Age- and Sex-Adjusted Myocardial Flow Reserve Percentiles for Personalized Cardiovascular Risk Assessment

Area of Science:

• Cardiovascular Imaging and Diagnostics
• Preventive Cardiology
• Biostatistics and Risk Modeling

Background:

• Positron emission tomography (PET) myocardial flow reserve (MFR) is a key indicator of coronary vascular health and cardiovascular risk.
• Current clinical guidelines rely on fixed MFR thresholds (<2.0) for risk stratification, which do not account for individual variations in age and sex.
• This limitation can lead to suboptimal cardiovascular risk assessment, overlooking personalized vascular health nuances.

Purpose of the Study:

• To establish age- and sex-adjusted MFR reference percentiles.
• To evaluate the prognostic and predictive performance of these percentiles for cardiovascular risk assessment.
• To compare the efficacy of percentile-based MFR models against conventional fixed-threshold MFR approaches.

Main Methods:

• Utilized data from the REFINE PET registry (24,820 patients) to measure PET MFR.
• Derived age- and sex-adjusted MFR percentiles using quantile regression in patients without known coronary artery disease.
• Assessed major adverse cardiovascular events (MACE) using survival models and compared predictive performance metrics (discrimination, calibration, reclassification) between percentile-based and fixed-threshold models.

Main Results:

• Age- and sex-adjusted MFR quartile groups were strong independent predictors of MACE, with increasing hazard ratios (HR) across lower quartiles.
• Percentile-based models showed consistently superior discrimination, calibration, and net reclassification for MACE compared to fixed-threshold models at 1 and 5 years.
• Cardiovascular risk increased progressively across MFR percentiles, even in patients with MFR >2.0, highlighting the value of percentile-based assessment.

Conclusions:

• Age- and sex-adjusted MFR percentiles offer a clinically actionable measure of vascular health, enhancing cardiovascular risk stratification.
• This approach effectively captures age- and sex-related heterogeneity in vascular risk, providing a more personalized assessment.
• MFR percentiles demonstrate improved predictive performance for cardiovascular risk compared to traditional fixed-threshold methods across diverse populations.