CAM 188

Cardiovascular Disease Risk Assessment

Category:Laboratory   Last Reviewed:April 2019
Department(s):Medical Affairs   Next Review:April 2020
Original Date:January 2018    

Description
Cardiovascular risk assessment comprises of 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.

Tests typically used to assess cardiovascular risk include: 

  1. Lipid profile or panel 
  2. Novel Biomarkers 
  3. Other Cardiovascular Markers 
  4. Cardiovascular Risk Panels

Background 
Statistics show that cardiovascular disease is America's leading health problem, and the leading cause of death.

The most recent statistics released by the American Heart Association: (Johns Hopkins Medicine, 2016)

  • Approximately 84 million people in this country suffer from some form of cardiovascular disease, causing about 2,200 deaths a day, averaging one death every 40 seconds
  • Almost one out of every three deaths results from cardiovascular disease
  • The direct and indirect costs of cardiovascular disease and stroke are about $315 billion. This figure is increasing every year
  • An estimated 15 million U.S. adults have coronary heart disease and approximately 78 million U.S. adults have high blood pressure
  • Heart failure affects well over 5 million U.S. adults
  • Cardiovascular disease is the cause of more deaths than cancer, chronic lower respiratory diseases, and accidents combined
  • Cardiovascular diseases are the number one killer of women (and men).
  • About one-third of cardiovascular disease deaths occurred before age 75.
  • On average, someone in the U.S. suffers a stroke every 40 seconds. Stroke is a leading cause of serious, long-term disability
  • Women have a higher lifetime risk of stroke than men.
  • Approximately 20 percent of U.S. adults smoke cigarettes, costing (CV risk factor)
  • An estimated 68 percent of U.S. adults are overweight or obese (CV risk factor)

Cardiovascular Risk Assessment
Traditionally, the most important indicators for cardiac risk are those of a person's personal health history. These include:

  •  Age
  • Family history
  • Weight
  • Cigarette smoking                                
  • Blood pressure
  • Diet
  •  Exercise, physical activity
  • Diabetes                              

 

Tests typically used to assess cardiovascular risk include:

  1. Lipid profile or panel, which is the most important blood test for cardiac risk assessment
  2. Novel Biomarkers
  3. Other Cardiovascular Markers
  4. Cardiovascular Risk Panels

Lipid Profile or Panel
Lipid profile or lipid panel is a panel of blood tests that serves as an initial broad medical screening tool for abnormalities in lipids, such as cholesterol and triglycerides. The results of this test can identify certain genetic diseases and can determine approximate risks for cardiovascular disease, certain forms of pancreatitis, and other diseases. The lipid profile typically includes:

  1. Low-density lipoprotein (LDL)
  2. High-density lipoprotein (HDL)
  3. Triglycerides
  4. Total cholesterol

Using these values, a laboratory may also calculate:

  • Very low-density lipoprotein (VLDL)  
  • Total cholesterol/HDL cholesterol ratio

Individuals with elevated LDL cholesterol have approximately twice the risk for heart disease as those with lower levels. Lowering LDL cholesterol has been shown to reduce risk of coronary heart disease and associated morbidity and mortality. LDL cholesterol can be lowered by lifestyle changes such as diet, exercise, and smoking cessation and also by medications such as statins (CDC, 2015)

High density lipoprotein (HDL) cholesterol is associated with a protective effect against heart disease, and elevated HDL cholesterol levels are correlated with lower disease risk. HDL cholesterol levels can be raised by lifestyle changes such as diet and exercise, and may also be positively impacted by medications used to lower LDL cholesterol.

Lipid panel results are used to help determine risk and to identify who should undergo treatment and/or lifestyle changes. Treatment goals typically are identified as specific LDL cholesterol and HDL cholesterol levels, based on the patient's situation and risk. The National Cholesterol Education Program defines optimal LDL cholesterol levels for adults as less than 100 mg/dL, and optimal HDL cholesterol levels for adults as greater than 60 mg/dL to achieve lowest risk of a cardiac event. The American Academy of Pediatrics identifies an "acceptable" level of non-HDL cholesterol as less than 120 mg/dL for children and adolescents, and less than 150 mg/dL for young adults.

Novel Biomarkers
According to MacNamara et al. (2015), traditional risk algorithms may miss up to 20% of cardiovascular disease (CVD) events. Therefore, there is a need for new cardiac biomarkers. Many fields of research are dedicated to improving cardiac risk prediction, including genomics, transcriptomics and proteomics. To date, even the most promising biomarkers have only demonstrated modest associations and predictive ability. A number of biomarkers are targets to new therapies aimed to reduce cardiovascular risk. Currently, some of the most promising risk prediction has been demonstrated with panels of multiple biomarkers (MacNamara et al., 2015).

Numerous lipid, non‒lipid, and metabolic biomarkers have been proposed as potential risk markers CVD. These biomarkers include apolipoprotein B (apo B), apolipoprotein AI (apo AI), apolipoprotein E (apo E), B-type natriuretic peptide, cystatin C, fibrinogen, high-density lipoprotein (HDL) subclass, leptin, low-density lipoprotein (LDL) subclass, and lipoprotein (a). These biomarkers have been studied as an alternative or addition to standard lipid panels for risk stratification in CVD or as treatment targets for lipid-lowering therapy. However, there is no evidence that measurement of these biomarkers leads to changes in management and improved health outcomes.

Apolipoprotein B
Apolipoprotein B (apo B) is the major protein moiety of all lipoproteins except for high-density lipoprotein (HDL). There are two forms of apo B. The most abundant form is known as large B or B100, and is the major protein found in LDL and VLDL. Each LDL particle has one molecule of apo B per particle. Therefore, the apo B concentration is an indirect measurement of the number of LDL particles. Because LDL particles can vary both in size and in cholesterol content, for a given concentration of LDL-C, there can be a wide variety of both size and numbers of LDL particles.

Therefore, it has been suggested that apo B is a better marker of atherogenic particles than total LDL and even nonHDL levels. Apo B testing has not been validated as a tool for risk assessment in the general population.

