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

Francesco Gianfagna¹Simone Poli²Simona Costanzo^1,3Augusto Di Castelnuovo³Teresa Panzera³Amalia De Curtis³Sara Magnacca³Mariarosaria Persichillo³Lorenzo De Santi²Claudia Cristofani²Daniele Loffredo¹Chiara Cerletti³Donati Maria Benedetta³Giovanni De Gaetano³Licia Iacoviello^3,4*

• ¹Department of Medicine and Surgery, University of Insubria, Varese, Italy
• ²Novartis Farma SpA, Milan, Italy
• ³Research Unit of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli - IS, Italy
• ⁴Department of Medicine and Surgery, LUM University 'Giuseppe Degennaro', Casamassima, Italy

Epidemiological studies have revealed a role for Lp(a) in the etiopathogenesis of cardiovascular disease (CVD). We aimed at analyzing the association between Lp(a) and risk of a major cardiovascular event in subjects with previous CVD. The analysis was conducted on the Moli-sani Study population (24,325 individuals aged ≥ 35 years, recruitment 2005-2010), focusing on subjects with prior CVD. Data from standardized questionnaires, as well as blood pressure, anthropometric and lab measurements were collected. Lp(a) levels were dosed on biobanked samples. The cohort was followed for cardiovascular events.The association between Lp(a) levels and risk of major adverse cardiovascular events were analysed using Kaplan-Meyer and Cox regression models.Results. 1,284 subjects reported a history of CVD at baseline. Mean ±SD Lp(a) 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) levels group (≥90 mg/dL) showed a worse trend during early follow-up compared with the lowest levels group (<30 mg/dl), with a peak during the first 18 months (HR=3.43, 95%CI:1.43-8.27). This increase was higher in subjects with dyslipidemia not treated with statins or with multiple previous CVD events (HR=11.0, 95%CI:1. 98-61.1 and 25.6, 7.83-83.8).High Lp(a) levels were associated with increased hazard of early secondary cardiovascular events in individuals with a history of multiple CVDs or non-treated dyslipidemia, suggesting lipoprotein(a) as a modifiable biomarker to be measured at different times for CVD risk assessment.