Figures
Abstract
Background
Elevated Lipoprotein(a) [Lp(a)] is a genetic risk factor for cardiovascular diseases affecting 20% of the world’s population, with multiple published consensus statements that recommend testing and management strategies. However, elevated Lp(a) remains under-detected and under-treated worldwide. Our qualitative study explored the perspectives of cardiology healthcare professionals regarding the barriers and enablers for Lp(a) detection and management.
Methods
Guided by Theoretical Domains Framework, we conducted 41 qualitative semi-structured one-on-one interviews in a cardiology department at a high-volume hospital in Singapore from October to December 2023. Healthcare professionals were purposively sampled across role and seniority to include doctors (specialists and interns), specialist nurses and dedicated pharmacists. Through an inductive process, we constructed qualitative codes followed by code-mapping to arrive at higher-order sub-categories, categories, and eventually themes.
Results
Analysis revealed 4 themes: rationale for routine testing, barriers to testing and follow-up, enablers of testing and follow-up, and ideal system to enhance patient management. Critical barriers to Lp(a) testing included a perceived lack of guidance in testing and follow-up, and misperception that Lp(a)-mediated cardiovascular risk cannot be managed resulting in low confidence of healthcare professionals to detect and manage elevated Lp(a). Inadequate institutional support to alleviate workload and presumed patient aversion to testing further hindered Lp(a) testing. We identified enablers and strategies to testing and management of Lp(a), notably these were the need for hospital-wide adequate training and education, guidelines and risk management pathways applicable to local settings, integration of Lp(a) testing into existing clinical pathways for high-risk patients, and user-friendly decision aids for healthcare professionals.
Citation: Loh W-J, Thai L, Poon B-L, Yeo J, Tan J-J, Lum E (2025) Barriers and strategies in detection and management of elevated Lipoprotein(a) in hospital: A pre-implementation qualitative study of cardiology healthcare professionals. PLoS One 20(10): e0333789. https://doi.org/10.1371/journal.pone.0333789
Editor: Chiara Pavanello, Universita degli Studi di Milano, ITALY
Received: June 8, 2025; Accepted: September 18, 2025; Published: October 15, 2025
Copyright: © 2025 Loh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The full datasets generated and analysed during the current study are not publicly available. Due to the roles and seniority disclosed in the de-identified transcripts, there is a non-negligible risk of participants being re-identified based on discussion content. Any data not available within this article or its supplementary materials can be obtained from corresponding author, last author and/or via Changi General Hospital (Department of Endocrinology, 2 Simei Street, Singapore 529889).
Funding: This study was partly funded by Singapore NMRC Population Health New Investigator Grant. No additional external funding was received for this study.
Competing interests: The authors have read the journal’s policy and have the following competing interests: WJL has received honoraria from DKSH, Novartis, Kowa, Medtronic, Abbott, Amgen and Inova. WJL was awarded research training fund from National Medical Research Council (NMRC) Singapore for PhD as well as awarded the NMRC Population Health New Investigator Grant. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
1. Introduction
Lipoprotein(a) [Lp(a)] is a pro-inflammatory, atherogenic and thrombogenic type of lipoprotein that when elevated is associated with increased risk of atherosclerotic cardiovascular diseases (ASCVD) [1,2]. Concerningly, elevated Lp(a) affects one-fifth of the global population as the most commonly inherited condition related to hypercholesterolemia [1,2]. As ASCVD is one of the major leading cause of mortality and morbidity affecting one-third of global population, the pressing concern for adequate diagnosis and treatment has led to clinical recommendations and implementation suggestions by lipid and cardiology consensus statements [2–6] as well as the recent Brussels International Declaration to promote integration of Lp(a) testing and management as a necessary action into routine clinical care [7]. Given the evidence supporting Lp(a)’s role in cardiovascular risk reduction, multiple lipid and cardiology guidelines since 2017 have recommended a simple non-fasting blood test for high-risk individuals to detect the condition of elevated Lp(a). Some consensus statements and guidelines further advocate that all adults in the general population should also be offered Lp(a) testing at least once in their lifetime [2–6]. Upon detection of severely elevated Lp(a), cascade testing of family members is also recommended [1–3,5,8–11].
However, despite evidence-based guidelines and expert recommendations, many countries have not adopted routine Lp(a) testing in clinical practice [12–15]. A retrospective study of 70 million individual health records from a US-based international research network revealed a testing rate of only 0.1% [16]. The practice of Lp(a) detection and result interpretation varies greatly even among specialists managing ASCVD. Some overlook testing entirely: a study in Singapore found Lp(a) testing was not conducted on hospitalised patients with ischaemic heart disease or myocardial infarction prior to 2021, whereas other studies in different countries have also reported severe under-testing of Lp(a) in patients at very high cardiovascular risk [14,15,17,18]. A follow-up study in 2024 reported almost half of cardiology and endocrinology specialists in Singapore never tested for Lp(a) previously, reflecting major awareness gaps, partially contributed by lack of local guidance [18]. This under-detection and consequently under-treatment of elevated Lp(a) is alarming given the growing burden of ASCVD, especially in Asia where stroke and ischaemic heart disease consistently remain leading causes of death and the cardiovascular mortality rate in the region is expected to double by 2050 [19,20].
