Social Vulnerability Is an Important Predictor of Cardiovascular Disease Risk after Allogeneic Hematopoietic Cell Transplantation

Introduction: Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment for malignant and non-malignant hematologic diseases. However, HCT survivors have a >4-fold risk of developing cardiovascular disease (CVD) compared to the general population, and CVD is a leading cause of excess non-relapse related mortality in long-term HCT survivors. Comorbidities that emerge after HCT such as hypertension (HTN), diabetes mellitus (DM), and dyslipidemia are established risk factors for CVD, and there is growing evidence in non-oncology populations (J Am Heart Assoc 2023; PMID 37345825) that social and environmental determinants of health mediate the onset of these risk factors. We previously reported on the association between social vulnerability and short-term (<1y after HCT) non-relapse mortality after allogeneic HCT, which was in part attributed to CVD (J Natl Cancer Inst 2022; PMID 35980163). However, the longer-term impact of social and environmental vulnerability on CVD risk in HCT survivors has not been well-characterized. To address this gap, we evaluated the association between census-tract level environmental justice index (EJI) and development of CVD risk factors after HCT in ≥1y survivors.

Methods: This retrospective cohort study included 789 consecutive patients who underwent an allogenic HCT at age >18y between 2013 and 2019 at City of Hope and survived ≥1y after HCT. Patient follow-up was censored at relapse or subsequent malignancy. Demographic, disease, treatment, comorbidity, and health outcomes data were abstracted from medical records. The EJI, obtained from the Center for Disease Control, consists of 4 indicators of social vulnerability (racial/ethnic minority status, socioeconomic status, household characteristics, and housing type) and 5 indicators of environmental burden (air pollution, potentially hazardous & toxic sites, built environment, transportation infrastructure, and water pollution) calculated for each U.S. census tract. EJI ranges from 0 for lowest to 1 for highest burden. EJI scores were derived using patients' addresses at HCT. Among patients without a history of CVD or its risk factors and treating death as competing risk, Fine-Gray regression analysis was used to evaluate the association between EJI (overall and by social and environmental burden separately) and the risk of de novo HTN, DM, and dyslipidemia present at >1y post-HCT, adjusted for age and BMI at HCT. We also evaluated the association between having 0, 1, or ≥2 CVD risk factors (de novo HTN, DM, and dyslipidemia) on the incidence of developing clinically significant CVD (heart failure, coronary artery disease, pericarditis, stroke) after HCT, adjusted for EJI.

Results: Mean age (±standard deviation) at HCT was 48.7y (±16.3y); 56.5% were male, 48.2% were non-Hispanic White, 30.8% were Hispanic, and 13.8% were Asian. The most common diagnosis was acute myeloid leukemia (41.8%); 52.5% received reduced intensity conditioning. Higher overall EJI significantly increased the risk of de novo dyslipidemia (adjusted Hazard Ratio per 0.1 unit increase in EJI [aHR] 1.13, 95%CI 1.01-1.27), DM (aHR 1.10, 95% CI 1.00-1.22), and HTN (aHR 1.07, 95% CI 0.99-1.15). The elevated risk of dyslipidemia, DM, and HTN was primarily attributed to increased social vulnerability, rather than environmental burden (p>.05). Accumulation of de novo cardiovascular risk factors after HCT was associated with an incremental 5y cumulative incidence of CVD (None: 6.2% [95%CI 3.4%-10.2%]; 1 risk factor: 12.0% [95%CI 4.5%-23.3%]; >2 risk factors: 25.3%, 95%CI [9.3%-45.1%]; p=0.007). In the multivariable model, development of HTN, DM, or dyslipidemia was associated with a >3-fold (aHR 3.4, 95%CI 1.6-7.5; reference: no risk factors) risk of CVD after HCT, and survivors with >2 risk factors had >8-fold (aHR 8.1, 95%CI 3.2-20.6; reference: no risk factors) risk.

Conclusion: Higher social vulnerability but not environmental burden was associated with increased risk of HTN, DM, and dyslipidemia in 1y allogeneic HCT survivors, which in turn were associated with incrementally higher 5y incidence of CVD. These findings underscore the impact of social determinants of health on clinically important outcomes after allogeneic HCT and may inform tailored approaches for risk-based screening, implementation of preventive measures, and resource allocation for long-term survivors.

Al Malki:Incyte: Research Funding; NexImmune: Consultancy, Research Funding; Tr1X: Consultancy; Stemline therapeutics: Research Funding; CareDx: Consultancy; Tscan: Consultancy. Artz:Astra Zeneca: Honoraria; Magenta Therapeutics: Honoraria; Abbvie: Consultancy. Nakamura:Mitarisan: Research Funding; Blue Bird (ended): Consultancy; Omeros (ended): Consultancy; Helocyte: Research Funding; Maat Pharma: Research Funding; Pfizer: Consultancy; Sanofi: Consultancy; Ono Pharmaceutical: Consultancy. Rhee:Pfizer: Research Funding. Armenian:Pfizer: Research Funding.