholesterol, high- and low-density lipoprotein cholesterol. A race- and sex-specific PCE ASCVD Risk Estimator is available at https://tools.acc.org/ldl/ascvd_risk_estimator/index.html#!/calulate/estimator/.

The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol affirms that “the PCE is a powerful tool to predict population risk, but it has limitations when applied to individuals.” Hence a clinician-patient risk discussion can individualize risk status based on PCE, but with the inclusion of additional risk-enhancing factors. These additional factors may include:

• A family history of premature ASCVD (males, age < 55 y; females, age < 65 y)
• Primary hypercholesterolemia (LDL-C, 160 – 189 mg/dL [4.1 – 4.8 mmol/L); nonHDL-C 190 – 219 mg/dL [4.9 – 5.6 mmol/L])
• Metabolic syndrome (increased waist circumference, elevated triglycerides [> 150 mg/dL], elevated blood pressure, elevated glucose, and low HDL-C [< 40 mg/dL in men; < 50 in women mg/dL] are factors; tally of 3 makes the diagnosis)
• Chronic kidney disease (eGFR 15 – 59 mL/min/1.73 m2 with or without albuminuria; not treated with dialysis or kidney transplantation)
• Chronic inflammatory conditions such as psoriasis, RA, or HIV/AIDS
• History of premature menopause (before age 40 y) and history of pregnancy-associated conditions that increase later ASCVD risk such as preeclampsia
• High-risk race/ethnicities (e.g., South Asian ancestry)
• Lipid/biomarkers: Associated with increased ASCVD risk
• Persistently elevated, primary hypertriglyceridemia (≥ 175 mg/dL)
• Elevated high-sensitivity C-reactive protein (≥ 2.0 mg/L)
• Elevated Lp(a): A relative indication for its measurement is family history of premature ASCVD. An Lp(a) ≥ 50 mg/dL or ≥ 125 nmol/L constitutes a risk-enhancing factor especially at higher levels of Lp(a)
• Elevated apoB ≥ 130 mg/dL: A relative indication for its measurement would be triglyceride ≥ 200 mg/dL. A level ≥ 130 mg/dL corresponds to an LDL-C ≥ 160 mg/dL and constitutes a risk-enhancing factor
• ABI < 0.9

Table of Terminology    

Term	Definition
AA	Arachidonic acid
AACE	American Association of Clinical Endocrinologists
AACVPR	American Association of Cardiovascular and Pulmonary Rehabilitation
AAPA	American Academy of Physician Assistants
ABC	Association of Black Cardiologists
ABI	Ankle-brachial index
ACC	American College of Cardiology
ACCF	American College of Cardiology Foundation
ACE	American College of Endocrinology
ACPM	American College of Preventive Medicine
ADA	American Diabetes Association
ADMA	Asymmetric dimethylarginine
AGS	American Geriatrics Society
AHA	American Heart Association
Anti-CCP	Anti–cyclic citrullinated peptide
APhA	American Pharmacists Association
Apo A-I	Apolipoprotein A-I
Apo B	Apolipoprotein B
Apo C-III	Apolipoprotein C-III
Apo E	Apolipoprotein E
APs	Antipsychotics
ART	Antiretroviral therapy
ASCP	American Society for Clinical Pathology
ASCVD	Atherosclerotic cardiovascular disease
ASH	American Society of Hypertension
ASPC	American Society for Preventive Cardiology
BMI	Body mass index
BNP	Brain natriuretic peptide
CAC	Coronary artery calcium
CAD	Coronary artery disease
CCS	Canadian Cardiovascular Society
CDC	Centers for Disease Control and Prevention
CHARGE	Cohorts for Heart and Aging Research in Genomic Epidemiology
CHD	Coronary heart disease
CIMT	Carotid intima media thickness
CK	Creatine kinase
CKD	Chronic kidney disease
CRP	C reactive protein
cTnl	Cardiac troponin l
cTnT	Cardiac troponin T
CVD	Cardiovascular disease
DHA	Docosahexaenoic acid
DM	Diabetes mellitus
DoD	Department of Defense
DPA	Docosapentaenoic acid
EACPR	European Association for Cardiovascular Prevention & Rehabilitation
EAS	European Atherosclerosis Society
EASD	European Association for the Study of Diabetes
EEG	Electroencephalography
ELISA	Enzyme-linked immunosorbent assay
EPA	Eicosapentaenoic acid
ES	Endocrine Society
ESC	European Society of Cardiology
FDA	Food and Drug Administration
FH	Familial hypercholesterolemia
Fix	Family history
GDMT	Guideline-directed medical therapy
GFR	Glomerular filtration rate
GGT	Gamma-glutamyltransferase
GlycA	Glycoprotein acetyls
HDL	High-density lipoprotein
HDL-C	High-density lipoprotein cholesterol
HF	Heart failure
HIV	Human immunodeficiency virus
HRs	Hazard ratios
hsCRP	High-sensitivity C reactive protein
hs-cTnI	High-sensitivity cardiac troponin i
hs-cTnT	High-sensitivity cardiac troponin t
IDL	Intermediate density lipoproteins
LDL	Low-density lipoprotein
LDL-C	Low-density lipoprotein cholesterol
LDTs	Laboratory developed tests
Lp(a)	Lipoprotein A
LPA	Apolipoprotein(a) locus
Lp-PLA2	Lipoprotein-associated Phospholipase A2
LSP	Lipids Standardization Program
MACE	Major adverse cardiovascular event
NICE	National Institute for Health and Care Excellence
NLA	National Lipid Association
NMA	National Medical Association
Non-HDL-C	Non-high-density lipoprotein cholesterol
NT-proBNP	Amino-terminal pro-B-type natriuretic peptide
PAD	Peripheral artery disease
PCEs	Pooled cohort equations
PCNA	Preventive Cardiovascular Nurses Association
proBNP	Pro-B-type natriuretic peptide
RR	Risk ratio
sdLDL	Small dense low-density lipoprotein
SDMA	Symmetric dimethylarginine
SIGN	Scottish Intercollegiate Guidelines Network
SMC™	Single Molecule Counting
T1DM	Type 1 diabetes mellitus
T2DM	Type 2 diabetes mellitus
TC	Total cholesterol
TG	Triglyceride
USPSTF	U.S. Preventive Services Task Force
VA	Veterans Affairs
VLDL	Very low-density lipoprotein

Rationale  

Proprietary Testing
Cardiovascular Risk Panels/Profiles
Cardiovascular risk panels refer to combinations of cardiac markers that are used for the risk assessment of developing cardiovascular disease, major adverse cardiovascular events, or ischemic cerebrovascular events. Commercially available risk panels use different combinations of lipids, inflammatory, genetic, and metabolic markers. Risk panels report the results of multiple individual tests, whereas quantitative risk scores generally use proprietary algorithms to combine the results of multiple markers into one score. The clinical utility of risk panels is lacking as the impact of results on patient management is unknown. 

Examples of commercially available cardiovascular risk panels include, but are not limited to:

1.   Genova Diagnostics Cardio Check™ Panel:

• Lipid markers (LDL; total cholesterol; HDL; triglycerides; lipoprotein (a); total cholesterol/HDL ratio; triglycerides/HDL ratio)
• Independent risk factors (hs-CRP; homocysteine)
• Insulin
• Sex hormone markers (testosterone, total; sex hormone binding globulin) (Genova Diagnostics, 2023).

2.   Cleveland HeartLab CVD Inflammation Testing Profile

• F2-isoprostanes; oxidized LDL; hs-CRP; ADMA/SDMA; microalbumin; myeloperoxidase; Lp-PLA2 activity (HeartLab, 2023).

3. Thorne various packages:

• Basic offerings include panels with markers such as Apo A-1 and Apo-B; the e-checkup comes with markers such as total cholesterol, HDL, LDL and Triglycerides, the basic panel adds additional biomarkers and the “premium” panel assesses 92 markers (Thorne, 2024). 

American College of Cardiology (ACC) and the American Heart Association (AHA) 

• The 2019 ACC and AHA guidelines state that “Adults who are 40 to 75 years of age and are being evaluated for cardiovascular disease prevention should undergo 10-year atherosclerotic cardiovascular disease (ASCVD) risk estimation and have a clinician–patient risk discussion before starting on pharmacological therapy, such as antihypertensive therapy, a statin, or aspirin. In addition, assessing for other risk-enhancing factors can help guide decisions about preventive interventions in select individuals, as can coronary artery calcium scanning” (Arnett et al., 2019).

  Laboratory testing was not addressed in this update.

