Abstract

Introduction: Case reports and smaller observational studies have suggested an association between monoclonal gammopathy of undetermined significance (MGUS) and various cardiovascular diseases. We aimed to explore the association of MGUS with a broad spectrum of incident cardiovascular disease further, using the Danish nationwide administrative databases. Methods: Between 1995-2018, all patients eighteen years and older with MGUS were matched (10:1) with controls from the general population based on age and sex. Patients with a diagnosis of multiple myeloma were excluded. Incident cardiovascular diseases were identified using ICD coding. Hazard ratios for cardiovascular outcomes were calculated using Cox proportional hazard regression. Results: Patients with MGUS (n= 8,445, mean age 69.9 years, 51.3% male) had a higher risk of developing most cardiovascular diseases after multivariable adjustment, including heart failure (HR 1.65, 95% CI 1.51-1.81), atrial fibrillation (HR 1.47, 95% CI 1.37-1.58), acute myocardial infarction (HR 1.24, 95% CI 1.08- 1.43), stroke (HR 1.25, 95% CI 1.12-1.40), aortic aneurysm (HR 1.49, 95% CI 1.23-1.80), aortic stenosis (HR 1.72, 95% CI 1.52-1.96), aortic regurgitation (HR 1.70, 95% CI 1.36-2.12), conduction disease (HR 1.52, 95% CI 1.25-1.82), pericarditis (HR 1.62, 95% CI 1.03-2.55), peripheral arterial disease (HR 1.86, 95% CI 1.61-2.14), cor pulmonale (HR 2.32, 95% CI 1.76-3.06), venous thromboembolism (HR 1.29, 95% CI 1.12-1.48), and implantation of a cardiac pacemaker or defibrillator (HR 1.34, 95% CI 1.14-1.59). Conclusions: MGUS is associated with a broad spectrum of cardiovascular diseases, with somewhat greater risk estimates observed for cardiovascular disorders that have previously been associated with infiltrative diseases (such as heart failure, pulmonary hypertension, aortic valvular disease, atrial fibrillation, and conduction abnormality) than for atherosclerotic and thrombotic disorders. Further studies are warranted to understand the underlying mechanisms.

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