The definition of elevated Lp(a) is biochemical but hitherto there is no agreed universal threshold criterion. The 2022 European Atherosclerosis Society (EAS) consensus defined Lp(a) above 125nmol/L (50 mg/dL) as elevated Lp(a), but other expert consensus groups uses different threshold levels (e.g.,90 nmol/L, 100 nmol/L) [2,8,9,11]. The recently published European consensus (ESC/EAS 2025) acknowledges Lp(a) above 105 nmol/L (50 mg/dL) to be elevated [21]. Current recommendations for Lp(a) management include intensifying control of low-density lipoprotein cholesterol (LDL-C), blood pressure, diabetes, and obesity among other modifiable cardiovascular risk factors [2,8,9,11]. LDL-C reduction involves lipid-lowering agents targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) pathways (e.g., evolocumab, alirocumab, and inclisiran), which also lower Lp(a) by 20–30%. This reduction likely accounted for the additional decrease of cardiovascular events in patients with elevated Lp(a) observed in post-hoc analyses studies [22,23]. Lipoprotein apheresis studies and large-cohort Mendelian randomisation analysis suggested that significant reduction of Lp(a) may decrease cardiovascular risk, thus providing impetus for rigorous management to mitigate adverse ASCVD outcomes [24,25]. Targeted Lp(a)-lowering agents (e.g., pelacarsen, olpasiran, and muvalaplin) have demonstrated encouraging clinical efficacy in Phase 1 and 2 studies [26–28], although results from its cardiovascular outcome trials are still eagerly awaited [9].
Given Lp(a)’s heavily overlooked potential to inform treatment and improve ASCVD prognosis, there is an urgent need to identify key obstacles to its detection and management, particularly in an Asian context. We conducted a pre-implementation study on the perspectives of healthcare professionals (HCPs) in a cardiology department of a large hospital in metropolitan Singapore. Our study aimed to explore the barriers and enablers affecting routine detection and management of elevated Lp(a) in patients at high risk for ASCVD and thereby inform the design of implementation strategies.
2. Methods
2.1. Study design
Three researchers (WJL, JJT, EL) developed a qualitative semi-structured interview guide (S1 Table) informed by the Theoretical Domains Framework (TDF), a validated framework comprising 14 domains: knowledge, skills, social/professional role and identity, beliefs about capabilities, optimism, beliefs about consequences, reinforcement, intentions, goals, memory/attention/decision processes, environmental context and resources, social influences, emotion, and behavioural regulation [29]. These domains encompass barriers to behaviour change at an individual level and can be used to select or design strategies to address modifiable barriers [30]. Since Lp(a) testing and management is initiated by individual clinicians, TDF was selected to underpin our study.
2.2. Study setting and participants
The study was conducted in Singapore, a multicultural hub in the Asia-Pacific region with a diverse ethnic population including Chinese, Malay, Indian and other ethnicities. Citizens rely on a robust public healthcare network well regarded for its efficiency, supported by national initiatives such as Healthier SG with a focus on preventive care and patient empowerment [31]. Participants were recruited from Changi General Hospital (CGH), a 1000-bed tertiary hospital serving a densely populated and aging community of over one million people in east and northeast Singapore. Handling among the highest cardiovascular workload in Singapore, its cardiology department recorded approximately 1000 admissions annually under the acute myocardial infarction pathway, along with many acute coronary syndrome cases admitted to other departments due to non-cardiovascular comorbidities.
HCPs in the cardiology department at the time of the study were invited to participate on a voluntary basis without reimbursement. Clinicians of varying seniority, together with dedicated nurses and pharmacists trained in cardiology care were purposively sampled to gain a range of perspectives within the department. Recruitment started on 18/10/2023 and concluded on 10/12/2023 upon data saturation, defined as the absence of further diversity of views or no new data. All participants provided informed written consent prior to the interviews. This study was approved by the SingHealth Centralised Institutional Review Board (reference number 2023–2429).
2.3. Procedures
Two researchers (BLP, JY) conducted 40 one-on-one interviews in-person and one remotely over Zoom, from October to December 2023. Researchers had minimal contact with participants before and after the interview concluded. Audio recordings were transcribed verbatim using an adapted version of Jeffersonian Transcription Notation (S2 Table) for consistency. Field notes replaced transcript for one interview (C013) due to technical errors. Transcripts were de-identified prior to data analysis.
2.4. Data analysis
Transcripts underwent analysis from April to June 2024 using Microsoft Word (2016, version 16.0.5452.1001). We conducted inductive coding followed by code-mapping to cluster codes into higher level categories and to generate themes. We elected not to conduct deductive coding based on the TDF for two reasons: to avoid imposing a pre-determined coding framework on the data and to allow a broader set of codes, beyond the level of individual actors, to be generated. The usage of TDF as a deductive coding framework would have restricted codes to the framework’s domains focussed on personal motivations and capabilities [32].