  The ACC and AHA published joint guidelines on the assessment of cardiovascular risk in asymptomatic patients in 2010 (Greenland et al., 2010), and updated in 2013 (Goff et al., 2014).

  In adults between the ages of 20 and 79 who are free from CVD, the ACC/AHA state that it is reasonable to assess risk factors (smoking, hypertension, diabetes, total cholesterol, high density lipoprotein cholesterol) every four to six years so as to calculate 10-year CVD risk (Goff et al., 2014).

  The ACC/AHA also made the following recommendations on reclassification or contribution to risk assessment when high-sensitivity C-reactive protein (hs-CRP), apolipoprotein B (ApoB), glomerular filtration rate (GFR), microalbuminuria, family history, cardiorespiratory fitness, ankle-brachial index (ABI), carotid intima-media thickness (CIMT), or coronary artery calcium (CAC) score are considered in addition to the variables that are in the traditional risk scores:

• If, after quantitative risk assessment, a risk-based treatment decision is uncertain, assessment of one or more of the following—family history, hs-CRP, ABI or CAC may be considered to inform treatment decision making.
• CIMT is not recommended for routine measurement in clinical practice for risk assessment for a first ASCVD event.
• The contribution to risk assessment for a first ASCVD event using ApoB, chronic kidney disease, albuminuria, or cardiorespiratory fitness is uncertain at present (Goff et al., 2014).

• The 2010 guidelines contained the following statement concerning testing for Lp-PLA2: Lipoprotein-associated phospholipase A2 might be reasonable for cardiovascular risk assessment in intermediate-risk asymptomatic adults. However, the 2013 guidelines on the assessment of cardiovascular risk do not mention Lp-PLA2 testing (Goff et al., 2014; Greenland et al., 2010).

  The updated guidelines do not address arterial compliance, lipoprotein-associated phospholipase, long-chain omega-3 fatty acids, or endothelial function assessment as methods to assess initial CVD risk (Goff et al., 2014; Greenland et al., 2010).

  The ACC notes cutoffs of certain biomarkers for increased ASCVD risk, which are as follows: persistently elevated, primary hypertriglyceridemia ≥ 175 mg/dL, ≥ 2 mg/L hs-CRP, ≥ 50 mg/dL or ≥ 125 nmol Lp(a), ≥ 130 mg/dL Apo B (corresponding to > 160 mg/dL LDL-C), and < 0.9 ankle-brachial index (ABI) (ACC, 2018; Grundy et al., 2018). 

  The ACC and AHA also released joint guidelines with the AAPA, ABC, ACPM, AGS, APhA, ASH, ASPC, NMA, and PCNA, stating that screening and management of dyslipidemia/hypercholesterolemia is recommended in adults with hypertension (defined as >130/80 mmHg) (Whelton et al., 2018).

2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines 
This joint report discusses management of blood cholesterol. The report addresses treatments, populations of interest, and serum assessments of relevant cardiovascular biomarkers such as Apo B and lipoprotein A. The relevant recommendations are listed below:

The report notes that although measurement of Apo B may be “unreliable,” persistent elevation of Apo B may be considered a risk factor. The report remarks that a level of >130 mg/dL Apo B should be considered a risk-enhancing factor [of ASCVD], as it corresponds to an LDL-C level of ≥160 mg/dL. 

The report also remarks that Lp(a) is considered a risk factor for ASCVD at levels of “≥ 50 mg/dL or ≥ 125 nmol/L.” However, the authors write that it should be “considered in women only in the presence of hypercholesterolemia and with the understanding that the improvement in risk prediction in adult women in a large clinical trial was minimal.”

Authors also recommend assessing “adherence and percentage response to LDL-C–lowering medications and lifestyle changes with repeat lipid measurement 4 to 12 weeks after statin initiation or dose adjustment, repeated every 3 to 12 months as needed.”

The power of these risk factors can be seen in the “pooled cohort equation”, “the single most robust tool for estimating 10-year risk in US adults 40 to 75 years of age.” These algorithms have strong representative power for larger populations. However, a notable limitation of these algorithms is that they are not as accurate for individuals. Hence a clinician-patient risk discussion can individualize risk status based on PCE, but with the inclusion of additional risk-enhancing factors. These additional factors may include: 

• “A family history of premature ASCVD (males, age < 55 y; females, age < 65 y)
• Primary hypercholesterolemia (LDL-C, 160 – 189 mg/dL [4.1 – 4.8 mmol/L); non-HDL-C 190 – 219 mg/dL [4.9 – 5.6 mmol/L])
• Metabolic syndrome (increased waist circumference, elevated triglycerides [> 150 mg/dL], elevated blood pressure, elevated glucose, and low HDL-C [< 40 mg/dL in men; < 50 in women mg/dL] are factors; tally of 3 makes the diagnosis)
• Chronic kidney disease (eGFR 15 – 59 mL/min/1.73 m2 with or without albuminuria; not treated with dialysis or kidney transplantation)
• Chronic inflammatory conditions such as psoriasis, RA, or HIV/AIDS
• History of premature menopause (before age 40 y) and history of pregnancy-associated conditions that increase later ASCVD risk such as preeclampsia
• High-risk race/ethnicities (e.g., South Asian ancestry)
• Lipid/biomarkers: Associated with increased ASCVD risk
• Persistently elevated, primary hypertriglyceridemia (≥ 175 mg/dL)
• Elevated high-sensitivity C-reactive protein (≥ 2.0 mg/L)
• Elevated Lp(a): A relative indication for its measurement is family history of premature ASCVD. An Lp(a) ≥ 50 mg/dL or ≥ 125 nmol/L constitutes a risk-enhancing factor especially at higher levels of Lp(a)
• Elevated apoB ≥ 130 mg/dL: A relative indication for its measurement would be triglyceride ≥ 200 mg/dL. A level ≥ 130 mg/dL corresponds to an LDL-C ≥ 160 mg/dL and constitutes a risk-enhancing factor
• ABI < 0.9” (Grundy et al., 2018)

American Diabetes Association (ADA)
The updated ADA Standards of Medical Care in Diabetes document also includes a section focused on cardiovascular disease and risk management. Relevant guidelines and notes are captured below.

• “Blood pressure should be measured at every routine clinical visit. When possible, individuals found to have elevated blood pressure (systolic blood pressure 120 – 129 mmHg and diastolic < 80 mmHg) should have blood pressure confirmed using multiple readings, including measurements on a separate day, to diagnose hypertension.”
• “All people with hypertension and diabetes should monitor their blood pressure at home .”
• “In asymptomatic patients, routine screening for coronary artery disease is not recommended as it does not improve outcomes as long as atherosclerotic cardiovascular disease risk factors are treated.”
• “Consider investigations for coronary artery disease in the presence of any of the following: atypical cardiac symptoms (e.g., unexplained dyspnea, chest discomfort); signs or symptoms of associated vascular disease including carotid bruits, transient ischemic attack, stroke, claudication, or peripheral arterial disease; or electrocardiogram abnormalities.”
• “Candidates for advanced or invasive cardiac testing include those with 1) typical or atypical cardiac symptoms and 2) an abnormal resting electrocardiogram (ECG). Exercise ECG testing without or with echocardiography may be used as the initial test. In adults with diabetes ≥ 40 years of age, measurement of coronary artery calcium is also reasonable for cardiovascular risk assessment. Pharmacologic stress echocardiography or nuclear imaging should be considered in individuals with diabetes in whom resting ECG abnormalities preclude exercise stress testing (e.g., left bundle branch block or ST-T abnormalities). In addition, individuals who require stress testing and are unable to exercise should undergo pharmacologic stress echocardiography or nuclear imaging.”
• “The screening of asymptomatic patients with high ASCVD risk is not recommended, in part because these high-risk patients should already be receiving intensive medical therapy — an approach that provides benefit similar to invasive revascularization.”
• “In adults not taking statins or other lipid-lowering therapy, it is reasonable to obtain a lipid profile at the time of diabetes diagnosis, at an initial medical evaluation, and every 5 years thereafter if under the age of 40 years, or more frequently if indicated.”
• “…risk scores and other cardiovascular biomarkers have been developed for risk stratification of secondary prevention patients (i.e., those who are already high risk because they have ASCVD) but are not yet in widespread use.”
• “The American College of Cardiology/American Heart Association ASCVD risk calculator (Risk Estimator Plus) is generally a useful tool to estimate 10-year risk of a first ASCVD event. … The 10-year risk of a first ASCVD event should be assessed to better stratify ASCVD risk and help guide therapy, as described below.”
• “Obtain a lipid profile at initiation of statins or other lipid-lowering therapy, 4 – 12 weeks after initiation or a change in dose, and annually thereafter as it may help to monitor the response to therapy and inform medication adherence” (ADA, 2020, 2021b, 2023).

