Antithrombotic treatment is associated with intraplaque haemorrhage in the atherosclerotic carotid artery: a cross-sectional analysis of The Rotterdam Study

Abstract

AimsAntithrombotic treatment plays a key role in stroke prevention, but their direct effects on the composition of carotid artery atherosclerotic plaques are unknown. To investigate the association of antithrombotic treatment with carotid artery plaque composition, with a specific focus on an intraplaque haemorrhage (IPH).Methods and resultsFrom the population-based Rotterdam Study, 1740 participants with carotid atherosclerosis on ultrasound (mean age 72.9 years, 46.0 women) underwent magnetic resonance imaging of the carotid arteries to assess plaque composition. Information on the use of oral anticoagulants [vitamin K antagonists (VKA)] and antiplatelet agents (salicylates), including duration of use and dosage, was obtained from pharmacy records for all participants. We used logistic regression models to assess the association between the use of anticoagulants and antiplatelet agents, and the different plaque components adjusting for confounders. Current and past use of VKA [adjusted odds ratio (OR): 1.88, 95% confidence interval (CI): 0.74–4.75 and OR 1.89, 95% CI: 0.91–3.93] and antiplatelet agents (OR: 1.22, 95% CI: 0.91–1.62), and (OR: 1.23, 95% CI: 0.86–1.75) showed positive trend with a higher presence of IPH. Also, a longer duration of use was associated with a higher frequency of IPH (OR: 3.15, 95% CI: 1.23–8.05) for the use of VKA, and longer duration of the use for antiplatelet agents showed a positive trend (OR: 1.21, 95% CI: 0.88–1.67). We also found that higher levels of international normalized ratio above 2.97 for VKA (OR: 1.48, 95% CI: 1.03–2.15) and higher daily defined dosage than 1.0 for antiplatelet agents (OR: 1.50, 95% CI: 1.21–1.87) were related to a higher frequency of IPH. We found no association with lipid core or calcification.ConclusionsThe use of antithrombotic treatment relates to a higher frequency of IPH in carotid atherosclerotic plaques.

Objectives, design and main findings until 2020 from the Rotterdam Study

“…We showed both visual progression and regression of intra-plaque hemorrhage (IPH) volume during 17 months of follow-up [136], suggesting IPH as a dynamic process with potential for growth or resolution over time. Moreover, antithrombotic treatment related to a higher frequency of IPH in carotid plaques [137].…”

“…With respect to carotid atherosclerosis and vulnerable plaque components on imaging, we have demonstrated recently that antithrombotic treatment relates to intraplaque hemorrhage [137] and that statin use seems to beneficially influence composition of carotid atherosclerosis by shifting towards more stable calcified plaque [135].…”

“…Furthermore, studies were published on the association between statins and diabetes of which the risk was increased in users [436], and carotid plaque composition which was associated with a more calcified stabilized form while on statins [135]. On the other hand, anticoagulants increased the risk of intraplaque hemorrhage in carotid arteries [137]. In a comparison of the American ACC/AHA and European ESC guidelines for prescribing statins, considerable differences were found [437].…”

Serum insulin levels are associated with vulnerable plaque components in the carotid artery: the Rotterdam Study

“…In model 2, additionally adjusted for smoking, serum high-density lipoprotein, serum total cholesterol, systolic and diastolic blood pressure, diabetes mellitus, BMI, waist circumference, use of anti-diabetic medication, use of antihypertensive medication, and insulin or glucose levels, dependent on the determinant under investigation. In model 3, additionally adjusted for the use of lipid-lowering medication (13), vitamin K antagonists and antiplatelet agents (18). Second, we categorized serum insulin and glucose levels into tertiles and investigated the association of tertiles of insulin and glucose (lowest tertile was used as the reference category) with carotid plaque components using regression model 1.…”

Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis

“…Whether VKA affects plaque stability in humans is still uncertain. Observational studies suggest more plaque instability in patients on VKA due to intraplaque hemorrhage particularly upon prolonged exposure and higher intensity of anticoagulation (Mujaj et al 2018;Li et al 2014). However, in the Rotterdam study, the effects were comparable for anticoagulants (VKA) and aspirin, so the specificity and causal contribution of anticoagulation versus antiplatelet effects remain unproven.…”