Impact of Multiple Non-Invasive Biosignals on Cardiovascular Biomarker Estimation via Simulation-Based Inference

Cardiovascular disease remains the leading cause of global mortality, yet scalable cardiac monitoring is hindered by the gap between diagnostic-rich ECG and ubiquitous wearable PPG. Bridging this gap requires representations that are compact, transferable across modalities and devices, and deployable without task-specific retraining. Here we introduce biosignal fingerprints: compact latent representations of cardiovascular state derived from a cross-modal foundation model, the Multi-modal Masked Autoencoder (M2AE), trained on over 3.4 million paired ECG and PPG signals. M2AE integrates modality-specific encoders with a shared bottleneck and dual decoders, jointly optimized using reconstruction and cross-modal contrastive objectives, yielding generalizable fingerprints that retain intra- and inter-modality features. Like a biometric fingerprint, these representations uniquely encode an individual's cardiovascular state in a modality-agnostic, privacy-preserving form reusable across clinical tasks without exposing raw waveform data or requiring model retraining. Across 7 downstream tasks, spanning cross-modal reconstruction, cardiovascular disease classification, hypertension detection, mortality prediction, and demographic inference, biosignal fingerprints achieve competitive or superior performance compared to leading domain-specialist foundation models in frozen settings, including an AUROC of 0.974 for five-class CVD classification and 0.877 for hypertension detection, with a maximum improvement of 27.7% in AUROC across 5 classification tasks. Critically, strong performance is maintained with only a single modality, enabling deployment in resource-constrained, single-sensor environments typical of real-world wearable monitoring, with direct implications for continuous cardiovascular monitoring across clinical and consumer health settings.

Foundation models for wearable biosignals have matched or exceeded supervised specialists across a range of clinical tasks, yet all rely on modalities that require deliberate user action--wearing a device or visiting a sleep lab. We introduce BCG-FM, the first foundation model for ambient mechanical biosignals. A piezoelectric sensor embedded in the bed surface records ballistocardiography (BCG) each night without user effort; we pretrain BCG-FM with participant-level contrastive learning and using a total of 2.75 million hours of nightly recordings from 145,985 individuals, the largest raw-waveform biosignal pretraining corpus to date. Frozen BCG-FM embeddings achieve 3.26-year MAE on biological-age estimation (the lowest reported for any ambient, contactless modality) and yield clinically relevant discrimination across 15 self-reported health conditions and three independent external cohorts. Pretrained representations from only 500 labeled participants outperform a fully supervised baseline trained on 3,372, and representation quality scales log-linearly with contrastive batch size. These results establish ambient, longitudinal mechanical biosignals as a viable modality for health foundation models.

Continuous cuffless blood pressure (BP) monitoring is essential for connected health systems and wearable devices, enabling early detection, longitudinal tracking, and personalized management of cardiovascular disease. Many prior approaches attempt to estimate BP indirectly by reconstructing electrocardiography (ECG) from photoplethysmography (PPG), assuming ECG provides a stronger physiological link to BP. However, ECG sensing is less accessible in wearable settings and may introduce unnecessary complexity. In this work, we first perform a large-scale physiological correlation analysis on the MIMIC-III waveform database, revealing that PPG exhibits substantially stronger coupling with arterial blood pressure (ABP) ($|r|=0.247$, $p<0.001$) than ECG does ($r=0.018$, $p=0.187$), challenging the assumption that ECG provides a superior intermediate representation. Motivated by this insight, we conduct a systematic comparison between direct PPG-to-BP prediction and ECG-mediated pipelines using multiple state-of-the-art deep learning models. Across 1.74M segments from 3,127 patients, direct PPG-to-BP prediction achieves British Hypertension Society Grade A performance ($\mathrm{MAE}_{\mathrm{SBP}} = 4.82 mmHg$, $\mathrm{MAE}_{\mathrm{DBP}} = 4.31 mmHg$), outperforming all ECG-mediated approaches, which achieve only Grade B accuracy. Our findings suggest that accurate continuous BP monitoring can be achieved directly from wearable PPG signals, enabling simpler, more efficient pipelines for real-world connected health systems.