The role of lipoprotein(a) [Lp(a)] in cardiovascular disease (CVD) is increasingly recognized, yet it remains largely overlooked in routine clinical practice. While its pathophysiologic association with atherosclerosis and cardiovascular risk is well-documented, its precise contribution to various disease settings continues to be elucidated. Nowadays, evidence is accumulating about the association between Lp(a) levels and coronary heart disease, aortic valve stenosis, peripheral artery disease, ischaemic stroke, and cardiovascular but also all-cause mortality. New evidence linking Lp(a) levels to ischemic heart failure are now reported, notably by Zhang et al., suggesting Lp(a) as a standalone risk factor for MACE in these patients, also over LDL-C plasma levels.
Although awareness of Lp(a) and its role in cardiovascular disease has significantly increased in Western countries to date, there remain many areas outside mainstream healthcare systems where the contribution of Lp(a) to patients’ health is either underestimated or entirely unconsidered. For instance, the study by Hillmeister et al., which focused on a representative cohort from a non-metropolitan region in Germany, uncovered a previously unknown high prevalence of elevated Lp(a) levels among cardiovascular patients, many of whom had never been tested for Lp(a). This was largely due to a lack of awareness of Lp(a) as a risk factor for CVD.
The growing body of evidence supporting the role of Lp(a) in cardiovascular disease is helping to raise global awareness. This is highlighted by the INTERHEART study from the Middle East-Gulf region, which enrolled 595,658 subjects. Manla et al. reported that the rate of Lp(a) testing doubled from 2017 to 2022, although it still remained low, with only one in fifty enrolled patients being tested.
Given this evidence, one might assume that a large number of patients under the care of cardiologists or endocrinologists would have undergone at least one Lp(a) test. However, the proportion of specialists who have never tested their patients for Lp(a) is surprisingly high. A recent report from Singapore by Loh et al. confirmed that the lack of effective treatment is the most common barrier to testing.
Despite the accumulating evidence supporting the role of Lp(a) in cardiovascular disease and coronary artery vasculopathy, its integration into clinical practice remains inconsistent. Although Lp(a) testing is now recommended at least once in a lifetime, it is still rarely performed in many healthcare settings, even among high-risk individuals. While several therapeutic strategies are under evaluation, until targeted treatments are widely available, aggressive management of other cardiovascular risk factors remains the most effective approach to mitigating the risks associated with elevated Lp(a).
We believe that the future of lipidology must extend beyond LDL-C, focusing also on the atherogenicity and valvulopathy associated with Lp(a). Universal Lp(a) screening, enhanced clinician awareness, and the rapid development of targeted therapies aimed at Lp(a) should be key priorities in reducing residual cardiovascular risk and improving outcomes for patients with elevated Lp(a).
Statements
Author contributions
GM: Conceptualization, Writing – review & editing, Writing – original draft, Supervision. LD: Writing – review & editing, Supervision, Validation.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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The author(s) declare that no Gen AI was used in the creation of this manuscript.
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Summary
Keywords
lipoprotein(a), Lp(a), atherosclerosis, cardiovascular risk factors (CVRFs), cardiovascular biomarkers, advancing knowledge
Citation
Mandraffino G and D'Erasmo L (2025) Editorial: Cardiovascular risk and lipoprotein(a): beyond LDL cholesterol. Front. Cardiovasc. Med. 12:1607395. doi: 10.3389/fcvm.2025.1607395
Received
07 April 2025
Accepted
14 May 2025
Published
29 May 2025
Volume
12 - 2025
Edited and reviewed by
Chieko Mineo, University of Texas Southwestern Medical Center, United States
Updates
Copyright
© 2025 Mandraffino and D'Erasmo.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Giuseppe Mandraffino gmandraffino@unime.it
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.