AUTHOR=Gianfagna Francesco , Poli Simone , Costanzo Simona , Di Castelnuovo Augusto , Panzera Teresa , De Curtis Amalia , Magnacca Sara , Persichillo Mariarosaria , De Santi Lorenzo , Cristofani Claudia , Loffredo Daniele , Cerletti Chiara , Donati Maria Benedetta , de Gaetano Giovanni , Iacoviello Licia ,  the Moli-sani Study Investigators , Iacoviello Licia , de Gaetano Giovanni , Donati Maria Benedetta , Cerletti Chiara , Bonaccio Marialaura , Bonanni Americo , Costanzo Simona , De Curtis Amalia , Di Castelnuovo Augusto , Gialluisi Alessandro , Gianfagna Francesco , Persichillo Mariarosaria , Vermylen Jos , Pegoraro Renzo , Spagnolo Antonio G. , Assanelli Deodato , Rago Livia , Costanzo Simona , Orlandi Sabatino , Panzera Teresa , Di Castelnuovo Augusto , Bonaccio Marialaura , Bracone Francesca , Costanzo Simona , Di Costanzo Giuseppe , Esposito Simona , Gialluisi Alessandro , Ghulam Anwal , Gianfagna Francesco , Morelli Martina , Venegas Maria Loreto Muñoz , Pepe Antonietta , Ruggiero Emilia , De Curtis Amalia , Civitillo Concetta , Cretella Alisia , Magnacca Sara , Persichillo Mariarosaria , Bracone Francesca , Di Costanzo Giuseppe , Morelli Martina , Bonanni Americo 

TITLE=Lipoprotein(a) as an early marker of cardiovascular events in high-risk subjects: insights from the Moli-sani cohort study

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1571395

DOI=10.3389/fcvm.2025.1571395

ISSN=2297-055X

ABSTRACT=Background and aimsEpidemiological studies have revealed the role of lipoprotein(a) [Lp(a)] in the etiopathogenesis of cardiovascular disease (CVD). We analyzed the association between Lp(a) and the risk of a major cardiovascular event in subjects with previous CVD.MethodsThe analysis was conducted on the Moli-sani study population (24,325 individuals aged ≥35 years, recruitment from 2005 to 2010), focusing on subjects with prior CVD. Data from standardized questionnaires and blood pressure, anthropometric, and lab measurements were collected. Lp(a) levels were measured using biobanked samples. The cohort was followed for cardiovascular events. The association between Lp(a) levels and risk of major adverse cardiovascular events was analyzed using Kaplan–Meier and Cox regression models.ResultsIn total, 1,284 subjects reported a history of CVD at baseline. The mean ± SD Lp(a) level was 23.3 ± 26.0 mg/dl and 51 subjects (4.0%) had levels ≥90 mg/dl. After a median of 7.3 years, 307 CVD events were recorded and validated. Subjects belonging to the highest Lp(a) level group (≥90 mg/dl) showed a worse trend during early follow-up compared with the lowest level group (<30 mg/dl), with a peak during the first 18 months [hazard ratio (HR) = 3.43, 95% confidence interval (CI): 1.43–8.27]. This increase was higher in subjects with dyslipidemia not treated with statins and those with multiple previous CVD events (HR = 11.0, 95% CI: 1.98–61.1; HR = 25.6, 95% CI: 7.83–83.8).ConclusionsHigh Lp(a) levels were associated with an increased risk of early secondary cardiovascular events in individuals with a history of multiple CVDs or non-treated dyslipidemia, suggesting that lipoprotein(a) is a modifiable biomarker that can be measured at different times for CVD risk assessment.