A coronary artery calcium (CAC) score of 0 is traditionally associated with low cardiovascular risk but reflects only calcified plaque burden. This study published in the Journal of Nuclear Medicine assessed the prevalence and prognostic significance of impaired myocardial flow reserve (MFR) measured by positron emission tomography (PET) in symptomatic patients with CAC score of 0.

The analysis included 2,270 symptomatic patients from 2 centers who had a CAC score of 0 and underwent clinically indicated PET imaging. Multivariable logistic regression identified predictors of impaired MFR. Nested Cox models evaluated associations between MFR and a composite endpoint of all-cause death, myocardial infarction/late revascularization, and heart failure admission. Model discrimination was assessed using the C-index and net reclassification improvement (NRI).
Impaired MFR was present in 30.5% of patients. Independent predictors included older age, morbid obesity (body mass index ≥40 kg/m²), diabetes, hypertension, and chronic kidney disease.

Over a median follow-up of 1.63 years, impaired MFR was associated with higher event risk (hazard ratio 4.69; 95% confidence interval 2.69–8.2). Adding MFR improved risk prediction (C-index 0.784 to 0.815; P<0.001; categorical NRI 0.163; continuous NRI 0.899). The effect of MFR on risk stratification was greatest among patients classified as intermediate risk, reclassifying 16.8% to a higher risk category (4% annual event rate) and 53.9% to a lower risk category (0.9% annual event rate).

One in three symptomatic patients with a CAC score of 0 had impaired MFR. MFR showed incremental prognostic value beyond CAC scoring.