Initially, four researchers (BLP, JY, LT, EL) read through the interview transcripts independently to familiarise with the dataset. The same three transcripts, randomly selected, were each examined independently by BLP, JY, and LT to identify ideas or concepts relevant to the research question from participant interviews. Each discrete idea or concept (a “unit of meaning”) was then given a label (a code). A codebook was developed iteratively as coding progressed. Codes were reviewed, and discrepancies were resolved via consensus discussion moderated by EL. The remaining transcripts were then randomly allocated to four researchers for independent coding (BLP, JY, LT, EL). Revised inductive codes were continuously reviewed as coding progressed (S3 Table). Two cycles of code-mapping were subsequently completed (LT, EL) to arrive at higher-order sub-categories, categories, and themes. The outputs were presented to the rest of the study team for sense-checking and refinement. We constructed a thematic network diagram to visually represent linkages between the themes and nested categories (Fig 1).
Enablers were often discussed in direct response to the barriers, illustrated by arrows linking different categories.
3. Results
The recruitment response rate was 80% (41/51). We interviewed 41 participants comprising 32 doctors (15 cardiology specialists, 5 cardiology registrars and 12 medical officers), 3 dedicated specialist nurses, and 6 dedicated pharmacists for an average of 15 minutes each. Table 1 shows the characteristics of participants and duration of interviews.
The process of inductive coding generated 106 codes, arranged into 13 categories and 32 sub-categories, and ultimately forming four themes regarding barriers and enablers of Lp(a) testing and management (S3 Table, Fig 1). To illustrate the different categories in each of the 4 themes, verbatim quotes from selected codes are provided in Tables 2–5, formatted in plain text without Jeffersonian Transcription Notation for ease of reading. Fig 1 illustrates the thematic network diagram to visually represent linkages between the 4 overarching themes and nested categories. Enablers were often discussed in direct response to the barriers, illustrated by arrows linking different categories.
3.1. Theme 1: Rationale for routine testing
Theme 1 (Table 2) captures participants’ rationale for Lp(a) routine testing in hospitals. First, testing was generally perceived to be straightforward and feasible, easily done on-site, and is not more invasive than routine blood tests. Second, the clinical utility of Lp(a) testing was appreciated as part of prevention based on recommendations from existing guidelines. However paradoxically, we noted low awareness of guidelines on target population and management strategies. Third, Lp(a) testing was perceived as useful for patient stratification, thus empowering HCPs to intensify treatment and reducing clinical inertia. Similarly, patients might be more open to aggressive lipid management strategies given an elevated Lp(a) result.
3.2. Theme 2: Barriers to testing and follow-up
In contrast to Theme 1’s perceived advantages of Lp(a) testing, Theme 2 (Table 3) explores current challenges and foreseeable barriers leading to scepticism towards the diagnosis and management of elevated Lp(a) in practice.
3.2a). Knowledge gap among HCPs.
The first and foremost barrier was a lack of medical knowledge. Regarding general understanding of Lp(a), almost all reported uncertainty on pathophysiology, prevalence and risk thresholds; including clinicians who acknowledged elevated Lp(a) as a risk factor for ASCVD. The clinical significance of Lp(a) in ASCVD management was deemed unestablished: Lp(a)’s role as a risk factor only gained prominence recently and key strategies such as cascade testing was unknown to many. Given the recency of consensus on management strategies (within the last 5–7 years), HCPs especially non-cardiologists or non-endocrinologists were likely not abreast regarding recent developments on testing and treatment. This perceived lack of clinical recommendations on both patient selection and subsequent follow-up emerged as a major barrier to routine testing.
Beyond limited knowledge leading to poor capability to manage patients, Lp(a) testing and treatment was also deemed futile. Elevated Lp(a) was considered relatively uncommon, casting doubt over cost-effectiveness of routine testing. Another common perception was that patients’ current lipid-lowering regime is already optimised with little room for more intensive intervention. Therefore, even with increased diagnosis, existing patient management strategies would likely remain unchanged.
There was also a perception that no effective Lp(a) treatment currently exists to warrant testing, as typical lipid-lowering medications yielded insufficient Lp(a) reduction. Targeted agents such as muvalaplin were still undergoing clinical trials. Other interventions such as plasma apheresis were locally unavailable as a therapeutic option and its cost-effectiveness untested. Lifestyle modifications such as exercise and diet management were deemed ineffective. Equally vexing was the perceived lack of conclusive evidence that reducing Lp(a) improves patient outcomes. Consequently, there was concern that Lp(a) testing might present medico-legal and insurance claims issues, as diagnosing an inheritable condition without effective follow-up strategies would raise the spectre of medical negligence.
3.2b). Institution-level constraints.
Another key barrier was institution-level roadblocks, particularly limited formalised local guidance, which together with the knowledge gap, further contributed to reticence towards Lp(a) testing. Self-reported differences in practice ranged from ordering Lp(a) tests once or twice to testing every patient. This inconsistency was attributed to differing emphasis on Lp(a) management and unclear guidelines. Guidelines and actual practice being in flux complicated treatment decisions: pharmacists reported difficulty titrating medications against constantly changing targets in lipid management without a clear timeline for therapy and lipid targets. Embedding standard practices typically takes time due to the slow pace of adopting new guidelines in large institutions, further aggravating the issue.
