Korean Circ J.  2021 Mar;51(3):202-221. 10.4070/kcj.2020.0537.

Ethnic Difference of Thrombogenicity in Patients with Cardiovascular Disease: a Pandora Box to Explain Prognostic Differences

Affiliations
  • 1Department of Cardiology, Chosun University Hospital, Gwangju, Korea
  • 2Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, MD, USA
  • 3Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea
  • 4Division of Cardiology, Gyeongsang National University Hospital, Jinju, Korea
  • 5Division of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
  • 6Department of Cardiology and Angiology, University Hospital of Tübingen, Tübingen, Germany
  • 7National Heart and Lung Institute, Imperial College, London, United Kingdom
  • 8Postgraduate Medical School, University of Hertfordshire, Hertfordshire, United Kingdom
  • 9Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon, Korea
  • 10Institute of the Health Sciences, Gyeongsang National University, Jinju, Korea

Abstract

Arterial and venous atherothrombotic events are finely regulated processes involving a complex interplay between vulnerable blood, vulnerable vessel, and blood stasis. Vulnerable blood (‘thrombogenicity’) comprises complex interactions between cellular components and plasma factors (inflammatory, procoagulant, anticoagulant, and fibrinolytic factors). The extent of thrombogenicity may determine the progression of atheroma and the clinical manifestation of atherothrombotic events, with the highest thrombogenicity in African Americans and lowest in East Asians. Inherent thrombogenicity may influence clinical efficacy and safety of specific antithrombotic treatments in high-risk patients, which may in part explain the observation that East Asian patients have reduced anti-ischemic benefits and elevated bleeding risk with antithrombotic therapy compared to Caucasian patients. In this review, we discuss available evidence regarding the racial differences in thrombogenicity and its impact on clinical outcomes among patients with atherosclerotic cardiovascular disease.

Keyword

Thrombogenicity; Coagulation; Inflammation; Race; Antithrombotic treatment

Figure

  • Figure 1 Age-adjusted death rates for CAD and stroke by race/ethnicity (deaths per 100,000 men of 35–74 years old). This figure was modified from the original version.2)CAD = coronary artery disease; ICH = intracranial hemorrhage.

  • Figure 2 Risk of VTE across race & postulated mechanisms. This figure was modified from the original version.1)HIV = human immunodeficiency virus; VTE = venous thromboembolism; vWF = von Willebrand factor.

  • Figure 3 Role of coagulation cascade in progression of atherothrombosis. Factor Xa and thrombin contribute to atherothrombotic events through various mechanisms. Factor Xa (via PAR-1 and PAR-2) and thrombin (via PAR-1 and PAR-4) regulate the activation of endothelial cells, leukocytes, platelets, and vascular SMCs. PAR-mediated signaling are involved in endothelial cell activation and dysfunction, inflammatory process by production of pro-inflammatory cytokines and chemokines, and proliferation and apoptosis of vascular SMCs. Sustained inflammation in the lesion induces plaque instability and promotes plaque rupture. Thrombin is critical for platelet activation (via PAR-1 and PAR-4) and fibrin formation, which contribute to platelet-fibrin clot formation after plaque rupture. This figure was modified from the original version.17)PAR = protease-activated receptor; PFCS = platelet-fibrin clot strength; SMC = smooth muscle cell; TEG = thromboelastography.

  • Figure 4 Obesity-related inflammatory response and an enhanced thrombotic risk.IL = interleukin; PAI-1 = plasminogen activator inhibitor-1; TAFI = thrombin-activatable fibrinolysis inhibitor; TNF = tumor necrosis factor; vWF = von Willebrand factor.

  • Figure 5 (A) TEG parameter and (B) the level of platelet-fibrin clot strength (MA) across the races.ANOVA = analysis of variance; CAD = coronary artery disease; MA = maximal amplitude; TEG = thromboelastography.

  • Figure 6 Ischemic and bleeding events according to prolonged- vs. short-term DAPT in East Asians vs. Westerners. This figure was modified from the original version.81)DAPT = dual antiplatelet therapy.


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