Apolipoprotein AI
Apo AI is a lipid-binding protein that forms complexes with other proteins and lipids to form HDL particles. HDL contains two associated apolipoproteins, i.e., AI and AII, and together they constitute more than 90% of total HDL protein. Because all HDL particles contain apo AI, this lipid marker can be used as an approximation for HDL number

Direct measurement of apo AI has been proposed as more accurate than the traditional use of HDL level. Low levels of apo A–1 may be associated with an increased risk for CVD. Testing for apo A–1 is often performed with apolipoprotein B and reported as a ratio (apo B: apo A-1), thus providing a measure of atherogenic to antiatherogenic lipoprotein particles.

Apolipoprotein E
Apolipoprotein E (apo E) is the primary apolipoprotein found in VLDLs and chylomicrons. Apo E is essential in the metabolism of cholesterol and triglycerides and helps to clear chylomicrons and VLDL. Apo E polymorphisms have functional effects on lipoprotein metabolism. Some APOE genotypes are more atherogenic than others, and their measurement could provide additional information of risk of coronary artery disease. However, the clinical utility of apo E testing in the diagnosis and management of CHD needs further research.

B-type or Brain Natriuretic Peptide
Brain natriuretic peptide (BNP) is a hormone released by the ventricles of the heart when pressure to the cardiac muscles increases or there is volume overload. Plasma levels of BNP are less than 100pg/mL in most healthy individuals. When elevated, BNP may be an indication of congestive heart failure. A major limitation of BNP is that a wide range of values is observed in patients with and without heart failure. Currently, evidence for screening for CHF using BNP is inconclusive despite its sensitivity and prognostic significance.

High Density Lipoprotein (HDL) Subclass
Apart from apolipoprotein content (AI and AII), HDL can be classified by size (small and large), by density (HDL2, HDL3), and by electrical charge (pre-beta, alpha and pre-alpha). HDL subclass testing may be performed by nuclear magnetic resonance (NMR), gradient gel electrophoresis (GGE), and ultracentrifugation. There has been substantial interest in evaluating whether HDL subclass testing can be used to provide additional information on cardiovascular risk compared to HDL alone. HDL2, the larger, less dense particles may have the greatest degree of cardioprotection. However, the superiority of HDL subspecies over HDL cholesterol has not been demonstrated in large, prospective studies. There is no evidence to support improved clinical outcomes with the use of HDL subclass testing, and therefore, it has not been recommended as a routine test of cardiac risk evaluation.

Low Density Lipoprotein (LDL) Subclass 
LDL subclass testing is a source of quantitative and qualitative LDL information. This test measures the cholesterol content of lipoprotein particles in the blood and determines the LDL particle size and/or density pattern. A discrepancy between the quantity of LDL particles and the serum level of total LDL could indicate a source of unrecognized cardiovascular risk.

The two main subclass patterns of LDL are called A (particle diameter >25nm, less dense) and B (particle diameter<25, higher density). The mechanism of how LDL subclass particles impact risk of CVD has not been determined. Even though LDL cholesterol levels may be normal, an elevation of small, dense LDL particles may be associated with CVD. One theory is that the small LDL particles can be more easily deposited into the intima and lead to atherosclerosis. A consensus statement by the American College of Cardiology (ACC) and the American Diabetes Association (ADA) stated "it is unclear whether LDL particle size measurements add value to measurement of LDL particle concentration" (Brunzell et al, 2008)

Lipoprotein(a)
Lipoprotein(a) (Lp[a]) is a low density, lipid-rich particle similar to low-density lipoprotein (LDL) and has been determined to have atherogenic potential and be an independent risk factor for coronary artery disease (CAD). Although research has shown it accumulates in atherosclerotic lesions, the actual process remains unclear. In general, lipoprotein(a) levels above 30mg/dl are considered elevated with levels > 50 considered high risk. The overall degree of risk associated with Lp[a] levels appears to be modest, and the degree of risk may be mediated by other factors such as LDL levels and/or hormonal status. There are no published studies that provide evidence that Lp(a) reduction reduces the incidence of first or recurrent CVD events. Therefore, widespread screening for Lp(a) excess is not indicated and treatment of Lp(a) excess should only be considered in specific circumstances (UpToDate, 2017). The standard method for measuring Lp(a) is density gradient ultracentrifugation. Although ELISA techniques are widely available; they are insensitive and unable to distinguish between apo(a) isoforms. This results in significant underestimation or overestimation of Lp(a) levels (UpToDate, 2017).

Cystatin C
Cystatin C is a serine protease inhibitor protein encoded by CST3 gene. Serum testing has been proposed to diagnose impaired kidney function. There is no published literature proving the effectiveness of Cystatin C as a biomarker for predicting cardiovascular risk.

Fibrinogen
Fibrinogen is a circulating glycoprotein that plays an important role in platelet aggregation and a determinant of blood viscosity. Fibrinogen has been suggested as a possible indicator of inflammation that accompanies atherosclerosis. The independent predictive power, impact on management strategies and clinical utility of fibrinogen measurement is unclear, and therefore, routine measurement of fibrinogen is not recommended.

Leptin
Leptin is a protein secreted by fat cells. Further research is required to evaluate the effectiveness of Leptin as a predictor of CVD. Measurement of Leptin or other similar tests (adiponectin, apelin, galectin 3, resistin, retinol binding protein, visfatin) is not recommended at this time.

Homocysteine
Homocysteine is an amino acid that is produced by the body. Elevated levels of homocysteine may result in damage to the walls of the artery, increases potential for thrombosis and leads to advanced atherosclerosis. Elevated plasma levels have been demonstrated in patients with CVD. Testing of homocysteine levels is not consistently recommended because their independent predictive power is still unclear. Additionally, the impact of testing on clinical outcomes and reduction in cardiac disease risk has not been demonstrated. Further research is required to support the clinical utility of lowering homocysteine levels.

