Inflammation
Lp(a) improves 20-year cardiovascular risk reclassification beyond the Framingham and Reynolds scores, the ATTICA study (J Clin Lipidol 2024)
Original title: Discrimination and net-reclassification of cardiovascular disease risk with lipoprotein(a) levels: The ATTICA study (2002-2022)
In the ATTICA cohort of 3,042 adults free of cardiovascular disease recruited in Athens in 2002 and followed for 20 years (1,988 with complete outcome data), Lp(a) was significantly associated with 20-year atherosclerotic cardiovascular disease incidence in a crude model (HR per 1 mg/dL 1.004, P=0.048), but not after adjustment for demographic, lifestyle and clinical factors. Adding Lp(a) to the Reynolds Risk Score and Framingham Risk Score produced positive net reclassification improvement (0.159 and 0.160 respectively). Mediation analysis suggested C-reactive protein, interleukin-6 and fibrinogen partly explain the Lp(a)-cardiovascular disease relationship. The findings support adding Lp(a) to established risk scores to improve long-term risk classification in the general population.
Original abstract
Background: Lipoprotein(a) [Lp(a)] is recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, its influence on clinical risk evaluations remains unclear.
Objective: This study aimed to determine whether Lp(a) improves CVD risk prediction among apparently healthy adults from the general population.
Methods: In 2002, n = 3,042 adults free of CVD, residing in the Athens metropolitan area, in Greece, were recruited. A 20-year follow-up was conducted in 2022, comprising n = 2,169 participants, of which n = 1,988 had complete data for CVD incidence.
Results: Lp(a) levels were significantly associated with 20-year ASCVD incidence in the crude model (hazard ratio per 1 mg/dL: 1.004, p = 0.048), but not in multi-adjusted models considering demographic, lifestyle, and clinical factors. Adding Lp(a) to the Reynolds Risk Score (RRS) and Framingham Risk Score (FRS) variables resulted in positive net reclassification improvement (NRI) values (0.159 and 0.160 respectively), indicating improved risk classification. Mediation analysis suggested that C-reactive protein, interleukin-6, and fibrinogen mediate the relationship between Lp(a) and ASCVD. No significant interaction was observed between Lp(a) and potential moderators.
Conclusion: Lp(a) levels can predict 20-year CVD outcomes and improve CVD risk prediction within the general population, possibly via the intricate relationship between Lp(a), systemic inflammation, atherothrombosis.
epidemiologyinflammationrisk prediction
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.