More Than ADAMTS13: The Impact of Area Deprivation on Major Adverse Cardiovascular Events in Ittp Survivors
Authors: Sukumar Senthil , Brown Jenna , Mazepa Marshall , Cataland Spero , Chaturvedi Shruti 
Published: December 2024

Introduction: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors experience significant cardiovascular morbidity and mortality even in clinical remission, and Black patients have disproportionately high rate of events. We conducted this retrospective cross-sectional study to determine the association between area deprivation index (ADI), a multifaceted proxy measure for socioeconomic disadvantage, and MACE.

Methods: Adults (≥18 years of age) with confirmed iTTP in the Ohio State University (OSU) TTP registry and Johns Hopkins University thrombotic microangiopathy registry from 06/2003 to 05/2024 with at least 1 year follow up were included. Exclusion criteria included age under 18 at enrollment (n = 9), out of regional residence (n=7), and inadequate address for geocoding (i.e. PO Box listed or address not available, n=11). The primary outcome was MACE, defined as myocardial infarction, stroke, and any cardiac revascularization. ADI was calculated using the full address of each participant and is a measure of socioeconomic conditions of specific geographic areas, considering factors such as income, education level, employment rates, housing, and access to services. Higher ADI scores indicate greater deprivation. Differences between the cohorts were tested using the chi-squared test for categorical variables and Mann-Whitney U test for continuous variables. Multivariable logistic regression was utilized to assess association between baseline variables, ADI, and MACE. All statistical analyses were performed in R and ArcGIS Pro. Missing data for ADI calculations was handled by imputation.

Results: A total of 182 participants from OSU (n=52) and JHU (n=130) were eligible for analysis. Mean age was 43 (±15) years and 69% were female. The majority self-identified as Black (51%), followed by White (46%), and Asian (3%). MACE occurred in 49% (n=90) over a median follow up of 10.03 years since registry enrollment. Sixty-two percent had hypertension and 27% had diabetes. The median ADI of the overall cohort was 47.5. Between sites, there were no significant differences in age (40 vs. 45 years), sex (71% vs 68% female), rate of MACE (40% vs 53%), hypertension (63% vs 62%), or diabetes (27% vs 28%) at OSU and JHU respectively. Race was significantly different with OSU being predominantly White (67% White, 31% Black, 2% Asian) and JHU being predominantly Black (38% White, 58% Black, 4% Asian, p=0.001). Median (IQR) ADI was also significantly greater at OSU (70, 58-81) vs JHU (32, 22-60, p &lt;0.001) indicating higher level of deprivation. Given parameters of ADI calculation, rurality likely plays a large role in access to services calculations. ADI and race appear correlated, with median ADI significantly differing by group (White 52.2 vs Black 47.5 vs Asian 22.3; p=0.038).

ADI was significantly associated with MACE when adjusting for age with an OR of 1.01 (1.001, 1.02) indicating a 1% increase in risk of MACE for every unit increase in ADI score. Stratified analyses revealed that this is driven largely by the significant association of ADI with MACE in the JHU cohort [OR 1.02 (1.001-1.03)] and not in the OSU cohort [1.02 (0.99-1.06]. Due to the demographic heterogeneity between cohorts, multivariable logistic regression was conducted separately by site. At JHU (n=130) non-Black race (OR 0.34, p=0.012), age (OR 1.03, p=0.023), hypertension (OR 2.44, p=0.036), and diabetes (OR 4.43, p=0.004) were significantly associated with MACE when adjusting for each other and ADI. At OSU (n=52) neither non-Black race, age, hypertension, diabetes, nor ADI were significantly associated with MACE, but this is likely affected by the smaller cohort size.

Conclusions: ADI is significantly associated with MACE, with the odds of MACE increasing by 1% for every unit increase in ADI. Our results suggest that socioeconomic disadvantage may impact cardiovascular outcomes in TTP survivors. These results further affirm that race is a social construct and likely a surrogate representation of environmental stressors, like those measured by ADI. Mechanisms have not been evaluated but may include the effects of social determinants on traditional cardiovascular risk factors and the inflammatory effects of allostatic load.