Trends and disparities in lipoprotein(a) testing in a large integrated US health system, 2000–23

Lipoprotein(a) [Lp(a)] is a highly heritable, atherogenic lipoprotein that has implications for both primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Clinical trials of Lp(a)-directed therapeutics are underway in individuals with elevated Lp(a) and established ASCVD. The European Atherosclerosis Society recommends measurement of Lp(a) at least once in all adults, and the American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology endorse using Lp(a) to guide allocation of statins for primary prevention of ASCVD.^1–3 Furthermore, endocrine societies advise particular consideration of Lp(a) testing in individuals with African or South Asian ancestry given higher Lp(a) concentrations in these populations.⁴ However, the degree to which clinicians are measuring Lp(a) in practice remains incompletely characterized. Here, we aimed to characterize rates, trends, and disparities in Lp(a) testing among patients with and without coronary heart disease (CHD) across a large, integrated US healthcare system.

We extracted all Lp(a) testing performed between 1 January 2000 and 17 November 2023, within a large healthcare system in the Northeastern United States (Mass General Brigham) serving more than 1.6 million patients (73% White), encompassing seven academic and community hospitals and their affiliated practices. Patients with Lp(a) testing were stratified by the presence of CHD (defined by International Classification of Diseases-10 codes I20–25) and were compared with CHD patients who did not undergo Lp(a) testing. We then examined Lp(a) testing among primary prevention individuals with a 10-year estimated ASCVD risk between 5% and <20% using the PCE—a group specifically recommended for Lp(a) testing by ACC/AHA guidelines—between the years 2010 and 2012, who were then followed for incident CHD diagnosis through the end of the study period. Characteristics between groups were compared using the Pearson’s χ² with two-sided P < 0.05 denoting statistical significance.

A total of 66 937 Lp(a) assays were performed in 50 841 patients over the 23-year study period. The median [IQR] number of Lp(a) tests per patient was 1 [1,1]; testing was performed ≥2 times in 8482 individuals (16.7% of all tested). Lp(a) testing was performed in 23 966 patients without a CHD diagnosis and in 26 875 patients with CHD out of 465 814 total patients with CHD (i.e. in 5.8% of those with CHD). Between 2020 and 2023, overall Lp(a) testing volumes increased by 60% annually, with an even steeper increase in testing among primary prevention individuals (Figure 1A). Trends were consistent across race and gender groups (Figure 1B and C).

Figure 1

(A) Trends in lipoprotein(a) testing between 2000 and 2023 stratified by presence or absence of coronary heart disease (CHD). (B) Trends in lipoprotein(a) testing between 2000 and 2023 stratified by race/ethnicity. (C) Trends in lipoprotein(a) testing between 2000 and 2023 stratified by gender.

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Primary prevention individuals who underwent Lp(a) testing were 51.1% female, 78.7% White, 4.2% Black, 7.9% Asian, and 9.2% Other (Table 1a). Among individuals with CHD, those who did vs. did not have Lp(a) testing were more likely to be White (84.6% vs. 77.9%; P < 0.001). Compared with testing in White individuals, Lp(a) testing was less commonly performed in Black patients [odds ratio (OR) 0.58; 95% CI 0.55–0.61], less commonly performed in Other patients (OR 0.59; 95% CI 0.57–0.61), and more commonly performed in Asian patients (OR 1.13; 95% CI 1.06–1.20). Tested vs. untested individuals with CHD were also less likely to be female (OR 0.73; 95% CI 0.72–0.75).

A total of 65 001 patients without CHD at baseline had an estimated 10-year ASCVD risk between 5% and <20% by the PCE between 2010 and 2012. In this borderline-to-intermediate risk subgroup, 4.4% underwent Lp(a) testing overall. Mean estimated 10-year ASCVD risk did not differ between those who did vs. did not undergo Lp(a) testing (10.1% in both groups). Among both subgroups with incident CHD and those without incident CHD, those tested for Lp(a) vs. those not tested were more likely to be White (Table 1b). Among those with incident CHD, females were less likely than males to undergo testing (OR 0.86; 95% CI 0.77–0.97). During up to 13 years of follow-up (January 2010–November 2023), 35.6% of this subgroup was diagnosed with incident CHD. Lp(a) testing was more frequently performed in those who did vs. did not develop CHD (7.3% vs. 2.7%; P < 0.001). Among the subgroup of patients with incident CHD and Lp(a) testing, only 40.0% (680 of 1701) had Lp(a) testing performed prior to their CHD diagnosis. Among patients Lp(a) testing performed prior to their CHD diagnosis (n = 680), 253 (37.2%) were diagnosed with CHD within two years following Lp(a) testing.

Our principal findings are as follows: (1) rates of Lp(a) testing remain low, though they have been increasing since 2020; (2) significant disparities exist in Lp(a) testing practices, with Black and female patients with CHD significantly underrepresented among those screened for Lp(a); and (3) Lp(a) testing rates are low in primary prevention patients with borderline-to-intermediate ASCVD risk, a group specifically recommended for Lp(a) testing by ACC/AHA guidelines.

These results call for a redoubling of efforts to promote equitable, guideline-directed preventive cardiovascular care. Our results indicate that Lp(a) is underutilized as a risk-stratification tool to guide intensity of primary prevention efforts, especially in Black patients, despite this group being highlighted by guidelines for testing. Notably, among individuals with borderline-to-intermediate baseline risk who developed incident CHD, most Lp(a) testing was performed after diagnosis; earlier Lp(a) testing may have enabled improved risk stratification and earlier intensification of primary prevention.

Strengths of our analysis include a study period incorporating over two decades of laboratory testing, a sample size larger than that of recent studies on this topic,^5–9 and, uniquely, examination of a key subgroup recommended by contemporary guidelines for Lp(a) testing (borderline-to-intermediate ASCVD risk individuals). Focus on a healthcare system in the Northeastern United States may limit translatability to European practice settings, although recent Israeli data similarly indicate low rates of testing,⁹ and both US and European guidelines endorse the use of Lp(a) testing to aid in risk stratification. Individuals followed longitudinally in the Mass General Brigham system may be enriched for high risk, as indicated by a higher rate of incident CHD in borderline-to-intermediate risk individuals than predicted by the PCE. Finally, given the large sample size, ICD codes were used to ascertain CHD, and family history was not available. Nonetheless, our findings highlight the need to address disparities in Lp(a) testing and further efforts to promote the implementation of guideline-directed Lp(a) screening in appropriate patients.

Author contribution

C.C.F.-A. and M.C.H. contributed to the conception and design of the work, the acquisition, analysis, or interpretation of data for the work, drafted the manuscript, and revised the manuscript. S.M.J.C. contributed the analysis of data for the work. P.N. and M.C.H. critically revised the manuscript. All gave final approval and agreed to be accountable for all aspects of work ensuring integrity and accuracy.

Funding

P.N. is supported by grants from the National Heart, Lung, and Blood Institute (NHLBI R01HL127564) and Fondation Leducq (TNE-18CVD04). M.C.H. is supported by NHLBI (K08HL166687) and the American Heart Association (940166, 979465).

Data availability

The data underlying this article cannot be shared publicly for the privacy of individuals that participated in the study. The data will be shared on reasonable request to the corresponding author.

References

Author notes