Also, for children and adolescents, the following recommendations were given for dyslipidemia testing:

• “Initial lipid testing should be performed when initial glycemic control has been achieved and age is ≥ 2 years. If initial LDL cholesterol is ≤ 100 mg/dL (2.6 mmol/L), subsequent testing should be performed at 9 – 11 years of age. Initial testing may be done with a nonfasting non-HDL cholesterol level with confirmatory testing with a fasting lipid panel.
• If LDL cholesterol values are within the accepted risk level (< 100 mg/dL [2.6 mmol/L]), a lipid profile repeated every 3 years is reasonable” (ADA, 2020, 2021a).

National Lipid Association (NLA)
The NLA published a scientific statement for lipid measurements in the management of cardiovascular disease, and their recommendations (with evidence rating of “B” or higher) are included below:

• “It is recommended to follow up abnormal screening lipid measurements with fasting lipid measurement (Strength: IIa. Evidence: B-NR)
• LDL-C in adults ≥ 190 mg/dL (≥160 mg/dl in children) is recommended to be reported as possible Familial Hypercholesterolemia (Strength: I. Evidence: B-NR)
• Non-HDL-C in adults ≥ 220 mg/dL is recommended to be reported as possible inherited hyperlipidemia (Strength: I. Evidence: B-NR)
• Triglyceride concentration ≥ 500 mg/dL is recommended to be reported as severe hypertriglyceridemia (Strength: I. Evidence: B-NR)
• Lipid measurements are recommended at 3 – 12 months for those on a stable medication regimen (Strength: I. Evidence: B-NR)
• Lipid measurements are recommended 4 – 12 weeks after a change in lipid treatment (Strength: I. Evidence: B-NR)
• LDL-C measurement is recommended for screening (Strength: I. Evidence: B-NR)
• LDL-C measurement is recommended on lipid therapy (Strength: I. Evidence: B-NR)
• Non-HDL-C measurement is recommended for screening (Strength: I. Evidence: B-NR)
• Non-HDL-C measurement is recommended on lipid therapy (Strength: I. Evidence: B-NR)
• Apolipoprotein B measurement may be reasonable for initial evaluation (Strength: IIb. Evidence: B-NR)
• Apolipoprotein B measurement is reasonable on lipid therapy (Strength: IIa. Evidence: B-NR)
• Apolipoprotein B measurement is recommended to facilitate diagnosis of Familial Dysbetalipoproteinemia and Familial Combined Hyperlipidemia (Strength: IIb. Evidence: B-NR)
• Lipoprotein (a) measurement is reasonable for initial evaluation in those with premature ASCVD, family history of premature ASCVD or of elevated Lp(a), history of LDL-C >190 mg/dL or suspected FH, or those with very high ASCVD risk (Strength: IIa. Evidence: B-NR)
• Lipoprotein (a) measurement may be reasonable on lipid therapy to determine those who may benefit from PCSK9 therapy who are already on maximal dose statin therapy ± ezetimibe, whose LDL-C remains above 70 mg/dl (Strength: IIb. Evidence: B-NR)”

Wilson et al. (2019) published a scientific statement to provide an update on the use of lipoprotein A [Lp(a)] in the clinical setting, particularly for atherosclerotic cardiovascular disease (ASCVD).

The Association lists the following recommendations for Lp(a) testing in clinical practice:

For adults over 20 years old, “Measurement of Lp(a) is reasonable to refine risk assessment for ASCVD events in:

• Individuals with a family history of first-degree relatives with premature ASCVD (<55 y[ears] of age in men, 65 y of age in women)
• Individuals with premature ASCVD (males aged < 55 y and females aged < 65 y), particularly in the absence of traditional risk factors
• Individuals with primary severe hypercholesterolemia (LDL ≥ 190 mg/dL) or suspected FH [familial hypercholesterolemia]
• Individuals at very high** risk of ASCVD to better define those who are more likely to benefit from PCSK9 inhibitor therapy.”

**Very high risk is defined as “Individuals with a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions.”

The guidelines further remark that “Measurement of Lp(a) may be reasonable with:

• Intermediate (7.5% – 19.9%) 10-y ASCVD risk when the decision to use a statin is uncertain, to improve risk stratification in primary prevention.
• Borderline (5% – 7.4%) 10-y ASCVD risk when the decision to use a statin is uncertain, to improve risk stratification in primary prevention.
• Less-than-anticipated LDL-C lowering, despite good adherence to therapy.
• A family history of elevated Lp(a).
• Calcific valvular aortic stenosis.
• Recurrent or progressive ASCVD, despite optimal lipid-lowering therapy.”

Finally, the guidelines list recommendations for “youth” (< 20 years old), stating that “Measurement of Lp(a) may be reasonable with:

• Clinically suspected or genetically confirmed FH.
• Individuals with a family history of first-degree relatives with premature ASCVD (< 55 y of age in men, 65 y of age in women)
• An unknown cause of ischemic stroke
• A parent or sibling found to have an elevated Lp(a)” (Wilson et al., 2019).

A 2021 update was published, focused on practical and analytical recommendations (Wilson et al., 2021):

“Highlights include the following:

• It is acceptable to screen with nonfasting lipids.
• Non-high-density lipoprotein HDL-cholesterol (non-HDL-C) is measured reliably in either the fasting or the nonfasting state and can effectively guide ASCVD prevention.
• Low density lipoprotein cholesterol (LDL-C) can be estimated from total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglyceride (TG) measurements. For patients with LDL-C > 100 mg/dL and TG ≤150 mg/dL it is reasonable to use the Friedewald formula. However, for those with TG 150 – 400 mg/dL the Friedewald formula for LDL-C estimation is less accurate. The Martin/Hopkins method is recommended for LDL-C estimation throughout the range of LDL-C levels and up to TG levels of 399 mg/dL. For TG levels ≥ 400 mg/dL LDL-C estimating equations are currently not recommended and newer methods are being evaluated.
• When LDL-C or TG screening results are abnormal the clinician should consider obtaining fasting lipids.
• Advanced lipoprotein tests using apolipoprotein B (apoB), LDL Particle Number (LDL-P) or remnant cholesterol may help to guide therapeutic decisions in select patients, but data are limited for patients already on lipid lowering therapy with low LDL-C levels. Better harmonization of advanced lipid measurement methods is needed. Lipid measurements are recommended 4 – 12 weeks after a change in lipid treatment. Lipid laboratory reports should denote desirable values and specifically identify extremely elevated LDL-C levels (≥ 190 mg/dL at any age or ≥ 160 mg/dL in children) as severe hypercholesterolemia. Potentially actionable abnormal lipid test results, including fasting triglycerides (TG) ≥ 500 mg/dL, should be reported as hypertriglyceridemia. Appropriate use and reporting of lipid tests should improve their utility in the management of persons at high risk for ASCVD events.”

Centers for Disease Control and Prevention (CDC)
The CDC highlights the importance of cardiovascular disease biomarkers and has developed a reference laboratory and clinical standardization program to provide reference measurements for HDL-C, LDL-C, TG and total cholesterol (TC). The accuracy of the labs that analyze these biomarkers is also monitored by the CDC (CDC, 2024a).

The CDC notes that several health conditions increase the risk of heart disease including smoking, diabetes mellitus, obesity, high blood pressure, excessive alcohol use, physical inactivity, and unhealthy blood cholesterol levels. It is stated that “High blood cholesterol usually has no signs or symptoms. The only way to know whether you have high cholesterol is to get your cholesterol checked. Your health care team can do a simple blood test, called a “lipid profile,” to measure your cholesterol levels (CDC, 2024b).

The CDC has also developed the Lipids Standardization Program (LSP). This program ensures that the measurements reported in research studies and clinical laboratories are accurate. Blinded samples traceable to the CDC Reference Laboratory are provided to participants. The samples will be measured for total cholesterol (TC), glycerides (TG), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (apo A-I), and apolipoprotein B (apo B). LSP participants report their results from the provided samples back to the CDC where these results are then analyzed; if results are accurate, those laboratories receive a certificate and are considered CDC-certified (CDC, 2023).

