Language

English

Publication Date

11-1-1970

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

Animals, Basophils, Cell Division, Cell Nucleus, Chromatids, Collagen, Cytoplasm, Female, Glycogen, Male, Mitosis, Muscle Development, Organ Size, Pineal Gland, Rats, Staining and Labeling, calibration, cardiovascular, MACE, risk prediction, thrombotic thrombocytopenic purpura

Published Open-Access

yes

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.