BackgroundThe mechanisms behind residual platelet reactivity (RPR) despite aspirin treatment are not established. It has been shown that coronary artery disease (CAD) patients with high on-aspirin RPR have elevated levels of von Willebrand factor (vWF). ADAMTS13 is a metalloprotease cleaving ultra large vWF multimers into less active fragments.Our aim was to investigate whether ADAMTS13 and vWF/ADAMTS13 ratio were associated with high RPR, and further with clinical endpoints after 2 years.MethodsStable aspirin-treated CAD patients (n = 999) from the ASCET trial. RPR was assessed by PFA-100. ADAMTS13 antigen and activity were analysed using chromogenic assays. Endpoints were a composite of acute myocardial infarction, stroke and death.ResultsThe number of patients with high RPR was 258 (25.8%). Their serum thromboxane B2 (TxB2) levels were low, indicating inhibition of COX-1. They had significantly lower levels of ADAMTS13 antigen compared to patients with low RPR (517 vs 544 ng/mL, p = 0.001) and significantly lower ADAMTS13 activity (0.99 vs 1.04 IU/mL, p = 0.020). The differences were more pronounced when relating RPR to ratios of vWF/ADAMTS13 antigen and vWF/ADAMTS13 activity (p < 0.001, both). We found an inverse correlation between vWF and ADAMTS13 antigen (r = −0.14, p < 0.001) and ADAMTS13 activity (r = −0.11, p < 0.001). No correlations between TxB2 and ADAMTS13 antigen or activity, were observed, implying that ADAMTS13 is not involved in TxB2 production. Patients who experienced endpoints (n = 73) had higher vWF level (113 vs 105%, p = 0.032) and vWF/ADAMTS13 antigen ratio (0.23 vs 0.20, p = 0.012) compared to patients without. When dichotomizing vWF/ADAMTS13 antigen at median level we observed that patients above median had higher risk for suffering endpoints, with an adjusted OR of 1.86 (95% CI 1.45, 2.82).ConclusionThese results indicate that ADAMTS13 is of importance for RPR, and that it in combination with vWF also is associated with clinical endpoints in stable CAD patients on aspirin.Trial registrationClinicaltrials.gov NCT00222261. Registered 13.09.2005. Retrospectively registered.Electronic supplementary materialThe online version of this article (10.1186/s12959-017-0151-3) contains supplementary material, which is available to authorized users.

Inherited and acquired mutations in hematopoietic stem cells can cause clonal expansion with increased risk of cardiovascular disease (CVD), a condition known for the clonal hematopoiesis of indeterminate potential (CHIP). Inherited genetic variants in two CHIP-associated genome loci, the telomerase gene telomerase enzyme reverse transcriptase (TERT) (rs7705526) and the epigenetic regulator ten–eleven translocation 2 (TET2) (rs2454206), were investigated in 1001 patients with stable coronary artery disease (CAD) (mean age 62 years, 22% women), with regards to cardiovascular outcome, comorbidities, and leukocyte telomere length. Over 2 years, mutated TERT increased the risk two-fold for major clinical events (MACEs) in all patients (p = 0.004), acute myocardial infarction (AMI) in male patients (p = 0.011), and stroke in female patients (p < 0.001). Mutated TET2 correlated with type 2 diabetes (p < 0.001), the metabolic syndrome (p = 0.002), as well as fasting glucose, HbA1c, and shorter telomeres (p = 0.032, p = 0.003, and p = 0.016, respectively). In conclusion, our results from stable CAD patients highlight TERTs’ role in CVD, and underline TET2s’ role in the epigenetic regulation of lifestyle-related diseases.

Introduction ADAMTS13 cleaves von Willebrand factor (VWF) multimers into less active fragments. Both markers have been related to cardiovascular disease (CVD). We aimed to investigate the influence of ADAMTS13 single nucleotide polymorphisms (SNPs) on levels of ADAMTS13 and VWF, and CVD. Methods The c.1342C>G, g.41635A>G and c.2699C>T polymorphisms were determined in patients with chronic coronary syndrome (n = 1000). VWF and ADAMTS13 were analyzed. Clinical endpoints after 2 years (n = 106) were unstable angina pectoris, myocardial infarction, non-hemorrhagic stroke and death. Results The SNPs did not affect ADAMTS13 levels. The 41635A-allele associated with higher VWF levels ( P < .001). Patients with the 1342G-allele had significantly higher frequency of previous atrial fibrillation (n = 26, P = .016) and cerebral ischemic events (n = 47, P = .030). Heterozygous of the 1342CG variant experienced more clinical endpoints compared to homozygous (CC and GG) ( P = .028). Conclusion The association between the 41635A-allele and VWF indicates a role for this polymorphism in VWF regulation. ADAMTS13 has previously been linked to atrial fibrillation and ischemic stroke, and our findings suggest that the 1342G-allele may be of significance. The association between the 1342CG genotype and endpoints needs further investigations. Clinicaltrials.gov, ASCET, NCT00222261. https://clinicaltrials.gov/ct2/show/NCT00222261?term=NCT00222261&draw=2&rank=1