Intermediate Density Lipoproteins (IDL)
Decades of research have identified atherogenic cholesterol-containing lipoprotein particles as having a central, causal role in CVD. Despite this, only a minority of subjects with elevated LDL and cholesterol levels will develop clinical disease (Stone et al., 2013). Thus, there is continuing research into additional biomarkers which could help predict which individuals with elevated LDL levels will develop CVD.

More detailed assessments of lipoprotein particle size and number as well as other lipid carrier proteins have been investigated as a more reliable method to quantify the cardiovascular risk of the lipoprotein fractions (Di Angelantonio et al., 2009). Very low density lipoproteins (VLDL), LDL-C, large LDL, intermediate LDL and large intermediate density lipoproteins (IDL) were significantly associated with premature myocardial infarction (Dutheil et al., 2014; Goliasch et al., 2012).

Remnant cholesterol, the cholesterol content of triglyceride-rich lipoproteins, composed of VLDL and IDL in the fasting state and of these 2 lipoproteins together with chylomicron remnants in the nonfasting state, can be estimated by triglyceride (TG) levels in the absence of advanced lipoprotein testing (Anette Varbo et al., 2016). Elevated nonfasting plasma triglyceride is associated with increased risk for CVD(A. Varbo et al., 2013). Triglycerides themselves are unlikely to directly to cause CVD, thus VLDL and IDL are more likely to be the source of this increased risk for CVD (Quispe et al., 2015). VLDL and IDL have been shown to be proatherogenic, with both proinflammatory and prothrombotic effects (Joshi et al., 2016).

Genetic case studies have shown that elevated levels of remnant cholesterol are causally associated with both low-grade inflammation and CVD. Elevated levels of LDL cholesterol are associated with CVD, but not with low-grade inflammation. This indicates that elevated LDL cholesterol levels cause atherosclerosis without inflammation, whereas elevated remnant cholesterol levels lead to both atherosclerosis and inflammation (A. Varbo, Benn, & Nordestgaard, 2014; Anette Varbo et al., 2016).

Another measure which includes IDL is Non-HDL-C, which is derived from the simple calculation of total cholesterol minus HDL-C and is the sum of all the cholesterol transported in atherogenic lipoprotein. The Emerging Risk Factors Collaboration concluded that apoB and non-HDL-C predicted risk similar to directly measured LDL-C and that fasting did not affect the hazard ratios (HRs)(Di Angelantonio et al., 2009). These tests are better indicators and more cost effective than direct measurement of IDL.

Lipoprotein-associated phospholipase A2(Lp-PLA2)  
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory enzyme expressed in atherosclerotic plaques, and it has been proposed that Lp– PLA2 testing may aid in detecting CVD risk.

Population studies have shown that individuals with elevated circulating Lp-PLA2 are at higher risk for cardiovascular and stroke events. Lp-PLA2 levels greater than 200 mg/dl warrants risk reclassification and reduction of LDL levels. Lp-PLA2 is more specific for the vascular inflammation associated with CVD than other biomarkers as it is not an acute phase reactant (Donato, 2016).

Lp-PLA2 is produced by macrophages, monocytes, T lymphocytes, and mast and liver cells and although it can be bound to many types of lipoproteins, it primarily circulates bound to LDL particles (Zalewski & Macphee, 2005). Lp-PLA2 activity has been shown to be up-regulated in atherosclerotic lesions and in rupture prone fibrous caps. Lp-PLA2 is responsible for the hydrolysis of oxidized phospholipids on low density lipoprotein (LDL) particles producing two highly inflammatory mediators which result in a cascade of events that have been linked to atherosclerotic plaque formation (Davidson et al., 2011).

The rationale for Lp-PLA2 as a key inflammatory biomarker is attractive because this enzyme is produced in atherosclerotic plaques and is specifically linked to plaque inflammation, and presumably, rupture, suggesting a possible causal pathway leading to clinical events. In preclinical studies investigators have shown that inhibition of Lp-PLA2 attenuates the inflammatory response and slows atherosclerotic plaque progression. Lp-PLA2 shows less variability than CRP, making it a practical tool for CVD risk assessment.

There are numerous studies evaluating Lp-PLA2 as a predictor of cardiovascular risk (Collaboration, 2010; Garg et al., 2015; Sudhir, 2006). These studies demonstrate that Lp-PLA2 is an independent predictor of CVD. Preliminary clinical trials of Lp-PLA2 inhibitors showed some improvements in physiologic measures, such as reduction in high-sensitivity C-reactive protein (Sudhir, 2006). However, further clinical trials of Lp-PLA2 inhibitors failed to demonstrate significant improvements in patient outcomes (Mohler et al., 2008).

Long-Chain Omega-3 Fatty Acid
Omega-3 fatty acids (double bond three carbons from terminal methyl end of molecule), a specific group of polyunsaturated fatty acids (PUFA), are main building blocks of many fats and oils. Long-chain omega 3 fatty acids (≥C20, LC) include eicosapentaenoic acid (EPA, 20:5ω3), docosapentaenoic acid (DPA, 22:5ω3) and docosahexaenoic acid (DHA, 22:6ω3) and are thought to be beneficial in the prevention of coronary heart disease (CHD).

Circulating blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are inversely and significantly associated with reduced CHD event risk (de Oliveira Otto et al., 2013). Blood levels of omega-3 fatty acids achieved may be more related to CVD benefit than the daily dose of fish oil supplements (Superko et al., 2014). The blood EPA/AA ratio may be a clinically relevant measurement and also has substantial individual variability. An EPA/AA ratio >0.75 has been associated with a significantly lower number of major coronary events in a Japanese population (Itakura et al., 2011). In the United States, the Physician Health Study suggests an omega-3 index (EPA+DHA) > 4.17% reflects a 72% reduction in CVD risk (Albert et al., 2002; Superko et al., 2014). Determination of blood omega-3 levels may help guide the appropriate use of dietary fish or omega-3 supplements in a personalized heart disease prevention strategy.

