Trends in mortality from thrombotic microangiopathies with underlying cardiovascular comorbidities as a contributing cause in the United States (1999–2020)

Abstract Background: Thrombotic microangiopathies (TMAs) are life-threatening disorders often complicated by cardiovascular comorbidities. Despite advances in management, long-term mortality trends and demographic disparities in TMA-related deaths remain poorly characterized in the U.S. population. This analysis examines national patterns over 21 years to identify critical mortality trends and racial disparities. Methods: We conducted a cross-sectional analysis using the Centers for Disease Control and Prevention's National Vital Statistics System (via the Wide-ranging ONline Data for Epidemiologic Research - WONDER platform) from 1999 - 2020. Mortality data were extracted using ICD-10 code M31.1 (Thrombotic Microangiopathy) as the underlying cause and cardiovascular comorbidities (codes I00-I99) as contributing causes. Complete demographic data (age, sex, race, ethnicity) were included, and cases with missing data were excluded from the analysis. Annual mortality trends were assessed using Pearson's chi-square tests for categorical variables (sex, race) across years, with α = 0.05 for significance. Observed-to-predicted ratios and 95% confidence intervals (CIs) were calculated to evaluate trend deviations. All analyses were performed using SPSS version 26. The dataset included 2,150 valid cases after exclusion of missing data. Results: Over the study period, female decedents accounted for 65.8% (n=1,415) of deaths, which was substantially higher than the 34.2% (n=735) of deaths observed among males. Annual female mortality counts fluctuated between 118 in 1999 and 46 in 2019, whereas male mortality ranged from 50 to 12 in the same timeframe. Race-stratified analysis revealed white individuals comprised 66.2% (n=1,424) of deaths, compared to 33.8% (n=726) of deaths among black individuals. Chi-square tests indicated these distributions were statistically significant: sex differences (χ² = 39.457, df = appropriate, p = 0.009) and racial differences (χ² = 38.761, df = appropriate, p = 0.010) were both associated with mortality trends over the years. The temporal trend showed a reduction in the disparity between white and black deaths, with counts in 1999 at 116 vs. 52, respectively, and by 2017 narrowing down to 62 vs. 42, respectively (p = 0.010). Population denominators displayed right-skewed distributions, indicating a predominance of years with similar population sizes. Conclusion: Our study reveals persistent sex and racial disparities in TMA mortality with cardiovascular comorbidities, with significantly higher burden among females and white individuals over two decades. These findings underscore the need for targeted interventions addressing demographic-specific risk factors. Limitations in crude mortality rate reporting highlight the necessity for improved data standardization to better inform public health strategies for high-risk TMA populations.