Language
English
Publication Date
8-1-2025
Journal
Research and Practice in Thrombosis and Haemostasis
DOI
10.1016/j.rpth.2025.103005
PMID
40994890
PMCID
PMC12454890
PubMedCentral® Posted Date
8-13-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare hematologic disorder with improved survival due to advancements in treatment. However, long-term cardiovascular morbidity and mortality remain significant. Established cardiovascular risk calculators, such as the 2008 Framingham Heart Study (FHS) global cardiovascular disease (CVD) and the American College of Cardiology/American Heart Association (ACC/AHA) atherosclerotic CVD (ASCVD) risk estimators, may not adequately account for the elevated and unique cardiovascular risks in iTTP survivors.
Objectives: To evaluate the discrimination and calibration of the ACC/AHA ASCVD and FHS global CVD models in predicting major adverse cardiovascular events (MACEs) among iTTP survivors.
Methods: This retrospective study analyzed 135 iTTP survivors from Johns Hopkins University (1994-2024). Presence of MACEs, including myocardial infarction, stroke, and cardiac revascularization, was the primary outcome and was assessed during clinical remission. Discriminatory ability of the model was assessed using c-statistics, while calibration was evaluated with Hosmer-Lemeshow tests and calibration plots. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were also calculated.
Results: MACEs occurred in 37.8% of the cohort over a median follow-up of 3.8 years. The ASCVD and FHS models demonstrated poor discrimination (c-statistics, 0.54 and 0.52, respectively) and poor calibration, with observed MACE rates exceeding predicted probabilities (Hosmer-Lemeshow P < .05). The ASCVD model showed sensitivity of 56.5%, specificity of 49.4%, PPV of 36.6%, and NPV of 64.9%, while the FHS model showed sensitivity of 69.6%, specificity of 39.3%, PPV of 37.2%, and NPV of 67.9%.
Conclusion: Standard cardiovascular risk models inadequately predict MACE risk in iTTP survivors, underscoring the need for tailored tools that incorporate iTTP-specific factors to improve cardiovascular risk stratification and management.
Keywords
calibration, cardiovascular, MACE, risk prediction, thrombotic thrombocytopenic purpura
Published Open-Access
yes
Recommended Citation
Javed, Binish; Brown, Jenna; Meade, Jay; et al., "Standard Cardiovascular Risk Prediction Scores Underestimate Risk in Immune-Mediated Thrombotic Thrombocytopenic Purpura Survivors" (2025). Faculty and Staff Publications. 4153.
https://digitalcommons.library.tmc.edu/baylor_docs/4153