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Background  Elevated lipoprotein(a) [Lp(a)] and fibrinogen (Fib) are both associated with coronary artery disease (CAD). The atherogenicity of Lp(a) can be partly due to the potentially antifibrinolytic categories. We hypothesize that patients with higher Lp(a) and Fib may have worse outcomes.    Methods  In this prospective study, we consecutively enrolled 8,417 Chinese patients with stable CAD from March 2011 to March 2017. All subjects were divided into 9 groups according to Lp(a) (Lp(a)-Low, Lp(a)-Medium, Lp(a)-High) and Fib levels (Fib-Low, Fib-Medium, Fib-High) and followed up for CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan–Meier, Cox regression and C-statistic analyses were performed.    Results  During a median of 37.1 months’ follow-up, 395 (4.7%) CVEs occurred. The occurrence of CVEs increased by Lp(a) (3.5 vs. 5.3 vs. 5.6%,  p  = 0.001) and Fib (4.0 vs. 4.4 vs. 6.1%,  p  < 0.001) categories. When further classified into 9 groups by Lp(a) and Fib levels, the CVEs were highest in the 9th (Lp(a)-High and Fib-High) compared with the 1st (Lp(a)-Low and Fib-Low) group (7.2 vs. 3.3%,  p  < 0.001). The highest risk of subsequent CVEs was found in the 9 th  group (HR adjusted  2.656, 95% CI 1.628–4.333,  p  < 0.001), which was more significant than Lp(a)-High (HR adjusted  1.786, 95% CI 1.315–2.426,  p  < 0.001) or Fib-High (HR adjusted  1.558, 95% CI 1.162–2.089,  p  = 0.003) group. Moreover, adding the combined Lp(a) and Fib increased the C-statistic by 0.013.    Conclusion  Combining Fib and Lp(a) enhance the prognostic value for incident CVEs beyond Lp(a) or Fib alone.

Prognostic utility of lipoprotein(a) combined with fibrinogen in patients with stable coronary artery disease: a prospective, large cohort study