Geographic disparities in cardiovascular mortality among patients with myelodysplastic syndromes: A population-based analysis.

1Introduction

Myelodysplastic Syndromes (MDS) are malignant hematopoietic disorders characterized by clonally restricted hematopoiesis leading to dysplasia, cytopenia, and risk of acute myeloid leukemia. Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant precursor to MDS defined when cellular clones harboring mutations with carcinogenesis potential are identified in the absence of phenotypical evidence of cytopenia or dysplasia [12] . These acquired somatic mutations not only can cause hematologic cancer but are also associated with accelerated atherosclerosis and atherothrombosis [34] , promoting plaque build-up and disruption in the arterial endothelium and resulting in increased risk of cardiovascular disease (CVD) [56] .

In subjects without MDS, CHIP is recognized as a novel and potent CVD risk factor with rising clinical relevance [78] . Although CVD risk is elevated in most cancer patients, including patients with other hematologic malignancies [9] , the CVD risk from CHIP persists after clonal evolution and progression into MDS, making the burden of cardiovascular morbidity and mortality particularly elevated in these patients [1011] . In a previous population-based study, we demonstrated that MDS was an independent risk factor for incident CVD events in older adults, compared to propensity matched non-cancer controls [12] . Furthermore, CVD is the most common non-cancer cause of death in MDS, accounting for over 25% of deaths in certain subgroups such as long-term survivors and those with low-risk disease [1314] .

Geographic location is a factor contributing to CVD clustering [15] . Rural residence, defined as living in areas outside of metropolitan areas or urban centers, typically with a low population density, is associated with increased CVD morbidity and mortality [1617] , as well as transportation barriers and delay in care for cancer patients and survivors [18] . In the United States, about 14% of the population lives in rural areas [19] . Rural communities are affected by poverty and decreased access to health care, as well as lower health literacy resulting in high-risk behaviors with respect to physical activity, nutrition, and cigarette smoking [2021] . These factors translate into a substantial disparity between rural and urban CVD mortality rates [2223] .

The rural to urban disparity in CVD mortality is an important equity target for population health research [24] . Individuals with a higher intrinsic risk of CVD death, such as patients with MDS, may be particularly vulnerable to poor CVD outcomes in rural settings, and certain rural MDS subgroups, who otherwise have limited MDS-directed therapeutic options [25] , may benefit from prompt CVD interventions. Geographical inequalities in CVD death among patients with MDS have not been addressed. We conducted a population-based analysis to determine rural disparities in CVD mortality within a nationally representative sample of patients with MDS in the United States.