Lipoprotein (a) Testing in Patients With Atherosclerotic Cardiovascular Disease in 5 Large US Health Systems

Abstract

Background: Lipoprotein (a) is an independent risk factor for atherosclerotic cardiovascular disease. However, lipoprotein (a) testing remains variable and it is unclear what factors influence testing and if testing changes clinical management.

Methods and results: A retrospective study using electronic medical record data from 5 health systems identified an atherosclerotic cardiovascular disease cohort divided into those with and without a lipoprotein (a) test between 2019 and 2021. Baseline characteristics and lipid-lowering therapy patterns were assessed. Multivariable regression modeling was used to determine factors associated with lipoprotein (a) testing. Among 595 684 patients with atherosclerotic cardiovascular disease, only 2587 (0.4%) were tested for lipoprotein (a). Those who were older or Black individuals were less likely to have lipoprotein (a) testing, while those with familial hypercholesterolemia, ischemic stroke/transient ischemic attack, peripheral artery disease, prior lipid-lowering therapy, or low-density lipoprotein cholesterol ≥130 mg/dL were more likely to be tested. Those with a lipoprotein (a) test, regardless of the lipoprotein (a) value, were more frequently initiated on any statin therapy (30.3% versus 10.6%, P < 0.001), ezetimibe (7.65% versus 0.8%, P < 0.001), or proprotein convertase substilisin/kexin type 9 inhibitor (6.7% versus 0.3%, P < 0.001) compared with those without a test. Those with an elevated lipoprotein (a) level more frequently initiated ezetimibe (11.5% versus 5.9%, P < 0.001) or proprotein convertase substilisin/kexin type 9 inhibitor (10.9% versus 4.8%, P < 0.001).

Conclusions: Lipoprotein (a) testing in patients with atherosclerotic cardiovascular disease is infrequent, with evidence of disparities among older or Black individuals. Testing for lipoprotein (a), regardless of level, is associated with greater initiation of any lipid-lowering therapy, while elevated lipoprotein (a) is associated with greater initiation of nonstatin lipid-lowering therapy. There is a critical need for multidisciplinary and inclusive approaches to raise awareness for lipoprotein (a) testing, and its implications on management.

Keywords: ASCVD; lipids; lipoprotein (a).

Figure 1. Consolidated Standards of Reporting Trials diagram describing study cohort.

sASCVD indicates atherosclerotic cardiovascular disease; and Lp(a), lipoprotein (a).

Figure 2. Forest plot of multivariable regression model describing factors associated with likelihood of testing for lipoprotein (a).

Units: blood pressure, mm Hg; BMI, kg/m²; creatinine, mg/dL; eGFR, mL/min per 1.73 m²; total cholesterol, mg/dL; HDL, mg/dL; triglycerides, mg/dL; LDL, mg/dL. ACE/ARB indicates angiotensin‐converting enzyme/angiotensin receptor blocker; BMI, body mass index; CAD, coronary artery disease; CKD, chronic kidney disease; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; HDL, high‐density lipoprotein cholesterol; HbA_1c, glycosylated hemoglobin; LDL, low‐density lipoprotein cholesterol; LLT, lipid‐lowering therapy; PAD, peripheral artery disease; SBP, systolic blood pressure; and TIA, transient ischemic attack.

Figure 3. Initiation of therapy during follow up among patients with atherosclerotic cardiovascular disease with a lipoprotein (a) test.

Initiation defined by no prescription in the year before index date, but a prescription is present in the 6 mo following a lipoprotein (a) test. Above lipoprotein (a) threshold is defined as lipoprotein (a) ≥50 mg/dL or ≥125 nmol/L). Any LLT indicates a patient was initiated on ≥1 of the following prescriptions: statins, PCSK9i, ezetimibe, or bempedoic acid. BA indicates bempedoic acid; Eze, ezetimibe; LLT, lipid‐lowering therapy; Lp(a), lipoprotein (a); and PCSK9, monoclonal antibody‐based proprotein convertase subtilisin/kexin type 9 inhibitor.