This meta-analysis aims to quantify the association of reduced coronary flow with all-cause mortality and major adverse cardiovascular events (MACE) across a broad range of patient groups and pathologies.

Methods and results

We systematically identified all studies between 1 January 2000 and 1 August 2020, where coronary flow was measured and clinical outcomes were reported. The endpoints were all-cause mortality and MACE. Estimates of effect were calculated from published hazard ratios (HRs) using a random-effects model. Seventy-nine studies with a total of 59 740 subjects were included. Abnormal coronary flow reserve (CFR) was associated with a higher incidence of all-cause mortality [HR: 3.78, 95% confidence interval (CI): 2.39–5.97] and a higher incidence of MACE (HR 3.42, 95% CI: 2.92–3.99). Each 0.1 unit reduction in CFR was associated with a proportional increase in mortality (per 0.1 CFR unit HR: 1.16, 95% CI: 1.04–1.29) and MACE (per 0.1 CFR unit HR: 1.08, 95% CI: 1.04–1.11). In patients with isolated coronary microvascular dysfunction, an abnormal CFR was associated with a higher incidence of mortality (HR: 5.44, 95% CI: 3.78–7.83) and MACE (HR: 3.56, 95% CI: 2.14–5.90). Abnormal CFR was also associated with a higher incidence of MACE in patients with acute coronary syndromes (HR: 3.76, 95% CI: 2.35–6.00), heart failure (HR: 6.38, 95% CI: 1.95–20.90), heart transplant (HR: 3.32, 95% CI: 2.34–4.71), and diabetes mellitus (HR: 7.47, 95% CI: 3.37–16.55).


Reduced coronary flow is strongly associated with increased risk of all-cause mortality and MACE across a wide range of pathological processes. This finding supports recent recommendations that coronary flow should be measured more routinely in clinical practice, to target aggressive vascular risk modification for individuals at higher risk.