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

Hernan Mejia-Renteria, Alejandro Travieso, Jordi A Matías-Guiu, Miguel Yus, Carolina Espejo-Paeres, Francesca Finocchiaro, Sara Fernández, Carlos Ignacio Gomez-Escalonilla, Blanca Reneses-Prieto, Maria Dulcenombre Gómez-Garré, Alfonso Delgado-Alvarez, Ana Bustos, Leopoldo Perez de Isla, Jose Juan Gomez de Diego, Javier Modrego-Martin, Adriana Ortega-Hernandez, Petros Papadopoulos, Juan Arrazola-García, Jorge Matías-Guiu, Javier Escaned, Coronary microvascular dysfunction is associated with impaired cognitive function: the cerebral-coronary connection study (C3 study), European Heart Journal, 2022;, ehac521, https://doi.org/10.1093/eurheartj/ehac521

Abstract

Background

It remains unknown whether the presence of coronary microcirculatory dysfunction (CMD) correlates with its equivalent condition in the brain, cerebral small vessel disease (CSVD). The cerebral-coronary connection (C3), a prospective blinded study, investigated the prevalence of CMD in patients with coronary artery disease (CAD) and its association with CSVD and cognitive function.

Methods and results

Patients with documented CAD fulfilling inclusion criteria underwent physiological assessment of epicardial vessels and the microcirculation using intracoronary pressure and Doppler. Coronary microcirculation-related indices included coronary flow reserve (CFR) and hyperaemic microvascular resistance. Brain magnetic resonance imaging, transcranial Doppler (TCD), and neurocognitive examination were performed. Overall, 67 patients were included in the study (mean age 66 years, 73% female). Patients with abnormal CFR (<2.0) (55.2%) showed higher burden of white-matter hyperintensities: 43.2 vs. 20.0% (P = 0.044). After statistical adjustment, low CFR was associated with lower grey matter volume (P = 0.024) and with parameters of white-matter microstructural damage in diffusion-tensor imaging (lower fractional anisotropy and higher mean diffusivity, P = 0.029 and P = 0.032, respectively). Low CFR was associated with higher resistive (P = 0.027) and pulsatility (P = 0.043) values on TCD, and worse neurocognitive test scores (lower mini mental state examination, P = 0.025, and slower Trail Making Test A, P = 0.034).

Conclusions

Coronary microcirculatory dysfunction is frequent in patients with CAD and correlates with CSVD, abnormal cerebral flow haemodynamics, and significant cognitive impairment. These findings support the hypothesis that microvascular dysfunction in the heart and the brain are part of a single pathological process affecting microcirculation in patients with CAD.

Clinical Trial Registration

ClinicalTrials.gov NCT04131075.

Structured Graphical Abstract


CFR, coronary flow reserve; FFR, fractional flow reserve; MMSE, mini mental state examination; ACE-III, Addenbrooke’s Cognitive Examination (attention domain); TMT-A, Trail Making Test A; MRI, magnetic resonance imaging; WMH, white-matter hyperintensity; FA, fractional anisotropy; MD, mean diffusivity; GM, grey matter.

Introduction

Ischaemic heart disease (IHD) and degenerative brain disease are two major sources of death and disability affecting all countries. While the consequences of obstructive disease in major vessels supplying blood to both organs have been widely documented, less attention has been paid to disease processes affecting the microcirculation that, ultimately, may affect cardiac and cerebral function. Yet, over the last decade significant progress has been made in understanding the substrate of microvascular disease in both organs. In the heart, arteriolar thickening and capillary rarefaction that reduce the conductance of the microvasculature and its ability to vasodilate in response to increased myocardial oxygen demands constitute the leading cause of coronary microvascular dysfunction (CMD). In the brain, concentric hyaline thickening of deep penetrating small arteries (arteriolosclerosis) with associated fibrosis of the vessel wall constitutes the most frequent substrate for cerebral small vessel disease (CSVD). Of note, both CMD and CSVD share common risk factors, such as age, hypertension, and diabetes. These factors might have a common effect on the microvascular domain of cardiac and cerebral vascular beds.

Although a potential link between both conditions has been hypothesized based on the similarities between pathological changes and risk factors, advance in knowledge exploring this has been hampered by lacking objective evidence of CMD and pathological brain changes indicative of CSVD in prior research studies. Thus, the relationship between CMD and CSVD is unknown.

The main objective of this study was to analyse the relationship between cerebrovascular disease and CMD in patients with atherosclerotic coronary artery disease (CAD).

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https://doi.org/10.1093/eurheartj/ehac521

 

Authors: Hernan Mejia-Renteria, Alejandro Travieso, Jordi A Matías-Guiu, Miguel Yus, Carolina Espejo-Paeres, Francesca Finocchiaro, Sara Fernández, Carlos Ignacio Gomez-Escalonilla, Blanca Reneses-Prieto, Maria Dulcenombre Gómez-Garré, Alfonso Delgado-Alvarez, Ana Bustos, Leopoldo Perez de Isla, Jose Juan Gomez de Diego, Javier Modrego-Martin, Adriana Ortega-Hernandez, Petros Papadopoulos, Juan Arrazola-García, Jorge Matías-Guiu, Javier Escaned

Publication: European Heart Journal

Publisher: Oxford University Press on behalf of the European Society of Cardiology

Date published: November 7th, 2022

 

Copyright © 2022, Published by Oxford University Press on behalf of the European Society of Cardiology.