The relationship of fish and dietary omega-3 fatty acids and cardiovascular disease (CVD) has been investigated in numerous studies and comprehensive reviews and recommendations exist, but guidance on blood concentrations is missing. Some prospective fish oil treatment investigations report a significant reduction in CVD events but others do not (Bosch, et al, 2012) and (Itakura, et al, 2011) A recent meta-analysis did not find a statistically significant relationship between omega-3 consumption and CVD mortality, but it failed to take into account the implications of variability in individual blood levels of omega-3 fatty acids (Rizos EC et al, 2012).

Blood levels of omega-3 fatty acids can be influenced by dietary intake of omega-3 fatty acids and intake with oral supplements. The Multiple Risk Factor Intervention Trial reported in 1995 that serum omega-3 fatty acids blood levels were inversely correlated with coronary heart disease (CHD). An association of dietary sources of nonfried fish and blood levels of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) were reported in the Atherosclerosis Risk In Communities (ARIC) investigation and the Multi-Ethnic Study of Atherosclerosis (MESA) investigations.

Genetic Markers
Genomics serves several roles in cardiovascular health and disease, including disease prediction, discovery of genetic loci influencing CVD, functional evaluation of these genetic loci to understand mechanisms, and identification of therapeutic targets. "For single-gene CVDs, progress has led to several clinically useful diagnostic tests, extending our ability to inform the management of afflicted patients and their family members" (Santhi / Gonesh et al 2013). However, there has been little progress in developing genetic testing for complex CVD because individual common variants have only a modest impact on risk. The study of the genomics of complex CVDs is further challenged by the influence of environmental variables, phenotypic heterogeneity, and pathogenic complexity. Characterization of the clinical phenotype requires consideration of the clinical details of the diseases and traits under study (Santhi / Gonesh et al, 2013).

Cardiovascular Risk Panels/Profiles
Cardiovascular risk panels refer to combinations of cardiac markers that are used to evaluate risk of future cardiovascular disease. Cardiovascular risk panels are used for assessment of risk 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. Hence use of cardiac risk panels for predicting risk of CVD is considered investigational

Some examples of commercially available cardiovascular risk panels are as follows:

  1. Cardiovascular Risk Marker Panel, Serum: Non-HDL cholesterol; calculated LDL; HDL Cholesterol, CDC; Cholesterol, Total, CDC; Triglycerides, Total, CDC; Lipoprotein (a); high sensitivity C-Reactive Protein
  2. Health Diagnostics Cardiac Risk Panel: MTHFR gene analysis, common variants; vitamin D, 1,25 dihydroxy; B-type natriuretic peptide (BNP); Lp-PLA2; myeloperoxidase; apolipoprotein; immune complex assay; lipoprotein, blood; electrophoretic separation and quantitation; very long chain fatty acids; total cholesterol; HDL; LDL; triglycerides; (high-sensitivity CRP, hs-CRP); lipoprotein (a); insulin, total; fibrinogen; apolipoprotein analysis; multiple SNPs associated with coronary artery disease (CAD).
  3. Genova Diagnostics CV Health Plus™ Panel:
    • Lipid markers (LDL; total cholesterol; HDL; triglycerides; LDL size; LDL particle number; HDL size; HDL particle number; lipoprotein (a))
    • Independent risk factors (hs-CRP; fibrinogen; homocysteine; LP-PLA2)
    • Insulin Resistance Score by Lipid Fractionation (LDL size; Small LDL particle number; HDL size; Large HDL particle number; Large very low-density lipoprotein (VLDL) particle number; VLDL size)
  4. Genova Diagnostics CV Health Plus Genomics™ Panel:
    • Lipid markers (LDL; total cholesterol; HDL; triglycerides; LDL size; LDL particle number; HDL size; HDL particle number; lipoprotein (a))
    • Independent risk factors (hs-CRP; fibrinogen; homocysteine; LP-PLA2)
    • Insulin Resistance Score by Lipid Fractionation (LDL size; Small LDL particle number; HDL size; Large HDL particle number; Large very low-density lipoprotein (VLDL) particle number; VLDL size)
    • Single Nucleotide Polymorphism in four select genes (MTHFR gene; apo E; prothrombin; factor V leiden)
  5. Cleveland HeartLab CVD Inflammation Testing Profile: F2-isoprostanes; oxidized LDL; hs-CRP; ADMA/SDMA; urinary microalbumin; myeloperoxidase; Lp-PLA2.   
  6. ingulex® clinical lab test panels:
    • Cardiac Function panel: SMC™ cTnl; NT-proBNP
    • Vascular Inflammation panel: SMC™ Endothelin; SMC™IL-6; SMC™ IL-17A; SMC™ TNFα; Ferritin; homocysteine; Lp-PLA2; hs-CRP; uric acid; vitamin D; anti-CCP; rheumatoid factor; folate; vitamin B12.
    • Lipid Management panel: Total Cholesterol, LDL-C (direct), apo A-1, apo B, sdLDL, HDL-C, HDL with fractionation (HDL + HDL2 + HDL3), triglycerides, Lp(a), total CK. 
  7. MIRISK VP:
    • MIRISK VP is a protein-based assay that measures serum levels of seven specific biomarkers - CTACK, Eotaxin, Fas Ligand, HGF, IL-16, MCP-3, and sFas. These markers are associated with the formation of vulnerable plaque. The test relies on a proprietary algorithm applied to 4 clinical risk factors and 7 biomarker measurements to provide the absolute risk score for coronary heart disease within a 5-year period.