Current manpower resources were also deemed insufficient to support Lp(a) management, especially in non-cardiology settings. High turnover of staff necessitates constant re-training of incoming junior HCPs on testing procedure, counselling approaches, and long-term management, which may stretch beyond the index case to family members for cascade testing.
3.2c). Challenges in practice.
The already thin workforce is further strained by daily on-the-ground realities such as fatigue. Difficulty communicating with patients in a stressful working environment, coupled with multiple competing concerns to attend to, further burdened HCPs.
Clinicians reported logistical roadblocks in outpatient clinic setting such as difficulty capturing potential patients within the appointment period, significant time lag between ordering the test and receiving results, restrictions in prescribing privileges or referral to the relevant specialists or clinics for follow-up. These challenges informed a preference for inpatient management and the belief that the responsibility for detecting and managing elevated Lp(a) patients largely rested with the inpatient team.
Nurses and pharmacists offered a different view: while intervention might be initiated in the inpatient setting, outpatient clinics should be responsible for long-term follow-up. Contrary to junior doctors who reported no issues raising concerns on treatment strategies to their superiors, nurses and pharmacists were reluctant to do so, preferring instead to be delegated tasks and to reiterate clinicians’ recommendations. Pharmacists doubted their role and capability to counsel patients to accept treatment, citing patients’ deference to doctors. The perceived lower clinical influence compared to clinicians suggested a hierarchy in clinical decision-making among HCPs, further hindering pharmacists and nurses from proactively engaging in Lp(a) management.
3.2d). Patients’ resistance to testing and treatment.
Tangential to on-the-ground constraints for HCPs were patient-related challenges; specifically, a presumption that some patients might be resistant to Lp(a) testing and treatment. Financial concern was presumed a key issue since testing may incur out-of-pocket expenses for the patient. However, many participants could not provide cost estimates for the test and recanted their opinion when informed that the actual cost of Lp(a) test was lower than SGD $40 (USD $30) per test for patients in our hospital. The cost may vary depending on patient’s subsidy program, with the highest rate of SGD $60–70 (USD $50) for patients in private class. Treatment cost was also a potential barrier, with reports of patient complaints or treatment refusal, citing long-term financial burden as a key reason. Furthermore, there was concern that an elevated Lp(a) result might hypothetically affect patients’ future eligibility for health insurance, leading to higher insurance premiums and restricted access to affordable care.
Apart from financial concerns, patients might be unmotivated to test and confirm the diagnosis, given the condition’s genetic underpinning with no apparent cure and the emotional distress that might follow. Long-term treatment might be considered demanding and inconvenient, especially self-injectable PCSK9 inhibitors or newer Lp(a) lowering agents. The use of needles for administration, dosing schedule that might require recurring visits to specialists, and relative unfamiliarity compared to oral medications such as statins, might contribute to treatment aversion. Patient adherence to treatment was also a concern. Adding or intensifying existing medications to target Lp(a) or overall lipid control, especially given the lack of clear unified guidance on management might risk treatment failure.
3.3. Theme 3: Enablers of testing and follow-up
In response to the barriers in Theme 2, Theme 3 (Table 4) discussed enablers of Lp(a) testing and management.
3.3a). Stronger clinical evidence.
To address the knowledge gap barrier, stronger clinical evidence may convince HCPs that elevated Lp(a) warrants treatment. Specifically, data that clearly demonstrates improvement in clinical outcomes among the local population following testing and prescribing of Lp(a)-lowering agents.
3.3b). Institution-level enablers.
Many of the barriers identified such as poor awareness of Lp(a), lack of standardised protocol, limited resources and on-the-ground challenges in practice stem from underlying systemic constraints. Participants felt that a multi-pronged top-down approach, initiated by healthcare authorities and providers, is needed to effectively incorporate Lp(a) into mainstream care practices.
Within the healthcare institution, educational initiatives can boost awareness of Lp(a)’s role in ASCVD, especially among non-cardiologists, nurses, and pharmacists. Continuing medical education is needed on test result interpretation and management strategies. For pharmacists, a checklist for patient counselling on treatments such as PCSK9-targeted agents would be useful. Standardised workflows and clinical protocols should be established for Lp(a) testing with clear patient inclusion criteria; and integrated into existing protocols where appropriate. For instance, the Lp(a) test should be included in existing blood panels for ease of ordering [33]. Patient-facing materials such as health reports could provide additional information about Lp(a) in plain English.
Technological innovations may further enhance Lp(a) management in practice. Existing medical record systems can be improved to support clinical decision-making: electronic reminders prompting clinicians to order Lp(a) test for suitable patients upon admission; pre-programmed clinical checkpoints highlighting missing result or skipped test; and clear visual displays to aid result interpretation based on pre-programmed Lp(a) thresholds requiring clinical action. Social media and mobile applications (health apps) can be harnessed for patient education to encourage a healthy lifestyle between clinic visits.
Improved treatment affordability and subsidies may lower financial barriers and encourage HCPs and patients to proceed with Lp(a) testing. However, funding would require involvement of the local ministry of health. A national cross-sector approach may support long-term management, including national clinical protocols, and provider partnerships beyond hospitals and clinics.