Centers for Disease Control and Prevention (CDC)/American Heart Association (AHA)
In 2002, the CDC and AHA held the “CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease: Applications to Clinical and Public Health Practice” and released these recommendations in 2003. In this workshop, they looked at evidence surrounding multiple inflammatory markers and based on all considerations, they stated that “it is most reasonable to limit current assays of inflammatory markers to hs-CRP, measured twice, either fasting or nonfasting, with the average expressed in mg/L, in metabolically stable patients.” More specifically, they indicate that the two measurements of hs-CRP should optimally occur two weeks apart. If results are abnormal, hs-CRP testing should be repeated and the patient should be examined for sources of infection or inflammation. Furthermore, they provide the following recommendation specific to hs-CRP: “On the basis of the available evidence, the Writing Group recommends against screening of the entire adult population for hs-CRP as a public health measure. The Writing Group does conclude that it is reasonable to measure hs-CRP as an adjunct to the major risk factors to further assess absolute risk for coronary disease primary prevention. At the discretion of the physician, the measurement is considered optional, based on the moderate level of evidence (Evidence Level C). In this role, hs-CRP measurement appears to be best employed to detect enhanced absolute risk in persons in whom multiple risk factor scoring projects a 10-year CHD risk in the range of 10% to 20% (Evidence Level B). However, the benefits of this strategy or any treatment based on this strategy remain uncertain. The finding of a high relative risk level of hs-CRP (> 3.0 mg/L) may allow for intensification of medical therapy to further reduce risk and to motivate some patients to improve their lifestyle or comply with medications prescribed to reduce their risk. Individuals at low risk (< 10% per 10 years) will be unlikely to have a high risk (> 20%) identified through hs-CRP testing. Individuals at high risk (> 20% risk over 10 years) or with established atherosclerotic disease generally should be treated intensively regardless of their hs-CRP levels, so the utility of hs-CRP in secondary prevention appears to be more limited” (Pearson et al., 2003). 

Centers for Medicare & Medicaid Services (CMS)
In 2005, CMS published national coverage determination that discuss appropriate frequency of monitoring for individuals receiving long term pharmacologic treatments that may affect lipid levels and thus may affect that individuals risk of developing CVD. The indications and limitations of coverage state:

“When monitoring long term anti-lipid dietary or pharmacologic therapy and when following patients with borderline high total or LDL cholesterol levels, it is reasonable to perform the lipid panel annually. A lipid panel at a yearly interval will usually be adequate while measurement of the serum total cholesterol or a measured LDL should suffice for interim visits if the patient does not have hypertriglyceridemia” (CMS, 2005).

“Any one component of the panel or a measured LDL may be medically necessary up to six times the first year for monitoring dietary or pharmacologic therapy. More frequent total cholesterol HDL cholesterol, LDL cholesterol and triglyceride testing may be indicated for marked elevations or for changes to anti-lipid therapy due to inadequate initial patient response to dietary or pharmacologic therapy. The LDL cholesterol or total cholesterol may be measured three times yearly after treatment goals have been achieved” (CMS, 2005).

“If no dietary or pharmacological therapy is advised, monitoring is not necessary" (CMS, 2005).

American Heart Association (AHA)
In 2022, the AHA published a scientific statement to highlight the history, biology, pathophysiology, and emerging clinical evidence in the lipoprotein a (Lp[a]) field, where they addressed the “key knowledge gaps and future directions required to mitigate the atherosclerotic cardiovascular disease risk attributable to elevated Lp(a) levels.” In this statement, they noted that “levels of Lp(a) have not been shown to substantially change across the life course, although some variability occurs, as documented by intraindividual temporal variability in serial measurements from placebo-treated subjects in clinical trials.” They also note that “various organizations have proposed to obtain a level once in every adult” (Reyes-Soffer et al., 2022). 

American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) 
The 2017 AACE and ACE Guidelines for Management of Dyslipidemia and Prevention of Cardiovascular Disease recommend:

• Screening guidelines for dyslipidemia vary by age group;
• Although ASCVD risk in young adults is low, adults older than 20 years should be evaluated for dyslipidemia every five years as part of a global risk assessment
• Middle-aged individuals (Men 45 – 65 years, Women 55 – 65 years) should be screened for dyslipidemia at least every one to two years.
• All individuals with diabetes should be screened with a lipid profile at the time of diagnosis and annually thereafter. Some individuals with diabetes can be screened less frequently based on clinical considerations
• Annual screen for dyslipidemia for adults over 65 is recommended
• In children at risk for FH (e.g., family history of premature cardiovascular disease or elevated cholesterol), screening should be at three years of age, between 9 and 11, and at age 18
• Screen adolescents older than 16 years every five years or more frequently if they have ASCVD risk factors, have overweight or obesity, have other elements of the insulin resistance syndrome, or have a family history of premature ASCVD
• Direct measurement of LDL-C should be used to assess LDL-C in certain high-risk individuals, such as those with fasting TG concentrations greater than 250 mg/dL or those with diabetes or known vascular disease
• Apolipoproteins, Apo B and/or an apo B/apo A1 ratio calculation and evaluation may be useful in at-risk individuals.
• hsCRP is recommended to stratify ASCVD risk in individuals with a standard risk assessment that is borderline, or in those with an intermediate or higher risk with an LDL-C concentration <130 mg/dL.
• Lp-PLA2 measurement, is recommended when it is necessary to further stratify an individual’s ASCVD risk, especially in the presence of hsCRP elevations.
• The routine measurement of homocysteine, uric acid, plasminogen activator inhibitor-1, or other inflammatory markers is not recommended because the benefit of doing so is not sufficiently proven.
• Coronary artery calcification measurement has been shown to be of high predictive value and is useful in refining risk stratification
• Carotid intima media thickness (CIMT) may be considered to refine risk stratification (Jellinger et al., 2017).

The AACE/ACE published an updated algorithm in 2020. This algorithm focuses on “management of dyslipidemia and prevention of cardiovascular disease” and “complements” the above guidelines but includes information not available in 2017. Their relevant recommendations are listed below:

The guideline lists Apo B, LDL, Lp(a), and hs-CRP as biomarkers that may be “considered” in assessment of ASCVD risk for patients. The guideline also remarks that “measurement of apo B is useful in assessing the success of lipid-lowering therapy, since apo B may remain above goal after achieving the LDL-C goal.” Apo B is listed as a component of treatment goals, alongside LDL-C, Non-HDL-C, and TG [triglycerides]. 

The guideline recommends “considering” measurement of Lp(a) (lipoprotein A) in the following settings:

• “All patients with clinical ASCVD, especially premature or recurrent ASCVD despite LDL-C lowering;
• Individuals with a family history of premature ASCVD and/or increased Lp(a);
• Individuals with South Asian or African ancestry, especially with a family history of ASCVD or increased Lp(a);
• Individuals with a 10-year ASCVD risk ≥10% (primary prevention setting), in order to stratify risk;
• Patients with a personal or family history of aortic valve stenosis;
• Patients with refractory elevations of LDL-C despite aggressive LDL-C-lowering therapy (i.e., statin resistance)” (AACE, 2021).

The AACE also published a “consensus statement” on the “comprehensive type 2 diabetes management algorithm.” The guideline includes a set of PowerPoint slides at the bottom, which recommend measuring Lp(a) in the following settings: presence of family history of premature ASCVD and/or increased Lp(a), and all patients with premature or recurrent ASCVD despite LDL-C lowering (Garber et al., 2020).

European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Guidelines for the Management of Dyslipidaemias 
The ESC published 2021 guidelines on cardiovascular disease prevention in clinical practice. Their recommendations for CVD risk assessment are included below (Visseren et al., 2021):

The authors include additional recommendations for CVD risk estimation and modification that are tabulated in the full guideline.

The 2019 guidelines from ESC and EAS provided the following recommendations:

• “Lp(a) measurement should be considered at least once in each adult person’s lifetime to identify those with very high inherited Lp(a) levels > 180 mg/dL (>430 nmol/L) who may have a lifetime risk of ASCVD equivalent to the risk associated with heterozygous familial hypercholesterolemia.
• “Persons with documented ASCVD, type 1 or type 2 DM (T1DM and T2DM, respectively), very high levels of individual risk factors, or chronic kidney disease (CKD) are generally at very-high or high total CV risk. No risk estimation models are needed for such persons…”
• ApoB analysis is recommended for risk assessment, particularly in people with high TG, DM, obesity or metabolic syndrome, or very low LDL-C. It can be used as an alternative to LDL-C, if available, as the primary measurement for screening, diagnosis, and management, and may be preferred over non-HDL-C in people with high TG, DM, obesity, or very low LDL-C.
• CAC score assessment with CT may be helpful in reaching decisions about treatment in people who are at moderate risk of ASCVD. Obtaining such a score may assist in discussions about treatment strategies in patients where the LDL-C goal is not achieved with lifestyle intervention alone and there is a question of whether to institute LDL-C-lowering treatment. Assessment of arterial (carotid or femoral) plaque burden on ultrasonography may also be informative in these circumstances” (Mach et al., 2019).

