ASCENDgpt: A Phenotype-Aware Transformer Model for Cardiovascular Risk Prediction from Electronic Health Records

We present ASCENDgpt, a transformer-based model specifically designed for cardiovascular risk prediction from longitudinal electronic health records (EHRs). Our approach introduces a novel phenotype-aware tokenization scheme that maps 47,155 raw ICD codes to 176 clinically meaningful phenotype tokens, achieving 99.6\% consolidation of diagnosis codes while preserving semantic information. This phenotype mapping contributes to a total vocabulary of 10,442 tokens - a 77.9\% reduction when compared with using raw ICD codes directly. We pretrain ASCENDgpt on sequences derived from 19402 unique individuals using a masked language modeling objective, then fine-tune for time-to-event prediction of five cardiovascular outcomes: myocardial infarction (MI), stroke, major adverse cardiovascular events (MACE), cardiovascular death, and all-cause mortality. Our model achieves excellent discrimination on the held-out test set with an average C-index of 0.816, demonstrating strong performance across all outcomes (MI: 0.792, stroke: 0.824, MACE: 0.800, cardiovascular death: 0.842, all-cause mortality: 0.824). The phenotype-based approach enables clinically interpretable predictions while maintaining computational efficiency. Our work demonstrates the effectiveness of domain-specific tokenization and pretraining for EHR-based risk prediction tasks.