Policy 

1. Lipid Panel

  • Measurement of total cholesterol, HDL-C, LDL-C and triglycerides as part of an assessment of cardiovascular risk factors is considered MEDICALLY NECESSARY:
    1. Every five years in patients ages 20 to 79 years.
    2. Annual screening for patients of all ages at increased risk for cardiovascular disease.
  • Increased risk for cardiovascular disease includes of one or more of the following risk factors below and more risk factors indicates greater risk:
    1. Diabetes mellitus
    2. Previous personal history of CHD or non-coronary atherosclerosis (e.g. abdominal aortic aneurysm, peripheral artery disease, carotid artery stenosis)
    3. A family history of cardiovascular disease before age 50 in male relatives or 60 in female relatives
    4. Hypertension
    5. Tobacco use/Smoking
    6. Obesity (BMI > 30)
    7. Advanced age (>65)
  • A lipid panel is considered MEDICALLY NECESSARY when evaluating an individual diagnosed with diseases associated with dyslipidemia, including but not limited to:
    1. Nephrotic Syndrome
    2. Hypothyroidism
    3. Hyperthyroidism
    4. Pancreatitis 
  • Before beginning statin therapy, a lipid panel is considered MEDICALLY NECESSARY forestablishing baseline levels for monitoring therapy.
  • For individuals receiving statin therapy, lipid panel testing is considered MEDICALLY NECESSARY upto every four to twelve weeks after initiation or change of therapy.
    Subsequently, annual lipid panel testing is considered MEDICALLY NECESSARY for individuals receiving statin therapy.
  • A lipid panel is considered MEDICALLY NECESSARY when evaluating and managing an individual diagnosed with HIV and receiving antiretroviral therapy (ART):
    1. Prior to initiating ART (baseline)
    2. Within one to three months after starting or modifying ART every 6 to 12 months thereafter

2. High-Sensitivity C-Reactive Protein (hs-CRP)

  •  High-sensitivity C-reactive protein (hs-CRP) testing is considered MEDICALLY NECESSARY for members who meet all of the following criteria:
    • Individual has 2 or more coronary heart disease (CHD) major risk factors. Major risk factors include the following:
      • Age (men aged 45 years or older; women aged 55 years or older)
      • Current cigarette smoking
      • Family history of premature CHD (CHD in male first-degree relative less than 55 years of age; CHD in female first-degree relative less than 65 years of age)
      • Hypertension (blood pressure [BP] of 140 mm Hg or higher, or on anti-hypertensive medication)
      • Low high-density lipoprotein (HDL) cholesterol (less than 40 mg/dL).
        • Individual has low-density lipoprotein (LDL) cholesterol levels between 100 to 130 mg/dL; and
        • Individual has been judged to be at an intermediate-risk of cardiovascular disease by global risk assessment (i.e., 10 to 20 % risk of CHD per 10 years using the ATPIII guidelines or Framingham point scoring).
      •  hs-CRP testingis considered INVESTIGATIONAL for all other indications, including
        • Use as a screening test for the general population
        • For monitoring response to therapy 

3. High-sensitivity Cardiac Troponin 

Measurement of High-sensitivity cardiac troponin T (hs-cTnT) is NOT MEDICALLY NECESSARY for cardiovascular risk assessment and stratification. 

4. Apolipoprotein B (Apo B) 

Measurement of apolipoprotein B (apoB) is INVESTIGATIONAL. 

5. Corus CAD

Corus CAD gene testing is INVESTIGATIONAL.

6. Homocysteine

Homocysteine testing is INVESTIGATIONAL for assessing CHD or stroke risk.

7. Novel Cardiovascular Biomarkers

Measurement of novel lipid and non‒lipid biomarkers (i.e., apolipoprotein AI, apolipoprotein E, B-type natriuretic peptide, cystatin C, fibrinogen, leptin, LDL subclass, HDL subclass, lipoprotein[a])  INVESTIGATIONAL as an adjunct to LDL cholesterol in the risk assessment and management of cardiovascular disease.  

8. Cardiovascular Risk Panels

Cardiovascular risk panels, consisting of multiple individual biomarkers intended to assess cardiac risk (other than simple lipid panels, see Policy Guidelines below), are INVESTIGATIONAL and do not meet coverage criteria.  

9. Serum Intermediate Density Lipoprotein

Measurement of serum intermediate density lipoproteins is considered INVESTIGATIONAL and does not meet coverage criteria as an indicator of cardiovascular disease risk.

10. Lipoprotein-associated Phospholipase A2

Measurement of lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered INVESTIGATIONAL and does not meet coverage criteria as an indicator of risk of cardiovascular disease.  

11. Long-chain Omega-3 Fatty Acid

Measurement of long-chain omega-3 fatty acids in red blood cell membranes, including but not limited to its use as a cardiac risk factor is INVESTIGATIONAL. 

12.  The use of genotyping for 9p21 single nucleotide polymorphisms is INVESTIGATIONAL for all indications, including identification of patients who may be at increased risk of cardiovascular disease or its manifestations. (e.g., MI, ischemic stroke, peripheral arterial disease, coronary artery calcification) or identification of patients who may be at increased risk for aneurysmal disease (abdominal aortic aneurysms, intracranial aneurysms, polypoidal choroidal vasculopathy).

13.  KIF6 Genotyping is INVESTIGATIONAL for predicting cardiovascular risk and/or the effectiveness of statin therapy. 

14. All other tests for assessing CHD risk is considered INVESTIGATIONAL.

Rationale  
American College of Cardiology (ACC)/American Heart Association (AHA)
The American College of Cardiology Foundation (ACC) and American Heart Association (AHA) published joint guidelines on the assessment of cardiovascular risk in asymptomatic patients in 2010 (Greenland et al., 2010), that were then updated in 2013 (Goff et al., 2014).

In adults between the ages of 20 and 79 who are free from cardiovascular disease (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 (Vijan, 2017).

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:

  1. If, after quantitative risk assessment, a risk-based treatment decision is uncertain, assessment of 1 or more of the following—family history, hs-CRP, ABI or CAC may be considered to inform treatment decision making.
  2. CIMT is not recommended for routine measurement in clinical practice for risk assessment for a first ASCVD event.
  3. The contribution to risk assessment for a first ASCVD event using ApoB, chronic kidney disease, albuminuria, or cardiorespiratory fitness is uncertain at present.

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. However, the 2013 guidelines on the assessment of cardiovascular risk do not mention Lp-PLA2 testing (Goff et al., 2014).

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.