Total cholesterol may be used to estimate total cardiovascular risk. LDL-C is recommended to be used as the primary lipid analysis for diagnosis, management, screening, and risk estimation. HDL-C and Non-HDL-C are also strong, independent risk factors (Catapano et al., 2016).

Apolipoprotein B , Lp(a), Apo B/Apo A-I, and Non-HDL-C/HDL-C may all be used as alternative markers for cardiovascular risk. The guidelines note that measuring Apo B and Apo A-I is convenient, accurate, does not require fasting, and is not susceptible to TG levels. The guidelines also recommend against routine measurement of Apo C-III as its use is unknown (Catapano et al., 2016).

In the 2021 ESC Guidelines on cardiovascular disease prevention, the authors stated that “New studies confirm that C-reactive protein has limited additional value. There is renewed interest in lipoprotein(a), but it too provides limited additional value in terms of reclassification potential. Cardiac biomarkers are promising, but further work is needed” (Visseren et al., 2021). 

European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) 
This joint guideline was published for “diabetes, pre-diabetes, and cardiovascular diseases”. Their specific recommendations relating to cardiovascular risk assessment in patients with diabetes and pre-diabetes are as follows:

• “Routine assessment of microalbuminuria should be carried out to identify patients at risk of developing renal dysfunction and/or CVD.”
• “A resting electrocardiogram (ECG) is indicated in patients with DM and hypertension, or if CVD is suspected.”
• “Other tests, such as transthoracic echocardiography, coronary artery calcium (CAC) score, and ankle–brachial index (ABI), may be considered to test for structural heart disease or as risk modifiers in those at moderate or high risk of CVD.”
• “Routine assessment of novel biomarkers is not recommended for CV risk stratification.”

The guideline noted that “the addition of circulating biomarkers for CV risk assessment has limited clinical value” and stated that “in patients with DM [diabetes mellitus] without known CVD, measurement of C-reactive protein or fibrinogen (inflammatory markers) provides minor incremental value to current risk assessment”. Cosentino et al. (2020) guideline also noted high-sensitivity cardiac troponin T as not adding incremental “discriminative power” for patients with DM without known CVD, although elevated high-sensitivity cardiac troponin T was noted as an independent predictor of renal decline and CV events in patients with type 1 diabetes (Cosentino et al., 2020)

Endocrine Society (ES) 
This guideline was published with the intent to assess and treat dyslipidemia in patients with endocrine disorders. Their relevant recommendations are listed below:

• “In adults with endocrine disorders, we recommend a lipid panel for the assessment of triglyceride levels and for calculating low-density lipoprotein cholesterol.”
• “In adults with endocrine disorders, we recommend conducting a cardiovascular risk assessment by evaluating traditional risk factors, including the calculation of 10-year atherosclerotic cardiovascular disease risk using a tool such as the Pooled Cohort Equations.”
• “In adults with endocrine disorders at borderline or intermediate risk (10-year atherosclerotic cardiovascular disease risk 5%–19.9%), particularly those with additional risk-enhancing factors, in whom the decision about statin treatment and/or other preventive interventions is uncertain, we suggest measuring coronary artery calcium to inform shared decision making.”

The guideline also remarks that certain “advanced” lipid testing (assessment of markers such as Apo B, lipid fractionation, and Lp(a)) may be helpful in “characterizing” lipid abnormalities, but “add little” to risk prediction beyond the standard lipid profile. 

The guideline goes on to discuss Lp(a), noting that the marker can be helpful in assessing familial risk, but adds “little” in terms of global risk assessment across the general population. The guideline acknowledges other evidence supporting Lp(a)’s use as a marker to manage treatment. Other serum biomarkers and biomarker panels were also considered to add “little” to global risk assessment. Finally, the guideline recommends the use of hs-CRP as a “risk-enhancing factor that may drive more aggressive treatment or the need for advanced risk assessment” (Newman et al., 2020).

Rosenzweig et al. (2019) published on the Primary Prevention of ASCVD and T2DM in Patients at Metabolic Risk. A summary of the recommendations is included below (Rosenzweig et al., 2019):

• “In individuals aged 40 – 75 years in the office setting, we suggest providers screen for all five components of metabolic risk at the clinical visit. The finding of at least three components should specifically alert the clinician to a patient at metabolic risk (at higher risk for atherosclerotic cardiovascular disease and type 2 diabetes mellitus).
• In individuals aged 40 – 75 years in the office setting who do not yet have atherosclerotic cardiovascular disease or type 2 diabetes mellitus and already have at least one risk factor, we advise screening every 3 years for all five components of metabolic risk as part of the routine clinical examination.
• To establish metabolic risk in the general population, we recommend that clinicians measure waist circumference as a routine part of the clinical examination.
• In individuals previously diagnosed with prediabetes, we suggest testing at least annually for the presence of overt type 2 diabetes mellitus.
• We recommend that all individuals at metabolic risk in the office setting have their blood pressure measured annually and, if elevated, at each subsequent visit.
• For individuals with elevated blood pressure above 130 mmHg systolic and/or 80 mmHg diastolic who are not documented as having a history of hypertension, we recommend confirmation of elevated blood pressure on a separate day within a few weeks or with a home blood pressure monitor.”

Components of “metabolic risk” are defined as:

• elevated blood pressure
• increased waist circumference
• elevated fasting triglycerides
• low high-density lipoprotein-cholesterol, and
• elevated glycemia

American Society for Clinical Pathology 
The ASCP recommends against routinely ordering expanded lipid panels (such as particle sizing or nuclear magnetic resonance) as screening for cardiovascular disease (ASCP, 2016).

In 2022, the ASCP published a set of clinical recommendations aiming to provide the guidance and the tools for assessment of ASCVD risk with the goal of appropriately targeting treatment approaches for prevention of ASCVD events, as shown below:

“1 Assessing a patient's risk for ASCVD is the foundation of preventive cardiology and the initial step for determining the appropriateness and intensity of preventive treatment.

2 In primary prevention, global risk scoring is the initial stage for ASCVD risk assessment, providing a calculation of ASCVD risk from a set of standard office-based risk factors for a specified duration (e.g., 10 years) of time, from which a clinician-patient risk discussion is used to discuss the best ways to reduce CVD risk.

3 The presence, quantity, and/or extent of one or more risk enhancing factors, including premature family history, persistently elevated LDL-C, or CKD, as well as severity of certain inflammatory factors such as hsCRP and laboratory measures such as lp(a), can further inform the treatment decision.

4 In women, it is important to take a comprehensive reproductive history from menarche to menopause, including preeclampsia, premature menopause, and autoimmune disease as “risk-enhancing” factors.

5 Race/ethnicity may have a significant impact on the validity of current risk assessment tools and certain higher risk race/ethnic groups may further inform the use of preventive therapy.

6 Social determinants of health may exert independent effects beyond race/ethnicity and need also to be part of the clinician-patient discussion when discussing the most appropriate ways to optimize ASCVD risk.

7 Among subclinical atherosclerotic disease screening tests, CAC is probably the most useful, providing substantial improvement of risk reclassification over global risk scoring in most primary prevention groups, including diabetes. In addition to the consideration of risk enhancing factors (discussed earlier), CAC testing can be used to further inform treatment decisions for preventive therapy, including statin and aspirin use in particular.

8 The use of ABI for assessment of PAD is also valuable and can improve risk reclassification beyond global risk scoring.

9 Carotid ultrasound imaging, if accompanied by carotid plaque assessment may also be useful for risk assessment, especially as an option when CAC scoring is not available.

10 In patients with pre-existing ASCVD, stratification into those at highest risk (e.g., very high risk ASCVD status) for more aggressive treatment is based on the history of multiple major ASCVD events or one major event and multiple high-risk conditions. Moreover, those with recurrent ASCVD events in the short-term define an extreme risk condition warranting even more aggressive risk factor management” (Wong et al., 2022).

National Institute for Health and Care Excellence (NICE)
A baseline lipid profile should be taken before treatment. This should include total cholesterol, HDL cholesterol, non-HDL, and triglyceride levels. Total and HDL cholesterol should be measured for best estimate of CVD risk. 