3.3c). Enhance health literacy.
In addressing the perceived patient resistance against testing and treatment, healthcare institutions could engage community outreach activities to improve awareness on Lp(a), its health implications, and encourage testing among the general population. Suggestions included leveraging the institution’s social media presence via posts or blogs and partnering with relevant health promotion agencies, thus improving health literacy for the general population.
3.4. Theme 4: Ideal system to enhance patient management
Theme 4 (Table 5) describes participants’ perception of what Lp(a) testing and management should entail, given the constraints and possible solutions they proposed in Theme 2 and 3, respectively. Fig 2 shows the mapping of the 32 sub-categories from the study to 26 Consolidated Framework for Implementation Research (CFIR) constructs in the Innovation, Outer Setting, and Inner Setting domains.
3.4a). Context and setting for Lp(a) testing.
Inpatient was the ideal opportunistic setting to initiate testing and follow-up before discharge, especially in cardiology and vascular departments. Selected outpatient clinics might also initiate testing, for example post-acute myocardial infarction clinics. Clinicians reported no preferred testing period following an index cardiovascular event. Repeat testing was deemed unnecessary unless the result was ambiguous or for monitoring response to treatment. Clinicians were in favour of cascade testing beyond the index case when provided with additional explanation.
3.4b). Selection of patients for Lp(a) testing.
Inclusion criteria varied significantly between all cardiology inpatients (including non-ASCVD cases such as atrial fibrillation) and favoured a targeted selection to conserve limited resources. Specifically, a sub-population of ASCVD patients should be prioritised: those without apparent or well-controlled cardiovascular risk factors, younger people (40–50 years old), with history of familial hypercholesterolaemia or referred for cascade testing. Conversely, there were also opinions by cardiologists that older patients (>80 years old), those with lower risk profiles (non-cardiac related symptoms, low cholesterol level, stable condition) were deemed unlikely to benefit and should be excluded.
3.4c). Post-Lp(a) testing follow-up.
Participants reported different, at times contradicting, viewpoints on treatment strategies. While clinicians agree that lipid-lowering regime can be strengthened by either increasing the dosage of existing medications or adding PCSK9-targeted agents as part of combination therapy, opinions differed regarding lifestyle modifications as useful adjuncts for a genetically determined condition. Management strategies included referral to the hospital’s lipid clinic, albeit without a consensus on Lp(a) referral thresholds ranging from 60 to 150 nmol/L. Uncertainty about LDL treatment goal post-diagnosis was also reported.
3.4d). Resources to support Lp(a) management.
Lp(a) management should be a cross-specialty team effort preferably led by experienced cardiologists or endocrinologists (lipid specialists). Having multi-disciplinary HCPs involved in an integrated clinic would promote collaborations and optimise patient care. Specialist pharmacists and allied health professionals could play a proactive role: pharmacists are well-positioned to address medication adherence issues, while dietitians could provide dietary education and strategies for healthy eating. With sufficient training, other clinicians including general practitioners can be in charge. Over time, elevated Lp(a) should ideally be managed in the primary healthcare setting.
4. Discussion
Our study captured new insights and reaffirmed previously known barriers and enablers for Lp(a) testing and management. First, low awareness of Lp(a) even among specialists remained a major and well reported hurdle that contributed to low adoption of Lp(a) testing [15,17,18,34]. Misperceptions such as futility of testing, low utility in CVD risk re-classification, perceived lack of actionable guidelines and effective therapeutic options contradicted current evidence [2–5,8,9]. These misperceptions were prevalent despite extensive coverage about Lp(a) in conferences, medical resources, and international guidelines published between 2018 and 2023 prior to our study. Therefore, the need remains for extensive continuing medical education to fill knowledge gaps and address misconceptions, and for the development of local protocols based on international guidelines and consensus [2]. The participants of this study voiced their opinions that more studies are needed on the clinical significance of Lp(a) in the local and broader Asian setting to better support its implementation as an important risk factor into practice, not just to reflect current understanding of the topic based on international guidelines but also to contribute towards Healthier SG’s goal on preventive care in an aging population [31].
Second, participants cited unaffordability of testing and treatment as a key patient deterrent. Interestingly, this concern stemmed from a perceived notion that Lp(a) testing was too expensive rather than knowledge of the actual cost. Interestingly, many participants changed their opinion to be now in favour of testing, when informed of the actual cost of Lp(a) testing which was cheaper than renal, liver or thyroid panel in our hospital. Therefore, this perceived barrier of ‘expensive test’ can easily be rectified with adequate information dissemination including explanation that most patients only needed to be tested once if normal. While the solutions to patient’s financial issues lie beyond individual clinicians’ capability, more clarification on the cost and subsidies on testing and treatment would help HCPs be better informed to counsel patients accordingly. High-risk patients were also thought to be resistant to testing and treatment procedures, although patient advocacy groups would likely disagree with such a presumption. A high level of public awareness is a critical enabler for large-scale Lp(a) testing and management, and implementation efforts are necessary to improve health literacy among patients, families and public.
