Epidemiology
First demonstration that combining Lp(a) with fibrinogen nearly quintuples stroke risk in 8,263 coronary disease patients (Eur J Clin Invest 2024)
Original title: Synergetic impact of lipoprotein(a) and fibrinogen on stroke in coronary artery disease patients
In a prospective study of 8,263 patients with stable coronary artery disease enrolled between 2011 and 2017 and followed for a median 37.7 months, 157 (1.9%) experienced an ischaemic stroke. Stroke incidence rose across Lp(a) tertiles (1.1% to 2.1% to 2.5%, P < .001) and fibrinogen tertiles (1.1% to 2.0% to 2.6%, P < .001) individually. When patients were cross-classified into nine groups by both markers, those with high Lp(a) and high fibrinogen had significantly higher stroke incidence than those with low Lp(a) and low fibrinogen (6% vs. 3.1%, P < .001), and the highest combined-risk group carried an adjusted hazard ratio of 4.907 (95% CI 2.154-11.18, P < .001), exceeding the risk from high Lp(a) alone (hazard ratio 2.290) or high fibrinogen alone. Adding fibrinogen to Lp(a) improved the model's C-statistic by 0.045 (P = .004). This is the first study to show that combining Lp(a) and fibrinogen assessment enhances ischaemic stroke risk prediction in coronary artery disease patients beyond either marker alone.
Original abstract
Background: Emerging data suggested that lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. Previous studies indicated fibrinogen (Fib) had synergetic effect on Lp(a)-induced events. However, combined impact of Fib and Lp(a) on ischemic stroke has not been elucidated.
Methods: In this prospective study, we consecutively enrolled 8263 patients with stable coronary artery diseases (CAD) from 2011 to 2017. Patients were categorized into three groups according to tertiles of Lp(a) levels [Lp(a)-low, Lp(a)-medium, and Lp(a)-high] and further divided into nine groups by Lp(a) and Fib levels. All subjects were followed up for the occurrence of ischemic stroke.
Results: During a median follow-up of 37.7 months, 157 (1.9%) ischemic strokes occurred. Stroke incidence increased by Lp(a) (1.1 vs. 2.1 vs. 2.5%, Cochran-Armitage p < .001) and Fib (1.1 vs. 2.0 vs. 2.6%, Cochran-Armitage p < .001) categories. When further classified into nine groups by Lp(a) and Fib levels, the incidence of ischemic stroke in group 9 [Lp(a)-high and Fib-high] was significantly higher than that in group 1 [Lp(a)-low and Fib-low] (3.1 vs. 6%, p < .001). The group 9 was associated with a highest risk for ischemic stroke (adjusted HR 4.907, 95% CI: 2.154-11.18, p < .001), compared with individuals in the Lp(a)-high (adjusted HR 2.290, 95% CI: 1.483-3.537, p < .001) or Fib-high (adjusted HR 1.184, 95% CI: 1.399-3.410, p = .001). Furthermore, combining Lp(a) with Fib increased C-statistics by .045 (p = .004).
Conclusions: Current study first demonstrated that elevated Lp(a) combining with Fib evaluation enhanced the risk of ischemic stroke in patients with CAD beyond Lp(a) or Fib alone.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.