Omega-3 compounds have “no evidence” to help prevent CVD and NICE recommends against distribution of these compounds for CVD treatment (NICE, 2023).

US Preventive Services Task Force (USPSTF) 
The USPSTF Task Force Recommendations include periodic assessment of cardiovascular risk factors from ages 40 to 75 years, including measurement of total cholesterol, LDL-C, and HDL-C levels. The optimal intervals for cardiovascular risk assessment are uncertain. Based on other guidelines and expert opinion, reasonable options include annual assessment of blood pressure and smoking status and measurement of lipid levels every five years. Shorter intervals may be useful for persons at higher risk, and longer intervals are appropriate for persons who are regularly at average risk (Bibbins-Domingo et al., 2017).

The USPSTF found insufficient evidence that screening for dyslipidemia in younger adults influences cardiovascular outcomes, and no studies that evaluated the effects of screening vs no screening, treatment vs no treatment, or delayed vs earlier treatment in adults in this age group. Thus, the USPSTF recommends neither for nor against screening for dyslipidemia in this age group. The USPSTF also noted there was insufficient evidence to assess the balance of benefits and harms of screening for dyslipidemia in children and adolescents (Chou et al., 2016).

The USPSTF states that “current evidence is insufficient to assess the benefits and harms of adding ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) level, or coronary artery calcium (CAC) score to traditional risk assessment for cardiovascular disease (CVD) in asymptomatic adults to prevent CVD events” (USPSTF, 2018a). However, the USPSTF recommends screening for abnormal blood glucose for adults aged 40-70 who are overweight or obese (USPSTF, 2015).

For adults at low risk of CVD events, “The USPSTF recommends against screening with resting or exercise electrocardiography (ECG) to prevent cardiovascular disease (CVD) events” (recommendation grade D, discouraging the use of the service). Moreover, “The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening with resting or exercise ECG to prevent CVD events in asymptomatic adults at intermediate or high risk of CVD events” (recommendation grade I, insufficient evidence) (USPSTF, 2018b).

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for primary hypertension in asymptomatic children and adolescents to prevent subsequent cardiovascular disease (Moyer, 2013). A 2020 recommendation statement by the USPSTF confirmed that the current evidence is insufficient to assess the balance of benefits and harms of screening for high blood pressure in children and adolescents (in general) (USPSTF, 2020). In adults, however, The USPSTF recommends screening for hypertension (persons 18 years or older) with office blood pressure measurement (OBPM). The USPSTF recommends obtaining blood pressure measurements outside of the clinical setting for diagnostic confirmation before starting treatment (USPSTF, 2021). 

Finally, screening for obesity in children six years or older is recommended (Bibbins-Domingo et al., 2017).

Canadian Cardiovascular Society (CCS)
In 2021, the CCS published updated their recommendations on the management of dyslipidemia for the prevention of cardiovascular disease in adults. A summary of the society’s recommendations that are relevant to CVD risk assessment is provided below:

• “Among women whose pregnancy was complicated by the hypertensive disorders of pregnancy — gestational hypertension and/or preeclampsia — or a preterm birth before 34 weeks’ gestation, a stillbirth and/or a placental abruption, we recommend screening with a comprehensive lipid panel at least 12 weeks postpartum. These women have a higher risk of premature CVD and stroke within 10 – 15 years after the affected pregnancy (Strong Recommendation, Moderate Quality Evidence).
• To assist with decisions about initiating lipid-lowering pharmacotherapy in a nonpregnant woman who had one or more of these pregnancy complications, we recommend referral to a specialized postpartum cardiovascular health clinic or specialized lipid clinic, if locally available. If such resources are not locally available, we recommend using standard risk assessment tools to decide about lipid-lowering pharmacotherapy. However, when interpreting their 10-year CVD risk using a risk calculator, it is important to note that most women in this group will be found to have a low calculated absolute risk of CVD, short-term, which may give a false sense of reassurance to both the patient and her health care provider. (Weak Recommendation; Low-Quality Evidence).
• For any patient with triglycerides > 1.5mM, use non-HDL-C or apoB instead of LDL-C as the preferred lipid parameter for initial screening and treatment target (< 2.6 mM for non-HDL-C or < 0.8 g/L for apoB) in intermediate or high risk individuals (Strong Recommendation, High-Quality Evidence).
• We recommend measuring lipoprotein (a) level once in a person’s lifetime as a part of the initial lipid screening (Strong Recommendation; High-Quality Evidence).
• We suggest that CAC [coronary artery calcium] screening using computed tomography imaging might be considered for asymptomatic adults 40 years or older and at intermediate risk (FRS 10% 20%) for whom treatment decisions are uncertain (Strong Recommendation, Moderate-Quality Evidence).
• We recommend that CAC screening using computed tomography imaging not be undertaken for: (1) high-risk individuals; (2) patients receiving statin treatment; or (3) most asymptomatic, low-risk adults (Strong Recommendation; Moderate-Quality Evidence).
• We suggest that CAC screening might be considered for a subset of low-risk individuals 40 years or older (Weak Recommendation; Low-Quality Evidence)” (Pearson et al., 2021).

The 2021 guidelines affirmed those from 2016, stating that “Screening should be repeated every 5 years for men and women aged 40-75 years using the modified FRS or Cardiovascular Life Expectancy Model (CLEM) to guide therapy to reduce major CV events.” 

A revision of the 2016 recommendation is the role of Lp(a): “Lp(a) is not currently considered a treatment target and repeat measures are therefore not indicated.” Moreover, non-fasting lipid testing is recommended during the CV risk assessment, and “It is now generally preferable to follow non-HDL-C or ApoB levels over LDL-C when interpreting lipid results, particularly when TG are ≥ 1.5 mmol/L” (Pearson et al., 2021). 

HIV Medicine Association of the Infectious Diseases Society of America 
HIV-infected patients commonly develop dyslipidemia after starting antiretroviral therapy (ART). The lipid abnormalities developed in HIV-infected patients are associated with increased cardiovascular risk. HIV Medicine Association of the Infectious Diseases Society of America have updated their guidelines in 2013 to include a new section on metabolic comorbidities. They recommend obtaining a fasting lipid profile prior to and within 1 – 3 months after starting ART and every 6 – 12 months in all patients. The 2020 update affirms this, as under the workup for routine healthcare maintenance considerations for persons with HIV, they recommend the following steps: “Lipid profile: perform every 5 years if normal; more frequently if abnormal or other cardiovascular risk factors present (every 6 – 12 months); if abnormal, repeat fasting” and ask that clinicians “Follow the atherosclerotic cardiovascular disease risk calculator. Consider testing 1 – 3 months after starting or changing ART” (Thompson et al., 2020).

The Association also notes that HbA1c may be tested or used for screening and states that a lower cutoff of 5.8% for diabetes may be used for patients on ART instead of the higher 6.5%. Finally, the Association recommends measuring HbA1c every six months in patients with diabetes (Aberg et al., 2014; Thompson et al., 2020).

According to the Association, an initial evaluation and an immediate follow-up for persons with HIV includes “A comprehensive present and past medical history that includes HIV-related information, medication/social/family history …, review of systems, and physical examination … should be obtained for all patients upon initiation of care, ideally at the first visit or, if not feasible, as soon as possible thereafter,” and this includes testing for “Cardiovascular disease and risk factors, including hyperlipidemia, hypertension, diabetes mellitus, smoking” (Thompson et al., 2020).

U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) 
The United States VA and DoD published a joint guideline regarding management of dyslipidemia for reducing CVD risk in adults. Their relevant recommendations are listed below:

• “For primary prevention in patients over age 40 and not on statin therapy who have not developed new cardiovascular risk factors (e.g., diabetes, hypertension, tobacco use), we suggest against offering a cardiovascular disease risk assessment more frequently than every five years.”
• “For primary prevention in patients not on statin therapy, we suggest against routinely ordering a lipid panel more frequently than every 10 years.”
• “For cardiovascular risk assessment in primary prevention, we suggest using a 10-year risk calculator.”
• “We suggest against the routine use of coronary artery calcium testing.”
• “We suggest against the routine use of additional risk markers (e.g., high-sensitivity C-reactive protein, ankle-brachial index, coronary artery calcium) when assessing cardiovascular risk.”

The guideline also remarks that several other markers, such as “coronary artery calcium (CAC), high-sensitivity C-reactive protein, ankle–brachial index, and apolipoprotein evaluations” have been proposed as useful tools to determine risk. However, these markers have been deemed “limited in further refining risk.” Although CAC was considered to best of the markers listed, the guideline still recommended against routine CAC testing.

