Association Between Monoclonal Gammopathy of Undetermined Significance and Cardiovascular Disease Risk: A Veterans...

Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased risk of cardiovascular disease (CVD). However, its potential to provide additional prognostic information beyond traditional CVD risk assessments remains unknown. This study aimed to examine the association between MGUS and incident CVD and to determine whether MGUS status offers additional prognostic value beyond the established atherosclerotic cardiovascular disease risk calculation.

We conducted a retrospective, matched observational study using 2010 to 2021 Veterans Health Administration data. MGUS status, confirmed through a validated natural language processing algorithm, were 1:5 matched to individuals without MGUS. The outcome of interest was an incident CVD event. Cumulative incidence functions were compared using Gray's test. Multivariable Fine and Gray's subdistribution models were performed to estimate the adjusted hazard ratios (aHRs) for incident CVD. Analyses were also stratified by atherosclerotic CVD risk category (low/borderline, intermediate, high).

The analytic cohort included 70 320 individuals (11 720/58 600 with/without MGUS); MGUS was associated with a higher 10-year CVD incidence (29.5% versus 9.7%; P<0.001) and increased risk (aHR, 1.70 [95% CI, 1.62-1.78]; P<0.001), compared with non-MGUS. The increased risk remained across atherosclerotic CVD risk category: low/borderline risk (aHR, 2.53 [95% CI, 2.10-3.05]), intermediate risk (aHR, 1.82 [95% CI, 1.65-2.00]), and high risk (aHR, 1.59 [95% CI, 1.50-1.68]) (all P<0.001).

MGUS is an independent risk factor of incident CVD across all atherosclerotic CVD risk categories in a heterogeneous cohort of US veterans. These findings underscore the connection between the immune system and CVD and suggest that determination of MGUS status is of clinical utility in adults at risk for CVD.