Diastolic Age predicts MACE and discriminates LVDD in heart failure cohorts

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medRxiv Published April 19, 2026 Medically reviewed April 25, 2026 Study authors: Fahed, G.; Cauwenberghs, N.; Santana, E. J.; Chen, R.; Celestin, B. E.; Gomes Botelho Quintas, B. F.… DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Note that Diastolic Age independently predicts MACE (HR 2.30) and discriminates LVDD (AUC 0.89) in this observational cohort.

Participants from the Project Baseline Health Study (median age 50 [36-64] years, 54% female) and external validation cohorts (WASE and Stanford Cardiovascular Aging) were included in this cohort study. The total sample size was 1,952 in the primary cohort, 1,708 in WASE, and 313 in the Stanford cohort. The exposure was Diastolic Age, derived from echocardiographic parameters weighted against the PREVENT-HF risk score, compared against chronological age, Levine epigenetic clock, Horvath epigenetic clock, and ASE-defined LV diastolic dysfunction.

Diastolic Age demonstrated strong correlation with chronological age (r=0.78) and robust correlations in external validation cohorts, with r=0.76 in WASE and r=0.82 in Stanford. The measure correlated with the Levine epigenetic clock (r=0.76) and the Horvath epigenetic clock (r=0.41). Regarding diastolic dysfunction, Diastolic Age achieved an AUC of 0.89 for discrimination, which was comparable to ASE-defined LVDD (C-index 0.83 vs. 0.82).

The study assessed associations with hypertension, diabetes, elevated C-reactive protein, and epigenetic clocks. Diastolic Age independently predicted MACE with a hazard ratio of 2.30 (95% CI 1.70-3.18). Safety data, including adverse events, serious adverse events, discontinuations, and tolerability, were not reported. No specific limitations were detailed in the provided data, and funding or conflicts were not reported.

Diastolic Age provides a continuous, echocardiography-derived measure of cardiac biological aging that complements categorical diastolic grading and epigenetic aging clocks, and independently predicts cardiovascular outcomes. Clinicians should interpret these results as observational associations rather than causal relationships, noting that adverse event profiles remain uncharacterized in this dataset.

Study Details

Study typeCohort

Sample sizen = 1,708

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

Background: Among cardiac measures, diastolic parameters demonstrate the earliest and most consistent age-related changes. This can be leveraged to develop a continuous left ventricular (LV) Diastolic Age from routine echocardiographic parameters. Analogous to how epigenetic clocks weight molecular markers against mortality risk, we calibrated Diastolic Age by weighting echocardiographic features against the validated PREVENT-Heart Failure (HF) risk score. Methods: We analyzed 1,952 participants from the Project Baseline Health Study (median age 50 [36-64] years, 54% female). The measure was derived using partial least-squares regression anchored on PREVENT-HF and calibrated within a healthy reference subgroup. External validation was performed in the WASE (n=1,708) and Stanford Cardiovascular Aging (n=313) cohorts. Associations with ASE-defined LV diastolic dysfunction (LVDD), epigenetic clocks, and major adverse cardiovascular events (MACE) were examined. Results: Diastolic Age correlated strongly with chronological age (r=0.78) with robust external validation (WASE r=0.76; Stanford r=0.82; calibration slopes {approx}1.0). It increased progressively across grades of diastolic dysfunction and discriminated LVDD with an AUC of 0.89 (95% CI 0.87-0.92), and was independently associated with hypertension, diabetes, and elevated C-reactive protein. While correlated with the Levine (r=0.76) and Horvath (r=0.41) epigenetic clocks, residual analyses indicated that Diastolic Age captures a distinct cardiac-specific dimension of biological aging. Over median follow-up of 4.2 years, it independently predicted MACE (HR 2.30, 95% CI 1.70-3.18), with accelerated diastolic aging across all age groups among those with events. Discrimination was comparable to ASE-defined LVDD (C-index 0.83 vs. 0.82). Conclusion: Diastolic Age provides a continuous, echocardiography-derived measure of cardiac biological aging that complements categorical diastolic grading and epigenetic aging clocks, and independently predicts cardiovascular outcomes.