ABO(H) blood groups and vascular disease: a systematic review and meta-analysis

Background: Associations between vascular disease and ABO(H) blood groups have a long history, but no consensus exists regarding its magnitude and significance, or whether it relates to all disorders equally. An accurate calculation of risk would allow direct assessment of whether the effects of non-O status on thrombosis risk are of the magnitude predicted by its effect on von Willebrand factor/FVIII levels. Methods and results: We conducted a systematic review and meta-analysis of studies reporting associations with non-O blood groups. This gave pooled odds ratios of 1.25 [95% confidence interval (CI) 1.14-1.36] for myocardial infarction (MI), 1.03 (95% CI 0.89-1.19) for angina, 1.45 (95% CI 1.35-1.56) for peripheral vascular disease, 1.14 (95% CI 1.01-1.27) for cerebral ischemia of arterial origin, and 1.79 (95% CI 1.56 to 2.05) for venous thromboembolism (VTE). However, restriction to prospective MI studies only did not confirm the association (OR 1.01; 95% CI 0.84-1.23), although these studies may have failed to capture early-onset disease. For VTE, using a combined group of OO/A(2)A(2)/A(2)O as index, the combination of A(1)A(1)/A(1)B/BB gave an OR of 2.44 (95% CI 1.79-3.33) and A(1)O/ BO/A(2)B an OR of 2.11 (95% CI 1.66-2.68). Conclusions: This study confirms the historical impression of linkage between some vascular disorders and non-O blood group status. Although the odds ratios are similar to those predicted by the effect of ABO(H) on von Willebrand factor levels, further work is required to assess risk prospectively and to refine the effect of reducing O(H) antigen expression on thrombosis. However, as non-O and particularly A(1)A(1), A(1)B, BB constitute a significant proportion of the population attributable fraction of VTE, there may be a role for more widespread adoption of ABO(H) typing in testing strategies.