Physicians' Academy for Cardiovascular Education

Coronary microvascular dysfunction associated with cerebral small vessel disease

Coronary microvascular dysfunction is associated with impaired cognitive function: the cerebral-coronary connection study (C3 study)

Literature - Mejia-Renteria H, Travieso A, Matías-Guiu JA, et al - Eur Heart J. 2022 Nov 7:ehac521. doi: 10.1093/eurheartj/ehac521.

Introduction and methods


Coronary microvascular dysfunction (CMD) and cerebral small vessel disease (CSVD) share common risk factors, such as age, hypertension and diabetes [1]. Based on similarities between risk factors and pathological changes, it is hypothesized that microvascular dysfunction in the heart and brain may be part of a single pathological process affecting microcirculation in CAD patients [2]. However, to date, objective data supporting this hypothesis are lacking.

Aim of the study

The aim of this prospective cohort study was to investigate the prevalence of CMD in CAD patients and its association with CSVD and cognitive function.


In this prospective cohort study (C3 study), 67 adult CAD patients (mean age: 66 years; 73% female) underwent cardiac catheterization during which the epicardial vessels and coronary microcirculation were assessed using intracoronary pressure and Doppler. Additionally, brain MRI, transcranial Doppler and comprehensive neurocognitive assessment were performed. Neurocognitive assessment included the min-mental state examination (MMSE), Addenbrooke's Cognitive Examination III (ACE-III) and Trail Making Test A (TMT-A). Only patients with one or more stable intermediate coronary stenoses suitable to fractional flow reserve (FFR)-guided revascularization were included.


In CAD patients, the prevalence of CMD was investigated and its association with CSVD and cognitive function. Coronary microcirculation-related indices included coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR). A CFR value <2.0 was considered abnormal and a marker for CMD.

Main results


This prospective cohort study shows that CMD is frequent (55%) in CAD and is associated with CSVD, abnormal cerebral flow hemodynamics and significant cognitive impairment. These findings support the hypothesis that microvascular dysfunction in the heart and brain are part of a single pathological process affecting the microcirculation in CAD patients.


Show references

Find this article online at Eur Heart J.

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