Clonal hematopoiesis, a precursor to myelodysplastic syndromes (MDS), constitutes a novel cardiovascular disease (CVD) risk factor, causing growing interest in cardiovascular outcomes in MDS. Rurality is associated with increased CVD but studies on cardiovascular geographic disparities in MDS are lacking.
Using the U.S. Surveillance, Epidemiology, and End Results (SEER) registry, we identified 52,750 MDS patients between 2001 and 2016. Rurality was defined using Rural-Urban Continuum Codes. Cox regression estimated the association of rurality and cardiovascular death.
MDS incidence was equal in urban and rural populations (6.7 per 100,000). Crude probability of cardiovascular death was higher among rural MDS patients. Adjusting for age, sex, race/ethnicity, marital status, insurance, and MDS risk (defined from histology), rural patients had 12% increased risk of CVD death compared to urban patients (HR=1.12, 95%CI 1.03–1.21). HR for CVD death was 1.22 (95%CI 1.01–1.5) in patients from the most rural areas (less than 2500 urban population). Among MDS patients younger than 65 years, rurality was associated with 25% increased risk of CVD death (HR=1.25, 95%CI 1.01–1.59).
This population-based analysis suggests that rural residence is linked to higher burden of cardiovascular death in patients with MDS. The disparity is not explained by demographic factors or MDS risk. Interventions targeting CVD may improve outcomes in rural MDS patients.
- • Rural MDS patients had 12% increased risk of cardiovascular mortality compared to urban patients.
- • Demographic factors and MDS risk did not explain the rural/urban difference in cardiovascular death.
- • The rural to urban disparity in cardiovascular death was larger in MDS patients younger than 65.
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 . These acquired somatic mutations not only can cause hematologic cancer but are also associated with accelerated atherosclerosis and atherothrombosis , promoting plaque build-up and disruption in the arterial endothelium and resulting in increased risk of cardiovascular disease (CVD) .
In subjects without MDS, CHIP is recognized as a novel and potent CVD risk factor with rising clinical relevance . Although CVD risk is elevated in most cancer patients, including patients with other hematologic malignancies , 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 . 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 . 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 .
Geographic location is a factor contributing to CVD clustering . 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 , as well as transportation barriers and delay in care for cancer patients and survivors . In the United States, about 14% of the population lives in rural areas . 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 . These factors translate into a substantial disparity between rural and urban CVD mortality rates .
The rural to urban disparity in CVD mortality is an important equity target for population health research . 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 , 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.