The guideline also recommends against “routine lipid level testing for risk assessment and monitoring, unless it is specifically intended to guide decision making” (O'Malley et al., 2020).

2021 European Society of Cardiology (ESC) and Other Societies on Cardiovascular Disease Prevention in Clinical Practice 
In 2021, the Seventh Joint Task Force of the ESC and Other Societies on Cardiovascular Disease Prevention in Clinical Practice published guidelines on cardiovascular disease prevention in clinical practice. 

The 2021 update has the same goals and targets for LDL-C, BP, and glycemic control in patients with diabetes mellitus as the previous 2016 guideline.

The authors state that routine assessment of circulating or urinary biomarkers is still not recommended for CVD risk stratification. The Task Force states that there is conflicting data on the utility of these biomarkers (such as hsCRP, various apolipoproteins, etc.) and that new studies confirm that C-reactive protein has “limited additional value.” The authors concede that there is renewed interest in lipoprotein a, but that it doesn’t add additional value in risk stratification. While cardiac biomarkers show promise, additional clinical studies are necessary.

The Task Force recommends repeating risk assessment every five years, and more often for higher risk patients. However, the Task Force only recommends this screening procedure for men >40 years and women >50 years, declaring that, though it is not cost-effective, a systematic CVD risk assessment is shown to “increase detection of CV risk factors” (Visseren et al., 2021).

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9. Elashoff, M. R., Wingrove, J. A., Beineke, P., Daniels, S. E., Tingley, W. G., Rosenberg, S., Voros, S., Kraus, W. E., Ginsburg, G. S., Schwartz, R. S., Ellis, S. G., Tahirkheli, N., Waksman, R., McPherson, J., Lansky, A. J., & Topol, E. J. (2011). Development of a blood-based gene expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients. BMC Med Genomics, 4, 26. https://doi.org/10.1186/1755-8794-4-26
10. Ganesh, S. K., Arnett, D. K., Assimes, T. L., Basson, C. T., Chakravarti, A., Ellinor, P. T., Engler, M. B., Goldmuntz, E., Herrington, D. M., Hershberger, R. E., Hong, Y., Johnson, J. A., Kittner, S. J., McDermott, D. A., Meschia, J. F., Mestroni, L., O'Donnell, C. J., Psaty, B. M., Vasan, R. S., . . . Waldman, S. A. (2013). Genetics and genomics for the prevention and treatment of cardiovascular disease: update: a scientific statement from the American Heart Association. Circulation, 128(25), 2813-2851. https://doi.org/10.1161/01.cir.0000437913.98912.1d
11. Goff, D. C., Jr., Lloyd-Jones, D. M., Bennett, G., Coady, S., D'Agostino, R. B., Sr., Gibbons, R., Greenland, P., Lackland, D. T., Levy, D., O'Donnell, C. J., Robinson, J. G., Schwartz, J. S., Shero, S. T., Smith, S. C., Jr., Sorlie, P., Stone, N. J., & Wilson, P. W. (2014). 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. J Am Coll Cardiol, 63(25 Pt B), 2935-2959. https://doi.org/10.1016/j.jacc.2013.11.005
12. Gransbo, K., Almgren, P., Sjogren, M., Smith, J. G., Engstrom, G., Hedblad, B., & Melander, O. (2013). Chromosome 9p21 genetic variation explains 13% of cardiovascular disease incidence but does not improve risk prediction. J Intern Med, 274(3), 233-240. https://doi.org/10.1111/joim.12063
13. Greenland, P., Alpert, J. S., Beller, G. A., Benjamin, E. J., Budoff, M. J., Fayad, Z. A., Foster, E., Hlatky, M. A., Hodgson, J. M., Kushner, F. G., Lauer, M. S., Shaw, L. J., Smith, S. C., Jr., Taylor, A. J., Weintraub, W. S., Wenger, N. K., Jacobs, A. K., Anderson, J. L., Albert, N., . . . Yancy, C. W. (2010). 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, 56(25), e50-103. https://doi.org/10.1016/j.jacc.2010.09.001
14. Hopewell, J. C., Parish, S., Clarke, R., Armitage, J., Bowman, L., Hager, J., Lathrop, M., & Collins, R. (2011). No impact of KIF6 genotype on vascular risk and statin response among 18,348 randomized patients in the heart protection study. J Am Coll Cardiol, 57(20), 2000-2007. https://doi.org/10.1016/j.jacc.2011.02.015
15. Iakoubova, O. A., Tong, C. H., Rowland, C. M., Kirchgessner, T. G., Young, B. A., Arellano, A. R., Shiffman, D., Sabatine, M. S., Campos, H., Packard, C. J., Pfeffer, M. A., White, T. J., Braunwald, E., Shepherd, J., Devlin, J. J., & Sacks, F. M. (2008). Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary
16. heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J Am Coll Cardiol, 51(4), 435-443. https://doi.org/10.1016/j.jacc.2007.05.057
17. Kessler, T., Vilne, B., & Schunkert, H. (2016). The impact of genome-wide association studies on the pathophysiology and therapy of cardiovascular disease. EMBO Mol Med, 8(7), 688-701. https://doi.org/10.15252/emmm.201506174
18. Lin, J. S., Evans, C. V., Johnson, E., Redmond, N., Coppola, E. L., & Smith, N. (2018). Nontraditional Risk Factors in Cardiovascular Disease Risk Assessment: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. Jama, 320(3), 281-297. https://doi.org/10.1001/jama.2018.4242
19. Newman, C. B., Blaha, M. J., Boord, J. B., Cariou, B., Chait, A., Fein, H. G., Ginsberg, H. N., Goldberg, I. J., Murad, M. H., Subramanian, S., & Tannock, L. R. (2020). Lipid Management in Patients with Endocrine Disorders: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 105(12). https://doi.org/10.1210/clinem/dgaa674
20. O’Sullivan, J. W., Raghavan, S., Marquez-Luna, C., Luzum, J. A., Damrauer, S. M., Ashley, E. A., O’Donnell, C. J., Willer, C. J., & Natarajan, P. (2022). Polygenic Risk Scores for Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation, 146(8), e93-e118. https://doi.org/doi:10.1161/CIR.0000000000001077
21. Palomaki, G. E., Melillo, S., & Bradley, L. A. (2010). Association between 9p21 genomic markers and heart disease: a meta-analysis. Jama, 303(7), 648-656. https://doi.org/10.1001/jama.2010.118
22. Palotie, A., Havulinna, A. S., De Livera, A. M., Tikkanen, E., Sijbrands, E. J., Abraham, G., Schunkert, H., Yetukuri, L., Perola, M., Bhalala, O. G., Byars, S. G., Inouye, M., Samani, N. J., Ripatti, S., & Salomaa, V. (2016). Genomic prediction of coronary heart disease. European Heart Journal, 37(43), 3267-3278. https://doi.org/10.1093/eurheartj/ehw450
23. Patel, R. S., Asselbergs, F. W., Quyyumi, A. A., Palmer, T. M., Finan, C. I., Tragante, V., Deanfield, J., Hemingway, H., Hingorani, A. D., & Holmes, M. V. (2014). Genetic variants at chromosome 9p21 and risk of first versus subsequent coronary heart disease events: a systematic review and meta-analysis. J Am Coll Cardiol, 63(21), 2234-2245. https://doi.org/10.1016/j.jacc.2014.01.065
24. Paynter, N. P., Chasman, D. I., Buring, J. E., Shiffman, D., Cook, N. R., & Ridker, P. M. (2009). Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3. Ann Intern Med, 150(2), 65-72.
25. Pearson, G. J., Thanassoulis, G., Anderson, T. J., Barry, A. R., Couture, P., Dayan, N., Francis, G. A., Genest, J., Grégoire, J., Grover, S. A., Gupta, M., Hegele, R. A., Lau, D., Leiter, L. A., Leung, A. A., Lonn, E., Mancini, G. B. J., Manjoo, P., McPherson, R., . . . Wray, W. (2021). 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. Can J Cardiol, 37(8), 1129-1150. https://doi.org/10.1016/j.cjca.2021.03.016 Quest. (2024). Cardio IQ® 9p21 Genotype https://testdirectory.questdiagnostics.com/test/test-detail/90648/cardio-iq-9p21-genotype?p=r&q=cardio%20IA%209p21%20genotype&cc=MASTER
26. Ridker, P., MacFadyen, J., Glynn, R., & Chasman, D. (2011). Kinesin-Like Protein 6 (KIF6) Polymorphism and the Efficacy of Rosuvastatin in Primary Prevention. Circulation: Cardiovascular Genetics, 4(3), 312-317. https://doi.org/10.1161/CIRCGENETICS.110.959353
27. Ruiz-Ramos, D., Hernández-Díaz, Y., Tovilla-Zárate, C. A., Juárez-Rojop, I., López-Narváez, M. L., González-Castro, T. B., Torres-Hernández, M. E., & Baños-González, M. A. (2015). The Trp719Arg polymorphism of the KIF6 gene and coronary heart disease risk: systematic review and meta-analysis. Hereditas, 152, 3. https://doi.org/10.1186/s41065-015-0004-7
28. Samani, N. J., Erdmann, J., Hall, A. S., Hengstenberg, C., Mangino, M., Mayer, B., Dixon, R. J., Meitinger, T., Braund, P., Wichmann, H. E., Barrett, J. H., Konig, I. R., Stevens, S. E., Szymczak, S., Tregouet, D. A., Iles, M. M., Pahlke, F., Pollard, H., Lieb, W., . . . Schunkert, H. (2007). Genomewide association analysis of coronary artery disease. N Engl J Med, 357(5), 443-453. https://doi.org/10.1056/NEJMoa072366
29. Seth S. Martin, A. W. A., Zaid I. Almarzooq, Cheryl A.M. Anderson, Pankaj Arora, Christy L. Avery, Carissa M. Baker-Smith, Bethany Barone Gibbs, Andrea Z. Beaton, Amelia K. Boehme, Yvonne Commodore-Mensah, Maria E. Currie, Mitchell S.V. Elkind, Kelly R. Evenson, Giuliano Generoso, Debra G. Heard, Swapnil Hiremath, Michelle C. Johansen, Rizwan Kalani, Dhruv S. Kazi, Darae Ko, Junxiu Liu, Jared W. Magnani, Erin D. Michos, Michael E. Mussolino, Sankar D. Navaneethan, Nisha I. Parikh, Sarah M. Perman, Remy Poudel, Mary Rezk-Hanna, Gregory A. Roth, Nilay S. Shah, Marie-Pierre St-Onge, Evan L. Thacker, Connie W. Tsao, Sarah M. Urbut, Harriette G.C. Van Spall, Jenifer H. Voeks, Nae-Yuh Wang, Nathan D. Wong, Sally S. Wong, Kristine Yaffe, Latha P. Palaniappan and on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. (2024). 2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association. Circulation, 149. https://doi.org/10.1161/CIR.0000000000001209
30. Trenkwalder, T., Nelson, C. P., Musameh, M. D., Mordi, I. R., Kessler, T., Pellegrini, C., Debiec, R., Rheude, T., Lazovic, V., Zeng, L., Martinsson, A., Gustav Smith, J., Gadin, J. R., Franco-Cereceda, A., Eriksson, P., Nielsen, J. B., Graham, S. E., Willer, C. J., Hveem, K., . . . Samani, N. J. (2019). Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis. Int J Cardiol, 276, 212-217. https://doi.org/10.1016/j.ijcard.2018.11.094
31. Virani, S. S., Brautbar, A., Lee, V.-V., MacArthur, E., Morrison, A. C., Grove, M. L., Nambi, V., Frazier, L., Wilson, J. M., Willerson, J. T., Boerwinkle, E., & Ballantyne, C. M. (2012). Chromosome 9p21 single nucleotide polymorphisms are not associated with recurrent myocardial infarction in patients with established coronary artery disease. Circulation journal : official journal of the Japanese Circulation Society, 76(4), 950-956. https://doi.org/10.1253/circj.cj-11-1166
32. Visseren, F. L. J., Mach, F., Smulders, Y. M., Carballo, D., Koskinas, K. C., Bäck, M., Benetos, A., Biffi, A., Boavida, J.-M., Capodanno, D., Cosyns, B., Crawford, C., Davos, C. H., Desormais, I., Di Angelantonio, E., Franco, O. H., Halvorsen, S., Hobbs, F. D. R., Hollander, M., . . . Group, E. S. C. S. D. (2021). 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). European Heart Journal, 42(34), 3227-3337. https://doi.org/10.1093/eurheartj/ehab484
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Coding Section 