Third, junior clinicians, nurses and pharmacists also expressed low confidence and were forthright about their lack of experience and understanding when discussing Lp(a) testing and management. While the test can be conducted fairly easily, there was an unsubstantiated perception that Lp(a) detection and by extension its management exceeded the current capabilities of junior HCPs, although participants also expressed an openness to rectify their limited understanding. Suggested educational modalities included topic presentations of Lp(a), workshops, case-based discussions, journal clubs, internal emails, posters, and brochures: focussing on knowledge of aetiology and prevalence, testing instruction, result interpretation, counselling points, and other patient management skills. Notably, there was a heartening sense of eagerness among participants to be well-prepared, so any HCP involved in the ASCVD care pathway can competently address questions from patients about Lp(a) testing and management. Given the high degree of overlap between elevated Lp(a) and high ASCVD risk, Lp(a) training efforts should also be extended beyond cardiology HCPs to include medical officers, interns, nurses and allied health at acute admission wards.
Key insights from this study have enabled implementation of Lp(a) into patient care in our hospital locally. Efforts consisted of an Lp(a) guide for healthcare professionals made available on the hospital’s intranet and an easy referral system to the Lipid Clinic for management of patients with elevated Lp(a). An Lp(a)-cardiology pathway was launched, accompanied by a series of educational talks on Lp(a) using the #LILAC-for-Lp(a) concept to HCPs [35]. As ASCVD management is multidisciplinary, the educational talks on Lp(a) were not limited to cardiology and endocrinology departments, but also included internal medicine, stroke, rehabilitation, surgical departments, allied health, nursing, and primary care. Other implementation efforts included Lp(a) educational awareness events, notably Singapore’s inaugural Lp(a) Awareness Day event for HCPs, patients and public held in CGH on 23/04/2024, followed by a ‘Changi General Hospital Lipid and Lp(a) Awareness Week’ in April 2025 [35,36]. From our experience, the use of the novel #LILAC-for-Lp(a) concept via a short 8-minute educational video was particularly useful to positively influence practicing doctors, nurses and allied health professionals to test and manage Lp(a) [35]. The LILAC mnemonic was designed by the corresponding author (WJL) as a cognitive-aid tool to remind HCPs to use Lp(a) to improve cardiovascular risk stratification, and importantly, to advocate a healthy lifestyle and control other cardiovascular risk factors such as elevated LDL-C, blood pressure, blood glucose, and obesity [35].
With the implementation of these strategies informed by our study, Lp(a) testing has improved significantly to a sustained rate of >80% of all patients admitted to our hospital for acute myocardial infarction [37]. More than 2000 cardiology patients with high cardiovascular risk were tested for Lp(a) one year after integration of Lp(a) into cardiology pathways, of which 16% of patients were detected to have elevated Lp(a) [37]. Our positive experience of integrating Lp(a) into clinical care is in line with other centre’s experience that integration of Lp(a) into lipid profiling in Lipid Clinic and clinical care helps improves cardiovascular risk stratification of patients at high cardiovascular risk, including patients with familial hypercholesterolaemia and/or have ASCVD [38,39].
Such encouraging outcomes of local implementation efforts demonstrate that the pre-implementation findings reported in this study can be translated into impactful strategies, benefitting not just patients and individual HCPs in practice but also the broader healthcare community and institution. While being guided by an individual-centric framework (the TDF) for data collection, our approach to data analysis using inductive coding yielded insights that influence implementation on a wider scale, beyond behavioural change at an individual level. In particular, the findings are concordant with the domains covering intervention characteristics, institutional setting, and wider societal context as articulated in the Consolidated Framework for Implementation Research (CFIR) [40]. Fig 2 demonstrates how each construct under these CFIR domains can be mapped one-to-many to the sub-categories generated in our study. Future research may choose to use the CFIR framework to focus on constructs not extensively covered in our study such as trialability, critical incidents, relative priority and incentive systems for Lp(a) testing and management. In view of the recent implementation efforts as described, subsequent studies may further use CFIR’s individuals and implementation process domain as guidance to identify relevant stakeholders, post-implementation challenges and follow-up strategies to effectively support diagnosis and treatment.
This study has several limitations. First, recruitment was limited to HCPs in the cardiology department at a single large healthcare institution. However, we recruited clinicians of various seniority, nurses, and pharmacists, many of whom rotate across multiple similarly resourced hospitals during training in a culturally diverse community. Thus, we believe their views would be broadly consistent with peers in other institutions and generalisable to a certain extent across the Asian context. We did not interview patients, hence the views offered by HCPs on patients’ preference are only presumed. Strengths of this study include a theory-driven qualitative approach and a multidisciplinary study team comprising an endocrinologist (WJL), a cardiologist (JJT), pharmacists (BLP, JY), and researchers in health services research and implementation science (EL, LT).
5. Conclusion
This pre-implementation study identified critical barriers to be addressed at the individual and institutional level to optimise adoption of Lp(a) testing and management. Foremost of these barriers is the major knowledge gaps regarding the importance, utility, and benefits of Lp(a) testing and its subsequent management amongst HCPs and patients. Effective education strategies and protocol-driven clinical workflows are needed to increase Lp(a) testing and management. The enabling strategies proposed by the participants corresponded to key barriers identified and thus informs future implementation.
