A Maino1,2, B Siegerink1,3,4, L A Lotta2, J T B Crawley5, S le Cessie1,6, F W G Leebeek7, D A Lane5, G D O Lowe8, F Peyvandi2, F R Rosendaal1,3,9. 1. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. 2. A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy. 3. Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands. 4. Center for Stroke Research, Charité-Universitätsmedizin, Berlin, Germany. 5. Centre for Haematology, Faculty of Medicine, Imperial College London, London, UK. 6. Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands. 7. Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands. 8. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. 9. Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
Abstract
BACKGROUND: Low ADAMTS-13 levels have been repeatedly associated with an increased risk of ischemic stroke, but results concerning the risk of myocardial infarction are inconclusive. OBJECTIVES: To perform an individual patient data meta-analysis from observational studies investigating the association between ADAMTS-13 levels and myocardial infarction. METHODS: A one-step meta-analytic approach with random treatment effects was used to estimate pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for confounding. Analyses were based on dichotomous exposures, with the 5th and 1st percentiles of ADAMTS-13 antigen levels as cut-off values. Quartile analyses, with the highest quartile as a reference category, were used to assess a graded association between levels and risk ('dose' relationship). Additionally, we assessed the risk of the combined presence of low ADAMTS-13 and high von Willebrand factor (VWF) levels. RESULTS: Five studies were included, yielding individual data on 1501 cases and 2258 controls (mean age of 49 years). Low ADAMTS-13 levels were associated with myocardial infarction risk, with an OR of 1.89 (95% CI 1.15-3.12) for values below the 5th percentile versus above, and an OR of 4.21 (95% CI 1.73-10.21) for values below the 1st percentile versus above. Risk appeared to be restricted to these extreme levels, as there was no graded association between ADAMTS-13 levels and myocardial infarction risk over quartiles. Finally, there was only a minor synergistic effect for the combination of low ADAMTS-13 and high VWF levels. CONCLUSIONS: Low ADAMTS-13 levels are associated with an increased risk of myocardial infarction.
BACKGROUND: Low ADAMTS-13 levels have been repeatedly associated with an increased risk of ischemic stroke, but results concerning the risk of myocardial infarction are inconclusive. OBJECTIVES: To perform an individual patient data meta-analysis from observational studies investigating the association between ADAMTS-13 levels and myocardial infarction. METHODS: A one-step meta-analytic approach with random treatment effects was used to estimate pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for confounding. Analyses were based on dichotomous exposures, with the 5th and 1st percentiles of ADAMTS-13 antigen levels as cut-off values. Quartile analyses, with the highest quartile as a reference category, were used to assess a graded association between levels and risk ('dose' relationship). Additionally, we assessed the risk of the combined presence of low ADAMTS-13 and high von Willebrand factor (VWF) levels. RESULTS: Five studies were included, yielding individual data on 1501 cases and 2258 controls (mean age of 49 years). Low ADAMTS-13 levels were associated with myocardial infarction risk, with an OR of 1.89 (95% CI 1.15-3.12) for values below the 5th percentile versus above, and an OR of 4.21 (95% CI 1.73-10.21) for values below the 1st percentile versus above. Risk appeared to be restricted to these extreme levels, as there was no graded association between ADAMTS-13 levels and myocardial infarction risk over quartiles. Finally, there was only a minor synergistic effect for the combination of low ADAMTS-13 and high VWF levels. CONCLUSIONS: Low ADAMTS-13 levels are associated with an increased risk of myocardial infarction.
Authors: David Green; Lu Tian; Philip Greenland; Kiang Liu; Melina Kibbe; Russell Tracy; Sanjiv Shah; John T Wilkins; Mark D Huffman; Yihua Liao; Donald Lloyd Jones; Mary M McDermott Journal: Clin Appl Thromb Hemost Date: 2016-06-17 Impact factor: 2.389
Authors: Maria Teresa Pagliari; Luca A Lotta; Hugoline G de Haan; Carla Valsecchi; Gloria Casoli; Silvia Pontiggia; Ida Martinelli; Serena M Passamonti; Frits R Rosendaal; Flora Peyvandi Journal: PLoS One Date: 2016-11-01 Impact factor: 3.240
Authors: Frank J Wolters; Johan Boender; Paul S de Vries; Michelle A Sonneveld; Peter J Koudstaal; Moniek P de Maat; Oscar H Franco; M Kamran Ikram; Frank W Leebeek; M Arfan Ikram Journal: Sci Rep Date: 2018-04-03 Impact factor: 4.379
Authors: Christopher J Ng; Keith R McCrae; Katrina Ashworth; Lucas J Sosa; Venkaiah Betapudi; Marilyn J Manco-Johnson; Alice Liu; Jing-Fei Dong; Dominic Chung; Tara C White-Adams; José A López; Jorge Di Paola Journal: Res Pract Thromb Haemost Date: 2018-03-24