Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle additionally bound to apolipoprotein(a) [apo(a)], and it is an independent causal risk factor for cardiovascular disease.1,2 Lp(a) confers risk due to its complementary atherogenic, prothrombotic, and proinflammatory effects of its LDL and apo(a) components, the combination of which increases the severity of the effects of elevated Lp(a) levels for cardiovascular health.3,4 Plasma Lp(a) levels are strongly heritable with genetic determinants explaining 70% to 95% of the levels; additionally, Lp(a) levels differ between historically and geographically defined ethnic or racial groups.1,4 Specifically, about 30% to 70% of Lp(a) levels are genetically determined by repeat polymorphisms in the LPA gene and to a lesser degree by common single-nucleotide polymorphisms, which differ between ethnic groups causing differing typical Lp(a) levels.5 Elevated Lp(a) affects roughly 1 in 10 South and Southeast Asian individuals, 1 in 5 European individuals, and 1 in 4 African individuals;4,6 however, most people go undiagnosed without standardized testing recommendations.1

While standardized and widely accepted testing recommendations are limited in the US or Europe, they each have testing guidelines for symptomatic individuals, although the guidelines differ and lack consistency. Previous guidelines from the National Lipid Association (NLA) recommended Lp(a) testing in people experiencing symptoms, such as high LDL cholesterol (LDL-C) without improvement with medications, and/or who have a family history of elevated Lp(a); however, a very recent statement from the NLA is consistent with the European Atherosclerosis Society (EAS) recommendations for universal testing in adults.3,7, 8, 9 There is consensus across various organizations that anyone with a personal or family history of premature atherosclerotic cardiovascular disease should undergo Lp(a) testing; however, in the United States, less than 4% of people who qualify for Lp(a) testing by these standards receive Lp(a) testing.10 The American Heart Association recommends discussing Lp(a) testing with a clinician if there is a family history of elevated Lp(a), personal or family history of early cardiovascular/heart disease, or a diagnosis of familial hypercholesterolemia (FH). Research suggests that Lp(a) status and FH improve the prediction of cardiovascular outcomes.11,12 However, there is a lack of data on patients’ views of testing and/or whether they experience decision regret or anxiety regarding Lp(a) testing.

Although there is an association between high Lp(a) levels and a 2- to 2.5-fold increased risk for cardiovascular disease in adulthood, there are no comprehensive Lp(a) testing protocols or guidelines for pediatric populations.13 The EAS recommends that children should be tested if there is a personal history of ischemic stroke or if a parent has premature atherosclerotic cardiovascular disease and no other known risk factors.5 There have been editorials and commentaries from health professionals regarding testing Lp(a) in adolescents,7,14 or adding Lp(a) testing to the current recommendation for universal lipid screening in childhood.14 However, many primary care physicians and other clinicians are not aware of the influence of Lp(a) levels on cardiovascular disease or that this testing may be recommended.7

Management of elevated Lp(a) presents several challenges. Owing to its genetic determinants, lifestyle changes—like diet and physical activity—do not influence plasma Lp(a) levels.15 Additionally, common lipid-lowering medications are not effective, and some studies suggest statins paradoxically increase plasma Lp(a) by 10% to 20%, although this may not be clinically significant.1,16 Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to slightly reduce plasma Lp(a), this effect has not yet been determined to be clinically meaningful for risk reduction; these changes are not influenced by duration of PCSK9 inhibitor use or sex assigned at birth.17,18 The only medical treatment that can directly lower Lp(a) levels is lipoprotein apheresis. Due to the untargeted way lipoprotein apheresis impacts lipids, lipoprotein apheresis is currently only used for people who have very high Lp(a) levels and progressive atherosclerotic disease.5 Clinical trials are ongoing in pursuit of Lp(a)-lowering medications as an alternative.5 This lack of Food and Drug Administration-approved Lp(a) targeted therapies may be contributing to the underutilization of Lp(a) testing. Identifying people with elevated Lp(a) is important for prioritizing individuals at higher risk of cardiovascular disease who would benefit from more aggressive control of additional risk factors like residual LDL-C, triglycerides, hypertension, and diabetes.5

Despite the recommendations for Lp(a) screening in adulthood, there are no previous studies assessing views of testing or uptake of Lp(a) cascade screening by relatives of people with elevated Lp(a). Additionally, it is unclear what barriers patients experience, such as access to Lp(a) testing, clinician knowledge, or currently limited treatment opportunities for Lp(a). It may be possible that several of these factors influence the decision to have or request Lp(a) screening in addition to the success of family cascade Lp(a) screening. Moreover, there are no studies that have investigated how people with elevated Lp(a) perceive the utility of testing in minors.

Cardiovascular disease risk factors have been found to be impacted by psychosocial health, including depression and anxiety.19 Depression and anxiety are known to be associated with worse health outcomes in terms of morbidity, mortality, and quality of life in those with cardiovascular disease.19 Additionally, optimism may impact depression and has been found to be associated with a lower risk of cardiovascular disease and mortality.20 Decision regret, described as distress or remorse over a healthcare decision, has been studied in the context of the decision-making process about a treatment or screening decision, specifically regarding whether decision aids are helpful in making a treatment or screening decision, of which they were not significant.21

Considering the risk of undertreatment, the challenges of screening, and the lack of information regarding patient perspectives, we sought to explore and describe the experiences of people living with elevated Lp(a). Our aims were to investigate how patients experience testing and care for Lp(a), specifically, identifying barriers to testing access and what personal utility people find in knowing their elevated Lp(a) status. Moreover, we aim to determine whether parents with elevated Lp(a) test their children’s Lp(a) levels, and what factors influence this testing decision and the barriers to testing children. We hope to illustrate how these factors may relate to decisional regret and anxiety regarding Lp(a) and Lp(a) testing in addition to optimism and family testing practices. Our findings have the potential to impact clinical care and help to inform clinical guidelines.