Individuals with elevated concentrations of lipoprotein(a) [Lp(a)] and increased levels of inflammatory markers are at substantially higher risk of developing coronary artery disease, according to a study conducted by researchers at Radboud university medical center. The analysis, based on data from more than 43,000 participants, demonstrates that inflammation significantly modifies the cardiovascular risk associated with elevated Lp(a) levels and may help identify individuals most likely to benefit from preventive treatment strategies.
Elevated cholesterol levels are a well-established risk factor for cardiovascular disease. While low-density lipoprotein cholesterol (LDL-C) is widely recognized as a major contributor to atherosclerosis, accumulating evidence suggests that lipoprotein(a), or Lp(a), may confer an even greater cardiovascular risk. Lp(a) consists of an LDL-like particle bound to an additional protein, apolipoprotein(a), which is believed to enhance its atherogenic and pro-inflammatory properties.
A key challenge is that circulating Lp(a) concentrations are largely genetically determined and are minimally influenced by lifestyle modification. Furthermore, no Lp(a)-specific therapies have yet been approved for routine clinical use, limiting the implementation of population-wide screening strategies. According to cardiologist and principal investigator Saloua El Messaoudi, approximately one in five individuals in the Netherlands is estimated to have elevated Lp(a) levels. ‘Although elevated Lp(a) is a recognized cardiovascular risk factor, not all individuals with high Lp(a) develop cardiovascular disease, suggesting the presence of additional modifying factors.’
To investigate this heterogeneity in risk, El Messaoudi and colleagues analyzed data from more than 43,000 participants of the UK Biobank who had no history of cardiovascular disease at baseline. The study examined the contribution of inflammatory activity to cardiovascular risk among individuals with elevated Lp(a). Participants, with a mean age of 56 years, were followed for more than 13 years to assess the incidence of cardiovascular events.
The role of inflammation
The study confirmed that elevated Lp(a) levels are associated with an increased risk of cardiovascular disease. Importantly, however, this excess risk varied considerably between individuals. The extent of chronic low-grade inflammation emerged as a critical determinant of disease risk.
Individuals with both elevated Lp(a) concentrations and high circulating levels of interleukin-6 (IL-6), a key inflammatory biomarker, exhibited a markedly increased risk of cardiovascular disease. By contrast, those with elevated Lp(a) but low levels of inflammatory activity demonstrated a substantially lower risk.
These findings suggest that cardiovascular risk is determined not only by lipid burden but also by the inflammatory milieu in which these lipoproteins operate. According to El Messaoudi, ‘Our results support a more personalized approach to cardiovascular prevention. Elevated Lp(a) alone may not warrant identical treatment strategies for all individuals. Rather, those with concomitant inflammatory activation appear to be most likely to benefit from targeted preventive interventions.’
Several international clinical trials are currently evaluating novel therapies designed to reduce circulating Lp(a) levels. ‘Should these agents prove effective’, El Messaoudi explains, ‘they may provide an opportunity to intervene before irreversible vascular injury develops. Our findings may also contribute to more precise patient selection by identifying those most likely to derive clinical benefit from Lp(a)-lowering therapies.’
Targeting inflammation as a therapeutic strategy
In parallel with investigations into Lp(a)-lowering agents, El Messaoudi’s research group is exploring therapeutic approaches that directly target inflammation. Previous work by the team demonstrated that colchicine, an anti-inflammatory medication, not only suppresses systemic inflammation but may also attenuate the expansion of age-related clonal hematopoiesis, a process increasingly implicated in cardiovascular disease development.
Notably, the group also observed a relationship between elevated Lp(a) levels and the therapeutic effects of colchicine. ‘Among individuals with increased Lp(a) concentrations, the benefits of colchicine appeared to be more pronounced. This observation suggests that inflammatory activity may amplify the pathogenic effects of Lp(a). In other words, inflammation may modulate the extent to which Lp(a) contributes to vascular injury, further highlighting inflammation as a promising therapeutic target.’
In this photo: main researcher and cardiologist. Photo by Janne van de Weijer.
About these publications
This article appeared in JAMA Cardiology: Lipoprotein(a), Inflammation, and Risk of Coronary Artery Disease and Aortic Valve Stenosis – Niekbachsh Mohammadnia, Linke Li, Niels P Riksen, Pradeep Natarajan, Jan H Cornel, Michael C Honigberg, Saloua El Messaoudi. DOI: 10.1001/jamacardio.2026.1852.
Previous research was published in Journal of the American College of Cardiology: Colchicine and Longitudinal Dynamics of Clonal Hematopoiesis: An Exploratory Substudy of the LoDoCo2 Trial – Niekbachsh Mohammadnia, Liying Xue, Lucas T W Vestjens, Niels P Riksen, Pradeep Natarajan, Jan H Cornel, Saloua El Messaoudi, Michael C Honigberg. DOI: 10.1016/j.jacc.2025.08.025.
And in European Journal of Preventive Cardiology: The effects of colchicine on lipoprotein(a)- and oxidized phospholipid-associated cardiovascular disease risk - Niekbachsh Mohammadnia, Amber van Broekhoven, Dominique P V de Kleijn, Sotirios Tsimikas, Jan H Cornel, Calvin Yeang, Saloua El Messaoudi. DOI: 10.1093/eurjpc/zwae355.
-
Want to know more about these subjects? Click on the buttons below for more news.
More information
Pauline Dekhuijzen
wetenschaps- en persvoorlichter
