Original Research

Lipoprotein(a) Elevation: A New Diagnostic Code with Relevance to Service Members and Veterans

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As often happens in the progress of medicine, patients and their families drive change based on their personal experiences with the gaps in standard clinical practice. It was this foundation—not a member of the medical establishment—that submitted the formal request for the addition of new ICD-10-CM diagnostic and family history codes for Lp(a) elevation during the Centers for Disease Control and Prevention (CDC) September 2017 ICD-10-CM Coordination and Maintenance Committee meeting. 50 In June 2018, the final ICD-10-CM code addenda for 2019 was released and included the new codes E78. 41 (Elevated Lp[a]) and Z83.430 (Family history of elevated Lp[a]). 52 After the new codes were approved, both the American Heart Association and the National Lipid Association added recommendations regarding Lp(a) testing to their clinical practice guidelines. 43,52

Practically, these codes standardize billing and payment for legitimate clinical work and laboratory testing. Prior to the addition of Lp(a) elevation as a clinical diagnosis, testing and treatment of Lp(a) elevation was considered experimental and not medically necessary until after a cardiovascular event had already occurred. Services for Lp(a) elevation were therefore not reimbursed by many healthcare organizations and insurance companies. The new ICD-10-CM codes encourage the assessment of Lp(a) both in individuals with early onset major CVD events and in presumably fit, healthy individuals, particularly when there is a family history of Lp(a) elevation. Given that Lp(a) levels do not change significantly over time, the current understanding is that only a single measurement is needed to define the individual risk over a lifetime. 41,42,44,45 As therapies targeting Lp(a) levels evolve, repeated measurements may be indicated to monitor response and direct changes in management. “Elevated Lipoprotein(a)” is the first laboratory testing abnormality that has achieved the status of a clinical diagnosis.

Lp(a) Measurements

There is considerable complexity to the measurement of lipoproteins in blood samples due to heterogeneity in both density and size of particles as illustrated in the Figure. 53

For traditional lipids measured in clinical practice, the size and density ranges from small high-density lipoprotein (HDL) through LDLC and intermediate- density lipoprotein (IDL) to the largest least dense particles in the very low-density lipoprotein (VLDL) and chylomicron remnant fractions. Standard lipid profiles consist of mass concentration measurements (mg/dL) of TC, TG, HDLC, and LDLC. 53 Non-HDLC (calculated as: TC−HDLC) consists of all cholesterol found in atherogenic lipoproteins, including remnant-C and Lp(a). Until recently, the cholesterol content of Lp(a), corresponding to about 30% of Lp(a) total mass, was included in the TC, non-HDLC and LDLC measurements with no separate reporting by the majority of clinical laboratories.

After > 50 years of research on the structure and biochemistry of Lp(a), the physiology and biological functions of these complex and polymorphic lipoprotein particles are not fully understood. Lp(a) is composed of a lipoprotein particle similar in composition to LDL (protein and lipid), containing 1 molecule of ApoB wrapped around a core of cholesteryl ester and triglyceride with phospholipids and unesterified cholesterol at its surface. 48 The presence of a unique hydrophilic, highly glycosylated protein referred to as apolopoprotienA (apo[a]), covalently attached to ApoB-100 by a single disulfide bridge, differentiates Lp(a) from LDL. 48 Cholesterol rich ApoB is an important component within many lipoproteins pathogenic for atherosclerosis and CVD. 45,47,53

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