Supporting information
S2 Table. Adapted Jeffersonian Transcription Notation.
https://doi.org/10.1371/journal.pone.0333789.s002
(PDF)
References
- 1. Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, Heffron SP, Kamstrup PR, et al. Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2022;42(1):e48–60. pmid:34647487
- 2. Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925–46. pmid:36036785
- 3. Koschinsky ML, Bajaj A, Boffa MB, Dixon DL, Ferdinand KC, Gidding SS, et al. A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice. J Clin Lipidol. 2024;18(3):e308–19. pmid:38565461
- 4. Pearson GJ, Thanassoulis G, Anderson TJ, Barry AR, Couture P, Dayan N, et al. 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. Can J Cardiol. 2021;37(8):1129–50. pmid:33781847
- 5. Wilson DP, Jacobson TA, Jones PH, Koschinsky ML, McNeal CJ, Nordestgaard BG, et al. Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipidol. 2019;13(3):374–92. pmid:31147269
- 6. Clair V, Zirille FM, Gill E. Rethinking cardiovascular risk: The emerging role of lipoprotein(a) screening. Am J Prev Cardiol. 2025;21:100945. pmid:40103685
- 7. Kronenberg F, Bedlington N, Ademi Z, Geantă M, Silberzahn T, Rijken M, et al. The Brussels International Declaration on Lipoprotein(a) Testing and Management. Atherosclerosis. 2025;406:119218. pmid:40340180
- 8. Cegla J, Neely RDG, France M, Ferns G, Byrne CD, Halcox J, et al. HEART UK consensus statement on Lipoprotein(a): A call to action. Atherosclerosis. 2019;291:62–70. pmid:31704552
- 9. Loh WJ, Watts GF. Detection strategies for elevated lipoprotein(a): will implementation let the genie out of the bottle? Curr Opin Endocrinol Diabetes Obes. 2023;30(2):94–102. pmid:36468313
- 10. Loh WJ, Pang J, Chakraborty A, Ward NC, Chan DC, Hooper AJ, et al. Cascade testing of children and adolescents for elevated Lp(a) in pedigrees with familial hypercholesterolaemia. J Clin Lipidol. 2024;18(1):e33–7. pmid:38040538
- 11. Ward NC, Watts GF, Bishop W, Colquhoun D, Hamilton-Craig C, Hare DL, et al. Australian Atherosclerosis Society Position Statement on Lipoprotein(a): Clinical and Implementation Recommendations. Heart Lung Circ. 2023;32(3):287–96. pmid:36707360
- 12. McGowan M, Wilemon K, Ahmed C, Myers K, MacDougall D. Characterization of Lipoprotein(a) Measurement in a Large US Healthcare Dataset. Journal of Clinical Lipidology. 2022;16(3):e36–7.
- 13. Nissen SE, Wolski K, Cho L, Nicholls SJ, Kastelein J, Leitersdorf E, et al. Lipoprotein(a) levels in a global population with established atherosclerotic cardiovascular disease. Open Heart. 2022;9(2):e002060. pmid:36252994
- 14. Chua F, Lam A, Mak YH, Lee ZH, Dacay LM, Yew JL, et al. Undiagnosed cardiovascular risk factors including elevated lipoprotein(a) in patients with ischaemic heart disease. Front Epidemiol. 2023;3:1207752. pmid:38455910
- 15. Catapano AL, Tokgözoğlu L, Banach M, Gazzotti M, Olmastroni E, Casula M, et al. Evaluation of lipoprotein(a) in the prevention and management of atherosclerotic cardiovascular disease: A survey among the Lipid Clinics Network. Atherosclerosis. 2023;370:5–11. pmid:36894469
- 16. Bansal A, Cho L. Prevalence of Lipoprotein(a) Testing in a Contemporary Cohort. Circulation. 2025;151(9):649–51. pmid:40029944
- 17. D’Souza J, Soffer DE, Bajaj A. Attitudes and barriers to lipoprotein(a) testing: A survey of providers at the University of Pennsylvania Health System. J Clin Lipidol. 2024;18(5):e873–6. pmid:39289122
- 18. Loh WJ, Pang J, Simon O, Chan DC, Watts GF. Deficient perceptions and practices concerning elevated lipoprotein(a) among specialists in Singapore. Front Cardiovasc Med. 2025;12:1527351. pmid:40027516
- 19. Goh RSJ, Chong B, Jayabaskaran J, Jauhari SM, Chan SP, Kueh MTW, et al. The burden of cardiovascular disease in Asia from 2025 to 2050: a forecast analysis for East Asia, South Asia, South-East Asia, Central Asia, and high-income Asia Pacific regions. Lancet Reg Health West Pac. 2024;49:101138. pmid:39100533
- 20. GBD 2021 Causes of Death Collaborators. Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2100–32. pmid:38582094
- 21. Mach F, Koskinas KC, Roeters van Lennep JE, Tokgözoğlu L, Badimon L, Baigent C, et al. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2025;:ehaf190. pmid:40878289