CPT	Code Description
81402	Molecular pathology procedure, Level 3 (e.g., > 10 SNPs, 2 – 10 methylated variants, or 2 – 10 somatic variants [typically using non-sequencing target variant analysis], immunoglobulin and T-cell receptor gene rearrangements, duplication/deletion variants of 1 exon, loss of heterozygosity [LOH], uniparental disomy [UPD])
81403	Molecular pathology procedure, Level 4 (e.g., analysis of single exon by DNA sequence analysis, analysis of > 10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning or duplication/deletion variants of 2 – 5 exons)
81404	Molecular pathology procedure, Level 5 (e.g., analysis of 2 – 5 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 6 – 10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis)
81405	Molecular pathology procedure, Level 6 (e.g., analysis of 6 – 10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 11 – 25 exons, regionally targeted cytogenomic array analysis)
81406	Molecular pathology procedure, Level 7 (e.g., analysis of 11 – 25 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 26 – 50 exons)
81407	Molecular pathology procedure, Level 8 (e.g., analysis of 26 – 50 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of > 50 exons, sequence analysis of multiple genes on one platform)
81408	Molecular pathology procedure, Level 9 (e.g., analysis of > 50 exons in a single gene by DNA sequence analysis)
81479	Unlisted molecular pathology procedure
81493	Coronary artery disease, mRNA, gene expression profiling by real-time RT-PCR of 23 genes, utilizing whole peripheral blood, algorithm reported as a risk score Proprietary test: Corus®CAD Lab/Manufacturer: CardioDx Inc.
84512	Troponin, Qualitative
0401U	Cardiology (coronary heart disease [CAD]), 9 genes (12 variants), targeted variant genotyping, blood, saliva, or buccal swab, algorithm reported as a genetic risk score for a coronary event Proprietary test: CARDIO inCode-Score (CIC-SCORE) Lab/Manufacturer: GENinCode U.S. Inc
0439U	Cardiology (coronary heart disease [CHD]), DNA, analysis of 5 single-nucleotide polymorphisms (SNPs) (rs11716050 [LOC105376934], rs6560711 [WDR37], rs3735222 [SCIN/LOC107986769], rs6820447 [intergenic], and rs9638144 [ESYT2]) and 3 DNA methylation markers (cg00300879 [transcription start site {TSS200} of CNKSR1], cg09552548 [intergenic], and cg14789911 [body of SPATC1L]), qPCR and digital PCR, whole blood, algorithm reported as a 4-tiered risk score for a 3-year risk of symptomatic CHD Proprietary test: Epi+Gen CHD™ Lab Manufacturer: Cardio Diagnostics Inc
0440U	Cardiology (coronary heart disease [CHD]), DNA, analysis of 10 single-nucleotide polymorphisms (SNPs) (rs710987 [LINC010019], rs1333048 [CDKN2B-AS1], rs12129789 [KCND3], rs942317 [KTN1-AS1], rs1441433 [PPP3CA], rs2869675 [PREX1], rs4639796 [ZBTB41], rs4376434 [LINC00972], rs12714414 [TMEM18], and rs7585056 [TMEM18]) and 6 DNA methylation markers (cg03725309 [SARS1], cg12586707 [CXCL1, cg04988978 [MPO], cg17901584 [DHCR24-DT], cg21161138 [AHRR], and cg12655112 [EHD4]), qPCR and digital PCR, whole blood, algorithm reported as detected or not detected for CHD Proprietary test: PrecisionCHDTM Lab/Manufacturer: Cardio Diagnostics Inc.
0466U	Cardiology (coronary artery disease [CAD]), DNA, genomewide association studies (564856 single-nucleotide polymorphisms [SNPs], targeted variant genotyping), patient lifestyle and clinical data, buccal swab, algorithm reported as polygenic risk to acquired heart disease Proprietary test: CardioRisk+ Lab/Manufacturer: Gene by Gene, Ltd, Open DNS, Ltd.

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

"Current Procedural Terminology © American Medical Association. All Rights Reserved" 

History From 2024 Forward    

10/23/2024	Annual review, updating policy intent, rationale, references, and adding CPT code 84512.
07/30/2024	Annual review, no change to policy intent. Updating description, rationale, references and coding.
07/29/2027	Changing the Review dare to 10/01/2024
06/26/2024	Interim review to add PLA code 0466U to coding section.
03/26/2024	Updating Coding section. Adding CPT codes 0439U and 0440U effective 04/01/2024. No other changes made.
01/01/2024	New Policy