Coronary Microvascular Dysfunction Associated with Cerebral Small Vessel Disea

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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

  • Patients with abnormal CFR (n = 37; 55%) more often had high burden of white matter hyperintensities than patients with normal CFR (n = 30; 45%) (43.2 vs. 20.0%; P=0.044), but less often had intermediate burden of white matter hyperintensities (21.6 vs. 46.7%; P=0.030).
  • Abnormal CFR was associated with a 0.94% lower gray matter volume (corrected β coefficient: 11.33; P=0.024) and with specific parameters of white matter microstructural damage, such as a 2.7% lower radial diffusivity (corrected β coefficient: -9.73 x 106; P=0.029) and a 1.2% higher mean diffusivity (corrected β coefficient: -8.27 x 10-6; P=0.032), on brain MRI.
  • Abnormal CFR was associated with a 7.4% higher resistive index (corrected β coefficient: -0.02; P=0.027) and a 12.7% higher pulsalitity index (corrected β coefficient: -0.06; P=0.043) on transcranial Dopper.
  • Abnormal CFR was associated with worse neurocognitive test scores, such as a 3.9% lower MMSE score (27.4 vs. 28.5; P=0.025), a 5.9% lower ACE-III score (16.0 vs. 17.0; P=0.023) and a 29.2% slower TMT-A time (P=62.8 vs. 48.6; P=0.034).


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

1. Wassenaar TM, Yaffe K, van der Werf YD, et al. Associations between modifiable risk factors and white matter of the aging brain: insights from diffusion tensor imaging studies. Neurobiol Aging. 2019;80:56-70.

2. Berry C, Sidik N, Pereira AC, et al. Small-vessel disease in the heart and brain: current knowledge, unmet therapeutic need, and future directions. J Am Heart Assoc. 2019;8:e0111104.

Find this article online at Eur Heart J.

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