- 22. Raal FJ, Giugliano RP, Sabatine MS, Koren MJ, Langslet G, Bays H, et al. Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials. J Am Coll Cardiol. 2014;63(13):1278–88. pmid:24509273
- 23. Raal FJ, Giugliano RP, Sabatine MS, Koren MJ, Blom D, Seidah NG, et al. PCSK9 inhibition-mediated reduction in Lp(a) with evolocumab: an analysis of 10 clinical trials and the LDL receptor’s role. J Lipid Res. 2016;57(6):1086–96. pmid:27102113
- 24. Burgess S, Ference BA, Staley JR, Freitag DF, Mason AM, Nielsen SF, et al. Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies: A Mendelian Randomization Analysis. JAMA Cardiol. 2018;3(7):619–27. pmid:29926099
- 25. Schumann F, Kassner U, Spira D, Zimmermann FF, Bobbert T, Steinhagen-Thiessen E, et al. Long-term lipoprotein apheresis reduces cardiovascular events in high-risk patients with isolated lipoprotein(a) elevation. J Clin Lipidol. 2024;18(5):e738–45. pmid:38908966
- 26. Nicholls SJ, Ni W, Rhodes GM, Nissen SE, Navar AM, Michael LF, et al. Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial. JAMA. 2025;333(3):222–31. pmid:39556768
- 27. Hardy J, Niman S, Goldfaden RF, Ashchi M, Bisharat M, Huston J, et al. A Review of the Clinical Pharmacology of Pelacarsen: A Lipoprotein(a)-Lowering Agent. Am J Cardiovasc Drugs. 2022;22(1):47–54. pmid:34490591
- 28. O’Donoghue ML, Rosenson RS, López JAG, Lepor NE, Baum SJ, Stout E, et al. The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering: OCEAN(a)-DOSE Extension Period Results. J Am Coll Cardiol. 2024;84(9):790–7. pmid:39168564
- 29. Cane J, O’Connor D, Michie S. Validation of the theoretical domains framework for use in behaviour change and implementation research. Implement Sci. 2012;7:37. pmid:22530986
- 30. French SD, Green SE, O’Connor DA, McKenzie JE, Francis JJ, Michie S, et al. Developing theory-informed behaviour change interventions to implement evidence into practice: a systematic approach using the Theoretical Domains Framework. Implement Sci. 2012;7:38. pmid:22531013
- 31.
Ministry of Health Singapore. White paper on Healthier SG. In: Ministry of Health, editor. Singapore: Ministry of Health Singapore Singapore; 2022.
- 32. Atkins L, Francis J, Islam R, O’Connor D, Patey A, Ivers N, et al. A guide to using the Theoretical Domains Framework of behaviour change to investigate implementation problems. Implement Sci. 2017;12(1):77. pmid:28637486
- 33. Bhatia HS, Ma GS, Taleb A, Wilkinson M, Kahn AM, Cotter B, et al. Trends in testing and prevalence of elevated Lp(a) among patients with aortic valve stenosis. Atherosclerosis. 2022;349:144–50. pmid:35144769
- 34. Catapano AL, Daccord M, Damato E, Humphries SE, Neely RDG, Nordestgaard BG, et al. How should public health recommendations address Lp(a) measurement, a causative risk factor for cardiovascular disease (CVD)?. Atherosclerosis. 2022;349:136–43. pmid:35292153
- 35. Loh WJ, Watts GF, Lum E. A short educational video for improving awareness and confidence of healthcare professionals in managing lipoprotein(a): a pilot study based on LILAC-for-Lp(a). Eur J Cardiovasc Nurs. 2025;24(5):796–9. pmid:40156158
- 36.
The Asia Pacific Cardio Metabolic Consortium. Singapore’s Inaugural Lipoprotein (a) Awareness Day: The Asia Pacific Cardio Metabolic Consortium; 2024 [cited 2025]. Available from: https://apcmc.net/singapores-inaugural-lipoprotein-a-awareness-day/
- 37. Jun-Wei Wong A, Lum E, Loh WJ. Implementation of a lipoprotein(a) guide and pathway to detect elevated Lp(a) in patients at high risk for cardiovascular events. Atherosclerosis. 2025;407:119830.
- 38. Bosco G, Di Giacomo Barbagallo F, Di Marco M, Scilletta S, Miano N, Esposto S, et al. Effect of inclisiran on lipid and mechanical vascular profiles in familial hypercholesterolemia subjects: results from a single lipid center real-world experience. Prog Cardiovasc Dis. 2025:S0033-0620(25)00078-7. pmid:40436259
- 39. Di Giacomo Barbagallo F, Bosco G, Di Marco M, Scilletta S, Miano N, Musmeci M, et al. Evaluation of glycemic status and subclinical atherosclerosis in familial hypercholesterolemia subjects with or without LDL receptor mutation. Cardiovasc Diabetol. 2025;24(1):126. pmid:40114220
- 40. Damschroder LJ, Reardon CM, Widerquist MAO, Lowery J. The updated Consolidated Framework for Implementation Research based on user feedback. Implement Sci. 2022;17(1):75. pmid:36309746