Cardiovascular disease is a major health problem in the United States. According to the Centers for Disease Control (CDC), over 700,000 people suffer heart attacks and 600,000 people die annually from heart disease.1 Atherosclerosis – plaque buildup in the artery walls that prevents blood flow to the heart – may cause heart attacks, cardiovascular disease, and heart failure.2 Ideally, clinicians would like to prevent these cardiac issues, rather than prescribe a treatment in reaction to an adverse cardiovascular event such as a heart attack. The National Institutes of Health (NIH) reports there are many things patients can do to improve their health including: controlling blood pressure, maintaining a healthy weight and diet, regular exercise, and reducing stress. However, there are some risk factors that one cannot control: age, family history, biological sex, and race/ethnicity.3
In 2007, the Framingham Heart Study was published. It provided the clinical evidence for using body mass index (BMI), blood pressure, LDL cholesterol, triglycerides, and blood glucose as risk factors for cardiovascular disease . This article gave rise to the Framingham risk score, which uses these biomarkers, with other clinical measurements, to provide a 10-year risk assessment for coronary heart disease (CHD). 4, 5 It is still being used today by clinicians to assist patients in maintaining their heart health.
Based on the above publication, the Centers for Medicare & Medicaid Services (CMS) allows for coverage, under preventative services, of a basic lipid panel (total cholesterol, high density lipoprotein-cholesterol [HDL-C], triglycerides, and low density lipoprotein-cholesterol [Also, patients diagnosed with symptomatic atherosclerotic cardiovascular disease may also have a basic lipid panel covered annually. Nevertheless, these same tests are NOT covered when used as prophylactic screening in asymptomatic individuals.5,6
There are other cardiac biomarkers that may be ordered individually but will not be covered by CMS if ordered with a basic lipid panel. These may include apolipoproteins, cystatin c, homocysteine, and lipoprotein(a) among others . Additionally, high-sensitivity C-reactive protein (hs-CRP) may be covered in the following scenario:
- Patient has intermediate CV risk (10-20% risk of CVD per 10 years using the Framingham point score) AND
- Patient has LDL-C between 100-130 mg/dL AND
- Patient has two or more of these CHD major risk factors:
- Age (Men> 50 years; Women >60 years
- Current cigarette smoker
- Family history – CHD in male first degree relative <55; CHD in female fist degree relative
- Hypertension (Systolic > 140 mm Hg, or on anti-hypertensive medication)
- Low HDL-C
Currently, there are multiple non-lipid biomarkers (biochemical, immunological, hematological, and genetic markers) that are commercially available for physicians to order. Yet, CMS will not cover these tests when ordered with a basic lipid panel.
The Framingham risk score, based on the results from a basic lipid panel, is a common choice for physicians when managing their patients’ cardiovascular health. Recent advances in molecular and genetic research and technologies have given rise to interest in new biomarkers. Some of these biomarkers have even shown to alter Framingham-based risk categorization of patients (either higher or lower risk). Still, CMS reports there have been no high-quality studies showing medically actionable results that improve patient outcomes based on some of these new biomarkers. It is clear that further research is warranted, but it may take considerable time to gather a large enough population and observe long-term outcomes. For example, the Framingham Heart Study had a mean follow up of 19 years and included over 3,500 participants. 4
The American Heart Association published guidelines regarding how to objectively evaluate novel biomarkers prior to introducing into clinical practice. Indeed, the time and effort to commercialize even a single biomarker from proof of concept stage, to demonstrating clinical validity and utility, to making it clinically available is considerable.7 Generally, a biomarker should have high accuracy, precision, sensitivity, and specificity if it is to be used as a predictor of CHD . Ideally, such a biomarker should also demonstrate a response to therapy, add to known prognostic index (i.e. Framingham risk score), and possess low interindividual variability .8 Many biomarkers are being researched that are categorized by pathophysiology (inflammation, oxidative stress, etc.) or by disease type (heart failure, atherosclerotic disease, etc .).8
The basic lipid panel has been available for years and continues to be a tool for physicians in managing cardiovascular health in their patients. It is recognized that the Framingham risk score does not encompass all variables that may contribute to one’s heart health. There are other biomarkers that may be covered by insurance if clinically indicated and ordered as a single test. However, CMS discourages physicians from ordering large panels simultaneously by not providing coverage for certain biomarkers when ordered with a basic lipid panel. There are numerous researchers trying to add new biomarkers to increase precision, and perhaps capture information that is not included in the lipid panel. It is vital, as new discoveries are made in cardiac biomarkers, that well-designed studies that provide clinical validity and utility are published. These studies may give the evidence needed for CMS to cover new tests in the future.
- https://www.cdc.gov/heartdisease/facts.htm Accessed 7/13/2019.
- https://www.heart.org/en/health-topics/consumer-healthcare/what-is-cardiovascular-disease accessed 7/13/2019.
- https://medlineplus.gov/howtopreventheartdisease.html accessed 07/13/2019.
- Lee DS, Evans JC, Robins SJ, et al. Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study. Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:127-33.
- Local Coverage Determination (LCD): MolDX: Biomarkers in Cardiovascular Risk Assessment (L36129).
- Medicare National Coverage Determinations (NCD) Manual, Pub 100-03, Cpt 1, §190.23: Lipid Testing.
- Hlatky MA, Greenland P, Arnett DK, Ballantyne CM, Criqui MH, Elkind MS, et al. Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association. Circulation. 2009; 119:2408–2416.
- Dhingra R, and Ramachandran VS. Biomarkers in cardiovascular disease: Statistical assessment and section on key novel heart failure biomarkers. Trends Cardiovasc Med. 2017 Feb;27(2):123-133.