Monoclonal gammopathy of undetermined significance and the risk of thrombotic events: Results from iStopMM, a prospective population‐based screening study
Sæmundur Rögnvaldsson, Alessandro Gasparini, Sigrún Þorsteinsdóttir, Ingigerður Sverrisdóttir, Elías Eyþórsson, Þórir Einarsson Long, Róbert Pálmason, Brynjar Viðarsson, Páll T. Önundarson, Bjarni A. Agnarsson, Margrét Sigurðardóttir, Isleifur Olafsson, Ingunn Þorsteinsdóttir, Jón Þórir Óskarsson, Ásbjörn Jónsson, Runólfur Pálsson, Ólafur S. Indridason, Andri Ólafsson, Malin Hultcrantz, Brian G.M. Durie, Stephen Harding, Ola Landgren, Þorvarður Jón Löve, Sigurður Y. Kristinsson
Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma and related diseases but has also been associated with thrombosis. Prior studies have not been based on screened cohorts leading to bias. We assessed the risk of thrombosis in a cohort of 75 422 individuals over 40 years old who were screened for MGUS in Iceland. We also evaluated the association of M protein concentration with thrombotic risk. A total of 3668 participants had MGUS. After a median follow-up of ~3.7 years, 124 venous and 252 arterial thrombotic events (10.3 and 21.0 per 1000 person years respectively) were observed in the MGUS group, compared to 1509 and 3471 in the non-MGUS group (6.0 and 13.8 per 1000 person years respectively). After adjusting for multiple confounders, MGUS was associated with an increased risk of venous thrombosis (hazard ratio [HR] = 1.43; 95% confidence interval [CI]: 1.19-1.73) but not arterial thrombosis (HR = 0.96; 95% CI: 0.87-1.13). M protein concentration was not associated with venous (p = 0.72) or arterial (p = 0.95) thrombosis. The findings show, in a screened cohort, that MGUS is associated with venous, but not arterial, thrombosis. Furthermore, they suggest that there is a subset of individuals with MGUS with subclinical monoclonal gammopathy of thrombotic significance.