American Diabetes Association
The ADA recommends screening for lipid disorders at the time of diabetes diagnosis, at an initial medical evaluation, and every five years thereafter and more often if indicated ("Standards of Medical Care in Diabetes-2017: Summary of Revisions," 2017; Vijan, 2017)

ADA guidelines state that some experts recommend a greater focus on non-HDL cholesterol, apolipoprotein B (apoB) or lipoprotein particle measurements to assess residual CVD risk in statin-treated patients who are likely to have small LDL particles, such as people with diabetes, but it is unclear whether clinical management would change with these measurements (ADA, 2015).

National Academy of Clinical Biochemistry (NACB)
The NACB (2009) makes the following recommendations on emerging biomarkers for CVD risk assessment

  • Lipoprotein subclass determination is not recommended. Lipoprotein subclasses, especially the number or concentration of small, dense LDL particles, have been shown to be related to the development of initial CHD events; however, the clinical evidence is not adequate to show added benefit over standard risk assessment
  • Lipoprotein (a) screening is not warranted for primary prevention and assessment of cardiovascular risk. Based on lower quality evidence, routine testing for lipoprotein may be considered under the following circumstances:
    • patient or family history of premature atherosclerotic heart disease,
    • familial history of hyperlipidemia,
    • stablished atherosclerotic heart disease with a normal routine lipid profile,
    • hyperlipidemia refractory to therapy and a history of recurrent arterial stenosis.
  • Although studies indicate that apolipoprotein B is a good predictor of CHD risk, it is only marginally better than the standard lipid profile and should not be routinely measured for CHD risk assessment.

American Association of Clinical Endocrinologists
The 2017 American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Dyslipidemia and Prevention of Cardiovascular Disease recommend(Jellinger et al., 2017): 

  • 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 5 years as part of a global risk assessment
  • Middle-aged individuals (Men Aged 45-65 Years, Women Aged 55-65 Years) should be screened for dyslipidemia at least every 1 to 2 years.
  • All individuals with diabetes should be screened with a lipid profile at the time of diagnosis and annually thereafter. Based on individual clinical considerations, some individuals with diabetes can be screened less frequently
  • Because many older individuals (over 65 years) may benefit from lipid-lowering therapy, even those with 0 to 1 ASCVD risk factors should be screened for dyslipidemia annually
  • In children at risk for FH (e.g., family history of premature cardiovascular disease or elevated cholesterol), screening should be at 3 years of age, again between ages 9 and 11, and again at age 18
  • Screen adolescents older than 16 years every 5 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
  • Lipoprotein-associated phospholipase A2 (Lp-PLA2), which in some studies has demonstrated more specificity than hsCRP, 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 (CAC) 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

European Society of Cardiology and Other Societies
In 2012, the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice issued guidelines on cardiovascular disease prevention (Perk J etal, 2012) These guidelines include the following statement about Lp-PLA2 testing: "LpPLA2 may be measured as part of a refined risk assessment in patients at high risk of a recurrent acute atherothrombotic event (Class IIb recommendation; Level of Evidence B; weak evidence)."

U.S. Preventive Services Task Force
The 2017 USPSTF Task Force Recommendations include(Bibbins-Domingo et al., 2017; Chou et al., 2016):

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 5 years. Shorter intervals may be useful for persons whose risk levels are close to those warranting therapy, and longer intervals are appropriate for persons who are not at increased risk and have repeatedly normal levels.

The USPSTF found insufficient evidence that screening for dyslipidemia before age 40 years has an effect on either short- or longer-term 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. Insufficient evidence to assess the balance of benefits and harms of screening for dyslipidemia in children and adolescents.

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 (Aberg et al, 2014). 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.

