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

More precise assessment of risk factors during preventative care, as well as after a diagnosis of CVD, may improve the timeliness and precision of earlier interventions (both lifestyle and therapeutic) that reduce CVD morbidity and mortality ^.27 Personalized or precision medicine approaches take into account differences in socioeconomic, environmental, and lifestyle factors that are potentially reversible, as well as gender, race, and ethnicity. ^28-31 Current methods of predicting CVD risk have considerable room for improvement. ²⁷ About 40% of patients with newly diagnosed CVD have normal traditional cholesterol profiles, including those whose first cardiac event proves fatal. ^29-33 Currently available risk scores (hundreds have been described in the literature) mischaracterize risk in minority populations and women, and have shown deficiencies in identifying preclinical atherosclerosis. ^34,35 The failure to recognize preclinical CVD in military personnel during their active duty life cycle results in missed opportunities for improved health and readiness sustainment.

Most CVD risk prediction models incorporate some form of blood lipids. Total cholesterol (TC) is most commonly used in clinical practice, along with high-density lipoprotein (HDLC), low-density lipoprotein (LDLC), and triglycerides (TG). ^23,27,36 High LDLC and/or TC are well established as lipid-related CVD risk factors and are incorporated into many CVD risk scoring systems/models described in the literature. ²⁷ LDLC reduction is commonly recommended as CVD prevention, but even with optimal statin treatment, there is still considerable residual risk for new and recurrent CVD events. ^{28,32,34,35,37-42}

Incorporating novel biomarkers and alternative lipid measurements may improve risk prediction and aid targeted treatment, ultimately reducing CVD events. ²⁷ Apolipoprotein B (ApoB) is a major atherogenic component embedded in LDL and VLDL correlating to non-HDLC and may be useful in the setting of triglycerides ≥ 200 mg/d as levels > 130 mg/ dL appear to be risk-enhancing, but measurements may be unreliable. ⁴³ According to the 2018 Cholesterol Guidelines, lipoprotein(a) [Lp(a)] elevation also is recognized as a risk-enhancing factor that is particularly implicated when there is a strong family history of premature atherosclerotic CVD or personal history of CVD not explained by major risk factors. ⁴³

Lp(a) elevation is a largely underrecognized category of lipid disorder that impacts up to 20% to 30% of the population globally and within the US, although there is considerable variability by geographic location and ethnicity. ⁴⁴ Globally, Lp(a) elevation places > 1 billion people at moderate to high risk for CVD.44 Lp(a) has a strong genetic component and is recognized as a distinct and independent risk factor for MI, sudden death, strokes and CAVS. Lp(a) has an extensive body of evidence to support its distinct role both as a causal factor in CVD and as an augmentation to traditional risk factors. ^44-48

Lipoproteni(a) Elevation Use For Diagnosis

The importance of Lp(a) elevation as a clinical diagnosis rather than a laboratory abnormality alone was brought forward by the Lipoprotein(a) Foundation. Its founder, Sandra Tremulis, is a survivor of an acute coronary event that occurred when she was 39-years old, despite running marathons and having none of the traditional CVD lifestyle risk factors. ⁴⁹ This experience inspired her to create the Lipoprotein(a) Foundation to give a voice to families living with or at risk for CVD due to Lp(a) elevation.