Lipoprotein(a), also known as Lp(a), is a lipid particle with pro-inflammatory properties whose blood concentration is determined mainly by genetic factors. Its involvement in the development of atherosclerotic cardiovascular disease is well documented, but one key question remains in the field of primary prevention: Does Lp(a) also pose a relevant risk in people without classic cardiovascular risk factors?
To address this question, a large international study published in the European Journal of Preventive Cardiology analyzed data from 66,495 individuals across eight European population cohorts, followed over a median of 9.7 years. All participants were free of coronary heart disease at the time of enrollment. The study included the participation of Dr. Teresa Padró, researcher in the Biomarkers of Cardiovascular Disease group at the Sant Pau Research Institute (IR Sant Pau) and member of CIBERCV.
Researchers stratified participants based on the number of modifiable cardiovascular risk factors they had at the start of the study: high blood pressure, diabetes mellitus, hypercholesterolemia, and smoking. A total of 41,770 individuals had none or only one of these risk factors, while 24,725 had two or more. Participants were also classified by their Lp(a) levels, using the 90th percentile of the distribution (43.2 mg/dL) as the cutoff.
Over the follow-up period, a total of 3,467 new cases of ischemic heart disease were recorded among the participants. This category includes myocardial infarction, coronary death, unstable angina, coronary revascularization procedures, and deaths of undetermined cause but with a possible cardiac origin. Of these, 1,191 occurred in individuals who, at the start of the study, had no cardiovascular risk factors or only one. The remaining 2,276 cases occurred in participants with two or more traditional risk factors.
The study results show that having elevated Lp(a) levels —above 43.2 mg/dL, which corresponds to the top 10% of the population—increases the risk of developing coronary heart disease, such as a heart attack, in both people with few cardiovascular risk factors and those with several. In fact, the increased risk was very similar in both groups: 38% higher in those with none or only one risk factor and 27% higher in those with two or more. This difference was not statistically significant, meaning that the impact of high Lp(a) on coronary risk is essentially the same, regardless of a person’s prior risk profile.
“This study indicates that people with elevated Lp(a) levels are at increased risk of coronary heart disease even if they don’t have high blood pressure, diabetes, high cholesterol, or a history of smoking,” explains Dr. Teresa Padró. “This poses a significant clinical challenge, since traditional prevention strategies based on risk factor reduction don’t apply in these cases.”
Currently, there are no approved treatments specifically designed to lower Lp(a) levels, although many clinical trials are underway. According to the authors, until these drugs become available, the only option to mitigate the cardiovascular risk associated with Lp(a) remains intensive control of modifiable risk factors—a strategy that is not feasible in individuals who do not have any.
“These findings also reinforce the need to develop therapies that target Lp(a) in the context of primary prevention,” adds Dr. Padró. “They also highlight the importance of including Lp(a) in cardiovascular risk assessment, even in people who appear to be healthy.”
The study is part of the BiomarCaRE project (Biomarker for Cardiovascular Risk Assessment across Europe), funded by the European Union through the Seventh Framework Programme (FP7/2007–2013). Lp(a) levels were measured in a central laboratory using a standardized immunoturbidimetric method, ensuring the reliability of the data analyzed.
Arnold N, Goßling A, Bay B, Weimann J, Blaum C, Brunner FJ, Ferrario MM, Brambilla P, Cesana G, Leoni V, Palmieri L, Donfrancesco C, Padró T, Andersson J, Jousilahti P, Ojeda F, Zeller T, Linneberg A, Söderberg S, Iacoviello L, Gianfagna F, Sans S, Veronesi G, Thorand B, Peters A, Tunstall-Pedoe H, Kee F, Salomaa V, Schnabel RB, Kuulasmaa K, Blankenberg S, Waldeyer C, Koenig W. Lipoprotein (a) and incident coronary heart disease in the community: Impact of traditional cardiovascular risk factors. Eur J Prev Cardiol 2025. https://doi.org/10.1093/eurjpc/zwaf340