References 

  1. Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA, Infectious Diseases Society of America (2014). Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis., 58(1):e1-34. doi: 10.1093/cid/cit665. Epub 2013 Nov 13.
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  3. Bosch J, Gerstein HC, Dagenais FR, Diaz R, Dyal L, Jung H, Maggiono AP, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S;. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012; 367:309–318
  4. Brunzell, J.D., Davidson, M., Furberg, C.D.,f et al (2008). Lipoprotein management in patients with cardiometabolic risk. Consensus statement from the American Diabetes Association and the the American College of Cardiology Foundation. Retrieved February, 2017, from https://www.ncbi.nlm.nih.gov/pubmed/18375431
  5. Centers for Disease Control and Prevention. (2015). Heart disease facts. Retrieved February 15, 2017, from https://www.cdc.gov/heartdisease/facts.htm
  6. Davidson, M. H., Ballantyne, C. M., Jacobson, T. A., Bittner, V. A., Braun, L. T., Brown, A. S., . . . Dicklin, M. R. (2011). Clinical utility of inflammatory markers and advanced lipoprotein testing: advice from an expert panel of lipid specialists. J Clin Lipidol, 5(5), 338-367. doi:10.1016/j.jacl.2011.07.00510.1016/j.jacl.2011.07.005.
  7. de Oliveira Otto, M. C., Wu, J. H., Baylin, A., Vaidya, D., Rich, S. S., Tsai, M. Y., . . . Mozaffarian, D. (2013). Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc, 2(6), e000506. doi:10.1161/jaha.113.000506
  8. Di Angelantonio, E., Sarwar, N., Perry, P., Kaptoge, S., Ray, K. K., Thompson, A., . . . Danesh, J. (2009). Major lipids, apolipoproteins, and risk of vascular disease. Jama, 302(18), 1993-2000. doi:10.1001/jama.2009.1619
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  15. Jellinger, P. S., Smith, D. A., Mehta, A. E., Ganda, O., Handelsman, Y., Rodbard, H. W., . . . Seibel, J. A. (2012). American Association of Clinical Endocrinologists' Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis. Endocr Pract, 18 Suppl 1, 1-78.
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  38. de Oliveira Otto, M. C., Wu, J. H., Baylin, A., Vaidya, D., Rich, S. S., Tsai, M. Y., . . . Mozaffarian, D. (2013). Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc, 2(6), e000506. doi:10.1161/jaha.113.000506
  39. Di Angelantonio, E., Sarwar, N., Perry, P., Kaptoge, S., Ray, K. K., Thompson, A., . . . Danesh, J. (2009). Major lipids, apolipoproteins, and risk of vascular disease. Jama, 302(18), 1993-2000. doi:10.1001/jama.2009.1619
  40. Donato, L. J. (2016). Testing for Lipoprotein Associated Phospholipase A2 - AACC.org.
  41. Dutheil, F., Walther, G., Chapier, R., Mnatzaganian, G., Lesourd, B., Naughton, G., . . . Lac, G. (2014). Atherogenic subfractions of lipoproteins in the treatment of metabolic syndrome by physical activity and diet– the RESOLVE trial. Lipids Health Dis, 13, 112. doi:10.1186/1476-511x-13-112
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  44. Goliasch, G., Oravec, S., Blessberger, H., Dostal, E., Hoke, M., Wojta, J., . . . Wiesbauer, F. (2012). Relative importance of different lipid risk factors for the development of myocardial infarction at a very young age (</= 40 years of age). Eur J Clin Invest, 42(6), 631-636. doi:10.1111/j.1365-2362.2011.02629.x
  45. Greenland, P., Alpert, J. S., Beller, G. A., Benjamin, E. J., Budoff, M. J., Fayad, Z. A., . . . 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. doi:10.1016/j.jacc.2010.09.001
  46. Itakura, H., Yokoyama, M., Matsuzaki, M., Saito, Y., Origasa, H., Ishikawa, Y., . . . Matsuzawa, Y. (2011). Relationships between plasma fatty acid composition and coronary artery disease. J Atheroscler Thromb, 18(2), 99-107.
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  49. Mohler, E. R., 3rd, Ballantyne, C. M., Davidson, M. H., Hanefeld, M., Ruilope, L. M., Johnson, J. L., & Zalewski, A. (2008). The effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study. J Am Coll Cardiol, 51(17), 1632-1641. doi:10.1016/j.jacc.2007.11.079
  50. Quispe, R., Manalac, R. J., Faridi, K. F., Blaha, M. J., Toth, P. P., Kulkarni, K. R., . . . Jones, S. R. (2015). Relationship of the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to the remainder of the lipid profile: The Very Large Database of Lipids-4 (VLDL-4) study. Atherosclerosis, 242(1), 243-250. doi:10.1016/j.atherosclerosis.2015.06.057
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  55. Varbo, A., Benn, M., & Nordestgaard, B. G. (2014). Remnant cholesterol as a cause of ischemic heart disease: evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment. Pharmacol Ther, 141(3), 358-367. doi:10.1016/j.pharmthera.2013.11.008
  56. Varbo, A., Benn, M., Tybjaerg-Hansen, A., Jorgensen, A. B., Frikke-Schmidt, R., & Nordestgaard, B. G. (2013). Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol, 61(4), 427-436. doi:10.1016/j.jacc.2012.08.1026
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Coding Section

Code Number Description 
CPT 0111T Long-chain (C20-22) omega-3 fatty acids in red blood cell membranes
  0052U  Lipoprotein, blood, high resolution fractionation and quantitation of lipoproteins, including all five major lipoprotein classes and subclasses of HDL, LDL, and VLDL by vertical auto profile ultracentrifugation 
  80061 Lipid Panel
  81291

MTHFR (5,10-methylenetetrahydrofolate reductase) (eg, hereditary hypercoagulability) gene analysis, common variants (eg, 677T, 1298C)

  81400-81408

Molecular pathology 

  81479

Unlisted molecular pathology procedure 

  81493

Coronary artery disease, mRNA, gene expression profiling by real-time RE-PCR of 23 genes, utilizing whole peripheral blood, algorithm reported as a risk score 

  81599

Unlisted multianalyte assay with algorithmic analysis 

  82163 

Angiotensin II 

  82172 

Apolipoprotein, each

  82465

Cholesterol, serum or whole blood, total

  82652

Vitamin D; 1,25 dihydroxy, includes fraction(s), if performed

  82725

Fatty acids, nonesterified 

  83006

Growth stimulation expressed gene 2 (ST2, Interleukin 1 receptor like-1)

  83090

Homocysteine 

  83520

Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified [adiponectin] [leptin] [interleukin-6 (IL-6)] [tumor necrosis factor alpha (TNF-a)] [Oxidized phospholipids]  

  83695

Lipoprorotein (a)  

  83698

Lipoprotein-associated phospholipase A2 (Lp-PLA2)  

  83700

Lipoprotein, blood; electorophoretic separation and quantitation 

  83701

Lipoprotein, blood; high resolution fractionation and quantitation of lipoproteins including lipoprotein subclasses when performed (eg, electrophoresis, ultracentrifugation) [VAP cholesterol test]

  83704

Lipoprotein, blood; quantitation of lipoprotein particle numbers and lipoprotein particle subclasses (eg, by nuclear magnetic resonance spectroscopy)  

  83718

Lipoprotein, direct measurement; high density cholesterol (HDL cholesterol)  

 

83719

Lipoprotein, direct measurement; VLDL cholesterol  

  83721  Lipoprotein, direct measurement; low density cholesterol (LDL cholesterol)
  83722 (effective 01/01/2019) 

Lipoprotein, direct measurement; small dense LDL cholesterol 

  83880

Natriuretic peptide  

  84478 Triglycerides
  84484

Troponin, quantitative  

  84512 

Troponin, Qualitative  

  85384

Fibrinogen; activity 

  85385

antigen 

  85415

Fibrinolytic factors and inhibitors; plasminogen activator  

  86141

C-reactive protein; high sensitivity (hsCRP) [2 or more major risk factors, LDL 100-300 mg/dl, and intermediate risk of CVD by global risk assessment  

ICD-10-CM  B20 

Human immunodeficiency virus (HIV) disease

  B25.2

Cytomegaloviral pancreatitis

  B52.0

Plasmodium malariae malaria with nephropathy

  E00.0-E00.9

Congenital iodine-deficiency syndrome

 

