Myelodysplastic syndromes and the risk of cardiovascular disease in older adults: A SEER-medicare analysis

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant precursor state to Myelodysplastic Syndrome (MDS). It is characterized by expansion of hematopoietic clones harboring MDS-initiating driver mutations without clinically evident cytopenia or dysplasia [1], and is associated with a 40% increased risk of cardiovascular disease (CVD), especially myocardial infarction (MI), independent of traditional risk factors [2, 3]. It is unclear if this risk persists after evolution into MDS and the relationship between CHIP mutations and CVD among MDS patients is an emerging area of research [4]. These patients experience high rates of CVD and cardiovascular mortality constitutes the most common non-disease-related cause of death in MDS [5, 6]. However, studies exploring cardiovascular risk in older adults with cancer largely exclude MDS [7] and a true estimate of the magnitude of MDS as a risk factor for CVD in the elderly remains unknown. We performed a matched cohort study of MDS patients and non-cancer controls in a heterogenous, nationally representative sample using the Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare administrative claims. The SEER-Medicare database represents 28% of the United States population from 20 disparate geographic regions and includes sociodemographic factors, clinical procedures, treatments and diagnoses from inpatient and outpatient settings in adults over 65 years, constituting a valuable resource for cancer research in the elderly [8]. The study was approved by the Albert Einstein College of Medicine Institutional Review Board. The MDS cohort included Medicare beneficiaries diagnosed with MDS between 2004 and 2014. Exclusion criteria included lack of continuous coverage, enrollment in plans not captured by administrative claims, diagnosis obtained solely from death certificates or autopsy, and documented ischemic stroke (CVA) or MI preceding MDS diagnosis. The control cohort was obtained from a 5% sample of randomly selected non-cancer Medicare beneficiaries residing in SEER regions during the study period. Comorbidity burden was estimated using the Charlson comorbidity index (CCI), a weighted score of 18 preexisting medical conditions validated to measure comorbidity from administrative data [9]. To effectively calculate prediagnosis CCI using at least 1 year of claims after Medicare eligibility, only patients diagnosed at 66 years or older were included. MDS was identified using International Classification for Diseases in Oncology morphology codes These author contributed equally: Diego Adrianzen Herrera, Kith Pradhan