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. 2022 Mar 7;43(10):971-981.
doi: 10.1093/eurheartj/ehab600.

Atherothrombotic factors and atherosclerotic cardiovascular events: the multi-ethnic study of atherosclerosis

Andrew P DeFilippis  1 , Patrick J Trainor  2 , George Thanassoulis  3 , Lyndia C Brumback  4 , Wendy S Post  5 , Michael Y Tsai  6 , Sotirios Tsimikas  7
Affiliations

Atherothrombotic factors and atherosclerotic cardiovascular events: the multi-ethnic study of atherosclerosis

Andrew P DeFilippis et al. Eur Heart J. .

Abstract

Aims: Traditional atherosclerotic cardiovascular disease (ASCVD) risk factors fail to address the full spectrum of the complex interplay of atherosclerotic and atherothrombotic factors integral to ASCVD events. This study sought to examine the association between atherothrombotic biomarkers and ASCVD events.

Methods and results: The association between atherothrombotic biomarkers and 877 ASCVD events with and without adjustment for traditional risk factors was evaluated via Cox proportional hazards models and factor analysis in 5789 Multi-Ethnic Study of Atherosclerosis participants over a median follow-up of 14.7 years. Factor analysis accounted for multidimensional relationship and shared variance among study biomarkers, which identified two new variables: a thrombotic factor (Factor 1), principally defined by shared variance in fibrinogen, plasmin-antiplasmin complex, factor VIII, D-dimer, and lipoprotein(a), and a fibrinolytic factor (Factor 2), principally defined by shared variance of plasminogen and oxidized phospholipids on plasminogen. In a model including both factors, the thrombotic factor was associated with the higher risk of ASCVD events [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.45, 1.70], while the fibrinolytic factor was associated with the lower risk of ASCVD events (HR 0.76, 95% CI 0.70, 0.82), with estimated ASCVD free survival highest for low atherothrombotic Factor 1 and high atherothrombotic Factor 2.

Conclusion: Two atherothrombotic factors, one representative of thrombotic propensity and the other representative of fibrinolytic propensity, were significantly and complementarily associated with incident ASCVD events, remained significantly associated with incident ASCVD after controlling for traditional risk factors, and have promise for identifying patients at high ASCVD event risk specifically due to their atherothrombotic profile.

Keywords: Atherosclerotic cardiovascular disease; Atherothrombosis; Factor analysis; Fibrinolysis; Risk prediction.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Continuous variable associations of study atherothrombotic biomarkers. Values represent the Pearson correlation coefficient between log-transformed values of each biomarker. Graded colours are utilized to depict strength of linear association (red represents negative association; blue represents positive association). Bartlett’s test of sphericity provided evidence that the covariance matrix for the biomarkers differed from the identity matrix (P < 0.0001).
Figure 2
Figure 2
Kaplan–Meier plot for participants with discordant levels of the factors (low thrombotic factor and high fibrinolytic factor; high thrombotic factor and low fibrinolytic factor), and two concordant levels (low thrombotic factor and low fibrinolytic factor; high thrombotic factor and high fibrinolytic factor).
See this image and copyright information in PMC

Comment in

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