E01.8

Other iodine-deficiency related thyroid disorders and allied conditions

 

E02

Subclinical iodine-deficiency hypothyroidism

 

E03.0-E03.9

Congenital hypothyroidism

 

E05.00-E05.91

Thyrotoxicosis (hypothyroidism)

 

E06.0 -E06.9

Thyroiditis

 

E08.00-E13.9

Diabetes mellitus

 

E24.0-E24.9

Cushing's Syndrome

 

E40

Kwashiorkor

 

E41

Nutritional marasmus

  E42

Marasmic kwashiorkor

  E43

Unspecified severe protein-calorie malnutrition

  E44.0

Moderate protein-calorie malnutrition

  E44.1

Mild protein-calorie malnutrition

  E46

Unspecified protein-calorie malnutrition

  E64.0

Sequelae of protein-calorie malnutrition

  E66.01-E66.9

Obesity

  E71.30

Disorder of fatty-acid metabolism, unspecified

 

E72.00-E72.09 

Disorders of amino-acid transport 
 

E72.11 

Homocystinuria/Cystathionine synthase deficiency  
 

E74.20-E74.29 

Disorder of galactose metabolism 
 

E75.21-E75.22 

Other sphingolipidosis 
 

E75.240-E75.249 

Niemann-Pick disease 
 

E75.3 

Sphingolipidosis, unspecified 
  E75.5  Other lipid storage disorders 
  E75.6 Lipid storage disorder, unspecified 
  E77.0-E77.9  Disorders of glycoprotein metabolism 
  E78.0-E78.9  Disorders of lipoprotein metabolism and other lipidemias 
  E79.0   Hyperuricemia without signs of inflammatory arthritis and tophaceous disease
  E85.0-E85.9 Amyloidosis 
  E88.1-E88.2   Lipodystrophy;Lipomatosis  
  E88.89   Other specified metabolic disorders  
  E89.0  Postprocedural hypothyroidism 
  G45.0-G45.9   Transient cerebral ischemic attacks and related syndromes  
  G46.0-G46.2   Vascular syndromes of brain in cerebrovascular diseases  
  I10-I15.9   Hypertension  
  I20.0-I25   Ishemic Heart Diseases  
  I25.1-I25.9   CAD  
  I125-10-I125.119 Atherosclerotic heart disease of native coronary artery
  I25.700-I25.799 Atherosclerosis of coronary artery bypass graft(s) and coronary artery of transplanted heart with angina pectoris
  I50.1-151.9   Heart Failure  
  I61.0-I61.9   Nontramatic intracranial hemorrhage  
  I63.00-I63.9   Cerebral infarction  
  I65.01-I66.9   Occlusion and stenosis of vertebral artery  
  I67.2   Occlusion and stenosis
  I67.5   Moyamoya disease  
  I67.81-I69.998   Sequelae of cerebrovascular disease  
  I70.0-I70.92   Atherosclerosis of aorta  
  I71.00-I71.9   Aortic aneurysm and dissection  
  I72.1-I72.3   Aneurysm of artery 
  I74.01-I74.9   Embolism and thrombosis  
  I79.0   Aneurysm of aorta in diseases classified elsewhere  
  K55.1   Chronic vascular disorders of intestine  
  K74.1-K74.2   Hepatic sclerosis  
  K75.81   Nonalcoholic steatohepatitis (NASH) 
  K76.0-K76.1   Other diseases of liver  
  K76.5   Hepatic veno-occlusive disease  
  K76.81-K76.9   Other specified diseases of liver  
  K77  Liver disorders in diseases classified elsewhere  
  K85.0 -K85.9   Acute pancreatitis  
  K86.0-K86.9   Disease of pancreas  
  K87   Disorders of gallbladder, biliary tract and pancreas in diseases classified elsewhere  
  N02.0-N04.9   Nephrotic Syndrome  
  N17.0   Acute kidney failure with tubular necrosis  
  N18.4-N18.9   Chronic Kidney Disease  
  N25.0-N25.9   Other Disorder of kidney and ureter  
  N26.2   Page kidney  
  R07.2   Precordial pain  
  R07.82-R07.9  Chest pain 
 

R16.0 - R16.2 

Hepatomegaly 
 

R74.0 -R74.9 

Abnormal serum enzyme level 
 

R78.89 

Finding of other specified substances, not normally found in blood 
  R79.0  Abnormal level of blood mineral 
  R79.89  Other specified abnormal findings of blood chemistry 
  R79.9  Abnormal finding of blood chemistry, unspecified 
  R93.3  Abnormal findings on diagnostic imaging of other parts of digestive tract 
  Z00.00  Encounter for general adult medical examination without abnormal findings 
  Z00.01  Encounter for general adult medical examination with abnormal findings 
  Z13.1  Encounter for screening for diabetes mellitus 
  Z13.6  Encounter for screening for cardiovascular disorders 
  Z15.89 Genetic susceptibility to other disease
  Z21  Asymptomatic human immunodeficiency virus infection status 
  Z51.81  Encounter for therapeutic drug monitoring 
  Z72.0  Tobacco use 
  Z13.220  Encounter for screening for lipoid disorders 
  Z82.41  Family history of sudden cardiac death 
  Z82.49  Family history of ischemic heart disease and other diseases of the circulatory system 
  Z83.41  Family history of multiple endocrine neoplasia [MEN] syndrome 
  Z83.49  Family history of other endocrine, nutritional and metabolic diseases 

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 and Blue Shield Association technology assessment program (TEC) and other non-affiliated 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 2018 Forward     

04/03/2019 

Annual review, adding medical necessity criteria for high sensitivity C reactive protein (hs-CRP) testing. Also updating coding. 

12/19/2018 

Updating with 2019 codes.  

04/18/2018 

Interim review adding investigational statements relating to 9p21 and KIF6 testing. No other changes made. 

02/28/2018 

Updating coding with E72.11 and Z51.89. No other changes made. 

01/24/2018

New Policy

 


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